MANUA

A Guide for Authors and Editors 10th Edition

JAMA
ARCHIVES
JOURNALS

OXFORD
U N I V E R S I T Y PRESS
JAMA

OXFORD
UNIVERSITY PRBSS

Oxit,rd University Press. lnc., publishes works that further

Oxforrl University's objective of excellence
in research. scholarship, and education.

Oxford New York

Auckland Cape Town Dar es Salaam Hong Kong Karachi
Kuala Lumpur Madrid Melbourne Mexico City Nairobi
New Delhi Shanghai Taipei Toronto

With offices in
Argentina A u d a Brazil Chile CzechRepublic France Greece
Guatemala., Hungary Italy Japan Poland Pormgal Singapore
South Korea Switzerland Thailand Turkey Ukraine Vietnam

Copyright O 2007 by the American Medical Association

Puhlislied by Oxford University Press, Inc.

198 Madiwn Avenue. New York, New York 10016
www.oup.com
Oxford is a registered trademark of Oxford University Press
All rights reserved. No pan of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording, or otherwise,
without the prior permission of Oxford University Press.

Library of Congress Cataloging-in-PublicarionData

AMA manual of style : a guide for authors and editors.-10th ed. / Cheryl
.
lverson . . Let a1.l.
p. ; cm.
Rev. rd. of: American Medical Aswciation manual of style. 9th ed. 81998.
Includes bil~liographiulreferences and indexes.
ISBN 978-0-19-517633-9
1. Medical writing-Handbooks, manuals, etc. 2. Authorship-Handbooks,
n~anuals.etc. I. Iverson, Cheryl. 11. American Medical Association. 111. American
Medical Association manual of style. IV.'Tide: Manual of style. V. Title:
Guide for authors and editors.
[DNLM: 1. Writing. WZ 345 A511 m 7 1
R119.P.533 2007
808'.066614c22 2006037192
What's new in this edition? Below is a short response to a question that can only be

A completely updated.Nomenclature chapter, with.4 new subsections (molecular

medicine, ophthalmology, psychiatry, and radiology), the latest nomenclature in
many fields (eg, virology, chromosomes), molecular medicine subsections added
to many fields (eg, cardiology, neurology), more material on complementa~and
alternative medicine, and a more international approach to drug nomenclature.
8 Expanded, and now separate, chapters on manuscript preparation, visual display
of data, and references. The References chapter includes almost all new examples,
with about 50 examples of electronic references alone.
8 A change in'the policy for table footnotes from using superscript symbols to using
superscript lowercase letters.
8 A greatly expanded chapter on ethical and legal considerations, inclucling jjust
some of the following:
New responsibilities for authors, including identifying contributions of all
authors as well as substantial contributions of nonauthors.
New policies on group authorship.
Updates on conflict of interest, including requirements for ca~lpletcfinan-
cial disclosure, transparency of the role of the sponsor, ancl indepenrlcnt
statistical analysis for industry-supported studies.
New information on editorial freedom in the wake of the firings of rhc
editors of J A M and other general medical journals.
New policies and procedures for journal editors, including corrcsponrlcnr.c.
columns, corrections, and the role of editorial boards.
Updated definition of scientific nlisconduct, procecli~resfor 11;rnclling r!illlcga-
tions of fabrication, falsification, and pl:rgi;rrism ;rncl publishing ret~xctions.
* New information on data sharing ancl open ;~cccss.

New privacy concems-for patients in scientific puhlicirtion.

New case law on libel and suggestions for minimizing risk o f 1il)c.l.
Revised guidelines on advertising, inclucling online :~cl\.c.~.ti~ing
Upclated information on author and ctlitor ~.cl;~tions\ v i \ l ~rlw nc\\ 1 1 1 ~ ~ 1 1 . 1
\

ancl early release o f inli)rnr:~tionro rl~vpul>li{..

 c . ~ ~ ; L I ) I c1' ~0, include homonyms, idioms, COIIO-
~ I I ~ V . C . L : . :. I ! : 1 1 1 ~ . (;r.i111111;1r

c ~ L ~ I . I\I.$:::: ~ I ~ ~~ I~ I~ \ ~. ~ I I ~ ;tnd ~ I ~clicl~es.

~ J ~ I I ~ S ,
:\ decision to clrop the c-orrlrnas previously used to set off "Jr" and "Sr."
Inclusion o f guiclclines for capitalization of computer terms and intercapped .
compoitncls.
.L\cldition of many new terrns to the Correct and Preferred Usage and to the Study
1)c:sign and Sr;~tistics.glossaries.
policy o n al~l)reviationor expansion of state names.
Revised policy on SI units and updated conversion table.
- New material in the statistics chapter on cost-effectiveness analysis and survey
stitdies ancl rccluircment of clinical trial registration.
Information on online editing and coding, with samples of a marked-up and
c g e d page.
Expanded typography chapter, with emphasis on improving readability.
3 Updated and expanded publishing glossary and resources chapters.
As with the previous edition, nothing has been deleted and much-used chapters such
as Numbers and Percentages, Punctuation, and Eponyms have been thoroughly
updated.
The tradition of working with a committee of 10, begun with the eighth edition,
has continued through the tenth, with committee members dividing the work at the
outset, doing independent research and writing, obtaining critiques from outside
peer reviewers, and providing critiques on all of each other's material. Often, several
cycles of writing, reviewing, discussing, and rewriting were necessary. As with the
last edition, in cases in which complete agreement among all committee members
was not possible, we have agreed to disagree, with the majority opinion becoming
the policy.
We have continued to attribute each chapter to a "principal author." Because w e
have found it inlpossible to otherwise assess the relative contributions of the corn;
mittee members, their names appear in alphabetical order on the title page. Others
who have made substantial contributions are Jeni Reiling,JAMA, who is the principal
author of 2 updated chapters, and Bruce McGregor, who coauthored the indexing
chapter. Many other people who added strength to the work are listed in the Ac-
knowledgnlents section.
In the preface to the ninth edition, I expressed hope that the print book would
be follon~edby an electronic version. That did not come to pass, but for this edition,
the hope will be realized. Sign up at http://www.amamanualofstyle.corn for in-
forn~ational>out;I future clkctronic version of the Manual. We also welcome your
comments on the rnanual regarding suggestions for improvement or to note cor-
rections. Write to Cheryl Iverson at [email protected].
Cheryl Iverson, IMA
Chair, R%fAAlo?zualof Sgle Committee
Chic:l~o,Illinois
Oc.rolxr 19. L!)o6

viii
[AMA MANUAL OF STYLE
IA Guidefor Authors and Editors 10th Edition
 Cheryl Iverson, MA (Chair).

Stacy Christiansen, MA

Annette Flanagin, RN, MA

Phil B. Fontanarosa, MD, MBA

Richard M. Glass, MD

Brenda Gregoline, ELS

Stephen J. Lurie, MD, PhD

Harriet S. Meyer, MD

Margaret A. Winker, MD

Roxanne K. Young, ELS

I never cease to be amazed by the general inability .of physicians, other health
professionals, and scientists to communicate through the written word. Their schol-
arly and creative ideas and insightful data interpretation often seem to get lost in the
translation from brain to page. The sad state of this art became vividly clear to me
when I was invited to become the editor of Archives of Pediatrics & Adolescent
Medicine in 1995 and subsequently in 2000 to become the editor in chief ofJAMA, the
Journal of the American Medical Association. Among the reasons I was invited was
that the search committees considered me to have "superior" writing skills. Good
grief, I thought, we are indeed in big trouble.
My most vivid recollection of.being taught formal writing was by Theresa Ca-
morata Wozniak, my high school "English" (with those last names?) teacher. She
would begin each lesson by writing something like the following on the blackboard
(yes, blackboard; it was the 1950s, after all): "Do not waste time; that's the stuff of
which life is made." Mrs Camorata Wozniak obviously chose to ign0r-r more
likely to correct-ken Franklin's "Do not squander time, for that is the stuff life is
made of." Her grammar lesson was, of course, not to end a sentence with a prep-
osition; the moral lesson is obvious. Both remain with me to this day. However,
despite this background and the hundreds of other lessons from various editors and
colleagues, I still do not consider myself to have "superior" writing skills. Hence, my
continuing reliance on this manual of style.
My amazement at the difficulty so many bright, accomplished health profes-
sionals have in communicating through the written word has contiwed to be aug-
mented daily when I read the various manuscripts submitted to JAUA that reach my
desk. Simply comparing the original submitted manuscript with the published ver-
-sion clearly illustrates the value and skills of the editors, and especially the manu-
script (nee copy) editors. And therein lies the value of this manual.
The issue of communicating well in writing is certainly not new, and good
writing will become even more important but perhaps more challenging as the.use of
online written communication becomes the norm. Computer-based programs, such
as spell-check, are fine for some words (unless your name is DeAngelis, which spell-
check translates as "dunghill"), but grdmmar, punctuation, correct usage, and ref-
erence style are only a few items simply not covered reliably. But, all is not yet lost.
The AMA Manual of Style, 10th edition, contains everything that a group of editors
from the JAMA and Archiues family of journals believe is essential to produce :I
manuscript that is well organized, clear, rendable, ancl authoritative.
The first book on nledical writing written Ily ;I jAMA editor \v;ts pc~l,lishccl in
1938.' However, the IOth edition of the manual represents the collective ;~ntlupd;ttctl
work of editors over more than 40 yrzlrs. Thc first etlition was n.rittcn in tlic ~ i i i t l -
1 m s when the then-editors of j r ~ ;tssc~nl,lecl
; ~ ;and ctdificcl their collccti\.r.
knowledge and experience. Th;~tfirst volume. \v;~s:I trim 70 pagr. o r .c, itntl I1.1rl ;I
p l ~ I!IC r l ~the
~ , i ~ , u n ~ l . ~ of n previous editions' material have resulted in a much more
r.\lc.nbl\.c and conlprel~ensivemanual.
The 5 sections--Preparing an Article for Publication, Style, Terminology, Mea-
surement and Quantitation, and Technical Information-are chock-full of valuable
information for authors, editors, publishers, reviewers, and anyone else interested in
scientific writing. If you look for information that is not found herein, please contact
us so that we c l n arlcl it to the next edition, which is already on the minds of those
who will carry the torch to the 11th edition.
Itead ancl ilndcrstand, write and be understood, and mostly, enjoy.
Catherine D. DeAngelis, MD, MPH
Editor in Chief, J A M and the Archives Journals

REFERENCE
1. Fishbein M. Medical Writing: 7be Technic and the Art. Chicago, IL: American
Medical Association; 1938.
Acknowledgments

The individuals listed below reviewed part or all of the manual in draft form. Their
advice and comments were invaluable in adding clarity, polish, and addition;~l
substance to the manual. Any errors are solely the responsibility of the AIM rVIarrrtrrl
of Style Committee.
Laura Adamczyk Judith Dickson, MS, ELS(D1
Archives Journals Science Editing Inc, Rockville, Mar).land
Karen Adams-Taylor, MS John H. Dirckx, MD
JAMA and Archives Jouinals Dayton, Ohio
Daniel M. Albert, MD, MS . Pierre Durieux, MD, MPH
Zditor, Archim of Ophthalmology Rene Descartes University and H6pit;ll
University of Wisconsin, Madison EuropCen Georges Pompiclou.
Paris, France
Lynn M. Alperin
Taxas Medicine Karl Elvin
JAMA and Archives Journals
Jessica S. Ancker, MPH
Columbia University College Allison Frank Esposito
of Physicians and Surgeons, Dallas, Texas
New York, New York
Ronald G. Evens, MD
David Antos Washington University School
JAMA and Archives Journals of Medicine, St Louis, Missouri
Christine A. Arturo Lauren B. Fischer
American Academy of Ophthalmology, JAMA and Archives Journals
San ~rancisco,California
Fred Furtner, MAMS
Michael L. Callaham, MD Archives Journals
University of California, San Francisco
Barbara Gastel, MD, MPH
Diane L. Cannon Tesns A&M University, college Station
Archives Journals
Maxine A. Gere, MS
Terri S. Caiter Blue Cross and Blue Shield Association,
Archives of Surgery, Chicago, Illinois
Baltimore, Maryland
Julie T. Gerke, ELS
Hclenc M. Cole, MD (J11inli1i.sh.li.tlic.:rl C : o ~ l ) ~ ~ l ~ ~ n ):i\,
ii.;~li(
./A A4A l ' ; ~ ~ , ~ i l ) l )Nc.iv
: ~ ~ iJc.I..x.~
y.
Peter Cummings Erin &I. Giannini
University of Washington, Seattle Sonvich. Enpl:rncl
Pam Diamond 1';rtrI:r G I I I I I I ; I I ~
I'fizer Inc, New York, New Yodi : I I I l ~ t / t , \( C I I I ~ I I . I I -
Acknowledgments

Rohert M. Goluh, MD Povl Kiib, SlD

,journ;tlh
//1/1.IA iintl Archirlc~.~ 1; I I I V C ~
o f~CI o[ ~
lx~~l~.~gcn,
Copenhagen. I>c.nmark
C. K.Gunsalus, JD
Univer~ityof Illinois, Champaign/ June K. Robinson, MD
IJrbana Editor, Archives of Dermatology
Northwestern University, Feinberg
Cindy W. Hamilton, I'harll~D, ELS
School of Medicine, Chicago, Illinois
Hamilton House, Virginia Beach,
Virginia Roger N. Rosenberg, MD
Editor, Archives of Neurology
Lisa Y. Hardin
University of Texas Southwestern
JAMA and Archives Journals
Medical Center at Dallas
Wayne G . Hoppe, JD
Gale L. Saulsberry
JAMA and Archives Journals
JAMA and Archives Journals
13obJohnson, ELS
Karon Schindler, MA
WordHawk Editorial Services,
Emory University, Atlanta, Georgia
Palo Ako, California
Philip Sefton, ELS
Mary Ellen Johnston
JAM and Archives Journals J M
Heather A. Shebel
Sheldon Kotzin, MIS
National Library of Medicine, JAM
Bethesda, Maryland Valerie Siddall, PhD, ELS
AstraZeneca, Cheshire, England
Hope J. Lafferty, MD
Memorial Sloan-Kettering Cancer Center, ~ris.tineB. s-o&, BA
New York, New York Archives Journals
Trevor Lane, MA, DPhil Cheryl Smart, MA, MBA
University of Hong Kong St Louis, Missouri
Diane Bemeath Lang, BS Joan Stephenson, PhD
Radiological Society of North America, J M
Oak Brook, Illinois
Naomi Vaisrub, PhD
Connie M~Mo, ELS J M
Archives Journals
Elizabeth Wager, MA
Diana J. Mason, RN, PhD, FAAN Sideview, Princes Risborough,
American Journal of Nursing England
Richard W. Newman Cars M. Wallace, BS(Hons)
JAMA and Archives Journals J M
Kim S. Penelton-Campbell , Jane C. Wiggs, MLA, ELS
J M Mayo Clinic, Jacksonville, Florida
Margaret Perkins, MA, ELS Flo Witte, MA, ELS
New England Joulnal of Medicine AdvancMed LLC, Lexington, Kentucky
'.
Drummond Rennie, MD, FRCP, MACP Caroline Woods, PA-C, MS
J4A f/l Duluth, Minnesota
 Acknowledgments

In addition, 2 others deserve to he singled out for special thanks: Catherine I).
DeAngelis, MD, MPH, editor in chief of JAMA and editor in chief of Scientific I'ul,-
lications and Multimedia Applications for JAMA and the Archives Journals, for her
support of the work done on this edition by members of her staff, and Nicole Nctter
Snoblin, Lake Forest, Illinois, who copyedited this edition as she has the 2 previous
editions.
Contents

Foreword u
Preface uii
Acknowledgments Lx
Preparing an Article for Publication
1 Types of Articles 3
2 Manuscript Preparation 7
3 References 39
4 Visual Presentation of Data 81
5 Ethical and Legal Considerations 125
6 Editorial Assessment and Processing 301
Style
7 Grammar 315
8 Punctuation 333
9 Plurals 367
10 Capitalization 371
11 Correct and Preferred Usage 381
12 Non-English Words, Phrases, and Accent Marks 421
13 Medical Indexes 425
Terminology
14 Abbreviations 441
15 Nomenclature 529
16 Eponyms 777
17 Greek Letters 781
Measurement and Quantitation
18 UniQ of Measure 787
19 Numbers and Percentages 821
20 Study Design and Statistics 835
21 Mathematical Composition 907
Technical Information
22 Typography 91 7
23 Manuscript Editing and Proofreading 929
24 Glossary of I'ublishing Terms 9.35
25 Resources 367
Index 977
Preparing an Article for Publication
Types of Articles

Reports of Original Data Articles of Opinion

1.6
Correspondence

1.7
Reviews of Books, Journals,
and Other Media

Consensus Statements and Clinical 1.8

Practice Guidelines Other Types of Articles

Effective written communication requires the author to consider the intended

message and audience and use a form appropriate to both. Medical journal articles
usually fit into one of the following 7 main types.

Reports of Original Data. Published reports of original research are the backbone
of medical and scientific communications. Critical evaluation and replication of the
findings of such reports are key aspects of quality control and progress in science and
medicihe; ' h e clinical.applicationsof original research are a major source of benefits
for patients. ~ournalsoften categorize reports of original data as Original Articles.
Original Communications, or Original Reports, section headings that emphasize the
new findings such articles intend to communicate. Short articles repprting original
data may be called Brief Reports.,Studies that address basic issues of physiology or
pathology may be called Research Reports or Clinic.z!Investigations. InJhMA, articles
that report preliminary findings are called Preliminary Con~munications.
Articles that report original research results usually follow the traditional IMIWD
(Introduction, Methods, Results, and Discussion) format. Changing the acronym t o
AIMRAD would give appropriate emphasis to the abstract, which has becolnc in-
creasingly important in the era of electronic databases. Many readers scan only the
title and abstract (eg, from a search of an electronic database) and often use the
abstract to decide whether to obtain or read the full text of the article. This highlights
the importance of the abstract in communicating a brief but accurate and infor-
mative summary of the article.' Structured abstracts, which provide summary infor-
mation in a standard format, have enhanced value and are now required by many
medical journals for all reports of original (See 2.5, Manuscript Preparation.
Abstract, and 2.8, Manuscript Preparation,. Parts of a Manuscript, Headings, Sub-
headings, and Side Headings, for guidance in preparing these sections.)

Review Articles. Review articles collate and sunimarize the avail:il~leinformation

a l m ~ n~ pnrtic~ilar
t topic, in contr.tst to repolts of original data. Review articles have
~ ; ~ ; t pr;~<ic.;~l
t i ~ i l l w ~ f l ; l n cIWC:I~ISC
c c1inici:ins ofrcn use them 3 s guides for clinical

3
1.5 Articles of Opinion

rlc.c.ision.s. 'I'llih t ~ h c .III.<IIII~III\ \ C c.n.urinp I ~ I : I I I<.\

1 1 , ~ . I I I I ~ ~ , I I . I I ~ of I C \ \ \ .irr \)ar.nl-

>tic., inclucle all ~-clc\.;~n~ cla1.1. d r c riot o\.erly inllilenccd 1)) ttlc opinions and
I,iases of the authors. Thus, review articles should specify the methods used to
search for, select, synthesize, :~ndsummarize the information.' Some reviews employ
tneta-analysis, statistic:~ltechniques that cornbine quantitative results from indepen-
dent studies. (Se.e 20.4, Study Design and Statistics, Meta-analysis.) Structured abs-
tracts for review articles give authors a helpful framework for the information that
should be provided and enable readers to grasp quickly the methods, main findings,
and conclusions of the review. (See 2.5.1, Manuscript Preparation, Abstract, Structured
Abstracts for Systematic Reviews [Including Meta-analyses].)

Descriptive Articles. Descriptions, summaries, or observations that lack the sys-

tematic rigor of original research or systematic reviews may be published as Case
Reports (for patient descriptions), Clinical Observations, Special Articles, or Special
Communications. To merit publication, such articles should make novel observa-
tions that can stimulate research or should provide useful information about topics
of particular interest to a journal's readership. Since the scientific value of single case
reports is often limited, many journals prefer to consider them as Letters to the
Editor and publish them only if they make a unique observation that merits more
n . ~ medical journals publish case reports as educational
systematic i n ~ e s t i ~ a t i oSome
tools. Grand Rounds or Case Conference presentations published in journals typi-
cally combine descriptive case material (used to highlight clinical features of a dis-
order) with a review of the major issues illustrated by the case. Because of the
variability of their content, there is n o standard format for descriptive articles. A
short abstract may be helpful and usually is written in an unstructured narrative
form. Such abstracts summarize the main points of the article and are useful for
inclusion in electronic databases.

Conseni~usStatements and Clinical Practice Guidelines. Governmental and

private organizations often develop recommendations for the prevention, diagnosis,
and treatment of various disorders. These recommendations regarding appropriate
clinical decisions are usually made by a group of experts after they assess the avail-
able evidence. Recommendations may be published as consensus statements de- .
veloped at a conference or as clinical practice guidelines (sometimes calledprmice
parameters) developed over time. In either case, publication of the recornmen-
dations should identify the sponsor and the participating experts, explain how the
participants were selected, describe the evidence that supports the recommenda-
tions, and explain the process for achieving consensus in reaching the conclusions.
Structured abstracts can be helpful in summarizing this inf~rmation.~.'

Articles of Opinion. Editorials are short essays that usually reflect the views of the
editor or the policies of the journal. Editorials may be written by the editor, a rnern-
ber of the editorial staff or editorial board, or an invited author. Editorials may
comment on an article in the same issue of the journal, providing additional context
and opinion regarding its implications, or may deal with a separate topic of interest
to the journal's readers or editois. In the past, it was common for authors of medical '
joornal editori;rls not to he identified, as is still the usual practice for newspaper
ccIi!ori:~ls.I'his ha:, Ix.co~nemuch less common as authorship responsibility and
h;rt.c rcc.ci~.c.dincrz:tsing emphasis in medical publishing. (See 5.1.3,
;~cc-ot~nt;~l>ility
 1.8 Other Types of Articles

Ethical and Legal Considerations, Unsigned Editorials, Anonymous Articles. Pseu-

donymous Authors.) Journals generally do not publish unsolicited articles of opin-

Correspondence. Letters to the Editor are an essential aspect of postpul>licntion

review. The International Committee of Medical Journal Editors has recommencled
, that all biomedical journals provide "a mechanism for submitting comments, clues-
tions, or criticisms about published articles, as well as brief reports and comliientrln

the form of a correspondence section or column. The authors of articles discussed in

_ correspondence should be given an opportunity to respond, preferably in the snmc
issue in which the original correspondence appears."' Published letters usually com-
, ment on an article previously published in the same journal, and replies froni thc

: period (often about a month) after publication of the original article. Journals rely

or 2 letters are chosen for publication as being representative of the responses to a

particular article.

follow the same IMRAD format as a full-length research article but in a substantially
truncated length. Journals usually have strict limitations for the length and the

sibility, disclosure of conflicts of interest, and copyright transfer. Correspondents

should indicate whether letters sent to the editor are to be considered for pub-

Reviews of Books, Journals, and Other Media. Readers of such reviews seek
both an overview of the product and an assessment of its quality relative to similar
: works. Thus; these reviews usually include description and opinion, both of which
may extend to broader issues raised by the work. There is often considerable room
for individual style and expression in these critiques, but supporting evidence for
the reviewer's praise or criticism is essential.

Other Types of Articles. Journals pul~lisliotlic~.ilenis ancl articles tlwt do not fit
into any of the major categories. Examples inclucle personal reflections and essays
(eg, A Piece of My Mind in J A M ) , news articles, poetry, ol~ituaries,reports on con-
ferences, and articles based on clinical photographs. Ai~thorssho~~lcl examine se\.-

5
1.8 Other Types of Articles

*
ACKNOWLEDGMENT
Principal author: Rich:~rcl M. Glnss. XI11

REFERENCES
1. Winker MA. The need for concrete improvement in abstract quality. JAtfA. 1999,
281(12):1129-1130.
2. Kennie D, Glass KM. Structuring abstracts to make them more informative. /fill.
1991;266(1):116-117.
3. Taddio A, Pain T, Fassos FF, Boon H, Ilersich AL, Einarson TR.Quality of non-
structured and structu~.edabstracts of original research articles in the British Medical
the Clr~rtrtlir~r~
Jorrr~~r~l, and the Jotirnril of !he American
M ~ ~ l i cA.~~ocic1rio~z./ot117zaI,
~tl
Medicat Associatio~r.CMA/. 1994;150(10):1611-1615.
4. Cook DJ, Mulrow CD, I-lnynes KB. Systematic reviews: synthesis of best evidence
for clinical decisions. .inn Illtern Med. 1997;126(5):376-380.
5. Riesenl~crg1)K. Casc rcposls in the mcclical l i t e ~ ~ t u rJAMA.
e. 1986;255(15):2067.
6. Hayward RS, Wilson MC, Tunis SR, Bass EB, Rubin HR, Haynes RB. More informative
al~strastsof :~rticlesdcscrilIing clinical practice guidelines. Ann Intern Med. 1993;
118(9):731-737.
7. Olson C. consensub statements: applying structure. J A M . 1995;273(1):72-73.
8. International Committee of Medical Journal Editors. Correspondence. Uniform Re-
quirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for.
Biomedical Public~tion.http://www.icmje.org. Updated February 2006. Accessed
September 1, 2006.
Manuscript Preparation
I-

2.1 2.7
Titles and Subtitles Epigraphs
21. Quotation Marks
2.1.2 Numbers 2.8
2.1.3 Drugs Parts of a Manuscript, Headings, Subheadings,
2.1.4 Genus and Species . and Side Headings
2.1.5 Abbreviations 2.8.1 Levels of Headings
2.1.6 Capitalization 2.8.2 Number of Headings
2.1.7 Names of Cities, Counties, States, 2.8.3 Items to Avoid in Headings
Provinces, and Countries
2.9
2.2 Addenda
Bylinesand Endof-Text Signatures
2.2.1 Authors' Names 2.10
2.2.2 Authorship Acknowledgment Section
2.2.3 Degrees 2.10.1 Acceptance Date
2.2.4 Multiple Authors, Group 2.10.2 Online Publication Ahead of Print
Authors 2.10.3 Affiliation Notes That Would Not Fit
on Page 1
2.3 2.10.4 Correspondence Address
Footnotes to Title Page 2.10.5 Author Contributions
2.3.1 Order of Footnotes 2.10.6 List of Participants in a Group Study
2.3.2 Death 2.10.7 Financial Disclosure
2.3.3 Author Aff~liations 2.10.8 Funding/Support
2.10.9 Role of the Sponsor
2.4 2.10.10 Independent Statistical Analysis
Running Foot 2.10.1 1 Disclaimer
2.4.1 Name of the Publication 2.10.12 Previous Presentations
2.4.2 Title of the Article 2.10.13 Additional Information (Miscellaneous
Acknowledgments) '
2.5 2.10.14 Additional Contributions
Abstract 2.10.15 Preferred Citation Format
2.5.1 Structured Abstracts
2.5.2 UnstructuredAbstracts 2.11
2.5.3 General Guidelines Appendixes

2.6 2.12
Keywords Online-Only (Supplementary) Material

~ r e ~ a r a t i oofn a scholarly manuscript requires thoughtful consideration of the topic

and anticipation of the reader's needs and questions. Certain elements either are
standard parts of all manuscripts or are used so often as to merit special instruction.
These elements are discussed in this section in the order in which they appear in the
manuscript. References are discussed separately in chapter 3 and tables and figures
in chapter 4.
The preparation of any manuscript for p~il>lication should take the requirements
of the intended journal into account; this rnay enh;~nccthc ch;lnccs of ;lccept;~ncc
and expedite publication. For the author. m;~nclscriptprtbpar.1ttonrccluires f;~lnil-
iarity with the journal to which the ;~niclcis su1,mittcd. >lost jc,ilrn:1l3 pul>lish in-
stnrctions for authorr;. which semr. ;IS i~>eftrl p~iitli.>.
holnc. i c ) \ ~ r n .in\tr
~ l l i t 1 1 1 )n\ Ic ~r
2.1 Titles and Subtitles

authors contain a manuscript checklist (see that from JAM' [reproduced in this
chapter as the Table1 as an example). Some publishers also publish style manuals,
which provide in-depth instruction (see 25.0, Resources). For journals that subscribe
to the Uniform Requirements for Manuscripts Submitted to ~iomedical~ournals,' as
JAMA and the Archives Journals do, adherence to these guidelines will be accept-
able, although the individual journal may require more than the Uniform Require-
ments or make changes to suit its house style.
Many journals request submission of material through a Web-based manuscript
sul>missionand peer review system; Illany journals require such submission. Others
n ~ a yrequest materials on disk or as e-mail attachments; some may still accept printed
paper copies ("hard copy") (see 6.2, Editorial Assessment and Processing, Editorial
I'rocessing).

Titles and Subtitles. Titles should be concise, specific, and informative and should
contain the key points of the work. For scientific manuscripts, overly general titles
are not desirable (but see also 2.1.7, Names of Cities, Counties, States, Provinces,
and Countries).
Avoid: Cocaine Use and Homicide
Better Cocaine Use and Homicide Among Men in New York City
(Note: The shorter, more general title might be appropriate for an editorial or an .
opinion piece.)
Simila~iy,although the subtitle is frequently useful in expanding o n the title, it
should not contain key elements of the study as a supplement to an overly general
title.
Avoid: Psychiatric Disorders: A Rural-Urban Comparison
Better: Rural-Urban Differences in the Prevalence of Psychiatric
Disorders
Avoid: Multiple Sclerosis: Sexual Dysfunction and Response to
Medications
Better: Sexual Dysfunction and Response to Medications in Multiple
Sclerosis
Avoid: Hospitalization for Congestive Heart Failure: Explaining Racial
Differences
Belter: Racial Differences in Hospitalization Rates for Congestive Heart
Failure
Avoid: Cardiovascular Evaluation of Competitive Athletes: Medical and
Legal Issues
Better: Medical and Legal Issues in the Cardiovascular Evaluation of
Conlpetitive Athletes
However, too much detail also should be avoided. Subtitles should complement the
title by providing supplementary information that will supply more detail about the
content and aid in information retrieval. Several examples of informative title and
subtitle combinations appear below:
 2.1 Titles and Subtitles

BRCiil Testing in Families With Hereditary Breast-Ovarian Cancer: A Pro-

spective Study of Patient Decision Making and Outco~nes
Prevention of Systemic Infections, Especially Meningitis, Caused by Hae-
mophilus inJluenzae Type b: Impact on Public Health and Implications for
Other Polysaccharide-Based Vaccines
Long-term Outcome of Patients With Essential Thrombocythemia: Prog-
nostic Factors for Thrombosis, Bleeding, Myelofibrosis, and Leukemia
Prevalence of CutaneousAdverse Effects of Hairdressing: A SystematicReview
Subtitles of scientific manuscripts may be used to amplify the title; however, the
main title should be able to stand alone (ie, the subtitle should not be a continuation
of the title or a substitute for a succinct title):
Avoid: An Unusual Type of Pemphigus: Combining Features of Lupus
Erythematosus
Better: Pemphigus With Features of Lupus Erythematosus
Avoid: Von Hippel-Lindau Disease: Affecting 43 ~ e m b e r sof
' a Single
Kindred
I
Befter: Von Hippel-Lindau Disease in 43 Members of a Single Kindred
Phrases such as "Role of," "Effects of," "Treatment of," "Use of," and "Report of a
Case of" can often be omitted from both titles and subtitles.
Avoid: Effect of Smoking on Lung Cancer Risk
Better: Smoking and Lung Cancer Risk
Avoid: Use of Gastric Acid-Suppressive Agents and Risk of Community-
Acquired Clostridum drflcileAssociated Disease
Bettet: Gastric Acid-Suppressive en& and the Risk of Community-
Acquired Clostridium difJcile-Associated Disease
Sometimes, especially in randomized controlled trials, in which causality can be
demonstrated, the use of such phrases as "effects of" is appropriate.
Effects of Protein, Monounsaturated Fat, and Carbohydrate Intake on Blood
Pressure and Serum Lipids: Results of the OmniHeart Randomized Trial
Declarative sentences are used frequently as titles of news stories and opinion
pieces (eg, "Experts Set 2005 Influenza Vaccine Policy and Plan for Unpredict-
able Pandemic," "Spate of Lawsuits May Finally Fincl Chink in T o h ~ c c oIntlustry's
'Impenetrable Armor"'). However, sentences in scientific ;~rticletitles tcntl to over-
emphasize a conclusion and are best avoided.
Avoid: Fibromyalgia Is Common in a Postpoliolnyelitis Clinic
Better Prevalence of Fibromyalgia in Patients With I~ostpoliomyeliris
Syndrome
Similarly, questions should not be used for titles of scientific manuscripts
Avoid: Is Television Viewing Associated With Soci;ll Isol:~tion?1<01~~5
of
Exposure Time, Viewing Context, ;mtl Violcnt Conrcnr
 : : I I <.It.\ \'~c\\.lng2nd Social Isolation: Roles of Exposure
I\II PI]

-1-llnz.\'~~-\ving
~ o n t e x iand
, Violent Content
Qucb[lon5 arc gcnc.~-allymore appropriate for titles of editorials, commentaries, and
opinion pieces:
Levothyroxine and Osteoporosis: An End to the Controversy?
'fow~trdImprovetl Glyccmic Control in Diabetes: What's on the Horizon?
I'os~r;ttliotI~er:tpyI'clvic 1:ractures: Cause for Concern or Opportunity for
Further Research?
Randomized controlled trials should be identified in the title or subtitle because this
alerts readers to the level of evidence and the study design and is helpful to re-
searchers performing a meta-analysis:
Physical Rehabilitation for Frail Nursing Home Residents: A Randomized
Controlled Trial
Other aspects of study design or methods may b e included in the title or subtitle.
Sex Differences of Endogenous Sex Hormones and Risk of Type 2 Diabetes:
A Systematic Review and Meta-analysis
Oxycodone for Cancer-Related Pain: eta-analysis of Randomized Con- .
trolled Trials
Depression, Apolipoprotein E Genotype, and the Incidence of Mild Cog-
nitive Impairment: A Prospective Cohort Study
Incidence of Multiple Primary Melanoma: Two-Year Results From a
Population-Based Study
An Observational Study of Cognitive Impairment in Amyotrophic Lateral
Sclerosis
Sometimes a subtitle will contain the name of the group responsible for the study,
especially if the study is large and is best known by its group name o r acronym or if
it is a part of a series of reports from the same group (see also 14.9, Abbreviations,
Collaborative Groups):
Lowering Dietary Intake of Fat and Cholesterol in Children With Elevated
Low-Density Lipoprotein Cholesterol Levels: The Dietary Intervention Study
in Children (DISC)
Prevention of Stroke by Antihypertensive Drug Treatment in Older Patients
With Isolated Systolic Hypertension: Final Results of the Systolic Hyper-
tension in the Elderly Program (SHEP)
Administrative Data Feedback for Effective Cardiac Treatment: AFFECT, a
Cluster Randomized Trial
Some journals, such asjAMA, have moved away from including the study name in
the title or subtitle for any but the original report of outcomes or secondary analyses
that provide unique information.
 2.1.4 Genus and Species

Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer: The Women's
Health Initiative Randomized Controlled Dietary Modification Trial
For the majority of secondary analyses, having the study name in the abstract is
sufficient for information retrieval. In the following example, the study participants
were members of the Framingham Offspring Study, an inception cohort of tllc
Framingham Heart Study.
Sibling Cardiovascular Disease as a Risk Factor for Cardiovascular Disease in
Middle-aged Adults

Quotation Marks. If quotation marks are required in the title or subtitle, they should
be double, not single (see- 8.6.3, Punctuation, Quotation'Marks, Titles).
Above All "Do No Ham": How Can Errors Be Avoided in Medicine?

Numbers. Follow the style for numbers included in titles as described in 19.0. Nuln-
bers and Percentages.
Educational Programs in US Medical Schools, 2004-2005'
Comparison of 2 Methods to Detect Publication Bias in Meta-analyses
Skin Reactions in a Subset of Patients With Stage IV Melanoma Treated With
T-Lymphocyte Antigen 4 Monoclonal Antibody as a Single Agent
If numbers appear at the beginning of a title or subtitle, they-and any unit of
measure associated with them--should be spelled out. Exceptions may be made for
years (see also 19.2.1, Numbers and Percentages, Spelling Out Numbers, Beginning
a Sentence, Title, Subtitle, or Heading).
Primary and Secondary Prevention Services in Clinical Practice: Twenty
Years' Experience in Development, Implementation, and Evalyation
Three-Day Antimicrobial Regimen for Treatment of Acute Cystitis in
Women: A Randomized Trial
Seventy-five Years of the Archives of Sutgety: 1920 to 1995
Six-Month Trial of Bupropion With Contingency Management for Cocaine
Dependence in a Methadone-Maintained l'opulation

Drugs. If drug names appear in the title or subtitle, (1) use the approved generic or
nonproprieta'iy name, (2) omit the nonbase moiety unless it is required (see 15.4,
Nomenclature, Drugs), and (3) avoid the use of proprietary names unless ( a ) several
products are being compared, (b) the article is specific to a particular formulation of
a drug (eg, the vehicle, not the active substance, caused adverse reactions), or (c) the
number of ingredients is so large that the resulting title would be clumsy and a
generic term, such as "multivitamin tablet," wo~~lcl not clo.

Genus and Species. Genus and species should be expanded and italic~zcdin the t~rlc
or subtitle and an initial capital letter should Ile used for tlle gcnu, 1>i1t not rlv.
species name, just as in the text. (See also 15.14.1, Korncnc.l;~rurc.( ) I . ~ . I ~ I ~.~ntl
I \

Pathogens, Biological Nomenclature.)

11
..
b w 1 Abbreviations. Avoid thc use of al,l)reviations in the title and subtitle, unless space
consideralions rcquirc an exception (see the first example below) or unless the
title or si~l,title inclildes the name of a group that is best known by its acronym
(see the seconcl es;umplc I~elow).In both cases, the abbreviation should be ex-
p;mded in the abstract and at first appearance in the text. (See also 10.6, Capitali-
zation, Acronyms and Initialisms, and 14.0, Abbreviations.)
IJrev:~lcnc'co f 111\I-1 in Blood Donations Following Implementation of a
Stri~cti~~.ccl
I%looclSafety I'olicy in South Africa
I<cl>or~ing01' No~linkriorily;~ntlIkli~iv:ilcncc Randomized Trials: An Ex-
tension of the CONSOItT Statement

Capitalization. Capitalize the first letter of each major word in titles and subtitles. Do
ar~iclcs(ex,u, ua, be), prepositions of 3 or fewer letters, coordinating
not c:~pi~alizc
conjunctions (ancl, or, for, nor, but), or the to in infinitives. Do capitalize a 2-letter
verb such as Is or Be. Exceptions are made for some expressions, such as com-
pound terms from languages other than English and phrasal verbs:
Ethical Questions Surrounding In Vitro Fertilization
Permanent Duplex Surveillance of In Situ Saphenous Vein Bypasses
Choice of Stents and End Points for Treatment of De Novo Coronary Artery
Lesions
Weighing In on Bariatric Surgery
Researchers Size Up Nanotechnology Risks
Universal Screening for Tuberculosis Infection: School's Out!
See 10.0, Capitalization, for overall guidelines. For capitalization of hyphenated
compounds, see 10.2, Capitalization, Titles and Headings.

Names of Cities, Counties, States, Provinces, and Countries. Include cities, states,
counties, provinces, or countries in titles only when essential, especially for results
th::t may not be generalizable to other locations (eg, unique to that site).
Epidemic of Gang-Related Homicides in Los Angeles County From 1999
Through 2004
Equity of Use of Home-Based or Facility-Based Skilled Obstetric Care in
Rural Bangladesh
Idcntific;~lionof' a Ncw NeF~.c~'riu
nzenitzgiticiis Serogroup Clone From Anhui
l'rovince, China
Comparison of Stage at Diagnosis of Melanoma Among Hispanic, Black,
ancl White Patients in Miami-Dade County, Florida
(;c.litlcr I)i\;~clv;~nt;igc :rntl Iteproductive Health Risk Factors for Common
: < : o ~ i ~ ~ i ~Survey
1lv1r1.1lI ) I ~ O I C I C . ~ Z i l l W ' ~ I I I C - 1 1A i ~ n i t yin Intlia
 2.2.1 Authors' Names

In other cases, include this geographic information in the abstract and the text only.
(See also 14.5, Abbreviations, Cities, States, Counties, Territories, Possessions; Prov-
; inces; Countries.)

I:I Avoid:

Better:
Pertussis Infection in Adults With Persistent Cough in Nashville,
Tennessee
Pertussis Infection in Adults With Persistent Cough
Avoid: Hospitalization Charges, Costs, and Income for Trauma-Related
'
Injuries at the University of California, Davis, Mdical Center in
Sacramento
Better: Hospitalization Charges, Costs, and Income for Trauma-Related
Injuries at a University Trauma Center

I Atmid

Better:
Prevalence of Erectile Dysfunction in Men Seen by Primary Care
Physicians in Canada
Prevalence of Erectile Dysfunction Seen by Primary Care
Physicians

Bylines and End-of-Text Signatures. In major articles, authors are listed in a by-
line, which appears immediately below the title or subtitle. In letters, editorials, book
reviews, essays, poems, and news stories, the authors' names may appear as signatures
at the end of the text, rather than as a byliie under the title. The authors' names and
academic degrees are used, as in the byliie. Further information given in the signature
varies with the journal. The author should consult a recent issue for style and format.

Authors' Names. The byline or signature block should contain each author's full
name (unless initials are preferred to full names), including, for example, Jr, Sr, 11,
111, and middle initials, and highest academic degree(s). Authors should be consis-
tent in the presentation of their names in all published works for ease of .use by
indexers, cataloguers, readers, and data searchers.
If the byline includes names of Chinese, Japanese, or Vietnamc.~origin, or
other names in which the family name is traditionally given first, some journals-
and some author-may westernize the order and give the surname last. For ex-
ample, an author whose name is conventionally given as Zliou Jing, where Zhou is
the surname, might list his name as Jing Zhou for publication in asWestern journal,
or the journal might elect to publish it that way regardless of the author's preference.
For journals that choose to follow the author's preference in presentation of the
order of first name (given name, familiar name) and surname, and that therefore
might retain the conventional (ie, non-Western) presentation of such names in
the byline, the surname may be distinguished from the first name by capital letters
(eg, ZHOU in^)^ or some other typographic distinction (eg, Zhou Jing or ZHOU Jing).
Alternatively, a preferredcitation might be published, as suggested by p lack^ in a
discussion of treatment of names of authors from Spanish- and Portuguese-speaking
countries. Although this would address only the authors shown in the citation, it is a
viable alternative and one that might be used for all citations or only those that might
otherwise be incorrectly cited (see also 2.2.4, Multiple Authors, Group Authors).
.JAMA and the Archives Journals favor following the authors' preferences on
presentation of their names and recornn~enclqllerying tlie :ulthor at the editing stage
2.2 Bylines and End-of-Text Signatures

to ensure that the surnanie is properly identified in rh'. onllnc ragg1nK (.)nllnc.1:rkvng
is critical for accurate indexing since searching by autliors surnJlne dc.pc.ncl.4 o n
appropri;~tetagging I,y the journal ;~ntlidentification of surn~meI>y thc w;rrc.hc.r- (See
2.10.15, Preferred Citation Format.) See the Chicagoh~fu~~ual for niorc. detail:;
o/.S!)~lc~
on conventional presentations of names from various cultures."

Authorship. All persons listed as authors should qualify for authorship (see 5.1,
Ethical and Legal Considerdtions, Authorship Responsibility, and 5.1.2, Ethical and
Legal Considerations, Authorship Kesponsibility, Guest and Ghost Authors). Ordcr
,of authorship should be determined by the authors (see 5.1.5, Ethical and Legal
Considerations, Authorship Responsibility, Order of Authorship). According to the
1ntcm:itionnl Conimittcc o f Mcdic:il Journal ~ t l i t o r s , ~
Authorship credit should be based on 1) substantial contributions to con-
ception and design, or acquisition of data, gr analysis and interpretation of
cl;~r:i;2) tl~~fting
the :irticlc or revising it critically for important intellectual
content; and 3) final approval of the version to be published. Authors should
. meet conditions 1, 2, and 3.
Some journals (including JAMA, several of the Archives Journals, BMJ and Lancet)
may publish authors' specific contributions. See 2.10.5, Acknowledgment Section,
Author Contributions.
Persons who made other contributions but who d o not qualify for authorship
may be listed in the Acknowledgment section (see 2.10.14, Acknowledgment Sec-
tion, Additional Contributions), with their permission (see 5.2, Ethical and Legal
Considerations, Acknowledgments).
If an author requests that his or her name be withheld from publication, this
should be allowed only in rare cases with compelling justification. In those rare cases,
the author must meet the authorship criteria, but the byline may reflect the author's
desire for anonymity (see 5.1.3, Ethical and Legal Considerations, Authorship Re-
sponsibility, Unsigned Editorials, Anonymous Authors, Pseudonymous Authors).
See also 2.2.4, Multiple Authors, Group Authors.

Degrees. Journals should establish their own policies on the inclusion of authors'
degrees. The policy of JAMA and the Archive. Journals is as follows: The highest.
level of degree or professional certification will be published with each author's
name. If an author holds 2 doctoral degrees (eg, MD and PhD, or MD and JD), either
or both may be used, in the order preferred by the author. If the author has a
doctorate, degrees at the master's level are not usually included, although excep-
tions may be made when the master's degree represents a specialized field or a field
different from that represented by the doctorate (eg, MD, MPH).
Academic degrees below the master's level are usually omitted unless these are
the highest degree held. Exceptions are made for specialized professional certifi-
cations, degrees, and licensuie (eg, RN, RD, COT, PA) and for specialized bachelor's
degrees (eg, BSN, BPharm) and combination degrees (eg, BS, M[ASCPI).
Generally, US fellowship designations (eg, FACP or FACS) and honorary de-
grees (eg, PhDIHonl) are omitted. However, non-US designations such as the British
FIICIJ or FRCS and the Canadian FRCI'C are included. (See 14.1, Abbreviations, Aca-'
demic Degrees, Certifications, and Honors, for the rationale for this policy.)
 2.2.4 Multiple Authors, Group Authors

J A M and the Archives Joumals prefer that authors in the military, or retired
from the military, use their academic degrees rather than their military titles.

Multiple Authors, Group Authors. When the byline contains more than l'name, use
semicolons to separate the authors' names. See also 5.1.7, Ethical and Legal Con-
siderations, Authorship Responsibility, Group and Collaborative Authorship.

Multiple Authors. The following examples show bylines with multiple authors.
. Melvin H. Freedman, MD, FRCPC; E. Fred Saunders, MD, FRCP; Louise
Jones, MD, PhD; Kurt Grant, RN
John E. Ware Jr, PhD; Martha S. Bayliss, MSc; Wiiam H. Rogers, PhD; Mark
Kosinski, MA; Alvin R. ~arlov,MD
Thomas G. ~ e i aFRCS;
~ , Antonios Kaberos, MD;William E. Grant, FRCSI;
Michael P. Steams, FRCS

Individual Authors for a Group. When a byline or signature contains i or more

individuals' names and the name of a group (not all members of which meet the
qualifications for authorship), use for followed by the name of the group if the
qualify for authorship and are writing for the group.
WGam k Tasman, MD;for the Laser ROP Study Group

Individual Authors and a Gmup. When a byline or signature contains 1 or more

:& individuals' names, and the name of a group (all members of which meet the
,-use and followed by the name of the group if the
individuals as we22 as all the qtembers of the gmup qualify for authorship. In this
case, every member of the group must qualify for authorship, and for journals with
specific authorship criteria, like JAUA and the A h i u e s Journals, every member of
the group must sign a statement that he or she has met the criteria for authorship.
(See 5.1.7, Ethical and Legal Considerations, Authorship Responsibility, Group and
: - - . Collaborative Authorship, and 14.9, Abbreviations, Collaborative Groups.)

Debra L. Hanson,MS; Susan Y. Chu, PhD; Karen M. Farizo, MD;John W. Ward,

MD; and the Adult and Adolescent Spectrum of HIV Disease Project Group

Subgroup as Author. Occasionally a specific subgroup of a larger group will be

listed as the author:
Executive Committee for the symptomatic Carotid Atherosclerotic Stutly
The Writing Group for the DISC Collaborative Research Group
In this case, the names of the members of the subgroup should be clearly lister1 as
authors and each member of the subgroup must sign a statement indicating that h e
or she met the authorship criteria.

Group Name andAsterisk (Linking to NamedAuthors). If only a group is given in tllc

byline but not all members of the group qualify as authors, an asterisk milst folio\\.
the group name in the byline and refer to an asterisk footnote at the hottom o f thc
first page of the article. The footnote must list the actual authors o r refer !o the list

15
2.3 F o o t n o t e s t o Title Page

elsewhere in the article if the list is too long to provide on rhe first page E.~ch
member of this group must sign a statement indicating that he or she tias mct thc
authorship criteria.
Bylilze: Collaborative Ocular Melanoma Study Group*
'This report was prepared on behalf of the COMS Group by Marie Diener-
West, IJhD;Sandra M. Reynolds, MA; Donna J. Agugliaro, RN, BSN; Robert
Caldwell, PA; Kristi Cumming, RN, MSN; John D. Earle, MD; Barbara S.
Hawkins, PhD; James A. Hayman, MD; Ismael Jaiyesimi, MD; Lee M. Jampol,
MD; John M. Kirkwood, MD; Wui-Jin Koh, MD; Dennis M. Robertson, MD;
John M. Slraw, ML);Ur-dley K. Strzatsma, MD, JD; and Jonni Thoma, IW, BSN.
Group Information: A list of the COMS Group members as of September 30,
2000, was published in Archives of Ophthalmology (2001;119[71:961-965).
Byline: Cryotherapy for Retinopathy of Prematurity Cooperative Group*
This article was prepared on behalf of the Cryotherapy for Retinopathy of
IJrematurity Cooperative Group by Velma Dobson, PhD (chair); Graham E.
Quinn, MD, MSCE; C. Gail Summer, MD; Robert J. Hardy, PhD; and Betty
Tung, MS.
Group Information: A complete list of the members of the Cryotherapy for
Retinopathy of Prematurity Cooperative Group at the 10-year examination
was published in Anhives of Ophthalmology (2001;119[8]:1110-1118).
Note that, in conjunction with the mention of a group in the byline, reference to the
names of the members of the group may be given as shown immediately above or
may be given in a box in the article or at the end of the article, in the Acknowl-
edgments. (See also 2.3.3, Footnotes to Title Page, Author Affiliations.)

Group Name in Byline, With All Group Members Qualifjing as Authors. If each
member of the group qualifies for authorship, the group name may be listed in the
byline or signature block without an asterisk (see 2.3.3, Footnotes to Title Page,
Author Affiliations, and 2.10.6, Acknowledgment Section, Lit of Participants in a
Group Study). The group members would be listed at the end of the article or in a box
within the article and would be identified as authors. (See also 5.1.7, Ethical and Legal '
Considerations, Authorship ~es~onsibility, Group and Collaborative Authorship.)

Footnotes t o Title Page. Footnotes should be avoided within the text. Such ex-
planatory material can usually be incorporated into the text parenthetically. The
footnotes discussed below are those that may appear at the bottom of the first page
of major articles.

Order of Footnotes. The preferred order of the footnotes at the bottom of the first
page of an article in JAMA ind the Archives Journals is as follows (see also 22.0,
Typography). No&: Not all articles will include all of these.
(,;Ir.2
. ..4:,
.... 7; JAMA
(-. Author affiliations
, r)eath of an a ~ ~ t h (death
or dagger [t])(see 2.3.2, Footnotes to Title Page. Death)
I

2.3.3 Author Affiliations

! W Information about members of a group (see 2.10.6, Acknowledgn~entSection, List

of Participants in a Group Study)
Corresponding author contact information
Byline: John A. Doe, MD; Myrtle S. Coe, MDt; Simon T. Foe, RN; for the
XYZ Group

Author Affiliations: Department of Pediatrics, Baylor College of Medicine,

Houston, Texas.
tDied November 3, 2005.
A List of the & Group members appears at the end of this article.
Corresponding Author. John A. Doe, MD, Department of Pediatrics, Baylor
College of Medicine, 1 Baylor Plaza, Houston, TX 77030 (jdoeQ
baylor.edu).

Archives Journals
* Author affiliations
Death of an author (death dagger [TI) (see 2.3.2, Footnotes to Title I'age, Death)

Group Information: The members of the XYZ Group are listed at the end o f
this article.

Group Information: The members of the XYZ Group are listed in a box o n

(In the Archives Journals, the contact information for the corresponding author,
which is published o n the first page of an article in JAMA, is given in the Ackno\vl-
edgment section [see 2.10, Acknowledgment Section] immediately after the ;~cccp-
tance date.) See also 22.0, Typography.

Death. If a n author of an article has died before the article goes to press o r is posted
online, a death dagger (t) should follow the author's name in the hylinc, and oncbof'

tDied November 17, 2005.

tDeceased.

Author Affiliations. The institutions with which an author is profession~lly:~ffiliatecl,

including locations, are given in a footnote. The authors' last names are given parcn-
thetically in the footnote following their respective institutions. If 2 or more authors
: share the same last name, their initials should be used in addition to the last name to
distingu~rhthem. Title and academic r.tnk arc not inclucled in this footnote. If all
authors in the byline are affiliated with the sanle c!cp;~rtinentancl institution, there is
no need to i n c l ~ d etheir nnmcs in the f(xxno(c.

17
.' j ~ ~ ~ 10 T~tle
~ Page
~ t r ~ ~ ~ : ~ ~

rhc :~f'iiIii~rions
I.ib[ in tlie order of tlie authors' names as given in the byline, but,
tor o f g~.oi~l>ing,
cast coriil>inc the listings of authors affiliated with the same in-
brr~iition(eg, if rlic I>ylincincli~tlesauthors A, B, and C and if authors A and C are at
the same institution, list the institution of authors A and C first and then the insti-
tution of author B) and for authors in private practice list the information at the end. .
Byliize G a y T . Jeng, MS; James R. Scott, MD; Leon F. Burmeister, PhD
Author hffiliations: Department of Preventive Medicine, University of Iowa,
Iowa City (Mr Jeng and Dr Burmeister); and Department of Obstetrics and
Gynecology, University of Utah, Salt Lake City (Dr Scott).
Byliita Daniel G. Descl!ler, MD; Robert Osorio, MD; Nancy L. Ascher, MD,
PhD; Kelvin C . Lee, MD
Author Affiliations: Departments of Otolaryngology-Head and Neck Sur-
gery (Drs Deschler and Lee) and General Surgery (Drs Osorio and Ascher),
University of C-alifomia, San Francisco.
Byline: Carol L. Shields, MD; Arrnan Mashayekhi, MD; Jacqueline Cater,
PhD; Abdullah Shelii, MD; Steven Ness, MD; Anna T. Meadows, MD; Jerry A.
Shields, MD
Author Affiliations: Ocular Oncology Service, Wils Eye Hospital, Thomas
Jefferson University, Philadelphia, Pennsylvania (Drs C. L. Shields, Masby-
ekhi, Cater, Shelil, Ness, and J. A. Shields); and Division of Oncology, The
Children's Hospital of Philadelphia (Dr Meadows).
Byline: Yves Vander Haeghen, PhD;Jean Marie Naeyaert, P ~ D
Author Affiliations: Department of Dermatology, University Hospital, Ghent,
Belgium.
Byline: Mariangela Lo Guidice, BS; Marcella Neri, MD; Michele Falco, BS;
Maurizio Stumio, BS; Elisa Calzolari, MD; Daniela Di Benedetto, PhD; Marco
Fichera, PhD
Author Affiliations: Genetic Diagnostic Laboratory, Instituto di Ricovero e
C L I3~Crrc~ttereScientific0 (IlICCS) Oasi Maria SS, Troina, Italy (Mss Lo '
Guidice and Falco, Mr Stumio, and Drs Di Benedetto and Fichera); and
Department of Experimental Medicine and Diagnostics, Medical Genetics
Service, University of Ferrara, Ferrara, Italy (Drs Neri and Calzolari).
Note that the authors are also grouped by their degrees or honorifics (or courtesy
titles), so that in the example below, Drs Brown and Stone are listed together,
followed by Mr Fingert and Ms Taylor, even though Dr Stone comes afterMr Fingert
ant1 Ms Taylor in the byline.
Jeremiah Brown Jr, MD;,John H. Fingert; Chris M. Taylor; Max Lake,
Qllit~e:
MD; Val C. Sheffield, AD, PhD; Edwin M. Stone, MD, PhD
Author Affiliations: Departments of Ophthalmology (Drs Brown and Stone,
Mr Finge~t.ant1 Ms T~ylor)and Pediatrics (Dr Sheffield), University of Iowa
College OF >ledicine,Iowa City. Dr Lake is in private practice in Salina, Kansas. .
If there is ;I single author and a single institution with which he or she is affiliated,
use the singular for the sidellead:
 2.4.1 Name of the Publication

Byline: James R. Keane, MD

Author Miation: Department of Neurology, University of Southern Cali-
fornia Medical School, Los hgeles.
an author is affiliated with different institutions or different departments at the
same institution, this information should be indicated parenthetically.
Author Affiliations: Rocky Mountain Poison and Drug Center, Denver De-
partment of Health and Hospitals (Dr Dart, Ms Stark, and Mr Fulton), and
Colorado Emergency Medicine Research Center, University of Colondo
IIealth Sciences Center (Drs Dart and Lowenstein and Ms Koziol-McLain),
Denver, Colorado.
The affiliation listed, including departmental affiliation if appropriate, should reflect
the author's institutional affiliation at the time the work was done. If the author has
since moved, the current affiliation also, should be provided.
Author Affiliations: Department of Health Policy and Management, The
Johns Hopkins' University Bloomberg School of Public Health, Baltimore,
Maryland. Dr L1oyd.i~new with the Department of ~rnetgencyMedicine, St
Luke's Hospital, Milwaukee, Wisconsin.
For large groups, the name of the group may be given in the byline, and the affili-
ation footnote may refer the reader to the end of the article, a boxed listing within
the article, or another publication for a complete listing of the participants. (See also
2.2.4, Bylines and End-of-Text Signatures, Multiple Authors, Group Authors, and
2.10.6, Acknowledgment Section, List of Participants in a Group Study.) b

A complete list of the members of the Human Fetal Tissue Working Group
appears at the end of this article.
A complete list of the members of the Cryotherapy for Retinopathy of
Prematurity Cooperative Group was published previously (Arth Ophthal-
mol. 2001;119[81:1110-1118).

Running Foot. ~riniedpages customarily carry the journal name or abbreviation,

volume number, date of issue, and page number. They may also include a shortened
version of the article title. When this information appears at the top of the page, it is
lled a running head; when it appears at the bottom of the page, it is called a running
foot. These are typically added during the editing ancl production process, and au-
thors are not usuallyrequired to submit such information. (See also 22.0, Typography.)

Name of the Publication. Use the accepted List of Jo~irnak~ndexed for MEDLINE~
abbreviations of journal names (see 14.10, Abbreviations, Names of Journals) and
the following forms, as applicable to the journal involved:
JAM: J A W , Decembcr 14, 2005-Vol 294. N o . 22
Archives journals: Arch Pediatr Adolesc hterl/Vol 159, k c 2005
www.archpediatrics.com
Note that journals will differ in the amount of infonn;~tion~nclilclctl1n rtlcir n l n n t n ~
feet and that the style for some abbreviations (eg,rhc nlontll Iri rl~c.:I r r . / ~ i r r ,(-\;
.~-
ample above) may differ from that used cIw\vhcrc In rllc. p u l ) l ~ ~ . : ~ r t o ~ l

19
Title of the Article. 111'. \lionenrJ version of the title should be kept brief but
\ i l t l c l i t l C ~ I ~ ; ~ ~rtlc I . I~ii;~in
\I~C point of the article (see the options suggested in the.
\ L c o ~ l c Cl X . I I I ~ , ~ L .I)clo\v. Ixtsttd on the desired emphasis), not just repeat the first few
ivol.cls o f the title. Different journals have different limits (eg, approximately 45
c.h:ir:~ctcrs :tnd spaccs in JAMA). No punctuation follows the running footlheader. .
Titlc: Taking Health Status Into Account When Setting
Capitation Rates
H~rrrnirrgFool: Adjusting Capitation Rates
Titkc): Decline in Hospital Utilization and Cost Inflation
Under Managed Care in California
Runtzing Foot: Decline in Wspital Utilization and Costs
or
Managed Care in California
Title: Domestic Production vs International Immigration:
Options for the US Physician Workforce
Running Foot: Domestic vs International Physician Workforce
Title: Neurologic Adverse Events Associated With Smallpox
Vaccination in the United States, 2002-2004
Running Foot Smallpox vaccination and Neurologic Events
Careful use of abbreviations inay help meet space limitations.
. Title: Ventilatory Management of Acute Lung Injury and
Acute Respiratory Distress Syndrome
Running Foot: Management of Acute Lung Injury and ARDS
In some instances the editorial department, eg, Editorials, Commentary, Letters, rather
than the article's title, will constitute the running headlfoot.

Abstract. In this age of electronic data dissemination and retrieval, in which ab-
stracts are typically indexed and freely available, a well-written abstract has become
increasingly important in directing readers to articles of potential clinical and re-
search interest. The abstract of a research report summarizes the main points of an
article: (1) the study objective or background, (2) the study design and methods, (3)
primary results, and (4) principal conclusions. For scientific studies and systematic
reviews, narrative expressions, such as "X is described," "Y is discussed," "Z is also
reviewed," do not add meaning and should be avoided. Results should be presented
in quantitative fashion, but authors and editors should be scrupulous in verifying the
accuracy of all data and numbers reported and ensuring consistency with the results
published in the full a r t i ~ l e . ~

Structured Abstracts. For reports of original data, systematic reviews (inclyding

mcta-analyses), and clinical reviews, structured abstracts that use predetermined
sideheads are recommended. Specific advice taken from JAMA's Instructions for
~uthors,'adapted from Haynes et al? is given below. Note that Design, Setting, and
 2.5.1 Structured Abstracts

Patients or Other Participants may be combined depending on the description. If no

intervention was performed, that sideheading may be omitted. Many journals limit
the number of words to 250, but some (such asJAMA) allow 300 for reports of orig-
inal data and for systematic reviews.

Structured Abstracts for Reports of Original data. In reports of original data, include
an abstract of no more than 300 words using the following headings: Context,
Objective, Design, Setting, Patients (or Participants), Interventions (include only if
there are any), Main Outcome Measure($, Results, and Conclusions. For brevity,
phrases rather than complete sentences may be used. Include the following content
in each section:
Context: Begin the abstract with a sentence or two explaining the clinical (or other)
importance of the study question.
Objective: State the precise objective or study question addressed in the report (eg,
"To deterpine whether.. ."1. If more than 1 objective is addressed, indicate the
main objective and state only key secondary objectives. If an a priori hypothesis was
tested, state that hypothesis.
Design: Describe the basic design of the study. State the years of the study and the
duration. of follow-up. If applicable, include the name of the study (eg, the Fra-
mingham Heart Study).
Setting: Describe the study setting to assist readers to determine the applicability of
the report to other circumstances, for example, general community, a primary care
or referral center, private or institutional practice, or ambulatory or hospitalized care.
Patients or Other participants: State the clinical disorders, important eligibility cri-
teria, and key sociodemographic features of patients. Provide the numbers of par-
ticipants and how they were selected (see below), including the number of otherwise
eligible individuals who were approached but refused. If matching. is used for
comparison groups, specify the characteristics that are matched. In follow-up
studies, indicate the pzoportion of barticiPants who completed the study. In inter-
vention studies, provide the number of patients withdrawn because of adverse
effects. For selection procedures, use these terms, if appropriate: random sample
(where random refers to a formal, randomized selection in which all eligible indi-
viduals have a fixed and usually equal chance of selection); population-based
sample; referred sample; consecutive sample; volunteer sample; convenience sample.
Intervention(s): Describe the essential features of any interventions, including their
method and dubtion of administration. Name the intervention by its most common
clinical name, and use nonproprietary drug names.
Main Outcome Measure(s): Indicate the primary study outcome measureinent(s) as
planned before data collection began. If the manuscript does not report the main
planned outcomes of a study, state this fact ant1 intlic;~icthe reason. St;~tcc1c:rrly
whether the hypothesis being tested was formulated during or after data collection.
Results: Provide and quantify the main outcomes of the study, including confidence
intervals (eg, 95%) or P values. For comparative stuclies, cxl>rcss tllc clilTcrr-nccs
between groups with confidence intervals. Explain outconics or Inc.;lsnrcmvnlx
unfamiliar to a general medical readership. Decl;~rcirnl,on:~nt ri)c.;lsrIrcslllc:r,r. n~~r
2.5 Abstract

presented in rcsultb. As rclcv.int. ~r~cllc.dtr.

\vhcther ol,x-mcrb \verc t>llndcclt o p;lticnt
groupings, particul;~rlyfor sublcitivc Incasurcmcnts. If diffcrcnccs tor thc r~l.ijorstud!.
outcome measurtt(s) are not sign~ficant,state the clinically irnlwnunt Jlffercncz
sought and provide the confidence interval for the difference between the groups.
When risk changes or effect sizes are given, indicate absolute values. ~pproaches
such as number needed to treat to achieve a unit of benefit ire encouraged when
appropriate; reporting of relative differences alone is insufficient. For studies of
screening and diagnostic tests, report sensitivity, specificity, and likelihood ratio. If
predictive value or accuracy is given, provide prevalence or pretest likelihood as well.
For all randomized controlled trials, include the results of intention-to-treat analysis,
and for all surveys include response rates.
Conclusions: Provide only conclusions of the study directly supported by the results,
taking into account the limitations (eg, observational study, selected popylation),
along with implications for clinical practice, avoiding speculation and overgener-
aiization. Indicate whether additional study is required before the information
should be used in usual clinical settings. Give equal emphasis to positive and
negative findings of equal scientific merit.
Trial Registration: For clinical trials, provide the name of the trial registry, registra-
tion number, and URL of the registry.

Structured Abstracts for Systematic Reviews (Induding Meta-analyses). in manu-

scripts reporting the results of meta-analyses, include an abstract of no more than
300 words using the following headings: Context, Objective, Data Sources, Study
Selection, Data Extraction, Data Synthesis, and Conclusions. In the text of the
manuscript, include a section describing the methods used for data sources, study
selection, data extraction, and data synthesis. Follow each heading with a brief
description:
Context: Provide a sentence or two explaining the importance of the review
question.
Objective: State the precise primary objective of the review. Indicate whether the
review emphasizes factors such as cause, diagnosis, prognosis, therapy, or preven-
tion and include information about the specific population, intervention, exposhe,
and tests or outcomes that are being reviewed.
Data Sources: Succinctly summarize data sources, mcludin~years searched. Include
in the search the most current information possible, ideally conducting the search
several months before the date of manuscript submission. Potential sources include
computerized databases and published indexes, registries, abstract booklets, con-
ference proceedings, references identified from bibliographies of pertinent articles
and books, experts or research institutions active in the field, and companies or
manufacturers of tests or agents being reviewed. If a bibliographic database is used,
state the exact indexing terms used for article retrieval, including any constraints (for
example, English language or human subjects). If abstract space does not permit this
level of detail, summarize sources in the abstract including databases and years
searched, and place the remainder of the information in the "Methods" section of
the text.
 2.5.2 Unstructured Abstracts

. Study Selection: Describe inclusion and exclusion criteria used to select studies for
detailed review from among studies identified as relevant to the topic. Under details
of selection include particular populations, interventions, outcomes,or methodo-
logical designs. Specify the method used to apply these criteria (for example,
, blinded review, consensus, multiple reviewers). State the proportion of initially
identified studies that met selection criteria.

Results:State the main results of the review, whether qualitative or quantitative, and
outline the methods used to obtain these results. For meta-analyses, state the major

erating characteristic curves, and predictive values.' For assessments of prognosis,

summarize survival characteristics and related variables. State the major identified
sources of variation between studies, including differences in treatment protocols,
co-interventions, confounders, outcome measures, length of follow-up, and dropout

Conclusions: Clearly state the conclusions and their applications (clinical or other-
wise), limiting interpretation to the domain of the review.

Structured Abstracts for 'Clinical Reviews. For Clinical Review articles, include an
abstract of no more than 250 wordswith the following sections: Context, Evidence
Acquisition, Evidence Synthesis, and Conclusions.
Context: Include 1 or 2 sentences describing the clinical question or. issue and its
importance in clinical practice or public heath.
Evidence Acquisition: ~ e s c r i b e - hdata
e sources used, including the search strate-
gies, years searched, and other sources of material, such as subsequent reference
searches of retrieved articles. Explain the methods used for quality assessment and
the inclusion of identified articles.
Results: Address the major findings of the review o f the clinical issue o r topic in :In
evidence-based, objective, and Imlanced fashion, crnph:~sizingthe highest-qu:ility
evidence available.

Unstructured Abstracts. For other major manuscripts, include a conventional un-

. structured abstract of no more than 150 words. Abstracts are not required for opin-
ion pieces, letters, and special features such as news articles. Consult the journal's
instn~ctionsfor authors for special requirements in individual publication:;.
2.7 Epigraphs

General Guidelines. A fen. specific guidelines t o consiclcr In prcp.~rinpc~rhvrtype o l

abstract follow:
Consult the joi~rnal'sinstructions for authors.
,: Follow the journal's specific sideheadings when preparing a structured abstract. ,

Do not begin the abstract by repeating the title.

:;I Do not cite references.
,! Provide absolute results for main outcome measures (eg, report incidence rates
rather than reporting only relative risks). In addition, provide confidence intervals
whcncvcr possil,lc (it' not, provitlc P values) (see 20.1, Study Design and Statistics,
The Manuscript: Presenting Study Design, Rationale, and Statistical Analysis).
;. Include n~ajorterms and describe databases and study groups (related to the .;ubject
uncler discussion) in the abstract, since the abstract can be text-searched in many
retrieval systems.
::%'Include'the stated hypothesis, if applicable.
vt Ensure that all concepts and data in the abstract are included in the text.
=; Include the active moiety of a drug at first mention (see 15.4, Nomenclature,
Drugs).
rr Avoid proprietary names or manufacturers' names unless they are essential to the
study (see 15.5, Nomenclature, Equipment, Devices, and Reagents).
% Spell out abbreviations at first mention.
a If an isotope is mentioned,.spell out the name of the element when first used and
provide the isotope number on the line (see 15.9, Nomenclature, Isotopes).
a Provide the dates of the study, or date ranges for studies and other data included
in reviews.
s Verify the numbers provided in the abstract against those provided in the text and
tables to ensure internal consistency. .

Keywords. Some medical journals publish a short list (3-10) of keywords at the end
of the abstract. These descriptors are provided by the author and are the terms the
author believes represent the key topics presented in the article. These may also be
. used for some journals to categorize manuscripts, to help guide in the selection of
peer reviewers, and to assist the journal's indexer. JAMA and the Archives Journals
do not publish keywords. Articles in JAMA and the Archives Journals are indexed by
professional indexers by means of, for example, Medical Subject Headings (MeSHj
for indexes9 such as List of Joumak Indexed for MEDLIA'E and databases such as
MEDLINE. See 13.0, Medical Indexes.

Epigraphs. Epigraphs are rarely used for research papers. On occasion an author
will use an epigraph, a short quotation set,at the beginning of a nonresearch article, .
to suggest the theme of the article. In JAMA and the Archives Journals, epigraphs are .
 2.8 Parts of a Manuscript. Headings. Subheadings, and Side Head~ngr

set in italics, beginning flush left, with the signature set in roman type untlcrneath
the quotation, flush right with the longest line of the quotation. If the \ ~ o r kcited .
appears in the reference list, a superscript number should indicate the sourcc.
.Otherwise, the title of the work should be indicated;
l%e rnedicalpmfession seems to have no place for its
mistakes. .. .And if the medical pmfession has no
room for doctors' mistakes, neither does society.
David ~ilfiker'
Gas! Gas! Quick, boys!-An ecstasy of fumbling
Fitting the clumsy helmets just in time;
But someone still wasyelling out and stumbling,
AndJoundJring like a man in fire or lime.. . .
Wilfred Owen, Dulce et Decorum Est

Parts of a Manuscript Headings, Subheadings, and Side Headings. A con-

sistent pattern of organitation for all headings should be used for original research
articles (see also 20.1, Study Design and Statistics, The Manuscript': Presenting Study
Design, Rationale, and Statistical Analysis); many scientific articles follow the IMRAD
pattern (introduction, methods, results, and discussion). However, not all articles
will conform to a single pattern because format and section headings vary with the
type of article (see 22.0, Typography).
Introduction: The introduction should provide the context for the article, the ob-
jective of the study, and should state the hypothesis or research question (purpose
statement), how and why the hypothesis was developed, and why it is important. It
should convince the expert that the authors know the subject and should fill in gaps
for the novice. It should generally not exceed 2 or 3 paragraphs.
Methods: The "Methods" section should include, as appropriate, a detailed de-
scription of (1) study design or type of analysis and dates and period'of study, as
well as mention of institutional review board or ethics committee approval (in-
formed consent; see also 5.8, Ethical and Legal considerations, Protecting Research
Participants' and Patients' Rights in Scientific Publication); (2) condition, factors, or
disease studied; (3) details of sample (eg, study participants and the setting from
which they were drawn, inclusion and exclusion criteria); (4) intervention(s), if any;
(5) outcome measures or observations; and (6) statistical analysis. Enough infor-
mation should be provided to enable an informed reader to replicate the study, or, if
a methods article has already been published, that article should I,e cited and
important points should be summarized.
Results: The results reported in the manuscript should be specific and relevant to the
research hypothesis. Characteristics of the sti~clyparticipants should be followed by
presentation of results, from the broad to the specific. The "Results" section should
not include implicxtions or weakncsscs of thc stucly, l ~ u sliould
t incluclc vsliclation
measures if conducted as part of the study. Results shoulcl not discuss the rationale
for [he statistical procedures used. Data in tables and figures should not be dupli-
cared in the text. (See 4.0. Visual Presentation of Data.)
2.8 Parts of a Manuscript, Headings, Subheadings, and Side Headings

Discussion: The "Discussion" section should be a formal consideration and critical

examination of the study. The research question or hypothesis should be addressed
in this section, and the results should be compared to and contrasted with the findings
of other studies. (Note: A lengthy reiteration of the results should be avoided.) The
study's limitations and the generalizability of the results should be discussed, as well
'
as mention of unexpected findings with suggested explanations. The type of future
studies needed, if appropriate, should be mentioned. This section should end with a
clear, concise conclusion that does not go beyond the findings of the study.JAM2 and
the Archives Journals traditionally have used "Comment" rather than "Discussion"
here, as the latter heading is often used for symposium proceedings or articles in
which a discussion follows the presentation of a paper.

Levels of Headings. A consistent style or typeface should be used for each level of
heading throughout a manuscript so that the reader may visually distinguish be-
tween primary and secondary headings.
The styles used for the various levels of headings will vary from publisher to
.publisher and publication to'publication, even within the same publishing house.
They may also vary within a single publication, from one category of article to another
(see also 22.0, Typography).
Headings are often used as navigational l i i for online articles. Consideration '
should be given to appropriate online use (eg, avoidance of excessive length and
citation of images and references within headings).

Number of Headings. There is no requisite number of headings. However, because

headings are meant to divide a primary part into secondary parts, and so on, there
should be a minimum of 2.
Headings reflect the progression of logic or the flow of thought in an article and
thereby guide the reader. Headings also help break up the copy, making the article
more attractive and easier to read. Headings may be used even in articles such as
editorials and reviews, which usually do not follow the organization described
above for research articles. (Other typographic and design elements, such as pullout
quotations, bullets [*I, enumerations, tabulations, figures, and tables, may also be
used for these purposes [see also 22.0, Typography].)

Items to Avoid in Headings

cl Avoid using a single abbreviation as a heading, even if the abbreviation has been
expanded earlier in the text. Ifthe abbreviationappears as the sole item in a heading,
spell it out. (See 14.11, Abbreviations, Clinical, Technical, and Other Common
Terns.)
a; Avoid expanding abbreviations for the first time in a heading. Spell the ab-
breviation out in the. Ileading if that is its first appearance and introduce the
abbreviation, if appropriate, at the next appearance of the term. (See 14.11, Ab-
breviations, Clinical, Technical, and Other Common Terms.)
Avoid citing figures or tables in headings. Cite them in the appropriate place ir
the test that follows the heading.
.;, Avoid citing references in headings.
 - --

2.10.2 Online Publication Ahead of Print

Addenda. Addenda may be material added to an article late in the publication

be material that is considered supplementary to the article. (Note: This
supplementary Web-only material, although addenda may sometimes
be presented as supplementary Web-only material. For that, see 2.12, Online-Only
[Supplementary) Material.) The use of addenda is discouraged in J A M and the
Archives Journals. If material is added late in the publication process, well after a
manuscript has been accepted for publication (eg, the addition of another case re-
port, extended follow-up, data or information on recent legislation or other relevant
event, or additional studies that bear on the present article), this is best handled by
incorporating lhe information into the text. If there is a compelling reason to set this
terial apart as an addendum, this may be done by adding a final paragraph to the
existing rnanuscripc:
ADDENDUM
After the manuscript was accepted for publication,. . .
'

;!. If desired, this paragraph may be set off by extra space and/or a half-column-wide
centered hairline rule. Any references cited for the first time in .this final paragraph
or addendum should follow the numbering of the existing reference list.
Note: If substantial material (eg, new figures, new tables, several additional
cases) is added after acceptance of the manuscript or if the conclusions change after
ptance, the editor must approve all such changes; additional peer review may

Acknowledgment Section. "Acknowledgments" is the blanket term used to cover

the information that follows the body of the article and precedes the references. The
"
Acknowledgment section is considered to. be a continuation of the text, so that
abbreviations expanded in the text may stand without expansion here. If a footnote
. that would normally appear on the first page of the'article (eg, the affiliation foot-
! note) is too long to be placed on the first page, it may be placed here immediately
after the acceptance date and, if applicable, the online-publication-ahead-of-print
information; if the journal does not publish acceptance dates, the affiliation footno:?
fit on the first page would be placed first in the Acknowledgment
' section. (Note: See also 2.3, Footnotes to Title Page, where some additional types of
. acknowledgment footnotes are discussed. Placement of these may vary among jour-
. nals.) Examples of various parts of the Acknowledgment section follow, in the order
i. used by J A M and the Archives Journals. (See also 5.2, Legal and Ethical Consider-
ations, Acknowledgments, Box.)

Acceptance Date. Some journals include the date of the manuscript's acceptance;
others include the date of manuscript submission, the date the revision was re-
ceived, and the date accepted. Examples are shown below:
Accepted for Publication: December 16, 2006.
Submitted for Publication: November 22, 200.4: finill revision rccci~.ctl.\1;1y
13, 2005; accepted May 23, 2005.

Online Publication Ahead of Print. If an articlc was put,ll>htul onllnc. ;\hc.;lcl of prtlll.
thedateit~as~ublishedonline, alongwith thc tIiglt.il c)hj~c.!
~clc.nrlficr(I)OI)r c r c:?wlrc.

27
2.10 Acknowledgment Section

thal all arlicle vctsions can Ile identified,should follow the acceptance date footnc
(or, if the journal tloes not publish the acceptance date, it should be placed first).
Published Online: October 20, 2005 (doi:10.1001/JAMA.294.20.joc50147).

Affiliation Notes That Would Not Fit on Page 1. Limited space on the first page of: .
article nlay sometimes not allow the author affiliation footnote to appear on the f i x
page. If the author affiliation footnote does not fit there, it would appear at the er
of the article, after the acceptance date and the online-publication-ahead-of-pril
information, if applicable.

Correspondence Address. Contact information for the corresponding author (stre1

address, if possible, with zip or postal code, and e-mail address, if the author wishe:
is provided in a footnote. Even for a single author, the full name of the person shoul . I

be included. Follow the custom of individual countries regarding the placement (:

the zip or postal code. Note: ForJAMA,this information is provided on the first page c
the print article, not in the Acknowledgment section, and the heading uSed is "Ca
responding Author."
Correspondence: John H. Alexander, MD, MS, Box 3300, Duke University
Medical Center, Durham, NC 27715 (john.h;[email protected]).
Correspondence: Patrick J. Gullane, MB, FRCS, University Health Network,
University of Toronto, 200 Elizabeth St, Suite 8N-800, Toronto, QN M5G
2C4, Canada ([email protected]).
COrrespondence: Christoph Kniestedt, MD,Department of Ophthalmology,
Cantonal Hospital Winterthur, Brauerstrasse 15,8400Winterthur, Switzerland
([email protected]).
Correspondence: Mutsuhito Kikura, MD, PhD, Department of Anesthesia
and Intensive Care, Hamamatsu Medical Center, 328 Tomizuka-cho, Ha-
mamatsu 432-8580. Japan ([email protected]).
Correspondence: N. J. Hall, MD, Department of Pediatric Surgery, Institute
of Child Health, 30 Guilford St, London WClN lEH, England (n.hall@ich
.ucl.ac.uk).
Correspondence: Jacqueline C. M. Witternan, PhD, Department of Epide-
miology and Biostatistics, Erasmus Medical Center, PO Box 1738, 3000 DR
Rotterdam, the Netherlands ([email protected]).
Correspondence: Kenneth F. C. Fearon, MD, University Department of
Surgery, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, Scot-
land.
For smaller item (eg, letters to the editor, book reviews) with signature blocks 1

rather than bylines, and where the signature block contains only the names and
degreecs) of the authods), a shortened form of address for the corresponding author
may be used: Dr Jones, Mr Thomas, etc.
, I
block: Philip Lempert, MD
Sig??uli~~~
 .... -

2.10.5 Author Contributions

Correspondence: Dr Lempert, Park View Health Care Campus, 10 Brent-

wood Dr, Suite A, Ithaca, NY 14850 ([email protected]).
In JAMA, the signature block typicilly contains the author's affiliation and e-mail
address:
Brian Budenholzer, MD
[email protected]
Group Health Cooperative
Spokane, Washington
: To break an e-mail address in print, always break before a punctuation mark so that
it is clear that the address includes the mark.
cheryl.iverson@jarna-archives
.org
cheryl.iverson@jama
-archives.org
This is especially important with hyphens and periods. There i; no need to set the
e-mail address in italics or to precede it by the word e-mail.,

Author Contributions. Editors may ask authors to describe what each author con-
tributed, and these contributions to the work may be published at the editor's dis-
cretion. (See also 5.1.1, Legal and Ethical Considerations, Authorship Responsibility.
Authorship: Definition, Criteria, Contributions, and Requirements.) An example from
the Archives of Dermatology is shown below:
'
Author Contributions: Study concept and design: Fortes, Melchi, and Abcni.
Analysis and interpretation of data: Fortes, Mastroeni, and Leffontlri..
Drafting of the manuscript: Fortes. Critical &ion of the manrrso-iptfir
important intellectual content: Mastroeni, Leffondre, Sampogtka, hlelchi,
Mazzotti, Pasquini, and Abeni. Statistical a n a l ' : Fortes and Mastoeni.
Obtained funding: Pasquini and Abeni. Study supvision: Fortes, Melchi.
and Abeni.
JAMA and some of the Archives Journals require authors of manuscripts reporting
original research and meta-analyses to provide an access to data statement (see 5.1.1,
Legal and Ethical Considerations,Authorship Responsibility, Authorship: Definition,
Criteria, Contributions, and Requirements). If such a statement is provided, it is given
under the sid6head "Author Contributions," before the other contributions.
Author Contributions: Dr Stolzenberg-Solomon had full access to all of the
data in the study and takes responsibility for the integrity of the data ancl the
accuracy of the data analysis.
Some journals require that at least 1 author serve ;IS "gi~;rr;rntor."tzrking "responsi-
bility for the integrity of the work as a whole, from inception to puhliihrtl :~nicle.
and publish that information."*
Author Contributions: Yoon Kong Loke clc\.c.lopcclrhc c >r~qn.rl rlic
~tl~..r; ~ n d
protocol, abstracted and analyzed data, wrote rhc rn;llltlw-rtpr .II;~!
, I $ Ku:tr.

antor. Deirdre Price and Sheena Derry c.onrril,~trrdr o rllc Jt.\c.lo[~t~~c.n~ of

as
 !!I<- ;:rt ,:, h r 11. ;~l)<r.~\I<.\!~1.1t.i. -111~1I ~ T c ~ ; Itht'
~ c .manuscript.
~ Jeffrey K. Aror
WJII ,!c.\ (.I#ljwd 1 1 j ~~r > l ' % ( > ~
I rld llclpcd \virh the manuscript.

List of Participants in a Group Study. If the study was by a group of persons,

n.lmcs c ~ tl~c
t p.rnlclpants may be listed in the Acknowledgment section (see . .
2 3.3. Footnotes to Title Page, Author Affiliations). Alternatively, the list of pa
i~xlntsmil!. Ilc p1:lcc.d in a hox wherever it best fits in the layout, or the reader car
wl'e~-rcclto .I pre\,~ously published list of the group's members. See also 5.2.2, Eth
:und Legill Considerations. Acknowledgments, Group and CollaborativeAuthor Li:

Financial Disclosure. ./AMA and the Archiues Journals require each author to :
:~nclsilll~lli~IIIC li)l!i)wing financi:il disclosure statement: "I certify that all my at
:itions \vith or financial involvement within the past 5 years and foreseeable fut
(eg, employment, consultancies, honoraria, stock ownership or options, expert :
timony, grants or pdtents received or pending, royalties) with any organizatio~l
entity wit11 a financial interest in or financial conflict with the subject matter
materials discussed in the manuscript are completely disclosed."' (See also !
Legal and Ethical Considerations, Conflicts of Interest.)
Authors are expected to provide detailed information about any relevant
nancial interests or financial conflicts within the past 5 years and for the foreseed
future, particularly those present at the time the research was conducted and UF
the time of publication, as well as other financial interests, such as relevant filed
pending patents or patent applications in preparation, that represent potential fun
financial gain. Although many universities and other institutions and organizatic
have established policies and thresholds for reporting financial interests and otl
conflicts of interest,JAMA and the ArchivesJournalsrequire complete disclosure of
relevant financial relationshipsand potential financial conflicts of interest, regard11
of amount or value. If authors are uncertain about what might constitute a potenl
financial conflict of interest, they should err on the side of full disclosure and shol
contact the editorial office if they have questions or concerns. In addition, authc
who have no relevant financial interests are asked to provide a statement indicati
that they have no financial interests related to the material in the manuscript.
For some joumls, financial information is for the editorial offi~ea
is not shared with peer reviewers. Other journals, such asJAMA and the Archives
Dermatology, require authors to include all such disclosures on the title page or
the Acknowledgment section of the manuscript, or both, and Bese are shown
peel- reviewers. However, for all accepted manuscripts, each author's disclosures
relevant financial interests or declarations of no relevant financial interests shou
be published. Decisions about whether financial information provided by authc
should he published, and thereby disclosed to readers, are usually straightforwar
Although editors are willing to discuss disclosure of specific financial informatic
with authors, the policy of jAMA and the Archives Journals is one of full disclosu
of all relevant financial interests.
The policy requiring disclosure of financial conflicts of interest should apply B
all manuscript sul~mlssions,including letters to the editor, opinion pieces, inform
essays, ancl I~ookrc.\,iews.
Financial Disclosures: Dr Morrow reported having received research grant
:~drnini~terecI
SLIP~>OII vi:l Brigham and \vomen2s Hospital from Bayer
 Healthcare Diagnostics, -Beckman Coulter, Biosite; Dade Behring, Merck,
and Roche Diagnostics; and having received honoraria for educational pre-
sentations from Bayer Healthcare Diagnostics, Beckman Coulter, and Ilade
Behring. Dr de Lemos reported receiving research grants and honoraria and
consulting fees for speaking from Biosite and Roche. Dr Blazing reported
receiving honoraria from Merck and Pfizer.
F i c i a l Disclosure: Dr Neuzil reported receiving research funding from
MedImrnune for participation in a multicenter trial of an LAIV in 2004-2005.
Financial Disclosure: Dr Smith reported serving as an expert witness for
plainms in US tobacco litigation.
Note:The financial disclosuie may be a disclosure of no potential financial conflicts
of interest. This is not obligatory, and the choice not to include such a statement
should not be misinterpreted as an indication of a conflict. However, the inclusion
of a statement like that below removes iny ambiguity.
Financial Dixlosuff: None reported.

1 FundinglSuppohJMand the Anhives Journals require each author to provide

detailed information regarding all financial,and material support for the research
and work, including but not limited to grant support, funding sources, and provi-
sion of equipment and supplies. This is outlined in the journals' instructions for
authors.
All financial and material support for the research and the work should be
clearly and completely identified in the Acknowledgment section. Grant or contract
numbers should be included whenever possible. The complete name of the funding
institution or agency should be given.
If individual authors .were the recipients of funds, their names should be listed
parenthetically.
Funding/Support: This study was supported in part by grant CA34988 from
the National Institutes of Health and by a teaching and research scholarship
from the American College of Physicians (Dr Fischl).
~unding/Support:This study was supported by a 2000 Special Projects Award
of the Ambulatory Pediatric Association (Dr Hickson).
~unding/Support:This work was supported by research grant R01 MH45757
from the National Institute of Mental Health (Dr Klein).
Funding/Support: Funding for this study was provided by Agency for
Healthcare Research and Quality grant 5 U18 HS011885 and through
subcontracts with the Utah Department of Health (contract 026429) and
the Missouri Department of Health and Senior Services (contract AOC
02380132).
Funding/Support: This study was supported by Merck and Co and Bayer
Healthcare Diagnostics Division.
FundinglSupport: Alefacept was provided to the patients at no cost through .
a Biogen Idec patient assistance program.
2.10 Acknowledgment Sectlor1

Role of the Sponsor. .i'hc bpecific. r c k 01 rt~r-lundlng org.irllr-lrlc,n o r sponsor in

each oi rhc. follo\\.~ngsliould tx. spcificd. Jcslgn and conduct o f thc study; col1c.c-
tion, nianagtrmcnt, and analysis of the data; and preparation, review, and approval
of the manuscript. For articles that do not include original research, "design and
conduct of the study" is omitted.
Role of the Sponsor: The funding organizations are public institutions and
had no role in the design and conduct of the study; collection, management,
and analysis of the data; or preparation, review, and approval of the manu-
script. The Utah and Missouri health departments provided practical support
for the focus group and survey processes, including letters of endorsement,
hospit~lcontact information, and assistance with logistic arrangements for
focus group sessions.
Role of the Sponsor: Staff from Merck assisid in 'monitoring the progress
and conduct of the A to Z trial. Bayer Healthcare provided reagents for
B-type natriuretic peptide testing. The sponsors were not involved in the -
biomarker testing, analysis, or interpretation of the data, or in preparation of
the manuscript for this substudy. Medical specialists employed by the spon- -
sors reviewed the manuscript prior to submission.

Independent Statistical Analysis. For industry-sponsored studies in which the stati-

stical analysis was conducted only by statisticians employed by the sponsor, some
journals, such asJ A M and several of the Arcbiues Journals, require that data analysis
be conducted by an independent statistician at an academic institution. If issues J
regarding the analysis should emerge, the academic institution provides an additional
level of oversight independent of the commercial sponsor. This independent analysis
should be conducted using the raw data set, and the results of that analysis should be
the findings that are published in the manuscript. Some journals, such as J A M ,
specify whether compensation was received for conducting the independent statis-
tical analysis. (See also 5.5.5, Legal and Ethical Considerations, Conflicts of Interest,
I
Requirements for Reporting Industry-Sponsored Studies, and Fontanarosa et al.lO)
Independent Statistical Analysis: Independent statistical review of the data .
included in this analysis was performed by Stuart Pocock, PhD, and Duolao
Wang, both of the London School of Hygiene and Tropical Medicine.
.Independent Statistical Analysis: The accuracy of the data analysis was in-
dependently verified by Yingbo Na, MSc, and Martin Fahy, MSc, both from
the Cardiovascular Research Foundation, an affiliate of Columbia Univer-
sity, who received the entire raw database and replicated all the analyses
that were reported in the accepted manuscript. No discrepancies were
discovered. Neither Mr Na nor Mr Fahy nor the Cardiovascular Research
Foundation received any funding for this independent statistical analysis.
Independent Statistical Analysis: All study data were transferred from Sanofi-
Aventis to the Department of Medicine at St Luke's-Roosevelt Hospital
Center for independent analysis by Stanley Heshka, PhD. Statistical reanal-
ysis of the raw data was performed by Dr Heshka. There were no dis-
crepancies between the reanalysis and the original 'interpretation of the
results and conclusions. In lieu of financial compensation for Dr Heshka's
 2.10.1 1 Disclaimer

time and effort in performing the statistical analysis, an unrestricted edu-

cational grant from Sanofi-Aventis was given to the Obesity Research Center
at St Luke'sRoosevelt Hospital Center, New York, New York.
Independent Statistical Analysis: Christopher E. Minder, PhD, professor of
medical statistics at the University of Bern, Bern, Switzerland, and Peter
Jiini, MD,senior lecturer in clinical epidemiology at the University of Bern,
.received a complete copy of the raw data from Cordis Corporation and
performed an independent statistical analysis. They received no compen-
sation for this work and had no conflicts of interest, not receiving any type
of payment, equity, or reimbursement from' either of the companies
manufacturing the stents compared in the trial. They confirmed that they
were able to replicate the analyses of the primary abgiographic and sec-
ondary clinical outcomes reported in the manuscript and that they consider
the analyses to be appropriate. . .

Independent Statistical Analysis: All study data .were transferred from

Hoffman-La Roche to the Department of Statistics at the British Columbia
Children's Hospital for independent reanalysis. Statistical reanalyses of the
raw data were performed by Ruth Milner and Victor M. Espinosa, MSc. There
were only minor diiepanaes between the reanalysis and the original in-
terpretation of the results and conclusions. When there was a discrepancy,
Dr Chanoine included the results. from the reanalyses performed at the
British Columbia Children's Hospital.

Disclaimer. A footnote of disclaimer is used to separate the views of the authors from
those of employers, finding agencies, organizations, or others. Editors should gen-
erally retain the author's phrasiig, especially if such phrasing is required by policy
of the entity mentioned.
Disclaimer. The views expressed herein are those of the authors and do not
necessarily reflect the views of the US Army or the Department of Defense.
Disclaimer: The opinions expressed herein are only those of the authors.
They do not represent the official views of the government of India, St
Michael's Hospital, University of Toronto, or the study sponsors.
Disclaimer: Use of trade names or names of commercial sources is for
information only and does not imply endorsement by the US Public Health
Service or the US Department of Health and Human Services.
Disclaimer: Opinions in this article should not be interpreted as the official
position of the International Committee of the Red Cross.
Disclaimer: The opinions expressed herein :Ire those o f the authors and do
not necessarily reflect the views of the Indian I-lealth Service.
ol' rlic
If the byline of a manuscript incli~destlie editor ol' rlic journal, ;I ~ncrnl~cr
editorial board of the journal, or a member of the editorial staff of the publication,
the following type of disclaimer is useful.
R,.linr?; Mehmet K. Aktas, MD; Volkan Ozduran, MD; Claire E. Pothier,
MPH; Richard Lang, MD, MPH; Michael S. lauer, MD
2.10 Acknowledgment Section

Disclaimer: Dr buer, a j M contributing editor, was not involved in the

editorial evaluation or decision to publish this article.

Previous Presentations. The following formats are used for material that has been
read or exhibited at a professional meeting. The original spelling and capitalization
of the meeting mume should be retained. Provide the exact date and location of the
lllcbc!ing.
IJrevious IJrc.sentation:The results of this study were presented at the British
Association of Dermatologists Annual Meeting; July 8, 2004; Glasgow,
Scotland.
Previous I'resentation: This study was presented in part at the European
Congress ,of Epidemiology; September 10, 2004; Porto, Portugal.
Previous Presentations: This study was presented in part at the American
Society of Nephrology 35th Annual Meeting; November 1-4, 2002; Phila-
ddphia, l'ennsylvania; and.at the American Transplant Congress; May 13-
19, 2004; Boston, Massachusetts.

Additional Information (Miscellaneous Acknowledgments). Occasionally, other

types of announcements are listed in the Acknowledgment section. However, p.er-
mission or credit for reproduction of a figure or a table, even if modified, should be
given in the figure legend or the table footnote, not in the Acknowledgment section.
See 4.0, Visual Presentation of Data. Notice of supplemental Web-only material may
also be given under this sidehead, as well as in the text.
Additional Information: This is report 54 in a series on chronic disease in
former college students.
Additional Information: This article has been reviewed by the Publications
Committee of the Collaborative Study of Depression and has its endorse:
ment.
Additional Information: This article is dedicated to the memory of my
mentor, friend, and father, Clifford C. Lardinois Sr, MD.
Additional Information: A complete list of documents surveyed is available
on request frzm the author.
Additional Information: The original data k t is available from the New York
State Department of Health, Albany.
Additional Information: The P sojae and P ramorum whole-genome shot-
gun projects have been deposited at DDBJ/EMBL/Genbank under the
project accessions AAQYOOOOOOOO and AAQX00000000, respectively.
Additional Information: These documents are also available online (http:/I
www.library.ucsf.edu/tobacco).
Additional Information: Additional studies are available from the UK Coch-
rane Centre, NHS R&D Programme, Summertown Pavillion, Middleway,
Oxford OX2 7LG, England ([email protected]).
 2.10.14 Additional Contributions

Additional Information: eTables 1 and 2 are available at http://www.jama

.corn.
Additional Information: -The eFigure is available at http://www
.archinternmed.com. .
Additional Information: This article is the first of a Ipart series. The second
part will appear next month.

Additional Contributions. Acknowledgment of other contributions and fonns of

assistance (eg, statistical review, preparation of the report, performance of special
tests or research, editorial or writing assistance, or clerical assistance) also should be
included. When individuak are named, their given names and highest academic
degrees (see 2.2.3, Bylines and End-of-Text Signatures,Degrees) are listed, and some
publications, such asJAMA, also list their affiliations, if appropriate, and whether they
received compensation for their assistance. For any individual named as providing
additional contributions, the author should obtain written permission from that per-
son indicating his or her authorization to be so named (see 5.2.1, Ethical and Legal
Considerations, Acknowledgments, Acknowledging Support, Assist:~nce. :mtl Con-
tributions of Those Who Are Not Authors, and 5.2.8, Acknowledgments. l'criiiission
to Name Individuals).
Additional Contributions: Robert C. Della Rocca, MD, performed the I~iopsy.
contributed the orbital computed tomographic scan, and provided the es-
enteration speciinen; Ramon Font, MD, confirmed the histopathologic di-
agnosis.
Additional Contributions: John Hewett, PhD, and Jane Johnson, MA, pro-
vided statistical support.
Additional Contributions: The photographs that constitute Figure 1 wcrc
provided by Hans-Peter M. Freihofer, MD, Department of ~axill6facialSur-
gery, University Hospital of Nijmnegen, Nijn~egen,the Netherlands.
Additional Contributions: The Branch Retinal Vein Occlusion Study Group
is grateful for the contributions of the many referring ophthalmologists,
without whom this study could not have been carried out, and to the sti~cly
patients, whose faithfulness to the study led to conclusions that promise
hope for others with branch vein occlusion.
JM and, some of the Archives Journals require authors to'clisclose any sull-
stantial writing and editing assistance and to recognize those persons responsible
for such assistance. (JAMA also notes whether compensation was recei\wcl for such
assistance.) This information should be included in the Acknowledgment section,
and permission to be identified should be oht;~incclfrom :ill named individuals (see
5.2.1, Ethical and Legal Consirlcr;~~ions, Ackno\\~lc~tlg~~~c~its,
Acknowlcrlging Sup-
port, Assistance, and Contributions of Tho.* \r:ht) Arc Not Airtl~ors).In such cases,
institutional affiliations m?ybc inclutlcd:
Additional Contributions: Wil11:lm \\'Iw*. I ' 1 1 1 ~ . I)yn:~l,l~:~r~ii In<..conrril>r~rc.tl
10 rhc writing of this ;~nicle:;~ntlS;rr;tl~.l,.\v~l. 51 ,I. blc.tlic.;~l \V'rilc+rs Corp.
hrlp<i CKIII !lie I I I I I I : ~ nl:Inuwrq>t
2.12 Online-Only (Supplementary) Material

hclditional Contributions: Cheryl Christensen assisted with manuscript prep-

;lr;~tionancl Stephen Ordway, ELS, provided editorial assistance.
Additional Contributions: We thank Petra Macaskill, PhD (School of Public
Health, Sydney, Australia), for her comments on an earlier draft and sug-
gestions for its improvernent. Dr Macaskill did not receive any compensation.
Adclitional Contributions: Lucia Taddio, BA, Erwin Darra, and Omar Parvez
(311 fro111 The Hospital for Sick Children) provided assistance with data
collection. Ms Tscldio and Mr Darra received compensation from the study
sponsor.
Additional Contributions: We thank Charlotte Gerczak, MLA, for her edi-
torial input and Keita Ebisu, MS, for his aid in collecting the particulate
matter data. Neither Ms Gerczak nor Mr Ebisu received any financial com-
pensation for their work.

Preferred Citation Format. Some journals may choose to list a preferred citation
format for articles to ensure correct citation. Some &y use this only for references
for which citation problems or questions are likely to arise (eg, manuscripts with
group authors). Although this is not used for any articles published inJAMA and the
Archives Journals, the format is suggested below. (See also 2.2.1, Bylines and End-
of-Text Signatures, Authors' Names, and 2.2.4, Bylines and End-of-Text Signatures, .
Multiple Authors, Group Authors.)
Preferred Citation Format: Gould PA, Krahn AD; for the Canadian Heart
Rhythm Society Working Group on Device Advisors. Complications asso-
ciated with implantable cardioverter-defibrillator replacement in response
to device advisories.J A M . 2OO6;295(16):1N7-1911.

Appendixes. Some journals publish appendixes, at least occasionally, for material

that might be considered ancillary to the content of the article itself (eg, derivation of
a complex formula used in the article, a survey instrument used in a study, statistical
modeling details). J A M and the Archives Journals generally d o not use appendixes.
If these are worthy of publication because they contain important information, they
could be considered for online-only publication (see 2.12, Online-Only [Supple-
mentary] Material). On rare occasions, however, they serve a useful purpose for data
that cannot easiiy be presented as a table or a figure and are too central to the article
to be deposited elsewhere. In these cases, appendixes are cited in the text as a table
or figure would be cited (eg, Appendix 1) and are usually placed at the end of the
article, before the references. If the appendix cites references, the references would
be numbered consecutively, following the last reference number in the text, and
included in the articlels.reference list.
Information contained in appendixes is published under the imprimatur of the
journal and therefore should undergo editorial evaluation and peer review and
should receive the same attention to detail in the editorial and production processes
as the main body of the article.

Online-Only (Supplementary) Material. Publishing online-only material permits

inclusion of :ludio :~ntl\.itlco c.on1p)ncnt.s. In addition, to conserve use of budgeted
 2.12 Online-Only (Supplementary) Material

- - -

Table. Manuscript Checklist Adapted From JAMA's Instructions for Authors

0 1. Review manuxript submission instructions on our Web-based submission and review system
(htQrJ1manuxripts.jama.com).
0 2. lnclude a cover letter as an attachment.
3. Designate a corresponding author and provide a complete postaVmail address, telephone and fax
numbers, and email address.
0 4. Provide first and last names, degrees, e-mail addresses, and institutional affiliations for any coauthors.
0 5. On the title page, include a word count for text only, exclusive of title, abstract, references. tables,
and figure legends.
6. Provide an abstract that Conforms to the required abstract format.
O 7. Double-space manuscript and leave right margins unjustified (ragged).
8. Check all referencesfor accuracy and completeness. Put references in proper format in numerical order.
making sure each is cited in sequence in the text.
0 9. Includea title for each table-andfigure (a brief, succinct phrase. preferably no longer than 10-15 words)
and explanatory legend as needed.
10. Have each author read, complete, and sign the Authorship Form with statements of authorship
responsibility, criteria, and contributions; financial disclosure; and cobyright transfer. After submis-
sion, add the manuscript number to the top of each author form and send in the author forms by mail
or fax to the editorial office.
11. Indicate specific contributions from each author (see authorship checklist on Authorship Form).
1 2 lnclude statement signed by corresponding author that written permission has been obtained from all
persons named in the Acknowledgment.
0 13. For reports of original data, indude statement from at least 1 author that she or he "had full access
to all of the data in the study and takes responsibility for the integrity of the data and the accuracy
of the data analysis."
14. lnclude research or p r o j e supportlfunding in the Acknowledgment.
15. Also in the Acknowledgment, specify the role of the funded9 or sponsoris) in each of the following:
design and conduct of the study; collection. management, analysis. and interpretation of the data;
-and preparation, review, or approval of the manuscript.
16. lnclude written permission from each individual identified as a source for personal communication or
unpublished data.
17. If appropriate, include information on institutional review boardlethics committee.approvalor waiver
and informed consent.
18. Reprinted tables and figures are discouraged. Original material should be provided, except under
extraordinary circumstances.
0 19. Includeinformedconsentformsfor identifiable patient descriptions, photographs, videos, and pedigrees.
20. For clinical trials, add the clinical trial identification number and the URL of the registration site.

print pages and yet allow interested readers access t o supplementary rnaterial (cg,
additional tables, figures, or references, derivation of complex equations. appendixes,
detailed description of methods, large amounts of relevant but detailed data), some
journals may publish Web-only material to supplement the material that appears in
print. In the print article, such items should Ix. crrllrrl o u t by cTablc 1. ctc, and a note
to indicate how to access this supplementary mdrerial should be published:
 l . t.l'.~l,lc 1.4 available at http://archderm.ama
. : d d ~ ~ ~ c , r1 i1 1~I*l, r l ~ ~ ~ t i t ) 1r11c
-,I,.II ~ I I X c X I L ~ ~ I I I C I I1 I~ 1, 1 1 ; I 11/12/ 1501/l)CM50003ETl.

Additional Iniorn~ation:A computer simulation of a 3-year-old child falling

do\\.n the stair:; is available at http://archpedia.ama-assn.org/cgi/content
/full/ 155/9/100H.
Additional Information: Supporting online material, including the "Methods"
section, the I-rkrcnccs, and Figures S1 through S6, is available at http://
sciencc.m:1g.org/cgi/content/full/l122771/DC1.
Whcncvcr possil>lc, 111c csi~ctIJIZI. of the supplementary material should be pro-
vided to help the reader more easily find the content. The Web version of the article
links directly to the online supplementary material.
Alternatively, such additional material may b e made available at the author's
Web site; however, because URLs change frequently, the first option is preferable.
It is the policy of J A M and the Archiws Journals that online-only material is
published under the imprimatur of the journal and s o should undergo editorial
evaluation and should receive the same attention to detail in the editorial and
production processes as if it were to be published in the print journal.

ACKNOWLEDGMENT
Principal author: Cheryl Iverson, MA

REFERENCES
1. J A M instructions for authors. http://jama.ama-assn.org/if~ra~current.dtl.
Accessed
I)ece~nhcr29, 7,005.
2. International Committee of Medical Journal Editors. Uniform Requirements for Manu-
scripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publi-
cation. hctp://www.icmje.org. Updated February 2006. Accessed June 15, 2006.
3. Sun X-L,Zhou J. English versions of Chinese authors' names in biomedical journals:
observations and recommendations. Sci Editor. 2002;25(1):3-4.
4. Black B. Indexing the names of authors from Spanish- and Portuguese-speaking
countries. Sci Editor. 2003;26(4):11&121.
5. The ChicagoManual of Style: l%eEssential ~ u ifor h Writm, JUitos, and Publishers.
15th ed. Chicago, IL: University of Chicago Press; 2003:778-782.
6. National Library of Medicine. List ofjoumals Indexed for MEDLINE. Bethesda, MD:
National Library of Medicine; 2005.
7. Pitkin RM, Brdnagan MA. Can the accuracy of abstracts be improved by providing
5pecific instructions? a randomized controlled trial. J A M . 1338;280(3):267-269.
8. Hayncs RB, Mulrow CD, Huth EJ, Altman DG, Gardner MJ. More informative abstracts
revisited. Ann I~itertzMed. 1990;113(1):69-76.
9. hleSH home page. http://~.nlm.nih.gov/mesh/meshhome.htm1. Accessed March
20, 2006.
10. Fonr:m;~ros;~ 1'13, Fl;~n;rginA, DcAngclis CD. Reporting conflicts of interest, financial
:tspccrs of rararcll, and role 'of sponsors in funded studies. J A M . 2005;294(1):
110-111.
:
References

3.1 3.12
Reference Style and the Uniform Requirements References to Print Books
3.12.1 Complete Data
33 3.12.2 Reference to an Entire Book
Reference Ust 3.12.3 References to Monographs
3.12.4 Reference t o a Chapter in a Book
3.3 3.12.5 Editors and Translators
References Given In Text 3.12.6 Volume Number
3.12.7 Edition Number
3.4 3.12.8 Place of Publication
Minimum Acceptable Data for References 3.12.9 Publishers
3.12.10 Year of Publication
3.12.1 1 Page Numbers or Chapter Number
Numbering
3.13
3.6 Special print Materials
Citation 3.13.1 Newspapers
3.13.2 Government or Agency Bulletins
3.7 3.13.3 Serial Publications
Authors 3.13.4 Theses and Dissertations
3.13.5 Special Collections
3.8 3.13.6 Package Inserts
Prefixes and Partides 3.13.7 Patents
3.13.8 UnpublishedMaterial
3.9 3.13.9 Personal Communications
r i ~ 3.13.10 Secondary Citations and Quotations
3.9.1 English-language Titles (Including Press Releases)
3.9.2 Non-English-LanguageTitles 3.13.1 1 Classical References
3.9.3 Names of Organisms
3.9.4 Non-English Words and Phrases 3.14
Other Media
3.10 3.14.1 Audiotapes, Videotapes, DVDs (Digital
Subtitles Video Disks)
3.14.2 Transcript of Television or Radio Broadcast
3.11
References t o Print Journals 3.15
3.1 1.1 Complete Data Electronic References
3.11.2 Names of Journals 3.15.1 Online Journals
3.11.3. Page Numbers and Dates 3.15.2 Books and Books on CD-ROM
3.11.4 Discontinuous Pagination 3.15.3 Web Sites
3.11.5 Journajs Without Volume or 3.15.4 Online Newspapers
lssue Numbers 3.15.5 Government/Organization Reports
3.1 1.6 Parts of an lssue 3.15.6 Software
3.1 1.7 Special or Theme lssue 3.15.7 Software Manual or Guide
3.1 1.8 Supplements 3.15.8 Databases
3.1 1.9 Abstracts and Other Material 3.15.9 E-mail and E-mail List (Listserve) Messages
Taken From Another Source 3.15.10 Online Conference
3.1 1.10 Special Department Feature, Proceedings/Presentations
or Column of a Journal 3.15.1 1 News Releases and Miscellaneous
3.11.11 Other Material Without Named 3.15.12 Legal References .
Author(s) or With Named Authors
and a Group Name 3.16
3.1 1.12 Discussants US Legal References
3.1 1.13 Corrections 3.16.1 Method of Citation
3.1 1.14 Retractions 3.16.2 ClJation of Cases
3.1 1.15 Duplicate Publication 3.16.3 Legislative Materials
 . v n c 3 I I , I . I~ ~L I S I IW>-I(
I < c . t r . r c . ~ ~t..
c U I I ~ .AL A I I ~ Icdg~i~cn[,
K L I I I I C ~ I I . ~III. ) ~ and di-
rr.~
1 1 1 1 ~o rI~nktng111v rc..~clcr 11, ;r~ltltrtonslrc.u)urcc, . A u ~ l ~ c , r .m;iy \ CIIC ;L reference to
hi~lyxrtrl~c.iro \ v n ;Il.girtiic.nr>1,s 1;1). rlic t'ouncl;rl~onl o r tllcir 111c.x~ (clocumentation);
;IS :I c.scrlit to rhc \\.ark o f other ;iuthors (ackno\vledgment); or to direct the reader to
more clctail or additional resources (directing or linking).
I(cfcrences :Ire 3 critic;rI element of a nunuscript and, as such, the reference list
clcm:lnds close scn~tinyby authors, editors, peer reviewers, manuscript editors, and
proofreaders. ~urhorsIxar primary responsibility for all reference citations. Editors
;tncl peer reviewers sh4uld esamine manuscript references for completeness, accu-
CLC)., :ind rele\ance. Manuscript editors and proofreaders are responsible for assess-
ing rhc completeness of references, for ensuring that references are presented in
proper style and format, and for checking to make sure that any reference links are
i~ccurateand functional.
Much has been written about problems with bibliographic inaccuracies1(eg, an
author's name is misspelled; the journal name is incorrect; the year of publication or .
the volume, issue, or page numbers are incorrect). Such errors make it difficult to
retrievethe documents cited. An even more serious problem is inappropriate citation
(eg, a speculative commentary is cited in a way that implies proved causality; an
article's results are generalized beyond what the data support). Not only is accuracy
critical for the integrity of the individual document, but because authors may some-
times rely on secondary rather than primary sources, an inaccurate citation in a
document's reference list may be'replicated in subsequent articles whose authors d o
not consult the primary source. Authors should always consult the primary source
and should never cite a reference that they themselves have not read.*" (See also
3.1 1.9, Abstracts and Other Material Taken From Another Source, and 3.13.10, Sec-
ondary Citations and Quotations [Including Press Releases].)

-Reference Style and the Uniform Requirements. For greater uniformity in

"technical requirements for manuscripts submitted to their journals," the Interna-
tional Committee of Medical Journal Editors, meeting in 1978 in Vancouver, British
Columbia, Canada, developed the Uniform Requirements for Manuscripts Submitted
to Biomedical ~ournals.' Suggested formats for bibliographic style, developed for
uniformity by the US National Library of Medicine (NLM), are included in that doc-
ument, which has been revised and updated several times. Editors of approximately
500 journals have agreed to receive manuscripts prepared in accordance with this
uniform style. Although Uniform Requirements is intended aid authors in the
preparation of their manuscripts for publication, not to dictate publication style to
journal editors, many journals have used them for developingtheir publication style.'
Formatting of references that adhere exactly to the Uniform Requirements will be
acceptable without challenge ili manuscripts submitted to J A M and the Archives
Journals, and any necessary formatting changes will be made by the JAMA and Ar-
chives manuscript editors.
The reference style followed by JAMA and the ArchivesJournals is also based on
recommendations of the NLM described in the National Libraty of Medicine Re-
commended Formatsfor Bibliographic Citation (hereinafter referred to as NLM Re-
cotnrnended ~ o r m a t s ) Both
. ~ the Uniform Requirements and JAMA/Archives style ,

represent modifications of the NLM style but follow the general principles outlined in
the NLM document. Whatever reference style is followed, consistency throughout
the document and throughout the publication (journal, book, Web site) is critical.
 3.3 References Given in Text

Each reference is divided with periods into bibliographic groups. (See 3.4,
M i m u m Acceptable Data for References, for an illustration of these for the prin-
cipal types of references.) The period serves as a field delimiter, making each bib-
liographic group distinct and establishing a sequence of bibliographic el-~ m e n t in
s a
reference. Bibliographic elements are the items within a bibliographic group. Bib-
liographic elements may be separated by the following punctuation marks:
w A comma: if the items are subelements of a bibliographic element or a set of
closely related elements (eg, the authors' names in the reference list)
A semicolon: if the elements in the bibliographic group are different (eg, between
the publisher's name and the copyright year) or if there are multiple occurrences
of logically related elements within a group; also, before volume identification
data
w A colon: before the publisher's name, between the title and the subtitle, and after
a connective phrase (eg, "In," "Presented at'')

Reference List. Reference to information that is retrievable is appropriately made in

the reference list. This includes but is not limited to articles published or accepted for
publication in scholarly or mass-circulation print or electronic journals, magazines, or
newspapers; books that have been published or accepted for publication; papers
presented at professional meetings; abstracts; theses; CD-ROMs, films, videotapes,
and audiofiles, package inserts or a manufacturer's documentation; monographs;
official reports, databases and Web sites; Iegal cases; patents; and news releases.
References should be listed in numerical order at the end of the manuscript
(except as specified in 3.3, References Given in Text, and 3.5, Numbering). T\vo
references should not be combined under a single reference number.
References to material not yet accepted for publication or to personal commu-
nications (oral, written, and electronic) are not acceptable as listed references nnrl
instead should be included parenthetically in the text (see 3.3, References Given in
Text; 3.15, Electronic References; and 3.13.8, Special Print Materials, Unpublisherl
Material).

References Given in Text. Parenthetical citation in the text of references that mccr
the criteria for inclusion in a reference list should be restricted to circunistances in
which reference lists would not be used, such as news :~rticlcsor ol~itti:~ries. Notc tli:tt
in the text (1) the author(s) may not IIe nvnctl, ( 2 ) tlic ~itlcinay 1101 Oc given. ( 3 ) tl~c
name of the journal is abbreviated only when enclosed in parentheses, and (4) inclu-
sive page numberi are given. Some resources, such as Web URLs, may be listecl in tlie
text when it is the Web site itself that is rcfcrrcd 10 I : I I ~ ItIi:ln
~ ~ conccnl o n tlic hitc.

Wiese et al recently reported that an extract from the fruit of the prickly pe:lr
cactus had a moderate effect on reducing the syinptoms of tlie alcohol hang-
over (Arch Intml Mcd. 2004;16/r[121:133/i-l.3/iO).
The effect of an extract from the fruit of the prickly pear cactus o n rctlucing
the symptoms of the alcohol hangover was reportecl in a recent issue of At--
chives of ~ntemalMedicine (2004;164[12]:1334-1340).
The Archives of Internal Medicine article (2004;1641 121:1334-1340) o n
the effects of an extract of the fruit of the prickly pear C;IC~LISo n rctlucing

41
3.6 Citation

> ~ I I I ~ I I O I01'I I [SI I C ; ~ l ~ o l1~111go\~cr

~ol reccivcil \vidcsprc:~d~ L I ~ ) I:!
I I Ct rg. .).-I
Today. June 29, 2004:7D).
Physicians may wish to consult the NIH Clinical Trials Kcgistry (Imp l j
c1inicaltrials.gov).

Minimum Acceptable Data for References. To be acceptable, a reference to

journals or 1kc)ks or Wcl, sites must include certain minimum data. The information
varies slightly for journals and books online and journals and books in print. For all of
these forms, please consult the specific section in this chapter devoted to that form
for more complete requirements. The summary below represents only a skeleton for
quick reference.
Journals:
Print: Author(s). Article title. Joumai Name.Year;vol(issue No.):
inclusive pages. .

Online: - Authors(s). Article title. Journal Name. Year;vol(issue No.):

inclusive pages. URL. Accessed [date].

Print: Authods). Book Title. Edition number (if it is the second edition
or above). City, State (or Country) of publisher: Publisher's name;
copyright year.
Online: Authorcs). Book Title. Edition number Ci it is the second edition
or above). City, State (or Country) of publisher: Publisher's name;
copyright year. URL. Accessed [datel.
Web Site: Author (or, if no author is available, the name of the organization
responsible for the site). Title (or, if no title is available, the name of
the organization responsible for the site). Name of the W e b site.
URL.Accessed [datel.
Enough information to identify and retrieve the material should be provided. More
complete data (see 3.11.1, References to Print Journals, Complete Data; 3.12.1,
References to Print Books, Complete Data; 3.15, Electronic References; And 3.13.8,
Special Print Materials, Unpublished Material) should be used when available.

Numbering. References should be numbered consecutively with arabic numerals

in the order in which they are dted in the text. Unnumbered references, in the form
of a resource or reading list, are rarely used in JAlMA and the Archives Journals. When
they are used, these references appear alphabetically, by the first author's last name,
in a list separate from the specifically cited reference list.

Citation. Each reference should be cited in the text, tables, or figures in consecu-
tive numerical order by means of superscript arabic numerals. It is acceptable for a
reference to be cited only in a table or a figure legend and not in the text if it is in
sequence with references cited in the text. For example, if Table 2 contains reference
13, which does not appear in the text, this is acceptable as long as the last reference
cited (for the first time) before the first text citation of Table 2 is reference 12. : .
C- .
d
.' .'
::i
\v:'":::
,

r...:.
 3.6 Citation

Use arabic superscript numerals outside periods and commas, inside colons and
semicolons. When more than 2 references are cited at a given place in the manu-
script, use hyphens to join the first and last numbers of a closed series; use commas
without space to separate other parts of a multiple citation.
As reported previously,11H~19
The derived data were as follow^^^^:
Avoid placing a supersaipt reference citation immediately after a number or an
abbreviated unit of measure to avoid any confusion between &e superscript refer-
ence citation and an exponent.
Amid: The 2 largest studies to date included 262 and 1 8 patients.
~
Better: The 2 largest studies to date included 26 patients2 and 18 patients.3
Amid: The largest lesion found in the first study was 10 cm.*
Better: The largest lesion found in the first study2was 10 cm.
When a multiple citation involves .sufficient superscript characters to create the
appearance of a "holen in the print copy (20-25 characters, including spaces
and punctuation, depending on the column width and type size), use an asterisk
in the text and give,the citation in a footnote at the bottom of the page (Figure).

generate inlormation based on arriving data and trigger

the action of the informed person without a preceding
spedfic request Passive systenis require the w r to rec-
ognize when advice would be w h l and to make an ex-
pliat d o n to start proeeaing."'l%e following success-
ful inlormation interventions were analyzed:
The pmdder promprlreminder intervention mstypb
cally used to improve the provision of preventive care
smices through computer-generatedreminders to phy-
sicians. For example, patients of physicians who re-
ceived reminders on the encounter forms were signifi-
cantly more likely to have a mammogram o ~ d e r e d . ~
Procedures frequently targeted by the provider prompt/
reminder ulals included cancer screening (stool oc-
cult b l o ~ d . l ~ " J ~ . ~ .s~i g. *m ~ i d o s c o p y ,rectal
~ . ~ ex-
a m i n a t i ~ n . ' ~ ~ mamm~graphy."~'~"'~~~~~~
*~~' breast
e x a m i n a t i ~ n Papanicolaou
. ~ ~ ~ ~ ~ ~test.' ~ ~ ~and~ ~pelvic
~
and vaccinations (influen~a.~""
pneumococcal."~* tetan~s.".~'and infantm immuni-
zations).
The patient promprlreminder intenention encour-
aged the action of patients through the use of tele-
phone2'3""' or mailt reminders. The main function
of the computer system was usually to identify pa-
tients and trigger the use of a particular clinical pro-
cedure. For example, in a trial testing the effect ofre-
minden on influenza vaccination, patient reminder
letters led to a significant (35.1%)improvement.* Most
trials of patient prompVrcminders focused on cancer
screening compliance ntcs (stool occult hlnod."'.wM
sigmo~doscopy.~~ rectal exarnin~~ion.~"' mammop
nphy.*MY breasr rxaminati~n.'~"Papanlcolaou

'lylh-mm 1.9. 14. 40. 57. 61. 64. 74, 90 9J

*R+-rr G. 39. b ! . 62. 64. M.M. 10:

Figure. For referenter Iha! occupy more than 2 3 characterr and %paces.botlom.of-pap footnotes
are rned Thn ~ r a r n ~ shows
le 2 such footnot~swtthln a rtncle column
3.7 Authors

Nore: (1) Reference numerals in such a footnote are set full size and on the line rather
th:~n3s superscripts. (2) The spacing is different from that in superscript reference
citations. (3) If 2 or more such bottom-of-the-page footnotes appear in a single
article, use an asterisk for the first footnote, a dagger for the second such footnote, a
dagger for the tliircl. Note: This is less relevant for the Web.
CIOLII)IC'

Note: In tables, if a cell in the table involves citation of a reference number and a
footnote symbol, give the reference number first, followed by a comma and the foot-
note symbol (eg, 3-") (see 4.1.3, Visual Presentation of Data, Tables, Table Compo-
nents).
If the author wishes to cite different page numbers from a single reference
source at different places in the text, the page numbers are included in the super-
script cication and the source appears only once in the list of references. Note that the
superscript may include more than 1page number, citation of more than 1reference,
or both, and that all spaces are closed up.
These patients showed no sign of protective sphincteric a d d u ~ t i o n . ~ ~ ~ ' ) ~ ~ I
~ e s m a n ~ ~
reported
~ ~ . 8~cases
' * ~in which vomiting occurred.
In listed references, do not use ibid or op cit.

Authors. Use the author's surname followed by initials without periods. In listed
references, the names of all authors should be given unless there are more than 6, in
which case the names of the first 3 authors are used, followed by "et al." Note: The
NLh4 guidelines do not limit the number of authors listed but, for space consider-
ations, we have elected to depart from the NLM guidelines on this point.
Ncte spacing and punctuation. Do not use and between names. Roman nu-
merals and abbreviations for Junior Ur) and Senior (Sr) follow author's initials. Note:
Although NLM uses "2nd," "3rd," and "4th,"JAMA and the Archives Journals prefer 11,
111, and IV, unless the author prefers arabic numerals.
Also, alchough JM and the Archive. Journals, in bylines, make a distinction
hetween a group of individuals writingfor a group and a group of individuals writing
cis a group or in addition to (ie, and) a group (see 5.1.7, Legal and Ethical Consid-
erations, Aut5orship Responsibility, Group and Collaborative Authorship), this dis-
tinction is not retained in the NLM database and hence in MEDLINE. If authors, in
their reference lists, provide this information, the for or and will be retained, but if
this informationis not provided, the reference will use the individuals named and the
group name, without for or and. Both styles are illustrated in the examples below.
Xore that the group name is preceded by a semicolon rather than a comma (to show,
noted in 3.1. Reference Style and the Uniform Requirements, that the information
r l u t follows is related to what precedes it but somehow distinct) and that articles (eg,
fbc.) in the group name are removed.
1 ai~thor: Doe JF.
2 authors: Doe JF, Roe JP 111
 3.8 Prefixes and Particles

3:
6 authors: Doe JF, Roe JP 111, Coe RT Jr,
I
Loe JTSr, Poe EA, van Voe AE.
>6 authors: DoeJF, Roe JP 111, Coe RT Jr, et al.
1 author for or and a group: Doe JF;Laser ROP Study Group.
\
or
Doe JF; for Laser ROP Study Group.
or
Doe JF; and Laser ROP Study Group.
>6 authorsfor or and a group Doe JF, Roe JP 111, Coe RT Jr, et al;
Laser ROP Study Group.
. or

1, Doe JF, Roe JP 111, Coe RT Jr, et al;

for Laser ROP Study Group.
or
DoeJF, Roe JP 111, Coe RT~ ret, al;
8:... and Laser ROP Study Group.
!,.'
When mentioned in the text, only surnames of authors are used. For a 2-author
reference, list both surnames; for references with more than 2 authors or authors and
n p u p , include the first authoir surname followed by "et al," " a d associates," or
"and colleagues."
Doe7 reported on the survey.
Doe and ~oe' reported on the survey.
F' '
$2. .; Doe et a19 reported on the survey.
E. .,
i.2. :
%.,I
:. . Note: Do not use the possessive form et al's; rephrase the sentence.
i - !

k:; The data of Doe et a19 support our findings.

b/ In material that is less clinical (eg, book reviews, historical features, letters to the
1I editor), the author's first name or honorific may be used at first mention:
We agree with Dr Tayeb that the prevalence of domestic violence is difficult
to determine.
In Growing QI Fast, Joanna Lipper profiles 6 teenaged mothers living in
1k . Pittsfield, Missachusetts, at the turn of the 21st century.

1Prefixes and Particles. Surnames that contain prefixes or particles (eg, von, de,
. La, van) are spelled and capitalized according to the preference of the persons
k named.
1P 1,van Gylswyk NO, Roche CI.
iv 2. Van Rosevelt RF, Bakker JC, Sinclair DM, Damen J, Van Mourik JA
!' 3. Al-Faquih SR.
I
C 4. Kang S, Kim KJ. Wong T-Y,et ai.
1-b Titles. 11. I I I ic. , I : .1111c.Ic.\, t,ooks, parts of books,
and other material, retain the
\ i ,t.li,:lg .11 )I ) r ~ - \I . I I I O I > . ~ , ;11ld style for nulnbers used
in the original. Note: Numbers
r11.1r I~.glrl.I rlrlc .Ire spelled out (although exceptions are made for years; see 2.1.2,
.\l;~~w~c.ript l'repamtion, Titles and Subtitles, Numbers).

English-Language Titles

Journal Articles and Parts of Books. In English-language titles, capitalize only (1) the
f rbt letter of the first worcl, (2) proper names, and (3) abbreviations that are ordinarily
c.:~pitalizecl(eg, DNA, EEG, VDRL). Do not enclose article and book chapter titles in
cli~ot:~tion 111:lrks. I lowcvcr, if 3 I~ook,book chapter, or article title conpains quotation
marks in the original, retain them as double quotation marks (unless both double and
single quotation narks are used).

, .;,.- ,:hBooks, Government Bulletins, Documents, and Pamphlets. In English-language titles,

5 ?--

italicize the titles of books, government bulletins, documents, and pamphlets and
capitalize the first letter of each major word. Do not capitalize articles, prepositions of
3 or fkwer letters, coordinating conjunctions (and, or,for, nor, but, yet), or the to in
infinitives (see 2.1.6, Manuscript Preparation, Titles and Subtitles, Capitalization, for
exceptions). Do capitalize a 2-letter verb, such as Is.

Non-English-Language Titles

Capitalization. In non-English-language titles, capitalization does not necessarily I

!
follom the same rules as in English-language titles. For example, in German titles
(both articles and books), all nouns and only nouns are capitalized; typically, in !
;
French, Spanish, and Italian book titles, capitalize only the first word, proper names,
and abbreviations that are capitalized in English. As with English-language books,
government bulletins, documents, and pamphlets, italicize the title,

Translation. Non-English-language titles may be given as they originally appeared,

without translation:
'
1. Richam E, Schott KJ, Wormstall H. Psychopharmakotherapie bei De-
menzerkrankungen. Dtsch Med Wochenschr. 2004;129(25/26):1434-1440.
2. Ohayon MM. Prevalencia y factores de riesgo de cefaleas matinales en la
poblaci6n general. Arch Intern Med Ed Espanol. 2004;1(1):41-47. Origi-
nally published, in English, in: Arch Intern Med. 2004;164(1):97-102.
If non-English-language titles are translated into English, bracketed indication of the
original language should follow the title:
3. Miyazaki K, Murakami A, Imamura S, et al. A case of fundus albipunctatus
I
with a retinol dehydrogenase 5 gene mutation in a child [in Japanese].
Nippon Ganka Gakkai Zasshi. 2001;105(8):530-534.
If both the non-English-language title and the translation are provided, both may be
given, as shown below, with the non-English-language title given first, followed by
1
the English translation, in brackets: I
 -- .
. . -.-. - --

3.1 1.1 Complete Data

4. Camia M. Cancro prostiitico e screening con test PSA [Prostate cancer and
prostate-specific antigen screeningl. Minsn~uMed. 2004;95(1):25-34.
Non-English-language titles should be verified from the original when possible.
:. Consult a dido& in the appropriate language for accent marks, spelling,5nd other

Reference to the primary source is always preferable, but if the non-English-

language article is not readily available or not accessible, the translated version is
The citation should always be to the version consulted.
Such words as tome (volume), fascicolo (part), Seite (page), Teil (part), Auflage
(section or part), Band (volume), Heft (number), 3eihefr (sup-
ng (part or number) should be translated into English.

Names of Organisms. In all titles, follow the style recommended for capitalization
and us; of italics in scientific names of organisms (see 10.3.6, Capitalization, Proper
i-: Nouns, Organisms, and 15.14, Nomenclature, Organisms and Pathogens). Use roman
.- type for genus and species names in Book titles.

Non-English Words and.Phrases.In all titles, follow the guidelines recommended for
use of italics or roman in non-English words and phnses (see 12.1.1, Noi1-English
,and Accent Marks, Non-English Words, Phrases, and Titles, Use of
Italics). For example, even if In Vimor n Vitm were set italic in a cited title. JAllA
and the Archives Journalswould set these in roman type.

Subtitles. Style for subtitles follows that for titles (see 3.9, Titles) for spelling. ah-
breviations, numbers, capitalization, and use of italics, except that for journal articles
with a lowercase letter. A colon and space separate title :~nd
subtitle, even if a period was used in the original. Do not change an em dash to a
colon. If the subtitle is numbered, as is common when articles in a series have tlic
same title but different-numbered-subtitles, use a comma after the title. followecl
by a roman numeral immediately preceding the colon.
1. Klein R, Hein BEK, MossSE, et al. The relation of retinal vessel ralilxtr to
the incidence and progression of diabetic retinopathy, XIX: the Wisconsin
Epidemiologic Study of Diabetic Retinopathy. Arch Ophthalt~~ol. 2004:
122(1):76-83.

References t o Print Journals

Complete Data. A complete print journal reference includes the following:

Authors' surnames and initials
r Title of article and subtitle, if any
u Abbreviated name of journal

8 Volilme number
m Issi~t.n i r m k

47
 Names of Journals. :\l>l>rc\.~:ite
and ital~cizenames of journals. Use initial capital
letters. r\l>l~rc\.iateac.cording to the listing in the PubMed Journals database (see also
14.10. Al~l>revi;~tions, Names of Journals). Include parenthetical designation of a city
if it is included in the I'uI>Mecl lil,l)reviation, for example, Medicine (Baltimore), Ann
U ~ n(Pnr-is).
l Infomation enclosed in brackets should be retained without brackets,
eg, ./ Ci)t)rl~I'/~-)aiol
A for./ Cotlrp I,hysiol [A].
If the name of a journal has changed since the time the reference was published,
use the name of the journal at the time of publication. For example, the journal
forillerly called Transactions of the Ophthalmological Societies of the United King-
donz is now called Eye. If a citation was from the older-named journal, do not change
the journal name to Eye; use the former title: Tram Ophthalmol Soc U K.When the
name has not changed but the abbreviation used by PubMed has changed (eg, Br
Med J to BMJ), use the abbreviation in use by PubMed at the time the reference was
published (so, Br Med J through 1987; BMJ from 1988 forward). This policy will
ensure that the online links to the citation will work.

Page Nurnbers and Dates. Do not omit digits from inclusive page numbers. The year,
followed by a semicolon; the volume number and the issue number (in parenthe-
ses), followed by a colon; the initial page number, a hyphen, and the final page
number, followed by a period, are set without spaces.
1. Rainier S, Thomas D, Tokarz D, et al. Myofibrillogenesis regulator 1gene
mutations cause paroxysmal dystonic choreoathetosis. Arch Neuml. 2004;
61(7):1025-1029.
2. Hyduk A, Croft JB, Ayala C, Zheng K, Zheng Z-J, Mensah GA. Pulmonary
hypertension surveillance-United States, 1980-2002.MMW7RSum'IISumm.
2005;54(5):1-28.

Discontinuous Pagination. For an article with discontinuous pagination, in one issue,

, follow the style shown in the example below:
1. Herr KA, Garand L. Assessment and measurement of pain in older adults.
Clin Geriatr Med. 2001;17:457-478, vi.

Journals Without Volume or Issue Numbers. In references to journals that have

no volume or issue numbers, use the issue date, as shown in example 1 below. If
there is an issue number but no volume number, use the style shown in example 2
below.
1. Flyvholm MA, Susitaival P, Meding B, et al. Nordic occupational skin
questionnaire-NOSQ-2002: Nordic questionnaire for surveying work-
related skin diseases on hands and forearms and relevant exposure. Tema-
Nord. April 2002518.
2. Keppel K, I'arr.uk E, Lynch J, et al. Methodologic issues in measuring
health disp:~ritics.Viral Hc.crltk Stul 2. 2005;(141):1-16.
 3.11.9 Abrtrbctr and Other Material Taken From Another Source

Parts of an Issue. If an issue has 2 or more parts, the part cited should be indicated in
accordance with the following example:
1. McCormick MC, Kass B, Elixhauser A, Thompson J, Simpson L. Annual
report on access to and utilization of health care for children and youth in
the United States: 1999. Pediatrics. 2000;105(1, pt 3):219-230.

Special or Theme Issue. The I ~ Z M~ecornmended~ o r m a t defines

s~ a special or then~e
issue as follows: "Special issues are frequently published to present the from
conferences.. ..They may also be published to commemorate a specific event or to
bring together papers o n a specific subject."J A M and the Arc-5iuesJournals refer to
these as theme issues. References to the complete contents of a special or theme issue
of a journal should be cited as follows:
1. Flanagin A, Winker MA, eds. Global health. JAMA. 2004;291(21, theme
issue):2511-2664.
2. Blodi BA, Ferris FL 111, guest eds. Blindness. Arch Ophthalmol. 2004;122(4.
theme issue):437-676. .

Special or theme issues may also be published as supplements (see 3.11.8, Supple-
ments, for the recommended style for these).

Supplements. The following example illustrates the basic format:

1. Body JJ, Greipp P, Coleman RE, et al. A phase I study of AMGN-0007, a
recombinant osteoprotegerin construct, in patients with multiple myeloma
or breast carchoma related metastases. Cancer. 2003;97(3)(suppl):887-
892.
If the supplement is numbered, and there is no issuxumber, use the following form:
2. h i c ~ o u ~CJ,
l e Stigler KA, Posey DJ. Treatment of aggression i n children
and adolescents with autism and conduct disorder.J Clin ~syc6iatry.2003;
64(supp14):16-25.
If the supplement is numbered, and there is an issue number, use the form below:
3. Crino L, Cappuzzo F. Present and future treatment of advanced *on-small-
cell lung cancer. Semin Oncol. 2002;29(3)(suppl 9):9-16.
When numbered supplements have several parts, denoted by "pt 1" or by letters,
each supplement having independent pagination, use the following form:
4. Rosenwasser LJ. Treatment of allergic rhinitis. Atn J Med. 2002;113(suppl
9A): 17s-24s.
Note: It is common for page numbers in supplements to include letters as well
as numbers (eg, 17s-24s in example 4 above). Also, example 4 has no issue
number.

Abstracts and Other Material Taken From Another Source. Several types of pub-
lished abstrdas may be cited: (1) an abstract of a i.omplc.[c~;~rticlctaken f r c m anr.)rher
publication, as in the Abstncts .wcTion of,/~,tM.( 2 ) :I rewritten ;thsrr;ic? o f :I plrl>-
lished article with an appended comment;lry. ;~ncl( 3 ) ;in :~l>str;rc.t pul~ll4rrilrrr tlrc

49
3.1 1 References t o Print Journals

society proceedings of a journal. (For exarnplcs of absrracu prc.wn[c.d at nlcctings,

puhlishecl or unpublished, see 3.13.3, Special Print Materials, Serial Put>l~carions,
and
3.13.8, Special Print Materials, Unpublished Material,)
Ideally, reference to any of these types of abstracts should lx permitted only
when the original article is not readily available (eg, non-English-language articles or
papers presented at meetings but not yet published). If an abstract is published in the
society proceedings section of a journal, the name of the society before which the
paper was read need not be included, but see example 3 below if this information is
included.
1. Abstract of a complete article taken from another publication:
1. Elner VM, Hassan AS, Frueh BR. Graded full-thickness anterior blephar-
otomy for upper eyelid retraction [abstract taken from Arch Ophthalmol.
2004;122(1):55-601. Arch Facial Plmt Sutg. 2004;6(4):277.
2. Rewritten abstract of a published article with an appended commentary:
2. Bigby ME. The end of the sunscreen and melanoma controversy [abstract
of Dennis LK, Beane Freeman LD,VanBeek MJ. Sunscreen use and the risk
for melanoma: a quantitative review. Ann Intern Med. :003;139(12):966
9781? Arch D e m ~ t o l2004;140(6):745-746.
.
3. Abstract of a paper published in the society proceedings of a journal:
3. Fliesler SJ, Richards MJ, Peachey NS, Buchan B, viughan DK, Organisciak
DT. Potentiation of retinal light damage in an animal model of Srnith-
'
Lemli-Opitz syndrome M V O abstract 33731. Invest Ophthalmol Vis Sci.
2001;42(suppl):S627.
Note: In example 3, the abstract number is also provided; if a number is included, it is
placed in brackets along with the "abstract" designation. Also, example 3 has no issue
number.

Special Department, Feature, or Column of a Journal. When reference is made to

Inaterial from a special department, feature, or column of a journal, the department
should be identified only in the following cases:
1. The cited material has n o byline or signature. (Note: This is preferable to citing
Anonymous, unless "Anonymous" or wmething similar was actually used [see
2.2, Manuscript Preparation, Bylines and End-of-Text Signatures].)
1. Who is responsible for adolescent health [editorial]?Luncet. 2004;363(9426):
2003. .

2. The column or depariment name might help the reader identify the nature of
the article and is not apparent from the title itself. Note: In these cases, the
inclusion of the department or column name is optional and should be used as
needed, at the editor's discretion.
2. Harris JC. D e d Mother I [Art and Images in Psychiatry]. Arch Gen Psy-
chiarty. 2004;61(8):762.
3. Gross R, Neria Y. Posttraumatic stress among survivors of bioterrorisrn
[letter].JAMA. 2004;292(5):566.
 .-

3.11.12 Discussants

Identification of other special departments, features, or columns may not require

additional notation (eg, book or journal reviews, cover stories) as their identity will
be apparent from the citation itself:
4. Calfee JE, reviewer. Nature. 2004;429(6994):807. Review of: Goozner M.
me $800 Million Pill: i%e Truth Behind the Cost of New Drugs.
5. Southgate MT. The Cover (Thomas Hart Benton, Pussycat and Roses).
J M 2004;292(6):661.
.

Other Material Without Named Author(s1 or With Named Authors and a Group
Name. Reference may be made to material that has no named author or is prepared
by a committee or other group. The following forms are-used:
1. Ferguson JJ, Califf RM,Antman EM, et al; SYNERGY Trial Investigators.
Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-
segment elevation acute coronary syndromes managed with an intended
early invasive strategy: primary results of the SYNERGY randomized trial.
JAMA. 2004;292(1):45-54.
2. Eye Diseases Prevalence Research Group. Prevalence of age-related mac-
ular degeneration in the United States. A& Ophthalmol. 2004;122(4):564-
572.
3. Centers for Disease Control and Prevention.(CDC). Prevalence of receiving
multiple preventiveare services among adults with diabetes-United States,
2002-2004. MMWR Morb Moltal Rep. 2005;54(44):1UO-1133.
References may also have bylines containing the names of individuals and the name
of a group or several groups.
4. Hemis A, Wu S-Y, Nemesure-B,Leske MC; Barbados Eye Studies Group.
Risk factors for incident cortical and posterior subcapsular lens opacities in
the Barbados Eye studies.' Arch Ophthalmol. 2004;122(4):525-530.
5. Taylor Z, Nolan CM, Blumberg HM; American Thoracic Society; Centers
for Disease Control and Prevention; Infectious Diseases Society of Arner-
ica. Controlling tuberculosis in the United States: recommendations from
the American Thoracic Society, CDC, and the Infectious Diseases Society
of America. MMV%R Recomm Rep. 2005;54(RR-12): 1-81.
In examples 4 and 5 above, a semicolon, not a comma, precedes the group name in
the author field and no articles (eg, the) are included with the group names.

Discussants. If reference-citation in the text names a discussant specifically rather

than the authods), eg, "as noted by aster,'" the following form is used (see also
3.13.10, Special Print Materials, Secondary Citations and Quotations [Including Press
Releases]).
1. Easter DW. In discussion of: ~ a r l eDH,
~ Greenlee SM, Larson DR. Har-
rington JR. Double-blind, prospective, mndomized study of n . ; ~ r m ~ t l
humidified carbon dioxide insufflationvs standard carbon diosirle for p : ~
tients undergoing laparoscopic cholccystectorny. Arch 5 1 i r ~200.1:
. 1O f - )
739-744.

II

..
3.12 References to Print Books

Corrections. If the reference citation is to an article with a published correction.

provide both the'information about the article and the information about the put>
lished correction, if available, as follows.
1. Korpi A, Mantyjarvi R, Rautiainen J, et al. Detection of mouse and rat
11ri11;ll-y:~cro;~llcrgcns
with an improved ELISA [pul~lishedcorrection ap- . .
pc:~rsill./ A / / C ~ I( ;~/ )i ~JIi I I L I I ~ I2004;113(6):1226].J
IO/. A / / ~ C'iili
J J /IIIIIZ~~IIV~.
2004;113(4):677-682.

Retractions. If the reference citation is to an article that has since been retracted, or to
the retraction notice itself, use the appropriate example below. Uniform Require-
ments notes, "Ideally, the first author should be the same in the retraction as in the
article, although under certain circumstances the editor may accept retractions by
other responsible persons."s (See also 5.4.4, Ethical and Legal Considerations, Sci-
entific Misconduct, Editorial Policy and Procedures for Detecting and Handling All-
egations of Scientific Misconduct.)
Citjng the retraction:
'
1. Duckmanton L, Tellier R, Richardson C, Petric M. Notice of retraction of
"The novel hemagglutinin-esterase genes of human torovirus and Breda
virus" [retraction of: Duckmanton L, Tellier R, Richardson C, Petric M. In:
V i m Res. 1339;64(2):137-1491. Virus Res. 2001;81(1-2):167.
Citing the article retracted:
2. Duckmanton L, Tellier R, Richardson C, Petric M. The novel hemagglutinin-
esterase genes of human torovirus and Breda virus [retracted in: Virus Res.
2001:81(1-2):1671. Virus R ~ s .1999;64(2):137-149.

Duplicate Publication. The following form is suggested for citation of a notice of

duplicate publication. (See also 5.3, Ethical and Legal Considerations, Duplicate
Publication.)
1. Mettler L. Notice of duplicate publication [duplicate publication of Mettler
L, Audebert A, ~ehmam-WillenbrkkE, Schive K, Jacobs VR. Prospective.
clinical trial of SprayGel as a bamer to adhesion formation: an interim
analysis. ] Am Assoc Gynecol Lupamc. 2003;10(3):339-3441. J Am Assoc
. Gynecol Luparosc. 2304;11(1):130.

References t o Print Books

Complete Data. A complete reference to a print book includes the following:

1. Authors' surnames and first and middle initials
2. Chapter title (when cited)
3. Surname and first and middle initials of book authors or editors (or translator, if
any)
4. Title of book and subtitle, if any
j Volulrlr ni~nliwr;irlcl volume title, when there is more than 1 volume
 ..
. -.

. 3.12.4 Reference to a Chapter in a Book

6. Edition number (do not indicate first edition)

7. Place of publication (see 14.5, Abbreviations, Cities, States, counties, Territo-
ries, Possessions; Provinces; Countries)
8. Name of publisher
9. Year of copyright
10. Page numbers, when specific pages are cited

Referenceto an Entire Book. When referring to an entire book, rather than pages or a
specific section, use the following format (see also 3.7, Authors).
1. Modlin J, Jenkins P. Decision Analysfs in Planningfora Polio outbreak in
the United States.'San Francisco, CA: Pediatric Academic Societies; 2004.
2. Adkinson N, Yunginger J, Busse W, Bochner B, Holgate S, Middleton E,
eds. Middleton's A l m : Principles and Practice. 6th e& St Louis, MO:
Mosby; 2003.
3. Sacks 0. Uncle Tungsti?n:New York, NY: Alfred A Knopf; 2001.
4. Weedon D. Skin Pathology. hildon, England: churchill Livingstone; 2002.
5. World Health Organization. 1 n j u A~ Leading Cause ofthe Global Burden
of Disease, 2000. Geneva, Switzerland: World Health Organization; 2002.
6. Galanter M, ed. Seruices Research in the Era of Managed CUR. New York,
NY: Kluwer Academic/Plenum; 2001. Recent Demlopments in Alcohol~m;
vol 15.
7. Simon LS, Lipman AG, Jacox AK, et al. Pain in Osteoarthritis, Rbeurnatoid
Arthritis, andJumile Chronic krthritis. 2nd ed. Glenview, IL: American
Pain Society, 2002.
8. Venables WN, Ripley BD. Modem Applied Statistics With S. 4th ed. New
York, NY:Springer Publishing Co; 2003.

Referencesto Monogaphs. ~eferences

to monographs should be styled the same as
references to books.

Reference to a Chapter in a Book. When citing a chapter of a book, apitalize as for

a journal articIe title (see 3.9, Titles); d o not use quotation marks. Inclusive page
numbers of the chapter should be given (see also 3.12.11, Page Numbers or Chaptcr
Number).
1. Solensky R. Drug allergy: desensitization and treatment of reactions to an-
- . tibiotics and aspirin. In: Lockey I), cd. Allelg~~~rs
arid Allc~t~crr
Irrrtr~rr~rr~-
therapy. 3rd ed. New York, NY: Marcel l>ekker; 2004:585606.
2. Yashiro M, Yanagawa H. Database constn~ctionfor infornlation on pa-
tients with Kawasaki disease. In: Yanagawa H, Nakamura Y, Yashiro hl.
Kawasaki T, eds. @idemiolo~of Kazum~ikiDiseuse: A ~ U - Y ~ Acbici.c.-
CII-
ment. Tokyo, Japan: Shindan-to-Chiryosha; 2004:57-77.
3. Bergeron C, b w e J. Frontoteniporal degeneration: introduction. In: 1)ic.k-
son DW, ed. Neurodegeneration: 7he Molecfrlar Pathofogy of' Denlrlrlirr

53
3 12 References to Pr~ntBooks

l)l.\c,nlt.r~ I 3 . t ~ - I . s\vktrcrlrnd: ISN Neuropath Press; 2003:

r ~ t i .\loit~111~~t:~
~l
3.1.2-3.iS.
c;, iicrins G, Uc.xl~ricK. Clinical approach to the older pa-
4. l'ang;uo';~~~g
tient: :In ovcn.ic\v. In: Cassel C, kipzig R, Cohen H, Larson E, Meier D,
eds. Geriur~ic.Ilcdici)ze. New York, NY: Springer-Verlag; 2003149-162.
Note that in example 2 alx)vc. 2 of the authors of the chapter are also editors of the
lxok. In cases like this, they are listed in both places: authors of the chapter and
editors of the book. The sJme policy would apply if the authors of a particular
chapter and the editors of the book were identical.

Editors and Translators. N:unes of editors, translators, translator-editors, or execu-

tive, consulting, and section editors are given as follows:
1. Plato. 7%e Laws. Taylor EA, trans-ed. London, England: JM Dent & Sons
Ltd; 1934:104-105.
I
[Plato is the author; Taylor is the translator-editor.]
I
2. Klaassen CD. Principles of toxicology and treatment of poisoning. In:
Hardman JG, Limbird LE,eds. Gilman AG, consulting ed. Coodman and
Gilman 's f i e Pharmacological Basis of 'Iherapeutics.10th ed. New York,
NY:McGraw-Hill Book Co; 2001:67-80.
[Klaassen is the author of a chapter in a book edited by Hardman and
Limbird, for which Gilman was the consulting editor.]
In the following 4 examples, no authors are named. Each book has an editor or
1
editors and is part o f a series. Note: The name of the series, if any, is given in the fi-
nal field. If the book has a number within a series, the number is also given in the
final field (see example 6).
3. Villarreal FJ, ed. Interstitial Fibrosis in Heart Failure. New York, NY:
Springer-Verlag; 2005. Developments in Cardioyascular Medicine.
4. Sharpe VA, ed. Accountability: Patient Safety and Policy Reform. Wash-
ington, DC: Georgetown University Press; 2004. Hasrings CenterShrcles in
Ethics.
.
5. Brune K, Handwerker HO, eds. Hyperalgesia: MolecularMechanisms and
Clinical Implications. Seattle, WA: IASP Press; 2004. Progress in Pain Re-
search ancl Management; vol 30.
6. Balducci L, Extermann M, eds. BiologicalBasis of Geriatric Oncology. New
York, IVY: Springer-Verlag; 2005. Rosen ST, ed. Cancer Treatment and
Research; vol 124.
'
Volume Number. Use arabic numerals for volume numbers if the work cited includes
more than 1 volume, even if the publisher used roman numerals.
If the volumes have no separate titles, merely numbers, the number should be
given xfter the general title.
1. US Department of Health and Human Services. Understanding and Zm-
ptur!ing Hctrlrh ~ t Objectives
~ d for Improving Health. Vol 1. 2nd ed. Wash-
inxton. DC: 11s 1)ept of Health and Human Services; 2000.

..
--- - - ..

-.

i
 3.12.8 Place of Publication

If the volumes have separate titles, the title of the volume referred to shoc~ldI,e given
first, with the title of the overall series of which the volume is a pan given in the final
field, along with the name of the general editor and the volume numl~cr,if appli-

2. Kleiss W, Marcus C, Wabitsch M, e d ~ Obesity

. in Childhood ancl At/oIc?;-
cence. Leipzig, Germany: Karger; 2004. Pediatrii: and Adolesce)~tJlc~di-
cine; vol 9.
In example 2 above, Pediatric find Adolescent Medicine is -the name of the entire
series; Obesiry in ChiMhood and Adolescence is the ninth volume.
When a book title includes a volume number or other identifying number. use
the title as it was published, Note: The volume number does not need to be repeated
in its customary place after the year if it is included in the book's title.
3. Field Manual 4-02.17.- P m t i ? Medicine Smaceses Washington, DC: US
Dept of the Army; 2000.
4. US V e t e m Health Administration/Department of Defense. ClinicalPrac-
tice GuMelines:mbetes MellitMF A I g o n t h ~ M o d u l F:
e Foot Care.Wash-
ington, DC: Veterans Health Administration; 2003.

Edition Number. Use arabic numerals to indicate an edition, even if the publisher has.
used roman numerah, but do not indicate a first edition. If a subsequent edition is
cited, the number should be given. Abbreviate "New revised editionn as "New rev
edn; "Revised edition" as "Rev edn;."American edition" as "American ed"; and "British
editionn as "British ed."
1. Glinoer D. Thyroid disease during pregnancy. In: Braverman LE, Utiger
RE, eds. Wemet and Ingbark 7Be Thyroid: A Fundamental and Clinical.
Tex.8th ed. Philadelphia, PA: Lippincott Williams &-WiUcins;2000:1013
1027.
2. Pratt-Johnson JA, Tilson G. Management of Strabismus and Amblyopia.
2nd ed. New York,:[-(\I Thieme Medical Publishers; 2001.
3. Green M, ed. Bright Futures: National GuidelinesforHealth Supervision of
Injirnts, Childm, and Adolescents. 2nd rev ed. Arlington, VA: National
Center for Education in Maternal and Child Health; 2002.

Place of Publication. Use the name of the city in which the publishing firm was
located at the time of publication. Follow the style used b y J M and the Archives
Journals for state names, as well as names of cities outside the United States (see 14.5,
Abbreviations,Cities, States,Counties, Territories, Possessions; Provinces; Countries).
Do nor list the state name if it is part of the publisher's name. If more than 1 location
appears, use the one that appears first in the edition you consulted. A colon separates
the place of publication and the name of the publisher.
1. Griffin JR, Grisham JD. Binoctrlar Anomalies: Diagnosis and Vzkion Ther-
apy: 4th ed. Boston, MA: Butterworth-Heinemann; 2002.
2. Dresser R. W%mScience OJm Salvation: Patient Advocacy and Research
Ethics. New York,NY: Oxford University Press; 2001.

55
3.12 References to Print Bookr

3. I ~ ~ c I - I I A .~AI ~~C~I J\ ~~I cXb r l{cx-~rcl\011 <;.I~\L.C*I (\.\KC 1 C . ~ I I Lt a r 1 9 1 , ~ i l a , p ~I ,t 1 ~ 1

Flit, c - o t i l ~ t i t , ~ ~ r . \\ ' ( ) I f i Lyon. Fr~n~.c:
l.\KC l J r c s , 2W.! l.\Kt. X . I C ~ ~ I I I ~ L
nul,lica~ion 155.
4. Cavanagh I'K. Uoone El'. Plumrner DL. 77?e Fmr it1 Diabetes: A Bihliogru-
phy. College Station: Pennsylvania State University; 2000.
5 . Health, U)~ite~lStates,
2004. Hyattsville; MD: National Center for Health Sta-
tistics: 2004.

Publishers. The full name of the publisher (publisher's imprint, as shown on the title
page) should be given. al>l,revi;ited in accordance with the style used by J A M and
the At-cI3iues Journals (see 14.7, Abbreviations, Business Firms) but without any
punctuation. Even if the name of a publishing firm has changed, use the name that
was given on the published work. The following is an example of the format for a
book with a joint imprint:
1. Henderson DA, Inglesby TV,OToole T, eds. Biotmrism. Chicago, IL:
.JAMA/Archivesand AMA Press; 2002.
Consult the latest Books in print to verify names of publishers, listings, online
bookstores, or the Library of Congress catalog.
If there is no publisher's name available, use "Publisher unknown" in the place of the
publisher's location and name.

E m m year of Publication.. If the book has been published but there is no year of publi-
cation available, use .'date unknown" in the place of the year. Use the full year (eg,
2006). not an abbreviated form (eg, not 06or '06).

Page Numbers or Chapter Number. Use arabic numerals, unless the pages referred to
use roman pagination (eg, the preliminary pages of a book).
1. Lewinsohn P. Depression in adolescerits. In: Gottlib IH, Hammen CL, eds.
Handbook of Depression. New York, NY: Guilford Press; 2002:541-553.
2. Mahan MDF. Preface. In: i%e Chicago Manual of Style. 15th ed. Chicago,
IL: University of Chicago Press; 2003:xi-xiii.
If a book uses separate pagination within each chapter, follow the style used in the
book. Notice that in the example below, because the page numbers contain hy-
phens, an en dash is used to separate them, rather than the usual hyphen.
3. Kasrnar AG. Climi SA, David BT. Infectious diseases. In: Sabatine MS, ed.
Pocket Medicine. 2nd ed. Baltimore, MD: Lippincott Williams & Wilkins;
2000:6-1-6-20.
Inclusive page numbers are preferred. The chapter number may be used instead
if the author does not provide the inclusive page numbers, even after being
queried.
4. Dybul M, Connors M, Fauci AS. Immunology of HIV infection. In: Paul
WE, ed. Fundamental Immunology. 5th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2003:chap 42.
 .. ..

3.13.2 Government or Agency Bulletins

Special Print Materials. Many of the special materi;~lscovered in this section may
also be accessed (and cited) in an online format. To see examples of these citation
formats, please consult 3.15, Electronic References. The version consulted (print or
online) is the version that should be cited.

Newspapers. References to newspapers should include the following, in the order

indicated: (1) name of author (if given), (2) title of article, (3) name of newspaper,
( 4 ) date of newspaper, (5) section (if applicable), and (6) page numbers. Note:
Newspaper names are not abbreviated. If a city name is not part of the newspaper
naine, it may be added to the official name, for clarity, as with Minneapolis in
' example 1. See example 5 for how to treat an article that "jumps" from one page to a
later page (see also 3.11.4,-~eferencesto Print Journals, Discontinuous Pagination).
. 1. Wolfe W. State's mail-order drug plan launched. Minneapolis Star Tri-
. .bune.May 14,2004:lB.
6.
2. Connolly C. A small win for proponents of drug impottation. Washington 1::
Post. April 23, 2004:EOl.
3. Richer S. America's new war on drugs targets Canadian pharmacists. Globe
and Mail. May 17, 2004.A1.
4. Goode E. Study finds jump in children raking psychiatric drugs. New York
Tisnes,Jquary 14, 2003:~21. i
1.
.!:.
5. Overbye D. A philanthropist of science seeks to be its next Nobel. New
Yo& T im. April 19,2005:Dl, D4. i.
t:i
1:
Government or Agency Bulletins. References to bulletins published by departments !:.:
. or agencies of a government should include the following information, in the order It;,
Li:
indicated: (1) name of author (if given); (2) title of bulletin; (3) place of publication;
(4) name of issuing bureau, agency, department, or other governmental division
(note that in this position, Department should be abbreviated Dept; also note that if
an author supplies US Government Printing Office as the publisher, it would be
preferable to obtain the name of the issuing bureau, agency, or departmea:-;if pos- ,

sible); (5) date of publication; (6)page numbers, if specified; (7) publication num-
ber, if any; and (8) series number, if given.
1.Johnston LD,O'Malley PM, Bachman JG. Monitoring the Future: National
Survey Results on Adolescent Dnrg Use: Overview of Key Findings. Be-
thesda, MD: National Institute on Drug Abuse, US Dept of Health and Hu-
man Services; 2003.
2. Health, lhzited Sfutes, 2004. Hyattsvilltt, MD: National Center for Health
Statistics; 2004.
3. US Department of Health and Human Services. Maternal, infant, and child
health. In: HealfbyPeople2010.2nded. ihshington, DC: US Dept o f Health
and Human Services; 2000.
4. Centers for Disease Control and Prevention. Sc~.vrrrrl!l. T r a ~ z s n ~ i Di.vc>(~.<c>
~fc~~f
Sumilfance, 2000. Atlanta, GA: Cenrcrr t o r I)iw;t.w Control :~ntlI'rv-
vention, US Dept of Health and f f u ~ n ; ~.kn.ic.ch.
n 3w)l
5. Shin HB. Bruno K. Ccsnsu.s 2000 Htic;/' (.'2Kllll.A / ~ ~ ~ I , L ~ I 1c :w I , Pt ~1 ~ 1 ~ 1

E P I ~ I ~ . < ~ - . ~ /AXh>1 (1Ji f~~2000

~: I I ~ \ V ; I ~ ~ I ~J I II . ~I ~ I1 {I 3 ( :C.INI\ I\LIIC;ILI. b5,

57
3.13 Special Print Materials

6. National Institutes of Health, US Department of Healrh and Humdn kr-

vices. Strategic Plan for NIH Obesity Research: A R c p r t to rbe h'fli Oh51ly
Research Task Force. Bethesda, MD: National Institutes of Health; 2004.
NIH publication 04-5493.
7. Central Bureau of Statistics. Statistical Year Book of Nepal 2001. Kath-
mandu, Nepal: Central Bureau of Statistics; 2001.
8. World Health Organization. World Health Report 2002: Reducing Risk,
Promoting Healthy Life. Geneva, Switzerland: World Health Organization;
2002.
0.Cotnliiission for the Assistance of liefugees and United Nations High
Commissioner for Refugees. 7he Guatemalans:A History [in Spanish]. Ge-
neva, Switzerland: United Nations High Commissioner for Refugees;
2000. '

'
10. Transitional Islamic Government of Afghanistan. Afghanistan National
Health ResourcesAssessment: Preliminary Results. Kabul: Ministry of Public
Health, Transitional Islamic Government of Afghanistan; 2002.
11. l b e Swedish Cancer Registry: Cancer Incidence in Sweden 1998. Stock-
holm, Sweden: National Board of Health and Welfare; 2001.
12. Danish National Board of Health. TelephonicInuestigation of the Sun Hab-
its of the Danes [in Danish]. Copenhagen, Denmark: Danish National
Board of Health; 2000.

Serial Publications. If a monograph or report is part of a series, include the name of

the series and, if applicable, the number of the publication.
1. Ministry of Health. National ALDS Control Program. Dar es Salaam: Minis-
try of Health, United Republic of Tanzania; 2001. HIV/AIDS/STI Surveil-
lance Report 16.
2. West S, King V, Carey TS,et al. Systems to Rate the Strength of ScienriJicEv-
idence. Rockville, MD:Agency for Healthcare Research and Quality; 2002.
Evidence Report/Technology Assessment 47.
3. US Department of Commerce. Population Division: Income, Poverty and
Health Insurance Coverage in the United States, 22003.Washington, DC:
US Bureau of the Census; 2003. Annual Social and Economic Supplement.

Theses and Dissertations. Titles of theses and dissertations are given in italics. Ref-
erences to theses should include the location of the university (or other institution),
its name, and year of completion of the thesis. If the thesis has been published, it
should be treated as any other book reference (see 3.12.1, References to Print
Books, Complete Data).
1. Fenster SD. Cloning and Characterization of Piccolo, a Novel Component
of the Presynaptic CytoskeletalMat* [dissertation]. Birmingham: Univer-
sity of Alabama; 2000.
2. Undeman C. Fully Automatic Segmentation of MRI Brain Images Us-
ing Probabilistic Diffuion and a Watershed Scale-Space Approach [mas-
 3.13.8 Unpublished Material

ter's thesis]. Stockholm, Sweden: NADA, Royal Institute.of Technology;

2001.

1. Hunter J. An account of the dissection of morbid bodies: a monograph or

lecture. 1757;No. 32:30-32. Located at: Library of the Royal College of Sur-
geons, London, England.

1. Ciaii [package insert]. Indianapolis, IN: Eli Lilly & Co; 2003.

Patents. Patent citationstake the following form. Examples 1and 2 and 4 and 5 are for
patents that have been issued and example 3 is for a patent that is pending. See the
US Patent and Trademark Office home page (http://www.uspto.gov/) or the Euro-

.php) for further details.

1. Rabiier RA, Hare BA, inventors; OrnniSonics Medical ~ e c h n o l o ~ i eInc,
s
assignee. Apparatus for removing plaque from blood vessels using ultra-.
sonic energy. US patent 6,866,670. March 15, 2005.
2. Guiliano K, Kapur R, inventors; Cellomics Inc, assignee. System for cell-
based screening. US patent 6,875,578. Apdl 5, 2005.
3. Castellano TP, inventor; Pillsbury Winthrop LLP, assignee. Method ;tntl
apparatus for administering a vaccine or other pharmaceutical. US patent
application 20,050,070,876. September 26, 2003. . .
4. Morris D, Coffey MC, ThompsonBG, inventors; Oncolytics Biotech lnc,
assignee. Method for reducing pain using oncolytic viruses. Europc;~n1 ~ 1 t -
ent ES223992m. October 16, 2005.

Unpublished Material. References to unpul~lishedmaterial may include articles o r

abstracts that have been presented at a sociely meeting I>ilt not pi~l~lisliccl
;inti 111:1-
terial accepted for publication but not published; If, during the course of 11.16pill>-
lication process, these materials are published or accepted for publication, anrl if the

tion should be included.

1. Durbin D, Kallan M, Elliott M, Arl,og;~stK, Comcjo I(. \Y'ill>rc)n F HI^ I )I

injury to restrained children from 1,;tsscngcr :tir Ix~gs.I';~jx.rI,rcw.llrt.<l .!i

59
3 1 3 Spec~alP r i n t Materials

46th Annual Meeting of the Association for the Advancement for Auto-
motive Medicine; September 2002; Tempe, AZ.
3. WcI>cr I(), I.cc J, 1)ccrescc It, Sul>hasis M, I'rinz K. Intraoperative PTH
monitoring in p;r~athyroidhyperplasia requires stricter criteria for success.
I';~pc~r
prc.xc.nlc.cl:It: 25111A I I I I ~ I :A~ncric:~n
~~ hssoci:~tiono f Endocrine Sur-
gvo~rsM~s~~lillg;hl)ril 0, 2004; Cl~arlollcsvillc,VA.
3. Greenspan A, Eerdekens M, Mahmoud R. Is there an increased rate of
cerebrovascular events among dementia patients? Poster presented at:
24th Congress of the Collegium Internationale Neuro-Psychophamaco-
logicum (CINP); June 20-24, 2004; Paris, France.
4. Khuri FR, Lee JJ, Lippman SM, et al. sotr re ti no in effects on head and neck
cancer recurrence and second primary tumors. In: Proceedings from the
Atnerican'Society of Clinical Oncology; May 31-June 3, 2003; Chicago, IL.
Abstract 359.
Once these presentntions are published, they take the form of reference to a book,
journal,.or other medium in which they are ultimately published, as in example 5 (see
3.12.1, References to Print Books, Complete Data):
5. Cionni RJ. Color perception in patients with W- or blue-light-filtering
IOL.. In: Symposium on Catarct, IOL, a n d Refractiue Surgery. San Diego,
CA: American Society of Cataract and Refractive Surgery; 2004. Abstract.
337.

. . ater rial ~ccepted

'Y:3:. for Publication but Not Yet Published. Formats suggested for both
journal articles and books, accepted for publication but not yet published, are shown
below:
6. Carrau RL, Khidr A, Crawley JA, Hillson EM, Davis JK, Pashos CL. The im-
pact of laryngopharyngeal reflux on patient-reported quality of life. Laryn-
goscope. In press.
7. Ofri D. Incidental Findings: Lessons From My Patients in the Art of Medi-
cine. Boston, MA: Beacon Press. In press.

Abrc~:Some ptiblications require that authors verify that acceptance for publication
has been granted (authors sometimes confuse submitted with accepted).6s8 Some
publishers also prefer the tenn'forthcoming to in press because they feel that inpress
is not appropriate for electronic citations,6.8 but J A M and the ArchiuesJ.ournals use
for
it1 p 1 - e ~ ~ both forms.

Material Submitted for Publication but Not YetAccepted. In the list of references, d o
not include material that has been submitted for publication but has not yet been
acccptccl. This mnterial, with its elate, shoi~lclbe noteci in the text as "unpublished
clat:~,"as follows:
These'findings have recently been corroborated (H. E. Maman, MD, un-
published clata, 1;rnllltry 2005 ) .
Similar findings have I)ccn noted by ~obens'and H. E. Marman, MD (un-
pi~l~lisli~d
<I:I~;I.
Lo()i)
 3.13.10 Secondary Citations and Quotations (Including Press Releases)

Numerous ~ t u d i e s ' ~(also

- ~ ~H. E. Marman, MD, unpublished cl~ita,2005)
have described simiiar findings.
If the unpublished data referred to are those of the author, indicate this as follo\vs:
Other data (H.E.M., unpublished data, 2005). . . .

Personal Communications. Do not include "personal communications" in the list of

references. The following forms may be used in the text:
In a conversation with H. E. Marman, MD (August 2005). . . .
Accordiig to a leper from H. E. Marman, MD, in August 2005.. ..
Similar findings have been noted by ~ o b e r t and
s ~ by H. E. Marman, MD
. (written communication, August 20051.'
~ c c o r d i n ~the
' t omanufacturer (H. R: Smith, oral communication, May 2005),

The author should give the date of the communication and indicate whether it was in
oral or written (including e-mail) f o ~Highest
. academic degrees should also be
. - given. If the afFiliation of the person would better establish the relevance and au-
thority of the citation, it should be included (see the example above, where H. R.
Smith is identified as the drug's manufacturer).
See also 3.15.9, Electronic ~eferences,E-mail and E-mail List (Listsenre) Mes-

Secondary Citations and Quotations (Including Press Releases). Reference may be

made to one-3uthor's citation of, or quotation from,. another's work. Distinguish
between citation and quotation (ie, between work mentioned and words actually
quoted). In the text, the name of the original author, rather than the secondary
source, should be mentioned. (See also 3.11.12, References to Print Journals, Disc-
ussants.) As with citation of an abstract of an article rather than citation of the original
document (see 3.11.9, References to Print Journals, Abstracts and Other Material
Taken From Another Source), citation of the original document is preferred unless it
is not readily available. Only items actually consulted should be listed. The forms for
listed references are as follows:
1. Cauley JA, Lui L-Y,Ensmd KE, et al. Osteoporosis and fracture risk in
women of different ethnic groups. JAMA. 2005;293(17):2102-2108. Cited
by: Acheson LS. Bone density and the risk of fractures: should treatment
thresholds vary by race [editoiialPJAMA. 2005;293(17):2151-2154.
2. Kato S, Sherman PM. What is new related to Helicobactwpylori infection
in children and teenagers? Arch Pediutr Adolesc Med. 2005;159(5):415-
421. Quoted by: Prazar G. How many pcc~i;\tricbnsdoes it take to ch;~ngc
a practice? or how to incorporate cIi;~ngcinto pc~cticclcrlitoriall. Arch
Pediatr Adofesc Med. 2005;159(5):500-502.

61
 3 , t ~ i > \ ;14k Can;ltl:l to ban Web pharmacies [press release]. New York, NY:

.-\hx~i:~tcJ 1'rc.s~;hlarch 30, 2004.

Classical References. Classical references may deviate from the usual forms in some
dctails. In lirany instances, the facts of publication are irrelevant and may be omitted.
Ihte of ~)~ll>lication should be given when available and pertinent.
1. Shakespeare W. A Midsummer Night's Dream. Act 2, scene 3, line 24.
2. Donne J. Second Anniversary. Verse 243.
For classical references, m e Chicago Manual of style9 may be used as a guide.
3. Ariaotle. Mdr~~/!)!sic.s.
3. 2.19661) 5-8.
In I)il)lical rcfcrcnccs, do not :~l,l)rcvi:~tc the names of hooks. The version may be
inclutlecl if the information is provided (see example 4). References
to tllc 13il)le ; ~ r cusually incluclccl in tllc tcxt.
The story begins in Genesis 3:l.
Paul admonished against succumbing to temptation (I Corinthians 106-13).
Occasionally they may appear as listed references at the end of the article.
4. I Corinthians 10:6-13 (RSV).

Other Media
*
-k Audiotapes, Videotapes, DVDs (Digital Video Disks). Occasionally, references may
include citation of audiotapes, videotapes, or DVDs. The form for such references is
as follows:
1. Moyers B. On Our Own T-: M o y m on Dying [videotape]. New York,
NY: ThirteenIWNET; 2000.
2. Ayers S. Terrorism: Medical Response [DVDI. Edgartown, MA: Emergency
Film Group; 2002.
3. Acland RD. Acland's D m Atlas of Human Anatomy [DVDI. Philadelphia,
PA: Lippincott Williams & Wilkins; 2003.
Note that the place of the author may be held by the host and the place of the
publisher may be held by the distributor.
For citation format for books on CD, see 3.15.2, Electronic References, Books
and Books on CD-ROM, and for audio presentations available online, see 3.15.10,
Electronic References, Online Conference Proceedings/Presentations.

Transcript of Television or Radio Broadcast. Citation of transcripts to television or

radio broadcasts take the following form:
1. Mental illness in children-part1 [transcript]. Morning Edition. National
Public Radio. September 22, 2003.
2. Shutting out Tourette's syndrome [transcript]. 60 Minutes. CBS television.
January 17, 2005.
 3.1 5 Electronic References

The Internet made a lot of tbings very simple.

Bibliographies a m ' t among them.
J. ~ronholz'~

.. . the basic rules of citation am still applicable

when referencing the Internet.
K . ~atrias"

Electronic References. Electronic references have become considerably more

common since the publication of the ninth edition of this manual. Internet refer-
ences, rather than being something that only authors, editors, publishers, and libr-
arians fretted about, were the subject of a front-page article in the Wall Street
~oumal.'~ Guidelines for handling electroac references are now readily available.
Although the American ~sychological~ssociation'~"~ was among the first to propose
such guidelines, those of the National Library of Medicine (NLM)'~ are more widely
used for medical research.
Print and electronic references differ in several ways. Below are some issues to
consider.
Web sites may be evanescent, vanishing much faster than books go out of print.
To address this phenomenon, the NLM "strongly recommend[sl that the user
produce a print or other copy when possible for future referen~e."~~'') Some
journals recommend this to authors in their inst~uctions.'~Dellavalle et all6
suggest that "the best current solution to improve access to Internet references is
to require capture and submission of all Internet information at the time of
manuscript consideration." In preparing a reference list, authors should check to
make sure any URts (uniform resource locators) they cite are still valid; editors
should check these again. Since typographical errors render URLs invalid, vali-
dation may be required several times in the publication process. Although it is
desirable to have functio~allinks,it is to be expected that, over time, some links
may break as sites cease to exist, much as books may go out of print. Any
updating of URLs in an effort to "fix" a link should be done with care, ensuring
that the material that was cited originally still exists on the revised link.
Some publishers are using other less-transient identifiers instead of, or in addition
to, URLs. Among these are the digital object identifier (DO11 and the Pubhled
identification number (PMID). The DO1 may be used to identify not just indi-
vidual journal articles, but any piece of content (eg, a single figure) within an ar-
ticle; DOIs may also be assigned to books and many other forms of intellectual
content.
The DO1 has 2 elements, separated by a forward slash: the prefix and the suf-
fix. The prefix is assigned by a DO1 registration agency (an organization 11x1)-have
multiple prefixes) and the suffix, which fonows the prefix and a foward slash.
identifies the particular item. All DOIs begin with 10. For example, in the DO1 in
example 6 below (10.1038/nature02312), "10.1038" is the prefix and "n;l-
turd)2312' is the suffix. (Note: Some publishers use other identifiers as a part o f
the suffix) The DOls can be any length and, once assigned, are not changecl. 'So
3.15 Electronic References

tind an article wing r l 1 ~1X>[.a ruder can enter lhc DO1 bn rl~r2*t'.irc.tl t*)s c)n [he
DO1 \Veb sire (hrtp:;/~fs.doi.orK/)
-
or in sonle journal x x s h cnglnes.I h c1o.w 35
possil>le lo pul~lica~~on. 11 is advisable to check all DOls to make surc that they
resolve.
The PMID is assigned to the journal articles cited in a journal indexed by
PubMed and is a part of the PubMed citation. To find an article, a reader can enter
the PMID in the "search" box on the PubMed Web site ( h t t p : / / ~ . n c l > i . n l m
.nih.gov/PubMed/). Some journals publish the DO1 with the article (seeexample
'
6 in 3.15.1, Online Journals); the PMID is usually not published but exists as a
behind-the-scenes identifier.
ri Web sites may be updated much more frequently than published books or jour-
nals; thus, it is critical to provide the date that the author accessed the site and, if
possible, the date on which the information was updated.
a Some journals and books may be available in print and online, but these versions I
may not be identical: the differences may be as minor as the online correction of a
typographical error discovered in the print journal, which is not formally corrected
and is impossible to track (see 6.2.7, Editorial Assessment and Processing, Editorial
Processing, Corrections), or as major as 2 versions of the same article, or situations
in which additional material (eg, tables or figures) is available only online. Books
I
are often adapted for the Web to enhance interactivity for readers and add features.
Because of these possible differences between various versions, it is critical &at
authors cite the version consulted. Note: The cited version may not be the version
of record (ie, the version that the publisher considers authoritative).

CckCk.srr Online Journals. The basic format for reference to an article in an online journal isas
follows:
Author(s). Title. Joumal Name [using National Library of Medicine
abbreviations-see 14.10, Abbreviations, Names of Journalsl. Year;vol(issue
No.):inclusive pages. URL Jprovide the URL in this field; no need to use
"URL:" preceding it]. Published [datel. Updated [datel. Accessed [datel.
Note: Use the URL that will take the reader most directly to the article, not a long
search string and not a short, more general URL (one to the publisher's home page,
for example); if a URL is provided, as close as possible to publication verify that the
link'stillworks. ~atrias"notes that NLM recommends using the location displayed in
the-Webbrowser as the URL.For a journal article, the accessed date will often be the
only date available. This is especially important for journals that provide no "vex-
sioning" (eg, date posted, date updated or revised).
1. Duchin IS. Can preparedness for biological terrorism save us from per-
tussis? Arch Pediatr Adolesc Med. 2004;158(2):106-107. http://archpedi
Accessed June 1, 2004.
.ama-assn.org/cgi/content/full/158/2/106.
Man). journals, such as Archives of Pediatrics G Adolescent Medicine in the example
:hove, have parallel print and online publication, and the page numbers of the print
article are included in the online citation. In this example, the date the article was .
postecl (ie, published) was not provided and there were no updates, so only the date
tlw article WIS accessed is listed. The inclusion of the URL and the date accessed,
 3.15.1 Online Journals

which differentiates this from the citation of the identical article in print, indicates h a t
the online version of the article was seen and hence is appropriately cited.
In the example below, however, the article is only available online and has no

2. Gore D, Haji SA, Balashanmugam A, et al. Light and electron microscopy

of macular corneal dystrophy: a case study. Digit J Opbthalmol. 2004;lO.
http://m.djo.harvad.edu/sit'e.php~url=/physicians/oa/671. Accessed
December 6, 2005.
Other online-only articles without page numbers may be noted by other identifiers,
eg, by e-page numbers (examples 3 and 4) or by article number (example 5).
3. Laupland KB,Davies HD, Low DE, Schwartz B, Green K;Ontario Group A
Streptococcal Study Group. Invasive group A streptococcal disease in
children and association with varicella-zoster virus infection. Pediatrics.
2000;105(5):e60. http://pediatri~~.aappublications.org/cgi/content/h~l/lO5
/5/e60. Accessed~April30,2004.

Examples 5 and 6 provide the DO1 rather than a URL. In this case, it is not necessary
to also provide the URL. When the DO1 is provided, it is preferable to cite it r.~tl~er
than the URL. Note: The DO1 is provided immediately after "doi:" and is set c l o . 4 up
to it, per convention. No accessed date is required for the DOI, making it the last iten]
in the reference.
5. Smeeth L, Iliffe S. Community screening for visual impairment in thc
elderly. Cocbrane Database Syst Rev. 2002;(2):CW01054. doi: 10.1002
/14651858.~~1001054.

protein shugoshin protects centromeric cohesior~during meiosis. Strtrrt-c..

2004;427(6974):510-5i7. doi:lO.l038/nature02312.
. .

In some cases, different versions of the same article are published in print :rnd online.
The BMJs ELPS (electronic long, print short) is one example.'* The print joiirn;~l
article (short version) is also made available online. Note: The version consulted is thc
version that should be cited. If the author consulted the article in the print jourmrl. tllc
reference would be cited like any other print jo~~rnal article (see 3.11, Rcfercnccs t o
Print Journals).
7. Deeks JJ, Smith LA, Dmdley MI>..Efficacy, tolcr:~l>ilily,nnd uppcr L.. r.~stro-
intestinal safety of celecoxil) for treatment of ostcoarthritis ancl rhcuma-
toid arthritis: systematic review of randomised controlled trials. L3.1!/. 2002;
3250365):619-623.
If the author consi~ltedthe same article online, the reference would be fornlattecl as

8.h e k s J , Smith IA.Bradley MD. Efficacy,tolerability, and upper gastro-

intestinal safety of celecoxib for twatment of osteoarthritis and rheuma-
toid arthritis: systematic review of r.tndorni.wd controllctl triiils Ial>ridged].

65
3.15 Electronic References

.'002;32 j(730j):O 1')-623. h111'. ;'1~1i~.I~m~~oi1rn~I~.con~/~gi/conk-nl

fs',!I/.
/abridgcJ/37j/736j/61~. I'ul)li~llcd k p [ c ~ n t x 21.
r LWZ. A c ~ c s . ~Oc7o-
d
ber 21, 2002.
j
-
If the author consulted the long version of this article, availal~leo ~ online,
b ~ the
reference would be forri~attedas follows:
9. Deeks JJ, Smith LA, Bradley MD. Efficacy, tolerability, and upper gastro-
intestinal safety of celecoxib for treatment of osteoanhritis and rheuma-
toid arthritis: systematic review of randomised controlled trials. BMJ. 2002;
325(7365):619. h~p://bn~j.bmjjoumals.com/cgi/content/fu~/325/7365/619.
I'ublished September 21, 2002. Accessed October 11, 2002. i

Note that the online citation of the long version (example 9) differs liom that of the
short version (example 8) in that it does not provide inclusive page numbers but
give; only the first page in the print journal. Many online journals, however. d o use i
inclusive page numbers. I
In the exanllile below, the online article includes a video. This is mentioned in
an editor's note in the print journal; in the online journal, a link to the video appears
in the table of contents and as a link within the article. The citation to the print article ,
appears as follows:
10. Bertocci GE, Pierce MC, Deemer El Aguel F. Computer simulation of stair
falls to investigate scenarios in child abuse. Arch PediatrAdolescMed: 2001;
155(9):100&1014.
The citation to the online article, containing the video, would be as follows:
11. Bertocci GE, Pierce MC, Deemer E, Aguel F. Computer simulation of stair
falls to investigate scenarios in child abuse. Arch PediatrAdolesc Med. 2001;
I
i
155(9):1008-1014. http://archpedi.arna-assn.org/cgi/content//l55/9 I
11008. Accessed February 27, 2004. I
A citation to only the video in the online version would be as follows:
12. Bertocci GE, Pierce MC, Deemer El Aguel F. Computer simulation of stair
falls to investigate scenarios in child abuse [video]. Arch Pediatr A d o k c
Med. 2001;155(9):100&1014. http://archpedi.ama-assn.org/cgi/content'
/fu11/155/9/1008/DCI. Accessed February 27, 2004.
In the following example, the online article contains 3 tables not included in the print
version. These are cited in the print article as eTable 1, eTable 2, and eTable 3; in the
online journal, these appear as links within the article; and on the PDF they appearps
pages e l to e7.
13. DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2
diabetes mellitus:, scientific review. J A M . 2003;289(17):2254-2264, el-
e7. http://jama.ama-assn.org/cgi/content/full/289/l7/2254. Accessed De-
cember 6, 2005. '
If an article is published online ahead of print publication, it may appear in 1 of 3 ,
ways: (1) posted without editing; (2) edited and posted as it will appear in print, only!
ahead of the print publication (with or without print pagination); or (3) edited and
posted as pan of a specific issue of the journal. The first is found more often in the
i
!

- i
1
 3.15.2 Books and Books on CD-ROM

hysical sciences (eg, physics preprint servers) than in medicine. Examples of the
second (example 14) and third (example 15) are given below:
14. van der Hoek L, Pyrc K, Jebbink MF, et al. Identification of a new human
coronavirus [published online ahead of print March 21, 20041. Nut hfed.
doi:10.1038.nml024.
In example 14, the article has not yet been paginated in the print journal and the DO1
, serves as the unique identifier for the article until publication. Once the article has been
ublished in print, the full citation is provided to facilitate linking (see example 15).
15. van der Hoek L, m c K, Jebbink MF, et al. ~ d e n t ~ c a t i oofn a new human
coronavirus [published online ahead of print March 21, 20041. Nat Med.
2004;10(4):368373. doi:10.1038.nm1024.
mple 16 is for an article not yet published in print and example 17 is for the
nce once it has been published-in print. Note: The title, byline, or other com-
ponents may have changed slightly between online-only and print publication.
16. Cannon CP, Braunwald E, McCabe CH, et al; Pravastatin or Atorvastatin
Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction
22 Investigators. Comparison of intensive and moderate lipid lowering
with statins after acute coronary syndromes [published online ahead of
print March 8,20041. N Engl J Med. doi:lO.l056/NEJMoa040583.
17. Cannon CP,Braunwald E, McCabe CH, et al; Pravastatin or Atorvastatin
Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction
22 Investigators. Intensive vs moderate lipid lowering with statins after
a&te coronary syndromes [published online ahead of print March 8,20041.
N Eng2 JMed. 2004;350(15):1495-1504. doi:l0.1056/NEJMoa040583.
Some journals allow the reader to submit an immediate online response to articles
(eg, BMJs Rapid Responses and Pediatrics' Posl-publication Peer Reviews [P~RI).
'Examples of these are below:
18. Deutsch J. Less is better [Rapid Response]. BMJ.http://bmj.bmjjournals
.com/cgi/eletters/328/7438/0-g#51798. Published February 27, 2004. Ac-
cessed April 30,2004.
19. Molloy EJ, Nigro K, Sandhaus L, Watson RWG, Walsh MC. Labor and stress
at delivery are confounders in the evali~ationof neonatal Sepsis [Post-
'

publication Peer Review]. Pediatrics. 2004;1136):1173. http://pediatrics

.aappublications.org/cgi/eletters/113/1173. Published May 28, 2004. Ac-
cessed June2,2004.

Books and Books on CD-ROM. The basic format for reference to an Internet-based
book is as follows: Note: If the reference is to the entire book, the information about
chapter title and inclusive pages is not included.
Author(s). Chapter title. In: Editor(s). Book firle. [Edition number, it' it is rhe
second edition or above; mention of first edition is nor necessavl rd. Ciry.
State (or country) of publisher: Publisher's n;lrnc; copyri~liryc.;~r-inr.l~~si~~c
pages. URL: [provide URL and verify that thc link \tili rvork4 c . 1 0 ~ ;I%
possible to the time of publication).hccessc.d Irl:~lcl

67
3.1 5 Electronic References

1. Kesnick NM. Geriatric medicine. In: Braunwald E, Fauci AS, Isselbacher KJ,
et al, eds. Harrison's Online. Based on: Braunwald E, Hauser SL, Fauci AS,
Kasper DL, Longo DL, Jameson JL, eds. Harrison's Principles of Zntenuzl
Medicine. 15th ed. New York, NY: McGraw-Hill; 2001. http://www.hsls
. p i t t . e d u / r e s o u r c e s / d o c u m e n t a t i o n / h a r r i s . Accessed Decem-
ber 6, 2005.
2. Lunney JR, Foley KM, Smith TJ,Gelband H, eds. Describing Death in
America: What We Need to Know. Washington, DC: National Cancer
Policy Board, Institute of Medicine; 2003. http://www.nap.edu/books
/0309087252/html/. Accessed December 6, 2005.
Citation of a book or monograph in CD-ROM format follows fairly closely the form
used for a book or monograph (see 3.12, References to Print Books), with.the key
difference being the inclusion of the name of the medium in brackets after the title
(eg, [CD-ROM]). Titles of books on CD-ROM follow the capitalition style of print
book titles and are italicized. Note: If the title of the book (eg, Cecil Textbook of
Medicine on CD-ROM)indicates the medium, no mention of the medium in brackets
is necessary.
3. Alberts B, Johnson A, Lewis J, Raff M, Roberts J& Walter P. Molecular
Biology of the Cell [CD-ROM]. 4th ed. New York, NY: Garland Science,
2002.
4. Longo DL. Immunology of aging. In: Paul WE, ed. Fundamental Immu-
nology [CD-ROM]. 5th ed.Philadelphia, PA: Lippincote Williams & Wikins;
2002;chap 33.

Web Sites. In citing data from a Web site, include the following elements, if available,
in the order shown:
Author(s), if given (often, no authors are given). Title of the specific item
cited (if none is given, use the name of the organization responsible for the
site"). Name of the Web site. URL [provide URL and verify that the link still
works as close as possible to publication]. Published [datel. Updated [datel.
Accessed [datel.
As ~atrias"notes, "the title page is the usual place to look for citation information in
a print publication, but no standards have been adopted for the Internet for the
content of what would equate to a title page." This can make consiructing a reference
for a Web site difficult, but as much relevant information as possible should be
included.
1. International Society for InfectiousDiseases. ProMED-mail Web site. hnp:]
www.promedmail.org. Accessed April 29, 2004.
2. Sullivan D. Major search engines and directories. SearchEngineWatch Web
site. http://www.searchenginewatch.com/links/aicle.php/2l56221. U p
dated April 28,2004. Accessed December 6, 2005.
3. Interim guidance about avian influenza A (H5N1) for US citizens living
a\>road.Centers for Disease Control and Prevention Web site, http://www
.cdc.gov/traveI/other/avian~flu~ig_americans~abroad~032405.htm. Up
dated Noven~ber18, 2005. Accessed December 6 . 2005.
 3.1 5.5 Government/Organization Reports

4. Sample size calculation. Grapentine Co Inc. http://www.grapentine.com

/calculator.htm.. Accessed December 6, 2005.
5. Recommendations for the care and maintenance of high intensity me-
tal halide and mercury vapor lighting in schools. National Electrical
Manufacturers '~ssociation: http://www.nema.org/stds/halide-schools
.cfm#download. Accessed December 6, 2005,
6. Truth and reconciliation: examining human rights violations in South
Africa's health sector: submission to the Truth and Reconciliation Com-
mission concerning the role of health professionals in gross violations of
human rights. American Association for the Advancement of Science Web
.aaas.org/trc-med/presub.htm. Published 1997. Accessed

Online Newspapers. Except for the.citation of the URI. and the accessed date, the ,

format is the same as that for citing a print newspaper reference shown in 3.13.1,

1. Weiss R The promise of precision prescriptions. Washington Post. June

24,2000Al. http://www.washingtonpost.com. Accessed October 10,2001.
2. Perez-Pena R Children in shelters hit hard by asthma. New York Times.
March 2,2004. http://~.nytimes.com/2004/03/02/nyregion/O2asthma
.html. Accessed March 2, 2004.

Government/Organization Reports. These are treated much like electronic joumal

and book references: use joumal style for articles and book style for monographs.
Note: As with electronic joumal references, of the dates published, updated, and
accessed, often only the accessed date will be available.
1.Jacob Siegel; Administration on Aging. Aging into the 21st century. hap://
w w w . a o a . g o v / p r o f / S t a t i s t i c s / f u t u r e _ g r o ~ l . a s p .Pub-
lished May 31,1996. Accessed December 6,2005.
2. World Medical Association. Declaration of Helsinki: ethical principles
. for medical research involving human subjects. http:/www.wma.net/e
/policy/b3.htrn. Updated June 10, 2002. Accessed February 26, 2004.
3. US Department of Health and Human Services. Protection of human sub-
jects. 45 CFR $46. http://www.hhs.gov/ohrp/humansubjects/guidance
/45cfr46.htm. Revised November 13, 2001. Effective December 13, 2001.
' Accessed February 27,2004.
4. World Health Organization.Equitable access to essential medicines: a frame-
work for collective action. http://whqlibdoc.who.int/hq/2004/WHOOEDM
-2004.4.pdf. Published March 2004. Accessed December 6,2005.
In the 2 examples below, the number of the working paper (example 5) and the
publication number (example 6) provide information' in addition to the URL and
could prove helpful should the URLs change.
5. Dafney L, Gruber J. Does public insurance improve the eI3c1enc-y o f
medical care?Medicaid expansions and child hospit;~liz;~rion\http //\\T\.w

69
3 1 5 Electronrc References

.nbcr.org/papers/w7555. National Bureau of Economic Research working

paper w75j5. 1JublishedFebruary 2000. Accessed February 26, 2004.
6. Johnson DL, O'Malley PM, Bachman JG. Secondary School Students.
Bethesda, M D : National Institute on Drug Abuse; 2001. Monitoring the Fu-
ture: National Survey Results on Drug Use, 1975-2000;vol 1. NIH publi-
cation 01-4924. http://www.monitoringthefuture.org/pubs/monog~pl~s
/vo11-2000.pdf. Published August 2001. Accessed February 27,2004.

Software. To cite software, use the following form:

1. Epi Info [computer program]. Version 3.2. Atlanta, GA: Centers for Disease
Control and Prevention; 2004.
2. Intercooled STATA (for Windows) [computer program]. Version 7.0. Col-
lege Station, TX:StataCorp; 2000.
Software need not be cited in the reference list if it is mentioned only in passing o r is
available without charge via the Internet (eg, shareware or freeware).

~o&are Manual or Guide. In ci.ting a print software manual or guide, use the fol-
lowing form, which follows that for citation of a book (see 3.12.1, References to Print
Books, Complete Data).
1. Bott E, Leonhard W. Special Edition Using Microsoft Ofice XP.Indianap
olis, IN: Que; 2001.
2. Dean AG, Dean JA, Coulombier D, et al. E$z Info, Vmion 6 A Word-
Processing, Database, and Stati3tic.s Program for Public Health on LBM-
Compatibk hficrocomputm. Atlanta, GA: Centers for Disease Control and
Prevention; 1994.
3. Dixon WJ,Brown MB, Engelrnan L, Jemirch RJ, eds. BMDP Statistical
Software Manual. Los Angeles: University of California Press; 1 9 0 .

Databases. In citing data from an online database, include the following elements, if
applicable, in the order shown:
AuthorCs). Title of the database [database online]. Publisher's location (city,
state, or, for Canada, city, province, country, or, all others, city, country):
publisher's name; year of publication'and/or last update. URL [provide URL
and verify that the link still works as close.as possible to publication]. Ac-
cessed [date].
Additional notes that might be helpful or of interest to the reader (eg, date the site
was updated or modified) may also be included.
1. PDQ: NCI's Comprehensive Cancer Database. Bethesda, MD: National Can-
cer Institute; 1996. http://www.cancer.gov/cancerinfo/pdq/cancerdatabase.
Updated December 18, 2001. Accessed April 29, 2004.
2. Genew, HUGO Gene NomenclatureCommittee(HGNC). Human Gene No-
menclature Database Search Engine. http://www.gene.ucl.ac.uk/cgi-bin !

/nomenclature/searchgenes.pl.Accessed February 27, 2004.

 -- .
- - - - ---

3.15.10 Online Conference Proceedings/Presentations

3. Online Mendelian Inheritance in Man, OMIM. Baltimore, MD: Johns Hop-

kins University Press, 2000. http://wmv.ncbi.nlm.nih.gov/entrez/query
.fcgi?db=OMIM. Accessed December 6,2005.

E-mail and E-mail List (Listsewe) Messages. References to e-mail and e-mail list
messages, like those to other forms of personal communications (see also 3.13.8,
Special Print Materials, Unpublished Material), should be listed parenthetically in the
text rather than in the reference list and should include the name and highest aca-
of the person who sent the message and the date the message was
sent. Note: As with all personal commuhcations, permission should be obtained
from the author.
An example of an e-mail citation, appearing in running text, is given below:
There have been no subsequent reports of toxic reactions in the exposed
groups (Joan Smith, MD,e-mail communication, March 29, 2004).
An e-mail list (listserve) message cited in running text would be cited as in the

The Editorial Committeeof the World Association of Medical Editors OVAME)

is preparing a statement on government embargoes and scientific exchange
(Margaret A. Winker, MD,WAME listserve, February 25,20041.
An e-mail(listserve) thread cited in running text would be cited as in the example

How authors learn writing skills. WAME listserve discussion. October 19-
22, 2005. http://~~~.wame.org/writingskills.htm. Accessed February 15,

Online Conference Proceedings/Presentations. These are treated much the same as

a "presented atnreference (see 3.13.8, Special Print Materials, Unpublished Material),
with the addition of the URL and the accessed date.
1. Chu H, Rosenthal M. Search engines for the World Wide Web: a compara-
tive study and evaluation methodology. Paper presented at: American So-
cietyfor Information Science 1996AnnualConference;October 19-24,1996;
Baltimore, MD. h ~ p : / / m . a s i s . o r g / a ~ u a 1 - ~ / e ~ e c t r o n i c p r ~ / c ~ 1 ~
.htrnl. Accessed February 26,2004.
2. Colliqs F. Talk presented at: National Human Research Protections Advi-
sory Cornminee; April 9, 2001; Bethesda, MD. http://www.hl~s.gov/ohrp
/nhrpac/mtg04-01/0409mtg.txt. Accessed February 26, 2004.
The presentation in example 2 did not have a title; hence, the "title" field and the
"presented at" field were combined.
3. Klausner R. Statement on fiscal year 2002 president's budget request
for the National Cancer Institute before the House Subcommittee on
Labor-HHS-Education Appropriations. http://cancer.gov/legis/testiinony
/house2002.html. Accessed February 26, 2004.
An audro pre.sentation would be cited as follows:

71
 3 16 US Legal Rrfrfence,

* ~ - l > l . ~ ~ cthcr.~py
t i o 1 1 1 1 1 1 1 1 ~r. ~ l ~ ~ n tIhlornlng Id~tlon~ucl101 Sarlonal Public
tt.1~11~): ! L J ~ I ~ I 5 , 2 ~ 2 l~ttp://\v\v\v.r~pr
. ~~r~/~~rn~~I~t~-s/s~o~/sto~.php
!htor).l~l=1 I - i 7 X j j . Acccsscd March 4. 2Wl.

News Releases and Miscellaneous

1. I-lopkins rCsponsc to FDA ol~scrvations[news release]. Baltimore, MD:
Iol~nsI Iopkins 0I'fic.c oFCom~nunicationsand I'ublic Affairs; Septen~ber7,
Lool. I11~~~://~~~\~w.l~o~~ki1is1ii~'dici1~c.org/pre~s/2001/SE1~MI3E1~/O1O~7A
.11\111.Ac~c~ssc'cl
J : C I ) I ~ ~ I ~ T26,
~ 2004.
2. If you want to quit for good-your doctor can help [patient brochure].
Kansas City, MO: hlerrell Dow Pharmaceuticals; 1984. http://www.pmdocs
.con1/PDF/202.17N793~9794~O.pdf. Accessed February 26, 2004.

Legal References. Legal references cited online contain the same basic information as
legal references cited in print (3.16, US Legal References), with the addition of the
URL and the accessed date.
1. US Food and Drug Administration. The Orphan Drug Act. 1983. http://
www.fda.gov/orphan/oda.htm.Accessed December 6, 2005.
2. Bybee JS [Office of Legal Counsel, US Department of Justice]. Standards of
conduct for interrogation under USC 512340-2340A [memorandum for Al-
berto R. Gonzales, August l, 20021. http:~news.hdlaw.com/wp/d~~~
/d'oj/hyhee80102mem.pdf. Accessed December 6,2005.

-b US Legal References. A specific style variation is used for references to legal cita-
tions. Because the system of citation used is complex, with numerous variations for
different types of sources and among various jurisdictions, only a brief outline can
be presented here. For more details, consult The Bluebook A UniJom S p m of
citation.19
Legal references, as with other references (eg, journal, book), may also be cited
as electronic references (see 3.15.12, Electronic References, Legal References).

Method of Citation. A legal reference may be included in the reference list in full,
with a numbered citation in the text, or it may be included in the text parenthetically
and not included in the reference list. In scholarly articles, a full citation in the
referexe list is preferred, but in a news article or book review, for example, a
parenthetical citation in the text might be adequate.
y
,~&~&$&$~
i
( *.1=,
Full Citation
In a leading decision on informed consent,' the California Supreme Court
stated. . . .
In the case of Cobbs v rant'
This reference would then appear in the reference list as follows:
1. Cobbs LJ Grunt, 502 P2dl (Cal 1972). .
 3.16.2 Citation of Cases

Parenthetical In-Text Citation

In a leading decision on informed consent (Cobbs u Grant, 502 P2d 1 [Cnl
1972D, the California Supreme Court stated. . . .
In the case of Cobbs v Grant (502 P2d 1 [Cal19721)... .

Citation of Cases. The citation of a case (ie, a court opinion) generally includes, in
the following order:
The name of the e s e (including the v ) in italics. To shorten the case name, use
only the names of the firstparry on each side; omit "et al" and "then;use only the
last names of individuals .
1 The volume number, abbreviated name, and series number (if any) of the re-
porter (bound volume of collected cases)
The page in the volume on which the case begins and, if applicable, the specific
page or pages on which is discussed the point for which the case is being cited
In parentheses, the name of the court that rendered the opinion (unless the court
is identified by the name of the reporter) and the year of the decision. If the
opinion is published in more than 1reporter, the citations to each reporter (known
as parallel citations) are separated by commas. Note that u (for versus), 2d (for
second), and 3d (for tbird) are standard usage in legal citations.
1. Canterbuty v Spence,464 F2d 772,775 (DC Cir 1972).
This case is published in volume 464 of the FederalReporter, second series. The case
begins on page 772, and the specific point for which it was cited is on page 775. The
case was decided by the US Court of Appeals, District of Columbia Circuit, in 1972.
The proper reporter to cite depends on the court that wrote the opinion. Table
T.2 in The ~luebook'~ contains a complete list of all current and former state and
federal jurisdictions for the United States The 18th edition of m e Bluebook also has
many examples of non-US cases.

US Supreme Court. Cite to US Reports (abbreviated as US). If the case is too recent to
be published there, cite to SupremeCourt Reporter(SCt), US Reports, Lawyer's Edition
(LEd), or U S h w Week (USLWI-in that order. Do not include parallel citation. The
format for these references includes the following, in the order specified (the
punctuation is noted; where none is given after a bulleted item, none is used):
First party v Secondpatty,
Reporter volume number
a Official reporter abbreviation
n First page of case, specific pages used
e (Year of decis~on).
Some example5 follow
2 School h r d of rvarsatr Ctty u Arlrtte, 480 US 273, 287 (1987).
3 Addtnglon v T-, 441 US 418, 426 (1979)

73
3.16 US Legal References

$$&!$
US~ ~ ~of~
Court Appeals (Formerly Known as C i m i t Courts of Appeals). Cite to Fc-rlt~ul
Reportel; original or scconcl (F or I-2d). ?hest. in~emlcdiateap~llutc-lc\.t-l
courts hear appeal's from US district courts. federdl administrative agctncics, and other
federal trial-level courts. Circuits are referred to by number (1st Cir, 2d Cir. etc)
except for the District of Columbia Circuit (DC Cir) and the Federal Circuit (Fed Cir),
which hears appeals from the US Claims Court and from various customs and patent
cases. Divisions are denoted by ED (Eastern Division), WD (Western Division), ND
(Northern Division), and SD (Southern Division). Citations to the Federal Reporter
must include the circuit designation in parentheses with the year of the decision. The
format for these references includes the following, in the order specified (the
punctuation is noted; where none is given after a bulleted item, none is used):
a First party v second party,
Reporter volume number
m Official reporter abbreviation
First page of case, specific page used
(Deciding circuit court and year of decision).
Some examples follow:
4. Wikox v United States, 387 F2d 60 (5th Cir i967).
5. Scoles v Mercy Healtb Corp, 887 F Supp 765 (ED Pa 1994).
6. Brad4 u Univemmty of T a a s M.D. Anderson Cancer Ctr, 3 F3d 922,924
(5th Ci 1993).
7. Doe u Washitzgton Unimsity, 780 F Supp 628 (ED Mo 1991).

US District Court and Claims Courts. Cite to Federal Supplement (F Supp). (There is
only the original series so far.) These trial-level courts are not as prolific as the ap-
pellate courts; their function is to hear the original cases rather than review them.
There are more than 100 of these courts, which are referred to by geographical
designations that must be included in the citation (eg, the Northern District of Illinois
[ND1111, the Central District of California [CD Call, but District of New Jersey [D NJI,as
New Jersey has only 1federal district).
8. Sierra Club u Fmehlke, 359 F Supp 1289 (SD Tex 1973).
.. :.Ci'
!~$.g!:,.&$2 State Courts. Cite to the appropriate official (ie, state-sanctioned and state-financed)
reporter (if any) and the appropriate regional reporter. Most states have separate
official reporters for their highest and intermediate appellate courts (eg, Illinois Re-
ports and Illinois Appellate Court Reports), but the regional reporters include cases
fro111both levels. Official reporte,rs are always listed first, although an increasing
number of states are no longer publishing them. The regional reporters are' the
Atlanlic Reporter (A or A2d), North Eastern Reporter (NE or NE2d), South Eastern
Itepor-ter(SE or SE2d), Southern Reporter (So or So2d), North Western Reporter (NW
or NW2d), South Western Repotler (SW or SW2d). and PaciJic Reporter(P or P2d). If
only the regional reporter citation is given, the name of the court must appear in
parentheses with the year of the decision. If the opinion is from the highest court of a
 3.16.3 Legislative Materials

state (usually but not always known as the supreme court), the abbreviated state
ame is sufficient (except for Ohio St). The full name of the court is abbreviated (eg,
Ill App, NJ Super Ct App Div, NY App Div). A third, also unofficial, reporter is pub-
shed for a few states; citations solely to these reporters must include the court name
(eg, California Reporter [Cal Rptrl, Nau York Supplement [NYS or NYS2dl). The for-
mat for these references includes the following, in the order specified (the punctu-
ation is noted; where none is given after a bulleted item, none is used).
First party v second party,
Reporter volume nuinber
,; m Official state reporter abbreviation
' a Fist page of case, specific page used
Regional reporter and page number
(Year of decision).
Some examples follow:
9. People v Carpenter, 28 I112d 116, 190 NE2d 738 (1963).
lo. Webb v Stone, 445 SW2d 842 (Ky 1969).
11. Beringer Estate v Princeton Med Ctr, 592 A2d 1251 (NJ Super Ct Law Div
1931).
12. Kerim v Hartley, 21 Cal Rptr 2d 621 (1993) (vacated and remanded for
. reconsideration), 28 Cal Rptr 2d 151 (1994).
13. Bensm uJustin, 1993 WL 515825 (Minn Ct App).

.. WL is Westlaw (www.westlaw.com), a legal citation database. Aversion of Westlaw's

database also exists for countries-other than the United States (eg, www.westlaw
o.uk for the United Kingdom). . .
When a case has been reviewed or otherwise dealt with by a higher court, the
subsequent history of the case should be given in the citation. If the year is the same
for both opinions, incluae it only at the end of the citation. The phrases indicating the
subsequent history are set off by commas, italicized, and abbreviated .(eg, aff"d
rmed by the higher court],.reu'd [reversed],vacated [made legally void, annulled],
appeal dismissed, ccert denied [application for a writ of certiorari, ie, a request that a
I court hear an appeal has been denied]).
14. Glazer v G k e r , 374 F2d 390 (5th Cir), cert cfenied, 389 US 831 (1967).
.. This opinion was written by the US Court of Appeals for the Fifth Circuit in 1967. In
the same year, the US Supreme Court was asked to review the case in an application
for a writ of certiorari but denied the request. This particular subsequent history is
important because it indicates that the case has heen taken to the hiphest court
available and thus strengthens the case's value ;IS prcccclcnt f o r fururc legal dcci-

Legislative Materials. The Library of Congrcss :I \l'rI, .\itc f ht~p-/~tI~oril:~i

lot.
.gov) where legislative materials mn be founcl.

75
3.16 US Legal References

This is volullle 4, page 750,of the Occupational Safety and Health Reporter, pub-
lished by the Bureau of National Affairs in 1980.

Law Journals. Law journal references follow the same rules as medical journal ref-
erences. List the authods) (if any), the title of the article, the name of the journal,
the volume number, issue number (or date, if there is no issue number), and page
nun~beds).
23. Doe v Westchestcv-County Med Center, NYState Dimion of Human Rights.
N Y Law J. Decelnber 26, 1990;91:30.
24. Studdert DM,Thomas EJ,Zbar BIW, et al. Can the United States afford a
"no-fault" system of compensation for medical injury?h w s ContempPmbl.
1997;60(2!;1-34.

ACKNOWLEDGMENTS
Principal author: ~ h e r y Iverson,
l MA

Coleen Adi~mson,jAn.IA,and Marg~retMills, JMand Archives Journals, pro-

vided helpful research and guidance for the section o n Legal References. Paul Frank,
JM and Archives Journals, and Monica M u n g l e , ' J M and Archives Journals,
gave careful review and comments for the section o n electronic references.

REFERENCES
1. Yallltauer A. The accuracy of medical journal references. CBE Views.April 1990;13:38
42.
2. Evans JT, Nadjari HI, Burchell SA. Quotational and reference accuracy in surgical
journals: a continuing peer review problem. J M .199O;263(10):135$1354.
3. Shenoy BV. Peer review [letter].JAMA. 1990;264(24):3142.
4. Schofield EK. Accuracy of references [letter]. CBE Viaus. June 1990;13:68.
5. International Committee of Medical .Journal Editors. Uniform Requirements for Man-
uscripts Submitted to Biomedical ~ournals.http://wwy.icmje.org. Updated February
2006.Accessed November 29, 2006.
6. I'atrias K. Nutionul Library of Medicine Recommended Fonnats for Bibliographic Ci-
tation. Bethesda, MD: National Library of Medicine, Reference Section; 1991.Note:
References G and 14 in this reference list are being updated and will be available
online as a single publication in late 2006,titled Citing Medicine: 7%eNLM Style Guide
for Authors, Editors, arzd Publishes.
7 . Books in Print, 2003-2004.New Providence, NJ:RR Bowker; 2004.Also available at
~~.booksinprint.com.
8. Style Manual Committee, Council of Science Editors. Scientific Style and Format: Zbe
CSE Afantrulfor At.iIhotq Editors, and Publishets. 7th ed. New York, NY: Rockefeller
University Press, in cooperation with the Council of Science Editors, Reston, VA'; 2006.
9. fie Chicago hlurztrnl of SryIr: 7be Essmztial Guidefor Writers, Editon, and Publishers.
15th ed. Chicago, IL: University of Chicago Press; 2003.
10. KronholzJ. Ril>liogr:~phy mess: the Internet wreaks havoc with the form: how do you
cite a \Vcl> ~xigc:'t11:lr.s :I rii:lttcr o f d e l x t ~arguing
~; over a period. Wall SfmetJotrnzal.
hla!. 2 . 7002:Al. h0
 3.16.3 Legislative Materials

11. Patrias K;for the CSE Style Manual Committee. Citations to the Internet. Sci Ii~lilor..
2002;25(3):90-92.
12. Publication Manual of the Ammican Psychological Association. 5th ed. Wr~shington.
DC: American Psychological Association; 2001.
13. American Psychological Association Web site. http://www.apastyle.org. Accessed
February 27, 2004.
14. Patrias IS.National Library of Medicine Recommended Formatsfor Bibliogrupl~icCi-
tation. Supplement: Internet Formats. Bethesda, MD: National Library of Medicine,
Reference Section; 2001.
15. Manuscript Criteria and Information: Archim of Internal Medicine. http://archinte
.ama-assn.org/iforaracumnt.dtl.Accessed February 26, 2004.
16. Dellavalle RP, Hester EJ, Heilig LF, et al. Going, going, gone: lost Internet references.
Science. 2003;302(5646>i787-788.
17. The Digital Object Identiller System. International DO1 Foundation (IDF). hnp://
www.doi.org/. Updated April 29, 2004. Accessed April 30, 2004.
18. Muher M,Groves T. Making research papers in the BMJaccessible: we're developing
ELPS and will soon publish papers shortly after acceptance. BMJ. 22002;325(7362):456.
19. l%e Bluebook A Uniform System of Citation. 18th ed. Cambridge, MA: Harvard Law
Review Association; 2005. Also available at www.legalbluebook.com. 1
Visual -Presentationof Data

4.1 4.2.3 Maps

Tables 4.2.4 Illustrations
4.1.1 Types of Tables 4.2.5 Photographsand Clinical Imaging
4.1.2 Organizing Information !n Tables 4.2.6 Components of Figures
4.1.3 Table Components 4.2.7 Titles. Legends. and Labels
4.1.4 Units of Measure 4.2.8 Placement of Figures in the Text
4.1.5 Punctuation 4.2.9 Figures Reproduced or Adapted From
4.1.6 Abbreviations Other Sources
4.1.7 Numbers 4.2.10 Guidelines for Preparing and Submitting
4.1.8 Tables That Contain Supplementary . Figures

4.1.9
Information
Guidelines for Preparing and
Submitting Tables A3
.
4.2.1 1 Consent for identifiable Patients

Nontabular Material .
A2 4.3.1 Boxes
Figures 4.3.2 Sidebars
4.2.1 Statistical Graphs
4.2.2 Diagram

Tables and figures demonstrate relationships among data and other types of infor-
mation. A well-structured table is perhaps the most efficient way to convey a large
amount of data in a scientific manuscript. As text, the same information may take
a
considerablymore space; if preseited in figure, key details and precise values may
be less apparent.
Text may be preferred ifthe information can be presented concisely (see Box). For
qualitative information, text should be used if the relationshipsamong data are simple
and data are few, whereas a figure should be used if the relationships are complex. For
quantitative information, a table should be used when the display of exact values is
important, whereas a figure (eg, a Iine graph) should be used to demonstratepatterns
or trends. Tables also are often preferable to graphics for small data.sets and are
preferred when data presentation requires many specific comparisons. Regardless of
the presentation, the same data usually should not be duplicated in a table and a figure
or in the text.
Priorities in the creation and publication of tables and figures are to emphasize
important information efficiently and to ensure that each table and figure makes a
clear point. In addition to presenting study results, tables and figures can be used to
explain or amplify the methods or highlight other key points in the article. Like a
paragraph, each table or figure should be cohesive and focused. To be most effec-
tive, tables and figures should present ideas and information in a logical sequence.
The relationship of tables and figures to the text and to each other should be con-
sidered in manuscript preparation, editorial evaluation and peer review, manuscript
editing, and article layout.
%%en used properly, tables and figures add variety to article layout and are
visually compelling and distinct components of scientific publications. However,
4 . 1 Tables

.-.

lor Uvng Text vs Tables vs f ~guresto Dtsplay Data

Box. Gu~del~nes

Uses of Text
Present quantitative data that can be given concisely and clearly
Describe simple relationships among data
Uses of Tables
Present large amounts of detailed quantitative information in a smaller space
than would be required in the text
Demonstrate detailed item-to-item comparisons
Display many quantitative values simultaneously
Display individual data values precisely
Demonstrate complex relationships in data
Uses of Figures
Highlight patterns or trends in data
Demonstrate changes or differences over time
Display complex relationships among quantitative variables
Clanfy or explain methods
Provide information to enhance understanding of complex concepts
Provide visual data to illustrate findings (eg, slides,.photographs, maps)
Illustrate scientific or clinical concepts, mechanisms, or pathophysiology I
authors and editors of scientific publications should avoid using tables and figures '
simply to break up text or to impart visual interest.

Tables. Because of their ability to present detailed information effectively and in

ways that text alone cannot, tables are an essential component of many scientific
articles. Tables can summarize, organize, and condense complex or detailed data and
therefore are commonly used to present study results.
The purpose of a table is to present data or idormation and support statements
in the text. Information in the table must be accurate and consistent with that in the
text in content and style. A properly designed and constructed table should be able to
stand independently, without requiring explanation from the text.

Types of Tables
*:t
& Table. A &le displays ififormation arranged in columns and rows (~xarnpleT1 and
4.1.3, Table Components) and is used most commonly to present numerical data.
Each table should have a title, be numbered consecutively as referred to in the text,
and be positioned as close as possible to its first mention in the text. Formal tables
usually are set off from the text by horizontal rules, boxes, or. white space.
, -..
i.':".'C ' "
..i!~?i.z:de;&: Tabulation. A tabulation is a brief, in-text tablethat may be used to set material off from
text. Tabulations require the text to explain their meaning. They are placed directly
in the text, unlike a table, which cannot always be placed next to its text citation.
 4.1.1 T y p e of Tables

Table 1. Baseline Characteristics of lnfahts With Initial and Table number

Follow-up Screening and title

Initial and 7
Initial
Screening Screening
Characteristics (n = 202) (n = 147)

Age, mean (SD), mo 9.9 (1.2) 9.8 (1.1)

Female, NO. (%) 107 (53 78 (53)
Weight, mean (SD), kg 9.5 (1.2) 9.5 (1.2)
Length, mean (SD), cm 72.7 (5.3) 72.6 (5.3)
Birth weight. mean (SD), ka 3.3 (0.5) 3.4 10.5)
-

Race/ethnicity, No. (%)a

BlackIAfricanAmerican 85 (42) 63 (43)

-White 17 (8) 13 (9)

Asian 8 (4) 4 (3)

1)
Other/unknown 28 (14) 19 (13)
'Parents or guardians self-determined the race/ethnicity of their infant.
Otherlunknown indudes any ra~e/ethnic'Itynot represented by any of Footnote
the aforementioned categories.

Exampre T1 Components of a table.

Tabulationsusually consist of 1or 2 columns of data; they generally should not escectl
half a column in length. A tabulation is set off from text by the use of sp&e above ant1
below and has boldface column headings. Titles, numbering, and rules are unncc-
essary. The tabulation should be centered within a single typeset column and nxiy l>c
set in reduced type (Example T2).
younger. A history of smoking was noted in 35 patients (39??),ant1 p r c ~ ~ i o u s
radiation exposure for a condition unrelated to MEC was reported for 10
patient. (11%). Presenting symptoms are listed in the following tabulation:
Symptom No. ('X) of Patients
Mass in parotid region 87 (98)
Pain or tenderness 13 (15)
Facial nerve weakness G (7)
Skin ulceration .3 ( 3 )
Facial twitching l(1)
Cxwicdl m s s sepante from tumor I(])
Other i (0,
k ) m c patien& p r r s e n t d w i t h more th:~n1 syrnlxo!r\
Example T2 In-text tabulat~on.
:.1 Tables

Matrix. A matrix is :I tal>ularstructure that uses numbers, short words (eg, no, yes), or
synlbols (cg, bullets, check marks) to depict relationships among items in colurnns
and rows and allow conlparisons among entries (Example T3).

Boxes, Sidebars, and Other Nontabular Material. Information that is complementary

to the text (eg, lists) can be set off in a box or sidebar within the article (see 4.3,
Nontabular Material).

Organizing Information in Tables. For a table to have maximum effectiveness, the

information it contains must be arranged logically and clearly so that the reader can
quickly understand the key point and find the specific data of interest. Information in
tables should be organized into columns and rows by type and category, thereby
simplifying access and display of data and information.
During the planning and creation of a table, the authorshould consider the primary
con~parisonsof interest. Because the English language is read first horizontally (from
left to right) and then vertically (from top to bottom), the primary comparisonsshould
be shown horizontally across the table. Data that depict cause-and-effect or before-
and-after relationships should be arranged from left to right if space allows or, alter-
natively, froh top to bottom. Information beiig compared (such as numerical data)
should be juxtapo-sed within adjacent rows or adjacent columns to facilitate compari-
sons anlong items of interest. The tables in Example T4 present the same information.
Note that the second table more easily allows the reader to compare the changes over
time, which is the primary outcome of interest.
Although tables frequently are used to present many quantitative values, authors
should remember that tabulating all collected study data is unnecessary and actually
may distract and overwhelm the reader. Data presented in a table should be pertinent
and meaningful.
The length of the table should also be considered. For ease of reading and
practical reasons, a table that would span horizontally or run vertically onto a second
page should, if possible, be recast into 2 or more smaller tables. If this is not possible,
the table may be set in smaller type. Another option is to publish the table in elec-
tronic form only, with a note in the print publication, but the same difficulty with
reading large tables in print occurs onliie as well. In general, tables in print publi-
c:~tionscan, depending on the content, contain up to 9 or 10 columns of data (in-
cluding the first column, or stub). Cells that contain words will be wider, thereby
reducing the number of colunms that will fit.

Table Components. Formal tables in scientific articles conventionally contain 5 major

elements: title, column headings, stubs (row headings), body (data field) consisting of
individual cells (data points), and footnotes (Example TI). Details pertaining to ele-
ments of style for tahle construction vary among publications; what follows is based
o n the general style of JAMA and the Archives Journals.

Title. E:~chtahle should have a brief, specific, descriptive title, usually written as a
phrase nither than as a sentence, that distinguishes the table from other data displays
in the article. The title should convey the topic of the table succinctly but should not
provide detailed background infor~nationor summarize or interpret the results.
Tables should be nu~nberedconsecutively according to the order in which they
:ire mentioned in the text. The word "Table" and the table number are part of the title.
 Table 3. Direction of the Association Between Birth Weight and Total Blood Cholesterol and Reported Associations With Other Components of the Lipid Profile
in Published Reports of Studies That Had Published Regression Coefficients
--

Age as Reported Direction of Birth Weight vs

Reported in Total Cholesterol Association Associations Also Reported With
Source No. of Study (Mean or
(Country of Study) !ndivldualsa Range), y I Inverse None Positive NA I I HDL-C LDL-C Triglycerides ApoA ApoB 1
~estbo,~'1996 (Denmark) 620 453 .'
~ u z u k i . ~2000
' (Japan) 299 23 J J

l ~ z e r m a n ,2001
~ ~ (Holland) 228 16 4 J J 4 J J

~ o n a , ~1996
' cotl land)^ 154 9 4

~esteloot," 1975 (Belgium) 303 0 4 4

0wen.l 2003 (United Kingdom) 1461 13-16 4

all,^' 1992 (United Kingdom) 794 59-70 4 J

~iura," 2001 (Japan) 4951 20 J

~ a u r e n 2002
, ~ (inland) 5792 31 .' J

~avdekar.' 1999 (India) 477 8 4 J 4 J

~avles,~'
2004 (United Kingdom) 25 843 36-39 4

Abbm~atm:A d , apolipoproteinA; ApoB. apolipoprotein 0; HDL-C, highdensity lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; NA. direction of asmiation not available in the
o r q ~plblocation.
~l
Number of individuals on whom regression coefficients in the pr&nt analps are based. which may differ from numbers reported in the original publication.
' A s r x l d t m reported in the original publicationwas obtained by combining results from 5 separate studies.

Example T3 Matrix.
4.1 Tables

Table 4a. Relative Risk for Death After Onset of Heart Failure Defined by the Framinqham Criter1aa
Men by Age, y Women by Age, y
I year 1 60 70 80 1 1 60 70 80 1
1979-1984 1 [Reference] 1 [Reference] 1 [Reference] 1 [Reference] 1 [Reference] 1 [Reference]
I -
1985-1990 C 34 0.84 0.85 0.80 0.91 1.02
(0.69-1.02) (0.73-0.97) (0.72-1 .OO) (0.63-1.03) (0.77-1.06) (0.90-1.1 5)
I --
: 1991-1995 0.63 0.74 0.88 0.95 0.99 1.03
I (0.50-0.80) (0.63-0.88) (0.75-1.04) (0.73-1.24) (0.83-1.18) ' (0.90-1.17)
1996-2000 0.48 0.59 0.72 0.67 0.79 0.94
(0.36-0.64) (0.49-0.71) (0.61-0.87) (0.48-0.92) (0.64-0.98) (0.82-1.09)

L Ddta are presented as relative risk (95% confidence interval).

Table 4b. Relative Risk for Death After onset of Heart Failure Defined by the Framingham Criteria.

Relative Risk (95% Confidence I n t e ~ a l )

Ages Y 1 1979-1984 1985-1990 1991-1995 1996-2000 1.
Men
60 1 [Reference] 0.84 (0.69-1.02) 0.63 (0.50-0.80) 0.48 (0.360.64)
70 1 [Reference] 0.84 (0.73-0.97) 0:74 (0.63-0.88) 0.59 (0.49-0.71)
80 1 [Reference] 0.85 (0.72-1 .OO) 0.88 (0.75-1.04) 0.72 (0.61-0.87)
Women
60 1 [Reference] 0.80 (0.63-1.03) 0.95 (0.73-1.24) 0.67 (0.484.92) '

70 1 [Reference] 0.91 (0.77-1.06) 0.99 (0.83-1.18) 0.79 (0.64-0.98)

80 1 [Reference] 1.02 (0.90-1.1 5) 1.03 (0.90-1.17) 0.94 (0.82-1.09)

Example T4 The first table is formatted with the primary comparison-years of study--running vertically (especially
evident in reading the first row across). The second table is formatted with the primary outcome running horizontally.

If the article contains only 1 table, it is referred to in the text as "Table." The capi-
talization style used in article titles should be followed for table titles (see 3.9, Ref-
erences, Titles). The following are examples of table titles:
Table 1. Symptoms and Signs of Chronic Fatigue Syndrome
Table. Relationship of Blood Pressure and Intraocular Pressure in Patients
With Open-Angle Glaucoma

.,
:
; LE';.,&$ Column Headings. The main categories of information in the table should have
fl

separate colun~ns.In tables for studies that have independent and dependent var-
iables, the independent variables conventionally are displayed in the left-hand
 4.1.3 Table Components

column (stub) and the dependent variables in the columns to the right. Each colunin
should have a brief heading that identifies and applies to all items listed in that
column. The stub, however, may not require a heading, particularly if the elements in
the stubs are very different. If relevant, the unit of measure should be indicated in the
column heading (unless it is given in the table stub) and is preceded by a comma.
Column headiings are set in boldface type. If necessary, column subheadings may be
used. For more complex headings, braces may be used (Example T4) or additional
explanatory information may be provided in the footnotes.
If all elements in a column are identical (eg, if all patients were women and a
colufixl indicated the patients' sex), this information could be provided in a footnote
or in the table title and the column deleted.
In column headings, style guidelines regarding numbers (eg, use of ordinals)
and abbreviations inay be relaxed somewhat to save space, with abbreviations ex-
panded in a footnote. However, when space allows spelled-out headings, expan-
sions are preferable to abbreviations. The capitalization style used in titles should be
followed (see 3.9, References, Titles).

Table Stubs (Row Headings). The left-most column of a table contains the table stubs
(or row headings),.whichare used to-labelthe rows of the table and apply to all items
in that row. If a unit of measure is not included in the column heading, it should be
included in the stub. Stubs are capitalized according to style for sentences, not titles.
Therefore, if a symbol (such as %I, an arabic numeral, or a lowercase Greek letter
(such & p) begins the entry, the firstword to follow should be capitalized. Stubs are
left-justified, and indentions are used to depict hierarchical components of the stubs
(Example T5). However, some publicitions use bold stubs or shading instead.
For a table that xnay be readily divided into parts to enhance clarity or for 2
closely related tables that would be better combined, cut-in headings may be con-
sidered.' The cut-in heading is placed above the table columns (below the column
heads) and applies to all tabular material below. cut-in headings are set boldface, are
centered, and have a rule above (but not below) them (Example TG). However, cut-
in headings may interfere with downward scanning and thus should be used with
care.2
Both column headings and stubs should be consistent in styie and presentation
between tables in the same article.

Field. The field or body of the table presents the data. Each data entry point is con-
tained in a cell, which is the intersection of a column and a row. Table cells may
contain numerals, text, symbols,or a combination of these. Data in the field sliould
be arranged logically so the reader can find an individual data point in the table
easily. For instance, time order should be used for data collected in sequence (Ex-
ample T4). Similar types of data should be grouped. Numbers that are added or
averaged should be placed in the same column. Text in the field cells should be
capitalized in sentence style (ie, the first word is capitalized and all that follow in the
cell are lowercased).
Missing data and blank space in the table field (ie, an enipty cell) m;iy crc;itc.
ambiguity and should be avoided, i~nlessan entry in a ccll tlocs not ;ipp/y (cg.;I
column head does not apply to one of the stul, i ~ ~ l ~ l'1'11~ s ) . 'ni~lncr:~l
0 ~ 1 ~ 0 ~ 1 Ir.
1~1
used to indicate that the value of the data in the cell is zero. A n ellip.si.s ( . . ) 111.1\ IN.
used to indicate that no data are avail;iblc for :I cell 01.t1i;it the c;rtcgo~c )lil;~r.~ I-.r r l 81

87
 Table 5. Characteristics of Patients With Ischemic Stroke
Treated With Intravenous Tissue Plasminogen Activator (tPA)a

All Patients Treated

With tPA, No. (%)
Characteristics (n = 1658)

Age group, Y
< 55
55-64
65-74
'75

1 Female
Male
Time from stroke onset
to hospital admission, h

/ Comorbidities
Diabetes mellitus 395 (23.8)
Hypertension 1158 (69.8)
Previous stroke 180 (10.9)
Atrial fibrillation 496 (29.9)
I Neurological signs
Weakness/paresis 1436 (86.6)
Aphasia 777 (46.9)
Dysarthria 580 (35.0)
Disturbed level of consciousness 407 (24.6)

I Hospital experience with

tPA use per year
<6 277 (16.7)
6-1 5 706 (42.6)
> 15 675 (40.7)
'Analyses were restricted to patients without missing values.
I

Example T5 Hierarchy of stubs.

applicable for a cell. However, ellipses should not be used to denote different types
of missing elements in the same table. Other designations such as NA (for "not
available," "not analyzed," or "not applicable") may be used, provided their meaning
is explained in a footnote (Example l7).
Blank cells may be acceptable when an entire section of the table does not
contain data (~xarn6leT8).
?;v;.r.:
v$,?;,.::A\
~~&e7z
,, Totals. Totals and percentages in tables should correspond to values presented in the
text and abstract : ~ n dshould be verified for accuracy. Any discrepancies (eg, because
of rounding) s t ~ o i ~ lIw
d c.spi;linctl in .I Irx)rnotc..
 . .

4.1.3 Table Components

Table 6. Trial Enrollment for Minorities vs Whites According to cancer Type, 2000-2002

No. of Trial Enrollment Odds Ratio P

Racial/Ethnic Group Participants Fraction, % (95% CI) Value

All Cancers
Total 37 635 1.7

White 32 633 1.8 1 [Reference]

Hispanic 1094 1.3 0.72 (0.68-0.77) < .001
Black 3062 1.3 0.71 (0.68-0.74) c .001
AsianfPacific Islander 745 1.7 0.95 (0.88-1.02) .16
American Indian/Alaskan Native 101 2.5 1.44 (1.18-1.76) e.001
Breast Cancer
Total 19 893 3.2
Whiie 17 344 3.3 1 [Reference]
Hinic 635 2.4 0.71 (0.66-0.77) < .001
Black 1393 2.5 0.74 (0.70-0.79) < .001
Asian/Pacific Islander 465 3.1 0.95 (0.86-1.04) .27
American Indian//llaskan Native 56 4.5 1.37 (1.65-1.80) -02
Colorectal Cancer ,

Total 8434 1.9

White 7408 2.0 1 [Reference]
Hispanic 264 1.5 0.74 (0.66-0.84) < ,001
Black 578 1.3 0.64 (0.59-0.70 < .001
AsianfPacific Islander % 161 1.5 0.76 (0.64-0.88) < .001
American IndianfAlaskan Native 23 2.5 1.30 (0.86-1.97) .21

Example T6 Cut-in headings divide the table into related sections.

Boldface type for true totals (ie, those that represent sums of values in the table)
: should be used with discretion. Boldface should not be used to overemphasize d:lt:~
in the table (eg, significant odds ratios or P values).

Alignment of Data. Horizontal alignment (across rows) must be considered in setting

tables. If the table stubs contain lines of text that exceed the width of the stub column
(runover lines in the table stub) and the cell entries in that row d o not, the field
entries should be aligned across the first or top line of the table stub entry (Example
T9). This top-line alignment of data applies to tables tlxlt I~nvenunlbers, words, o r
hoth as cell entries. If some entries within the table field contain inform;~tionthat
a n n o t be contained on a single line in the cell-(runover lines in the tnhle field), the
tahlr entries in that row also should be aligned across on the first line o f . t l ~stl~l,
e
entry.

89
4.1 Tables

Table 7. Phfi~cal R1sb.s From Spons In the Dally L~esof Heatthy C h ~ M r e nOlder Than
6 Yearsd

Risk per Million Instances of Participation

I Total Permanent Total Level Broken 1
Sport Injuries Disability IV lnjuriesb Surgeries Bones
Football 3800 42 500 270 910
Soccer 2400 38 300 NA NA
Basketball 1900 58 300 160 180
Cheerleading 1700 NA 100 NA NA
Baseball . 1400 61 300 120 30
Skateboarding 800 NA 200 20 170
Abbreviation: NA, not available.
'Data adapted from Arneriian Sports Data lnc.''
bThose resulting in emergency department treatment. wemight hospital M y , surgery, w ongoing physical therapy
and preventing participation'in sports for at least 1 month.

Example T7 Use of " N A to clarify cells with no data.

Vertical alignment within each column of a table is important for the visual pre-
sentation of data. Whenever possible, columns of data should be aligned on common
elements, such as decimal points, plus or minus signs, hyphens (used in ranges),
virgules, or parentheses (Example T8). If table entries consist of lengthy text, the
flush-left format should be used with an indent for runover lines. If entries in a
column are mixed (ie, if no common element exists or if the numbers vary greatly in
magnitude), primary consideration should be given to the visual aspects of the entire
table and the type of material being presented.

Rules and Shading. For JM and the Archives Journals, tables should be submitted
without rules drawn in (as opposed to table borders, which are appropriate) or
shading. If these elements are included they will have to be manually removed
during the editing process (see 4.1.9, Guidelines for Preparing and Submitting
Tables).
Many journals add rules and shading during the production process. For ex-
ample, JMuses horizontal rules to separate rows of data (Example T8). Other
journals use shading for the same purpose.

Footnotes. Footnotes may contain information about the entire table, portions of the
table (eg, a column), or -a discrete table entry. The order of the footnotes is deter-
mined by the placement in the table of the item to which the footnote refers. The
letter for a footnote that applies to the entire table (eg, one that explains the method
used to gather the data or format of data presentation) should be placed after the
table title (Example T4). A footnote that applies to 1or 2 columns or rows should be
placed after the column heading($ or stub(s) to which it refers (Example T7). A
footnote that applies to a single entry in.the table or to several. individual entries
should tx: pl;rced at the end of each entry to which it applies (Example T10).
 Table 8. Characteristics of Cases of Nonfatal Suicidal Behavior and Matched Control?

No. (%)
Characteristics I cases (n = 555) Controls (n = 2062) 1 OR (95% CI)

1: I Snaking status
I
I Ex-smoker 27 4.9 119 5.8 0.89 (0.56-1.42) 1

I Body mass index

I

I Unknown 167 30.1 598 29.0 1.03 (0.81-1.32) 1

Abbreviation: CI. confidence intewal. . .
'Controls were matched to cases by age, sex. index date. and duration of recorded history in the UK General Practice
6. Research Database before the index date. Odds ratiosi0Rs) for smokina and body mass index. which is calculated as

Example T8 Bldnk cells without definition. Because the footnote indicates that sex and age were
matching variables, no data appear in those cells.

letters in alphabetical order (a-2). The font size of the footnote letters should be large
enough to see clearly without appearing to be part of the actual data. While some
publications (including, formerly,JAMA and the ArchivesJournals) use symbols (', t,
etc) to indicate footnotes in tables, such symbols are ordered arbitrarily and are
; limited in number. Use of superscript letters ensures a logical order to the entries and

1 a much larger supply of notations (26 characters). For tables in which superscript
numben and/or leners are used to display data, care should he taken to ensur
4.1 Tables

-- -- - - - ------ - - - --

I
Table 9. Thrombos~sRelated to the Interval Between Symptom Onset and Surgery In Pattents
With Stroke

Interval Between the Acute Cerebral Event

and Carotid Endarterectomy, No. (%)
I 0-2 mo 3-6 mo 7-12 mo 13-24 mo 25-30 rno I
(32 Cases) (18 Cases) (15 Cases) (13 Cases) (18 Cases)

Thrombotically 32 (100) 13 (72.2) 11 (73.3) 7 (53.8) 8 (44.4)

active plaque
Only organized 0 4 (22.2) 4 (26.7) 5 (38.5) 10 (55.6)
thrombosis
No thrombosis 0 1 (5.6) 0 1 (7.7) 0

Example T9 Alignment of data with the first line in the stub entry.

superscript footnote letters are distinguished clearly from superscripts used for data
elements (for example, see Table 15.1.2, Nomenclature, Blood Groups, Platelet
Antigens, and Granulocyte Antigens, Platelet-Specific Antigens). In these situations,
use of the symbol footnotes may help avoid confusion.
Footnotes are listed at the bottom of the table, each on its own line. However, to
save space, tables with more than a few footnotes can run them in 2 columns
(Example T10).
Footnotes may be phrases or complete sentences and should end with a period.
Any operational signs, such as <, >, or =, imply a verb. For example, P = .O1 is
considered a complete sentence ("Pis equal to .01." when used as a table footnote.
Footnote letters should appear before the footnote text and are followed by a space
for clarity. InJAMA and the Archives Journals, the abbreviations and units of measure
conversion footnotes appear first and are set off with an introductory word or phrase
instead of a letter. In addition, abbreviations are expanded in alphabetical order;
units of measure and applicable conversion factors are listed in a separate footnote
(Example T11).
If several tables share a detailed or long footnote that explains several abbre-
viations or methods, this footnote may appear in the first table for which it is ap-
plicable, and a footnote in each succeeding table for which the footnote also is
applicable may refer the reader to the first appearance of the detailed information:
Study acronyms are explained in the first footnote to Table 1.
The reader also may be referred to a relevant discussion in the text by a footnote:
See the "Statistical Analysis" section for a description of this procedure.
Several of the most common uses of footnotes include the following.
To expand ubbreuicrtions:
Abbreviations: CI, confidence interval; OR, odds ratio.
 CBT With Fluoxetlne
Variable Fluoxetine Alone CBT Alone Placebo Total P Value

1
Characterlstlcs for Depression, Sulcldallty, and Functlonlnga
No. of persons randomized 107 109 111 112 439
Children's Depression Rating Scale-Revised 60.75 (11.58) 58.96 (10.16) 59.58 (9.21) 61.11 (10.50) 60.10 (10.39) 38
- scoreb
Raw ..-

T scoreC 75.67 (6 73) 74.73 (6.74) 75.37 (6.32) 76.14 (6.11) 75.48 (6.43) .43
Cl~n~cal
Global Impressions Improvement scored 4.79 (0:85) 4.66 (0.85) 4.77 (0.76) 4.84 (0.84) 4.77 (0.83) 43
Ch~ldren'sGlobal Assessment score* - 49.95 (7.52) 49.49 (7.26) 50.01 (7.58) 49.13 (7.59) 49.64 (7.471 .79
I Reynolds Adolescent Depression total scoref 79.91 (13.68) 77.00 (14.67) 78.83 (14.97) 81.20 (13.94) 79.24 (14.35) .18
I Suicidal Ideation Questionnaire Junior High Schml
.- - - total
Version .- -- -=ore9
-- -
27.32 (24.64) 21.86 (19.22) 22.03 (21.36) 23.69 (2166) 23.71 (21.83) .57h

I Current major depressive episode duration, wk 83.07 (94.00) 70.92 (94.33) , 71.71 (70.14) 61.16 (67.45) 71.59 (82.35) .28h

I
Comorbidity a t Baseline by Treatment ~ r o u p '
Comotbidity
Any. NO.(%Y 59 (55.66) 47 (43.12) 64 (58.18) 57 (51.35) 227 (52.06) .13
1 mount 0.88 (1.04) 0.83 (1.20) 0.93 (1.09) 0.90 (1.13) 0.88 (1.11) .SO
/ Dyrthymia. No. (%) 11 (10.28) . 6 (5.50) 17 (15.45) 12 (10.71) 46 (10.50) .12
/1 Type of dnorder. No. (%I
Anr!cty 30 (28.04) 26 (23.85) 36 (32.43) 28 (25.23) 120 (27.40) - .SOh
i D~vuptwbehavior 23 (21.50) 25 (22.94) 27 (24.32) 28 (25.00) - 103 (23.46) .93
I
Obwe-tompulwve/tic 4 (3.74) 2 (1.83) 2 (1.80) 4 (3.57) 12 (2.73) .73'
Subrfance
..--.
me 3 (2.80) 3 (2.75) 1 (0.90) 0 7 (1.59) .23k
Attentm-&flc~t/hyperactivity 14 (13.08) 13 (11.93) 14 (12.61) 19 (16.96) 60 (13.67) .70
Taklnq medrcat~ons 4 (3.74) 3 (2.75) 4 (3.60) 10 (8.93) 21 (4.78) .12'

/ noerwafm: CBT, cqnitive behavior therapy. he range for possible scores is 30 to 120.
I as mean (SD) unless otherwise indicated.
'Valuer arc clpmud qThe range for possible scores is 0 to 90.
, ''Ttufbnp~for001~WC~0~e5i~17t0113. h~orparametric Kruskal-Wallis test.
!he r a m p for pors~blpscores is 30 to,55. values are for the X2 test unless otherwise indicated.
, ' I he range fa PDIYMC scores is 1 to 7. 'Refers to the presence of 1 or more coexisting psychiatric disorders, including dysthymia.
'
' ihe ranqr fa por*tde scores is 1 to 100. 'Fisher exact test.
:
Example T I 0 When tables have many footnotes they can be presented in 2 columns instead of with a single footnote on each line.
4.1 Tables

Table 11. Distribution of Lipid and C-Reactive Protein Levels at Study Entry Among 15 632
Initially Healthy Women

Percentile Cutoffs
I
15th 10th 25th 50th 75th 90th 95thI

Cholesterol, mg/dL
Total 149 161 181 206 ' 234 263 283
LDL 76 85 102 124 147 171 187
HDL 32 35 41 49 59 69 77
Nan-HDL 98 109 1 2 9 . 155 184 213 234
Apolipoprotein, mg/dL

~igh-sensitivityCRP, mg/L- 0.2 0.3 0.6 1.5 3.5 6.6 9.1

Ratio .

1 Total cholesterol to HDL cholesterol 2.6 2.8 3.4 4.1 5.2 6.2 7.0
1 LDL cholesterol to HDL cholesterol 1.3 1.5 1.9 2.5 3.3 - 4.0 4.5
Apolipoprotein El00 to
apolipoprotein A-l 0.41 0.46 0.57 0.71 0.89 1.08 1.21
Apolipoprotein Blooto HDL cholesterol 0.97 1.1 1.5 2.0 2.8 3.6 4.2

) Abbreviations: CRP, C-reactive protein; HDL highdensity lipoprotein; ID1 low-density lipoprotein.
U cc?version fxmrr To c m n HDL LDL and total cholesterd to mmd/L multiply by 0.0259.

Example T I 1 Footnotes including separate entries for abbreviations (in alphabetical order)
and unit of measure conversion information.

To designate reporting of numeidca! values:

" Scores are based on a scale of 1to 10, with 1indicating least severe and 10,
most severe.
To provide informatio~zon statistical analyses or experimental methods:
Adjusted for age, smoking status, and body mass index.
To explain a discrepancy in numerical data:
" Because of rounding, percentages may not total 100.
To cite referencesfor infonnation used in the table. References are given as in the text
and are designated with superscript arabic numbers:
' Classified using International Classificationof Health Problems in Primary
 4.1.5 Punctuation

To acknowledge that data in the table are takenfrom or based on data from another

a Data from the US Census ~ u r e a u . ~

To acknowledge creditfor reproduction of a table. If the table has been reprinted or
I modified with permission from another source, credit should be given in a footnote:
a Adapted with permission from the American Medical ~ssociation.~~
ould be numbered and listed as if
ce, if the source from which the
: material referred to in the table or figure is one of the references used in the text, that
reference number should be used in the table or figure. If the reference pertains only
to the table or figure (ie, the source is not cited elsewhere in the text), the reference
should be Iisted and numbered according to the first mention of the table or figure in
the text (see 3.6, References, Citation). All references in an article should appear in
the reference lit.
Note that references cited at the end of table titles are ambiguous. Instead, a
'
footnote should be added with an explanation that it was
Adapted from ...
Reproduced with permission from . ..
Data were derived from ...
When both a footnote letter and reference number follow data in a table, set the
letter (see also 3.6, References.

427 patients51b

Units of Measure.JMand the Archives Journals report laboratory values in con-

ventional units (see 14.12, Abbreviations, Units of Measure, and 18.0, Units of Mea-
sure). In tables, units of measure, including the vz~iahilityof the measurement if
reported, should follow a comma in the table column heading or stub. The follo\\,ing
are examples of stub entries with units of measure:
Age, mean (SD), y
Systolic blood pressure, mean (SD), mm Hg
Body mass index, median (IQR)
Duration of hypertension, mean (SD) [rangel, y
Change in rate, % (SE)
J A M and the ArchivesJournals use a conversion footnote to indicate how to con\.cn
values to the SI or another system (Example TII).

punctuation. As with numbers and abbreviations, ri1lc.r for puncrir.ltlon 111.11Ix*Ic.\\

restrictive in tables to save space (see 8.0, Punctu,~t~on).
[:or cs.~rnplc..\ l . ~ r l i ~rn.t\
\ I>v

95
4 1 Tables

~lscclro present clates (eg, 04/27/03 for April 27, 2003) and hyphens may be used to
present ranges (eg, 60-90 for 60 to 90) (see 19.0, Numbers and Percentages). Phrases
;~ntlsentences in talies may use end punctuation if required for readability (eg, if
cclls contain multisentence entries).

Abbreviations. Within the body of the table and in column headings, units of measure
zinc1 numbers normally spelled out may be abbreviated for space considerations (see
14.12, Abbreviations, Units of Measure; 18.0, Units of Measure; and 19.0, Numbers
and IJercentages).However, spelled-out words should not be combined with abbre-
viations for units of measure. For example, "First Week" or "1st wk" or."Week 1" may
Ile tlsed ns a column hcacling, hut not "First wk." Abbreviations or acronyms should
I>cexplained in a footnote (see 4.1.3, Table Components, Footnotes).

Numbers. Additional digits (including zeros) should not be added, eg, after the de-
cim:~lpoint, t o pn)vitlc ; ~ l lcl;lt;~cntrics with the s:une number of digits. Doing so may
indicate nlore precise results than actually were calculated or measured. A percen-
tage or decimal quotient should contain no more than the number of digits in the
denonrinator. For example, the percentage for the proportion 9 of 28 should be
reported as 32% (or deci~nalquotient 0.321, not 32.1% (or 0.321) (see 20.8, Statistics,
Significant Digits and Rounding Numbers). Values reporting laboratory data should
be provided and rounded, if appropriate, according to the number of digits $at
reflects the precision of the reported results to eliminate reparting results beyond the
sensitiviv of the procedure performed (see 18.4.1, Units of Measure, Use of Numerals
With Units, Expressing Quantities).
Values for reporting statistical data, such as P values and confidence inter-
vals, also should be presented and rounded appropriately (see 20.8, Study Design
and Statistics, Significant Digits and Rounding Numbers). Although some publica-
tions2(ps1z) suggest use of specific designations for levels of significance (eg, a sin-
gle asterisk in the table to denote values for entries for which P< .05, a dagger for
P < .01),exact P values are preferred, regardless of statistical significance. In most
cases, P values should be expressed to 2 digits to the right of the decimal point,
unless the first 2 digits are zeros, in which case 3 digits to the right of the decimal
place should be provided (eg, P= .002). Pvalues less than .001 should be designated
as "P<.001," rather than using exact values, eg, P= .00006. For study outcomes,
individual statisticallysignificant values should not be expressed as "P< .05" either in
the table or in the table footnote,and nonsignificant Pvalues should not be expressed
as "NS" (not significant). For confidence intervals, the number of digits should cor-
respond to the number of digits in the point estimate. For instance, for an odds ratio
reported as 2.45, the 95% confidence interval should be reported as 1.32 to 4.78, not
as 1.322 to 4.784.

Tables That Contain Supplementary Information. Tables that contain important

supplementary information that is too extensive to be published in the'journalarticle
nuy be made available from other sources. These tables may be available from the
author or by electronic means (eg, online database, journal Web site, CD-ROM).
Supplementary tables posted on the JAMA and Archives Journals Web site undergo
review and editing because they are considered part of the journal's content.
..
k
4.1.9 Guidelines for Preparing and Submitting Tables

IGuidelines for Preparing and Submittincr Tables. Authors submitting tables in a

i erred table construction vary among journals, several general guidelines apply. Each
table should be created by means of a table editor program in word processing
software or a spreadsheet program and inserted in the electronic manuscript file.
i Reduced type should not be used. If a table is too large to be contained on 1 man-
uscript page, the table should be continued on another page with a "continued line

simplertables. Tablesshould not be submitted on oversized paper, as a graphic image,

or as photographic prints.
: The following table creation instructions for authors appear on the IAMA

Author Instructions for Table

Creation
variability are in the same cell as their cor-
responding statistic:
1i
: Creating the table
Table 2. Title I
Use the table editor of the word ~roces- Relative I
.; data needs to-be contained in itsown cell Women, N.; (1) 25 (50) 20 (40) 1.25
'-t in the table. (1.1 1-1.57)

3j Avoid creating tables using Spaces Or Age. mean (SD), y 35 (8) 37 (7) 0.98
tabs. Such tables must be retyped during (0.92-1.05)

Similarly, no cell should contain a hard stead, put the data in a cell near the middle of
return or tab. ~lthoughindividual empty the rows. In the example below, the final
cells are acceptable in a table, lx sure colunin lists tlic P v;tluc for the ovcrr~ll:~gc
there are no empty columns. comparison and will be bracketed to indicate
1: Each row of data must be in a separate
row of cells:
the comparison:
Table 3. Title

Medical 500 510 35-50 1 10/80 .08

Surgical 500 490 51-80 125/82

DOnot draw lines or rules-the table

Note that percentages are presented in grid feature will display the outlines of each
I
; the .samecell as numbers and measures of cell.
 Figures. I'lic 11.1111 /1,q1(w rcivrs to any graphical display used to present infoha-
Iton o r J J I ~ .~rl~.lurl~ng
' statistical graphs, maps, algorithms, illustrations, computer-
gc.ncr;ltr.d tlndges. and photographs. Figures may be used to c l a r ~or explain
methods, to present evidence and quantitative results, to highlight trends and rela-
tionships alnong data, to clarify complex concepts, or to illustrate items or proce-
.
dures. Figures should be accurate, clear, and concise.
In scientific articles, selection of a particular type of figure depends on the
purpose and type of information being displayed. Some of the most common types
of-figures in biomedical publications are discussed herein.

Statistical Graphs

:5.:-.q "
Line Graphs.
I.-Z-*~~C;~:;~ Line graphs have 2 or 3 axes with continuous quantitative scales on
which data points connected by curves demollstrate the relationship between 2 or
'
more quantitative variables, such as changes over time. Line graphs usually are
designed with the dependent variable on the vertical axis (y-axis) and the inde-
pendent variable on the horizontal axis (x-axis13 (Example F1, Example F2).
I
. .

80 -

-:
75-
2l
E @\@

\zz~z
w-
0
C

-g
0
70-
w
.-
C

-2
C
*-
65-
0

60 I I 1 a i
Baseline Year 1 Year 2 Year 3 Last Visit
Visit
-- -

Figlire 1. Creatinine clearance at baseline and at annual visits in patients treated with either
nifedipine gastrointestinal therapeutic system (GlTS) or hydrochlorothiazide-amiloride.Error bars
indicate SO. To convert creatinine clearance to milliliters per second, multiply by 0.0167.
L- -
Example F1 Line graph with the dependent variable on the vertical axis (y-axis) and the independent
variable on the horizontal axis (x-axis).
 4.2.1 Statistical Graphs

Figure 1. Rates of GBS and Non-GBS Reports Following Influenza Vaccination, VAERS
1990-2003

0.18- -3.0

0.16-
m
-2.5
P
5
- 0.14- s'
3z
0
S
J 0.12- -2.0 2
V1

1a
f- 0.10-

$ 0.08-
V)

8 0.0s-

88 0.04- w
R -0.5
0.02-
A Nm-Gas
0- .
1990-
-0
1991- 1992- 1993- 1994- 1 9 9 5 1996- 1997- 1998 1999- 2000- 2001- 2002-
b

1991 1992 1993 1994 1995 1958 1997 1998 1999 2000 2001 2002 2003
InfluenzaSssan

GBS indicates Guilbin-Bard syndrome; VAERS. Vaccine Adverse Events Reporting Sptern.

Example F2 Line graph with 3 axes to facilitatecomparison of related data.

Survival Plots. Survival plots of time-toevent outcomes, such as from Kaplan-Meier

analyses (see Figure 3 in 20.0, Study Design and Statistics), display the proportion of
individuals, represented on the y-axis as a proportion or percentage, remaining free
- - of or experiencing a specific outcome over time, represented on the x-axis. When the
outcome of interest is relatively frequent (occurs in approximately'>~O%of the study
population), event-free survival is plotted on the y-axis from 0 to 1.0 (or O
Oh to 10Wh),
with the curve starting at 1.0 (1000/o). \men the outcome is relatively infrequent
(occurs in <30%of the study population), it is preferable to plot upward starting at 0
so that the curves can be seen without breaking or truncating the y-axis scale.4The
curve should be drawn as a step function (not smoothed).
The number of individuals followed up for each time interval (number at risk)
should be shown underneath the x-axis. ~ime-to-eventestimates become less certain
as the number of individuals diminishes, so consideration should be given to not
displaying data when less than 20% of the study population is still in follow-up.4 Plots
should include some indication of statistical uncertainty, such as error'bars on the
curves at regular time points or, when time-to-event data are being compared for 2 or
more groups, an overall estimate of treatment difference, such as a relative risk (with
95% confidence interval) or log-rank P value (Example F3).

Scarterplots. In scarterplots, individual data points are plotted according to co-

o r d ~ n a tvalues
~ with continuous, quantitative x- and y-axis scales. By convention.

99
4.2 Figures

I Figure 2. Kaplan-Meier Estimates of lntubat~onRate 1

CPAP

lime, h
No.at Risk
Control 104 102 99 99 97 96 98 85 95
CPAP 105 104 104 104 104 104 104 104 104

Estimates of intubationrates are accordingto whether w not patients receivedorrygen abne (control)or oxygen plus
continuous positiveairwav Dreswre(CPAPI. The cumulative wobabilitv of remainina without intubation was hiaher in
- patients treated with CP* (P=.ws; log-rank test).

Example F3 Survival curve with the curves clearly marked by study group. The number of study
participants at risk is l i e d under each major time point and a log-rank Pvalue is included in the legend.

independent variables are plotted on the x-axis and dependent variables on the
y-axis. Data markers are not connected by a curve, but a curve that is generated
mathematically may be fitted to the data and summarize the relationship among the
variables. The statistical method used to generate the curve and the statistic that
summarizes the relationship between the dependent and independent variables,
such as a correlation or regression coefficient, should be provided in the figure or
legend (Example F4).

Histograms and Frequency Polygons. Histograms and frequency polygons display the
distribution of data in a data set by plotting the frequency (count or percentages) of
observations (y-axis) for each interval represented on the x-axis. In both histograms
and frequency polygons, the y-axis must begin at 0 and should not be broken, and
the x-axis is a continuous, quantitative scale. Histograms use continuous bars of
equal widths determined by the x-axis intervals, where bar height represents fre-
quency (Example F5).
Frequency polygons use data markers to represent frequency connected by a
curve. Data distributions from 2 data sets that overlap can be plotted in a frequency
polygon but not in a histogram (Example F6).
 .

4.2.1 Statistical Graphs

4.0 -

3.5 -
+
3.0 -
++
2.5 -

3
Z
2.0-

1.5-

1.0-

0.5 -
r=-0.361,P=.02

I I I I I 1 I I I
0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0
FSS
-
Figure 3. katterplot showing the relationship between Fatigue Severity Scale (FSS) score and
the N-acetyiaspartate-creatine (NAA/Cr) ratio. Solid line represents the linear regression fit
across all subjects. Spearman rank correlation coefficient and Bonferroni-corrected P value are 8

shown.
1
Example F4 Scatterplot including the regression line, correlation coefficient, and Pvalue in the plot.

Bar Graphs. Bar graphs have a single axis and are used to display frequenci& icounts
or percentages) on the axis according to categories shown on a baseline. A bar graph
is typically vertical, with frequencies shown on a vertical y-axis (Example F7), but
may be horizontal (Example F8). Data in each category are represented by a bar. Bars
should have the same width, be separated by a space, and be wider than the space
between them. Bar lengths are proportional to frequency, the scale on the frequency
axis should begin at 0, and the axis should not be broken. All bars must have e
common bsseline to facilitate cornpari~on.~ Categories of data should be presented in
logical order and cpnsistently with other figures and tables in the article. The baseline
of a bar graph is not a coordinate axis and therefore should not have tick marks.
Bar graphs may be used to compare frequencies between groups. In most cases,
the number of bars in a grouped bar graph should not exceed 3. Colors or tones used
to designate each group should be distinct. To ensure that bars in black-and-white
figures are distinguishable, a contrast in shading of at least 30% for adjacent bars is
suggested. Color or shades of gray should be usetl instt.:~tlof patterns and cross-
hatching (eg, diagonal lines) on bars.

Component Bar Graph. Component bar graphs (or di\,i<ledIxir grxphs) tfisp1;iy [he
proportion of components constituting the roral Kroul,, rcprt.rntc.tl by rhc whole lxir
(Example F9A). lndivitlual components are destgn:l(ed 1,1; disr~nguishingform;~th,

101
 . - -
. -. -- - -
,
Figure 1. Reported Cases of Paralyt~cPoliomyelit~s,United States, 1953-2003 I
Total No. of padjlc
pollornyelrtis IXSS, 1953-2003
110

1 100
90

= so
.-
vl
-
70
E
9 60

-
Z Year
.Y 50

C
40

0 20
.z
10
0
1961. 1964 1967 1970 1973 1976 1979 19e2 1985 1988 l
S1 1994 1997 20M) 2003
Year

Shaded region in the inset IS represented in the larger graph, which shows both total number of cases of paralytic
poliomyelitis and number of cases of vaccineassodaed paralytic poliomyelitis (VAPP) from 1961 (fint reported VAPP
case) through 2003..

Example F5 Histogram showing frequencies, centered over the bar, for each time period (bar height
represents number of cases). Note the use of a figure inset to show how the data fit into a larger context.

. Figure 3. Incidence of Pertussis Among Infants by Age in the United States, 1984-1999

1984 1885 1986 1987 1988 1989 1990 1991 1992 1693 1994 1895 1896 1997 1998 1990
Year
--
Dlphtherla and tetanus toxo~dsand acellular pertussis vacclnes were Introduced for Infant use In 1996 Data are from
the Supplementary Pertussis Surve~llanceSystem l2

Example F6 Frequency polygons can illustrate distributions for multiple groups

 Figure 2. Percentage of Children Aged 19 to 35 Months, by Race. Who Received Either 1 or
More or 3 or More Doses of Pneumococcal Conjugate Vaccine, by Year of National
Immunization Sulvey

21 Dose of p n e u m c a l
conjugatevaccine

Year of National Imrnun'aation Survey Year of National ImmunizationSurvey

E. Example F7 Vertical bar graph with shading to distinguishthe 3 groups that are compared. Note that
i-.
!9:
? ,. the bars are presented in the same order (white, black, other) in each grouping.

Figure. Predicted Change in Annual Days Supplied When Co-payments

Double by Drug Class and Population

caum@ly Ill
W1Vhdnqrtass (Xl(Me ciw~
dass
UImlkConWon

0 6 10 I 6 M 25 90 35 40 45 0 6 10 15 20 25 30 35 40 45

The percentage change in per-member annual days supplied when co-payments in-
crease by 100% in the aterage 2-tier plan is shown. This plan has retail co-payments of
$6.31 for generia and 112.85 for brand-namedrugs and has an index value of 168 For
each chronically illsubpopulation. we estimated the change in drug me wirhm cho (q.
use of antidepressants by depressed patients)and outride of darr (q. uu of au mhn
medications by depressed patients) when co-payments tncreav by 100%

I -.- . -. t

Example FS Horizontal bar graph with the frequencies on the x.axn and categor~eson the y-ax6
 ( Yes till No Do not recall 1
Did you consent
I
to the storage Male
of your blood
for future Female
research?

Did you consent

to let the Male
questionnaire
that you filled in
be used in Female
future research?

Figure 1. The level of awareness of respondents' donation of blood and questionnaire in-
formation, depicted with difference~between sex, is shown. There were 917 respondents to
both questions. In the first question, the sex difference wassignifint (P<.001), f i l e it was not
significant in the second (P=.24). The Swedish .word for "consent" (infomddd) can also be
translated as "agree to" or "accept."

Example F9A A 100% bar graph, a type of component bar graph, shows the components as part
the whole. However, the exact values are not easy to compare with one another in this format.

Yes DO ~ o Recall
t NO Yes DO NO^ Recall NO

Did you consent to the storage Did you consent to let the
of your blood for future research?questionnaire that you filled in
L- - - - . - - --- -. - -- -
be used in future research?
Example F9B The example In Example F9A replotled uvng clusters of bars
 4.2.1 Statistical Graphs

such as differentshading. When possible, it is preferable to use clusters of individual

bars to represent each component (Example F9B) because the only values easily
interpreted in a component bar graph are the total and the end segments.5

Pie Chart. Like the component bar graph, pie charts compare relationships among
component parts. Categories are represented by sections, with the area of the section
being proportional to the relative frequency of each category. Pie charts are used
commonly in publications intended for lay audiences but should be avoided in
scientific publications.6 he angular areas of the individual components of pie charts
may be difficult to compare between pie charts. Usually, data depicted in pie charts
can be summarized in the text or in a table?

[ Dot (Point) Graph. Dot or point graphs display quantitative data other than counts or
frequencies on a single scaled axis according to categories on a baseline (the scaled
axis may be horizontal or vertical). Like that in bar graphs, the baseline does not
represent a scale and therefore does not contain tick marks. Point estimates are re-
presented by discrete data markers, preferably with error bars to designate variability
(Example P10) or box and whisker symbols (Example F11). Dot or point graphs may
be used to compare data between study groups, including positive and negative data
talues relative to a centrally located 0 baseline ("derivation graph"), paired data from

Figure 1. Percentage Change in Daily Mortality for a 10-ppb Increase in Ozone for Total and
Cardiovaxular Mortality, for Singlelag and DiibutedLag Models

0 Cardlwdsalar and m t o r y deaths

- Single-Lag Models
u
Distributed-Lag Models

fhe single-lag model reflects the percentage increase in mortality for a 10-ppb increase in ozone on a single day. The
distributed-lag mod4 reflects the percentage change in mortality fw a 10-ppb increase in ozone during the previous
week. Error ban i n d i t e 95% poneria intervals.
I
I
II
I
!

Example F10 Point estimates plotted by category, including error bars and a marker (dotted line) of
significance.
a Figure 2. Dlstr~but~on
of CRST, ICARS, and UPDRS Total Scores, by Sex and Carrier Status

CRST UPDRS

1 :.

Men W m Men W- Men W m

CFST indkates Clinical Rating Scale for Tremors (score range, 0-120); ICARS, lnternationalcwperatiw Ataxia Rating
Scale (wore range, 0-100): and UPDFS, Unified Parkinson's Disease Rating Scale (score range, 0-108). The horizontal
line in the middle of each box idkates the median, while the top and bottom borders of the box mark the 75th and
25th percentiles, respectively. The whisken above and below the box mark the 90th and 10th percentiles. The polnts
beyond the whUers are outliers beyond the 90th or 10th percentiles.

I I
Example F11 Box and whisker plot with each element defined in the legend.

single hdividuals (Example ~12),or pooled data in meta-analyses and other analyses
that combine data from individual studies (Example F13).

Diagrams

Flowchart. Flowcharts demonstrate &e sequence of activities, processes, events, op-

erations, or organization of a complex procedure or an interrelated system of com-
ponents. Flowcharts are useful to depict study protocol or interventions (Example

Figure 2. Body Weight for Each Participant at Baseline and Post-Diet for the Low-Fat and Low-
Glycemic Load Diet Groups

Low-fat diet (n= 17) Low-glycemic load diet (n=22)

140 140

120 120

Example F12 Ind~vldudl-value

graphs of weight change for each study participant.
 4.2.2 Diagrams

Figure 3. All-Cause Mortality Among Patients With NICM Randomized to ICD or CRT-D vs
Medical Therapy in Primary Prevention

F w s lCD F-no lCD

Years of No. of RiskRatio
Study Enmllment Patients @5%CI) M s r q ~ r d t ~1.869
y
'P=.74
CAV6 1W1-1997 104 0.83(0.45-1.82) -1-
; i
AMIpvIFfP7 1996-2000 103 0.87(0.31-242) :
I . I
'i
MLlNrTE'6 1098-M02 458 0.65(0.40-1.06) 4-
SCD-Hf14 1997-2001 7%? 0.73(0.60-1.04) -b- I
COMPANION^ am-2002 397 o.so(o.m.eq .-a+: 8

ComMned I65d 0.W (0.5.5-0.87) -;

I I I
0.1 1.0 20
Risk Retio (95% CI) . 10

Number of patients with nonkhemic cardiomyopathy (NICM) enrolled is reported. Sine of the data marker corre
spends to the dative weight assigned m the poded analysis using fued-effects models. KD indicates implantable
cardioverterdefibriIlaV,r. CRT-0, cardiac resynchronizationplus defibrhator; CI, confidence intewal.

Example F13 Effect sizes and pooled (combined) data in a meta-analysis, with the size of the data
markers indicating the relative weight of each study. Note that the values plotted are also provided in
the risk ratio column. The dotted line at 1.0 represents no effect and allows for quick visualization of the
effect of each study listed. The overall X2 and P values are provided in the figure.

.- F14), to demonstrate participant recruitment and follow-up such as in a randomized

controlled trial CONS OR^ @ample F15, and Figure 1 in 20.0, Study Design
. and Statistics), or to show inclusions and exclusions of samples in other.types of
studies, such as in meta-analyses of observational studies (MOOSE)? meta-analyses
.. of randomized controlled trials (QUOROM),'~and studies of diagnostic accur:lcy
(STARD).'

Decision Tree. Decision trees are analytical tools used in cost-effectiveness ancl de-
cision analyses.'* The decision tree displays the logical and temporal sequence in
clinical decision making and usually progresses from left to right (Example F16). A
decision node is a point in the decision tree at which several alternatives can hc
selected and, by convention, is designated by a square. A chance node (prol,al,ility
node) is a point in the decision tree at which several events, determined by ch:lncc.
may occur and, by convention, is designated by a circle (see Figure 2 in 20.0. Stid!.
Design and Statistics).

Algorithm. Algorithms contain branched pathways to pcr~nitthe applic:~tion 01'

carefully defined criteria in the task of identification or classification,13such as to lid
in clinical diagnosis or treatment decisions. Standard box shapes are i~sedto inclicate
various steps in the algorithm. For example, an oval begins the algorithm with the
question to be answered or topic to be addressed. A cliamond or hexagon shape
indicates a decision box, which has at least 2 arrows Ic:itling t o tliffercnt paths in
the algorithm. A rectangle or square indicates an action or decision I~ox.Algorithms
 I
i
i
Figure 1. Treatment Plan for CCG-2961
I
I

Dexamethasone
Course 1

Dexamethasone

/ - . .- . - .. -
etai is of
I therapy are in the "~&hods" section and in Barnard et all0 and Lange et al." GCSF
indicates granulocyte colony-stimulatingfactor.
I -

Example F14 Flowchart of a study protocol. Note the use of ovals to indicate a randomization point. :
 Figure 1. Patient Flowchart

I J

230 Met poslqmnm &Mty mleria

7

21 Ex&&d
11 La& d mlensive care
LCYt beds
6 Mend oxygen salwalion
- caO%wthrnel
harndispbedo%&gen
I

3 &-lend pH ~ 7 . 3 mlh
0
Wm2>5OmnHQ
1 Sysld~cHocd WSSUB
<SO mm HQ

104 b s & d t o r e ~ o ~ t h m p y b y 105 Asslgnedtorearmor/gan~awwilh

,kltuimaak(~-' .; -sP-'m*p11)6g~~

.I I
2Dsv;Jcpsd-
-shldv-
C.,

I
%domD9cnd
1 I 4 Developedhealmenlinderanoesnd
dsmnbnuedaudy b e e m
I
I
Example F15 Flowchart for a randomized controlled trial usi;lg CONSORT criteria?
-
Figure 1. Policy Options and Clinical Outcomes After No Vaccination or Vaccination of All
Healthy Infants With Pneumococcal Conjugate Vaccine

No seqciae

Meniryjtis
ce€h€s3
a
-mamy
hvasive
pIEunococcd
,dsease
4
---------------
Death
a
No sequdae
Bactsrda 4
:~ramococcd + j
p -a- n- -m- -i -a- - - - - - - -
a
NoMcddm &
.-
Siwe
--4
w
cQiwe
Mmnedw
,OLitis
8
- - msdia +
- - - - - - - - - - - - -4
Wilh tyrnpnoslomy
€I j
----a
ttbe d a c e n ~ t

:-%-@-*:T- - - - - - .-.
Vaxinatim d all
hedthvinlms

-..- - - ..- ----- -

Dashed lines denote outcomes for which incidence estimates are used; these outcomes are not mutually exclusive.
Node 2 is identical in structure to node 1. but disease incidence is reduced due to vaccination.

Example F16 Decision tree showing options and possible outcomes from left to right. Decis~onsare
illustrated by squares and chance outcomes by circles.
4.2 Figures

Sensitivity

-
Figure 2. Algorithm for Patients With Coronary Artery D~sease(CAD) and Asplrln/Other NSAlD

I Patients with CAD and NSAlD sensitivity

or
t'

Type V reaction*
t
Unstable CAD?

.
Percutaneous comnaly Intewentlon (PCI)
Balloon angioplasty
Bare metal stent
(Plus periproceduralmedications: direct
thmmbin inhibitors or glycopmtein IlMlla
inhibitors)

Medlcal management following PC1or

medlcal management alone
Glycopmtein IlMlla inhibitors (short-term)
Thienopyridines
Warfarin

t
I
1
I

unstable CAM

I Desensitization
2) I 1 Continue management
of unstable CAD

Patients with unstable CAD and acetylsalicylic acid and/or other nonsteroidal anti-inflammatorydrug (NSAID) sensi-
tivity should have their medical management optimized and if appropriate undergo coronary ang'ography and KI
without acetylsalicylicacid treatment. Inthese patients, options during KIindude the use of balloonangioplany and a
bare metal sent along with pharmaceutical adjuncts including glycoprotein Ilb/llb inhibion and direct thrombin
inhibiton. In patients who undergo PC1 a d , also in those who do not undergo KI, pharmacological management
indudes short-termglycoproteinIlMllii inhibitors, t h i i i n e s , and warfarin therapy. Patientswith a type IIreaction
should be managed sirnilarty to an unstable patient as these patients cannot be desensitized to acetylsalicylt acid.
Asterisk indicates uw algorithms do not support a c e i y h l i i ~acid desemWation h patients with a history of
anaphylaxis (type V reaction); however, no data are available to support this recommendation.

-- - - --

Example F17 Treatment algorithm.

use arrows to guide readers through the process, and yes and no are marked directly
on the pathways (Example F17).

Pedigree. Pedigrees illustrate familial relationships and are often used in the study
and description of inherited disorders. Standard symbols are used to indicate each
person's sex, vital status (living or dead), and whether he or she has the condition or
genetic component in question, if known. Lines drawn horizontally and vertically
between symbols convey relationships, with the earliest generation at the top of the
figure (Example F18) (see also 15.6.6, Nomenclature, Genetics, Pedigrees). If the sex
of each person is not relevant to the discussion and there may be a concern about
identifiability/confidentiality, triangles can be substituted for the standard circles
and squares (see also 5.8.3, Ethical and Legal Considerations, Protecting Research
 4.2.3 Maps

Figure. Hypothetical Pedigree for a

Consultand W t h a Family History Suggestive
of a Hereditary Nonpolyposis Colon Cancer

. Co51 St53

I
Y 37Y 35y 32y
En32

A consultand 6 an individual under evaluation for p r e

dicting &/her own future risk. or the risk of histher
offspring. The anow identifies the consultand. The letter
d followed by a number (eg, d. 53) indiwtes the age the
i n d i u a l d i d and the 2-letter abbreviation with num-
ber (eg, Co 53) represents the diagnosis an individual
received followed by the age at the time of diagnosis.
This pedigree meets Amsterdam ll criteria,14 which in-
dudes (1) 3 rebtives with a hereditary nonpolyposis
colorectal c a n c e r - d a t e d tumor, such as colon can-
cer. endometrial cancer, ureteral cancer, cancer of the
renal pelvis, ovarian cancer, stomach cancer, or small-
bowel cancer; (2) one relative must be a first-degree
relative of the other 2; (3) cancers affect at least 2 gen-
erations; and (4) 1 or more cases diagnosed before age
M years.

Example F18 Hypothetical pedigree of 4 generations, with the proband indicated by an arrow. A key
inside the figure plot explains each symbol and abbreviation.

Participants' and Patients' Rights in Scientific Publications, Rights in Published Re-

ports of Genetic Studies).

Maps. Maps are useful to demonstrate relationships or trends that involve location
and distance or to illustrate study sampling methods (Example F19). Maps may be
used to demonstrate geographic relationships (eg, spread of a disease). Choropleth
maps depict quantitative data (eg, relative frequencies I>y county, statc, country,
province, or region), with differences in numerical dac:~.such as rates, shown I>y

111

C
4.2 Figures

Figure 1. Map of Gurage Zone of Ethiopia Displaying Villages Randomly Selected for the Study

Example F19 A map to explain the locations of various study sites, including an. inset to put the
smaller area into geographical context.

shading or colors. Authors should verify map details to avoid misspelled or incorrect
names, deleted features, distorted geographic relationships, misplaced or missing
cities, and misplaced boundaries.

.Illustrations. Illustrations may explain physiological mechanisms, describe clinical

maneuvers and surgical techniques, and provide orientation to medical imaging.
Complex interactions often are easier to convey and understand in an illustration
than in text or tables (Example F20).

Photographs and Clinical Imaging. Photographs and other images in biomedical

articles are used to display clinical findings, experimental results, or clinical proce-
dures. Such figures include r;~diographsand those from other types of medical im-
aging, pl~otomicrograpl~s, and photographs of patients and biopsy specimens. The
:~vailahilityof digital imaging hiis provided the ability to enhance images of photo-
graphic scientific data, such as clinical images or gel electrophoresis bands.14 Such
digital lnanipillation may produce misleading or fraudulent images. Some publica-
tions recluire that authors who submit digital images also submit the original gels,
while others ask authors to list image adjustments in the paper itself.I4
I

4.2.6 Components of Figures

Figure. Coupled Transport of Sodium and Glucose in Intestinal Epithelial Cells

--

i
Although nutreentindependentsodium absorption aaou the bnnh border membrane of intestinal epitheliil cells is
impaired in patients with diarrhea, coupled transport of sodium and glucose is preserved, allowing absorption of salt
and water provided by oral rehydration solutions (ORSs). Sodium-glucose transporter type 1 (SCLTl) mediates the
transport of glucoseagainst its c m t r a t i o n gradient by coupling it to sodium transport. Sodium that enters the cell is
pumped into the blood by the Na+K+ ATPase (adenosine triphosphatase) pump in the basolateral membrane, main-
taining the sodium electrcchemii gradient that drives the sodium-glucosk cotransport mechanism. ~iansportof
i
glucose into the blood is faciliied by glucose tranqmrter type 2 (GLUTZ).
f

Example F20 Illustration depicting physiological mechanisms.

Components of Figures. Clear display of data or information is the most in~port;lnr

aspect of any figure. For figures that display quantitative information, data values

Scales for Graphs. The horizontal scale (x-axis) and the vertical scale (y-axis) indicate
the values of the data plotted in a graph. In most graphs, values increase from left to
right (on the x-axis) and from bottom to top (on the y-axis).

Range of Values. The nnge of values on the axes should Ix slightly greater than tht.
range of values being plotted, so that the entire date set c:ln ;Ippc:lr within the area
defined by the axes and most of the possible range of val11c.so n the axes will be used.
Ideally, the nnge should include0 on both axes, if O is poxsiblc value for the vari:lble
k i n g plotted In line gr.~phs.if n large nnge of v;llucs is n e c c w r ) 1 ~ 1 c;tnnot
t Iw
tlepitrrrl with 3 continirous sale. discontinuity in the ilxis should Iw intlic.;lted with

113
 ~ x ~ i r ccli:~gon:ll
tl lines tli:il signity a missing portion of the range (//).I5 Numerical data
o n 2 sides of a scale break should not be connected to avoid the implication that data
on either side of the discontinuity are linear. For single-axis plots, data h a t exceed
the limits of the ases can be indicated with an arrowhead.

Axis Scales. Divisions of the scales on the graph axes should be indicated by intervals
chosen to be appropriate, simple multiples of the quantity plotted, such as multiples
of 2, 5, or 10." Numbers that represent the values on the axis scale are centered on
their respective tick marks. For linear scales, the axis must appear linear, with equal
intervals and equal spacing between tick marks. However, logarithmic scales may be
useful to show proportional rates of change (Example F13) and to emphasize the
change rate rather than the absolute amount of change when absolute values or
baseline values for data series vary greatly.

Axis Labels. Axes should be labeled with the type of data plotted and the unit of
measure used. Data nlay represent numerical values, percentages, or rates: For nu-
merical data, customary units of measure and their respective abbreviations or
symbols should be used (see 14.12, Abbreviations, Units of Measure). In single-axis
graphs, categories should be clearly labeled along the baseline.

Symbols, Patterns, Colors, and Shading. Symbols, line styles, colors, and shading
ch:tracteristics used in the figure must be explained, preferably by direct labeling of
components in the figure or in a key. Alternatively, this information may be included
in the legend. For a series of figures within an article, the types of symbols,line styles,
colors, and shading should be used consistently. For example, if data for the inter-
vention group and for the control group are designated as a heavy line and as a
lighter line, respectively, then these same line styles should be used for similar data
for these groups in subsequent figures.
When data points are plotted, symbols should be distinguished easily by shape
ancl color or shade. For example, if 2 symbols are needed, the recommended sym-
bols are 0 and ,I5 although 0 and Ior A and A may be used. A combination of
these sy~nbolscan be used when 3 or more symbols are required. The shading or
color of the syl~lbolscan designate specific data. For instance, in all figures in an
article. 0 may indicate dara for the placebo group and for the intervention group.
111bar charts and other figures (such as maps), shading is preferable to cross-
11:itching and other patterns to distinguish 'groups. Patterns can be difficult to read
both in print and online.' Shades should be of appropriate gradations to show
contrast (eg, lo%, 4096, and 70% black).
.,-- .-Si'f..% 1; :."
.....!..<... .-,.>j.<<,..C
,-
.,.,,r. Box
:. and Whisker Plots. Box and whisker formatting may be useful to illustrate the
nonnormal distribution of values within a group (data set). Typically, the top and
bottom of the box represent the 25th and 75th percentiles, the horizontal line inside
the box represents the median or mean, the whiskers are the 10th and 90th per-
centiles, and any outliers are shown as circles (Example F11). Because the value of
each of these components may vary, it is important to define them. Mean values in
box and whisker plots may be connected by curves to show trends, such as point
esrim3tes of mean v:tliies.
 4.2.7 Titles, Legends, and Labels

I 1

risk

1 0 - 6 9 9 v N o n - s m o k e r
>=700
Average arsenic status ,
exposure (pg/L)
n 4 5 pack-years
>=25 pack-years
I I

Example F2l Originally submitted 3-dimensional figure.

-
Error Bars. For plotted data, error bars (depicting standard deviation.'standard error.
range, interquartile range, or confidence intervals) are an efficient way to displ:ly
variability in the data.16Error bars should be drawn to encompass the entire range- of
f variability, not in just one direction (Example F7). Error bars should always be de-
! fined either in the legend or on the plot itself.

3-Dimensional Figures. Inmost cases, figures should not be presented in 3-dimen-

[-
i'
sional format, even when data for 3 variables are being displayed. A 3-dimensional
presentation is inappropriate for any figures that contain only 2 dimensions of clata.
!
Many software programs allow users to adcl enhancing elements to figures, I ~ u t
Sdimensional display may conFuse readers or distract fro111important graphical're-
lationships. For instance, it may be difficult to read from the bar to the correct value
on the axis. Most 3-dimensional presentations can be replotted into more straight-
forward graphics (Example F21, Example F22).

Titles. Legends, and Labels. Many journals. including jddfA, use both titles and
I
legends to describe and clarify figures. Others, likc the Anchi~mJournals, combine
the tirle and legend underneath the figure
 , .... - ~ - - . .- - -.- ... .--- - ---

Figure. Relat~veRlsks of Ldng Cancer by Average Anenic Exposure and Pack-Years of Cigarette
Smoking

--
Average Arsenic Relative Risk
Smking Status Exposure. p& (95%Confdence Interval) :

Nonsmdter <lo 1.00 *.

10-699 124 (0.532.91)
2700 221 (0.71-6.86) a

c25 Pack-yeas c10 2.55 (0.68-8.52) -+a

10-689 5.50 (1.86-15.5) -
2700 628 (1.53-25.7)

225 W - y e a r s c10 3.80(1.28112) +4-----

-
10-699
2700
5 . a (2.lQ-16.1)
11.I0 (3.32-372) j -
a
c
1
0 2 4 6 8 10 12 14 16
Relative R& (95% ConfidenceInterval)

Relativerisks and 95% confidence intervals are shown. The referencegroup was study participants who were exposed
to the lowest level of amnic ( 4 0 pg/Q and never smoked cigarettes. Data haw been adjusted for age at recruit- :
ment. sex, yean of schooling, and habiualakohd consumption in a proportional hazards analysis.
-.

Example F22 The same data in Example F21 replotted in a point graph.

single figure use the designator "Figure" (not "Figure 1'). The title is a succinct clause
or phrase that identifies the specific topic of the figure or describes what the data
show. Each major word in a figure title is capitalized and follows the same rules as for
article titles (see 3.9.1, References, Titles, English-Language Titles). Some publica-
tions print the figure title under the figure, in sentence style, followed immediately by
the legend.
Titles of figures, including diagrams, photographs, and line drawings, generally
should not begin with a phrase identifying the type of figure.
Avoid: Photograph Showing Prominent Physical Signs of Familial Hypercho-
lesterolemia
Better: Prominent Physical Signs of Familial Hypercholesterolernia
Hawever, a description of the type of figure may be required in certain circumst"ances
t o provide context and avoid confusion.
Figure 3. Fluorescein Angiogram Showing Widespread Retinal Capillary
Nonperfusion and Marked Optic Nerve Head Leakage
Figure 4. Autoracliograph Demonstrating Loss of Heterozygosity at the 3p25
Locus in Preneoplastic Foci and Corresponding Invasive Cancer

f Legend. The figure legend or caption is written in sentence format and printed below
or next to the figure. The legend contains information that identifies and describes
the figure, ant1 it shoultl proviclc sufficient cletail to make the figure comprehensible
w~rhoutrcfcrcnce to the text. Although the recommended maximum length for figure
icgencis is 40 words, longer legends may be necessary for figures that require more
 4.2.7 Titles, Legends. and Labels

f
detailed explanations or for multipart figures. Figure legends should contain expan-
sions of abbreviations and footnotes for information too cumbersome to include in
the figure itself.
F
Composite Figures. Compositefigures consist of several parts and should have a single
legend that containsnecessary information about each part. The legend should begin
with a brief description that pertains to all of the components. Each component of the
figure is then desaibed, usually by aseparatesentence beginning with the designation
for the part, followed by a comma. If the parts share much of the same explanation,
parentheticalmention of each par, % appropriate. Such information should be clearly
specified by designations corresponding to the figure components. However, the
designations must be consistent in all legends.
For composite figures with 2 or more panels, capital letters (A, B, C, D, etc)
should be-usedto label the parts of the figure. These letters should be placed in a
small insertbox that is positioned in the same place in each figure. The figure legend
should refer to each of the figurecomponents and the letter designators in a clear and
consistent format &ample F23).

Information About Methods and Statistical Analyses. Statements regarding metho-

dologic clemils are unnecessary for each figure if this information is provided in the
"Methods" section of the article and the text that refers to the figure clearly indicates
the source of the data. Reference to the "Methods" section or to other figures that
contain this information may & appropriate: At times, brief inclusion of methodo-
logic details in the legend may be necessary for understanding the figure.
For data that have beenranalyzedstatistically,pertinent analyses and significance
: values may be included in the figure or its legend.'' Values for data displayed in the
figure(eg, mean or median values) should be'indicated in the figure or ir;the legend.
I The meaning of error should be explained in the legend (Example E ').
V 4.

~hotomicm~ra'p'hs. legends for should include detail; about the

type of stain used and the d e b of mignilication. If the original illustration has been
modified (enlarged-or reduced), the original magnification should be noted. In fig-
ures with 2 or more parts, the stains or magnifications relevant to each individual part
should be noted after its description.
A, Histological sectionof the vertebral specimen showingthe typical "cookie-
bite" tunneling osteoclasia of the vertebral trabeculae (unstained, original
magnification x400). B, For comparison,a bone tissue section of a recent case
of hyperphthyroidism demonstrates very similar defects at the trabecular
surface (hematoxylin-eosin, original magnification x400).
Electron micrograph legends may spec~fymagnification, without information about
the stain.
H m o p b i l u s infuenzae microcolonies of middle ear mucosa 24 hours after
inoculation (~5000).

Visual Indicaton in Illustrations or Photographs. Visual indicators provided in illus-

trations or photographs, such as a reference bar or ruler denoting a measure of
dimension (eg, length) in a photomicrograph, arrows, arrowheads, or other markers,
 -- --

figure I.Qsseous Lslons of the Lumbar VerleDr&? drlc

S k ~ i .

. .. . .-
A, ~umbarvertebra showing a deep smooth-walled erosion at the
posterior aspect. 0. Fused lumbar vertebrae U and U showing focal
diagenetic fossilization and significant general demineralization. Ar-
rowheads indicate level of fusion. C. Osteopenic, granular appear-
ance of the skull vault with loss of distincl trabecular detail. This "salt
and pepper skull" represents trabecular resorption within medullary
bone.

Example F23 Multipart figure with each panel labeled in the upper left corner and also including a
brief description. Note the explanation of the arrowheads in panel 0.
 4.2.9 Figures Reproduced or Adapted From Other Sources

should be clearly defined in the figure or described in the figure legend (Example

Capitalization o f Labelsand Other Text. Capitalization should be kept to a minimum

within the body of the figure.2 Axis labels in figures are akin to column headings in.
tables, so each word should be capitalized (except minor words such as prepositions
of leis than 4 letters). In nonaxis areas of the figure, capitalizing each major word can
make comprehension difficult, especially when phrases or clauses are used. Using
sentence-style capitalization is easier to read' and takes less space.

Abbreviations. Abbreviations in figures should be consistent with those used in the

text and defined in the title or legend or in a key as part of the figure. Abbreviations
,
may be expanded individually in the text of the legend or may be expanded col-
lectively at the end of the legend.
Arachidonic acid is the precursor molecule from which all eicosanoids are
synthesized. Products of the cyclooxygenase 1(COX-1) enzyme include the
potent stimulatorof platelet activation and aggregation thromboxane Az, as
well as prostaglandin Ei (PGE2).
the same abbreviations and symbols, full ex-
planation may be provided in the first figure legend, with subsequent reference to
that legend. This prauice works relatively well in print but can make understanding
figures in online articles more diicult because readers may have to open separate

e published article, figures should be placed as

in the text. Figures should be cited in con-
secutive numerical order in tly text, and references to figures should include their
respective numb&. For example:
through the study are shown in Figure 1.
.' Figure 1shows patient participation and progre&&rough the study.

Patient participation and progress through the study were monitored by the
investigators F~gure1).
Given the potential for variability in the page layout and online publication process,
the text should not refer to figures by position on the page or by other designators.
such as "the figure opposite," "the figure on this page," or "the figure above."

Figures Reproduced or Adapted From Other Sources. It is preferable to use origin;~l

figures rather than those already published. When use of a previously publislictl
illustration, photograph, or other figure is determined necessary, written permission
to reproduce it must be obtained from the copyright holder (usually the puhlislier).
The original source should be acknowledged in the legend. If the original source in
which the illustration has been published is includecl in the reference list, tlic refc-
rence may be cited in the legend, with the citation numlxr for the reference corrc-
sponding to its first appearance in the text, tables, or figures (see 4.1.3. '1':ll)lc.
Components, Footnotes, and3.6, References, Citation). Pemiission shoi~lclI>c 01)-
tained to reproduce the material in print, online, ancl :III liccnsctl vcrsions ("g.

119
I L . ~ ) I . I I ~ I \ ) . 11 I ~ : I IIC
) ' ncccssaly to include additional information to comply with
yx.c-~licla ngil;ige recli~ired by the organization (usually a publisher) granting per-
~~iission t o rep~111lish the figure.
Iteprinted with permission from the American Academy of pediatrics.*

Guidelines for Preparing and Submitting Figures. The preferred format for submit-
rmg ligi1rc.s vi~ricsalnong scientific journals. Authors who submit figures with a
sr.ientific. m:lnusc.ript should consult the instructions for authors of the publication for
specific requirements. For example, some journals require all files to be submitted
111roi1g11 :I \Vcl>-l>:~secl
sul~missionsystem, others may request e-mail attachments,
;~ndstill others m;iy prefer to receive nlaterials in hard copy. Whcn high-resolution
g1.:11>lii~*
I'IIc~s ;ire ~-c~li~ired
tl~atare too large to be sent via e-mail or a Web-based
syhtcm, the images nay be loaded onto a fixed medium such as a CD. The following
gi~ictelinesapply for figures submitted to JAMA and the Archives journals.
Graplls, line art, diagrams, charts, and other black-and-white figures should be
submitted as an electronic file (acceptable formats include EPS, GIF, JPG,and TIF,as
well gs images pasted into Microsoft Word or Powerpoint as long as the vector digital
file is availal>leupon acceptance).
I'hotagraphs, photoinicrographs, or radiographs (whether in color or black and
white) should be submitted as high-contrast, right-reading glossy prints. Color il-
lustrations can be submitted as color transparencies, color slides, color prints, of in a
digital file (EPS, JPG, TIF) along with corresponding color prints. Transparencies
should not be submitted in glass slides. If color prints are submitted, the print should
be made oversized, and the negative of the print also should be provided. Polaroid-
type prints and color laser prints should not be used for reproduction because the
results inevitably are poor.
Providing digital files with adequate resolution is the primary key to printing
high-quality images. Most digital submissions are rejected because of low resolution.
The canvas size of images should be at least 5 in wide (depth is not important).
Generally, digital images should have a resolution of at least 350 ppi. To ensure that
color will be clinically correct, calibrated color proofs should be submitted along
with the digital files. The availability of computer software for generating figures,
such as statis:ical or graphic design programs, has simplified the creation of figures in
digital fonnat. However, the ability of publishers to use author-generated electronic
files containing figures for importing, reproducing, and incorporating into produc-
tion software v a ies ~ considerably. Authors should consult the instructionsfor authors
or the editorial office of the publication for information about preferred and com-
patible rormats for submission of figures in electronic files.
Clear, sharp images are essential for accurate reproduction. Dust and scratches
usually can be removed, but if details are blurred in the original, details will remain
blurred in reproduction. Good exposure is another important consideration in
providing the best-quality prints and transparencies. If necessary, several different
exposures of the sa111e image may be submitted, and the best candidate for image
reproduction will he selected.
All figures should be numbered according to their citation order in the text. For
figuressuhmittecl as hard copy, a label with the figure number, name of the first author,
short for111o f the m:lnuscript title, and the proper orientation (eg, "top") should be
 -- ? . .

4.2.1 1 Consent for Identifiable Patients

afKxed to the back of the print. Writing directly on the 1~1ck of the print should he
I avoided because it may damage the print.
Proper locations for visual indicators (eg, arrows indicating the area of interest in
illustration or photograph) should be identified cleaily. This can be accomplished
providing (in addition to the required clean, unmarked copies of the illustration or
photograph or copies of the 35-rnm slide) an extra paper copy of the illustration or
photograph with locations for indicators marked directly on the paper copy.
Titles and legends for figures should be included at the end of the text and
should riot appear on the illustrations.
submission of digital images have been fom~ulated
e International Digital Enterprise Alliance. The guidelines.
Criteria-(DISC), are available at http://www.disL-info.org

Journal editors should establish clear guidelines about the acceptable amount of
tion (eg, croppirig or contrast adjustment). The consequences of es-
nipulation, regardlew of intent, should be made clear to authors."

Consent for identifiable Patients. For photographs or videos in which an individual

(either by hielf/herself or by others), the author should obtain
and submit a signed statement of informed consent from the identifiable person that
grants permission to publish the photograph Ci print, online, in video, and all lice-
appropriate). Previously used measures to attempt to conceal the
.- identity of an individual in a photograph, such as placing black bars over the person's
eyes, are not effective and should not be used (see 5.8.2, Ethical and Legal Consid-
erations, Protecting Research Participants' and Patients' Rights in Scientific Publica-
tion, Patients' Rights to Privacy and Anonymity). Individuals can be identified in
1 body parts, usually from i d e n w i g features (eg,
.To avoid identifiabilityin such cases, photographs should be
therwise, permission must be obtained from the individual in

For figures that depict genetic information, such as pedigrees or fan:8y trees,
informed consent is required from all persons who can be identified. Authors should
:
not modlfy the pedigree, eg, by changing the number of persons inthe generation,
varying the number of offspring in families, or providing inaccurate infornlation
about the sex of pedigree members, in an attempt to avoid potential identification. If
of pedigree members is not essential for scientific purposes,
signated by triangles instead of circles (females) and squares
(males) (see 4.2.2, Diagrams, Pedigree, and 5.8.3,Ethical and Legal Considerations,
Protecting Research Participants' and Patients' Rights in Scientific Publication, Rights
f Genetic Studies).

Nontabular Material. Nontabular material does not contain cells of individual data.,
Usually it is set off from the text by a box, nrles, sll:~cling.or other elements. Some-
times the b o x or sidebar is cited in the text (following the citation n~iesfor tables) and
other times (eg, in news articles) it is not. Any references that appear in nontabular
material should aLw appear in the reference list and be numl>ereclin order of their
appearance (.see 4.1.3, Table Components).

121
 Step 1 . Mild to Modzra:? Pain
<;ivc p:ltienr nonsrr:roic!l! :!n:i-i:-.il.!r::r::.i:.;:..- . :![!.:; . . .!:-..! !-,!- i ,:.I,
2. ,-,: -I,,:.,-- ..... . . ....
. I. . . . ,..:,c
1
I ;~minophcn,jOO 1;:g or:i!!j (::,. :,., ': -.... . i l ! ' - ....'.I' -1)
I
Step 2. Mode:3t2 t3 S 2 ~ 2 i 2P3;::
, . .
--- ,.[...... : \::.,I.:
,
Gi\re patienr sus~3i;l~c!.;-~ld ,- .... ... .,:!.;!,:. !! :!.:..: p t:i.::::'::., :,,. ,- . . . .
--'
+.L.. i:., ...:jr

oral and recc::l r0~!;253 r 2 n.7; j?.>i:!?'-, ; ::r1:?.;.:!5;:11~1: ;':::11:7./-' ..:. .1. : ., . . - .: ,:.- . .. ., .. - ,

tained-release oi.:il!).
With addicion;i!2j-necilc,i :;>:,:-.;I-:' .... : ..:.-.--, L--;.::!~I.;: pi!! ,: :!::.:: . -:I1.; . -' .'-; . 1
.-I;-)-
,,.-L..d , , I .
,.
A 1..
i
,
-,.- , , .. -
~)::~. .. .~. .~. -. : ...:.......... .'. ...'.
oxycodone 1;~.i[[la < ~ [ 3 ~t ~ ~ p j~.: 3;r,;
, "1:. i.. -
1.. 3 ; .. ?
..-..I .2.'

-.
Examp!? B1 Box 3r ;2,(1;;jl ;25:?3: ; * , > ; ? - , ~ 2j; - j 2bjd;<5 ,,.,. .,..
..-
>

I. 2;:: tj.2 :+(: L! ,,~2':;:.:: ;<' ',' , ! ,"

section.

Avian Influenza: An E:ne;;ic; ?:-5i:m:

~ - , -c]:.!:-)[
I
While the US Cn:-:s fz: D:j.3.7-..' y:7:.,-;;,,-:..l:,, is;f:i-!.; ::-.rcj.....
:I$;,:[ ,.-,- i: L,.?., ,:

handle on [hi.; y?l:'5 ;:li :,

. .
:: ,,; ::<-. . 7
. . .. .
. ,. . > . .-:. . .....,. . . .. .-. -..,.. :, ' . : . . . . . . .. ., , .. . ,
. . . .

flu is ;.lori:;ocr;- b,.:2!-!;2 :r :-.>, ;-; ..:- ...... .

. . . !..;, . . .-,
. . ,..
. .. .-, . . ..' ..- .: ..... . . . '. -:
...,: .
. . .. . . .. . . .. . . . . :
8 >

to have a big':: :r-!c-,;i:il::;- ;I:.:

, . . . -
Earlier t i l i j yc:!.', 1;' .J~L:;~,-.:J..~ :.:; .. .;. .. : .i ::: :'. : . :. :..:. . . .
..... : . . . .
-. ,
5 . . I . , > ( 1

. .
birds dying of;!1, .:!-i;<! .,..2 ;:. :-.:i:. , , ! ' -. - . . ,..- , ' . - .
. . '
, ; . '

[her? v,,er? 3 $ ;gdi.:i..I:.;.~!.,:;,. -r!. :,: . ,.-:. : . ,.:-.> : , . .,'.: . : . ' > .
wich 23 dyin,;. Ti::: ~::-'.r::!l.: :. ,I:..!-:.! - . - .. ' .. , ,
. .
. . . .
......
.
. . .. - . .
- . . . -
land, ahd t'i-i;-La;:i 7'h.: * . . . .--;:
. 5...........
. . . ;. . . . . . . . . . .
S T : . . .
~

... .
12, wit!] 3 inc!iv.ii!i.~lj '.'ii:;.-:,!.,:!. ::-,2.- . . . . . -
,. !
1 . 1
. l i
'
. -

.., .
Adding :i?=en::,:x:-:.. ::-:.--- : .'- . . . . .: ,.. . .. L : ., . . . . . .
. . .-. . . . .. . - . .
-
. . - i . ,

Beca~lse:IV~:L:I ;, !. .,: .; , . , -. . . . . , ' . : , . .

>
c,:~:-,. :.,-.:, - !. j .
.,:i:l.!:;::3 ,.L: ,

plgS, 1.5 :t ill:l;?i- .:C::.:-rii i-,.:'.;.. .. : .. ,. . .. . . . . .. . .. . . . :.. ..:. . ., . .-"-. . . . . . . . . . . .

'
' I ' -'

becnc~scpig.; xr.: t
- . : ,, ::: . . . .. . .. . .: . .. . .. .. . .. .. .. . .. -.. . .. . .. .. . .. . . . .
,3-r.-;i:r-.-:,::2
'

[ha[ [he pig.; \xi!! ; ~ i - . . : .!..: J ..!;,:<::-.; ,~ :.,,:, . :. .,;:: : ::,.:; .:. :: :.. :.
a na . ! : : . : . . , - , , :. : , i .: , . :

r f ; , , .
, : :.......... - , . . . . . .. . .- . . . . . , .. ;'.:,I : . . .: . , :
,?
.

, . . . .#.-
. . . .
The \V.\;'i)slcl!Ic.:lr'l G:..-:::r:.:.!; ..!:- ..i:., .:.: . ., \..L.;...:. ; f : I : . . ..: : . . . . . I;:::
 4.3.2 Sidebars

For More Information '

Onliie information is available from several organizations involved in polio

eradication efforts.
Global Polio Eradication Initiative: http//www.polioeradication.org
Rotary International (Polio Plus program): http//www.rotary.org/foundation
/polioplus/
US Centers for Disease Control and Prevention: http//www.cdc.gov (using the
page's search function for "polio eradication" elicits links to more than 700
reports and other materials on the subject)
UNICEF (United Nations Children's Fund): http//www.unicef.org/immunization
/index-polio. html

Example 83 Sidebar of sources for further reading.

ACKNOWLEDGMENTS
Principal author: Stacy Christiansen, MA
All table and figure examples in this chapter are from J A M and the Archives
Joumals 0 American Medical Association.
Thanks to the following individuals for their contributions: Rbma Henry Siegel,
MD,J MJessica
; S. Ancker, MPH, Department of Biomedical Informatics, Columbia
University College of Physicians and Surgeons, New York, New York; Char1Jensen,
J A M ; and Robert M. Golub, MD,JAUA and Archives Journals.

REFERENCES
1. Svle Manual Committee, Council of Science Editors. Scientific Style and Fomzat: 7he
CSE Manual for Authors, Editors, and Publishers. 7th ed. New York, NY: Rockefeller
University Press, in cooperation with the Council of Science Editors, Reston, VA; 2006.
2. 7he Chicago Manual of Style. 15th ed. Chicago, IL: University of Chicago Press; 2003.
3. Huth EJ. Writing and Publishing in Medicine. 3rd ed. Baltimore, MD: Williams &
Wilkins; 1939.
4. Pocock SJ, Clayton TC, Altrnan DG. Survival plots of time-to-eventoutcomes in clinical
trials: good practice and pitfalls. Lance!. 2002;359(9318):1686-1689.
5. Peterson SM. Editing Science Graphs. Reston, VA: Council of Biology Editors; 1999.
CBE Guidelines No. 2.
6. Tufte ER. 73e Visual mplay of Quantitative Infonnafion. Cheshire, CT:Graphics
Press; 1983.
7. Schriger DL, Cooper RJ. Achieving grdp11ic;ll excellence: . ~ u ~ e s t i oand
n s methods for
creating highquality visual displays of experimental data. Ann Emerg Med.
2001;37(1)75-87.
8 Moher D.Schulz KF. Alunan D; for the CONSORT Group. The CONSORT statement:
=pi.& recommdations for improving the quality of reporb of parallel-group ran-
trials jA.M.4
tio~n~zed 2001,285( 15) 1387-1'991

123
1.3 Nontabular Material

5).Stro~11'I )I:. 1k1l11r ~ x.. C.I ;tI; (or lllc. S~C.I.I-.III.I~~>I>.O~

,lA. \ I t B I I ,I\ ( ) l b w . n J I I ~p1r.11 \ I ~ L ~ I L I .r l~

Ey,trlc.rnioIog! ( 3IOOhk:) Grotrl,. htcta-3n;llya1so f tA>.wn.;rt~oml dudlcs I r r cpldcniiol-

ogy: a propc)sal f o r rqx)ning. JcMiA. 2OOO;Z&IJ(15):L008-2012.
10. Moher D. Cook 111. Esst\vood S . Olkin I, Rennie D,Stroup DF; for the QUOHOM
Group. Iniproving the qi~alityof rrpons of meta-analyses of nndomised controlled
tri:tls: tlic QlJOItOM st;~tclncnt.Irrrrcel. 1933;354(9193):18%-1W.
11. Bossilyt I'M, Keirsma JI3, L3ri1nsDE, et al; lor tlie STAKD Group. Towards complete and
accurate reporting of studies of diagnostic accuracy: the STARD initiative. Clin Chem.
2003;49(1):1-6.
12. Sos HC, Blatt MA, Higsins MC, Manon KI. Medical Decision Making. Boston, MA:
Butterwonhs; 1988.
13. Hadorn DC. Use of algorithliis in clinical guideline development. In: Clinical Practice
~ u i d e [ i nDevelopntenf:
e Melbodolog~Perspectiues. Rockville, MD: US Agency for
Healthare Policy and Research; 194:93-104.
14. Pearson H. Imagine m;~nipul;~tion: CSI: cell biology. Nature. 2005;434(7036):
952-953.
15. ScientificIllustration Committee of the Council of Biology Editors. Illustrating Science:
Standards for Pzil~1ication.- Betliesda, MD: Council of Biology Editors; 1988.
16. Cleveland WS. me E/en~len!.$ of Graphing Data. Rev ed. Summit, NJ: Hobart Press;
1994.
17. Singer PA, Feinstein AR. Graphical display of categorical data. J Clin J$ndemiol.
1993;46(3):231-236.
18. Rossner M. How to guard against image fraud. Scientist. 2006;200):24.

ADDITIONAL READING AND GENERAL REFERENCE

Hall GM, ed. How to mite a Paper. London, England: BMJ Publishing Group; 1994.
Ethical and Legal Considerations

5.1 5.5
Authorship Responsibility Conflicts of lnterest
5.1.1 Authorship: DefinltIun, Criteria. 5.5.1 Requirements for ~ i h o r s
Contributions, and Requirements 5.5.2 Reporting Funding and Other Support
5.1.2 Guest and Ghost Authors 5.5.3 Reporting the Role of the Sponsor
5.1.3 Unsigned Editorials, Anonymous 5.5.4 Access to Data Requirement
Authors, Pseudonymous Authors 5.5.5 Requirementsfor Reporting Industry-
5.1.4 Number of Authors Sponsored Studies
5.1.5 Order of Authorship 5.5.6 Requirementsfor Peer Reviewers
5.1.6 Changes In Authorship 55.7 Requirementsfor Editors and Editorial
5.1.7 Group and CollaborativeAuthorship Board Members
5.5.8 Handling Failure to Disclose Financial
5.2 Interest ' .
Acknowledgments
5.2.1 Acknowledging Suppoh Assistance, 5.6 '
and Contributions of Those Who Intellectual Property: Ownership, Access, Rights,
Are Not Authors and Management
522 Group and Collaborative Author Lists 5.6.1 Ownership and Control of Data
5.2.3 Author Co@ibutions 5.6.2 Open-Access Publication and Scientific
5.2.4 Authors' Conflicts of Interests and Journals
Financial Disclosures 5.6.3 Copyright: Definition, History, and
5.2.5 Access t o Data Statement Current Law
5.2.6 'Funding and Role of Sponsors 5.6.4 Types of Worksand Copyright Duration in
5.2.7 Acknowledgment Elements and the United States
Order of Elements 5.6.5 Copyright Assignment or License
5.2.8 Permissiont o Name Individuals 5.6.6 Copyright Notice and Registration
5.2.9 Personal Communlcation and 5.6.7 Copying, Reproducing, Adapting, and
Credit Lines Other Uses of Content
5.6.8 Publishing Transcripts of Dix6ssions.
5.3 Symposia, and Conferences
Duplicate Publivt\on 5.6.9 Permissions for Reuse
5.3.1 Secondary Publication 5.6.10 Standards for Commercial Reprints
5.3.2 Editorial Policy for Preventing and and E-prints
Handling Allegations of 5.6.1 1 Standards for Licensed lnternational
Duplicate Publication Editions
5.6.12 International Copyright Protection
5.4 5.6.13 Moral Rights
Scientific Misconduct 5.6.14 Copyright Resources
5.4.1 Misrepresentation: Fabrication, 5.6.15 Patents .
Falsification. and Omission 5.6.16 Trademark
5.4.2 Misappropriation: Plagiarism and
Breaches of Confidentiality 5.7
5.4.3 Inappropriate Manipulation of Confidentiality
Digital Images 5.7.1 Confidentiality During Editorial
5.4.4 Editorial Policj and Procedures for Evaluation and Peer Review and
Detecting and Handling Allegations of After Publication
Scientific Misconduct 5.7.2 . Confidentiality in Allegations of
5.4.5 Retractions, Expressions of Concern Scientific Misconduct
5.4.6 Allegations Involving Unresolved 5.7.3 Confidentiality in Legal Petitions and
Questions of Scientific Misconduct Claims for Privileged Information
5.4.7 Allegations Involving Manuscripts 5.7.4 Confidentiality in Selecting Editors
Under Editorial Consideration and Editorial Board Members
Ethical and Legal Considerations

5.8
Protecting Research Participants' and Editorial Responsibility for Manuxript
Patients' Rights in Scientific Publication Assessment
5.8.1 Ethical Review of Studies Editorial Responsibility for Peer
and Informed Consent Review
5.8.2 Patients' Rights to Privacy and Anonym Editorial Responsibility for Rejection
5.8.3 Rights in Published Reports of Editorial Responsibility for Revision
Genetic Studies Editorial Responsibilityfor Acceptance
5.8.4 Patients' Rights in Essays and News Correspondence(Letters to the Editor)
.Reports in Biomedical Journals Corrections (Errata)
Role of the Editorial Board
5.9 Disclosure of Editorial Practices,
Defamal:ion, Libel Procedures, and Policies
5.9.1 Living Persons and Existing Entities Editorial Audits and Research
5.9.2 Public and Private Figures Editorial Quality Review
5.9.3 Groups of Individuals
5.9.4 Statements of Opinion 5.12
5.9.5 Works of Fiction Advertisements, Advertorials, Sponsorship,
5.9.6 Republication and News Reporting Supplements, Reprints, and E-prints
5.9.7 Defense Against Libel 5.12.1 Advertisements
5.9.8 Minimizing the Risk of Libel 5.12.2 Criteria for Advertisements Directed to
5.9.9 Demands to Correct, Retract, or Physicians and Other Health Care
RBmove Libelous Information Professionals
Other Liability Concerns- 5.12.3 Advertorials
5.12.4 Sponsored Supplements
5.10 5.12.5 Other Forms of Sponsorship
Editorial Freedom and Integrity 5.12.6 Advertising and Sponsorship in Online
5.10.1 Maintaining Editorial Freedom: Cases Publications
of Editorial Interference and the 5.1.2.7 Reprints and E-prints
Rationale for Mission, Trust and
Effective Oversight and Governance 5.13
5.10.2 Ensuring a Trust Relationship Release of Information t o the Public and
Between Journal Editors, Publishers, Joumal/Author Relations With the News Media
and Owners 5.13.1 Release of Information t o the Public
5.13.2 Expedited Publication and Release of
5.11 lnformation Early Online
Editorial Responsibilities, Roles, 5.13.3 Embargo
Procedures, and Policies 5.13.4 Suggestions for Authors Interacting With
5.11.1 The Editor's Responsibilities the News Media
5.1 1.2 Acknowledging Manuscript Receipt 5.13.5 News Releases

I f we are to live with this information txplosion, let

us not be tem$ed into dropping all our standards of
/he rlatntv.~aat?dcqbics of scholarship and science.
Derek J. de Solla price1

This chapter is intended to provide guidance to authors, editors, reviewers, and pub-
lishers in the fields of biomedicine, health, and the life sciences. The discussion
focuses on ethical and legal issu$s involved in publication.
~ , ~ behavior is regulated by 3 forces: morality,
According to ~ u n d b e r human
ethics, and law. If personal morality does not regulate acceptable and appropriate
behavior, we can rely on ethics. Ethical behavior is determined by norms, principles,
guidelines, and policies. This chapter cites examples of the determinants of ethical
behavior as they relate to scientific publication. If ethics do not regulate behavior, we
are forced to rely on public laws. Examples of cases involving scientific publication
when laws have been invoked or enforced are also provided in this chapter.
 5.1 Authorship Responsibility

Those ethical and legal considerations and dilemmas most commonly encoun-
tered in scholarly scientific publication are the focus of this chapter. References to
sources for additional guidance and information not discussed in this chapter are also
provided within the text and at the end of each subsection.

. ' ACKNOWLEDGMENT
I . Principal author: Annette Flanagin, RN,MA
Acknowledgments are provided at the end of each section of this chapter.

REFERENCES
1. de Solla Price DJ. Ethics of scientific publication: rules for authors and editorials may
depend on something more than taste and convention. Science. lW;144(3619):655-(557.
2. Lundberg GD. Perspective from the editor ofJAMA, fie Journal ofthe American
Medical Asiodation. Bull Med Libr Assoc. 1992;80(2):110-114.

Somejudge of authots' namesy not works, and then

Norpraise nor blame tbe m'tings, but the men.
Alexander pope1

Authorship Responsibility. More than 50 years ago, Richard M. Hewitt, MD, then
' head of the Section of Publications at the Mayo Clinic, described the ethics of au-
thorship in a JAUA article entitled "Exposition as Applied to Medicine: A Glance at
the Ethics of 1t."' The following excerpts from Hewitt's article demonstrate an app-
reciation of the basic ethical responsibilities and obligations of authorship:
7- ~ u t h o r s h cannot
i~ be conferred; it may be undertaken by one who will
shoulder the responsibility that goes with it.
The reader of a report issued by two or more authors has a right to
assume that each author has some.authoritative knowledge of the subject,
1 that each contributed to the investigation, and that each labored on the
r. report to the extent of weighing every word and quantity in it.
If we would define publication of unoriginal, repetitious medical ma-
terial as a violation of medical ethics, and would officially reprove it as such,
the tawdry author would be silenced and the genuine one helped.
The by-line, then, is not merely a credit-line. He who took some part in
the investigation, be it ever so minor, is entitled to credit for what he hid. . . .
Further, the geherous chap who would bestow authorship on another, per-
haps without even submitting the manuscript to him, may do his colleague no
favor. For the investigation is one thing, the report of it another, and, sad the
day that this must be admitted: The investigation may have been excellent but
the report, bad.
Since all of us necessarily adopt and absorb the ideas of others, we must
be scrupulous in maintaining the spirit of acknowledgment to others. Fun-
damentally, your integrity is at stake. Unless you make specific acknowl-
edgment, you claim the credit for yourself for anything that you write. In
general, it is better to say too much about your sources than too little.
The author who paraphrases or refers to an altirlc shoi~ldhave read it.
5.1 Authorship Responsibility

Authorship: Definition, Criteria, Contributions, and Requirements. Authorship of-

fers significant professional and personal rewards, but these rewards are accom-
panied by substantial responsibility. During the 1980s, biomedical editors began
requiring contributors to meet specific criteria for authorship. These criteria were first
developed for medical journals under the initiative of Edward J. Huth, MD? then
editor of the Annals of Internal Medicine, who cited ~ e w i t t ' swork
~ during discus-
sions at the 1984 meeting of the International Committee of Medical Journal Editors
(ICMJE). The ICMJE guidelines were first published in 1985~and are now part of the
Uniform Requirements for ~ a n u s c r i ~Submitted
ts to ~iomedical~ o u r n a l (see
s ~ also
2.0, Manuscript Preparation). These guidelines are reviewed, revised, and updated
regularly, and numerous biomedical journals use them as the foundation for policies
and procedures on authorship.

Authorship Definition and Criteria. According to the ICMJE guidelines, all authors
should have participated sufficiently in the work to take public responsibility for the
content, either all of the work or an important part of it. To take public responsibility,
an author must be able to defend the content (all or an important part) and con-
clusions of the article if publicly challenged. Sufficient participation means that
substantial contributions have been made in each of the following areas5:
1. Conception and design, or acquisition of data, or analysis and inter-
pretation of the data,
2. Drafting the manuscript or revising it critically for important intellectual
content, and
3. Approval of the version of the manuscript to be published
To justify authorship, an author must meet each of the 3 criteria. However, the term
subsluzzliul contribtilio~~ has not been adequately defined,(perhaps to allow for
wider application of the ICMJE criteria for authorship). As a result, the first criterion,
"conception and design, or acquisition of data, or analysis and interpretation of the
data," may be interpreted broadly. For example, an author of a nonresearch paper
may not have analyzed data per se but may have analyzed literature, events, theories,
argumem, or opinions. The following might be useful for those seeking an ex-
planation of substantial contribution: a substantial contribution is an important in-
tellectual contribution, without which the work, or an important part of the work,
could not have been completed or the manuscript could not have been written and
submitted for publication.
The ICMJE also notes that the following contributions, alone, are not sufficient to
justify authorship5: "Participationsolely in the acquisition of funding, or the collection
of data, or general supervision of the research group is not sufficient for authorship."
(See also 5.1.2, Guest and Ghost Authors.)

??I%F:#pm
Author Contributions. Authors mAy not be aware of the ICMJE authorship criteria. To
inform or remind authors of these responsibilities and to encourage appropriate
authorship, many journals require authors to attest in writing how they qualify for
authorship and to indicate their specific contributions to the work.'-' The ICMJE
guidelines state, "Editors are strongly encouraged to develop and implement a con-
tributorship policy, ;is well as a policy on identifying who is responsible for the in-
tegrity of the work as a wh01e."~Some journals ask authors to describe their spec~fic
 5.1.1 Authorship: Definition, Criteria, Contributions, and Requirements

contributions in an open-ended natrative format, some dcscril)cexamples o f v;lriou\

+
types of author contributions, and some journals provide a list of specificcontributions
in the form of a checklist. For example,JAUA and the Archives Journals require all
authorsto sign a statement of authorship responsibilitybased on the ICMJE guidelines
i and to indicate their specific contributions from a checklist based on the ICMJE au-
thorship criteria and empiric data from studies of authorship and author contribu-
tions. This statement is required for authors of all types of manuscripts, including
editorials, letters to the editor, and book reviewsp1' (see the Box on p 130). J A M and
the Arcbives Journals use a single form for information about authorship responsi-
biity, criteria, and contributions as well author's conflicts of interest disclosure,
copyright transfer, and an acknowledgment statement. An updated example of this
authorship form is available online in the J A M Instructions for Authors at http://
www.jama.com.
Some journals publish author contributions. This practice, first suggested by
Rennie et a1in 1997~ and endorsed by the ICMJE' and the Council of Science~ d i t o r s , ' ~
makes the specific contributions of authors transparent to editors and readers. For
example,JAUA and the Archives of Nacmlogy publish the specific coritributions of
each author for all articles reporting original data (eg, research and systematicreviews)
in the Acknowledgment section at the end of the article (see 5.2, Achowledgments).
According to the ICMJE,some journals also request that 1 or more authors (ie,
"guarantots") be identified as those who take responsibility for the integrity of the
work as a whole, from inception to published article, and publish the names of these
guarantors with the article.'

Additional Author Requirements. Depending on the journal, authors may also be

required to rransfer copyright or a publication license, identify relevant conflicts of
interest or to declaire no such interests, identify sponsorship and the role of the
sponsors in the work to be published, and attest that they had access to the data for
reports of original research (see also 5.6.5, Intellectual Property: Ownership, Access,
Rights, and Management, Copyright Assignment or License, and 5.5.1, Conflicts of
Interest, Requirements for ~uthors).'~

Access to Dafa Requirement The ICMJE recommends that journals ask authors of
studies funded by an entity with a proprietary or financial interest in the outcom~of
the study to sign a statement attesting that they had full access to the data and take
responsibility for the integrity of the data and accuracy of the analysis.5 Following
this recommendation,J A M requires at least 1 author who is independent of any
commercial funder (eb, the principal investigator) to indicate that she or he had full
'
access to all of the data in the study and takes responsibility for the integrity of the
data and the accuracy of the data analysis for all reports containing original data (eg,
research articles, systematic reviews, and meta-analyses).13See also 5.5.4, Conflicts
of Interest, Access to Data Requirement.

Corresponding Author. Every manuscript and published article should have at least 1
author who will serve as the primary contact and correspondent for all commu-
nicarions about the submitred work and, if it is accepted for publication, the pub-
lished article. It is not efficient for editorial offices or readers to have more than 1
formal corresponding author. However, it is helpful to provide the editorial office
 Box. JAh4A A u l n ~ r S h ~Respons~b~l~ty,
p Criteria. and Contributions
!
: li;lc.h : ~ i ~ t l \ cslloul~l
~r mcct all criteri:~I>elow(A, 13, C, and Dl and shoillcl indicate
I
i ~ ~ I I L - I .;; ~I ~l ~ 5pci.iIic.
1 1 1 ~ .:11q)rcq)ri:~It-
cl c.ol~~ril~i~~ions
I N ~xc-s.
Ily rcatling c.riteria A, 15, C, and 1) ;lncl checking
I
I
the manuscript represents original and valid work and that neither this
, manuscript nor one with substantially similar content under tny authorship
has been published or is being considered for publication elsewhere, except
.I
as described in an attachment; and
if requestetl;I will provide the data or will cooperate fully in obtaining and
providing the data on which the manuscript is based for examination by the
editor or the editor's assignees; and
for papers with more than 1 author, I agree to allow the corresponding
iuthor to serve as the primary correspondent with the editorial office, to
review the edited typescript and proof, and to make decisions regarding
release of information in the manuscript to the media, federal agencies, or
both, or, if I am the only author, I will be the corresponding author and agree
to serve in the roles described above.
B. I have given final approval of the submitted manuscript.
C. I have participated sufficiently in the work to take public responsibility for
(check 1 of. 2 below)
part of the content.
the whole content.
5. To qualify for authorship, you must check at least 1 box for each of the 3
categories of contributions listed below.
1 have made substantial contributions to the intellectual content of the paper as
described below:
1. (check at least 1 of the 3 below) I
conception and design 1
acquisition of data
analysis and interpretation of &dta
2. (check at least 1 of 2 below)
IJ drafting of the manuscript 1
critical revision of the manuscript for important intellectual content I
3. (check at l a s t 1 below) ,
statisticrd analysis
obtaining funding
IJ administrative, technical, or material support
ij
supelvision
IJ no additional contributions
0 orl1c.r contril)i~tions(specify)
 5.1.2 Guest and Ghost Authors

with contact information for coauthors in the event that the corresponding author
becomes unavailable during the editorial and publication processes. For example,
J A M and the Axhives Journals require a corresponding author for each submitted
i manuscript to serve as the primary correspondent with the editorial office and, if the
paper is accepted, to review an edited typescript and proof, to make decisions
regarding release of information in the manuscript to the news media and/or federal
agencies, and to have his or her name published as corresponding author in the
-
article. Corresponding authors forJAUA and the Archives Journals also sign a state-
: ment that they have identified all persons who have made substantial contributions
: to the work but who are not authom
I certify that all persons who have made substantial contributionsto the work
reported in thismanuscript (eg, data collection, analysis, or writing or editing
assistance) but who do not fulfill the authorship criteria are named with their
specific contributions in an acknowledgment in the manuscript.
I certify that all persons named in the Acknowledgment have provided me
with written perinission to be named.
I certify that if an Acknowledgment section is not included, no other persons
have made substantial contributions to this manuscript.
(Se& also 5.1.2, Guest and Ghost Authors, and 5.2, Acknowledgments.)

Deceasedor IncapacitatedAuthors. In the case of death or incapacitation of an author

during the manuscript submission and review or publication proc'ess, a family mem-
, ber o r an individual with power of attorney can sign a journal's authorship or pub-
lication form for the deceased or incapacitated author, including the transfer of
copyright or publication license, on behalf of the deceased or incapacitated author.
In-thisevent, the corresponding author can provide information on the deceased or
: incapacitated author's contributions (see also 2.0, Manuscript Preparation).

Guest and Ghost Authors. At least 1 author must be responsible for any part of an
article crucial to its main conclusions, and everyone listed as an author must.have
made a substantial contribution to that specific article.' As described in 5.1.1, Au-
thorship: Definition,Criteria, Contributions,and Requirements, many journals iequire
authors to sign statements of authorship responsibility and to indicate specific con-
tributions of all authors. In addition to improving the transparency of author respon-
sibility, accountability, and credit, these policies may help eliminate guest authors
and identify ghost author^.'^-'^

Guest (Honoraty)Authors. Traditionally, supervisors, department chairs, and mentors .

have been given guest, or honorary, places in the byline even though they hnve not
met all of the criteria for authorship. However, this custom is not acceptable I>cc:tiisc
it devalues the meaning of a ~ t h o r s h i ~ : ' ~ - "ICMJE
~ h e guitlclines state specifically that
"general supervision of the research group is not sufficient for authorship" ant1 that
. participation solely in the "acquisition of funding, collection of data. or gc.ncr:rl su-
pervision'. does not justify a~thorship.~ Such supervision ;tnd panicipation shoulcl
be noted in the ~cknowledgment(.set.5.2. Ackno~vlctlgnic.nts). Gucst ;~i~rhors II;I\.c.

131
.I~M)~rl~.lilclecl
n.cll-knc I \ < rl Ix.rNon\ 111jr p.rn~c.trl.rrticld \vlio have accepted money or
o~licrc.ol~ll>cnsatiorlt o I1:1\.ctl~cirn;rmcb ;~trlrcllc.dto a manuscript that has already
I~ccnrcsearchecl ;ultl prcl>:~rccl1)). :I ghost \vriter for an organization with a com-
mercial interest in the sul,jc.ct of the p~pcr.'5.'nSuch practice clearly is deceitful.14
Se\?ernl studies have documented the prevalence of guest authors in. biomedical
journals mnging from 10%1 o f research articles to 33% of review articles in journals that
were not requesting ;u~tIiorsto disclose their specific contribution^.^^'^

Ghost Authors. Ghost authors have participated sufficiently in the research or anal-
ysis :~nclwriting of a m:~nuscriptto take public responsibility for the work but are not
named in the byline or Acknowledgment section. Studies involving journals that did
not rcqi~ireauthors to disclose specific contributions found that the prevalence of
rcscarch :~nrlreview itrticles with ghost authors ranged from 2% to 26%?.19 In bio-
mcclical publication, ghost authors have included employeesof pharmaceutical com-
1>;111ies (eg, rescarchess, managers, statisticians, epidemiologists), medical writers,
marketing and public relations writers, and junior staff writing for elected or ap-
1x)inted officials.15As described elsewhere, ghost writers have been hied by firms
\\.ith commercial intcscsts to write reviews of specific subjects and their authorship is
not clis~losed.'~~'~~"~~~~~~Ghost writ& are not necessarily ghost authots. For ex-
ample, a writer nlay not have participated in the research or analysis of a study but
may have been given the data and asked to draft a report for publication. If partic-
ilwuitsiin the project do not ~iieetall the criteria for authorship,but have made
substantial contributions to the research, writing, or editing of the manuscript, those
persons should be named, with their permission, in the Acknowledgment along
\\,it11 their contributions and institutional affiliations, if rele~ant'~.~'(see 5.2, Ac-
knowledgments). Editors and authors should not permit anyone who has partici-
pated substantially to meet authorship criteria or any nonauthor who has made
other important contributions not to be appropriately identified in the byline or
Acknowledgment, respectively. (See 5.2, Acknowledgments, and 5.1.6, Changes in
Authorship.)
To give proper credit to medical writers and authors' editors, journal editors
should require authors to identify all persons who have participated substantially in
the writing or editing of the manuscript. Substantial editing or writing assistance
should be disclosed to the editor at the time of manuscript submission and men-
tioned in the ~ c k n o w l e d ~ m e n t .(See
' ~ ' ~5.2,
~ Acknowledgments.) Corresponding
authors ofjMA and the ArchivesJournals sign a statement that all persons who have
made substantial contributions to the work (eg, data collection, analysis, or writing or
editing assistance) but who do not fulfill the authorship criteria are named with their
specific contributions in an acknowledgment in the manuscript.
Journal editors and nlanuscript editors who substantially edit a manuscript to be
published in a journal generally are not specifically acknowledgedwhen their names
appear in the journal's masthead br elsewhere in the journal.

Unsigned Editorials, Anonymous Authors, Pseudonymous Authors. The practice of

publishing unsigned or anonymous editorials provides "vituperative editorialist^"'^
protection from the enemies they might make when taking unpopular stands in the
pages of their journds. However, without named authors and affiliations, readers
 5.1.4 Number of Authors

lack information to judge the objectivity and credibility of the articles. Althougli th~,
practice is the norm for newspaper editorial pages, it has fallen out of use in Inoht
peer-reviewed journals. One rationale for anonymity has been that editorials, signed
or not, represent the official opinion of the publication or the owner of the puldi-
cation. However, such anonymity distances the real authods) from accountal~ility.
For many years, JAMA published unsigned editorials. However, beginning in 1900
JAMA began to inconsistently publish signed or initialed editorials, and since 1970 all
JAMA editorials have been signed by their authors, including editorials written by t t l ~
journal's editors. The BMJ began publishing signed editorials in 1981.~~ AS of this
writing, the Luncet continues to publish unsigned editorials that reflect an unst;itecl
consensus among the editorsz4(see 1.5, Types of Articles, Articles of Opinion).
Journals that publish ukigned editorials and signed scientific articles may give
contradictory messages to their readers about the merits and responsibility of author-
ship. Authors who submit scientific papers must publicly stand by what they write,
whereas unsigned editorialists can hide behind a journal's masthead. Unattributed
editorials may also allow the publisher or owner of the journal and influential organi-
zations to compromisethe journal's editorialindependence(see 5.10, EditorialFreedom
and Integrity). Therefore, all editorials in J A M and the Avchim Journals are signed.
Occasionally, an author may request that his or her name not be used in pub-
lication. If the reason for this request is judged to be important (such as concern for
personal safety or fear of political reprisal, public humiliation, or job loss), the arti-
cle could be published without that author's name. However, justification for such
publication is very rare and should include careful consideration of the value of the
information to be published as well as the potential risks to the author. In such rare
cases, the phrase "Name withheld on request" or the word "Anonymous" could be
used in place of the author'sname (see 2.2, Manuscript Preparation,Bylines and End-
of-TextSignatures).
If anonymity is to be used, the author must still sign statements of.authorship
responsibility and copyright or publication license transfer (using his or her actual
name), and those records must be kept confidential as part of the manuscript file (see
also 5.7.1,Confidentiality, Confidentiality During Editorial Evaluation and Peer Re-
view and After Publication). For the rare case in which withholding of an author's
name is justified, the author's name should be withheld from peer reviewers as well
as readers. However, both reviewers and readers should be informed that the author
has requested anonymity. Citations to such articles in MEDLINE will note "No authors
listed" in the author field.
Pseudonyms are inappropriate in bylines of scientific reports because they are
misleading and cduse problems for literature citations.

31Number of Authors. The number of authors whose names appear in the byline of
scientific papers increased steadily during the second half of the 20th century.25This
increase occurred as a result of specialization, multiclisciplinary collabontion, and
the advent of large multicenterstudies. However, authorship inflation has diluted the
meaning of authorship. For example, which authors in a byline that contains morc
than 100 names can state that they actually wrote the paper or that they partrclpdted
sufficiently to take public responsibility for the work' In rcsponw to th1.l prol,lem.
suggestionswere made in the 1980sand 1990s to limit the rltl~ntwrof ; ~ ~ t r h o Ilucd
rs 111
the byline and database However, socll I~ni~t.at~on\
wr arbltrilry I I ~ I I ,
and may interfere with policies to encourage tnnsp.~rc.nc-\c ) f ~trthorcr>ntnl~utw)n\
1.1 Authorship Responsibility

and thus are not justifiecl. The US National Library of Medicine no longr.r I I I ~ ~ I L \111c
number of individual authors' names listed in an article's citation in MEI)LI~'E.* For
major articles,J A M does not set limits on the number of authors that can LK listtd, as
long as each author meets the journal's criteria for authorship and each author
completes an authorship form indicating specific contributions.JAMA does limit the
number of authors for an editorial or a commentary, and some Archives Journals
continue to request justification or explanation for long lists of authors. For practical
reasons (eg, space available on the first page of a print article), the names of all
authors in an article with a large number of authors may be listed at the end of
the article or elsewhere within an article instead of in the byline at the beginning of
the article (see 5.1.7, Group and Collaborative Authorship). For online versions, all
such lists are linked from the author byline.
Also for practical reasons, many journals limit the number of authors listed in
reference list citations (see 3.7, References, Authors, and 5.1.7, Group and Collab-
orative Authorship). However, the online versions of many journal articles contain
reference lists with links to original articles and to MEDLINE records in PubMed, both
of which list all authors for articles published in 2000 or later.

Order of Authorship. Before proposals for idenufying authors' contributions began

to be implemented, proposed guides for determining order of authorship ranged
from simple alphabetical listings to mathematical formulas for assessing specific
levels of individual contribution levels.2P31However, even the most systematic cal-
culations of contribution levels will require some measure of subjective judgment,
and determination of order of authors is best done by the authors' collective assess-
ment of each other's level of contribution. Moreover, as Remie et a16 have argued,
attempts to provide information to readers by ordering authors in particular ways is
not meaningful, especially if each author's contributions are not made public. The
following may help determine order of authorship3':
1. Only those individuals who meet the criteria for authorship may be listed as
authors (see 5.1.1, Authorship: Definition, Criteria, Contributions, and Re-
quirements).
2. The first author has contributed the most to the work, with other authors listed
in descending order according to their levels of contribution. (Note: Some
.
groups of authors choose to list the most senior author last, irrespective of
the relative amount of his or her contribution.)
3, Decisions about the order of authors should be made as early as possible (eg,
before the manuscript is written) and reevaluated later as often as needed by
consensus (see also 5.1.6, Changes in Authorship).
4. Disagreement about order should be resolved by the authors, not the editor.
5. Authors may provide a publishable footnote explaining the order of authorship,
if there is a compelling reason.
6. Editors may request documentation of authors' specific contributions.

Changes in Authorship. Changes made in authorship (ie, order, addition, and dele-
tion of authors) should he discussed and approved by all authors. Ariy such changes
macle after a manuscript has been submitted should be explained to the journal. The
 5.1.7 Group and Collaborative Authorship

BMJ's policy for alterations in authorship of papers under consideration is a useful

guide for other journals:
Any change in authors and/or contributors after initial submission must be
approved by all authors. This applies to additions, deletions, change of order
to the authors, or contributions being attributed differently. Any alterations
must be explained to the editor. The editor may contact any of the authors
and/or contributors to ascertain whether they have agreed to any a~teration.~~

Group and Collaborative Authorship. Group or collaborative authorship usually

involves multicenter study investigators,members of working groups, and official or
self-appointed expert boards, panels, or committees. Such group-author papers are
also referred to as colkaborati&, co'porate,and collectiveautborpapers. These groups
can comprise hundreds of participants and often represent complex, multidisciplinary
collaborations, and therefore, decisions about listing group authorship pose several
problems and dilemmas for authors, editors, journals, librarians, and bibliographic
databa.~&~' (see 14.9, Abbreviations, Collaborative Groups, and 2.2.4, Manuscript
Preparation, Bylines and End-of-Text Signatures,Multiple Authors, Group Authors).
Large trials and studies are often best known and frequently referred to by their
study name (eg, Women's Health Initiative) or by their abbreviation (eg, W3). As a
result, these groups often include the official name of the study group in an article's
byline (ie, the position on an article's title page where authors are listed). However,
not all members of a study group may meet authorship criteria (see 5.1.1, Authorship:
Definition, Criteria, Contributions, and Requirements), and having the group name in
the byline does not distinguish those members of the group who qualify for au-
thorship from those who do not. In addition, without a single person named as
author, no individual person can take responsibility and be held accountable for
the work. For this reason, at least 1individual (eg, the corresponding author or the
principal investigator) should be named as corresponding author or guarantor (see
also 2.0, Manuscript Preparation). To address these concerns, members of a writing
team or a subgroup are often identified as the authors for large groups.
For groupauthor articles, providing appropiiate credit and accountabilityfor the
many individuals involved-auhors and nonautho-and ensuring proper citation
and online searching and retrieval of the articles are important considerations.34v38
The guidelines that follow may help authors and editors determine who should be
listed and where.
One or more authors may take responsibility for a group (as the authors or
writing team). In this case, the names of individual authors are listed in the byline with
a designation that rhese authors are writing on behalf of or for the group. Those
members of the group who do not qualify for authorship would not be listed in the
byline but may be listed in the Acknowledgment-at the end of the article. In this
case, the byline might read as follows:
Jacques E. Rossouw, MBChB, MD; Garnet L. Anclerhon, 1'111); for the
Women's Health Initiative
or
Writing Group for the Women's Health Initiative

135
5.1 Authorship Responsibility
I
In the latter example, the writing group members are the authors for the group, a n d
their names should be listed in the author affiliation or Acknowledgment section
(with their specific contributions identified). Note: In these cases the formal group-
author name (eg, Women's Health Initiative) should be coded in the journal's online
version and in bibliographic databases so that the results of online searches for ar-
ticles from this group will include articles that combine individual names or sub-
group (eg, the Writing Group) with the formal group name in the byline.
The other nonauthor group members and their contributions may then be listed
separately in the Acknowledgment section (see 5.2, Acknowledgments).
Some authors and groups might prefer that only the group name appear in the
byline to emphasize the collaborative nature of their effort. Thus, another option is
for the byline to list only the group name followed by an asterisk, which refers to a list
of specific authors or a writing committee for the overall group:
Clinical Outcomes Trial Investigators*
The asterisk in the byline corresponds to another asterisk and note on the same
I
printed page of the article or linked affiliation in the online version that identifies a
list of authors who take responsibility for this article. This location of the list of au-
thors must be clearly indicated so that readers can identify the authors and indexers
of bibliographic databases can identify and properly index the names of all authors.
The note might read as follows:
*Authors/Clinical Outcomes Trial Investigators are John Smith, Mary Broad-
bent, Timothy Bowman, Jane Swanson, David Pearce, and Joan wallace.
I
*Authors/Writing Committee Members for the Uhtcal Outcomes Trial In-
vestigators are listed at the end of this article.
In the second example above, the names and affdiations of all authors/writing com-
mittee members and their specific contributions may be listed at the end of the article
(see 5.2.2, Acknowledgments, Group and CollaborativeAuthor Lists), Some journals
may choose to publish long lists of authors from a group in a box or separate list
\vithin the article. To ensure that authors are cited appropriately in bibliographic
databases, explicit use of the term Authors or Writers is preferred.
Authorship can be attributed to an entire group, although this practice is less
comnlon than the examples given above. However, as vith all articles, clear justi-
fication for all members of the group meeting all criteria and requirements for
authorship must be made, and for journals that publish authors' individual con-
tributions, all members of the group must identify their specific contributions (see
5.1.1,Authorship: Definition, Criteria, Contributions, and Requirements). In this case,
the byline might read as follow&
Clinical Outcomes Trial ~hvesti~ators
In cases in which every member of a large group qualifies for authorship and the
I
group name appears in the byline, the individual members of the study group should
be 1isted.separatelyin the Acknowledgment section or in a clearly identified position
within the article, such as a -box set off by rules (as described in 2.2.4, Manuscript
I'reparation, Bylines and End-of-Text Signatures, Multiple ~ b t h o r sGroup
, Authors).
 . .

5.1.7 Group and Collaborative Authorship

If the group name appears in the byline, it is recommended that at least 1person,
usually the corresponding author, be named as an individual who will coordinate
questions about the article. This person can be named in the affiliation footnote as
corresponding author. In this case, the bylirie might read
Clinical Outcomes Trial Investigators
and the affiliation footnote might read
Author AfUations: A complete list of the authors in the Clinical Outcomes
Trial Investigators appears at the end of this aiticle.
CorrespondingAuthor: James S. Smith, MD,Department of Neurology, Uni-
versity of Chicago Medical School, 555 S Main St, Chicago, IL 60615 (smithjsa
umc.edu).
(See also 2.3.3, Manuscript Preparation, Footnotes to Title Page, Author Affiliations,
and 2.10.4, Manuscript Preparation, Acknowledgment Section, Correspondence
Address.)
Publishing the names of all authors and their specific contributions, no matter
how many,with the specific article is preferred. However, a long list of investigators
and affiliated centers could occupy several journal pages and miy be of questionable
value to readers. Yet it is important to publish the names of each author with the
article, for reasons of accountability and credit and to allow proper searching and
retrieval of articles by individual author names in bibliographic databases. If the
identical list of authors h* been published previously in a group list in an indexed and
retrievable journal, the editor may choose to cite and link to that publication in an
affiliation footnote or acknowledgment rather than republish the entire list (see 5.2,
Acknowledgments). A journal that is simultaneously publishing 2 or inore articles from
the same group of authors may consider publishing the list of authors in the initial
article and then citing that article in, and linking to that article from, the otjler related
articles.Another option is to publish the list in the journal's online version of the article,
as long as there is clear indication (citation and iinking) of this list in the printed article.
The same options apply to long lists of other collaboAtors who are not authors.
Study or other group participants should not be promised authorship qatus ancl
a place in the byline merely for performing activities that alone do not qualify for
authorship (eg, cooperating in a study, collecting cl;lta, attcncling a working confer-
ence, lending technical assistance). However, perfornling any of those activities in
addition to writing or critically revising the manusaipt and approving the vcrsion to
be published would be sufficient to merit authorship (see 5.1.1, Authorship: 1)cl-
inition, Criteria, contributions, and Requircmcnts). Eclitors :lncl :1~1t11ors shoultl ;~sscss
the need to publish lengthy lists of authors and other group participants on an in-
dividual basis, and journals should publish their policies about group authorship in
their instructions for authors. .

Citation of Articles With Group Authon. ~rticleswith authors from a large group
have been difficult to locate in bibliographic databases and have resulted in citation
errors and miscalculated citation statistic^.^^-^' To help resolve these problems, the
following has been reconirnendetbM:
n Groi~p-;tuthor;~rticlesshould identify named indiviclu;~lauthors who :~cccptre-
sponsit)iltty for specific articles.

137
 I .iL1 1 ,<it r ~ ~ l ~ - ; ~ :~r[icIe
u ~ l i oshoi~ld
r clearly identify all individual authors (preferably
t u l l il.ltllc.3. IILII I:~sI n;lnles and initials are acceptable) as well as the complete
n;lmc. o f rhc group, whether they appear in the byline or author affiliation.
[ndi\-idi1:11~luthorsshoi11d be distinguished from other contributors and partici-
pants who are not authors.
The names of individual authors and the group name should be formatted and
coded for easy identifiability, searching, and retrieval of the article in print and
online and in bibliographic databases. See Box in 5.2, Acknowledgments.
a Each group-author article should clearly indicate a preferred citation (eg, along
with the abstract or at the end of the article).
ts Search re$.ult.son journal Web sites should clearly indicate a preferred citation, in
addition to relevant author information.
BB Citation standards for group-author papers should continue to be developed and
followed by journals, bibliographic databases, 'and authors.

ACKNOWLEDGMENTS
Principal author: Annette Flanagin, RN,MA
I thank Drummond Remie, MD,JAMA; Trevor Lane, MA, DPhil, University of
Hong Kong; Catherine D. DeAngelis, MD, MPH, J A M and Archives Journals; and .
C. K. Gunsalus, JD, University of Illiiois, ChampaignIUrbana, for reviewing and
providing substantial comments to help improve this section; Daniel M. Albert, MD,
MS, Archives of Ophthalmology;Teni S. Carter, Archives of Sutgery; Paula Gliunan,
Archives Journals; Cindy W. Hamilton, PharmD, EIS, Hamilton House; Sheldon
Kotzin, MIS, National Library of Medicine; Diana J. Mason, RN, PhD, American
journal of Nuvsing; Povl Riis, MD, University of Copenhagen; Valerie Siddall, PhD,
ELS, AstraZeneca; Liz Wager, MA, Sideview, and Flo Witte, MA, EIS, AdvancMed LLC,
for review and providing minor comments; and Sandra R. Schefris and Yolanda
Davis, James S. Todd Memorial Library, American Medical Association, Chicago,
Illinois, for bibliographic assistance.

REFERENCES
1. Pope A. A n Essay 012 Criticism. 17ll:part Ib, line 212.
2. Hewitt RM.Exposition as applied to medicine: a glanc: at the ethics of it. J A M .
1954;156(5):477479.
3:Huth EJ. Guidelines on authorship of medical papers. Ann Intern Med. 1986;
104(2):269-274.
4. International Committee of Medical Journal Editors. Guidelines on authorship. Bhv.
1985;291(6947):722.
5. International Com~nitteeof Medicdl Journal Editors. Uniform Requirements for Manu-
scripts Submitted to Biomedical Journals. http://wnw.icmje.org. Updated February
2006. Accessed September 2, 2006.
6. Rennie D, Yank V, Emanuel L. When authorship fails: a proposal to make contributors
accountal~le../A~rl/l. 1997;278(7?:579-585.
7. Rennie D, Flanrrgin A, Yank V. The contributions of authors.JAW.2000;284(1):89-91.
8. Shapiro DW, \Venger NS. Sl~apiroMF. The contributions of authors to ~nulriauthorrd
biomcdir:~lI.c.:.c;IFI.~~~ . I I X I,/.4.11.-\
.\ lY).i;2-1(~))..1~-~i42.
 5.1.7 Group and Collaborative Authorship

9. Flanagin A, Carey LA, Fontanarosa, PB, et al. Prevalence of articles with honorary au-
thors and ghost authors in peer-reviewed medical joumals.JAMA. 1998;280(3):222-224.
10. Drenth JPH. Multiple authorship: the contribution of senior authors. JAMA. 1998:
280(3):219-221.
11. Yank V, Rennie D. Disclosure of researcher contributions: a study of original research
articles in l%e Lancet. Ann Intent Med. 1999;130(8):661-670.
12. Davidqff F, for the Council of Science Editors Taskforce on Authorship. Who's the
author? problems with biomedical authorship, and some possible solutions. hap://
www.~~uncilscienceeditors.org/publiations/v23n4p111-1l9.pdff February 2000.
Accessed August 4,2006.
13. De~ngelisCD, Fontanarosa PB, Flanagin A. Reporting financial conflicts of interest and
relationships between investigatorsand research sponsors.JAMA. 2001;286(1):89-91.
14. Rennie D, Flanagin A. Authorship! authorship! guests, ghosts, grafters, and the two-
sided coin.J M .1994;271(6):469471.
15. FLanagin A, Rennie D. Acknowledging ghosts. JAMA. 1995;273(1):73.
16. Marusic A, Bates T, Anic A, Mamsic M. How the structure of contribution disclosure
statements affects validity of authorship: it randomized study in a' genenl medical
journal. Cum Med Res Opin. 2006;22(6>:1035-1044.
17. Smith J. Gi authorship: a poisoned chalice? BMJ. 1994;309(6967):1456-1457.
18. Breman TA. Buying editorials. N EnglJ Med. 1994;331(10):673-675.
19. Mowatt G, Shitran L, GrimshawJM,et al. Prevalence of honorary and ghost authorship
in Cochrane reviews. JAMA. 2002;287(21):2769-277l.
20. DeBakey L. ~ e w r i t k gand the b y h e : is the author the writer? ~&gery.1974;75(1):
38-48.
21. Hamilton CW,Royer MG; for the AMWA 2002 Task Force on the Contributions of
Medical Writers to Scientific Publications. AMWA position statement on the con-
tributions of medical writers to scientiFic publications. AMWA J. 2003;18(1):13-16.
22. Morgan P. An InsMet's Guidefor Medical Authots and Editon. Philadelphia, PA: IS1
Press, 1986.
23. Lock S. Signed editorials. BMJ 1981;283(4296):876.
24. 7Be Luncet. Signed-7%e Luncet. Lancet. 1933;341(8836):24.
25. Fye WB.Medical authorship: traditions, trends, and tribulations. Ann Intern Med.
1990;113(4):317-325.
26. Burman KD. "Hanging from the masthead": reflections on authorship. Ann Intern
Med. 1982;97(4):602-605.
27. Epstein RJ. Six authors in search of a citation: villains or victims of the Vancouver
convention? BMJ. 113;306(6880):765-767.
28. National Library of Medicine. MEDUNE/PubMed data element (field) descriptions.
NLM Tecb Bull. November-December 2005:347.
29. Schmidt RH.A worksheet for authorship of scientific articles. Bull Ecol Soc Am. 1987;
68(1):&10.
30. Davis PJ, Gregerman RI. Parse analysis: a new methoct for the evaluation of in-
vestigators' bibliographies. N E n ~Jl AfcJd. lM(,9;281(1H):ox9-'rn),
31. Chambers R, Boath E. Chambers S. The A to Z of autllorship: ;ln;llysis of influence of
initial letter of surname of order of authorship. BMJ. 22001 ;323(7327):1460-1461.
32. Ricsenberg D, Lundberg GD. The order of authorship: who's on first?JAMA. 1W,
Z64( 1-4 )-1857
-4 -3 St~htn~tlin~ an1~1t.s!o the Joc~rnal.ft.1!1 htrp jll~lnjI)~n~iourri.~l*
rc~~~~/;~clvic.c
/anlrlc..zul)m~\+,lonshtmlcturl~or.Ac-cey;ct! ht~gu\lI , 2tKK,.
 I I I . I I \ . I:\.
~ It~O ~ ~ ,~ I .1 ~
~ 1 %~I )~
t . . \.~li f ~
i ~ I,~CI).
> Autll~rsllipfor research groups. J A M .
2~K~2,2&s42il5 l i d ~ - j l ( s +
35. 1)ickrtrsin K. k1lerc.r K. Suci ES1'. Gil-hlontrro M. Problems with indexing and citation
o f a1-rir.1c.5 \\it11 grt)ul, :~uthorship. J.4hfA. 2002;287(21):2772-2774.
36. Errors in cirarion statistics. Sut1rt.r. 2002;415(6868):101.
37. Chcrli~s 1. \Kt11 ~nissingcitations reported: A'ature genome paper jumps. Sci Watch.
2002;13(1::8.
38. Flan~ginA. \Vrobel P, Barbour V, et al. CSE Recommendations for group-author
:~rticJcsin scienrific journals and biblioinetric databases. h t t p : / / v
Accessed.
.cc~~cnc.iIsc~ic~~ceccli~~~rs.or~/cclitori;~l~policies/~rou~~uthorarticle~.cfm.
I)cc.c.~~dicr28, LOOO.

Ifyou wish your merit to be ~ ~ Z O L U Iacknowledge

Z,
that of other people.
Proverl~

Acknowledgments. Acknowledgments typically are used to list grant or funding

support, donors of equipment or supplies, technical assistance, and important spe-
cific contributions from individuals who do not qualify. for authorship (see 2.10,
Manuscript Preparation, Acknowledgment Section, and 5.1.1, Authorship Respon- .
sibility, Authorship: Definition, Criteria, Contributions, and Requirements). Sufficient
space should be provided in publications, either in print or online, for acknowl-
edgments so that authors can properly credit all important contributions.

Acknowledging Support, Assistance, and Contributions of Those Who Are Not

Authors. In the Acknowledgment, authors identify important sources of financial and
material support and assistance and give credit to all persons who have made sub-
stantial contributions to the work but who are not Contributions com-
~nonlyrecognized in an acknowledgment include the following:
General advice, guidance, or supervision
Critical review of the manuscript
Critical review of study proposal, design, or methods
Data collection
Data analysis
Statistical assistance or advice
Technical assistance or advice
liesearch assistance or advice
Writing assistance
Editorial assistance
13il>liographicassistance a

Clerical assist;~ncc
klanuscript preparation
Financial support
hlatcrial support
(;r:int support
 ..

5.2.2 Group and Collaborative Author Lists

Acknowledgments should identlfy anyone who has made substantial intellectual

contributions to manuscripts but does not meet the criteria for authorship, including
medical writers and author's editors1" (see 5.1.2, Authorship Responsibility. Guest
and Ghost Authors). For example,JAMA and the Archirws Joi~rwalsrequire the cor-
responding author to identify such assistance in the Acknowledgment. JAMA also
discloses the affiliationand funding of individuals who contribute to manuscripts but
who are not authors. Such disclosure is supported by the American Medical Writers
~ssociation~ and the European Medical Writers ~ssociation~ as it is more helpful to
editors, reviewers, and readers than are vague statements about writing or editorial
assistance that give no indication about financial relationships. As an example, the
Acknowledgment might read as follows:
Additional Contribution: We thank Joan Smart, PhD; of Medical Biblio-
metrics Inc, Boston, Massachusetts, who received payment from the study's
sponsor, for research and editing assistance.
JAMA requires the corresponding author of all manuscripts to sign an acknowl-
edgment statement (on the authorship.form) that reads as follows:
, . -
I ceaify that all persons who have made substantial contributions to the work
reported in the manuscript (eg, data collection, analysis, or writing or editing
assistance) but do not fulfill authorship criteria are named with their specific
contributioni in an acknowledgment in the manuscript.
I certify that all persons named in the Acknowledgment have provided me
with written permission to be named..
I certify'that if an ~cknowled~ment
section is not included, no other persons
have made substantial contributions to this manuscript.
Nonspecific group acknowledgments, such as "the house staff," "the nurses in the
emergency department," or "patient participants" are often used to thank groups of
individuals. However, if specific people are identifiable, permission to inchde them
would be needed (see also 5.2.8, Permission to Name Individuals). ~cknowl&dgment
of unidentifiable p u p s , such as "the anonymous peer reviewers," is not informative,
and with current policies encouraging greater transparency, acknowledging any
anonymous contributions is best avoided.

Group and Collaborative Author Lists. A list of participants in a collaborative group

may also be included in the ~ c k n o w l e d ~ m e(see n t ~ 5.1.7, Authorship Responsibility,
Group and Collaborative Authorship). However, a lengthy acknowledgment may
occupy an excessi3e amount of journal space. Some editors have proposed limits on
the length of an acknowledgment (eg, 1 column of a journal page or 600 words of
reduced type): but such limits seem contrary to commitments to greater transpar-
ency of the contributions to scientific publication, and journals should carefully
evaluate the appropriatenessof any limits on the length ol'acknowledgrnents. Yct the
need to credit assistance from individuals, especially in large n~ulticentrrclinical
trials, varies considerably. Thus, the editor and corresponding riuthor should dc-
termine the length of published acknowledgments on ;I c.3.w-by-c;isebasih. If it is
. determined that there is not sufficient space in a print pt~l)lic;itic)n10 incli~tlc.I long
list of co1lalx)rjtive participants, [ l ~ elist c;in Ix- pul>lid~c.tlorilirlc ~virll;I ric ) ~ c
~rltll-
cating so in the ~cknowit-gment.wc-tion:

141
I"'
.r,
2 Acknowledgments

A list of study investigators and panic~pd~illg cc-nterb of the Europan 111s-

1,ctes Intervention Trial is :1\.3il;ll1lc. orllinc ;I[ t1rrp-//3rchintc.3m:i-i~~sn.org
/cgi/content/full/l65/22/2495.
Altern:~tively,if a long list of group members or collaborators has been published
previously and has not changed in the interim, tile list can be cited in the affiliation
li~otnotco r Acknowlerlgment section as follows, provided that the names of all
;tuthors are also indicated in the published article:
A full list of investigators and participating centers of the European Diabetes
Intervention Trial as of October 20, 2005, was published in the Archives of
(2005;165[221:24tM-2499).
Irrlcr-rlrrl AI~~cIicirre

Author Contributions. The International Committee of Medical Journal Editors

(ICMJE) encouziges authors and journals to disclose authors' individual contribu-
tions to tllc- work rc-l>o~tc-tl
in p~~l~lishr.tl
;~niclc.s.'Following this reconimeric~ation,a
number of journals now pul)lish lists of author contributions in the article's "Ackno-
wledgment" section.* For example, JAMA publishes each author's contributions, as
shown in the example in the Box on pages 143-144.

Authors' Conflicts of Interests and Financial Disclosures. Authors' financial disclo-

sures should be published with articles, either on the title page or in the Acknowl-
edgment section. JM and the Archives Journals include authors' financial
disclosures in the Acknowledgment section at the end of the article. JAUA requires
authors to include all potential conflicts of interest, including specific financial in-
terests and relationships and affiliations (other than those affiliations listed in the title
page of the manuscript) relevant to the subject of their manuscript in the Acknowl-
edgment section at the time the manuscript is submitted. Authors without conflicts
of interest, including specific financial interests and ielationships and affiliations
relevant to the subject of their manuscript, should include a statement of no such
interests in the Acknowledgment section of the manuscript? (See Box and 5.5.1,
. Conflicts of Interest, Reporting Funding and Other Support.)
Access to Data Statement. The ICMJE recommends that editors request authors of
studies funded by companies or agencies with proprietary or financial interests in the
study outcomes to sign a statement indicating that they had access to all of the data
and can vouch for the integrity of the data analyses? For example, for all reports
containing original data, JAMA and some of the Archives Journals require at least 1
author (eg, the principal investigator) who is independent of any commercial funder
to indicate that she or he "had full access to all of the data in the study and takes
responsibiliry for the integrity of the data and the accuracy of the data analysis."lO~"
J A M publishes such an access to data statement in the Acknowledgment sec-
tion. (See also 5.5.4, Conflicts of Interest, Access to Data Requirement.)
For industry-sponsored studies and any other studies in which proprietary con-
cerns could lead to bias in the analysis, the data analysis should be conducted by an
independent statistician at an academic institution, such as a medical school, aca-
demic medical center, or government research institute, that has oversight over the
person conducting the analysis and that is independent of the commercial sponsor
rather than only by statisticians employed by the sponsor of the research. For ex-
:tmple, for manuscripts in which the statistical analysis was performed exclusively
Box. Hypothetical Example of an Acknowledgment Including Order of Elements

Note. Not all of the elements listed below are relevant for all manuscripts, nor are they
pubiished by all journals. Asterisk indicates items that inay normally appear on page 1 of a
printed article but would appear here in this order if there were not sufficient space on the
first page.

For an Article With the Following Byline:

Jack Kroll, MD;Kathryn Smith, RN,PhD; Jake Otter, MPH; for the Stress Inter-
vention Trial Investigators
Submitted for Publication: August 1, 2006; final revision received September 10.
2006; accepted September 17,2006.
Published Online: October 20, 2006 (doi:10.1001/jama.2006.125).
'Author A£Eliations: Division of Cardiovascular Medicine, University of Florida
College of Medicine, Gainesville (Dr Kroll); Department of Behavioral Science.
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Dr Smith);
Department of Psychiatry, University of Oxford, Oxford, England (Mr Otter).
'Conresponding Author. Jack Kroll, MD,Division of Cardiovascular Medicine,
University of Florida College of Medicine, 25 Main St, Gainesville, FL 32601
([email protected]).
Author Contributions: As principal investigator, Dr Kroll had full access to all the
data in the study and takes responsibiiity for the integrity of the data and the
accuracy of the data analysis.
Study c m e p t and design: b l l , Smith, Otter
Acquisition of data: Kroll, Otter
Analysis and intepztation of data: Kroll, Smith, Oner
Dra$3ing of the manuscript: Kmll
Critical W i o n of the manuscripfor important intellectual content:Smith, Otter
Statistical analysis: Kroll, Smith
Obtainedfunding: Kroll
Administrative, technical, or material suppor~:Kroll
Study superuiion: Kroll .
Financial Disclosures: Dr Kroll has received resesrcll glxnis from and is a paid
consultant to Progen International Inc, manufacturer of the neurochen~icalassay
used in this study, and research grants from the International Society of Stress
Research. Dr Smith and Mr Otter have reported no relevant financial interests in
this publication.
Funding/Support: This study was funded by Progen International Inc and the
International Society of Stress Research.
Role of the Sponsor: Progen International Inc supplied the neurochemical
assay used in this study and funded the study. Through Ilr Kroll, Progen In-
ternational Inc participated in the design and conduct of the study; in the col-
lection, analysis, and interpretation of the data; and in the preparation of the
manuscript. Progen International Inc reviewed the manuscript before subniis-
sion and paid for editing assistance. The International Society of Stress Research
had no role in the design and conduct of the stutly; in the collection, an:~Iy\~s.
--
5.2 Acknowledgments

-- - - -

Box. Hypothetical Example of an Acknowledgment Including Order of Elements Itonr)

and interpretation of the data; or in the preparation of the manuscript or re-

view of the manuscript.
Independent Statistical Analysis: Data sets were forwarded to an independent
statistician, John Smythe, PhD, of the Medical Statistics Unit, Oxford University,
Oxford, England. Dr Smythe, who had no involvement in the planning and
conduct of the original analyses, analyzed the data and has verified that the
results presented in this publication are consistent with his analysis. Dr Smythe
received compensation for this analysis from Progen International Inc.
The Stress Intervention Trial Investigators: Steering Committee:Jeff Brown, MD,
David Chillow, MD, Jane Marshall, MBBS, Lionel1J. Roew, MD, Gilberto Felosa,
MD, Ulrich Teich, MD, Li Wang, MD, MPH, Alexandra Zeer, PhD; Data andSafe&
Maniton'ng Committee:Janice Frank, MD, chair; Michelle Dickersin, MD, William
Malden, MD, Adam Skowrenski, PhD, Anita Toole, MD. Research Coordinators:
Michael Billings, MPH, Timothy Downing, PharmD, Laura Grower, RN,Kenneth
Morrisey, MD, Frederic McLendon, RN,Wanda Smythe, MS, Anne Trafford, PhD.
A full list of principal investigators and participating centers has been published
( J St-. 2004;25[4]:42-50).
Disclaimer: The views expressed in this article are those of the authors and do not
necessarily reflect the opinions of the authors' institutions.
Previous Presentation: Presented in part at the 12th International Stress Man-
agement Congress; February 15, 2005; Chicago, Illinois.
Additional Information: Online Tables 1 and 2 are available at http://www
.jama.com.
Additional Contributions: We thank Joan Simpson, MS, of Write Services, who
was paid by Progen International Inc for editing the manuscript. We thank the
3 patients with serious adverse events, who reviewed the submitted manuscript,
for gr~ntingpermission to include the details about their cases in this article.
Preferred Citation: Kroll J, Smith H, Otter J; for the Stress Intervention Trial
Investigators. An intervention to reduce stress [published online ahead of print
October 20, 20061. J A M . 2006;294(22):1553-1559.

by employees of the commercial sponsor, JAUA editors will ask the authors to have
the analysis and results verified by an independent statistician at an academic in-
stitution; ask that statistician to provide a statement that he or she had access to all the
data (entire raw data set, study protocol, and prespecified plan for data analysis) and
has' independently verified the analysis and results; and publish a notice of this
independent verification in the Acknowledgment section along with information on
fi~ndingfor this additional-analysis? (See also 5.5.5, Conflicts of Interest, Require-
ments for Reporting Industry-Sponsored Studies.) See the examples below.
Independent Statistical Analysis: The accuracy of the data analysis was in-
dependently verified by Jasmine Singh, PhD, and Frank Martin, PhD, both
from the Experimental Research Foundation, an affiliate of Columbia Uni-
versity, nrho received the entire raw database and rep1icate.d all the analyses
that were reported in the accepted manuscript. No discrepancies were dis-
covered. Neither Dr Singh or Martin nor the Experimental Research Foun-
dation receivecl any funding for this independent analysis.
 5.2.6 Funding and Role of Sponsors

Independent Statistical Analysis: Data sets for the interim analyses were for-
warded by Labyx Biometries Inc to an independent statistician, Paul Wise,
PhD, of the Medical Research Unit, University of Reading, Reading, England.
Dk Wise, who had no involvement in the planning and .conduct of the orig-
inal analyses, conducted an independent analysis of the data and has verified
that the results presented in this publication are consistent with his analysis.
Dr Wise was compensated for this analysis by the sponsor of the study.

Funding and Role of Sponsors. Information about funding, sponsorship, or other

financial or material support should also be clearly and completely identified in the
Acknowledgment section, if not already reported in the "Methods" For
all manuscripts that are funded by commercial, governmental, or private entities, a
description of the role of the sponsor(s) in the work reported and the preparation,
submission, and review of the manuscript should be published as ~ e l i , ~For . ' ~ex-
ample, for all funded manuscripts, including letters to the editor,J A M and some of
the Archim Journals require the corresponding author to indicate the role of the
sponsor in each of the following:
Design and conduct of the study
Collection, management, analysis, and interpretation of the data
Preparation, review, or approval of the manuscript
If the sponsor had no role in the above activities, that information should be in-
dicated. If authors are employees of a sponsor, this information should include any
role of the sponsor above and beyond the contributions of the specific sponsor-
employed authors. Some journals publish this information in the "Methods" section.
jAUA and the Archim Journals publish it in the Acknowledgment section (see 5.5.1,
Conflicts of Interest, Requirements for Authors, and the following examples).
Role of the Sponsor:The Centers for Disease Control and Prevention bad no
role in the design and conduct of the study or the collection, management,
analysis, and interpretation of the data; it reviewed and approved the man-
,
I
uscript for submission.
, Role of the Sponsor: The Deutsche Krenshiie had no role in the design and
i
I conduct of the study; the collection, management, analysis, and interpreta-
I
tion of the data; and the preparation, review, or approval of the manuscript.
Authors who are employees of Biopharm Company participated in each of
these activities. The National Institutes of Health reviewed and approved the
study before funding.
Role of the Sponsor. The Medicines Co and the REPLACE-2 Steering Com-
mittee designed the trial, developed the protocol, and determined the
statistical analysis plan by consensus. Data were collected through an
Internet-based electronic case-report form managed by Etrials. The sponsor
had no access to the database or the randomization code, which were
housed at Etrials and Integrated Clinical Technologies Inc, respectively,until
finalization of the database. Data management and site monitoring were
performed by International Healthcare. The finalized database was elec-
tronically transferred simultaneously to the Clevel:~ndClinic Cardiovascu-
:!
lar Coordinating Center and to The Mcdicincs Co. nl~crciinhlincling : ~ n d
5
145
5 2 Acknowledgments

staristical analyses were separately performed. All analyses for scientific

publication were performed by the study statistician at the Cleveland Clinic,
indepenclently from the sponsor. Dr Lincoff wrote all drafts of the manu-
script and made revisions based on the comments of the study chairman, the
Steering Committee, coauthors, and the trial sponsor. The study contract
spccificcl 11i:i1 tlie sponsor had the right to review all publications prior to
submission and could delay submission of such publications for up to 60
clays if necess:tly to make new patent applications, but could not mandate
any revision of the manuscript or prevent submission for publication.

Acknowledgment Elements and Order of Elements. An example of the Acknowl-

cdg~ncntsection including all possible elements as it would appear inJAMA or any of
the Archives Journals is shown in the Box. In print journals, author affiliations and
c-orrespondezre information typically are published on the title page (or first page)
of an unicle. Iiowcver, in wmc cases (eg, articles wit11 lengthy abstracts and author
bylines) and in some journals, there may not be sufficient room for all of this infor-
Ination and it may be published in the Acknowledgment section at the end of the
;~~.~ii.lc
\;.it11 :I noccmit~tlit.:~ting
S L I C on
~ the first page of the article. Online, the author
inl'ol.lnation and Acknowledgmer~tsection usually appear at the end of the article
before the reference list and may be hyperlinked from the list of authors at the
Imginning of the article. '

Permission to Name Individuals. Identification of individuals in an acknowledgment

may imply their endorsement of the article's content. Thus, persons should not be
listed in an acknowledgment without their knowledge and consent. For this reason,
the ICMJE and JM require the correspondiig author to obtain written permission
from any individuals named in the Acknowledgment section and to certify in writing
to the editor that such per~nissionhas been
\

Personal Communication and Credit Lines. ~ollowingthe rationale that including a

person's name in 'an acknowledgment may imply endorsement of a manuscript's
content, citing an individual's name in a personal communication citation may carry
the same implication. The ICMJE recommends that authors who name an individual
'
as a source for information in a personal communication, be it through conversation,
telephone call, or a letter sent by mail, fax, or e-mail, obtain written permission from
the! individual to be named? J A M and the Archives Journals follow the ICMJE
recornmendati~nand require authors to forward copies of all personal communica-
t.ion permissions to the editorial office. The same policy might apply to idenhfying
names in credit lines in the legends of illustrations and photographs; however,
obtaining such permission from the owner of the illustration or photograph would be
part of obtaining permission to include such works as required under the auspices of
copyright law (see 5.6.7, Intelle~tualProperty: Ownership, Access, Rights, and Man-
agement, Copying, Reproducing, Adapting, and Other Uses of Content).

ACKNOWLEDGMENTS
Principal author: Annette Flanagin, RN,MA
I thank C. K. Gunsalus, JD, University of Illinois; Valerie Siddall, PhD, ELS,
AstraZeneca; and Liz Wager, MA, Sideview, for review and providing important
 5.2.9 Personal Communication and Credit Lines

suggeyions for improvement of this section; the following for also providing review
and minor suggestions: Daniel M. Albert, MD, MA, Archives of Opbtbalmology; Terri
S. Carter, Archives of Sutgay; Catherine D. DeAngelis, MD, MPH,JMand Archives
Journals; Cindy W. Hamilton, PharmD, ELS, Hamilton House; Wayne G. Hoppe, JD,
JAMA and Archives Journals; Trevor Lane, MA, DPhi, University of Hong Kong;
Diana J. Mason, RN,PhD, American Journal of Nutsing; Drummond Rennie, MD,
JAM; Povl Riis, MD, University of Copenhagen; Cheryl Smart, MA, MBA; and Flo
Witte, MA, MLS, AdvanceMed LLC; and Sandra Schefris and Yolanda Davis, James S.
Todd Memorial Library, American Medical Association, Chicago, Illinois, for biblio-
graphic assistance.

REFERENCES
1. Rennie D, Flanagin A. Authorship! authorship! guests, ghosts, grafrers, and the two-
sided coin.J A M . 1994;271(6):469-471.
2. Hanagin A, Rennie D. Acknowledging ghosts.J M .1995;273(1>73.
3. Hamilton CW,Royer MG; for the M A 2002 Task Force on the Contributions of
Medical Writers to Scientific Publications. AMWA position statement on the con-
tributions of medical writers to scientific publications. AMWA j. 2003;18(1):13-16.
4. Jacobs A, Wager E. EMWA guidelines on the role of medical writers in developing
peer-reviewed publications. Curr Med Res Opin. 2005;21(2):317-321.
5. Hanagin A, Fontanarosa PB, DeAngelis CD. Authorship for research groups. JM.
2002;288(24):3166-3168.
6. Kassirer JP, Angefl M. On authorship and acknowledgments. N EngI j Med. 1199;
325(21):1510-1512.
7. International Committee of Medical Journal Editors. Uniform Requirements for
Manusuipts Submitted to Biomedical Journals. http:lwww.icmjeorg. Updated Feb-
'
ruary 2006. Accessed September 2, 2006.
8. Rennie D, Flanagin A, Yank V. The contributions of authors.J A M . 2000;284(11:
W91.
9. Fontanarosa PB, Hamgin A, DeAngelis CD. Reporting conflicts of interest, financial
aspects of research, and role of sponsors in funded studies.Jm. 2005;2%(1):
110-111.
10. DeAngelis CD, Fontanarosa PB, Flanagin A. Reporting financial conflicts of interest
and relationships between investigators and research sponsors.jAMA. 2001:286(1):
89-91.
11. Rosenberg RN, Aminoff M, Boiler F, et al. Reporting clinical trials: full access to all of
the data. Arch Neuml. 2002;59(1):27-28.

Wastefulpublication includes dividing the resulk in i!j

a single study into two or more papers Csalami sci- i)i
1)
i::
ence'> npublisbing the same marenal in succes.sive
papen (which need not have identical format and
content), and blending data from one study wzlh
addttronal data to extract ye1 arlotberpaper that
colt Id r~otmake its way on the second set of ciata
alorre {nrciat ~xmrders)
F d n , ~ r c lI t i \ ~ [ t III)'
~

147
5 3 [ J u ~ I I c ~ : ~P. ~ ~ l t c d 1 1 0 n

I
Duplicate Publication. I>uplicate publication is the simultaneous or subsequent
I
rclxmmfi of t-hwnt~:~llythe same information, article, or major components of an
;~nlcle2 or more times in 1 or more forms of media (either print or electronic for-
m;~t).'-"1)uplic:lte reporting includes duplicate submission and may apply to both
~ ~ i ~ l ~ l i:lncl
~ l i ci~nl~i~l~lisliccl
cl works (cg, 1 or more manuscripts not yet published but
ullclcr conhiclc~~tion I)y ;~notlierjournal). Other terms used to describe this practice
include redundarrt,prior, repetitive, ove&pping, related, multiple, duul,parallt.l,frag-
,nerlted, fractionally divided, and topically divided
Duplicate subn~issionor publication is not necessarily unethical, but failure to
disclose the existence of duplicate articles, manuscripts, or other related material to
editors and readers (covert duplication) is unethical and may represent a violation of
copyright law. Moreover, reports of the same data in multiple articles waste pub-
lishing resources (ie, those of editors, reviewers, and readers as well as journal
'
pages),1 pollute the literature, result in double counting of data or inappropriate
weighting of the results of a study and thereby distort the available evidence? cause
problem5 for researchers and those who conduct systematic reviews and meta- ,

analyses,'.0." and may damage the reputation of authors.12

~ u ~ l i c apublication
te usually involves 1 or more of the same authors, but the
number of authors and order of authors may diier among the duplicate reports. ,
Duplication occurs when there is substantial overlap in 1 or more elements of an 1
article or manuscript. For reports of research, duplicative elements may include any
or all of the following: the design, materials and methods, samples or subsamples,
data, outcomes, tables, graphics and illustrative material, discussion, or conclusions.
Duplication also occurs in other types of articles (eg, reviews, case reports, opinion
pieces, letters to the editor, and online blogs).
A widely accepted method of quantwng the amount of overlap or duplication
does not exist. Authors and editors often disagree on how to define and quantify
duplication and whether duplicate articles are justified.13 Researchers in 2 studies of
duplicate publication classified an article as duplicative of another if 10% or more
of the content was identical or highly similar?.14 Others have described levels and
patterns of duplicate publication for research articles that emanate from 1study, such
as reporting identical samples and identical outcomes, identical samples and dif-
ferent outcomes, increasing or decreasing sample sizes and identical outcomes, and
different subsamples from the same overall large study and different outcomes.12~1s'
Studies have also shown that most duplicate articles are published within 1 year of
the publication of the first report.12p16
A number of studies of duplicate publication in various fields have found that
1.4% to 28% of published articles could be classified as duplicative of other arti-
C~eS~7.8.10.14.1G20 In addition, these studies have concluded that as many as 5% to 32%
of duplicative articles do not include a citation or reference to the original or primary
anicle (covert d ~ ~ l i c a t i o n ) ? ~ ' ~ ~ ' ~ ~
Following the recommepdations of the International Committee of Medical
Journal Editors (ICMJE),~a policy that prohibits or discourages duplicate publication
does not preclude consideration of manuscripts that have been presented orally or in
abstract or poster form at a professional meeting. This policy applies whether the
presentation is made in person or via Web cast or an online meeting presentation.
However, publication of complete manuscripts in proceedings of such meetings in !
 C. -.s;-.,
- +

5.3.1 Secondary Publication

print or online may preclude consideration for publication in a primary-source

journal. News reports that cover presentations of data at scheduled professional 1
meetings would not necessarily violate this policy, but authors shoulcl avoid tlis-
tributing copies of their complete manuscripts, tables, and illustrations during sucl~
meetings. Preliminary release of information directly to the news media. usually
through press conferences or news releases, may jeopardize an author's chance^ for \ [
I
publication in a primary-source journa~.~'However, exceptions are i a d e wllcn ;I i
...
government nealth agency . 3 . . .mat
aeternunes . .tnere
. IS an Immediate public ..
need for
such information8121(see 5.13.1, Release of Information to the Public and Journ;il/
- - - -- - - .. - . - - - 5

Author Relations Wlth the News Media, Release of Intormation to the l'uhlic). Src
Box 1for examples of duplicate reports that may be acceptable and necessary. ii -
I
I Secondary Publication. Secondary publication is the subsequent repuhlication. or
simultaneous publication (sometimes called dual or parallel publication). of an ;Ir- i
I
tide in 2 or more journals (in the same or another language) by mutual consent of tl~e
- .... - ....
journal editors. Secondary publication can be beneficial. For example, the editors of
- - - 1 ana a non-mglsn-language journal may agree to sec-
an bngmn-language jourm --3 i
ondary publication in mmlated fonn for the benefit of audiences who speak dif-
ferent languages. The ICMJE approves secondary publication if all of the following
conditions are me?:
1. -1ne authors have recelvea approval from the editors ot both journals;
the editor concerned with secondary publication must have a photo- - \.
copy, reprint, or manuscript of the primary version.
-2. -1-hepriority
- c -* ..... . m ..
or me pnmary puDllcauon 1s respected by a publication
interyl
. .
of at least 1week (unless specifically negotiated otherwise by
both editors).
3. The paper for secondary publication is intended for a differen! group of
-
I
, readers, an abbreviated version could be sufficient.
I 4. The secondary version faithfully reflea5 the data and interpretations of
I the primary version.
3 The footnote on the title page of the secondary version informs readers,
peers, and documenting agencies that the paper has been published in
1 .
wnole or in pat- - - A . .L - - c .....
swrs we pnnrary rererence. A sultatxe rootnote
~ I I U

1;
might read: "This article is based on a study first reported in the [title of
1, journal, with full reference]." Permission for such secondary publica-
tion should be free of charge.
6. The tide of the secondary publication shor~ldindicate chat it is a sec-
'
j
ondary publication (complete republic~tion,abridged republication,
1 complete translation, or abridged translation) of a primary publication.
i
Of note, the National Library of Medicine does not consider translations
to be "republications" and does not cite or index translations when the
original article was published In a joumal that is inclcxcd in MEDLINE.
i
I For example. the title of a translated edition of a journal should include the journal's
I name and an indication of the tnmlared edition in rne -' title
' reg.
' '- ' ' . .
jrt~m-/rutr~ozs).
"

I
Box 1. Dupl~cateReports Thd! Mdy p;lpcrs, editors a%k tll;rt a u t h r ~ ~l ~~ r o l k ' r l !rc-

1
Be Acceptable" Iccncc 211 ~ L I L . ~prcvruus
I ~>irl)l~c~t~uns ;lnd wnd
copies of these along with their sul~niittcd
Summaries or Abstracts of Findings manuscript.
Reported in Conference Proceedings
Short Reports in Print and Longer,
Editors do not discou~xgeauthors from More Detailed Reports Online
presenting their findings at conferences or
Some journals publish shorter versions of arti-
scientific meetings, but they recommend that
cles in print and longer versions online. The
authors refrain from distributing complete
existence of multiple versions of the same arti-
copies of their papers, which might later cle should be made clear to readers and hib-
appear in some form o f pill>lic:~tionwithout liographic databases.
their knowledge. Previous prcsentation(s)
should lie notid in suhmittctl ~n;lnuscripts Executive Summaries
(see 2.10.12, Manuscript l'reparation, Ac- Concise overviews or summaries of large, de-
knowledanlent Section, Previous I'resenta- tailed reports or documents that are regularly
tions). updated are handled on a case-by-case basis.
For all such summaries, editors ask that authors
News MediaRepoN of Authors' Findings
properly reference the larger, more detailed
Typically, editors d o not discourage authors
report.
from reporting their findings at conferences
covered by the news media, but they do Reports From Government Documents
discourage authors from distributing their or Reports in the Public Domain
full papers, tables, or figures, which might Decisions regarding republication of govern-
later appear printed in a newspaper, a ment documents or other reports in the public
newsletter, or the news section of a rnaga- domain are based on the importance of the
zine. Editors do not discourage authors from message, priority for the journal's readers, and
participating in interviews with tile news availability of the information. For example, a
~ncdiaafter a paper has been accepted but journal may publish reports from the US Cen-
before it is published. However, authors ters for Disease Control and Prevention that
should remind reporters that most journals were initially published in the Morbidity and
have an embargo policy that prohibits media Mortality WeeMy Report. The existence of mul-
covenlge of the manuscript under con- tiple versions of the same report should be
sideration and the article before it is pub- made clear to readers.
lished (see also 5.13, Release of Information
to the Public and Journal/Author Relations Translations of Reports in Another Language;
\Vit'ith the News Media). Translated Articles or Same-Language Articles
Republished in a Journal's International Edition
Fragments or Sequential Reports of Studies Translations are usually acceptable as long as
Editors nuke decisions about these types of they give proper attributi~nto the original
tluplicative research reports on a case-by- publication (see 5.3.1, SeCondary Publication).
case basis. For all such papers, editors ask Translations should be faithful to the original,
that authors properly reference previously should not introduce any new content or au-
reported parts of a study and send copies of thors, and should not omit any content or au-
these papers or articles along'with their thors. Translators should be acknowledged.
submitted manuscript.
For each of these cases, a query to the editorial
Detailed Reports Previously Distributed office is recommended, asking whether any
to a Narrow Audience previous publication or release of information
The scope of this audience and the nature jeopardizes a chance for subsequent publica-
of distril~ution(eg, s~nallprint run, time- tion in a specific journal.
limited placement on closed Web site)
woultl tletrrminc wherhcr ctlitors \vould "Adapted from Blancett et a17.with permission of
puI,li.;h :I clul,licitivc rcpon. 1:r)r all such Blackwell Publishing.
 5.3.2 Editorial Policy for Preventing and Handling Allegations of Duplicate Publ~cation

Editorial Policy for Preventing and Handling Allegations of Duplicate Publication.

Covert duplicate publication violates the ethics of scientific publishing and may .
constitute a violation of copyright law. Editors have a duty to inform prospective
authors of their policies on duplicate publication, which should be published in their
instructions for authors. Reviewers should notify editors of the existence of duplicate
articles discovered during their review. Authors should send copies of all duplicate
or overlapping articles and manuscripts with their submitted manuscripts. Authors
should also include citations to highly similar articles and any reports from the same
study under their authorship in the reference list of the submitted manuscript. When
in doubt about the possibility of duplication or redundancy of information in articles
based on the same study or topic, authors should inform and consult the editor.
The editors of J A W and the Archives Journals have adopted the following
policies to prevent the practice of duplicate publication or minimize the risk of its
occurrence:
At the time a manuscript is submitted, the author must inform the editor in the
event that any part of the material (1) exists elsewhere in unpublished form (eg, large
data sets or relevant data not included in the submitted manuscript); (2) is under
consideration by another journal; or (3) has been or is about to be published else-
where. In the case of a highly similar article or manuscript, the author should provide
the editor with a copy of the other article(s) or manuscript(s), so that the editor can
determine whether the contents are duplicative and whether such duplication affects
the editorial priority of the submitted manuscript. All authors are required to sign an
authorship criteria and responsibility statement, which includes the following de-
claration:
Neither this manusaipt nor another manuscript with substantially similar
content under my authorship has been published or is being considered for
publication elsewhere, except as described in an attachment, and copies of
related manuscripts are pmvided.
.' In addition, many journals require authors to transfer copyright ownership or grant a
publication license to the journal as a condition of publication (see 5.6.5, :ntellectual
I Property: Ownership, Access, Rights, and Management, Copyright Assignment or Li-
cense). In the case of duplicate submission, copyright or publication right is likely
owned by the first journal to publish the manuscript, depending on whether copy-
'
right ownership or an exclusive publication license was transferred. Journals that
require authors to grant a license (rather than transfer copyright) to publish a manu-
, script also expect authors to inform editors and prospective readers of any dupli-
cative material. ,
In a case of suspected duplicate submission or publication, editors should first .
contact the corresponding author and request a written explanation. Additional ac-
tions that may be considered are described below.

Duplicate Submission. If an author submits a duplicate manuscript without notifying

the editor($, the editor should act promptly when it is dis~overed.~ If duplicate
submission of a manuscript is suspected before publication, the editor should notify
the author and ask to see a copy of the potentially duplicative material, if not nlrc:ldv
in hand, as well as copies of any other similar articles ancl m:~nuscripts,ant1 rvcluc\t .I

151
4
5.3 Duplicate Publication

\vrittcn explzination. After reviewing all material, the edi~or\sfill rllcrl dr*~.~clc
\vllr.lI~~*r
to continue to consider or to reject the submitted manuscript. If [he rlunu.x'rlpt i h
reiected because of duplicate submission, this reason should be indicated clelrrl!. in
[he decision letter.

3 '.j? . Duplicate Publication. If an editor suspects that duplicate publication has occurred,
the editor should contact the authors and request a written explanation. If necessary,
the editor (possil~lywith the benefit of additional expert opinion) may consult the
editor of the other journal in which the material appeared. If both editors agree that
duplication has occurred, the editor of the second journal to publish the article
should inform the author of the intention to publish a notice of duplicate publication
in a subsequent issue of the journal. It is preferable that this notice be signed by the
author or be accompanied by a letter of explanation from the author, but a notice
of duplicate publication should be published without the author's explanation or
approval if none is f o ~ t h c o m i nDepending
~.~ on the situation, the editor may also
choose to notify the author's institutional supervisor (eg, department chair, dean) to
request assistance with acquisition of an appropriate letter from the author.

Notice of Duplicate Publication. The notice of duplicate publication should be pub-

lished on a numbered editorial page and listed in the table of contents of the journal
in a citable format to ensure that the notice will be indexed appropriatelyin literature
databases. The notice should be labeled or titled as "Notice of Duplicate Publication"
and it may be publiihed as correspondence or a s a correction or erratum. The US
National Library of Medicine identifies duplicate articles in its bibliographic database
by adding a publication type of "Duplicate Publication" to the record of each du-
plicate article and links subsequently published notices of duplicate publication to
the citations of the duplicate It is preferable to publish an explanation from
the author(s1 of the duplicate article with the notice, but this is not always possible or
necessary. The words Duplicate Publication should be included in the title of the
notice, which should include complete citations to all duplicate articles (since there
may be more than 1).Box 2 provides an example of such a notice (wording would
depend on the circumstances in each case), and Box 3, an example of a table of
contents listing. Note: The examples in Boxes 2 and 3 are not real and are intended to
show all of the elements needed for a publiihed notice of duplicate publication and '
to ensure appropriate identifiability and indexing of such notices.
All journals should develop and publish a policy on duplicate submission and
publication.6 In addition, journals should develop procedures for evaluating possi-
ble violations of such policy and actions to be taken once a violation has been
determined to have occurred. This includes requesting an explanation from the
authods), and, if duplicate publication is determined to have occurred, the editor
should notify the other journal(s) involved and may consider notifying the author's
dean, director, or supervisor (this may be necessary if the author does not provide a
satisfactory explanation), anh the editor should publish a notice of duplicate pub-
lication. Some journals in a specific field (eg, pediatrics)23 have decided to notify
each other about cases of proved duplicate publication and ban the offending au-
thor(~)from publishing in their journals for a specified period.
 Box t Hypothetical Example of a Notice of Duplicate Publication

Corn-on: Notice of Duplicate Publication: "Report of Multidrug-Resistant

Mycobacterium tuberculosis Among Residents of a Long-term Care Facility"
(Infect Dis Rep. 2004;270[121:2004-2008)
The article "Report of Multidrug-Resistant Mycobacterium tuberculosis Among
Residents of a Long-term Care Facility" by Anthony S. Smith, MD, published in the
December 2004 issue of Infectious m e m e ~eports,'is virtually identical to an
article by the same author, describing the ssrile 35 cases in similar words, pub-
lished in the Journal o f N w Results, September 2004.~
In June 2004, the author sent a signed statement of authorship responsi-
bility stating that hi manuscript had not been published and was not under
consideration for publication elsewhere. He also signed a document that
&erred copyright ownership in the manuscript to the publisher. Well be-
fore either publication, Dr Smith received a letter of acceptance from Infec-
#iousMseme Reports that included a reminder about our policy on duplicate
publication.
1. Smith AS. Report of multidrug-resistant Mycobacterium trrberculosis among re-
sidents of a long-term care facility. Infect Dis Rep. 2004;270(12):2004-2008.
2. Smith AS. Multidrug-resistant tuberculosis among the elderly: an epidemiolo-
gical assessment.J New Results. 22004;32(9):150-154.

i%e foUowing mponse was mcercertred

from DrSmith afterhe was infonned that the
' above norice wouM bepub1ished.-ED.
In Rep&.-I offer my sincere apologies to the readers of Infectious Disease Re-
poiis. 1 I d not understand that my 2 manuscripts would be considered dupli-
cative at the time I submitted them. I thought that since.the 2 journals are react by
diierent groups, some overlap in wording would be acceptal>le.
Antkony S. Smith, MD
Main University School of Medicine
Chicago, Illinois

Box 3. Hypothetical'~xarnp1eof a Duplicate Publication Notice Listing in a Journal's I

Table of Contents

Correction ....................................................146
i
I
Notice of Duplicate Publication: "Report of Multidrug-Resistant
Mycobacterium tuberculosis Among Residents of a Long-term Care Facility"
(Infect Dis Rep. 20004;70[121:2004-2008)
iI
A. S. Smith I
5.3 Duplicate Publication

ACKNOWLEDGMENTS
Principal author: Annette Flanagin, RN, MA
I thank C. K. Gunsalus, JD, University of Illinois, Champaign/Urbana; Wayne G.
Hoppe, JD, JAMA and Archives Joumals; and Liz Wager, MA, Sideview, for review
and providing important suggestions for improvement of this section; the following
for also providing review and minor suggestions: Daniel M. Albert, MD, MS, Archives
of Ophthalmology; Terri S. Carter, Archives of Surgery; Catherine D. DeAngelis, MD,
MPH,'JAMA and Archives Journals; Paula Glitman, Archives Journals; Cindy W .
Hamilton, PharmD, ELS, Hamilton House; Trevor Lane, hlA, DPhil, University of
Hong Kong; Povl Riis, MD, University of Copenhagen; Valerie Siddall, P ~ D ELS,,
AstraZeneca; Cheryl Smart, MA, MBA; and Flo Witte, MA, ELS, AdvancMed LLC; and
'Sandra Schefris and Yolanda Davis, James S. Todd Memorial Library, American
Medical Association, Chicago, Illinois, for bibliographic assistance.

REFERENCES
1. Huth EJ. Irresponsible authorship and wasteful publication. Ann Intern Med. 1986;
'104(2):257-259.
2. International Colnmittee of Medical Journal Editors. Uniform Requirements for
Manuscripts Submitted t i Biomedical Journals. http://www.icrnje.org. Updated
February 2006. Accessed September 2,2006. ,

3. Broad WJ. The publishing game: getting more for less. Science. 1981;211(4487):1137-
1139.
4. Angel1 M, Relman AS. Redundant publication. N Engl J Med. 1989;320(18):1212-1214.
5. Flanagin A, Glass RM,Lundberg GD. Electronic journals and duplicate publication: is a
byte a word?JAMA. 1992;267(17):2374.
6. Editorial Policy Committee, Council of Biology Editors. Redundant publication. CBE
views. 11336;19(4):76-77.
7. Blancett SS, Flanagin A, Young RK.Duplicate publication in the nursing literature.
ImageJ Nuts Sch. 1995;27(1):51-56.
8. Huston P, Moher D. Redundancy, disaggregation, and the integrity of medical re-
search. Lancet. 1396;347(9007):10241026.
9. Susser M, Yankauer A. Prior, duplicate, repetitive, fragmented, and redundant pub-
lication and editorial decisions. Am J Public Health. 1993;83(6):792-793.
10. von Elm E, Poglia G, Walder B, Tram& MR. Different patterns of duplicate publication:
an analysis of articles used in systematic reviews. JAM. 2003;291(8):974980.
11. Tramer MR, ~ e ~ n o l DJ,d s Moore RA, McQuay HJ. Impact of covert duplicate pub-
lication on meta-analysis: a case study. BMJ. 1997;315(7109):635-640.
12. DeAngelis CD. Duplicate publication, multiple problems. JAMA. 2004;292(14):1745-
1746.
13. Yank V, Barnes D. Consensus and contention regarding redundant publications in
clinical research: cross-se5tional survey of editors and authors. J Med Ethics. 2003;
29(2):109-114.
14. Bailey BJ. Duplicate publication in the field of otolaryngology-head and neck surgery.
Otolnryngol Head Areck Surg. 2002;126(3):211-216.
15. Melander H, Ahlqvist-Rastad J, Meijer G, Beermann B. Evidence b(i)ased medicine-
selective reporting from studies sponsored by pharmaceutical industry: review of ;
studies in new drug applications. BMJ.2003;326(7400):1171-1173.
 5.3.2 Editorial Policy for heventing and Handling Allegations of Duplicate Publication
' x I

16. Rosenthal EL, Masdon JL, Buckman C, Hawn M. Duplicate publications in the oto-
laryngology literature. haryngoscope. 2003;113(5):n2-n4.
17. Waldron T. Is duplicate publishing on the increase?BMJ. 1992;304(6833):1029.
!
18. Barnard H, Overbeke JA. Duplicate publication of original articles in and from the
Nedmhnds Ti]&chnift voor Geneeskunde. Ned Tijdschr Geneeskd. 1993;137(12):
593-597.
19. Mojon-Azzi'sM, Jiang X, Wagner U, Mojon DS. Redundant publications in scientific
ophthalmology journals: the tip of the iceberg? Ophthalmology. 2204;111(5):853-866.
20. Gwilym SE, Swan MC, Giele H. One in 13 "original" articles in the Journal ofBone and
Joint Surgery are duplicate or fragmented publications.J Bone Joint Surg Br. 2004;
86(5):743-745.
21. Fontanarosa PB, Flanagin A, &Angelis CD. THEJOURNAL'S policy regarding release of
idonnation to the public. J&. 2000;284(22):2929-2931.
22. US National Library of Medicine. Fact sheet: errata, retraction, duplicate publication,
comment, update and patient summary policy for MEDLINE. http://www.nlm.nih
.gov/pubs/factsheets/errata.html. Accessed September 2, 2006.
23. Bier DM, Fulginiti VA, GarfunkelJM, et al. Duplicate publication and related problems
Pediatrics. 1990;86(0.997-998.

We should ignore whining about the supposedly

awfulpressures of 'fpubl~h orper&hMwhen we have
little credible evidence on what motivates
misconduct, nor on what motivates the conduct
of honest, equally stressed colleagues. haziness,
desirefor fame, greed, and an inability to
distinguish right from wrong are just as likely
to be at the root of the problem.
Drumrnond ~ e n n i e '

Scientific Misconduct. In scientific publication, the phrase scientijic misconduct

(specifically termed mearch misconduct by US government regulations and com-
monly known as fraud) has both ethical and legal connotations for authors and
editors. A few studies (with limited methodologies) have estimated the prevalence of
scientists who have participated in scientific misconduct to range from 1%to 2%.24 In
a 2002 survey5of a random sample of scientists funded by the US National Institutes
of Health, 3247 participating scientists reported engaging in a number of unethical
behaviors, including falsifying research data (O.3%), sing another's ideas without
permission or credit (1.4%), and inadequate record keeping related to research pro-
jects (27.5%). Although inadequate record keeping is not a form of misconduct in
itself, it could permit misconduct to occur and make investigations of misconduct
difficult to conduct. Legal determinations of scientific misconduct in bion~edical
publication are uncommon, although, when discovered, such misconduct results in
serious questions about [he validity of scientific research and the credibility of au-
thors and journals. Proven cases of misconduct in the published literature as well as
allegations and concerns that do not result in an official finding of misconduct raise
 I I I .11 (1t1~,110113 ; I I ~ C I ililpose duties on authors and editors to protect and
I : I . ~ v1111t
I I I : ~ ~

t I1L.t 1 1 1 1 ~ ' IIICI.;I~LII~C.

,I

()\.L.s llle !.ears, \~a1.ioits definitions of scientific misconduct have been suggested
I)? 1:s government agencies and academic institutions, especially after highly pub-
licized ;ncidents of fraudulent research in the United States in the mid-1970s and
msly 1980s."-" In 1989, the US Public Health Service released the following definition
o f scientific misconduct: "fabrication, falsification, plagiarism, or other practices that
seriously cleviate from those that are commonly accepted within the scientific corn-
mu nit!^ for proposing, conducting, or reporting re~earch."~ This definition was con-
siclcrecl :I pl-~ctic.:~l tool for recognizing and dealing with allegations.of scientific
misconduct during the manuscript submission, review, and publication processes.10
tlowever, controversy grew over various interpretations of the definition (eg, how ,

n:Irro\v or broad should the definition be? does the definition address intent or levels i
o f seriousness of offense?can the definition stand up in court? can the definition serve i
multiple sciences?). !
In the wake of this controversy, the US Public Health Service appointed a Com-
lnission on Research Integrity in 1993.One of the charges of the commission was to
cleveltp a better definition of scientificmisconduct. In 1995,the commission released
;I cletailed report that included a recommendation that the definition be amended to
include offenses that constitute research misconduct: misappropriation, interference,
and misrepresentation." This definition replaced .the word plagiarism with the
I~roaderterm nzisappropriation; replaced the words fabrication and falspcation '
1 I
with the term etis~vpresentation;and added the term irzwerence to address in-
stances "in which a person's research is seriously compromised by the intentional I
and unauthorized taking, sequestering, or damaging of property he or she used in
the conduct of research."" In this context, pmperty included apparatus, reagents,
,
I
biologic materials, writings, data, and software.
The commission's definition was not adopted by the US Public Health Service for ]
many reasons, including protests from scientists and some science groups to which
the governlnent responded that it wanted a definition that would work for all gov-
ernmental departments (eg, both the' US Public Health Service and the National
Science Foundation, which at the time had different definiti~ns).'~"~ In 1936, the
National Science and Technology Council, a unit within the Office of Science and
Technology Policy responsible for coordinating policy among multiple government
research agencies, drafted a common definition, which, after review and comment,
was approved and released in 2000.13 This definition no longer contained a category
of misconduct in the original 1989 definition: "other practices that seriously deviate
from those that are con~monlyaccepted within the scientific community for pro-
posing, conducting, or reporting research."
The revised comnmon definition was reviewed again in 2004 and reissued with-
out substantial change in 2005 by the US ~epartmentof Health and Human Services
(DHHS) (although there were other changes to correct errors and improve clarity in
the overall policy).'i
The current common definition of research nlisconduct from the DHHS fol-
IO\\JS~~:

Research misconduct is defined as fabrication, falsification, or plagiarism in

proposing, pc~.forming,or reviewing research, or in reporting research
scs11I15.
 5.4.1 Misrepresentation: Fabrication, Falsification, and Omission

Fabrication is making up data or results and recording or reporting them.

Falsification is manipulating research materials, equipment, or processes, or
changing or omitting data or results such that the research is riot accurately
represented in the research record. ,

Plagiarism is the appropriation of another person's ideas, processes, results,

or words without giving appropriate credit.
Research misconduct does not include honest error or differences of opi-
nion. A finding of research misconduct requires that:
there be a significant departure'from accepted practices of the
relevant research community; and
the misconduct be committed intentionally, or knowingly, or
recklessly; and
the allegation be proven by a preponderance of evidence.
None of the definitionsof scientificmisconduct include honest error or dserences
in interpretation. Nor do they include or pertain to violations of human or animal
experimentation requirements (5.8, Protecting Research Participants' and Patients'
Rights in Saentific Publication), financial mismanagement/misconduct, or other acts
covered by existing laws, such as sexual harassment, copyright, confidentiality, libel
(see 5.6.3, Intellectual Property: Ownership, Access, Rights, and Management, Copy-
right: Definition, History, and Current Law; 5.7, Confidentiality; and 5.9, Defamation,
Libel), or other concerns, such as authorship disputes, duplicate publication, self-
plagiarism without indicationof one's previouswork, or conflicts of interest" (See 5.1,
Authorship Responsibili~,5.3, Duplicate Publication; and 5.5, Conflicts of Interest.)
The DHHS common definition of research misconduct is intended to apply to US
government-funded research, and academic and research institutions that accept
government Funding must comply with the definition and associated regulations.
However, this definition and associated regulations have become de fact6 rules for
US academic and other research institutions and are applied to any work done by
their employees or under their aegis regardless of the source of funding. These
institutions often have other rules that cover "other practices that seriously deviate
from those that are commonly accepted within the scientific community for pro-
posing, conducting, or reporting re~earch."~

Misrepresentation: Fabrication, Falsification, and Omission. Fabrication, falsifica-

tion, and omission are forms of misrepresentation in scientific publication. Fabrica-
tion includes statirig or presenting a falsehood and making up data, results, or "facts"
that do not exist. Falsification includes manipulation of ~naterialsor processes, '

changing data or results, or altering the graphic display of data or digital images in a
manner that results in misrepresentation (see also 5.4.3, Inappropriate Manipulation
of Digital Images). Omission is the act of delikrately not reporting certain infor-
mation for a desired outcome. Data fabrication,falsification,and omission occur when
an invmrgator or author creates, alters, manipulates. selects, or presents selected
or falls to repon selected information for a desired outcome {hat distorts the inter-
pret.~tir,nof thc orig~nald313. the research rccord. o r rllc rn~th."-'~
Misappropriation: Plagiarism and Breaches of Confidentiality. Misappropriation in
bc~ent~ficpul~l~c..trio~l
In<I~rclcspl.ig~rrrt.\rnand breaches of confidentiality during the
privileged review o f a nlmuscript."-" (ST also 5.7.1, Confidentiality,Confidentiality
During Editorial Evaluation and Peer Review and After Publication.) In plagiarism, an
author documents or reports ideas, words, data, w graphics, whether published or
unpublished, of another as his or her own and without giving appropriate credit."
IJlagiarism of pu1)lishcd work violates standards of honesty and collegial trust and
may also violate copyright law (if the violation is shown to be legally actionable) (see
5.6.7. Intellectual Property: Ownership, Access, Rights, and Management, Copying,
Reproducing, Adapting, and Other Uses of Content).
Four common kinds of plagiarism have been identified%
1. Direct plagiarism: Verbatim lifting of passages *ithout enclosing the
borrowed material in quotation marks and crediting the original author.
2. Mosaic: Borrowing the ideas and opinions from an original source and
a few verbatiln words or phrases without crediting the original author.
In this case, the plagiarist intertwines hi or her own ideas and opinions
with those of the original author, creating a "confused, plagiarized
mass."
3. Paraphrase: Restating a phrase or passage, providing the same meaning
but in a different form without attribution to the original author.
4. Insufficient acknowledgment: Noting the original source of only part of
what is borrowed or failing to cite the source material in a way that
allows the reader to know what is original and what is borrowed.
The common characteristic of these kinds of plagiarism is the failure to attribute
words, ideas, or findings to their true authors, whether or not the original work has
been published. Such failure to acknowledge a source properly may on occasion be
caused by careless note taking or ignorance of the canons of research and author-
ship. The best defense against allegations of plagiarism is careful note taking, record
keeping, and documentation of all data observed and sources used. Those who
review manuscripts that are similar to their own unpublished work may be especially
at risk for charges of plagiarism. Reviewers who foresee such a potential conflict of
interest should consider returning the manuscript to the editor without reviewing it. .
This recommendation may be stipulated in the letter that accompanies each manu-
script sent for review (see 5.5.6, Conflicts of Interest, Requirements for Peer Re-
viewers, 2nd 6.0, Editorial Assessment and Processing). Some have reported that the
Internet and subsequent rapid and widespread dissemination of findings and pub-
lications has resulted in an increase in plagiarism; however, the same technology as
well as antiplagiarism software may now give editors and publishers better tools to
detect plagiarism in submitted

Inappropriate Manipulation of ~ i g i t a Images.

l Image processing software, such as
Adobe Photoshop, has made it relatively easy for authors to manipulate images to
highlight a specific outcome or feature by cropping or by adjusting color, brightness,
or contrast. These same applications can be used by journal staff to screen digital
im:lgcs for evidence of inappropriate manipulation and fraudulent manipulati~n.'"~~
Sonw enhancements to figures, such as cropping or adjusting color of the entire
*
5.4.4 Editorial Policy and Procedures for Detecting and Handling Allegations of Scientific Mixonduct
I

\ image, may be appropriate if such manipulations do not alter the interpretation of the
original data or omit or obscure important data. However, any manipulation that
results in a change in how the original data will be interpreted or that selectively
reports, omits, or obscures important data (such as adding or altering a data element
or adjusting tone or compression of an image to make it appear as a uniquely
' different image) is considered scientific misconduct.19s20 Authors should indicate
i any changes or enhancements that have been made to digital images in the legend
! that accompanies the image. (See also 4.2.10, Visual Presentation of Data, Figures,
. Guidelines for Preparing and Submitting Figures.) These same principles apply to
r: images included in video files.
I- Journals should have policies and procedures in place for screening of digital
If resources are limited, screening can be limited to those images that are
included in papers that have been accepted for publication. The Journal of Cell
.. Biology has the followingpolicy and guidelines for authors that are a good model for
I other journalsz1:
No specific feature within an image may be enhanced, obscured, moved,
removed, or introduced. The grouping of images from different parts of the
I
same gel, or from different gels, fields, or exposures must be made explicit
by the arrangement of the figure (ie, using dividing lines) and in the text of
the figure legend. If dividing lines are not included, they will be added by
our production department, and this may result in production delays. Ad-
justments of brightness, contrast, or color balance are acceptable if they are
applied to the whole image and as long as they do not obscure, eliminate,
or misrepresent any information present in the original, including back-
grounds. W~thoutany background information, it is not possible to see ex-
actly how much of the original gel is actually shown. Non-linear adjustments
(eg, changes to gamma settings) must be disclosed in the figure legend. All
digital images in manuscripts accepted for publication will be scrutinized by
our production department for any indication of improper manipulafio?.
Questions raised by the production department will 1x referred to the Edi-
tors, who will request the original data from the authors for cornparson to
the prepared figures. If the original data cannot be produced, the acceptance
of the manuscript may be revoked. Cases of deliberate misrepresentation of
data will result in revocation of acceptance, and will be reported to the
correspondiig author's home institution or funding agency. [Reproduced
with permission of Journal of Cell Biology.]
During a 3-year period of screening images in all manuscripts accepted for pub-
lication, the Journal of Cell Biology had to revoke acceptance of 1%of papers after
detecting "fraudulent image manipulation that affected interpretation of the data."I9
In addition, 25% of the accepted manuscripts had at least 1 figure that had to be
remade because of inappropriate manipulation that did not affect the interpretation
of the data but that violated the above guidelines.

Editorial Policy and Procedures for Detecting and Handling Allegations of Scientific
Misconduct. Detection of scientificmisconduct in publishing is often the result of [he
alertness of coworkers and/or other authors of the same manuscript. and mucll less
commonly by editors, peer reviewers, or readers.
5.4 Scientific Misconduct

If an allegation of scientificmi.sconduct is 11laJcin rclat~ont o a rn;~nuscript1rnJr.r

considclntion o r pul)lishecl, tilt. editor Ilas ;I duty ro cnxurc confidential and ti~ncl!,
pursuit of that allegation. According to the Intcmational Committee o f Mcdic~lJ o u r -
nal Editors ( I C M J E ) , ~"If substantial doubts arise about the honesty and integrity of
work, either submitted or published, it is the editor's responsibility to ensure that the
question is appropriately pursued," but the editor is not responsible for conducting
the investigation. This recornmendation is supported by the World Association of
Medical Editors, the Council of Science Editors, and the UK Committee on Publica-
tion ~thics.'~-'' A study published in 2004 that reviewed the policies of 122 leading
biomedical journals (selected from those journals with the highest impact factors)
li~untlt1l;it 21 journals ( lHX,i,) I~ad:t retniction policy for their journals and 76 journals
reported having no policy on issuing retractions.'" Editors have a duty to develop
. antl.follow a policy on handling allegations of scientific misconduct and retractions.
The recommendathns'in this section are intended to help editors with such policies.
An editor's first step after receiving an allegation of falsified, fabricated, or pla-
giarized work published in her or his journal is to consider contacting the corre-
sponding author, depending on the circumstances, to request an explanationwhile
maintaining confidentiality, This initial contact can be made by telephone or brief
letter marked confidential. (See also 5.7.2, Confidentiality, Confidentiality in Alle-
gttions of Scientific Misconduct.) If the explanation received from the author'is
satisfiictory, and if guilt is admitted, the editor should request a letter of formal
retc~ctionfrom the author (preferably signed by the abthor and all coauthors); the
editor should also no* the author's institution and inform the author of this noti- ,

fication. If the explanation allays any concerns about misconduct, the editor may
need to publish some form of correction or clar%cation.or otherwise inform the
person making the allegation that no misconduct has occurred. If the explanation
received is not satisfactory or leads to additional concerns, or if no explanation is
received, the editor should contact the author's institutional authority to request ,a
fom~alinvestigation and should notify the author of this plan.
The responsibility to conduct an investigation lies with an'authority at the au-
thor's institution where the work was done (eg, dean, president, or ethical conduct/,
research integrity officer), with the funding agency, or with a national agency charged
to investigate such allegations, such as the US Office of Research Integrity, the UK
Medical Research Council, or the Danish Committees on Scientific Dishonesty. Many
countries do not have such national agencies to investigate allegations of scientific
rllisconduct or enforce regulations. In such cases, the journal editor must pursue
:un :tuthor*sloc:~l institution for an appropriate response." Editors should expect a
pronlpt acknowledgment of their notification of an allegation of misconduct. The
acknowledgment should include a .plan for the inquiry or investigation into the
matter and a timeline that specifies when the editor will be informed of the outcome.
The editor cannot conduct the investigation because he or she does not have the
appropriate institutional access or an employment relationship with the author
or other relationship such as th& between the author and a governmental funding
agency. If the editor does not receive a satisfactory or timely reply (eg, within 2
months) from the investigational authority, the editor should consider contacting
the authority again to request follow-up information. (Note that the DHHS 2005
policy recarnmends that institutions complete their initial inquiry to detem~ine
 5.4.5 Retractions. Expressions of Concern

whether an official investigation is warranted witllin 60 days o f its initi:ition iin1c.s~

circumstances clearly warrant a longer period.'4)
The editor should take great care to maintain confidentiality during ;in! coni-
munication about the allegation. However, the editor needs to identify the person o r
persons about whom the allegation is made when contacting the relevant instiru-
tional, funding, or governmental authority to request an investigation. This is Iwst
done by a telephone call or a brief formal letter ,marked confidential. During suc11
investigations, editors should avoid including details of the cases in e-mails that can
be widely circulated and should avoid posting details, even if rendered anonymous.
in e-mail lists or blogs (see also 5.7.2, Confidentiality,CohFidentiality in Allegations o f
Scientific Misconduct);

Retractions, Expressions of Concern. After receiving confirmation from the author or

authors and/or a report from the author's institution or other agency indicating that
fabrication, falsification, or plagiarism has occurred, the journal should pronlptly
publish a retraction. Preferably this retraction will be a signed letter from the cor-
responding author and all coauthoxi. If none of the authors will agree to publish a
signed retraction, the editor may request such a retraction from the investigating
institution, or the editor may issue a retraction on behalf of the journal. In each case,
the editor should inform the author(s) and institutional authority of the plan to pub-
lish a retraction. See Boxes: 1and 2 (pp. 163-1651for examples of retraction norices.
A retraction should include a complete citation to the original article and should
indicate the reason for retracting the original article. The retraction, whether a formal
letter or notice, should be labeled as a "Retraction,"be listed in the table of contents,
and be published in a prominent section of the journal on a numbered page in print
versions and in a citable format in online versions so that it can be identified easily by
indexers and included in bibliographic databases (see also 3.11.14, References, Ref-
erences to Print Journal, Retractions). The US National Library of Medicine will index
the retraction as long as it clearly states that an article in question is being' retracted or
withdrawn, whether in whole or in part, and is signed by an author, the author's legal
course1 or institutional representative, or the journal e d i t ~ rOnline
.~ versions of
journals and bibliographic databases shoiild provide reciprocal links to and from the
notice of retraction and the retracted article. Retractions should be inade freely
available and accessible on a journal's Web site (ie, rericlers should not have to pay an
access fee to see the retraction notice).*' A retracted article should be properly
labeled or watermarked as retracted in online versions of journals and should not be
removed from the online journal or archive. Such labeling may include the words
"Retracted Article" or "This Article Has Been Retracted" placed prominently at the top
of the online article and on each page of a PDF file of the article. These labels can b i
hyperlinked to the published retraction.
If an author of a fraudulent article, or any institutional authority, refuses to
submit an explanation for publication as a retraction, the editor can leverage the
authority and influence of his or her position and that of the journal to compel an
appropriate response, keeping in mind the journal's obligation to publish a retrac-
t i ~ n . ~If,
, ~however,
' the editor.is unable to receive a satisfactory or timely response
from an author or the investigating authority on the merit of the allegation, the editor
may publish an "expression of concern" to alert reaclers, librarians, ancl the scientific

161
5.4 Scientific Misconduct

community that there are concerns that an asticle may include fsl)r~c;lr'-d.1;11~111rcl.o r
pl;~gia~.izccl work, :uncl follow this larer with a formal retraction. This norict- of c.or~i-crn
S I I ~ L I I C I fo11o\v the same p~~blic~ition format as recommended for noticcs o f rc-rmc~lon.
If cviclence of misconduct is sufficient and the editor cannot obtain a retraction letter
f r o r ~thc ~ ;~iltI~oroncl is ;~w;litingthe results of an official investigation, the editor may
~.l~oost. ; I I I t.sl>l.~-ssion
101)11l)lisl1 oI'c.onc*c.m:111cl follow this with a fonual retraction
oncc 111cinslil~~tion Ilas co~lll~lcrc*clits invc.slifi~lion.
'She validity of other work published in the journal by the offending authors
should also be questioned. The ICMJE recommends that editors ask institutions to
~x.ovicleassurance of the validity of earlier work published in their journals or to
retnlct those as well. If this is not done, editors may chose to publish a notice or
expression of concern stating that the validity of such previously published work is
uncbrtain.22
Box 1 shows examples of retraction notices from authors, an institution, and an
editor and a listing in the table of contents. Examples of recent retractions in the
literature are shown in Box 2. Some authors may not want to explain the reason for
the retraction in a forthright manner. Editors should work with authors or their
1
institutidnal authority to make these notices as accurate as possibl In some cases,
publishing an author's evasive or incomplete statement might be b er than pub- &,
lishing nothing from the author; in such a case, the journal can also publish an
explanatory note from the author's institutional authority or the editor.
When an article is retracted, the original article should not be physically removed
from a journal's Web site or other online archival publication. However, it should be
made clear to all users of online archival material that the article has been retracted
and should not be used or cited. This requirement includes clear labeling of retracted
articles and 2-way linking between retraction notices and the original articles. The
National Library of Medicine does not remove the citation of a retracted article; the
citation is updated to indicate that the article has been retracted, and links between
the original citation and the citation to the retraction notice are added.28
Retractionsmay also be used for articles that are seriously and pervasively flawed
because of honest error that is not a result of fabrication, falsification, or plagiarism.
However, retraction of an article because of serious and pervasive errors should be
used cautiously. Indeed, Sox and ~ennie" have called for retractions to be reserved
solely for cases of scientific misconduct. Retractions should never be used for typical
errors; in these cases, a correction is appropriate (see also 5.11.9, Editorial Respon-
sibilities, Roles, Procedures, and Policies, Corrections [Errata]). A study of 395 articles I
retracted during the years 1982 through 2002 found that 107(27%) reflected scientific !
misconduct ant1 244 (6alwd represented unintentional errors (another 44 Ill%] rep- I
resented other issues or provided no information about the reasons for the re-
traction~).~'The National Library of Medicine cites examples of such serious and
pervasive errors as "concl~~sions based on faulty logic or computation" and data
olxained after inadvertent contqmination of cell lines or through poor instrumenta-
tion." If the errors in an article are substantial and pervasive (eg, incorrect data
I
throughout the text, tables, and figures), the journal may choose to publish a retraction
notice from the original authors as well as a replacement arti~le.~' In this case, online
versions of journals and bibliographic databases should provide reciprocal links to
and from the notice of retraction, the retracted article, and the replacement article, and
tllc ~ctlac~ccl :~rliclcshoultl hc I;ibelecl as retncted.
Box 1. Examples of Hypothetical Published Retraction Notices

Retraction Notices From Authors

Notice of Retraction: Falsification of Data .in "Effects of Low-Fat Diet on Risk of
Breast Cancer" (JMed Res. 2005;242[1]:135-139)
To the Editor.-We write to retract the anicle "Effects of Low-Fat Diet on Risk of
Breast cancer,"' published in the January 3,2005, issue of theJozrrnal ofMedical
Research. Two participants in the low-fat diet group were intentionally mis-
classified as not having breast cancer by one of us U.S.). Had the reporting of
these 2 cases not been falsified, our multivariate analysis would not have shown
statisticallysignificant results. We regret any problems our article and actions may
have caused and we retract it from the literature.
John Smith
Jane Doe
Medical University
Chicago, Illinois
1. Smith J, Doe J. ElTects of low-fat diet on risk of breast cancer. JMed Res.
2005;242(1):135-139.
Notice of Retraction: Plagiarism in "Effects of Low-Fat Diet on Risk of Breast
Cancer" (JMed Res. 2005;242[1]:135-139)
To the Editor.-We regret that the first 3 paragraphs in the "Discussion" section of
our article, "Effects of Low-Fat Diet on Risk of Breast cancer,"' published in the
January 3,2005, issue of theJouml of Medical Research, were taken from an-
other source without .proper attribution. We should have cited the following
article as the original source of the information contained in those paragraphs:
Scott RB.Low-fat diets and cancer risk. JMed Nutr Diet. 2002; 20(8):1450-1455.
We regret any problems our article1 may have caused and we rema it from the
literature.
John Smith
Jane Doe
Medical University
Chicago, Illinois
1. Smith J, Doe J. Effects of low-fat diet on risk of breast cancer. jhfed Res.
2005;242(1):135-139.

. Retraction Notice From Institution

Notice of Retraction: Falsification of Data in "Effects of Low-Fat Diet on Risk of j
Breast Cancer" (JMed Res. 2005;242[1]:135-139)
To the Editor.-An official investigation conductcrl I>ythe Research Integrity
Review Panel of Medical University of the data reporter] I>yJohn Smith andJ;lnc
Doe in the article "Effects of Low-Fat Diet on Risk of i3reast ~ancer.'"pi~l~lishccl in
, '

the January 3. 2005, issue of the Journal of M d i ~ c r I(csccirrh,

l h a s confirlncri
falsificationin the reporting. Two subjects in the lo\\,-f:it cliet group were
inren~ion;~lly ~niscl:~ssifictl
:IS not h:~vingI~,re;~sl
c.;llic.cr 11,yonc of thc :~t~tliors
(.I.?;.
).
.. --.
...-

Box 1. Examples of Hypothetical Published Retraction Notices (cont)

As a result, we retract this article from the literature. The review panel's in-
vestigation did not reveal any additional research misconduct in either author's
previously published works.
Joan Brown
Dean
Medical University
C h i c ~ g o Illinois
,
1. Smith J, Doe J. Effects of low-fat diet on risk of breast cancer.J Med Res.
2005;242( 1 ): 135- 1.39.

Retraction Notice From Journal Editor

Notice of Retraction: Falsification of Data in "Effects of Low-Fat Diet on Risk
of Breast Cancer" (JMed Res. 2005;242[1]:135-139)
We have received confirmation from the Research Integrity Review Panel of
Medical University that data reported by John Smith and Jane Doe in the article
"Effects of Low-Fat Diet on Risk of Breast Cancer,"' published in the January 3,
2005, issue of the J o u m l ofMedica1 Research, were falsified. Two subjects in the
low-fat diet group were intentionally rnisclassified as not having breast cancer by
one of the authors U.S.).As a result, we retract this article from the literature. The
review ganel's investigation did not reveal any additional research misconduct in
either author's previously publi~hed~works.
Mary Frank
Editor, Journal of Medical Research
1. Smith J, Doe J. Effects of low-fat diet on risk of breast cancer. J Med Res.
2005;242(1):135-139.

Expression of Concern From Journal Editor

Notice of Retraction: Falsification of Data in "Effects of Low-Fat-Diet on Risk of
Breast Cancer" (Jhfed Res. 2005;242[1]:135-139)
In the January 3,2005, issue of the Journal ofMedica1 Research, we published
.'Effects of Lonr-Fat Diet on Risk of Breast Cancer,"' by John Smith and Jane Doe.
On March 15, 2005, we received informaJon that cast serious doubt on the
v;~lidityof several cases that were reported in Tables 1 and 2 and that prompted
us to alert the author and the author's institution and to request a formal in-
vestigation. An interim report from the Medical University's Research Integrity
I<cvien~ Panel. received on April 10, 2005, indicates that "data were falsified for
t\vo participants in this study" and that a formal investigation is under way. We
have requested formal retractions from the authors and a final report from the
university's review panel, including information about the validity of the author's
previous publication in the Journal of Medical Research. In the interim, we
publish this esprcssion of concern to alert our readers to the serious concerns
Box 1. Examples of Hypothetical Published Retraction Notices (cont)

raised about the validity of the data, interpretations,and conclusions of the article
published in January 2005.'
Mary Frank
Editor, Journal of Medical Research
1. Smith J, Doe J. Effeas of low-fat diet on risk of breast cancer. J Med Res.
2005;242(1):135-139.

Listing of a Retraction Notice in the Table of Contents

Letters .................................................... 405
Notice of Retraction:Plagiatism in "Effects of Low-Fat Diet on Risk of Breast
Cancer" (JMed Res. 2005;242[1]:135139)-J. Smith, J. Doe

Box 2. Citations of Published Retraction Notices and Expressions of Concern

Retraction Notices From Authors II

Poehlman ET. Notice of retraction: final resolution. Ann Intern Med. 2005;
142@):798.
,
Poehlman ET. Retraction of Poehlman et al. journal of Applied Physiolo~y
76:2281-2287,1994.J Appl Pbysiol. 2005;99(2):779. I
No&: In the following 2 retractions, the coauthors signed the retraction, but the
offending author of the retracted article did not.
II
Cooper PK, Nouspikel T, Clarkson SG. Retraction of Cooper et al, Scierrcc.
275(5302):990-993.Science. 2005;308(5729):1740. I
Warloe T,Aamdal S, Reith A, Bryne M. Retraction of: Diagnostics and treatment ,

of early stages of oral cancer. fidsskr or Laegeforen. 2006;126(17):2287.

I

Retraction Notices From Editors !I

Sox H. Notice of retraction. Ann Interiz Med. 2005;139(8):702.
Horton R. Retraction-Non-steroidal anti-inflammatorydrugs and the risk of or;~l
cancer: a nested case-control study. Lattcet. 2006;3670508):382.
s ,
j
Expressions of Concern From Editors
Curfman GD, Momssey S, Drazen JM. Expression of concern: Sudbo J et al. DNA
content as a prognostic marker in patients with oral leukoplakia. N EjzglJ Med
2001;344:1270-8and SudboJ et al. The influence of resection and nneuploidy on
mortality in oral leukopiakia. N EugIJ bled. 22004;350:1405-1413. N fix1J ,wed.
2006;354(6):638.
Kennrdy D. Editorial expression of concern. Science. 2006;311t5757):.36
Allegations Involving unresolved Questions of Scientific Misconduct. Cases may
.!I I\\. I : ) \\ I I I < 11 .In ;LIICK.I~IOII rcqi~ires the journal editor to have access to the data on
~ I I I C r~~ar~uwrrpt
\\ 1 1 1 11 o r article in question was based. JAMA's authorship statement
~r~c.l~rrlc.?; the tollo\ving I:~ngu:~ge:
[I' rc.clue~wd.I sI1:tll produce the data on which the manuscript is based for
C . S ; I I I I ~ I l)y
I ; I ilic-
~ ~ Ic-rliiors
I I I (11.tl~c*ir
:~ssignees.
I:( 11- clisc.l~ssion 01' rc;~sonal,lctime limits for which authors should keep their data, see
5.0.1. In~~llectual Property: Ownership, Access, Rights, and Management, Ownership
; l l I l l ~:olllrolof l):11:1.
~ ~ ' : I I ;1111llor
I refuses a request for access to the original data, or if the author or the
:~l~tllor's institution refuses to con~plywith the journal's request for information about
tllc :lllCg:ition, the journal and its editor may be left in a precarious situation. The ICMJE
rcBr.:~lnmcnclsthat iournals pul>lish;In expression of concern detailing the unresolved
questions regarding an act of scientific misconduct in their publications (see also
5.4.5, Retractions, Expressions of

Allegations'lnvolving Manuscripts Under Editorial Consideration. In the case of a

manuscript under consideration that is not yet published in which fabrication, fal-
sification, o; plagiarism is suspected, the editor should ask the corresponding author
for a written explanation. If an explanation is not provided or is unsatisfactory, the
editor should contact the author's institutional authority (ie, dean, director, ethical
conduct/research integrity officer) or governmental agency with jurisdiction to in-
vestigate allegations of scientific misconduct to request an investigation. In all such
communicatiorls with authors and institutional authorities, the editor should take
care to maintain confidentiality and should follow the same procedures described in
5.4.4, Editorial Policy and Procedures for Detecting and Handling Allegations of
Scientific Misconduct. If the author's explanation or institutional investigation dem-
onstrates that the misconduct did not occur, the editor should continue to consider
the manuscript on its own merits. If the author's explanation or a formal investigation
demonstrates misconduct, the editor should promptly reject the paper. However, the
US Office of Research Integrity advises that rejecting and returning to an author a
manuscript associated with suspected or confirmed misconduct without confronting
the possible misconduct issues is inappropriate because it may result in the work
being published elsewhere.29

ACKNOWLEDGMENTS
Principal author: Annette Flanagin, RN,MA
I thank Catherine D. DeAngelis, MD, MPH, ] A M and Archives Journals; C. K.
Gunsalus, JD, University of ,Illinois, ChampaignIUrbana; and Drumrnond Rennie,
MD, JAMA, for reviewing and providing substantial comments for improvement of
the manuscript; the following for reviewing and providing minor comments: Teni S.
Carter, Archives of Surgery, Cindy W. Hamilton, PharrnD, ELS, Hamilton .House;
Trevor Lane, MA, DPhil, University of Hong Kong; Diana J. Mason, RN, PhD,
American Jozrnzal of Nursing; Povl Riis, MD, University of dopenhagen; Roger N.
Rosenberg, MD, Archives of Nnrrologt~,Cheryl Smart, MA, MBA; Valerie Siddall, PhD,
ELS, AstraZeneca; and Flo Witte, MA, ELS, AdvancMed LLC; and Sandra Schefris and
Yoliind.~Ihvis, Janlrs S. Todd Memorial Library, American Medical Association,
Cl~ir.;~po,
Illinois, f o r bil)liographic assistance.
 5.4.7 Allegations Involving Manuscripts Under Editorial Consideration

: REFERENCES
1. Rennie D. Dealing with research misconduct in the United Kingdom: an American
perspective on research integrity. BMJ 1998;316(7146):1726-1728.
2. Swazey JP,Anderson MS, Louis KS. Ethical problems in academic research. Am Sci.
1993;81(6):542-553.
3. Ranstam J, Buyse M, George SL; for the ISCB Subcommittee on Fraud. Fraud in
medical research: an international survey of biostatisticians. Contml Clin ninls.
2000;21(5):415-427.
4. Geggie D.A survey of newly appointed consultants' attitudes towards research fraud.
Med Ethics. 2001;270:344-346.

435(7043):737-738.
6. Re- AS. kssons from the Darsee affair. N Engl J Med. 1983;308(23):1415-1417.
7 . Knox'R'The Harvard h u d case: where does the problem lie?J A M . 1983;249(14):
1797-1799, 1802-1807.
8. Rennie D, G u n s a l ~CK. Scientific misconduct: new definition, procedures, and
office-perhaps a new 1eaf.JAMA. 1993;269(7):915-917.
9. US Department of H&th and Human Services, Public Health Service. Resppnsibilities
of awardee and applicant institutioils for dealing with and reporting mis-
conduct in science: final rule. Fed RegLst. 1989;54(151):32446.
10. National Academy of Sciences. Rqwnsible Science: Ensuring the Integrity of the Re-
search Pnxess. Washington, DC:National Academy Press; 1992.
11. Commission on ~esearchIntegrity. Integrity and Miscondtdct in Reseanh. Wash-
ington, DC: Office of Research Integrity; 1995.
12. Committee on Assessing Integrity in Reseatch Elements, Institute of Medicine. Integrtty
in Scientijic Researcb: Cmting an Environment mat Pmmotes RespomlLFlble Conduct.
Washington, DC:National Academy Press; 2002.
13. OSIP. Federal policy on research misconduct. Fed Regist. 2000;65(6):76260-76264.
14. US Department of H d t h and Human Services. Public health service policies on
research misconduct; final rule. Fed Regist. 2005;70(94):28386.
15. Marshall E. Suit alleges misuse of peer review. Science. 1335;270(5244):1912.
16. Northwestern ~nkersity.How to avoid plagiarism. http://www.northwestern.edu
/uacc/plagiar.htrnl. Accessed September 23, 2006.
17. Giles J. Taking on the cheats. Nature. 2005;435(7040):258-259.
18. Eysenbach G.Report of a case of cyberplagiarism-and reflections on detecting and
preventing academic misconduct using the Internet. J Med Internet Res. 2001;2(1):
article e4.
19. Rossner M. How to guard against image fraud. Scientist. 2006;20(3):24. http://
www.thescientist.com/2006/3/1/24/1. Accessed September 9, 2006.
20. Rossner M, Yama& K. What's in a picture? the temptation of image manipulation.
J Cell Biol. 2004;166(1):11-15.
21. jCB instructions to authors: image acquisition and manipulation. http://www.jcb.org
/misc/ifora.shtmlffimage-aquisition.Updated September 6,2006. Acceswd September

22. International Committee of Medical Journal Editors. Uniform Requirements for

Manuscripts Submitted to ~iomedicalJournals. h t t p : / / w ~ w . i c m ~ .Uplntml
q. Feb-
ruary 2006. ~ccessedSeptember 9, 2006.

167
:onfIicts of Interest I
23. World Associalion o f .\lr.d~c-:~lI'tl11i)r3 U'A\IE rcc.o~n~nenda~~ons on publ~i.~rlc)nc-1111i>
policies for 111edic:lI jo~1r11:iIb.
~ l l l i > . / ~. ~~~V ~ I ~ I I ~ . ~ ~ ~ ~ ~ ~ ~ ~ L I ~ C C S ! ~ U ~ ~ I ~ ~ J I I ~ ~ ~ ~ - ~ ~ ~ I I
Acc.ck~.dl)ccc~illwr28, 2006.
-policies-for-nieriic:~l-ioi~r~~~~I~.
24. Coi~ncilof Science Editors. CSE's \\.hire paper on promoting integrity in scientific
journal publications. l~ttp://~\~w\~~.councilscien~eeditors.org/editorial~p01icies
/white-paper.cfn1. Septcm\>cr13. 2006. Accessed Dccem1,er 28, 2006.
25. Commitlee on l*~~l>lication E~1iic.s.A code of conduct for editors of biornediczl journals.
l~ttp://ww.pul~licationetI~ics.~rg~~~k/uidelins/cocle. Updated November 29, 2004.
Accessed Septeml>er9, 2000.
26. MC Atlas. Retraction policies of high-impact bio~nedicaljournals. J Merl Libr ASSOC.
2004;9,2(2):242-250.
27. Sox HC, Kennie 11. Hcsrarch ~~iiscontluct, retr:~ction,and cleansing the nledical lit-
erature: lessons from the. l'oehlman case. Ann Intern Med. 2006;144(8):609-613.
28. N~tioni~l I.ibrai-y of Medicine. 15ct sheet: errata, retraction, duplicate publication,
comment, uprl;~rc~ ;~nrl~x~ric~lll
sunim:lly policy for MEDIJNE. http://www.nlm.nih
.gov/pubs/:~dcts11eets/erra1;1.I1tnil. Accessed September 9, 2006.
29. Office of Rssearch Integrity, Office of Public Health and Sciences, US Department of
Health and HurlIan Services. Managing allegations of scientific misconduct: a guidance
document for editors. l~t~p://ori.dlilis.g~v/dc~ummt.;/11~asn~~2000.pdf. January 2000.
Accessed September 23, 7006.
30. Dmss BG, Bressi S, Marcus SC. Retractions in the research literature: misconduct or
mistakes? Paper presented at: Fifth International Congress on Peer Review and Bio-
medical Publication; September 16,,2005;Chicago, IL. http://www.ama-assn.org
/public/peer/abstracts.html#scientif~c.Accessed January 15, 2006. '
31. Fontanarosa PB, DeAngelis CD. Correcting the literature-retraction and republica-
tion. J A M . 2005;293(20):2536.

Of all the causes which co~lspireto blind

Man's erring judgment, and misguide the mind,
m a t the weak head with strongest bias mla,
Is pride, the never-failing vice of fools.
Alexander pope1

Conflicts o f Interest. A conflict of interest occurs when an individual's objectivity is

potentially, but not necessarily, co~npromisedby a desire for prominence, profes-
sional advancement, financial gain, or a successFu1 outcome. Conflicts of interest that
arise from personal or financial relationships, academic competition, and intellectual
passion are not uncominon in science. In biomedical publication, a conflict of in-
terest may exist when an author (or the author's institution, employer, or funded has
financial or other relationships that could influence (or bias) the author's decisions,
\vork, or ~ n a n u s c r i ~ t .However,
*-~ rnu'ch concern has been directed toward the fi-
nancial interests of researchers and authors, perhaps because such interests are the
casiest to measure, and because of the complex relationships between them and the
fi~ndersof their work.'-" In addition, concerns have increased about author biases
:issoci:~tecl\\,it11 financial ties to industryGand pressures from commercial funders that
rcsulr in clelayecl or suppressed publication.'*'0
 5.5 Conflicts of Interest

Journal editors strive to ensure that information pul~lishedin their journals is as

balanced, objective, and evidence-based as possible. Because of the difficulty in
distinguishing the difference between an actual conflict of interest and a perceived
conflict,12many biomedical journals require authors to disclose all relevant, potential
conflicts of interest.24 Financial interests may include but are not limited to employ-
ment, consultancies,stock ownership, honoraria, expert testimony, royalties, patents
(filed, pending, or registered), grants, and material or financial support from industry,
government, or private agencies. Nonfinancial interests include personal or profes-
si~nal'relationshi~s, affiliations,.knowledge, or beliefs that might affect objectivity.
Many potential biases may be detected during the editorial assessment and peer
review of a manuscript (eg, problems with a study's methods and analysis, in-
appropriate interpretation of results, unbalanced selection or citation of the litera-
ture, unjustified emphasis or overly enthusiastic language, and conclusions that go
beyond a study's results) or are obvious from the author's affiliation or area of ex-
pertise. However, financially motivated biases are less easily detected. Therefore, in
the 1980s biomedical journals began.to require authors to disclose any financial
interests in the subject of their r n a n ~ s c r i ~ t .During
' ~ . ~ ~ the next 20 years, authors
typically included information about financial support from grant and funding
agencies in their submitted manuscripts, primarily because the funding agencies
require them to do so,but it was less common for authors to disclose other financial
interests, unless such information had been specifically requested.
Until recently, many journals did not have conflict of interest policies. A 1997study
of 1396 highlimpact biomedical and science journals identified only 181 journals
(13%)with &&a of interest policies; those journals with policies were overrep-
resented by medical A study conducted in 2005 of the 7 highest-impact,
peer-reviewed journals in 12 different scientific disciplines showed a higher prev-
alence of journals that reported having conflict of interest policies (SO??), although
only 33% mide these policiespublicly available (eg, in their instructions for authors).
All of the topranked general medical and multidisciplinaryscience journals had such
policies, but journals in other scientific disciplines were less likely to have such
policies and/or to publish them in their instructions for authors.16
Many biomedical journals, including J A M and'the Archiva Journals, require
disclosure of finaricial interest from everyone involved in the editorial process: au- .
thors, reviewers, editorial board members, and editors. The International Committee
of Medical Journal Editors (ICMJE): the Council of Science Editors (csE)," and the
World kociation of Medical Editors ( W A M E ) ' % U ~this ~ O policy.
~~ Many journals
also require indjviduals (such as editorial and publishing employees and full-time
and part-time editors) who have access to material during the review and publication
processes to comply with poliaes on conflicts of interest. The CSE has a framework
(recommendations and a list of questions) to help journals develop and review
current policies on conflicts of interest.I9
Different journals and publishers have various conflict of interest policies and
procedures (eg, some request disclosures, sonlk recluire clisclosures, and some ex-
clude authors, reviewers, and editors with conflicts of interest from participation in
the publication process).16 Journals also define relevant conflicts of interest in dif-
ferent terms; they may have a broad interpretation of conflictsof interest to include
financial and nonfinancial c d i c t s or may focus only on financial interests, 2nd for
financial interests, they may define relevance in terms of monetary amounts or lengths
of time. The following discussion addresses policies in general as recon~~nbndecl 1,).

169
Conflicts o f Interest

the ICMJE,~CSE," and W A ~ I E "and provides specific c.s;lmple.s o f polic~cs,p r x c -

dures, and terms as used ~!./AIVIAand the Archi~esJournals.

Requirements for Authors. Authors should disclose all relevant conflicts of interest in
their work at the time of manuscript submission either in the manuscript (if so
required by the journal) or in a cover letter to the editor or on the journal's disclosure
form (if the journal uses one). Journals should define conflicts of interest and the
types of disclosures required (eg, all types of conflicts of interest or only financial
interests). For example, JAnL-4 requires all relevant financial disclosures of each au-
thor and coauthor to be included in the Acknowledgment section of the manuscript
:~ndto I,e noted in the "Financi:~lDisclosure" section of the authorship form that each
author is required to complete and sign.'" The Archiues of Dermatology requires
authors to indicate their conflicts of interest, both financial and nonlinancial, on the
manuscript's title page.21 Both journals describe these p~liciesin their instructions for
authors :mcl in the online m:~nuscriptsubmission forms. Since these disclosures are
part of the manuscript, peer reviewers will see these when they review forJ A M and
tile Archives of Dematolog).
Some joirnals require authors to provide disclosure statements in a cover letter
or journal disclosure form and d o not share these disclosures with peer reviewers,
unless the journal routinely shares author correspondence and submission forms
\\!it11 peer reviewers. Whether a journal requires complete disclosure of financial
conflicts of interest or both financial and nonlinancial conflicts of interest and whether
the disclosures are to be nonconfidential and included in the manuscript or con-
fidential and listed only in documents and communications not shared with peer
reviewers, these policies should be made clear to all prospective authors and review-
ers and be publicly available in easily accessible instmctions for authors. However, if
a manuscript is accepted, whether the journal's disclosure policy is nonconlidential o r
confidential during the review process, the author's relevant conflicts of interest
should be published.
JAMA and the Archives Journals also require all authors to report detailed in-
formation. regarding all financial and material support for the research and work,
including but not limited to grant support, funding sources, and provision of e q u i p
nlent and supplies (see also 5.5.2, Reporting Funding and Other Support). ForJAMA,
each author also is required to sign and submit the following financial disclosure
statement in the authorship form:
I certify that all my affiliations 01- financial involvement, within the past 5
years and. foreseeable future (eg, employment, consultancies, honoraria,
'stock ownership or options, expert testimony, grants or patents received or
pending, royalties) with any organization or entity with a financial interest in
or financial conflict with the s u b j e ~matter
~ or materials discussed in the
manuscript are completely disclosed in the Acknowledgment section of The
manuscript.
JAMA authors are expected to provide detailed information about any relevant
financial interests or financial conflicts within the past 5 years and for the foreseeable
future, particularly those present at the time the research was conducted and u p to
the time of publication, as well as other financial interests, such as relevant filed or
pending patents or patent applications in preparation, that represent potential future
financial g a ~ i lThis
. ~ includes financial involvement with a product or service that is in
 5.5.1 Requirements for Authors

direct competition with a product or service described in the manuscript. Although

many universities and other institutions and organizations have established policies
and thresholds for reporting financial interests and other conflicts of interest, J A M
and the Atchiues Journals require complete disclosure of all relevant financial re-
lationshipsand potential financial conflicts of interest, regardless of amount or value.
If authors are uncertain about what might constitute a potential financial conflict of
interest, they should err on the side of full disclosure and should contact the editorial
office if they have questions or concerns. In addition, authors who have no relevant
financial interests are asked to provide a statement indicating that they have no
financial interests related to the material in the manuscript ntnd to include this in-
formation in the Acknowledgment section of the submitted m a n u ~ c r i ~ t . ~ . ~ ~ ~ ~
The ICMF, recommends that editors publish authors' conflict of interest stzte-
ments ifthky believe that the informationwill help readers2Decisions about whether
financial information provided by authors should be published, and thereby dis-
closed to readers, are usually straightforward. For example, authors of a manuscript
about hypertension should report all financial relationships they have with all
manufacturers of products used in the rninagement of hypertension, not only those
relationships with companies whose specific products are mentioned in the manu-
script. If authors are uncertain about what constitutes a relevant financial interest or
relationship, and whether or not the journal would deem a specific conflict of interest
relevant, they should contact the editorial office.
Although editors are dg to discuss disclosure of specific financial informa-
tion with authors,J A M and the ArchivesJournals require complete disclosure of all
relevant financial interests at the time of manuscript submission, and each author's
disclosure of relevant financial interests or declaration of no relevant financial in-
terests will be published in the Acknowledgment section of the a'rtic~e.~.~
A journal's conflict of interest policies should apply to all manuscript submis-
sions, including reports of research, reviews, opinion pieces (eg, editorials), letters to
the editor, and book reviews.
Some journals might not accept manuscripts from authors with financial interest
in the subject of the manuscript. For example, editors of some journals prefer that
authors of some types of articles, such as editorials, commentaries, and reviews, not
have relevant financial interests in the subject Unlike scientific reports.
editorialsand nonsystematic reviews contain no primary data and offer an evaluation
of a topic from a selection and interpretation of the literature; hence, they are more
susceptible to bias, which accompanying financial disclosures do not obviate. Au-
thors of opinion pieces and review articles are expected to provide an expert, un-
biased, and authoritative perspective, which they may not be able to do if they have
financial ties to products or services mentioned in the manuscript or are otherwise
related (eg, within the same area, category, or topic). However, such policies may be
overly restrictive and may limit the journal's ability to publish articles from some
qualified authors. Journals with concerns about the financial interests of authors of
opinion pieces and review articles must balance the risk of publishing potentially
biased discussion and comment against excluding potentially valuable contributions
to the literature, which in some fields may be the only espert contribution available.
The key is for the editor to ensure that the editorial or review is as I~alancecl,oh-
jective, and evidence-based as possible. If, after review ;mrl carcft~lronsiclcr;~tion,
the editor believes the work is biased and that the author is ilnal~leor unwilling to
revise the manuscript to eliminate such bias and prospective readers would I)e
 .. .

5 C o n f l ~ c t sof Interest

misled. tho editor shoulcl not accept the manuscript for publication. JAMA's policy
recognizes that conflicts of interest are common, and in some cases perhaps even
helpful (for example, from a knowledgeable and critical reviewer with an opposing
viewpoint). This policy favors conlplete disclosure from all authors over a ban of
authors with conflicts of interest. However, when inviting an author to write an
editorial t o comment on :I p:lper to be published, the editors will ask the prospective
;1i111ior 10 rliscslosr ; I I I ~I.CICV;IIII and consider this inl'or~~~ation
lill:~ilc:i;ll~IIICI.C'S~S
carefully, in light of the potential for har~nfrom bias vs benefit from expertise, before
confirming that the author is the best available person to write the editorial.
Information about relevant financial interest can be published in the "Acknowl-
edgment" section at the end orthe article (after the list of author contributions and
before information about grants and financial or material support) or on the title page
of the article near the author's affiliation. (See also 2.10.7, Manuscript Preparation,
Acknowledgment Section, Financial Disclosure, and 5.2, Acknowledgments.)
The following example shows placement in the Acknowledgment section:

Auteor Contributions: As principal investigator, Dr Jones had full access to

all the data in the study and takesresponsibiIity for the integrity of the data
and the accuracy of the data analysis.
Study concept and design: Jones, Jacques, Smith, Brown
Acquisition of data: Jones, Smith, Brown
Analysis and interpretation of data: Jones, Jacques, Smith, Brown
Drafting of the manuscript:Jones
Critical revision of the manuscript for important intellectual content:
Jacques, Smith, Brown
~tati&calanalysis: Jacques
Obtainedfunding: Jones
Study supervision: Brown
Financial Disclosures: Dr Jones has served as a paid consultant to Wyler
Laboratories. Dr Jacques owns stock in Wyler Laboratories.. Drs Smith and
Brown reported no financial interests.
[Or Financial Disclosures: None reported.]
Funding/Support: This study was funded in part by Wyler Laboratories.
The following example shows placement in the author affiliation footnote:
Author Affiliations: Department of Cardiology, Ambrose University Hospi-
tal, Boston, Massachusetts (Drs Jones and Smith), and Wyler Laboratories,
Geneva, Switzerland (Dr Jacques and Mr Dube).
Financial Disclosures: Dr Jones has served as a paid consultant to Wyler
Laboratories. Dr Jacques owns stock in Wyler Laboratories. Drs Smith and
Brown reported no financial interests.
Corresponding Author: John J. Jones, MD, Department of Cardiology,
Anibrose University Hospital, 444 N State St, Boston, MA 01022 (jonesj@
arnbroseuniv.edu)
 5.5.5 Requirements for Reporting Industrydponsored Studies

Reporting Funding and Other Support. In addition to individual financial conflicts of

interest, authorsshould report all financial and material support for the work reportccl
in the manuscript. This includes, but is not limited to, grant supportantl funding,
provision of equipment and supplies, and other-paidc~ntributions.~.~ All financiz~l
and material support should be indicated in the Acknowledgment section of tllc
manuscript, along with detailed information on the roles of each funding source or
sponsor (see also 5.2.6, Acknowledgments, Funding and Role of Sponsors). In addi-
tion, all individuals who provided other important paid contributions should I,c
identified, with t h ~ inames
r and affiliations listed in the Acknowledgment section of
the manuscript, or as authors if they meet the full criteria for authorship. These

include information about each nonauthor contributor's role/contribution, academic

degree($, affiliation, and indication3 compensation was received for each person
named in the Acknowledgment section (see also, 5.2.1, Acknowledgments,Acknowl-
edging Support, Assistance, and Contributions of Those Who Are Not Authors).

duct of the study; collection, management, analysis, and interpretation 'of the data;
and preparation, review, or approval of the manuscript." If the sponsor or funder had
no such role, this should bestated. Thisinformation may be included in the "Methods"
or Acknowledgment section of the manuscript2 (see also 5.2.6, Acknowledgments,
Funding and Role of Sponsors). Authors should not agree to allow sponsors with a
proprietary or financial interest in the outcome of a study or review article to control
the author's rights to publication, although review of such manuscripts by the funding
agency is typically permitted as long as such review does not impose an unacceptable
delay or s ~ ~ ~ r e s s i oAccording
n . ~ ~ ~to~the
' ~ICMJE,
~ ~ ~if a sponsor or funder with a
proprietary interest in a manuscript has "asserted control over the authors' right to
publish," editors should decline consideration of the n~anuscri~t.~

Access to-Data Requirement. For all reports, regardless of funding source, containing
original data (re~earchand systematic reviews), at least 1 named author should
indicate that she or he "had full access to all of the data in the study and takes'
responsibility for the integrity of the data and the accuracy of the data a n a ~ ~ s i s " ~ - ~
(see also 5.1.1, Authorship Responsibility, Authorship: Definition, Criteria, Contribu-
tions, and Requirements). This responsibility can vest with the principal investigator,
the corresponding author, or the article's guarantor. While in some research gmups,
particularly small ones, all authors may have access t o all of the data, it is usually not
meaningful to state gc*nrricnllp that all nilrhors had sirch access.

Requirements for Reporting Industry-Sponsored Studies. Ili:l\c.s :rrc po~cnri;~lly

in-
t ~ d u c t t d~ v h r - n\plr~:\(pr\ . ~ r ~r l i ~ ~ . c in\oI\(.~I ri\ ~n rr\c..lr-c11
'
, < I , . , I,, :, As ;I result, f o r
' industry-spnu>rtsdri~1tl1c~~../.~I.11.~1 : ~ n <rl~e l :~r~~hrr~~s~lorrrn;rIr rc.cllrirc ;In :tcccss to data
st;atc~nentt o 1~ pi<)\. ~ ( k x Il) \ . I ~ II [ ~ \ . L . \ I I ! ! . I I O ~ \ V \ I O I. I l o r C I I I ~ I O ~ ~ C Y bI y :III\, f i ~ n d i n ~
-(,ilr.c-c.\ \ - I I I I :I ~'rolxic'tar).int~rcstin the outcome of the study.4In addition,JAMA will
nor acrcpt f o r publication an industry-sponsored study in which the data analysis has
Ixen conclucted solely by statisticians employed by the company sponsoring the
research. For these studies, an additional analysis of the data (entire raw data set,
study protocol, and prespecified plan for data analysis) must be conducted by an
independent statistician at an academic institution, such as a medical school, aca-
demic meclical center, or government research institute, that has oversight over the
person conducting the ani~lysiswho is independent of the commercial sponsor.4 his
pro\ticlcs the crlitor with :in authority who does not have financial interest in the
finclings (eg, the indepcntlvnt st:~tistician'sdepartment chair or dean) to contact if
rhcre ;ire c.oncc~-11sal>oul tllc ;~nalysisor ;my allegations of nlisconduct that the
sponsor cannot or .rvill not adtlress for proprietary reasons. J A M publishes the
results o f si~chan:llysis, :11011g wit11tlie name and academic institution of the indepen-
dent statistici:~ii:lncI whcthc.r compcns:~tionor funding was received for conducting
the an;~lyses,in the Acknowledgmelit section (see 2.10, Manuscript Preparation, Ac-
knowledgment Section, and 5.2, Acknowledgments).

Requirements for Peer ~eviewers.Following the reconunendations of the ICMJE,

CSE,and WAME, reviewers should disclose conflicts of interest in reviewing specific
manuscripts and disqualify themselves from a specific review 'if n e ~ e s s a r ~ . ~ ~ ' ' ~ ' ~
Reviewers sliould never use information obtained from an unpublished manuscript .
to further their own interests. Followi~lgthe same rationale applied to authors, the
ICMJE also recommends that reviewers state explicitly if they have no relevant con-
flicts of interest to disclose.*
./AAfA includes the following instructions regarding conflicts of interest in the
letter sent requesting an individual to review a manuscript:
\Y1hile no st conflicts of interest are not disqualifying, ifyou perceive that you
have a disqualifying interest, either financial or otherwise, please contact the
reviewing editor iin~nediately(if possible, with the names of alternative re-
vie\vers). This will not affect your reviewer status.
Not :III confliczs of interest are necessarily disqualifying, and in some cases the
rc\-iewer with the most expertise may also have conflicts of interest. For example, if
;I porcnti:ll conflict of interest exists (financial or otherwise), but the editor and
rc\.ic\\.er agree t113t tlie reviewer can provide an objective assessment, J A M may
rtlcluc'st the re\rie\ver to disclose the specific conflict and provide the review. Other
journ:lls mny choose to exclude any reviewer with a conflict of interest from partic-
ip:~tingin the re\lienl process. A journal's policy on conflicts of interest for peer
~c\~ic\\crs shoulcl Ix communicated to the reviewer when the review is requested.
'Ilic. o~ilinereview system i~sedby JAMA and the Archives Journals also contains
:I field in the re\:ic\\.e~.recomlnendation form that requires reviewers to disclose
Cont1ic.t~of interest or st:ltc rh:it the); have no relevant conflicts of interest before
si~l>~nittitig tlieirreviews. This infomati011is kept confidential and is not revealed to
:~utllorsor other re\.ie\vers.
I o ~ r n l i .n l i I i ~ g . / A l Aand the Archives Journals, will consider authors'
rc.clilc'sls not ro strict papers t o specific reviewers. The ICMJE recommends that au-
~ l i o r s\\.lie \\.is11 t o L.SC.ILICI~sl)cci!ic re\.i~\\~ers explain the reasons for such requests
.II I I I ~ l l > ~ i l i ~ . s(hce
i o ~ ~also
. - ) 6.1.4, Editorial Assessment and
 -
..
-

5.5.7 Requirements for Editors and Editorial Board Members

Processing, Editorial Assessment, Selection of Reviewers, and 5.11, Editorial He-

sponsibiiities, Roles, Procedures, and Policies.)

Requirements for Editorr and Editorial Board Members. Editors may also have their
objectivity influenced or biased by conflicts of intere~t.~'-*~ As a result, the ICMJE,
CSE, and WAME recommend that editors follow policies on conflicts of interest that
require disclosure of all relevant conflicts of interest (financial and nonfinancial) and
also that they not participate in the review of or decisions on any manuscripts in
which they may have a conflict of intere~t.~"'"~Editors and journal editorial board
.
members should never use information obtained during the review process for per-
sonal or professional gain. Editors and editorial board members should refrain from
making any decisions or recommendations about manuscripts in which they have a
personal, professional, or financial interest. Editors should also consider how to
handle manuscriptsfrom an author who is from the same institution as the editor and
how to handle their own research and review articles. In the event that an editor
works alone and has a conflict of interest with a particular manuscript, he or she
should assign that manuscript to a guest editor or a member of the.editoria1 board
and should not take part in the review and editorial decision of such manuscripts.
J A M publishes a disclaimer with any articles that have an author who is also a
decision-making editor for the journal to inform readers that the author-editor was
not involved in the review or editorial decision.
Dkdaher: Dr Brown, the journal's deputy editor, was not involved in the
editorial review or decision to publish this article.
Editorials and announcements about journal poliaes written by journal editors are
exempt from such procedures, but it may be prudent for editors to ask other editors
or editorial board members to review and comment on these types of manuscripts
(see 5.11, Editorial Responsibilities, Roles, Procedures, and Policies).
J A M editors sign the following conflict of interest statement amually,.which is
kept confidential in the editorial office.
1 agree that I will disqualify myself from reviewing, editing, or participating
in editorial decisions about any JAMA and the Archives Joumals submission
that deals with a matter in which either I or a member of my immediate
family has direct financial interest or a conipeting financial interest (eg, em-
ployment, consultancies, stock ownership, honoraria, patents, patent appli-
cations, royalties, grants, or compensated expert testimony). I also agree that
I wilI prom~tlydisclose in writing to the editor in chief of J M all poten-
tially conflictingfinancial or other relevant conflicting interests pertaining to
JAMA and the Archives Journals.
I agree that I will not use any confidential infortnation obtained from ~ n y
activities with JAMA and the Archives Journals to fi~rthcrmy own or others'
financial interests.
J A M editorial board members also complete and sign the following conflict of
interest and financial disclosure statement, which is kept confidential in the eclitorial

I office.
I agree that 1 will promptly disclose all potenti;llly contlicting fin:~nci:~l
;~ncl

I other relevant interests pertaining ~o./AMAtluring thc course o f niy survic.~ :I..;
 ., II)L.III~R.I
)I IIIc,/:I.~/:Il i l i ~ o r ~ 1. ~hl) ~ r l(;III;IC.II
I o r d ~ - x . r ~tI x - 1A
~n! ~~urrclil
~
~ ~ L . I LI .I~II.II~~I I I01
C Iinlcrc.\t).
~ Fl~unci~I
lnrcrc.\t.\ 11)bt'dix.1ox.d can includc,
I)ut are nor lin1irc.d ro: honoraria, employment, stock ownership or options,
p;lrents. patent applications, grants, royalties, consultancies, expert witness
;~cti\.ities.large gifts, or paid travel and accommodations.
1 ;Igrcc ~ h : ~I t\vil! not tlisclosc or use any confidential information obtained
horn my rictivities \\.it11 JAIIA for my profit or advantage or that of anyone
else, \vl~ctheror not I remain a member of the J A M Editorial Board.

Handling Failure to Disclose Financial lnterest

, .. . ..
.:: For Authors of Manuscripts Not Yet Published. In the event that an undisclosed
-...-,.....,-.
financial interest on the part of an author is brought to the editor's attention (usu-
ally during the review process), the editor should remind the author of the journal's
policy and ask the author if he or she has anything to disclose. The author's reply may
affect the editorial decision on whether to publish the manuscript.

Box. Hypothetical Example of a Notice of Financial Interest and Lining in the Journal's
Table of Contents

Correction: Notice of Failure to Disclose Financial Interest: "Effective Vaccine

Strategies for Pertussis" (JMed. 2004;27[5]:440-441)
To the Editor.-I regret that at the time I submitted my manuscript, "Effective
Vaccine Strategies for ~ertussis,"'published in the March 17, 2004, issue of
the Jounzal of Medicine, I failed to disclose that I have served as a paid expert
witness in several diphtheria-pertussis-tetanusvaccine injury-related lawsuits.
I had signed the journal's financial disclosure statement, but I did not realize
that expert testimony was considered a potential conflict of interest. I do not
believe that my involvement in those legal proceedings biased me in any
way, and I believe the statements made in my article are both credible and
objective.
V. W. Brazen, MD
Virginia State University
Arlington
1. Brazen VW. Effective vaccine strategies for pertussis. JMed. 2004;27(5):
440-44 1 .

Listing in Table of Contents ,

Correction .................................................. 1520
Notice of Failure to Disclose Financid Interest:
"Effective Vaccine Strategies for Pertussis" (JMed. 2004;27[5]:440-441)
V. W. Brazen
 5.5.8 Handling Failure to Disclose Financial Interest

For Authors of Published Articles. If an editor receives information (usually from a

reader) alleging that an author has not disclosed a financial interest in the subject of
an article that has been published, the editor should contact the author and ask for an

. financial interest in the subject of the article, and if that author had previously sub-
: mitted a signed financial didosure statement that did not disclose that financial
interest, the editor should request a written explanation'from the author and publish
- it as a notice of financial disclosure in the correspondence column or elsewhere in
the journal, ciearly labeled as a correction (see Box).
As in the case of other types of allegations of wrongdoing (eg, scientific miscon-
duct), editors are not responsiblefor investigating unresolved allegations of financial
interest in an article or rnanusaipt That responsibilitylies with the author's institution,

For Reviewen, Editors, and Editorial Board ~ e m b e s The . discovery of an un-

disclosed conflict of interest on the part of peer reviewers may result in the journal
not asking that reviewer to consult again. Failure to disclose relevant conflicts of

ACKNOWLEDGMENTS
Principal author: Annette Flanagin, RN,MA
I thank C. K. Gunsalus,JD,Universityoflllinois,Champaign/:Jrbana; Catherine D.
DeAngelis, MD,MPH,JAUA and Archives Journals; and Liz Wager, MA, Sideview, for
reviewing and providing important comments to improve the manuscript; the fol-
lowing for reviewing and providing minor comtnents: Jessica S. Ancker, MI'H,

REFERENCES
1. Pope A. An Essay on Crificism. 1711:part 11, lines .I-4.
2. International Committee of Medical Joumdi Editors; Uniforni Requirements for
Manuscripts Submitted to Biomedical Journals. http://w.icmje.org. Updated
February 2006. ~ c c e s s e dSeptember 2. 2006.
3. DeAnpelis CD, Fontanarm PR. Flana~inA. Repminx fin:~nri:llronHicts of inrcrqst ;~ntl
relation~hipsbetween investigators and nx-~rcllsponu)rs.jAMA. 2001;286( 1):H')-91.
4 Fonunanxa PB, Fhnagin A, DeAngelis CD. Reporting conflicts of interest, financial
aspects of rt-smrch, and role of sponwfs in f t ~ n t l dstutlic.s.~/AMA.
2005;294(1):110-111.

177
; Conflicts of Interest

5. ~ ~ u n ~ c n t D,
l l : Cauhino
~l N, C:~~npIxll
E. Lou~\h3 Kelrr~onsli~ps
txrnc.cn JL adcnuc

institutions and industry in the life sclencc-an ~ndustr). survey. N t n g l J .\lid

1996;334(6):368-373.
6. Stelfox HT, Chua G,O'Rourke K, Detsky AS. Conflicr of interest In the dehare over
calcium-channel antagonists. N Engl J Med. 1998;338(2):101-106.
7. Boyd EA, Bero LA. Assessing faculty financial relationships with industry: a case study.
J A M . 2000;284(17):2209-2214.
8. Bekelman JE, Li Y, Gross CP. Scope and impact of financial conflicts of interest in
biomedical research: a systematic review. JAMA. 2003;283(4):454-465.
9. Flanagin A. Conflict of interest. In: Jones AH, McLellan F, eds. Ethical Issrres in Bio-
medical Publication. Baltimore, MD: Johns Hopkins University Press; 2000:137-165.
10. ltennic D.Thyroid storm. ./AMA. 1%7;277(15):1238-1243.
11. DeAngelis CD. The influence of money on medical science. J M .2006;296(8):996-
998.
12. Friedman PJ. The troublesome semantics of conflict of interest. Ethics Behav. 1992;
2(4):245-251.
13. Relrnan AS. Dealing with conflicts of interest. N Engl J Med. 1984;310(18):1182-1183.
14. Knoll E, Lundberg GD. New instructions for authors. JAMA. 1985;254(1):97-98. ,
15. Krimsky S,Rothenberg LS.Conflict of interest policies in science and medical journals:
editorial practices and author disclosures. Sci Eng Ethics. 2001;7(2):205-218.
'
16. Ancker J, Flanagin A. A comparison of conflict of interest policies at peer-reviewed
journals in multiple scientific disciplines. Sci Eng Ethics. In press.
17. Council of Science Editors. CSE's white paper on promoting integrity in scientific
journal publications. h t t p : / / w w n ~ . c o u n c i l s c i e n c e e d i t o r s . o r g / ~ s
/white-paper.cfm. September 13, 2006. Accessed January 5, 2007.
18. World Association of Medical Editors. WAME recommendations on publication ethics
policies for medical journals. http:~www.wame.org/resources/publication~~i~
-policies-for-medical-journals. Accessed December 29, 2006.
19. Council of Science Editors. Guidance for journals developing or revising policies
on conflict of interest, disclosure, or competing financial interests. h t t p : / / m
.counrilscienceeditors.org/events/retreatpar20052.. February 2005.
Accessed September 2, 2006.
20. Flanagin A, Fontanarosa PB, DeAngelis CD. Update on JAMA's conflict of interest
policy. JAMA. 2006;296(2):220-221.
21. Instructions for authors. Arcb ikrmatol. 2006;142(1). archdem.ama-assn.org/misc
/ifora.drl. Accessed January 20, 2006.
22. Publishing commentary by authors with potential conflicts of interest: when, why, and
how. Atztr Intern Med. 2004;141(1):73-74.
23. James A, Horton R. 7%eLancet's policy on conflicts of interest. Lancet. 2003;
361(9351):6-9.
24. Davidoff F, DeAngelis CD, Drazen JM, et al. Sponsorship, authorship, and account-
ability. JAnlA. 2001;286(10):1232-1234.
25. A medical editor's resignation. J M .1893;21(16):582.
26. I-Ioey J. When editors publish in their own journals. CM4J. 1999;161(11):1412-1413.
27. Watson G,Watson M, Chapman S, Byrne F. Environmental tobacco smoke research
published in the journal hzdmr and Built Enviro?zrnmtand associations with the
tobacco industry. Lcr~zcet.2005;365(9461):804-809.
 5.6.1 Ownership and Control of Data

28. Wright IC. Conflict of interest and the British Jo~rrnulo/lJs).chirr/ty.B I * .P.q~c-birr/t>~.
~
January 2002;180:82-83.
29. Pincock S. Journal editor quits in conflict scandal. Scimtisf. http://\\mw.the-scientist
.com/news/display/24445/#24969. August 28, 2006. Accessed October 21. 2000.

Will copyright surviue the new technologies?l n a r

question is about as bootless as asking whetherpol-
itics will sunnnnve
democracy. i%e real question is
what steps it will take to ensure that the promised
new era of information and entertainment s u m a m
copyright. History offm a clue.
Paul olds stein'

Intellectual Property: Ownership, Access, Rights, and Management. Intel-

kctualp'opeq is a legal term for that which results from the creative efforts of the
mind (intellectual) and that which can be owned, possessed, and subject to colll-
peting claims (proper~y).~ Three legal doctrines governing intellect~hlproperty are
relevant for authors, editors, and publishers in biomedial publishing: copyright (the
law protecting authorship and publication), patent (the law protecting invention and
technology), and trademark (the law protecting words and symbols used to identify
goods and services in the marketplace).' This section focuses primarily on intellec-
tual property and copyright law.

Ownenhip and Control of Data. Conceptual application of the term pmperty to

scientific knowledge is not new, but advances in science and technology and eco-
nomic factors have fueled disputes and concernsover ownership, control, and access
to original data.'-' Data used in biomedical research, increasingly complex, now
include large data sets, software, algorithms, and metadata (data that provibe infor-
mation or characteristics about other data). With the exception of coliunercially
owned information, scientific data are viewed as a public good, allowing others to
benefit from knowledge of and access to the information without decreasing the
benefit received by the individual who originally developed the data? Ideally, sci-
entific data would become a public good, regardless of the source of funding? The
US National Institutes of Health (NIH)policy on data sharing states that "data should
be made as widely and freely available as possi1,le while sakgu:~rclingthe privacy of
participants and protecting confidential and proprietary data."'0 However, personal,
professional, financial, and proprietary interests can often interfere with the altruistic
goals of data ~ h a r i n ~ . ~ ~ ~ ~ ' ' - ' ~

Ownership of Data. For purposes herein, dufu inclucle I>ut ;Ire not limitecl to written
and digital laboratory notes, dtxunients, rescarcl~;111cl ~>l.ojcct rccorrls, exl>criment;il
nlaterials (eg, reagents, cultures), descriptions o f collections of I~iologicalspecitnens
(eg, cells, tissue, genetic material), descriptions of mcrl~ocls;~ndprcKesses, patient
or research participant records and measurements. rest~lthof I)il>lio~netric ;~n<l other
tiatabase searches, illustrative material and jiraphlcx ;~n;llyx.h. t ~ n c y s cluestion-.
n:kires. resp)n.ws.data sets (ea,protein or D N A .stscltlcnc.c\.Ililc-rc):lxwyc ) r ~l~olcc.i~l;~r
structure t1;11a),databa.ws, metadal;~(d;~t;~ t l ~ a tdcsc-rllw I )I- C ~ I : I ~ . I rC ~ I t~l ; l-t :~~).I L ~
)ll\c.r
.6 Intellectual Property: Ownership, Access, Rights, and Management

sofcwale, and algorithms. The NIH policy definesjinal research data as "recorded
fr~ctualmaterial commonly accepted in the scientific community as necessary to
clocument, support, and validate research findings," which might include raw data
and derived varial~les.'~ The NIH delinition does not include summary statistics;
rather, it pertains to the data on which summary statistics are based. In scientific
rc.se;lrcIl. 3 primilly :Irenits exist for ownership of data: the government, the com-
mercial sector, ancl academic or private institutions or foundations. Although an
infrequent occurrence, when clata are developed by a scientist without a relationship
t o ;I government agency, a commercial entity, or an academic institution, the data are
o\\rnecl Ily that scientist.
An}) information prod~lcedby an office or employee of the US federal govern-
ment in the course of his or her employment is owned by the government.14 The
Frcedon~of Infor~nationAct (FOIA), enacted in 1966, is intended to ensure public
access to government-owned information (except trade secrets, financial data, na-
tional rlefense inform:~tion,and personnel or medical records protected under the
l'ri\lacy ~ c t ) . ' ~ Access
" to documents with such data that are otherwise unavailable
ma). I>eobtained through an FOIA request.
I);~taproduced by enlployees in the commercial sector (eg, a pharmaceutical,
clcvicc. or l>iotechnologycompany, health insurance company, or for-profit hospital
or m:maged care organization) are most often governed by the legal relationship
I)et\vecn the employee and the commercial employer, granting all rights of data
o\\.nership and control to the employer. However, if the data have been used to
sccurc a governlnent grant or contract, such data may be obtained by an outside
party through an FOIA request or by a court-ordered subpoena.'115
According to guidelines established by Harvard University in 1988 and sub-
scquently ;idopted by other US academic institutions, data developed by employees
of acadenlic institutions are owned by the institutions.16This policy allows access to
claw by university scientists and allows departing scientists to take copies of data with
them, hut the original data remain at the institution.
'
L. . '-1 Data Sharing and Length of Storage. The notion that data should be shared with
others for review, criticism, and replication is a fundamental tenet of the scientific
enterprise. Sharing research data encourages scientific inquiry, permits reanalyses,
pronlotes new research, facilitates education and training of new researchers, per-
mits creation of new data sets when data from multiples sources are combined, and
helps n~aintainthe integrity of the scientific re~ord.*'~.'~ Yet the practice of data
sharing has varied widely, and it was not until relatively recently that guidelines for
data sharing were d e v e ~ o ~ e d . ~ . ~ . ' ~
Although data sharing is essential for research, costs and risks may result in
restrictions on access to certain data imposed by the owner or initial investigator.
Potential costs and risks to the owner or initial investigator include technical and
financial obstacles for data storage, reproduction, and transmission; loss of academic
or financial reward or comn~ercialprofit; unwarranted or unwanted criticism; risk of
future discove~yor exploitation by a competitor; the discovery of error or fraud; and
breaches of confidentiality. The discovery of error or fraud and breaches of con-
fidentiality have important relevance in scientific publishing. Discovery of error or
fraud, if corrected or retracted in the literature, is clearly beneficial, and for research
involving humans, epidemiologic and statistical procedures are available to main-
tain conficlentiality for incliviclual study p a r t i ~ i ~ a n t s ~ (see ' ~ 5.4, Scientific
* ' ~ - also
 5.6.1 Ownership and Control of Data

Misconduct, and 5.8, Protecting Research Participants' and Patients' Rights in Sci-
entific Publication). A number of research sponsors and governmental agencies have
1: developed policies to encourage data sharing. For example, in 2003, the NIH began
requiring investigators to include a plan for data sharing in all grant applications
requesting $500000 or more in direct c ~ s t s . The
' ~ Wellcome Trust encourages it..
funded investigators to release data to the public from large-scale biological research
projects, such as the International Human Genome Sequencing ~ o n s o r t i u m . ~ ~
A number of proposals prescribe the minimum optimal time to keep daia (for
example, 2-7 years). However, there is no universally accepted standard fer data
retention by academic and research institutions. For example, the NIH requires its
funded scientiststo keep data for a minimum of 3 years after the closeout of a grant or
contract agreement and reco&es that an investigator's academic in&tution may
have additional policies regarding the required retention period for data.'' The NIH
also gives the right of data management, including the decision to publish, to the
principal investigator.''

Data Sharing, Deposit, Access ~equimmentsof Journals. In 1985, the US Committee

on National Statistics, which is part of the National Research Council (NRC)," re-
leased a repoit on data sharing that continues to serve as a useful guide for authors
and editors. Among the committee's recommendations, the following have specific
relevance for scientific publication.
Data sharing should be a regular practice.
Initial investigators should share their data by the time of the publication of
initial major results of analyses of the data except in compelling drcum-
stances, and they should share data relevant to public policy quickly and as
widely as possible.
Investigators should keep data available for a reasonable period after pub-
lication of results from analyses of the data.
Subsequent analysts who request data from others should bear the asso-
ciated increinental costs and they should endeavor to keep the burdens of
data sharing to a minimum. They should explicitly acknowledge the con--
tribution of the initial investigators in all subsequent publications.
Journal editors should require authors to provide access to data during the
peer review process.
Journals s@uld give more emphasis to reports of secondary analyses and to
replications.
Journals should require full credit and appropriate citations to original
data collections in reports based on secondary analyses.
Journals should strongly encourage authors'to makc dctailcd data acccssiljle
to other researchers (although some may view this as outside the purview
of a journal's responsibilities).
Similar to policies on data sharing and storage for academic and research institr~ror^.
policies for scientific journals are highly variable and not ;11\~;1ys av:lilablc. In Z o i j .:. .,
US NRC review of 56 of the most freqi~entl~ citccl lifc. scicncr. ; I I I ~iiccli(..~l
~ p ,t~rn.iI\

181
 --
5.6 Intellectual Property: Ownership, Access, Rights, and Management

reported tll;~t39% had policies on data sharing and 45% had no stated policy.4 Of the
18 ~nedicaljournals in this review; only 22% had policies on data sharing. To address
the lack of standard policies for data sharing among scientific journals and rec-
ognizing that no standards are expected given the diversity of disciplines in the life
sciences, the NRC recommends the following4:
Scientific journals should clearly and prominently state (in their instructions
for authors and on their Web sites) their policies for distribution of pub-
lication-related materials, data, and other information.
Policies for sharing materials should include requirements for depositing
materials in an appropriate repository.
Policies for data sharing should include requirements for deposition of
complex data setS in appropriate databases and for the sharing of software
and algorithms integral to the finding being reported.
The policies should also clearly state the consequences for authors who do
notadhere to the policies and the procedure for registering complaintsabout
noncompliance.
The NRC also has proposed a set of principles that may be useful to journals de-
veloping policies on data sharing4:
Authors should include in their publications data, algorithms, or other
information that is central or integral to the publication--that is, whatever is
necessary to support the major claims of the paper and would enable one
skilled in the art to verify or replicate the claims.
If central or integral information cannot be included in the publication for
practical reasons (for example, because a data set is too large), it should
be made freely (without restriction of its use for research purposes and at
no cost) and readily accessible through other means (for example, online).
Moreover, when necessary to enable further research, integral information
should be made available in a form that enables it to be manipulated, .
analyzed, and combined with other scientific data.
If publicly accessible repositories for data have been agreed on by a com-
munity of researchers and are in general use, the relevant data should be
dewsited in one of these repositoriks by the time of publication.
Authors of scientific publications should anticipate which materials integral
to their publications are likely to be requested and should state in the
'
"Materials and Methods" section or elsewhere how to obtain them.
If material integral to a publication is patented, the provider of the material
should make the material available under a license for research use.
A number of scientific jourrals (eg, Science,Nature) require authors to submit large
data sets (eg, protein or DNA sequences, microrray or molecular structure data) to
approved, accessible databases and to provide accession numbers as a condition of
publication. It is appropriate for authors and journals to include links to public re-
positories for such dat;~in the Acknowledg~nentsections of articles (see also 2.10.13,
 5.6.1 Ownership and Control of Data

Manuscript Preparation, Acknowledgment Section, Additional Information [Miscel-

laneous ~cknowledg&entsl).
\ Some journals have other conditions of publication that require authors to de-
posit specific information about their research in a public repository or archive,
although this is not data sharing per se. For example, followingthe recommendations
of the International Committee of Medical Journal Editors (ICMJE)," biomedical
journals that publish clinical trials require authors to have registered their trials in
approved, publicly accessible trial registries and to provide registration identifiers as
a condition of publication (see also 2.5.1, Manuscript Preparation, Abstract, Struc-
tured Abstracts, and 20.4, Study Design and Statistics, Meta-analysis). In addition, a
number of funders require authors to post articles describing the results of their
funded research in publicly available ,archives (see also 5.6.2, Open-Access Pub-
lication and ScientificJournals].
Some journals require authors to provide data available on request for exam-
ination by the editors or peer reviewers (see 5.4, scientificMisconduct). For example,
JAMA requires all authors to sign the following as part of their authorship respon-
sibiity statement:
If requested, I shall produce the data on which the manuscript is based for
examination by the editors or their assignees.
In addition, for reports containing original data (eg, research articles, systematic
reviews, and meta-analyses), JAMA requires at least 1author who is independent of
any commercial funder (eg, the principal investigator) to indicate that she or he "had
full access to all the data in the study and takes responsibility for the integrity of the
data and the 'accuracy of the data analysis." (See also 5.5.4, Conflicts of Interest,
Access to Data Requirement.)

Manuscripts Based on the Same Data. On occasion, an editor may receive 2 or more
manuscripts based on the same data (with concordant or contradictory interpreta-
tions and conclusions). If the authors of these manuscripts are not collaborators sntl
the data are publicly available, the editor should cansider each manuscript on its own
merit (perhaps asking reviewers to examine the manuscripts simultaneously). Au-
thors should attempt to resolve disputes over contrr~dicto~y intcrpreti~tionso f the
same data before submitting manuscripts to journals. When more than 1manuscript
is submitted by current or former coworkers or collaborators who disagree on tile
analysis and interpretation of the same unpublished data, the recipient editors arc.
faced with a difficult dilemma.21The ICMJE has stated that, since peer review will not
necessarily resolve die discrepant interpretations or conclusions, editors should
decline to consider competing manuscripts from coworkers until the dispute is re-
solved by the authors or the institution where the work was done." Arguments
against publishing both papers include that doing so coulcl confuse readers ancl
waste journal pages. However, publishing the competing manuscripts with an ex-
planatory editorial may allow readers to see and understand both sides of the dispute.
Alternatively, publishing the paper deemed of higher quality could result in biasing
the literature and postponing publication of legitimate research.

Record Retention Policies for Journals. Journals shoultl clcv~lopancl implerncnt

consistent policies for retention of records and rl:lta r~'latcdto the content tli:~t tl~cy
pul)lish. Legal document.. (eg, copyright tr:lnsfers, licenses, :~nclpermissions) slloulcl
5.6 Intellectual Property: Ownerrh~p.Access. Rights. and M.nagemm1 ., .

k kept indefinitely All ott~crrecords should be kept for a consistent period. For
example,JA4U and the A K ~ I I C ' SJ : O U ~ keep
~ S print and online copies of rejected
manuscripts, correspondence, and reviewer comments up to 1 year to permit con-
sideration of appeals of decisions. Print and digital copies of accepted manuscripts
and related correspondence and reviews are kept for 3 years. Journals also should
develop consistent policies for the retention of online metadata associated with manu-
script submissions, authors, and peer reviewers. (See also, 5.7.3, Confidentiality,
Confidentiality in Legal Petitions and Claims for Privileged Information.)

Open-Access Publication and Scientific Journals. The open-access movement began

in the late 1990s following the proliferation of onliie journals available via the
Internet (versions of print journals and journals published only online), the inability
of declining library budgets to keep pace with increases in the numbers of journals
and rising subscription prices, and demands to reduce the information gap between
developed and developing countrie~.~"~ Broadly defined, open access is the free
and unrestricted online ayailability of content. (In the context of biomedical publi-
cation, this refers primarily to research articles.) Strictly applied, open-access pub-
lishing m'eans that users can freely read, download, copy, distribute, print, search, or
link to full text of articles provided that authors are properly acknowledged and
cited.26There are 2 types of open access: self-archiving and open-accesspublishing.
Selfdrcbiving is the deposition of content in an open archive, sometimes before
formal publication. Archives may be subject based, such as the physics preprim
ArXiv, which was launched in 1991,or PubMedCentral,which focuses on biomedical
and life sciences. In addition, a growing number of institutions, such as universities,
have archives or institutional repositories. The Massachusetts Institute of Technol-
ogy's DSpace and the University of California's eScholarship Repository are among
the first and best-known examples of such archiving initiatives. Concerns have been
expressed that self-archiving may pose problems for version and quality control (eg,
users may not understand the difference between an article that has not undergone
peer review, revision, and editing and one that has undergone such measures to
improve quality) and that usage of self-archived versions of articles will result in
declining use of published versions of articles and journals, or even the demise of
journal^.^'-^^
. In open-accesspublkbing, all or part of a journal is freely open to unrestricted
use. The funding model for open-access publishing requires author, institution, or
funding agency payments, and/or a subsidy from the owner or publisher, and/or
external grants. This is commonly referred to as an "author pays" publishing model
(or "funder pays" in the event the research funder sets aside monies explicitly for
such use). This financial model differs from the traditional journal publishing model,
in which publication and sustainability of the publishing enterprise are based on
revenue from paid subscriptions, advertising, licensing, royalties, reprints, and other
forms of revenue.
Although a few journals were published in an open-access model before the
1990s, the majority began publication under that model after the year 2000, when
BioMed Central launched a series of open-access journals that were peer reviewed
but did not undergo editorial revision and editing.23 In 2006, BioMed Central
journals' article processing fees charged to authors ranged from $615 to $1775
per published article." In addition, individual organizations, such as universities,
In.iy purchase a ~ncml>ershipat a significantly greater collective fee, aIlowing their
 I , L- 5.6.2 Open-Access Publication and Scientific Journals
1

1 author-employees or affiliated authors to publish in BioMed Central journals without

I having to pay the initial author publication fees.
! i In 2003, the Public Library of Science (PLoS) launched its first in a series of open-
accessjournalswith an initial $9 million grant from the Moore ~oundation.~' The PLoS
journals are peer reviewed and do provide editorial revision and editing. In addition
to grants, journal operations are funded by an author-paysmodel: in 2003 the author
fee was $1500 to publish an article; in 2006 the fee was raised to $2500. Other journals
I experimenting with author-pay models had publication or processing fees that
ranged from $500 to $3500 in 2006, with most ranging from $2000 to $3000.~~ AC-
I coding to the Lund University Directory of Open AccessJournals, in 2006 there were
2345 suictly interpreted open-access, peer-reviewed scientific and scholarly journals;
. 326 of these were health science journals, including 206 in medicine.32
Supporters of complete open-access publishing cite the benefits of widespread
dissemination of research: universal access, enhanced global collaboration,improved
visibility of researchers' work, and the belief that open-access articles will be cited
more frequently than restricted-access a r t i ~ l e s . ~Opponents
~ . ~ ~ ~ express
~ - ~ ~ concern
about the quality of literature published in a system that may favor those who pay,
fairness of the author-pays model for researchers with limited funds (eg, those in
developing countries or who lack access to funding from government agencies or
industry), and the risks to the financial stability of journals with business models
based on more diversified, traditional sources of revenue and to their owner^.^'-^^
Coupled with the open-access movement in 2005, funding agencies (eg, NIH
and the Wellcome Trust) began requesting or requiring Funded investigators to
permit articles describing results of their funded research to be posted on publicly
accessible archives (such as PubMedCenual) in 2 0 0 5 . ~Negotiations~~ between
these agenaes and publishers resulted in another form of open access: delayed open
access. In this model, which has been in wide use by scientific and biomedical
publishers (especially those owned by not-for-profit professional socities) for sev-
eral years, content is made freely available after a defined interval of time, su$h as 6
months, 1year, or 2 years. The interval, which may be influenced by the frequency of
journal publication, is intended to protect subscription, licensing, advertising, and
other traditional forms of journal revenue.
A number of journals are experimenting with types of open access (eg, per-
mitting self-archivingon authors' individual or institutional archives, open access for
only some content, delayed open access, open access if author pays publication or
processing fees, or giving authors a choice of free delayed access or immediate access
if they choose to pay a publication fee). Open-access publishing models are evolv-
ing, and debate continues over which models might be sustainable in the long term.
Each model has advantages and disadvantages. A combination of models may be the '.
most appropriate for journals seeking to balance the advantages of open access with
the financial requirements of sustainable publication and ongoing maintenance of a
journal's Web site.
In addition, journals are developing and cxpcrimcnting with different pul>lication
licenses in lieu of standard copyright transfers to permit various access and L I Y J ~ ~
nghts. According to the Association of Learned and Professional Scholarly Publishers
( M S P ) , 61% of surveyed publishers required authors to transfer copyright for pub-
Ilc3tlon in 2 0 5 (down from 81% in 2003); 17% requirecl a pul>licationlicense from
authors. 2196 ln~tnllyrequested copyri~httclnsfer but acccptcd a license; and 3%did
not require any form;rlagreement.-K(~e also 5.6.5,Copyright Assignment or License.)

185
5.6 Intellectual Property Ownccsh~~,
Access. R~ghts.and Management

Copyright: Definition, History, and Current Law. C c ~ ~ n g13b ar rcrm ir.wd ro d r x . r l t ~

t11c Ic.~;ilr~ghrol' ;lutl~orsto control the conlrnun~cationand rtrprduclion of thc~r
original works of ;lu~horshi~.'." Thus, copyright law provides for the protection of
rights of parties involved in the creation and dissemination of intellectual property.
While a variety of people and entities derive benefits from copyright laws (authors,
publishers, editors, composers, artists, and the producers of television and radio
progrdms, films, sound recordings, video, computer programs, and software), few
tl~oroughlyunderstand the law and its basic applications. This section discusses
current copyright laws and applications in scientific publishing. Copyright laws,
scope, and protections vary by country (see also 5.6.12, International Copyright
I'rotection). The discussion in this section addresses US copyright law except where
specifically indicated. This section is intended to explain copyright law as it applies
to scientific publication; it is not intended to serve as legal advice. A media lawyer
shoi~ldbe consulted for any specific concerns about rights, protections, infringe-
ments, or remedies.
Copyright is a form of legal protection provided to the author of published and
unpublished original ~ o r k s .The ~ author,
~ ~or ~ anyone
~ to~ whom
~ ~the~author ~ ~ ) ~ ~ ~
transfers copyright, is the owner of copyright in the work. Current law gives the
owner of copyright the following exclusive rights:
ec To reproduce the work in copies
rr To prepare derivative works based on the copyrighted work . ,

s To distribute, perform, or display the work publicly .. ..

A copyrightable work must be fixed in a tangible medium of expression and includes

the f o l ~ o w i n ~ ~ ~ ~ ~ ~ " ~ ~ :
m Literary works (which includes computer software and works produced in digital
formats)
Musical works
s Dramatic works
1
Pantomimes and choreographic works 1
w Pictorial, graphic, and sculptural works
R Motion pictures and other audiovisual works
I
m Sound recordings I
E 'Architectural works
I
The following are not protected by copyright, although they may be covered by
patent and trademark la&s14(5102).37
(see 5.6.15, Patents, and 5.6.16, Trademark):
Works not fixed in tangible fbrm of expression (eg, speeches or performances
I
that have not been written or recorded)
r Titles

10 Names

a Short phrases
 5.6.3 Copyright: Definition. History. and Current Law

n Slogans
Familiar symbols or designs
Mere variation of typographic ornamentation, lettering, or coloring
, w Mere listings of ingredients or contents
\
m Ideas, procedures, methods, systems, processes, concepts, principles, discoveries,
and devices, as distinguished from a description, explanation, or illustration (al-
though ideas or procedures may not be protected by copyright, the written or
published expression of ideas and procedures may be subject to copyright pro-
tection)
Works consisting entirely of information that is common property and containing
no original authorship (eg, calendars; height and weight charts, rulers, and lists or
tables taken.from public documents or other common sources)
Some of the more common provisions of US copyright law as well as problems
encountered by scientific authors, editors, and publishers are discussed in sections
5.6.4 through 5.6.11.

PIBlb.History of Copyright Law. Copyright law evolved after Gutenberg's movable type
reduced the cost and labor required to make copies of written and printed
During the early 18th century, copyright became the mediator between
the author or publisher and the marketplace. In 1710, England created the Statute of
Anne, the first copyright act, which addressed exact copies only. Article 1, section 8, of
the US Constitution, enacted in 1798,serves as the foundation for US copyright law.4"
Since then, the US law has undergone a number of updates and general revisions in
response to innovations and changes in technology, to broaden the definition and
scope of copyright law, and to address mechanisms for protection among different
countries. In 1790,the United States created the first copyright law to covgr magazines
and books, but again, this was only for exact copies. During the 13th century, copy-
right law was extended to translations, works made for hire, music, dramatic com-
positions, photography, and works of art. During the 20th century, copyright law w a s
extended to cover motion pictures, performance and recording of nondran~aticlit-
erary works, sound recordings, computer programs, and architectural works. The US
Copyright Act of 1909added formal requirements to ensure protection, such as usc o f
copyright notice, official registration, and renewal of copyright terms.''

US CopyrightAct of 1976. Before 1978,2systems of copyright coexisted in the United

States. Common law copyright, regulated by individual states, protected works fro~ll
aeation until publication, and a separate federal law protected works from pul>-
lication until 28 years thereafter (with an option for a 1-time renewal of the 28-ye;~r
terrn13' The Copyright Act of 1976, which became effective January 1, 1978, con-
tained the first major revisions of US copyright law in almost 70 years. This act,
reversing many of the formalities required by the 1909 act, remains in force today.
Thus, for all works created after 1978, current law :~utomaticallyprovides protection
to the creator of the work at the time it is created, whether written. typewritten. or
entered into a computer; whether or not the work is put~lislied;and whether or not
the work bears a copyright notice. In ;addition. tile 1976 act changed the terms of
copyright duration, wid] most terms equaling the Ilfc of the author plus 50 years. In
5.6 Intellectual Property: Ownership, Access, Rights, and Management

1998, the term of copyright protection for most works was extended to the life of the
author plus 70 years40(see 5.6.4, Types of Works and Copyright Duration in the
United States).

international Conventions and Treaties. In 1886, the Beme Convention was created
by 10 European nations to protect copyright across national boundaries. The United
States did not sign on to the Beme Convention until 1 9 8 9 . ~The Universal Copyright
Convention was adopted in 1952 as an alternative for countries that disagreed with
some aspects of the Berne Convention. Anumber of conventions a d treaties adopted
in the 1990s address copyright as it has been affected by new economic, social,
cultural, and technological developments and by new international rules, including
the Trade-Related Aspects of Intellectal Property Rights (TRIPS), World Intellectual
Property Organization OJCrlPO)Copyright and Performances and PhonogramsTreaty,
and the WIPO copyright rea at^.^'^' For more details, see 5.6.12, International Copy-
right Protection.

Copyrightpnd New Technology. Throughout the 20th century, technological advances

have challenged copyright law: photomphs, motion pictures, radio, television, pho-
tocopying, cable television, computers, databases, new media, and the interne^'^**^
The most recent challenge began in the 1- with the increase of electronicpublishing
and new media. Although copyright law was designed to be technology neutral, it
applied only to tangible copies and to the physical distribution of these copies. Al-'
though early users of the Internet sent e-mail messages and posted information on
electronic mailing lists and bulletin boards without much concern for ownership and
copyright of their communications, editors and publishers grew concerned about
maintaining the integrity, quality, and ownership of their intellectual property once
content was easily and widely digitized, published, and transmitted electronically.
In 1 9 8 , the US Digital Millennium Copyright Act (DMCA) was enacted to extend
copyright protection to works created in a digital medium.14 Interpretingthe DMCA,
art^^ notes that "works created in digital media are considered 'fixed'if they can be
perceived, reproduced, or otherwise communicated for more than a transitory pe-
riod, including the fixation on a computer disc or in a computer's random access
memory." Among its major provisions, the DMCA implements the WIPO treaties,
limits certain liability of online providers that adhere to specific requirements, limits
liability of libraries and archives, prohibits the circumvention of technological bar-
riers to block unauthorized access to content (anticircumvention), establishes
penalties for such circumvention, addresses works now available through new tech-
nologies such as distance education and Web casts, and preserves existing rights of
copyright owner^.'^^^.^^
Since its enactment, the DMCA has addressed concerns about copyright protec-
tion and infringement in electronic publishing. However, continuing rapid advances
in technology predict future changes in copyright law, requiring the publishing com-
munity to be alert to such changes for the foreseeable future.

Types of Works and Copyright Duration in the United States. The length of copy-
right protection in the United States depends on several factors: when the work was
created (key dates are before or after January 1,1978),the number of authors, and the
'
type of work (eg, work made for hire or owned by the federal government).43 See the
Table f s r examples of types of works, conditions, and terms of copyright protection.43
 5.6.4 Types of Works and Copyright Duration in the United States

Works Created After 1978. To be protected by copyright law, a work must he orig-
inal. For works created by a single author, copyright belongs to that author from the
instant of its creation and for 70 years after the author's Copyright in
works published on or after January 1, 1978, is protected for a term that covers the
author's life plus 70 years after the author's See the Table for detai!~017
other conditions and terms and see also "Joint Works" and "Works Made for Hire"

Works Created Before 1978. &veral different rules apply to works created hefore
1978 arid depend on whether the work was published, previous copyright dumtion
terms, and whether the copyright has been renewed able).^'.^^ Unpublished \vorks
created before 1978 are protected for the life of the author plus 70 years. Work?;
published between 1923and 1977 are protected for 95 years after date of puhlicatio~~
provided that a copyright notice was published and appropriate renewals \\.cr~-
made4H5 (see also 5.6.6, Copyright Notice and Registration). Work.. tint \vc.rc.
published before 1923 are now in the public domain.43

Joint Works. A joiit work is a work prepared by 2 or more authors with the intention
that their contributions be merged into inseparable or interdependent parts of ;I
unitary whole. For such works, the 70-year term begins after the death of the Iilst
surviving a ~ t h o r . ' ~, ~ )

Works Made for Hire. Works created by an individual who is paid by another spe-
cifically for such work are covered by a particular provision of the copyright statute.
In these cases, the law recognizes the employer or the party contracting for the work
as the owner of the copyright in the work. Works made for hire generally fall into.2
' ~ ~first
~ a t e ~ o r i e s .The ~ category
~ ' ~ ~ is a work prepared by an employee within the
scope of his or her employment duties, such as a journal editorialwritten by an editor
who is employed by or otherwise contracted to work as an editor by the journal's
owner. The second category comprises certain specially ordered or commissioned
works. Examples include a news story written by a freelance journalist or an index
prepared by an individual under contract. In these cases, although a written copy-
right assignment is not necessary, the parties must sign a written agreement before

Works Created by Anonymous and Pseudonymous Authors. The same terms of

copyright duration that apply to works made for hire apply to works published by
anonymous or pseudonymous authors-95 years from the year of first publication or
120 years from the date the work was created, whichever is shorter. If 1 or more
authors' names are disclosed and registered with the US Copyright Office hefore the
95-year or 120-year term expires, the term changes to 70 ye;lrs after the 1:lst surviving
author's death.'4W02)'44

Works in the public Domain or Created by the US Government. :\ \vork i.; in t hcb[xll~l ic.
domain if it has f;~iledt o meet the recluir~1l1c.nr.5 (11' c.c q>yrixl\t prc ~icc~tc c )r 1 1 -
copyright protection has expired. Works in L I ~ CptrI,!~tt1( ) I I I : I111;iy
I I ~ In. 11\+.c1 Ircc.l\ I)!
anyone without permission. US works pul,li.;Il~.tIt ~ t ,;, 14): 4 .~n. no\\ 1111 11 I V 1 3 u l r l 1 ~

189
Table. Copyright Term and the Public Domain in the United Statesa

Unpublished Works

What was i n Public Domain

Type of Work Copyright Term as of January 1,2006~

Unpublished works Life of the author plus 70 years Works from authors who died before
1936
Unpublished anonymous and 120 years from date of creation Works created,before 1886
pseudonymous works, and works
made for hire
Unpublished works cre.ated before Gfe of the author plus 70 years or Nothing; the soonest the works
'
1978 that were published after December 31, 2047,whichever can enter the public domain
1977 but before 2003 is greater is January 1, 2048
. .

Unpublished works created before Life of the author plus 70 years Works of authors who died before
1978 that were published after 1935
December 31, 2002
Unpublished works when the death ' 120 years from date of creationd Works created before 1886~
date of the author is not knownc
Published Works

Date o f Publicatione conditions' Copyright 1ermb

Before 1923 None In the public domain ..

1923 throuoh 1977 Published without a cowriaht notice In the oublic domain
1978 to March 1. 1989 Published without notice, and In the public domain
without subseauent reaistration
1978 to March 1, 1989 Published without notice, but with 70 Years after the death of author, or
subsequent registration if work for hire, the shorter
of 95 years from publication
or 120 years from creationb
1923 through 1963 Published with notice but copyright In the public domain
was not renewedg
1923 through 1963 Published with notice and 95 Years after publication dateb
copyright was renewedg
1964 through 1977 Published with notice 95 Years after publication dateb
1978 to March 1, 1989 Published with notice 70 Years after death of author, or
if work for hire, the shorter of
95 years from publication or
120 years from creationb
After March 1, 1989 None 70 Years after death of author, or
if work for hire, the shorter of
95 years from publication or
120 years from creationb

'This table was adapted and reproduced with permission from ~irtle.~) It was first published in Hide PB. Recent changes to the
copyright law: copyright term extension. Archival Outlook. JanuaryIFebruary 1999.This version is current as of January 2006. The
most recent version is found at http://www.copyright.cornell.edu/training/Hirtle-hbli~Domin.h~.
The table is based in part on Gasaway LN. When US works pass into the public domain, http:/w.w.unc.edu/-undnglpublic-
d.htm, and similar tables found in Malaro MC. A Legal Primer on Managing Museum C d m s . Washington, DC: Srnithsonian
 5.6.4 Types o f Works and Copyright Duration in t h e United States

main on the first of the year fdlowing the expirationof its copyright term. For example, a book publishedon March 15. 1923, will

lished work, when the death date of the author is not known may still be copyrighted, but certification from the Copyright
that it has no record to indicate whether the pemn is living or died less than 70 years before is a complete defense to any
for infringement See 17 USC 5 302(e).

red by an officer or employee of the US government as part of that person's

United States. For much of the 20th century, certain formalities had to be
e, some books had to be printed in the United States to receive copyright
with the Register of Copyright could result in the Iw of copyright. The
copyight and that the copyright be renewed after 28 years were the most

lower: 7%. See Ringer B. Study No. 31: r e n d of c m g h t . In: CoppightLaw Revision: Studies Preparedfor the Subcommitte on
'Patents, Trademark. and CoWrighb ofthe Cannittee on fbe Judiciary. UnitedStates Senate, ~ighiy-sixthCongress, First [-Second]
&&on. Washington, DC: US Government Printing Office; 1%1:22O..A good guide to investigating the copyright and renewalstatus
of published work b Oemas 5, Bragdon JL ktemining copyright mtus for presewation and access: defining reasanable e f f m
library Resources and Technical- 1997;41(4):323-334. See also Library of Congress. Copyright Office. Circular 22: How to
hestgatethe ~ o p p i g h t ~ t a h o oMI&.
f a Wa$iqton, DC: Library of Congress, Copyright Office; 2004. http://w.copyrightgov

domain.@In 2006, the Project Gutenberg Web site included more than 19 000 books
that were in the public domain?' Works created by US federal goyernment em-
ployees in the course of their employment are also in the public domain'4G10" (.see
5.6.1,Ownership and Control of Data, and 5.6.5, Copyrigl~tAssignment or License,
&ception-us Federal Government Works). However, works produced by state
and local governments are subject to copyright protection.
Works created by other national governments are subject to the copyright laws of
their respective countries and perhaps the Beme Convention, WIPO Copyright Trea-
ties, or other international treaties (see 56.12, International Copyright Protection).

Collective Works. A collectiw work con~prisesa nnmher of independent contribu-

tions (usually from many authors), which constitute separate and independpt
works in themselves, and are assembled into a collective whole. Exa~nplesof col-
lective works include journals, magazines, niultiauthored textbooks, and encyclo-
pedias.14G101)Copyright in the independent contributions is separate from copyright
in the collective work as a whole and initially 1,elongs t o the individual authors until
they transfer copyright to the owner of the collective work, usually a publisher.
Publishers that require authors of collective works (such as authors of a journal
article) to transfer copyright should require such transfer from each author, not just
the corresponding author. Editors of collective works may also I>erccl~~irecl to transfer

191
5.6 Intellectual Property: Ownership, Access. R~gh:r. and Management

copyright assignment or a pul~licationI ~ c e n~f ~

thcir contributions are not already
covered under work for hire or other employment agreements. Thus, hoth the in-
diviclual ar xles (independent works) and the journal (collective work) can k
protected by copyright.

s?It:2:$L-#
Compilations and Derivative Works. According to US copyright law, compilations are
works "formed by the collection and assembling of preexisting materials or data that
are selected, coordinated, and arranged in such a way that the resulting work as a
whole constitutes original work of a u t h ~ r s h i ~ . " ' ~Examples
~'~" of compilations
include a conlpendium of previously published articles on a specific theme or topic
or a collection of abstracts. The basis for protection of a compilation is the judgment
required to select and arrange the rnateriaL3' In this context, the 1931 Supreme Court
ruling in Feist Publications v Rural Telephone S-ce Co is worth noting.48In that
case, a regional telephone company used a local telephone company's directory
without its permission. The lucal company sued for copyright infringement and lost.
The court held that the "data" in the directory (collections of public telephone num-
bers) had no substantial originality or creativity and that comprehensivecollections of
data arranged in conventional formats do not merit copyright protection.48
Derivative works are those based on 1 or more preexisting works, such as
an abridgment, condensation, or republication in a different format, language, or
media.14( slO1) Examples of compilations and derivative works include revised edi-
tions of books or translated articles that are republished individually or collected with.
others in an international edition.
Scientific journal publishers typically request that authors transfer broad rights to
their work in the form of either a copyright transfer or exclusive license, or a non-
exclusive license that includes rights to produce compilations and derivative works.
Such publishers often receive royalties from the distribution and sale of compilations
and derivative works. In addition, publishers who own copyright or have exclusive
licenses in individual articles are legally able to address misuse or piracy of such
works.

Revised Editions. A revised edition of a previously copyrighted work may be regarded

as a separately copyrighted work if there is substantial original new work in the
new edition. 7he ChicagoManual of Style defines substantial as change that occurs
in 1 or more of the essential elements of the work: text, introduction, notes, ap-
pendixes, or tables and illustrations (if they are integral to the ~ork)?~p'O) Thus, a
new foreword or preface, the addition of a few referercces, or corrections to the
original text do not constitute a revised edition, but they may be included in sub-
sequent printings with an explanation on the copyright notice page. For example,
this editic n of the AMA Manual of Style constitutes a major revision resulting in a new
copyrighted work. For revised editions, any unaltered material retained in a sub-
sequent edition remains protected under the original copyright, and copyright ap-
plicable to the new material does'not extend the duration of copyright in the old
material.
The ChicagoMantra1 of Style recommends that publishers use standard language
to designate specific editions: 2nd edition, 3rd edition, 4* edition, and so on.45If the
new edition is simply printed in a different format, eg, in paperback or in a different
language through a licensing agreement, the status can be designated as "Paperback
 -,
I

5.6.5 Copyright Assignment or License

edition 2005" or "French-language edition" (see 3.12.7, References, References to

Print Books, Edition Number).
Some publishers list the various dates of revisions on the copyright page as a
record of publishing history. The publishing history follows the copyright notice. For
example, this manual has had 9 previous editions:
2007, AM4 Manual of Syle: A Guidefor Authors and Editors, 10th ed
(Iverson et al)
1998, Amenencan Medical Association Manual of Style: A Guidefor Authors
and Editors, 9th 9th Overson et al)
1989, American Medical Association Manual of Style, 8th ed (Iverson et al)
1981, Manual for Autbm C Editors, 7th ed (Barclay et al)
1976, Stylebook/EditorialManual ofthe M,6th ed (Barclay)
1971, Stylebook/EditoriaI Manual of tbe A M , 5th ed (Hussey)
1966, Stylebook and Editorial Manual, 4th ed (Talbott) .
1965, Stylebook and Editortal Manual, 3rd ed (Talbott)
1963, Stylebook and Editorial Manual, 2nd ed (Talbott)
1962, Style Bmk Cralbott)

Copyright Assignment or License. Typically, copyright of a work vests initially with

the author of the work. As copyright owner, an author may transfer rights to a
publisher by copyright assignment, exclusive license, or nonexclusive ~ i c e n s e . ~A~ " ~
broadly worded exclusive license may provide much of the same rights to publishers
as would a copyright transfer agreement. Thus, an owner of an exclusive assignment
(through either copyright transfer or broadly worded exclusive license) way produce
derivative works and sublicense specific rights to others. Some publishers pemlit
authors to retain certain rights to their works, even when assigning copyright or
granting an exclusive license (such as making copies for educational purposes.
posting a copy on a personal or institutional Web site, or depositing a copy in an
institutional or other repository to comply with research funding requirements).
Examples of a model copyright transfer and license for publication are available from
the A L P S P . ~(Note:
~ The ALPSP models include provisions for moral rights, which
may not be covered for authors and journals under jurisdiction of US copyright law.)
A nonexclusive license for publication permit. a pul~lishercertain rights t o publish
and disseminate work, but the copyright remains wit11 the author who retains con-
trol over access, use, and distribution. Some open-access journals rely on nonexclu- ---
---.-.-sive l~censes
- -
to ~ublishsuch as those created by Creative Commons (http://creative
commons.org) and Science Commons (http://sciencecommons.org).
Publishers that have copyright or exclusive publication licenses may also grant
others nonexclusive secondary-use licenses to use, reproduce, or disseminate con-
tent. A nonexclusive licensee may have a one-time right to reproduce a work in a
specified manner (eg, permission to reprint or translate and distribute a specific
art~cle)(see 5.6.7, Copying, Reproducing, Adapting, and Other Uses of Content, and
5 6 10, Standards for Commercial Reprints and E-prints).

193
5.6 Intellectual Property: Ownership, Access, Rights, and Management

publishers that make substantial investments in their products typ~callyx c k

exclusive assignments from authors of written However, fcw visual an-
ists or professional photographers will agree to such terms and more co~nmonly
grant nonexclusive rights to publishers who want to include their works. In addition,
some institutions encourage or require authors to transfer nonexclusive or condi-
tional rights of their work to publishers (see also "Exception-Institutional Owners
of Copyright"). In such cases, a publisher must request permission from each author
before republishing the work in any derivative format, and this could include the
right to publish the article on the journal's Web site. Journals that accept such limited
conditional licenses need to be sure that they obtain licenses that cover all subsidiary
rights that the publisher may want to exercise or sublicense (eg, online and licensed
versions, reprints, e-prints, collections, and archival copies as well as versions in
multiple languages and multiple types of media). Increasing demands by authors and
their institutions and the increasing complexity of publishing models portend much
future debate among authors, institutions, and publishers with regard to copyright
assignments, licenses, and publication (see also 5.6.2, Open-Access Publication and
ScientificJournals).
Comnion arguments in favor of copyright transfer from authors to publishers
include the following:
r The publisher must have the opportunity to publish or license the publication of
the work in other forms to recoup or justify the expenses associated with the.
editorial and peer review, editing and quality assurance, publication, distribution,
and maintenance of the original work.
ff The publisher, with business and legal expertise and resources, is better able to
distribute and maintain the work in print and online, protect it from misuse and
piracy, and take advantage of new technologies and media.
xl The publisher is better equipped to invest in the work and take the risk that the
work may not be successful. ..
r The publisher serves the author's interest in self-promotion and professional
advancement.
Common arguments favoring author's retention of copyright include the following:
rs Authors who retain ownership of their works and distribute their works them-
selves, through their institutions or libraries or other means, can help to limit the
increasing subscription costs of scientific journals.
- Authors deserve to receive financial reward from both the original publication
and any subsequent republication or dissemination.
ti Authors' retention of copyright meets the traditional need for identification of
intellectual ownership. . I

. New technology enables misuse and theft of intellectual property and obviates the
allility of publishers to protect copyright, perhaps rendering copyright obsolete.

,: : ..,Written Assignmentpf Copyright or License. As a condition of considering a work for

publication, most publishers of scientific journals require authors to transfer copy-
right o r an esclusivr pul,lication license in the event that the work is published. This
 5.6.5 Copyright Assignment or License

requires authors to sign a specific license indicating the transfer of copyriglit or :I

license to the publisher. Since the transfer of copyright rnay not actually occur tlntil
the work is published, editors may choose to consider manuscripts submitted with-
out a statement of copyright tnnsfer or puhlication license from the author and tl1c.n
ask for it if a revision is requested or the manuscript is to be accepted. However. lo
simplify the submission process, JAMA and the Archives Journals request authors
to submit a statement of copyright assignment when they submit their manuscripts.
This statement is includedin an authorship form that all authors must sign. In ad-
dition, each author must affirm that the work submitted is original and has not been
previously published (see also 5.3, Duplicate Publication). These journals also re-
quire authors to identify their specific contributions to the work and to disclose
conflicts of interest at the same time and on the same authorship form (see also 5.1.1,
Authorship Responsibility, Authorship: Definition, Criteria, Contributions, and Ke-
quirements, and 5.5.1, Conflicts of Interest, Requirementsfor Authors; a copy of this
form is available online in the JAUA instructions for authors at http://www.jama
.corn). In the event that the work is.published by J A M or an Archives Journal, the
author agrees to transfer copyright to the American Medical Association (the owner
of these journals). If the work is not published, the copyright remains with the
author.J A M and the ArchivesJournals require all authors (including each coauthor)
who are not US federal government employees to sign the following copyright trans-
fer statement:
Copyright Transfer. In consideration of the action of the American Medical
Association (AMA) in reviewing and editing this submission (manuscript,
tables, figures, audio, video, and other supplemental files submitted for pub-
lication), I hereby transfer, assign,or otherwise convey all copyright owner-
ship, including any and all rights incidental thereto, exclusively to the AMA,
in the event that such work is published by the AMA.

Assignment by Coauthors. The authors of a joint work are co-owners of copyright in

the work. To.transfer co~tyrightor grant a publication license in a joint work, the
copyright assignment or license must be signed by ezch of the authors.
. .
Exception-US Federal Government Works, I3ec:luse copyright does not vcst in works
created by the US federal government, no assignment from the author is nec-
e s s a ~ ~ .However,
' ~ ' ~ ~journals should obtain a signed statement from each author
contributing to a work as a federal government employee. What constitutes a work of
a government employee as part of the person's official duties is not always clear, but
generally, the application of the federal employee exception is determined by thk
nature of the author rather than the nature of the work or its funding.JAMA and the
Archives Journals require all authors who contribute to a work as part of their duties
as an employee of the US federal government to sign the following:
Fcderal Employment: I was an employee of the US federal government when
this work was conduaed and prepared for publication; therefore, it is not
protected by the Copyright A a , and copyright ownership cannot bc trans-
fcmuf.
When sorne authors of n join1 work conti\>t~td ;I> C,IIIPIOYC'I'S of I ~ C \IS
' federal
government and other authors ditl nor. eac1.r govcmnic.nr-cmpIc~~rt-d author tnust sign

195
 ..
5.6 Intellectual Property: Ownership, Access, Rights, and Management

the federal employment statement and all other authors must sign the standard
copyright transfer agreement.
Works created by authors of other national governments may be subject to the
copyright laws of their respective countries.

Exception-Institutional Owners of Copyright. On occasion, a manuscript from an

author or authors from a single institution may be submitted with a copyright transfer
or publication license and signed on behalf of the institution, rather than by the
individual authors. The institution presumably has a written agreement with the
authors, following the work-for-hire provision of the copyright law, that all work
done while the authors are employees of the institution is owned by the institution.
Accordingly a representative of the institution may transfer copyright or grant a
publication license (see 5.6.4, Types of Works and Copyright Duration in the United
States, Works Made for'Hire).
Scientific journals should be cautious about accepting limits on copyright trans-
fers or licenses from institutions or commnerchl entities that could remove the journal's
ability and authority to approve subseqent uses of a journal article, and the journal's
imprimatui of that article, for.commericalor promotional purposes. Journals also need !

to avoid the possibility of comrnerckil use of a work in a manner deemed unsuitable

by the joumal. For these reasons, JMand the Arcbim Journals do not accept any ;
restrictions on the transfer of copyright, and all requests .for reuse of a journal article
.1..
must be submitted to the permissions depamnent for review and approval. i

Copyright Notice and Registration. Although use of a copyright notice is not re-
quired under copyright law, the US Copyright Office strongly recommends use of
such a notice." A copyright notice for all visual copies of a work should contain the
following 3 elementslmol':
The word "Copyright," or abbreviation "Copr," or the symbol 0,
The year of first publication of the work, and
The name of the copyright owner
Example: Copyright 2007 American Medical Association
Note: For j M and the Arcbiues Journals, the wording above includes the name of
the owner of the journals (American Medical Association), not the name of the
joumal. It is recommended that all copyright notices be placed in such a "manner and
location as to give reasonable notice of the claim of ~ o ~ y r i g h t . " ' ~he~ wording
~)'~~
and placement of copyright notices applies equally to print and online works.
The year in the copyright notice should be the year of publication.Journal home
pages and other main pages of journal Web sites should change the year of copyright
notice at the beginning of each year, but back-issue content should retain the copy-
right year for the original year of publication.
According to the US Copyright Office,"registration is a legal formality intended to
make a public record of the basic facts of a particular copyright."37Registration is not
required for copyright protection, and failure to register a work does not affect the
copyright owner's rights in that property. However, registration does offer several
benefits: it establishes a public record of the copyright claim and is a prerequisite to
bringing suit for copyright infringement in US courts.37Registration requires a com-
pleted application form, filing fee, and the deposition of copies of the work (usually
 5.6.7 Copying. Reproducing. Adapting. and Other Uses of Content

2 copies of printed materials or the sublnission of identifying material for electronic

publication^).^^ Registration is best made within 3 months of pul,lication.5'~"5 Reg-
istration filing fees vary for single original works, serials (including journals, peri-
odicals, newspapers, annuals, and proceedings), visual and performing arts, sound
recordings, and copyright renewals and are available online from the US Copyright
Office at http://www.copyright.gov.

opying, Reproducing, Adapting, and Other Uses of Content. To copy or reproduce

an entire work without authorization from the copyright owner constitutes copyright
infrhgement. However, a reasonable type and amount of copying of a copyrighted
work is permitted under the fair use provisions of US copyright law.14a107)

Fair Use.What constitutes fair use of copyrighted material in a given case depends on
the following 4 factors14<510n,
1. ~ u r p o &and character ~f the use, including whether such use is of a
commercial nature or is for nonprofit educational purposes
2. Nature of the copyrighted work
3. Amount and -substantialityof the portion used in relation to the copy-
righted work as a whole
4. Effect of the use on the potential market for or value of the copyrighted
work
Although each of these factors may provide a safe haven for use of copyrighted
works without permission from the owner, the fourth factor, the market value of the
original work, has been considered important by the courts in copyright infringe-
ment cases.
Fair use purposes include "criticism, comment, news reporting, teaching, scho-
larship, or resear~h.'!'~'~"This allows authors to quote, copy, or reproduce small
amounts of text or graphic material. Appropriate credit should always be given to
the original source. In the case of a d i r ~ cquote,
t quotation marks or setting off the
quoted material, with an appropriate reference or footnote to the original soilrcc. is
required (see 5.4.2; Scienrac Misconduct, Misappropriation:IJlagiarismancl 13rc:iches
of Confidentiality).

Text. The amount of text subject to fair use is determined by its propoltion of the
whole, .but this proportion is not measurable by word length. Contra~yt o pc)l)i~l:~r
belief, there are no specific numbers of words or lines or amount of content t11:lt niay
be taken withbut permission. The so-called 300-word rille has been citccl crro-
neously to justify quoting passages of text without permission. This em)neoi~..i:!s-
sertion probably originated with the custom of sending out ~.eviewtopics of' I>ooks
and allowing reviewers to quote passages of 300 worcls ur less in a pi~l>lisl~cd rc-
view.=' In 1985, the Nation magazine lost a lanclmark suit for copyright in~rit~g'.~i~c~i[
after publishing a 300-word excerpt from tl1c.n-l'rcsiclcn~(;cr;~lclI:orcl's 100000-\\.~ 1111
unpublished memoirs, which were to lx ~)i~l~lishccl ;13 ;I Inlok I)!: t-l:~t'l~cr & I(( I \ \
(Harper6 Row Publishem, Inc t ) ,Vuliot, f i ~ t c r p r i . ~'I ~ ~In. ~1lii3 ) r.:ihC. tlir tri;ll c , I U I I
ruled that the excerpt "was essentially the hr;lrt of tllc l,tu)k..." 7 7 C%,icr!yo ~ .\\,I , r r r c r l

of Style recommends that a quore ncvcr cs~cntl11101.~111.111; I ..IC'\\ co~iIigi~ot~\ I).II.I

~ S , if i n ~ r r n ~ ~ > t ,c) ~
grapl~s"and 111:11 ~ L I ~ Mcvcn I Il ~ I II LI. \.I ,I ~ N I I C I I M I\ t ~ ~ 4 ~
,-( A\ , ~ c l t

197
.6 Intellectual Prowrty Ownefrhlp. Access. Rights, and Management

[Ire quo[cr s own nlalttria~.""~

The length quoted should never be such that it would
Jlminull [he potential market for or value of the original work.

Tables, Graphs, and Illustrations. Fair use of tabular and graphic material and illus-
trations is more difficult to assess. ~lthough1 or 2 lines of information from a table
might be used without permission, reprinting the entire table without permission is
inappropiate and could result in a claim of copyright infringement. The same applies
to graphs and'illustrations.JAMA and the Archives Journals require all authors to
obtain permission to adapt a part of or reprint an entire table, graph, or illustration
that has been previously published. Unrestricted permission is needed to reproduce
this material in all "print, online, and licensed versions" of the journal. Online readers
of JAMA and the Archives Journals may download copies of tables, graphs, and
illustrations as Powerpoint slides for use in teaching. citation to the original pub-
lication is indicated on each downloaded slide.

Photographs and Works of Art. Photographs and works of art protected by copyright
may not be reproduced, enhanced, or altered without permission of the copyright
owner, who may be the photographer or artist, a museum or gallery, an academic
institution, a commercial entity, or a previous publisher. For example,J A M obtains
permission from owners of copyrights of works of art, typically museums and gal-
leries, to reproduce works of art on the cover of JAM. In this case,JAMA receives a
nonexclusive 1-time right to reproduce the art on the journal's cover in print and.
online; often the permission for online use is a separate permission (see also "Digital .

Images and Other Works" later in this section). This does not permit reuse of the
cover of a specific issue ofjAMA in other works or promotional material without
obtaining permission for such secondary use from the owner of the work of art
included on that issue's cover.

Unpublished Works. Authors should not rely on the fair use provision to justify .
quoting from unpublished manuscriptsand ~ e t t e r s .In
~ several
~ . ~ cases, the US courts
have taken a conservative view toward use of extensive quotationsand paraphrasing
from unpublished works without permission, making it difficultto justify such use.
In J. D. Salinger v Random House, ~ n c , 'the
~ Second Court of Appeals ruled that
inclusion of extensive quotes from Salingefs unpublished letters in Hamilton's un-
authorized biography of Salinger was improper. In a subsequent case, New Era Pub-
lications International, ApS v Henty Holt a n d Company, ~ n c , 'the
~ trial court ruled
that quotation from unpublished work was not fair use "even if necessary to docu-
ment serious character defects of an important public figure." For terms and con-
ditions of copyright protection for unpublished works, see the Table.

r m Correspondence and Reviews Regarding Manuscripts and the Editorial Process. All
correspondence regarding a manuscript and the editorial process is considered un-
published and thus should not bk used without knowledge of the owner of the
correspondence. In the case of a letter, the letter writer is the owner. In the case of a
manuscript review, the peer reviewer is the owner, unless the reviewer was con-
tracted under a work-for-hire provision. Thus, authors and journals have no legal
right to publish extensive quotes or paraphrases of reviews without the reviewer's
consent (see 5.7.1, Confidentiality, ConfidentialityDuring Editorial Evaluation and
Peer Review and After Publication) or of letters, not submitted for publication,
 5.6.7 Copying, Reproducing. Adapting, and Other Uses of Content

without the letter writer's permission (see "Quotes and Paraphrases From Oral and
Written Communications,"below). In addition, to date, the courts have not allowed
attempts to gain access to confidential peer review records or confidential in-
: formation about manuscripts that are not published or g o t included in published
articles (see 5.7.1,Confidentiality, Confidentiality During Editorial Evaluation and
Peer Review and After Publication),

Quotes and Paraphrases From Oral and Written Communications. Many journals
accept citations to personal communications (ie, oral and written cornrnur?ications).
Court decisions regarding use of unpublished indicate that written com-
munication, such as a letter or a memorandum (whether handwritten,typed, printed,
i or in digital format), if unpublished, may require permission from the letter or memo
* writer to be cited in a published work. Unless recorded, an oral communication,such
I., as a personal or telephone conversation, cannot be copyrighted. However, authors
should obtain written permission from the sources of quotations that are cited as oral
. and written communications in their manuscripts and should provide a copy of all
such permissions to the journal2' (see also 3.13.9, References, Special Print Materials,
Personal Communications).

Works in the Public Domain. Works in the public domain (which are not protected
by copyright) may be quoted from freely, with proper credit given to the original
source. Examples of works in the public domain include those funded completely by
the US government and those works on which the copyright term has expired (see
also 'Works in the Public Domain or Created by the US Government" in 5.6.4, Types
of Works and Copyright Duration in the United States). Other exanlples are available
from Project ~utenber~."

Abstracts. One widely debated application of fair use is the reproduction of a.bstrr~cts
of journal articles in other publications or databases. It can be argued that abstracts,
especially structured abstracts, represent the whole work. As a result, any secondary
publication or commercial use of abstracts of journal articles as derivative works
in print or online without permission of the copyright owner may be considered
copyright infringement.

Digital Images and Other Works. Fair use considerations apply equally to repro-
ductionsof copyrightedmaterial published in digital format.That is, what is considered
fair use in the print ,domain is likewise fair use in the electronic world. Copyright
infringement is a violation of the law-whether the infringed work is photocopied,
printed, or copied electronically (see also discussion of the US Digital Millennium
Copyright Act in 5.6.3, Copyright: Definition, History, and Current Law). Thus, digital
works (eg, digitally produced or reproduced photographs, slides, radiographs, scans,
chromatographs, and audio and video files) are protected under copyright law and
require permission from the copyright owner to be reproduced in a publication. ,
With high-performance computer technology, digital images can be manipu-
lated to enhance communication. However, digital adjustments could also be used
to bias findings or to deceive. Journals should have giiidelines for submission (in-
cluding recommended file formats and sizes for editorial review and pul>licatiou),
enhancement,and publication of digital images, audio, and video that require authors
5.6 Intellectual Propeny Ownemh~p.Accerr. R~ghtr,and Management I
to identify rllc wl~wlrrcu.*d .IS well as a record of' how* the orig~nduclrk
obtained a n d \vhcthcr 11 \vas altcrcd or nlanipulated.'4.5' Some j o u m l s tlsvc. dcfincd
acceptable alterations(such as cropping) and propoxd h e use of st;lncl.int for color.
brightness, and scale. Others have developed mechanisms to idenufy inappropriate
n ~ a n i ~ u l a t i o n(see ~ 5.4.3, Scientific Misconduq, Inappropriate Manipulation
~ " ~also
of Digital Images).

z&%$&@&C and Framing. Linking is a fundamental feature of any electronic publication.

Linking
Many online versions of articles contain hypertext links within the article (eg, to and
from citations to references, tables, and figures) and links external to the article (eg,
to other articles or resources). Such linking is generally considered appropriate use.
However, deep linking into a particular internal page of a Web site, especially if it
permits circumvention of access restrictions or bamers, may be considered an un-
lawful use of the linked-to Framing is the enclosure and display of
another's content within a frame that has the branding and navigation of the framing
site. Such framing may be argued to be the creation of a derivative work, which, if
done without permission, will likely be regarded as an i n f ~ ~ e m e n t ? ~ ( ~ ~ "

,L:$:z$zj
Fair Use Exclusions. If a portion of a copyrighted work is to be used in a subsequent
work and such use is not fair use, written permission must be obtained from the
copyright owner (see 5.6.9, Permissions for Reuse). Examples of such portions in-
clude text, tables, graphs, illustrations, or photographs. It is never permissible to use .
an entire article unless permission to do so is obtained in writing or the article is not
protected by copyright. If there is doubt about the copyright status of a particular
work, an inquiry should be directed to the author, publisher, or national copyright
office. In all cases, the material should carry a proper credit line and, if applicable,
copyright notice:

Data Adapted From Table and Used in SubsequentArticle

Table 1 is adapted with permission from Bax M, Tydeman C, Flodrnark 0.
Clinical and MRI correlates of cerebral palsy: the European Cerebral Palsy
Study. J A M . 2006;296(13):1602-1608. Copyright 2006 American Medical
Association.
.,
Reprinting Entire Article
Reprinted with permission from JAMA (2006;296[131:1602-1608).Copyright
2006 American Medical Association.

Publishing Transcripts of Discussions, Symposia, and Conferences. When sympo-

sium papers are published, transcripts of discussion (which consist of questions or
comments posed to the presenters of papers and the presenters' responses) may
accompany them and are printed at the end of the article in a separate section entitled
"Discussion." Journals should require named discussants to sign the same copyright
transfer or publication license that authors are required to sign. Publishing discus-
sions from online bulletin boards, "chat rooms," or electronic mailing lists requires
i
permission from individual discussants and the online service provider. An example
of a copyright transfer statement for discussants follows:
 5.6.1 1 Standards for Licensed lnternational Ed~tionr

Copyright Transfer. In consideration of the action of the lname of pul>lisherl

in reviewing and editing the transcript or text of my discussion, I hereby
transfer, assign, or otherwise convey all copyright ownership, including any
and all rights incidental thereto, exclusively to the [name of publisher] in the
event that such work is published by the [name of publisher].

Permissions for Reuse. The copyright owner has the right to attach conditions to
giving permission for reuse whether in print or electronic format, such as requiring
proper 'credit and copyright notice. The copyright owner may refuse pemssion
altogether. Permission is usually granted by most publishers without charge, or with a
small processing fee, to use portions (text, figures, or tables) of articlesor other works,
when sudl use will not result commercial gain. To expedite review of permission
requests, requestors should include the following information in each request:
Title and complete citation of the original work
ot the entire work
I n f o ~ t i o nabout the secondary use or publication in which. the work will
appear (including commercial or noncommercial use, method of dissemination,
and intended audience)
Scope of reuse rights (eg, nonexclusive, worldwide, all languages, print, online,
and licensed versions)
Some journals may provide authors with instructions and a form for obtaining iights
for reproducing or adapting material that is owned by others. See the sample form
used by the Archives of Dermatology in Box 1.

Standards for Commercial Reprints and E-prints. Pharmaceutical and device corn-
- . panies, institutions, and other organizations may purchase nonexclusive rights to re-
. produce scientific articles as reprints, or provide access to these as e-prints, as single
articles or collections of articles, to help market their products. A reprint is the re-
' publication of an article or collection of articles in which the content is unchanged

from -the original publication (except perhaps for the inclusion of postpublication
'' corrections). An e-print is a digital reproduction of or an online link to:.ail article
2.7, Advertisements, Ad-
ts; Reprints and E-prints.)
uted by custom publishing
companies and marketing agencies. To ensure the quality of these reprints and
e-prints and to protect the integrity of the scientific journals that originally published
the articles, the publishers and editors o f j M and the Archives Journals have ;
developed standards for sponsored reprints and e-prints (Box 2).s6

Standards for Licensed International Editions. A publisher may license others to

publish international editions of its scientificjournals. For example, agreements be-
meen the AMA (owner of JM and the Archives Journals) and international li-
censees give these publishers the right to publish and disseminate collections of
articles fromJAUA or the ArchivesJournals in specific markets (countries or regions)

20 1
.. .-
 Box 1. Request for Permission to Reproduce or Adapt Copyrqht-ProteCted Materlal for Publ~cat~on
a
Archives o f Dermatology

To Date
Name of Copyright Owner, publisher, or Other

I (we) request permission to reproduce or adapt the material specified below in Anhives
of Dermatology. Citation to the original publication or appropriate credit will be published.
A grant of permission form is included for your use.
Requestor's Contact Information (Please Print)
Name Title
Organization
Mailing Address
City State./Province Zip/Postal Code Country
Telephone Fax E-mail
Source Citation of Material to Be Used (Please Print)
For Journals: Authofls), article title, journal, year of publication, volume number, issue
number, and inclusive pages.
For Books: Authods) or editor(s), book title, place of publication, publisher, year of copy-
right, and inclusive pages.

Description of Material: Specify figure or table number(s) or description of text and page
numbeds).
I

How the Content Is to Be Used (Please Print)

Archives of Dermutology Manuscript Number Ci known)
CorrespondingAuthor:
Title of Article
Terms of Use: Use in print, online, and licensed versions of Archiues ofDennatology; includes
nonexclusive rights, unrestricted time, in all languages.
Note: We cannot accept permissions that resttict use to onetime only or to English-language

-- --

Grant of Permission: Please complete and return this to the requestor listed above.
I/we hold copyright to the material specified above and grant permission for its use in
association with the designated Archives of Dermatology article in print, online, and licensed
versions of Archives of Demzatology according to the terms listed above.
For previously published content, citation to the original publication will accompany the
content.
For unpublished content, copyright credit shduld read as follows (please print):

Date
Signature of Copyright Owner or Designate

I'rint Namc of Copyrig111Owner or Designate

Box 2. JAMA and Archives Journals Standards for Reprints and E-prints Purchased by
Organizations

Fundamental Principles
The guiding principle in all J A M and Archives Journals publishing endeavors
is that physicians and others receiving any scientificmaterials produced by J A M
and the Archives Journals are assured that the information
is as accurate and reliable as possible at the time,
has undergone the journal's rigorous editorial peer review,
has been prepared with the highest degree of professionalism throughout,
pro*des information that ultimately is intended to be of benefit to
individual patients and to the public at large.
To be considered for support of aJAUA and Archives Journals reprint, e-print, or
republication product, the supporting organization must work within and abide
by these standards. In addition, the organization must present &e content in a
way that maintains the integrity of the originalJAUA and ArchivesJournal article
and does not imply endorsement of a product or influence by an organization.
Responsibility for Editorial Content
The J A M and Archives Journals editor in chief has absolute and total control
over the scientific and editorial content of any J A M and Archives Journals
product at all times. TheJAUA and ArchivesJournals editor in chief (or designee)
has complete authority to oversee; review, and accept or reject any reprint, e-
print, or republication request or project at any point in the process.
Ownership of Copyright
Materials published inJAUA and the ArchimJournals, including translayions, are
owned and copyrighted by the American Medical Association (AMA). Materials
under AMA copyright remain the property of the AMA and may not be re-
produced without permission from the publisher.
Content
All editorial content from JMIA and the Archivc.~Journals must IIC rcproclucc.cl
verbatim for a reprint or e-print and should incorporate any publishecl correc-
tions to'the original content ,(with a notation that the article has been corrected)
or should append the correction to the end of the article. Preprints (reprints or e-
prints deliver& prior to publication) are not available. Articles publishetl onlinc.
ahead of print may be purchased as e-prints or reprints provided that they meet
the criteria listed above.
Article Reprints (Paper Format)
Description
Paper reprints of a singleJAMA or Archiues Journal article or niultiple articles
from the sahe issue that are linked in the original publication by an editorial
notation within the articles (eg, an article and a related editorial from the samc
issue).
 Box 2. JAMA and Archives ~obrnalsStandards for Reprints and E-prints Purchased
by Organizations (cont)

Policy and Procedures

1. All potential article reprints are subject to approval by theJ A M and Archives
Joumals publishing project manager and the editorial project manager.
2. With only rare exceptions and approvals, reprints must include a front
cover that includes the following:
Narne/logo of journal
Title of article, complete list of authors, and issue date
The word "lteprint" or its translation at the top of the cover
No other content is permitted on front cover.
3. Reprints must include the following information in the running f&ter of the
article:
Fboter will be the same as the original printed footer with the addition of
the words, "Reprinted from [Journal Namel" and copyright information.
If the article has been corrected since its original publication, the footer
will contain the words "Reprinted with corrections from Uournal Namel"
and copyright information.
4. Prescribing information or disclaimers required or approved by a govem-
nlent regulatory body (eg, US Food and Drug Adminkation) may be in-
cluded subject to approval by the J A M and Archives Journals publishing
project manager and the editorial project manager. When prescribing in-
formation is included, the printed product will consist of the article, fol-
lowed by a buffer page, and then by the prescribing information. The buffer
page will include a statement similar to the following:
"This reprint is provided courtesy of [company namel, which has a fi-
nancial interest in the product/topic discussed in this article. The fol-
lowing FDA-approved labeling has been provided by [company namel.
JAAlA and the Archives Journals and the AMA do not assume resp'onsi-
hility for the content of the following information."
~Vore:The above statement is only permitted on the buffer page for approved
prescribing information.
I 5. Reprint holders including all materials contained in the holder, cover letters,
or other materials printed as part of, attached to, or surroundiig a reprint
must be reviewed and approved by the J A M and Archives Joumals pub-
lishing project manager and ,editorial project manager.
6. No pron~otionalmaterial may be included with or attached to the reprint.
I
I Web and Other Electronic Formats (E-prints) I
/ Description
/AiIIA anti Arcbil~esJournals e-prints are
either a specific number of accesses to
1 . csi-;rlng an~clePDF hostetl at the JAMA and
. . .
Archives Journals Web sites or
Box 2. JAMA and Archives Journals Standards for Reprints and E-prints Purchased
I
!
by Organizations (cont)

electronic PDF reprints of J A M and Archives Journals articles. Either must bc ;

accessed from a Web page or e-mail message that has been approved by the
J A M and A r c h i m Journals editor in chief or designee. JAMA and Archi~vs
Journals e-prints allow a purchasing organization to offer defined audiences
access to the electronic full-text version of a JAMA or Archives Journals article. i
Two models are currently available: access to the PDF that resides on the J A M 1
and ArchivesJournals Web sites (PDF-based e-print) and rights-protected PDF- I
based e-print.
Policy and Procedures 1
J A M or Archives Journals e-prints may be purchased by organizations under the I
conditions outlined in the "Fundamental Principles" section and the following
product-specific conditions:
1. AN potential e-print requests as well as the Web page or e-mail message that
i
i

includes the link to the article are subject to approval by the J A M or Ar-
cbiues Journals publishing project manager and the editorial project man-
ager. The potential e-print must adhere to the following criteria:
The PDF content of the article will not be altered.
The Web page or e-mail message must not describe or interpret the article.
The link to the article(s) must be separate from any marketing or other
nonjournal content (ie, separate header stating "Journal Resources" or
similar title).
The link must consist of the full citation to the article (ie, authors, title, and
journal name, year, volume, issue, pages, or digital object identifier [DOII).
The sponsor ofthe Weh site or e-mail message must Ile clearly displayed.
After approval, the link and the information surrounding the link must not
change without prior approval of the publishing and editorial project
managers.
2. Following editorial approval, the publishing project nianrlger will grant
access to the electronic article.
PDF-Based E-print
Access to existing PDF residing on the JAMA and Archives Journals Web sites ,

Purchasing organizations wishing to link to aJA.hL-4 or Archim Journals article

PDF may purchase access to that PDF for a specific number of accesses or length I
of time, provided that the above stipulations are met and that the page from
which the article would link is provided for rcvicu,. S i ~ c ha page niay he a Web
page or an e-mail message, but either m u [ Ix rci~ic\v~rl and ;~pprovedby the
I
1
editorial project manager. !
I

Purchase of an e-print is contingent on ;~ppro\..tlr ~ l \ linking

c p e e h y the /A-lfct
and An-hitvs Journals publish in^ p r r ~ l crn;tn.igrr
~~ . ~ ~ r rrli~c,ri;tI
cl projec.1rii;ln;!gcr I
5 6 intellectual Property: Ownership. Access. Rights, and Management

Box 2. JAMA and Archives Journals Standards for Reprints and E-prints Purchased
by Organizations (cont)

The publishing project manager will establish password-free access from the
supporting company linking page to the e-print URL and will maintain this link
for the duration of the agreement.
Rights-Protected PDF-Based E-print
Access to a I'DF that does not reside on theJ A M and Archives Journals Web sites
This e-print is a rights-protected PDF of the article(s) that is similar in appearance
to a paper reprint. Rights protection will define aspects such as the number of
copies a user may print, e-mail, or download/open.
Rights-protected PI%-based e-prints will include the cover paae and running
footer requirements described in the paper format reprint section of these
standards.
Prescribing information or disclaimers required or approved by a government
regulatory body (eg, FDA) m y be included with a PDF e-print subject to approval
by theJM and Arcbives Journals publishing project manager and the editorial
project manager. When prescribing information included, a buffer page with
disclaimer information (described in "Article Reprints") will be required.
The company Web site and specitic page and/or e-mail from which the rights-
protected PDF e-print will link must be reviewed by theJAMA and Archives
Journals project manager and editorial project manager for compliance with
these standards and appropriate presentation.
The e-print will be produced and ielivered by: the publishing projeamanager.

and in specific languages. To ensure the quality of these editions, the following
standards are recommended:
Copyright in the international edition and all translated articles is owned by the
original publisher. . ,

Each issue must contain a minimum number of pages or amount of content.

I
a Articles republished from the original journal must account for a minimum of 50%
of each issue's total pages or content. The remaining 50%of total pages/content may
include local editorial material and local commercial content (eg, advertisements).
BI The licensed publisher will appoint an editorial director (whose appointment will
be approved by the editor of the original journal) to select articles from the original
edition to be republished in the international edition and review the quality of
translations.
R Each republished article must include a complete citation to the original article (ie, .
journai, year, volume and issue numbers, inclusive page numbers) and complete \
original titles, author bylines, and author affiliations.
I
5 Abridgments or changes to content, other than translation, are not permitted.
 5.6.12 International Copyright Protection

Content should be republished within a minimum amount of time (eg, 6 months

from date of original publication)
International editions may include local editorial material that cannot constitute
more than 50% of total pages/content. ,Local editorial includes the cover (if the
original journal cover is not used), masthead, table of contents, editorial indexes,
brief news reports, summaries of conferences, meeting calendars, announce-
ments, commentaries, editorials, letters, and explanations of original articles.
Local editorial does not include (1) any original clinical or scientific articles (ie,
quantitative or qualitative research reports or analyses, case descriptions, clinical
or produu reviews, product or therapeutic comparisons, scientific abstracts) or
(2) any articles previously published by other journal's.
H All.authors of all local editorial should have their complete names, academic
degrees or credentials, and affiliations published with each article.
For online publications, vanslated articles should l i d to the original article.
Journals with advertising must have multiple advertisements and may not be
sponsored by one commercial entity or interest.
a Advertisements may not appear adjacent to editorial content on the same topic.
Commercial content shall not be presented to appear as editorial content. Ap-
pearance, artwork, and format shall be of such a nature as to avoid confusion with
the editorial content of the publication.
See also 5.12, Advertisements, Advertorials, spo&orship, Supplements, Reprints, and
E-prints. ,,

International Copyright Protection. There is no international copyright law.57Copy-

right law, scope, protections, and remedies are governed by individual nations and
treaties between them. Thus,copyright laws do not automaticallyprotect an author's
work throughout the ~ o r l d . ~ ow ever, most countries offer protection to works
from other nations." For a detailed discussion of the copyright laws of individual
countries, consult WIPO (which is under the auspices of the United Nations) in
Geneva, Switzerland. See 5.6.14, Copyright Resources, for contact information for
WIPO.
The Beme Convention for the Protection of Literary and Artistic Works (com-
monly known as the Berne onv vent ion)^^ was originally signed by 10 European
countries in11886in Beme, Switzerland, to protect copyright across their national
Today, the Berne Convention is administered by WIPO. For many years,
the United States declined to sign the Beme Convention because of its lack of
formality and its minimalist approach. For example, the Beme Convention does not
require the use of a copyright notice, which was in conflict with prior US copyright
law. To accommodate the US need for a minimuni set of standards. the Univcrz:~l
Copyright Convention (UCC) was created by the Unitctl Nations Edi~c~tion;~l. 5' I -
entific, and Cultural Organization (UNESCO) in 1952. Under t h e UCC. \vork\ ~ r c . ~ ! c ~ l
in the United States could have multilateral protection without forfeiting 11icprlor I \
requirement for copyright notice.40
After amending its copyright law by e1iniin:lting 11icrequircmc.nt tor c o p \ r ~ p l ~ r
notice, the United States signed the Beme Convent on In 19W M04t I ~ C I I I \ I ~ I . I ~ I / ~ . ~ I
5.6 lntelltctual Propeny: Ownership, Access. R~ghts,and Management

'
n.it~on\.inti m.in) d~iclopingcountries s u t ~ c r ~ to
h rthfi convenuon, and there are
q'c'c'~.~l
Ixo\.islons tor developing countries dut wish to make use of them.% As of
2006, 16.2 natrons had signed the Beme ~ o n \ e n t m n .The ~ . ~Beme Convention has
no forma: requirements. However, each signatory country agrees to protect the
copyright in works created in other member countries. Although the United States no
longer mandates the use of copyright notice, the US Copyright Office still encourages
voluntary use (see 5.6.6, Copyright Notice and Registration). The significance of the
UCC is now largely historical after the adoption of the Trade-Related Aspects of
Intellectal Property Rights (TRIPS) agreement and other international agreements in
the 1990s, including WIPO's Copyright and Performances and Phonograms Treaty
and the WIPO Copyright rea at^.^' The WIPO Copyright Treaties, adopted in 1336,
provide additional protections for works aeated in other member countries and
address issues and questions raised by new economic, social, cultural, and techno-
logical developments as well as new international rules.41

Moral Rights. Moral rights, first introduced by the French as dmit moral, is a doc-
trine of copyright law intended to protect individual creators' noneconomic invest-
ments irf their work and the personality of the creator as it relates to the work
regardless of copyright ownership or uansfer.38<s26.01)*58 Two moral rights that are
most often recognized are the right to attribution and right to integrity (ie, right to
prevent destruction or mutilation of work).-"" This doctrine is endorsed by '
most member countries of the Berne Convention. Although the United States is a
member of the Berne Convention, US law does not provide for moral rights, except .
for certain visual works of art to protect them from mutilation or misattribution .
through the Visual Artists Rights Act of 1990.'~'~Creators of other works in the
United States are provided limited moral rights protection under other federal laws
(such as the Lanham Act), state laws, or contracts that include specific provisions for
moral rights.-6.01' Under interpretations of relevant US laws as well as any appli-
cable contract provisions, US editors and publishers may not give authorship credit
to someone who has not written the work and may not credit an author of a written
work without the author's permission (see 5.1.2, Authorship Responsibility, Guest
and Ghost Authors). In the United States, courts have also held that mutilation of a
work (distortion or substantial alteration of the work without consent of the author)
may result in a violation of the Lanham ~ct.-.O~~) However, authors are not
similarly protected against unauthorized changes made during editing, proofreading,
and typesetting of their ~ o r k . ~ ~ Because
. ~ ~ ' )of the ease of manipulation and
distortion of electronic works, concerns about moral rights in the context of elec-
tronic publishing are increasing in the United States and may portend changes in this
area of law in the f ~ t ~ r e . ~ ~ ' ~ ~ . ~ ~ ~ )

Copyrigllt Resources. Additional information about copyright law may be obtained

from several sources. For a detailed legal account, consult Perle and Williams on
Publishing ~ a u ?or~Nimmer on ~opynright~~ (although these resources are expen-
sive and may be best consulted via a library that has these in its holdings). Other ,
usefill texts include 7he ChicagoManual of Sfyle chapter !'Rights and ~ermissions"~~
1,
and Law of the Web: A Field Guide to Internet Specific information,
tiseful guides, and forins may be obtained free of charge from the US Copyright
0ff~cei4,37.40,44.'".'7.w.
I

'
 5.6.15 Patents

US Copyright Office
Library of Congress
101 Independence Ave SE
Washington, DC 20559-6000
Telephone: (202) 707-3000
www.copyright.gov
Additional useful information can also be obtained from the following:
Association of American Publishers (W)
50 F St.NW
Washington, DC 20001-1530
Telephone: (202) 247-3375
Fax:(202) 347-3690 -
wwW.publishers.org
Association of Learned and Professional Society Publishers (ALPSP)
South House
The Street

-
Clapham, Worthing BN13 3UU, West Sussex, United Kingdom
Telephone: 44 1903871 686
Fax:44 1903871 457
www.alpsp.org/defaul~htm
World Intellectual Property Organization (WIPO)
34, chemin d& Colornbettes
PO Box 18
CH-1211 Geneva 20, Switzerland
elkh hone: 41 22 338 91 11
Fax:41 22 733 54 28
www.wipo.int

Patents. Patent law protects invention and technology. A patent is a grant of property
right by the government to protect a newly created idea on the basis of its technical
and legal merita In biomedicine, patents aii commonly applied for and approved
for new products, such as pharmaceuticals, reagents, assays, devices; and equipment
and less commonly for procedures and methods. Patent law is intended to encourage
discovery and investment in research of new technology by rewarding an inventor
with a monopoly on the right to market the new product for a specified period. This
law restricts other parties from manufacturing, selling, or using the new product
without the patent holder's permission for 20 years.60
In the United States, patents are awarded by the US Patent and Trademark Office
(USPTO). For more details, instructions, and copies of patent forms, contact the
USF'TO:
US Patent and Trademark Office
Department of Commerce
Washington, DC 20231
Telephone: (703) 308-4357 or (800) 786-9199
F a : (703) 305-7786
E-mail: [email protected]
www.uspto.gov
5.6 Intellectual Property. Ownerrhlp. Acte,~. R~ghtr.and Management

As with copyrighr, illc.~.c13 n o irltcmational patcnr law or prc~cc-lion; pJlcnl\ A r t .

I
~xotec'teclIly individual countrlcs. In w m c rcgions. a regional patcnr olhce ( c ~tlrc
.
European Patent Office or thc Afric3n Regional Intellectual Propen) Organization)
accepts and grants patent applications in the member states of that region. Detrtiled
infor~l~ation about international treaties on patents is available from WIPO (for con-
tact information, see 5.6.14,Copyright Resources).
Controversy over claims for patents of naturally occurring substances, medical
and surgical methods, and even genetically altered cells and gene fragments has
appeared in the scientific ~iterature.~'"~ Desires for profit and primacy of discovery
have been motives causing delay or suppression of the publication of important
medical inf~rmation.~.'.~ For this reason, editors should request that authors disclose
information about patents, including ownership and upcoming and pending appli-
cations for patent grants, that are related to the work included in their submitted
manuscripts in their financial disclosures to journals (see 5.5, Conflicts of Interest).

BT
radernark. Trademark and unfair-competition laws are designed to prevent a com-
petitor from selling goods or services under the auspices of another. Trademark law,
not copydght law, protects trademarks, service marks, and trade names.65 Trade-
ntarks are legally registered words, names, symbols, sounds, or colors or any com-
bination of these items that are used to identify and distinguish goods from those
goods manufactured and sold by others and to indicate the source or origin of
the goods (eg, bnnd names).65 Examples of commonly recognized trademarks in-.
clude Time magazine, NBC, and Coca-Cola. A senrice mark is the same as a trade-
mark except that it is used to distinguish services, not goods, of a specific provider.65
Exa~nplesof service marks include McDonald's (restaurant services), AT&T (tele-
communications services), and Amazon.com (Internet services). The terms trade-
mark and mark are often used to refer to both trademarks and service mark~.~~ Trade
names are the names given by manufacturers or businesses to specific products or
services. For example, Promrdia is the trade name (or proprietary name) for the drug
nifedipine (see also 15.4.3, Nomenclature, Drugs, Proprietary Names). Trade names
are not legally protected in the same manner as are trademarks. Trademark law pro-
vides legal protection for titles, logos, fictional characters, pseudonyms, and unique
groupings of words, symbols, or Whereas copyright law protects an
authored work, trademark law protects the words and symbols used in the marketing
of that wcrk.
Trademarks are classified into 5 categories in order of their increasing distinc-
tiveness: generic, descriptive, suggestive, arbitrary, and Suggestive, arbi-
trary, and fanciful marks are more likely to receive trademark protection than are
generic or descriptive marks.% An example of an arbitrary mark (a common word
that has no specific connection to its product) is the Nova television series; an ex-
ample of a fanciful mark (created solely for use as a trademark) is ~ o d a k . ~To '
receive trademark status, a mark must be distinctive (ie, not similar to other marks)
and not generic or merely descriptite of a category of products. For example, trade-
mark status was not awarded to WorldBook or Farnets Almanac because both were
considered "merely descriptive of the contents of each publication,"50and Sofiware
News magazine was not considered protectable because it referred to a class of
I
products of which the magazine is a member (ie, it was generic).38 For additional !
information, contact the USPTO (contact information available in 5.6.15, Patents).
 5.6.16 Trademar

Titles. Book titles are rarely protected under trademark law because of juc1ici;rl rc
lilctance to protect titles that are used only o n ~ e . ~ ' ~ ~A~few
. ' " exceptions to thi
norm have occurred with book titles that have engendered common seco11rl:rr
meanings, ie, become widely recognized and associated with the name o f the a111 h( I
or publisher (eg, Gone With the The title of a series of creative \vorks (cp
book series, journals, magazines, newspapers, television series, or softwire) IW
more easily receive trademark protection than can the title of a single crcativc
~ o r k . ~ ~T~h .u 's ,~J '. ~is a~trademarked title. However, in the biomedical sci
ences it is often difficult to trademark journaltitles that are generic and may not Ix
distingishable from the science or field the journal serves, such as the At-cbii!c.s (!
Neurology or Neurology.

Logos. Logos, designs,-or synbols may also receive 'trademark-protection if the!

distinguish particular goods or services and identify the source of those goods anc
s e ~ i i c e s . ~ ~xampies
~~~.~~ of) such logos include. the Bantam publishing housc
rooster and Apple computer's apple: A background design, apart from the word:
imposed on it, can be protected by trademark if it is of a distinctive quality anc
functions to identify the source of a good.W25.05'

Fictional Characters and Pseudonym. Fictional characters'may be protected by trade,

mark if they achieve secondary meaning and are widely recognized (eg, Mickej
Mouse). Similarly, a pseudonym can be given trademark status.38

Trade Dress. 'Trade dress is the visual or physical appearance of a product or it:
packaging, which, if distinct from that of other similar product, may be protectec
under trademark law (eg, the Coca Cola bottle or the label on Campbell's soup)
Trade dress includes graphic elements and design, typography, shape, and color. FOI
example, the designs, including the borders, of the covers of the National Geo
graphic and Time magazine have been awarded trademark . s ~ a t u s . ~ ~ ~ ~ ~ . ~ ~ ' ~ ~ ~

Application and Registration for Trademark Protection. In the United States, appli.
cation for a trademark registration can be made under both federal and state laws. A
legal expert should be consulted for information about registering trademarks ir.
other countries. However, registering a trademark is not sufficient; actual use of the
trademark in a given market ensures protection (ie, tl~elonger the actual use of the
trademark, the stronger the legal protection).38'50Typically, the rights to a trademark
belong to the first user in a specific geographic market.
Trademark protection is also governed by the national laws of individual coun-
tries and international treaties, such as the TRIPS agreement. In the United States, an
application to register a trademark must be filed with the USPTO.~' Applying f o ~
trademark protection is more complicated than applying for copyright protection. The
USPTO requires a formalapplication to be submitted (preferably electronically), along
with a drawing of the mark, samples of the mark as it has been used, and a filing fee.6'
The USPTO conducts a formal review of the application, which may take several
months. The office may deny the request for registration if the mark is judged to be
generic, merely descriptive, or similar to another registered mark (or a mark for which
another application is under review). Registration may also be denied if the mark is no1
used or intended for use in interstate or international commerce. If the application
'is approved internally by the USPTO, a notice is published in the Ofjcial Cirzettc

21 1
5.6 Intellectual Property: Ownership, Access, Rights, and Management

to make the application publicly known. During the 30 days following the Oficial
Gazette notice, any third party can file a formal opposition to the application.65
If the application is approved, the USPTO will issue a certificate of registration if
the mark is in use. If the mark is not yet in use, the applicant is required to file a
statement describing the mark's intended use and has 6 months to use the mark in : .
commerce and submit a statement of such use or request a 6-month extension to file
a statement of use.6s
I

Trademark Symbols. Once registered, the mark is entitled to carry the trademark
I
symbol 8.Only those marks that are officially registered by the USPTO can use the
official symbol @. Marks that are under review may use the symbol TM or SM,but these '
do not have legal significancee6'
1- j

1
Duration ;f Trademark Protection. A US trademark registration extends for 10 years
and may be extended indefinitely provided the owner continues to use the mark on
or in connection with the applicable goods and/or services and files all required
docymentation with the USPTO at the appropriate times.For example, between the'
fifth and sixth years of the initial term and in the ninth year of every 10-year period
thereafter, additional forms must be filed with the USPTO to ensure legal protection.6?

Loss of Trademark Rights and Antidilution Law. A m& I

can lose its legal prote+on if ,
the owner discontinues using it (termed trademark abandonment), if the owner !
does not fde a statement that the trademark is still in use between the fifth and sixth-'-' .<
years of the initial term, or if the owner does not renew the registration,by the end of
each 10-year regismtion period.6' Trademark protection may also be forfeited if a .
mark becomes too generic or no longer identifies goods or services with a particular
source (ie, the mark becomes "dilutedn). In legal terms, t r d r k dilution is "the
lessening of the capacity of a famous mark to identify and distinguish goods and ,

service^."-'.^^)^ For example, Webster's is no longer a registered trademark be-

caus: the name lost its ability to identify a specific publisher of dictionaries, and
"Zipper" used to be a trademark for "slide fastener."
A mark used in multiple contexts by different product owners or service pro-
viders may diminish the ability of a given mark to serve as unique identifier,of that .
product or s e r v i ~ e . ~ ~ (Such - ' ~ ) of unique trademark status is known as
~ ~ ~dilution
blurring. A trademark may also be diluted by tarnisbment, when a well-known
trademark is improperly associated with an inferior or offensive product or ser-
v i ~ e . ~ ~ ' . The
' ~ ' following factors may be considered in judging such dilution of
unique trademark status of one mark by a n ~ t h e r ~ ~ ~ . ' ~ ) :
Q Similarity of marks
e Similarity of the products covered by the marks
Sophistication of consumek
re Predatory intent

a Renown of the senior mark

Renown of the junior mark
 ---- . ..- .

5.6.16 Trademark

For this reason, owners of trademarks will often send letters to editors and publishers

use "photocopied rather than "xeroxed"). '

Use of Trademarked Names in Publication. Under the US Federal Trademark Dilution

~ c trestricted
, ~ ~ use of trademark names applies mainly to commercial use of trade-
marks, not to editorial use in publication. For example, a photography magazine may
not use the word "~odak@" as part of its cover design and a computer manufacturer
may not place the word "~o&k@" on the front of a computer. However, an author or
editor may include the word "Kodak"-without the trademark symbol-in an article
about cameras and film development without risking trademark infringement.
The symbol @, or letters 'I'M or SM, should not be used in scientific journal

On occasion, a trademark owner will request that its trademark or trade name
appear in all capital letters or a combination of capital and lowercase letters often
with the trademark symbol. Authors and editors are not required by law to follow
: . such requests. It is preferable to use an initial capital letter followed by all lowercase
letters (eg, Xerox, Kodak) unless the trademark name is an abbreviation (eg, IBM,
J A M ) or uses an intercapped construction (eg, PubMed, iTunes) (see also 10.8,
Capitalization, "IntercappednCompounds; 14.0, Abbreviations; and 15.4.3,Nomen-
clature, Drugs, Proprietary Names). Online databases, iftrademarked, can be listed in
all capital letters (eg, MEDLINE, EMBASE,CINAHL).

International Trademark.Protection. Lie copyright law, there is no international

trademark law, and trademark protections are offered by d i f f e r jurisdictions in
diierent countries. However, WIPO (www.wipo.org) administersthe Midrid System
for the International Registration of Marks, which offers a route to trademark pro-
tection in multiple countries by filing a single application. Information is also avail-
able from the International Trademark Association (www.inta.org).

Trademark Protection Online. A new use of trademark has emerged in the context of
the Internet. Domain names are Internet addresses that point to a specific Web site,
usually a, home page. They are usually easily remembered names that are linked to
numeric Internet protocol addresses, such as uspto.gov or h a r ~ a r d . e d u . ~ ~ * ~ ~ . ~ )
Domain names include top-level domain (TLD) names (eg, ".corn," ".org,'' ".edu")
and second-level names (eg, "jama" in jama.com or "nih" in nih.gov). A domain
name is not automatically entitled to protection once registered; like other tndr-
marks, it must be used in connection with the Web site located at that address."
Since 1998,the Internet Corporation for Assigned Names and Numbers (ICANK)
has been responsible for managing the domain name system." Donlain nsnies c;~n
be registered by many different companies (knonrn ;IS .'rcgistr.~rs") r l ~ ; ~:\re
r ;~i~tliot.-
ized by ICANN. Domain name regisrrars llave ~ l i ~ r v tcrlns n r for renc\v:ll ol' rlo~ll;~iri
name registration, ranging from 1- to 10-year increments."' At [his \vriting. fC.t\l\;\
registrars manage the following TLD names: .rtero. .I>iz. c;rt. corn. .ccx)p..inti). . I ~ I , . .
.mob( .muxum, .nAme, .net. .orR. .pro. .tcrl. :inti tr:l\.cl. IC,\NN clews nc)t ; t < t r t 8 \ l t 1
registrars for n D s that are rc?itnctcul slwcific c.nllt1c.i ;111cl 13~1.1x).w.fr.
~ 1 c . 1 :I\
" 1 C.(~II

213
5.6 Intellectual Property: Ownership, Access, Rights, and Management

for educational institutions, ".govn for US government agencies, and ".miln for US
military sites. Country code TLDs may be obtained from host country agencies in
accordance with rules determined by the Internet Assigned Numbers Authority
(IANA).~'
Disputes over ownership and rights to use domain names are considered under
the principles of trademark infringement and dilution, with some specific additions
to address cybersquatting and typosquatting.m25.09)242 Cybenquatting is "the act of
obtaining a trademark associated domain name with the aim of selling it to the trade-
mark owner or otherwise benefiting from the association wij the mark."wa25.w'
Typosquatting is "the registration of a domain name that is similar to another's for the
purpose of capitalizing on typos that may lead the user to the squatter's Web site
rather than the site the user intends to l ~ c a t e . " ~In~1939,
~ ~ .the
~ ~Anticybersquatting
)
Consumer Protection Act was enacted to address these problems of misuse of domain
names.42
To make a successful claim against use of a specific domain name, the following
must be d e r n ~ n s t r a t e d ~ ~ ~ ~ - ~ ) :
re the domain name is identical or confusingly similar to a trademark or
service mark in which the complainant has rights,
ta the registrant has no rights or legitimate interests in respect to the do- .
. .
main name, and
s the domain name has been registered and is being used in bad faith. . .*.- .,

For more information on applying for and managing domain names and remedies for
misuse of domain names, consult ICANN or WIPO (contact information for WIPO is
available in 5.6.14, Copyright Resources).
Internet Corporation for Assigned Names and Numbers (ICANN)
www.icann.org
4676 Admiralty Way, Suite 330
Marina del Rey, CA 90292-6601
Telephone: (310) 823-9358
Fax: (310) 823-8649

6 Rond Point Schuman

Bt 5
Brussels B-1040, Belgium
Telephone: 32 2 234 7872
Fax: 32 2 234 7848

ACKNOWLEDGMENTS . I
Principal author: Annette Flanagin, RN, MA
1,
I
I thank the following for reviewing and providing substantive comments to help i
improve the manuscript: Wayne G. Hoppe, JD,J A M and Archives Journals; Maggie
Mills, JAMA and Archives Journals; Cheryl Smart, MA, MBA; Michael T. Clark, Amer- \.
ican Medical Association Periodic Publishing and Business; Catherine D. DeAngelis,
 5.6.16 Trademark

MD, MPH, J A M and Archim Journals; and Trevor Lane, UA,DPhil, University of
Hong Kong.

REFERENCES
1. Goldstein P. Cowght's Highway From Gutenberg to the Celestial Jukebox. Rev ed.
Stanford, CA:Stanford University Press; 2003.
2. Nelkin D. Science as Intellectuul Property: W o Controls Scientific Research? New
York, MI: Maanillan Publishing Co; 1984.
3. Mihkin B. Urgently needed: policies on access to data by erstwhile collabontors.
Science. 1995;270(5238):927-928.
4. Committee on Responsibilities of Authorship on the Biclogical Sciences, National
Research Council. Sharing Publkation-Related Data and Materials: Respomibilitim-of
Authorship in the Life Menc&. Washington, DC:National Academy of Sciences: 2003.
5. Blumenthal D, Campbell EG, Anderson MS, Causino N, Louis KS. Withholding re-
search results in academic life science. J A M . 1997;277(15):12241228.
6. Campbell EG, Clarridge BR, Gokhall M, et al. Data withholding in academic genetics:
evidence from a national survey.JM.2002;287(4):473480.
7. Arzberger P, Schroeder P, Beaulieu A, et al. Science and govemrnenk an intemation:~l
framework to promote access to data. Science. 22004;303(5665):1777-1778.
8. Straf ML. Who owns what in research data? In: Bailar JC 111, Angel1 M, Boots S, et al.
eds.Ethics and Policy in SiAxtifiG Publication. Chicago, IL: Council of Biology Editors
Inc; 1990:130-137.
9. Fienberg SE. Sharing statistical data in the biomedical and health sciences: ethical,
Mtutional, legal, >rid professional dimensions. Annu Rev Public Healtb. 1*4;15:
1-18.
10. National Institutes of Health Office of Extramural Research. NIH data sharing policy
and implementation guidance. hap://grant~.nih.gov/grants/policy/&ta~sharing
/data-sharing_goidance.htm. Updated March 5, 2003. Accessed August 6, 2006.
11. Kondro W. Dmg company experts advised staff to withhold data about SSRI use in
children. Ch4& 2200;170(5):783.
12. Whittington CJ, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington E. Selective
serotonin reuptake inhibitors in childhood depression: systematic review of pul~lishetl
versus unpublished dam. Lancet. 2004;363(9418):1341-1345.
13. Rennie D. Trial registration: a great idea switches from ignored to irresistible. JAMA.
2004;292(11):1359-1362.
14. US Copyright Office, Library of Congress. Circtclar 92: GoWright Law of the United
States. June 2003. http://www..copyright.gov/titlel7. Accessed August 25, 2006.
15. US Department of Justice. Department ofJustice Feedom of Information Act Refmnce
Guide. May 2006. http://www.u.~oj.gov/04foi:1/refe1~enc~guicle1~~~1~.htm~intro. Ac-
cessed August 6,2006.
16. National Academy of Sciences. Responsible Science: 1I:'rvriringlhe Inlc?p-ity rflthe Re-
seanh Process. Vol 2. Washington, DC: National Academy Press; 1333:127-128.
17. Fienberg SE, Martin ME, Straf ML. Sharing Research Dufu. \Vashington. DC: Nation:~l
Academy Press; 1985.
18. Duncan DT, l'earson RB. Enhancing acce.*4 t o ~nicrwl.i~;i \\ l111cprorcctlnR con-

fidentiality: prospects for the future. Sfat Sci 1931.6(3) 2 19-239

19. Fienberg SE. Conflict between the needs for access to \I.IIIS~ICJI informarlon dnd dc-
mands for confidentiality.J OffStat. 1394.1 O(2) 1 15- 132
5 6 Intellectual Property: Ownerrh~p.Atcerr. Rlghtr. and M a n a g e w n t

20 .</lr,r~irrglkrrtr / % > ~ I II r r ~ ~ ~ ~ -I~l r

c tuJlcc~P~ ~h'txutib
trl HIS. A System of Tripartite
Kt?;/x~,rr.srhr/rt~ Lt)n~l( In. England: U'c-llcomr Trust; 2003. http://www.wellcome.ac
.ul;/;1s.~ts/n1rl~)3lO~.pclt'. Accr?i.xJ August 26, 2006.
2 1. Intc.rnationl;l Co:nmiticc. of Medical Journal Editors. Uniform Requirements for
hl;~nir.srriptsSul~~~ii~tctl to I%iomcdicalJournals. llttp://www.icmje.org. Updated Feb-
rit:lry 2000. Acccas.\c.tlAi~gust26. 2006.
2 2 . 'l'cnopir C. King I). 'l'rentls in scientific scholarly publishing in the United States.
j .Scb 1~riI~lisl~i11,q. l(P)7;2S(3):135-170.
23. Clark MT. Open scsaliic? incre~~sing access to medical literattjre. Pediatdcs. 2004;
114(1):265-268.
24. Gibbs WW.Lost science in the Third World. Sci Am. 1995;273(3):76-83.
25. Horton R North and South: bridging the information gap. Lancet. 2000;355(9222):
2231-2236.
26. Budapest Open Access Initiative. http://www.soros.org/openaccess. Accessed August
6, 2006.
27. Frank M. Access to the scientific literature-a difficult balance. N Engl J Med.
2006;354(15):1552-1555.
28. ALPSP. Response to the Cowers Review from the Association of Learned and Pro-
fessional Society Publishers (ALPSP). http://www.alpsp.org/news/GowersReview
-response.pdf. Accessed August 6, 2006.
29. Ware M. Scientific publishing in transition: an overview of cument developments. .
http://www.alpsp.org/news/STM-ALPSPwhitepaper..September 2006. Accessed
October 7, 2006.
30. BioMed Central. Frequently asked questions about BioMed Central's article processing
charges. http://www.biomedcentral.com/info/about/aaq. Accessed October 7,
2006.
31. PLoS Journals. http://www.plos.org/joumals/index.hunl.Accessed August 20, 2006.
32. Lund University Directory of Open Access Journals.http://vmw.doaj.org. Accessed
August 6,2006.
33. Definition of open access publishing: Bethesda statement on open access publishing.
http://wnrw.earlham.edu/-peters/f~~/bethesda.htm#de~tion. Released June 20,
2003. Accessed August 20, 2006.
34. National Institutes of Health. Final NIH public access policy implementation.
http://publicaccess.nih.gov/publicaccessp.h. Accessed August 8, 2006.
35. Wellcome Trust. Wellcome ~rust'~osition statement in support of open and un-
restricted access to published research. http://www.weiicome.ac.uk~doc-wtd002766
.html. Updated February 9,2006. Accessed August 8, 2006.
36. Cox J, Cox L. Scboladv Publishing Practice: Academic Joumal Publishers' Policies and
Practices in Online Publishing. Worrhing, West Sussex, United Kingdom: Association
of Learned and Professional Society Publishers; 2006. Executive Summary also avail-
able at h t t p : ~ ~ w . a l p s p . o r g / p u b l i c a t i o n s ~ 2 s u m m a . pAccessed
df. October 7,
2006.
37. US Copyright Office, Library of Congress. Circular 1: Copyright Ofice Basics.
http://www.copyright.gov/circs.circl.html.Revised July 2006. Accessed August 20,
2006.
38. Fischer MA, Perle EG, Williams JT.Perle and Williams on Publishing Irrtu. 3rd ed.
Englewood Cliffs, NJ: Aspen Law & Business; 2006.
39. Nimmcr D. Mnzmeron Copyright. Vol 1-10. New York, JW:Matthew k n d c r Si Co Inc.
2002.
 .
9. ,
. .

5.6.16 Trademark

40. US Copyright Office, Library of Congress. Circular la: United States Copy~igbtOfice
A Brief Introduction and History. http://www.copyright.gov/circs/circla.htrnl. Re-
vised January 2005. Accessed August 20, 2006.
41. World Intellectual Property Organization. WIPO Copyright Treaty. http://nww.wipo
.int~treaties/en/ip/waltrtd0~~~~0033.htm. Adopted December 20, 19%. Accessed
August 25,2006.
42. Hart JD. Law of the Web:A Field Guide to Internet Publirhing. Denver, CO: Bradford
Publishing Co; 2003.
43.. Hirtle PB. Copyright term and the public domain in the United States: 1January 2006.
http://ww.copyright.corneU.edu/training/~ide~ublic~omainhm. Accessed
October 2, 2006.
44. US Copyright Office, Library of Congress. Circular 35a: Duration of Copyrighk Proui-
sions of the Law Dealing With the m g t b of Copyright Protection. December 2004.
http://www.copyright.gov/drcs/circl5a.html~duration.Accessed August 20, 2004.
45. Ihe Chicago Manual of Style. 15th ed. Chicago, IL: University of Chicago Press; 2003.
46. US Copyright Office, Library of Congress. Circular 9: Work Madefor Hire Undm the
1976 Copytight Act. 2004. http://w~.copyright.gov/circs/circ09.pdfpdf Accessed
August 20,2006. - .

47. Project Gutenberg. http://www.gutenberg.org. Modified August 26, 2006. Accessed

August 26,2006.
48. Fefst Publications ~ n vc Rural Tel Ser Co Inc, 499 US 340 (1991).
49. Association of Leamed and Professional Society.Publisbers.ALPSP guidelines.
http://www.alpsp.org/htp-grantli.hm. Acceskd August 6, 2006. .-.
50. Kirsch J. Kirsch's Handbook of Publishing Luw. Venice, CA: A m b a t Books; 1995.
'51. Harper c5. Row Publishers, Znc v.Nation Enmprises, 471 US 539 (1985).
52. J. D. Salinger v Random House, Znc, 811 F2d 90 (2d Ci 1987).
53. New Em PubltcaHons Zntmnational, ApS v H m y Holt and Company, Inc, 695F Supp
1493, 1524-1525 (SD NY 1988). '

54. Rossner M. How to guard against image fraud. Scientist. 2006;200):24: http://www
.the-scientist.~om/2006/3/1/24/1. Accessed ~ e ~ t e m b9,
e r2006.
55. Rossner M, Yarnada K. What's .iia picture? the temptation of image manipulation.
J Cell Biol. 2004;166(1):11-15.
56. JAUA and Archim Journals Standards for Scientific Journal Reprints, E-prints, and
~epublisheclArticles Purchased by Organijlations. Chicago, IL: ~mericanMedical
Association; 2006.
57. US Copyright Office, Library of Congress. International copyright. FL100. http://ww
.copyright.gov/fls/fl1OO.html.&vised July 2006. Accessed August 25, 2006.
58. US Copyright Office, Library of Congress. Circular 38a: International Copyright Re-
lations of the United States. http://ww~.copyright.gov/circs/circ~8a.htnil.Revised
June 2004. Accessed August 25,2006.
59. World Intellectual Property Organization. Berne Convention for the Protection of
Literary and Artistic Works. http://www.wipo.int/treaties/en/ip/beme/trtdocs
-woOOl.html. Accessed August 25, 2006.
60. US Patent and Trademark Office. General information concerning patents. h t t p : / / w
.uspto.gov/web/offices/pac/d~~/genera~/i~d~.htd. RevisedJanuary 2005. Accessed
August 25, 2006.
61. Patenting nature now. Nature. 1995;377(6545):89-90.
62. Deftos LJ. Haruani v Canada: the myc mouse that still squeaks in the maze of I>io-
patent law. Acad Med. 2001;76(7):684-692.

217
5.7 Confidentiality

63. Gittcr US1 Intcmsriorwl conflicts over patenting human DNA scqucnc-es In Ihr United
Stales and rile Europeln Union: an argument for compulsor).licensing and a fair-use
exemption. h' Y Urriu Law Rev. 2001;76(6): 1623-1691
64. Marshall E. Dispute slows paper on "remarkable" vaccine. Science. 1995;268(5218):
1712-1715.
65. US Patent and Trademark Office. Basic facts about trademarks. http://www.uspto
.gov/main/trademarks.htm.Modified May 25, 2006. Accessed August 25, 2006.
66. Federal Trademark Dilution Act of 1336. Pub L No. 104-98, 109 Stat 985 (January 16,
1996). C d i e d at 15 USC 1125.
67. Internet Corporation for Assigned Names and Numbers. http://www.icann.org.
Modified August 21, 2006. Accessed August 26, 2006.

Confidentialitypromises are wi'dely recognized as

a n ethical obligation, regardless of the legal duty
accompanying them.. . maintenance of con-
fidentiality promises fall withitt editorial discretion.
Jeffrey A. ~ichards'

Confidentiality. The author-editor relationship is an alliance founded on the ethical

rule of confidentiality. Confidentiality occurs when a person M o s e s information to
another with the understanding that the information will not be divulged to others
without In the context of scientific publication, this rule provides pri-
marily for authors' rights to have the information they submit to a journal, whether in
manuscript form or in communicationsto the editorial office, kept confidential and a
concomitant duty of editors and reviewers to maintain their obligations to ensure that
any information concerning a submitted manuscript is kept confidential. This com-
pact between author and editor preserves the integrity of the scientific review and
publication process. Under this compact, confidentiality may be breached only in
rare circumstances, and all such breaches must be handled with care (see additional
discussion in 5.7.1, Confidentiality During Editorial Evaluation and Peer Review and
After Publication).

Confidentiality During Editorial Evaluation and Peer Review and After Publication.
Strict confidentiality regarding the review and evaluxion of submitted manuscripts
and all relevant correspondence and other forms of coinmunication is essential to the
integrity of the editorial process (see 6.1, Editorial Assessment and Processing, Edi-
torial Assessment). Authors must feel free to submit manuscripts that contain their
unique ideas and information that may affect their reputations or careers or that may
be proprietary. Thus, editors and reviewers have an ethical duty to keep information
about a manuscript confidential, aqd authors have a right to expect that confiden-
tiality will be Policies supporting the confidential nature of the peer
review and editorial processes are well described by the International Committee
of MedicalJournal ~ d i t o r sthe, ~ Council of Science Editors: the World Association of
Meclical ~ d i t o r sand
, ~ the UK Committee on Publication ~ t h i c sThe
. ~ very existence
of a submission should not be revealed (by either confirmation or denial) to anyone
other than the editors, editorial staff, peer reviewers, and necessary publishing staff
(ic. t l l o w cs.wnti;il to prodi~cingthe journal but not others such as sales and mar-
 5.7.1 Confidentiality During Editorial Evaluation and Peer Review and After Publication

keting staff 1, unless and until the manuscript is released for publication (see also
5.13, Release of Information to the Public and Journal/Author Relations With the
News Media). In addition, editors should refrain from discussing any aspect of the
peer review process of a particular manuscript or any unpublished manuscripts
with anyone except authors, reviewers, and editorial staff. Even after publication,
information and communications about a manuscript, its review (including review-
ers' comments), or the editorial process should not be made public without consent
of the author, editor, or reviewer (see also "Record Retention Policies forJournals" in
5.6.1, IntellectualProperty: Ownership, Access, Rights, and Management: Ownership
and Control of Data, and 5.6.7, Intellectual Property: Ownership, Access,.Rights, and
Management, Copying, Reproducing, Adapting, and Other Uses of Content).
To maintain confidentiality, editors should deny requests or demands for con-
fidential information during editorial evaluation, d u ~ peer
g review, and after pub-
lication fromPanythird party, including readers, authors of other manuscripts, owners
of the journal, publishing staff other than those essential to producing the journal in
print/onliine, news media, advertisers, governmental agencies, academic institutions,
commercial entities, and representatives of those seeking inforrnation for use in ac-
tual or threatened legal proceedings (see 5.7.3, Confidentiality in Legal Petitions and
Claims for Privileged Information). Exceptions to this policy may be made in specific
circumstances provided that disclosures are limited and that anyone else given access
to confidential information agrees to keep the information confidential. Examples of
exceptions include the following:
H A prospective author who is invited by an editor to write an editorial commenting
on a paper that has not yet been published (Note: such authors should be re-
minded about the confidential nature.of the unpublished paper and not to consult
anyone about the paper without prior approval of the editor, including the author
,of the unpublished paper) .
rn A governmental agency representative consulted by the editor or-author on a
matter considered a public heal* emergency or a matter that by regulation re-
quires notification (eg, serious adverse drug event) ".
An attorney who is asked to advise an editor if legal concerns are raised or who
represents the joumal in legal proceedings
An institutional or funding authority requested by the editor to investigate an
allegation of scientific misconduct related to a manuscript under consideration or
a published article (for additional information, see 5.7.2, Confidentiality in Alle-
gations of Scientific Misconduct, and 5.4.4, Scientific Misconduct, Editorial Policy
and Procedures for Detecting and Handling Allegations of Scientific Misconduct)
An author's violation of public journal policy, such as prohibition of covert clu-
plicate publication or failure to disclose conflicts of interest (see also 5.3.2. Dupli-
cate Publication, Editorial Policy for Preventing and Handling Alleg;\tions o f
Duplicate Publication, and 5.5.8, Conflict of Interest, Handling Failure to Disclosc
Financial Interest)
An author's refusal to address an editor's questions about serious ethical concern..;.
such as whether research participants provided appropriate infor~neclconsent o r
whether a xtudy was appropri:~telyreviewed :incl ;ipprovct!, or w;~ivcclfor ; ~ p -
prov;~l,by an independent ethics committee (see also "Reports ol' L:nctliic;~l
5.7 Confidentiality

Studies" in 5.8.1, Protecting Research Participants' and Patients' Rights in Scientific

I'ublication, Ethical Review of Studies and Informed Consent)
Journals do not own or have licenses to unpublished works (because copyright and
publication licenses are typically transferred in the event of publication); thus, editors
should not keep print or electronic copies of rejected manuscripts. Copies should be
returned to the author or destroyed. However, a journal may choose to keep a copy
of a rejected manuscript for a predetermined, limited period iF it has a policy that
allows for author appeals of editorial decisions (see also "Record Retention Policies
for Journals" in 5.6.1, Intellectual Property: Ownership, Access, Rights, and Man-
agenlent, Ownership and Control of Data). Similarly, reviewers should not keep
copies of the manuscripts they are asked to assess. Reviewers should destroy any
print and digital copies of manuscripts they have reviewed. Reviewers should not use
others' manuscriots as teaching tools or in journal club discussions because doing so
would violate confidentiality.
Journals should publish details about the confidential nature of the editorial,
peer review, and publication processes in their instructions for authors, and editors
should inform all reviewers of the confidential nature of peer review in correspon-
dence to and instructions for reviewers3 (see 5.11, Editorial Responsibilities, Roles,
Procedures, and Policies).

Requirements During a Blinded (Masked) Peer Review Process. Journals should in-'
form reviewers in explicit terms what they mean by "confidentiality," "confidential
infonnation," and "privileged information" (ie, that not subject to dis~losure).~ our-
nals should also infonn reviewers and authors if the review process is single-blinded
(ie, only the reviewers' identities are not disclosed), double-blinded (ie, both the
reviewers' and the authors' identities are blinded), or open (ie, all author and re-
viewer identities are disclosed to all). For a detailed discussion of the various mech-
anisms of peer review (eg, single-blinded, double-blinded, open), see 6.1, Editorial
Assessment and Processing, Editorial Assessment. JMand the Archives Journals
and many other medical and scientific journals use a single-blind review process.
Peer reviewers should receive instructions reminding them to maintain con-
fidentialitywhen they are invited to review and also after they agree to review (see,
for example, the instructions in the Box and also 6.1, Editorial Assessment and
Processing, Editorial Assessment). Reviewersshould be instructed not to keep copies
of manuscripts they have reviewed and to refrain from discussing the information in
the manuscript with others. Reviewers should never contact authors directly to dis-
cuss their review without explicit permission from the editor.
In some circumstances, a reviewer may wish to enlist the aid of a colleague to
assist with the review. Some journals prohibit such consultation, and other journals
require that editorial permission be sought in advance of the consultation. If a re-
viewer is uncertain of a journal's policy, the reviewer should contact the editorial
office. For example, JAMA informs reviewers that they may enlist the aid of col-
leagues to assist with the review as long as confidentiality is maintained and all other
review policies (such as those pertaining to conflicts of interest) are followed.JAUA
reviewers are required to inform editors if such consultation has occurred.
After an initial editorial decision (eg, rejection or revision) has been made about
a reviewed paper, J A M provides the corresponding author with copies of the un-
named reviewers' comments.JAMA reviewers are also asked to provide confidential
 5.7.1 Confidentiality During Editorial Evaluation and Peer Review and After Publication

Box. Examples of Instructions to Peer Reviewers

lnstructions for Reviewers About Maintaining Confidentiality Included in Initial

E-mail Requesting Peer Review
We consider this request and the information in this e-mail to be strictly con- \
fidential. Please do not forward this e-mail to others and please delete or destroy j
any copies of this e-mail.
Instructions Given to Peer Reviewer Concerning Confidentiality After Reviewer Has
Agreed to Conduct Review
We consider this manuscript and your review of it to be strictly confidential. Any
'
use or distribution of the confidential information in this manuscript for any
reason beyond performing this review is prohibited. If you download any elec- :

Uonic files or print out copies, please delete and/or destroy these doci~ments
once you have completed your review; If you need to consult a colleague to help !

with the review, be sure to inform her or him that the information is confitlential
and indicate such consultation has occurred and include that .reviewer's.namc
in your review.
Reviewers' identities are not revealed to authors or to other.reviewers. Reviewers i
should not contact the authors. If you have any questions about this manuscript j
or the review process, please contact the editor.
./. I
comments to the editor, which include recommendations of acceptance, revision, or
rejection; these reviewer-specific recommendations generally are not shared with the
authors. However, comments directed to the editor may be summarized or excerpted
and included in a letter to the author if necessary.
To provide reviewers with constructive feedback, journal editors should send
to reviewers copies of other unnamed reviewers' ~ o m m e n t sEditors
.~ Qhould inform
reviewers how their reviews will -beused and who will have access to the reviews
and to the identities of the reviewers (see 6.1, Editorial Assessment and Processing,
Editorial Assessment). In blinded peer review, reviewers have a right to expect that
their identities will be protected. Thus, names and identifiers (eg, e-mail addresses,
fax numbers, and initials or names) should be removed from reviewers' comments
before they are disseminated to the authors or other reviewers.
Occasionally an editor may clioose not to send a reviewer's comment. to the
author, for eymple, when comments are considered libelous or hypercritical. Sim-
ilarly, an editor may choose to remove or mask any unhelpful or derogatory comments
from an otherwise valuable review.

Signed Reviews. Occasionally, reviewers will intentionally identify themselves in

their reviews or sign their reviews, even though they know the journal's peer review
process is blinded. Although such identification might imply that the reviewer has
waived the right to anonymity, it does not relieve the cditor or the reviewer of
the duty to maintain confidentiality. If [he editor ol' :I joi~rnalwith a blind review
proc- wi5hes to disclose the identity of a rcvlcwcr wllo h;~ssigned a review, the
editor should first contact the reviewer to verity r l 1 . 1 1 the rcvic\ver ;~ctu;~lly intencletl
for hcr o r his identity to Ix' revc;~lcrl.I l l c r ( t ~ t ~ , r .\11011l(t rc.11lintlthc rc.\.icwr.r :Inti tllc

221
5.7 Confidentiality

author that any communication about the manuscript should occur through the ed-
itorial office. IF the editor does not want to disclose any reviewer identities, the editor
may inform the reviewer that her/his identity or signature will be removed from the
review.

Disclosure of Reviewer Identities During Open Review and With Publication. Some
journals, such as the BMJ, have an open review process that encourages reviewers to
identify themselves to the authors and other reviewers?.1° Other jo.urnals, such as
those published by BioMed Central, also publish signed comments from the review-
ers with accepted papers." Here again, authors and reviewers should be informed of
policies regarding open review and publication of reviewer comments and identities
and be reminded that all communications about the peer review and editorial pro-
cess should be directed to the editor and editorial staff. Journals should clearly
describe such policies in instructions for authors and reviewers and in relevant
correspondence to authors and reviewers.

Acknowledging and Crediting Reviewers. An author may want to credit the help of
peer reviewers in an acknowledgment. Public acknowledgment of anonymous re-
viewers is not necessary or informative. However, some journals will honor authors'
requests to thank anonymous reviewers.
Many journals also publish the names of individuals who reviewed for the.
journal during the previous year to thank them publicly. Journals can notify re-
viewers of this plan in their instructionsfor reviewers or in relevant correspondence.
Rarely, an editor may receive a request from an author, who has made sub-
stantial suggestionsfor a complete revision, to include a peer reviewer as a coauthor.
If the author's request appears justified, the editor should contact the reviewer to
discuss the author's request and, if appropriate, the author and the reviewer should
communicate directly. If such an arrangement is to occur, the request must be made
early in the process (ie, before the major revision or complete rewrite) and the
reviewer would then need to participate fully in the revision and to meet authorship
criteria (see also 5.1.1, Authorship Responsibility, Authorship: Definition, Crite*,
Contributions, and Requirements). Such a scenario is unlikely to occur with reports
of original research.

Confidentiality in Allegations of ~hentificMisconduct. Allegations of scientific

misconduct (fabrication, falsification, and plagiarism) must be considered carefully
vis-8-vis rules of confidentiality. In cases of credible allegations of such misconduct,
an editor may need to disclose specific confidential information in a very controlled
and limited m a ~ e rFor . ~example, after a credible allegation of scientificmisconduct,
an editor may need to contact an author's or a reviewer's relevant institutional, fund-
ing, or governmental authority (eg, an academic president, dean, or ethics/integrity
officer) to request a formal iilvestigation. In this sipation, the editor will need to
identify the person about whom the allegation was made. This is best done by a
telephone call or a brief formal letter marked confidential. During such investiga-
tions, editors should avoid including details of such cases in e-mails that can be
wiclely circulated and should avoid posting details, even if rendered anonymous, in
c-mail lists or blogs. For more details on how an editor should handle such an
allc.g;~tion,see 5.4.4, Scientific Misconduct, Editorial Policy and Procedures for De-
tccting :lnd H:~ntllingAlleg:~tionsof Scientific Misconduct.
 5.7.3 Confidentiality in Legal Petitions and Claims for Privileged Information

Confidentiality in Legal Petitions and Claims for Privileged Information. A num1,er

of cases in US law have served as the foundation for or have directly supported the
confidential nature of the editorial and peer review process.
In 1972, the US Supreme Court ruled in Branzburg v Hayes that a reporter coulcl
be forced to testify if, during the course of news gathering, the reporter became a
witness to a crime.12However, the court also noted that individual states could create
their own standards with regard to a journalistic privilege (ie, a right) to keep sources
of information confidential, allowing lower courts in subsequent rulings to support
such privilege. With this bnderstanding, many states have enacted legislation that
protects the press from mandatory disclosure of sources, work product, and in-
f~rmation.'~"~ These state "shield laws" vary in scope but may offer qualified priv-
ilege to reporters to protect confidential information in legal settings unless it can be
established that (1) the information sought is relevant and/or material, (2) it is un-
available by other means or through other sources, and (3) a compelling need exists
for the information.13 However, recent challenges to journalists' privilege to keep
sources of information confidential are of concern.
After the 1993 US Supreme Court ruling in Daubert v Memli Dotv Pbarmaceu-
ticals, ~ n c , 'concerns
~ arose that attempts to breach the confidential nature of the
editorialprocess would increasethrough subpoenas for journal records.16 In this case,
the court identified standardsrequired for admissibility of scientific expert testimony.
These standards include, among others, whether the evidence on which the expert
opinion is based has been peer reviewed and published, and they have been applied
to limit admissibility of unreliable junk science as evidence in specific cases.
In 1394,a legal precedent was set regarding confidentialityand protection from
attempts to invade the confidentialand privileged nature of the editorial process.17 In
Cukier v American Medical Association, an author whose manuscript had been
rejected byJAMA sued to compel the journal to disclose the identity of those persons
responsible for allegedly defamatory statements made to the editors concerning the
author's financial interest." Citing the confidential nature of the peer reCiew process,
the editors refused to disclose the source of this information. The Circuit Court of
Cook County, Illinois, ruled that the editors were not required to disclose this in-
formation on the basis of the Illinois Reporter's Privilege AC~,'* which provides that
members of the news media (in this case, journal editors) cannot be compelled to
disclose sources unless the information cannot be obtained elsewhere and such
disclosure is essential to the protection of the public interest. This decision was
affirmed by the Illinois Appellate Court, and the Illinois Supreme Court declined to
hear the case.
Other cases that have supported the confidential n;lture of the peer review process
include Henke u US Depaltment of Commene and the National Science ~oundatio?d'"
and C&tmmBiotechnology Inc v Zmmunex ~ o r p . ' ~
With the case law supporting journals in resisting attempts to obtain confidential
information via litigation and quashing subpoenas, journals, editors, and publishers
can rely on legal precedents and principles to help them maintain confidenti;~lityof
the peer review and editorial process. Parrish and i3runs2' have summarized the
reasons journals should resist complying with s i ~ b p o c n :that~ ~ lntn~dcon such
confidentiality as follows:
t~ Violation of confidentiality ol>ligationsf o r onr ~ . i \ c . 1 1 1 . 1 ~r11;tkc I r riiorr d~fficulr
to defend future intrusions. rnay rc51111I , I Iwrc-rlvctl I>rcactl o f rnlst rh;lr
 . .

)uld damage a journal's reputation among authors and peer reviewers involved in
C-c
3spccific case as well as other current and prospective authors and reviewers, and
may result in an author or reviewer suing the journal for breach of confidentiality.
m Compliance with a subpoena disrupts the journal's acthities and processes and
consumes the journal's time and resources.
m Substantial costs can be incurred in respoiding to a subpoena, collecting ~ O C U -
I
ments, and providing depositions.
r A subpoena may be used as a means of harassment to prevent an author or a
journal from publishing.
If a journal receives a subpoena or request from an attorney for confidential in-
formation, the editor should consult the publishg, the journal's attorney, or both. j
The disclosure of confidential information to an attorney in this context would be
protected under attorney-client psivilege.22 However, it is important to l i t dis-
closure of such information to the publisher (eg, protecting the names of authors or ', i
reviewers). According to Parrish and ~runs?' in general, subpoenas are broad;
therefore, editors may object to the scope and burden of having to respond to such a
request. If negotiation with a party who served the subpoenamust occur, editors and I
their legal representatives should request a narrowing of scope of the subpoena, a ;
redaction of all irrelevant confidential information, the destruction or return of all
surrendered documents containing any confidential information, and a limit on who - --.
can view any confidential information. In addition, the journal may seek indemnifi-
cation from the authors or reviewers if they sue the journal for violation of con- I
. fidentiality. Pamsh and B ~ n recommend
s that if such negotiations fail or do not I
protect the journal properly, the journal can file a legal motion to quash the sub- I

p~ena.~' i I

Confidentiality in Selecting Editors and Editorial Board Members. When editors or

editorial board members are interviewed and evaluated for a prospective position with
a journal, all participants in the selection process should be reminded that all discus-
sions should remain confidential. In some cases, a signed statement of confidentiality
may be requested of members of search/interview committees. Without assurance of
such confidentiality, professional reputations and the journal's relationship with influ-
ential academic and political leaders may be jeopardized23 (see 5.11.10, Editorial Re-
sponsibilities,Roles, Procedures, and Policies, Role of the Editorial Board).
ACKNOWLEDGMENTS
Principal author: Annette Flanagin, RN,MA i

I thank C. K. Gunsilus, JD, University of ~llinois,UrbanaIChampaign; Wayne G.

Hoppe, JD,JAMA and Archive.,Journals; and Debra Pamsh, JD, Parrish Law Offices,
.
for reviewing and providing substantial comments to improve this section; the fol- :--

lowing for review and providing minor comments: Tem S. Carter, Archives of Sur- ';
gem Catherine D. DeAngelis, MD, MPH, JAMA and.ArchivesJournals; Cindy W. \
Hamilton, PharmD, ELS, Hamilton House; Trevor Lane, MA, DPhil, University of \
Hong Kong; Diana J. Mason, RN,PhD, AmericanJournal of Nursing; Povl Riis. MD, \
University of Copenhagen; Valerie Siddal1,-PhD, ELS, AstnZeneca; Cheryl Smart,
MBA; and Flo Witte, MA, ELS, AdvancMed LLC; and Sandra R. Schefris and Yolanda
 5.7.4 Confidentiality in Selecting Editors and Editorial Board Members

Davis, James S. Todd Meinorial Library, American Medical Association, Chicago,

Illinois, for bibliographic assistance.

REFERENCES
1. Richards JA. Note: confidentially speaking: protecting the press from liability for
broken confidential promises. Wmhington Luw Rev. 1992;67:501.
2. Beauchamp TL,Childress JF.Principles of Biomedical Ethics. 5th ed. New York, NY:
Oxford University Press; 2001.
3. International Committee of Medical Journal Editors. Uniform Requirements for
Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical
Publication. http://www.icmje.org. Updated February 2006. Accessed September 9,
2006.
4. Council of Science Editors. CSE's white paper on promoting integrity in scientific
journal publications. http://www..councilofscienceeditors.org/editorial~policies
/white-paper.cfm. Accessed January 3,2007.
5. World Association of Medical Editors. WAME recommendations on publication ethics
policies for medical journals. http://~.wame.org/resources/publicationethics
-policies-for-medical-journals. Accessed September 9, 2006.
6. Committee on Publication Ethics. A code of conduct for editors of biomedical journals.
http://www..publicationethics.org.uk/guidi/ce. Accessed September 9, 2006.
7. Cummings P, Rivara FP.Reviewing manuscripts for Archives of PediaMcs 6Adolescent
Medicine. Arch Pediatr Adolesc Med. 2002;156(1):11-13.
8. Marshall E. Suit all& misuse of peer review. Science. 1995;270(5244):1912-1914.
9. Smith R. Opening u p BhfJ peer review: a beginning that should lead to complete
transparency. BMJ. 1Wl3l8(7175):45.
10. Godlee F. Making reviewers visible: openness, accountability, and credit. JAMk.
2002;287(21):2762-2765.
11. BMC Medicine. Instructions for BMC Medicine authors. http://www.biomedcentral
.com/bmaned/ifora. Accessed September 9,2006.
12. Branburg v Hayes, 408 US 665 (1972).
13. Lening C, Cohzn H. Journalists' Privilege to Withhold Information in Judicial and Other
Proceedings: Shte Shield Statutes. CRS Report for Congress. Order Code RL32806.
http://fpc.state.gov/documents/organization/4411O.pdf. March 8. 2005. Accessed
November 2, 2005.
14. Kenworthy B. Branzburg u. Hayes, reporters' privilege & circuit courts. First
Amendment Center. http://www.firstamendmentcenter.org. July 12, 2005. Accessed
November 2, 2005.
15. Daubert v M m l l Dow Phannaceuticak, Inc, 113 S Ct 27866 (1993).
16. Gold JA, Zaremski MJ, Lev ER, Shefrin DH. Daubert v Memll Doza the Supreme Coi~n
tackles scientific evidence in the courtroom. J M .1993;270(24):29Gl-2967.
17. Cukier v Amerlcan Medical Association, 630 NE 2d 1198 (I11 App 1 Dist 1994).
18. Reporter's Privilege. Chapter 7835, Illinois Complied Statutes, Act 5, Article V111. I?ln 0.
Sections 901-909. 735 ILCS 518-301 to 909.
19. Henke v US Dt$artmenf of Commerce and the Nationul Science Founclaliotf,83
F3d 1445 (US App 1996).
20 Peer review and the courts. Nature. 1996;384(6604):1.
21 Pamsh DM, Bruns DE US legal principles and confidentiality of the peer review
prow\\ J/L\fA 2002.287C21).2839-2Ml.
5.8 Protecting Research Partlc~pdnt,. and Patfienu' RighO i n k i e n t i f i c P u b l ~ c a t ~ o n

u ~'XI.~ t Hauppugt.,
22. Gifih S1i- l ~ t c ~ l ) ~ ~ r ~5th cq.. KY:hrrow E c l u a t i m l k r ~ In<.
s 2UU3
-1
23. Bishop CI'.H o w lo Wi!u Ji-&rri/ic Jounul. Philadrlphn. PA: 151 Prcs, lYKJ

i%e right of the research subject to safeguard his or

her itztegri!y nztcsr always be mpected. Eoery
precautio?~should be taken to respect the privacy of
the subject and to minimize the impact of the study
on the subject's physical and mental integrity and
on the personality of the subject.
World Medical ~ssociation'

Protecting Research Participants' and Patients' Rights in Scientific Publica-

tion. Contemporary rules for protecting the rights of individuals (namely, research
participants and patients) in scientific publication have their foundations in doctrines
developed during the mid-20th century: the Nuremberg code: the World Medical
Associadon's Declaration of Genevan3and the World Medical Association's Declam-
tion of Helsinki,' as well as the 1979 US Belmont ~ e ~ o Today,
r t . ~ protection of such
'
rights is governed by national and international guidelines and
Biomedical editors and authors have a specific ethical duty to follow the principles
outlined in these doctrines (namely, autonomy, beneficence, and justice^^'^^ as well
as to honor individuals' rights to privacy when making decisions about publishing -,-=
studies that involve human experimentation and articles about patients who might be t
identifiable.'"16 In addition, privacy doctrines and laws in many countries protect
!
an individual's right to privacy?*v1' A legal claim for invasion of privacy (eg, pub-' I

lishing identifying details about or a photograph of an individual without his or her

permission) could be brought against a journal for publishing otherwise truthful I
statements about an individual." Privacy law differs from defamation law in that truth I

may not be used as a defense for invasion of privacy (see 5.9, Defamation, Libel).

Ethical Review of Studies and Informed Consent To protect the safety and dignity of
individuals who participate in research, academic institutions and grant agencies re-
quire that any study involving human participants be reviewed and approved by an ' ,

institutional review board (IRB) or independent ethics review committee. (Note:When

referring to individuals who participate in studies, the word participant is preferred
to subject [see 11.1, Correct and Preferred Usage, Correct and Preferred Usage of
Common Words and Phrases]. However, a number of guidelines and regulations cited I
herein refer to human "subjects.") I
The US National Institutes of Health (NIH) defines research as "any systematic
investigation designed to develop or contribute to generalizable knowledge" and l
a human subject as "a living individual about whom an investigator obtains either
(1) data through interaction or intervention with the individual, or (2) identifiable
private inf~rmation."~ The NIH considers the following to be componentsof research
not involving human participants: sampler from deceased individuals; samples col-
i
lected for diagnostic purposes only; samples or data that are available from com-
j
mercial or public repositories or registries; established cell lines that are publicly !

available; and self-sustaining, cell-free derivative preparations (eg, viral isolates,

cloned DNA or RNA). I
 5.8.1 Ethical Review of Studies and Informed Consent
. . ,-

The NIH also identifies 6 categories of research involving human participants

that may be exempt from IRE3 review and approval provided the study does not
.- i
' expose participants to physical, social, or psychological risks and does not permit
identiliability of individual living participants.5.6 These categories are study or col-
lection of publicly available existing records, surveys, interviews, use of educational
tests, observations of public behavior, and some types of research involving taste
testing of food.5v6
In addition, the nature and purpose of all procedures and their attendant pos-
sible risks must be fully explained to potential participants in advance, and partici-
pants m&t fully comprehendthe nature of the participat.i.onand voluntarily agree to
such participation. Research protocols for studies involving human participants typ-
ically address the following minimum set of protections: risks to all participants,
experimental procedures, anticipated benefits to participants (if any), anticipated
number of participants, proposed consent document and process to be used, and
- -
appropriate additional safeguards if the study .is to include vulnerable participants
(eg, children, incapacitated
..
Journal Policies and Procedures. In accordance with these requirements, joiimals
should require authors of manuscripts that report studies involving human participants
to state explicitly in the "Methods"section of the manuscript that an appropriate in-
dependkt ethics committee or IRB approved the study protocol or project or cle-
termined that the investigationwas exempt from such approval and why. The name of
the ethics committee(s) or IREKs) should be-specifiedin the "Methodsnsection. If the
. study protocol was approvedby several ethicscommittees/IRBs, as would be expecteel
in a multicenter study, it is appropriate to note that review and approval were con-
ducted by the ethics comrnittees/IRRs of all participating centers/institutions.
Journals should also require authors to indicate in the "Methods" section that
informed consent was obtained from all adult participants and from parents or legal
. guardians for minors or incapacitated adults and how such consent was obtained ( ie.
writen or oral).. If an IRB or ethics committee waived the requirement for informed
consent, the author should explain the reason for such waiver.
Ethical approval for research.involving animals and relevant animal-handling
protocols should be reviewed and approved by independent animal care and use
committees as required by national regulations, such as the NIH's Office of Lab-
oratory Animal Welfare requirements.18Suchreview and approval or waiver should
be adequately described in the "Methods" section of all mi~nuscriptsreporting re-
search involving animals.
Although numerous regulations and international documents require com-
pliance with these procedures, and groups such as the International Committee of
'
Medical Journal Editors (ICMJE),'~ World Association of Medical ~ d i t o r s ,I,' nc
~ I UK
Committee on Publicatioq ~ t h i c ssupport
'~ these requirements, authors and journals
continue to fail to properly report information on ethics con~mitteereview and ap-
proval and informed A s recommended by the ICMJE.'~ specific gnicle-
lines regarding documentation of formal ethical review and informed conwnt should
be included in a journal's instructions for authors.

h
Additional Regulations and Principles. US hiomedic;ll intpc>r~p.~tors who arc > i ~ I ~ ~r cel c t
jurisdiction of an IRB or formalethics revirw comri1irtc.c \ h o t ~ l t lfollo~v111,.~>r.rnc.il>lc-,i
descrihecl in the I3elmont ~ep01-I';~ntltllc IlS O V ~ : \ T I I 01~ \ Il~-;1lr11
V ~ N .r~ttlI ~ ~ I I ~ I ; I I ~
5.8 Protecting Research Participants' and Patients' Rights in kientific Publ~cation

Services Regulations for the Proteaion of Human ~ u b ~ e ~ t1nvcstig;rton

s.' oubldc h e
United States who are not subject to jurisdiction of an institut~onalethics revrew
committee should rely on and cite their relevant national regulations1';regional guide-
lines, such as the Council of Europe's Convention on Human Rights in Biomedi-
cine12;or international guidelines, such as the Council for International Organizations
of Medical Science's International Ethical Guidelines for Biomedical Research In-
volving Human ~ubjects," the Universal Declaration on Bioethics and Human
I3ights,l3or the Declaration of ~elsinki.'In addition to requiring researchers to have
the protocol describing the study reviewed by a "specially appointed committee .
independent of the investigator and sponsor," and to obtain study participants'
"freely given informed consent, preferably in writing," the Declaration of Helsinki
specifies that reports of experimentation not in accordance with the basic principles
described-in the Declaration "should not be published."'
For studies conducted in a specific country by investigators from another
country, regulations from both the local (host) country and the investigator's home
(sponsoring) country should be followed, and both IRB/ethics committees that re-
viewed and approved the study should be cited in the "Methods" section of the
manus~ri~t.'~"~ For
~ ~studies
~ ' " conducted in multiple countries, relevant regulations
of all host countries and any home/sponsoring countries and/or the Declaration of
~elsinki'or the Universal Declaration on Bioethics and Human ~ i g h t s should
followed, and all IRBIethics committees that reviewed and approved the study
'~ be

should be cited in the "Methods" section. In all multinational, multicultural studies,

!
1

attention should be given to the ethical requirements for protecting the interests of .
the research participants, namely, acquiring informed consent, avoiding harm, at-
tending to needs, and obligations when the study is completed.24Each of these
considerations should be addressed in the "Methods" section of the manuscript.

Reports of Unethical Studies. The past publication of unethical research does not
justify -&s. continued practice. In a 1966 pioneering article on ethics and clinical re-
search, ~ e e c h e ?identified
~ 50 unethical studies involving human participants that
were published in medical journals. Bee'cher concluded that "an experiment should be
ethical at its inception and is not made ethical by publicationn and that "failure to
obtain publication would discourage unethical e~~erimentation."~~ If the author of a
'
report of an experimental investigation that involves humans or animals does not
report in a submitted manuscript that formal ethics review and informed consent from
human participants were obtained or appropriately considered and waived, the editor
should ask the author why this information was not reported. The author may have
neglected to report this information because of inadvertent omission or a misunder-
standing. For example, an author may fail to report this information because ethics
review was considered unnecessary (such as in a retrospective audit of publicly
available data), or an informed consent requirement was formally waived by an IRB,
or a manuscript contains a secondary analysis and the information about IRB approval
and/or informed consent was reported in the primary publication. 4

All manuscripts, including those reporting studies in which IRB approval and/or
informed consent requirements were deemed unnecessary, formally waived, or I
previously reported, should include details about how the ethical requirements were :
met or why these requirements were considered unnecessary or waived.
Elsenwhen a study has been approved by an ethics committee or IRB, the ethics
' I
of the rvponcd research may be questioned by reviewers and editors. In such cases,
I '
'
1. ;
I
 5.8.2 Patients' Rights to Privacy and Anonymity

editors are obliged to ask the authors to clarify the situation and respond to ;my
concerns. Unless the authors can provide satisfactory responses and reassurance,
editors may choose to reject the manuscript in question.
If an author ref;ses to address serious concerns about such ethical requirements,
the editor may need to notify the author's institutional or funding authority (see also
5.7.2,.Confidentiality,Confidentiality in Allegations of Scientific Misconduct, and 5.4,
Scientiftc Misconduct).
Publication of an investigation that raises ethical dilemmas may be warranted if
such publication would encourage profeSsional and public debate and reform. Such
publication should be accompanied by ar, editor's note or an editorial describing the
I ethical issues and concerns. Research that violates established ethical principles
I should not be published. .
3 .

Patients' Rights to Privacy and Anonymity. Prii/acy is a state or condition of limited

access to matters of a personal nature, including but not limited to personal infor-
mation, as well as an individual's right to control such access." When individuals
grant others some f o e of access to themselves (eg, during a patient-clinician en-
counter), the individuals are exercising their right to privacy, but they are not waiv-
ing this right. Thus,a loss of privacy depends on the kinds or amount of access, who
has access, through what means, and to which aspect of a person.26 Historically,
medical journals have taken steps to protect patients' rights to privacy and anonym-
ity, including the deletion of patients' names, initials, and assigned numbers from
case reports; removal of identifying information from radiographs, digital images,
and laboratory slides; and the deletion of identifying details from descriptions of
patients or study participants in published articles. Until the late 1980s, placing black
bars over the eyes of patients in photographs was accepted as a way to protect the
identities of patients. However, journals began to discontinue this practice when it
became apparent that bars across eyes do not protect id en ti tie^.'^,"-^^ Photographs
with bars placed over the eyes of patients should not be used in publicaiion.
Case descriptions and case reports serve as important contributions to the
medical literature and make up a substantial portion of some journal content,
especially in some specialties. Traditionally, such reports have included specific
details about patients. However, as Pitkin and scott3' note, "The degree of detail and
specificity is sometimes sufficient to permit identification, and at the same time, it is
often much greater than necessary for any message the author means to convey."
Only those details essential for understanding and interpreting a specific case repoit
or case series should be provided. In most instances, the description can be more
general than specific to ensure anonymity, without loss of meaning. For example,
Pitkin and SCO$' suggest that "a 34-year-old para 2-0-0-2 black woman at 23 weeks'
gestation" can be described as "a multiparous woman in midgestation." Although the '
degree of specificity needed will depend on the context of what is being reported,
specific ages, racelethnicity, and other sociodemographic details should be pre-
sented only if clinically or scientifically relevant and important.
Patients have occasionally recognized descriptions of thenlselves in med~cal
articles without accompanying photographs and even after "superfluous ux1.1i
details" have been removed.= To protect a patient's riglit to prlv:lcy, nonessrtntl.3l
identifying data (eg, sex, age, occupation) generally shoulcl tw rcmovcd fron~
a manuscript, unless clinically or epiden~iologic:~lly 1fnpon:lnr Ilo~\c.\crc ) r n l t [ l n b
5.8 Protecting Research Participants' and Patients' Rights in Scientific Publication

certain details may be problematic.29.30For example, omitting a patient's occupation

frolll a case report might seen1 reasonable at first, but this informationmay be needed
later during an occupational exposure assessment or an epidemiologic investigation.
More important, authors and editors should not alter or falsify details in case de-
scriptions to secure anonymity because doing so may introduce false or inaccurate
data into the medical l i t e r a t ~ r eFor
. ~ ~example, changing the city in which the patient
lived may seem innocuous, until another investigator subsequently cites the case
report and the erroneous city in an epidemiologic analysis of locations of disease
outbreaks.
Several cases have occurred in which patients who had not consented to pub-
lication of their personal details in medical journals were recognized by themselves
or others in specific articles or subsequent news ~ o v e r a ~ e . ~ *The ' * ~ICMJEand a
number of medicxl journals have strengthened their rules for protecting patients'
rights to privacy by adding a specific requirement for informed consent from my
potentially identifiable
Therefore, when detailed case desaiptions or photographs of faces or identifi-
able body parts are included in a manuscript that might permit any patient to be
identified, authors should obtain written permission from the identifiable patients (or i
legally authorized representatives) to p u b l i i the information and should send a ,
copy of the permission to the journal. The same applies to video files submitted for I
publication. Such consent should include an opportunity for. the patient to read the I
'
nlanuscript to be submitted for publication or waive the right to do so.Nonspecific '
institutional consent forms that do not include a provision for a patient to review the
information to be published or waive that right are not acceptable. An example of the
patient permission form used byJ A M and the A ~ h i Journals m appears in the Box.
For manuscripts accepted for publication, when informed consent from identi-
fiable patient(s) has been obtained, journals should indicate that such consent was
obtained, either in the "Methods" section, if appropriate, or in the Acknowledgment
section at the end of the article.
Methods: This investigation was approved by the medical center's institu-
tional review board. The 12 patients in this case series provided wriuen
informed consent for the investigation. In addition, each patient was given
an opportunity to review the manuscript and consenled to its publication.
Acknowledgment: We are grateful to the 2 patients who graciously provided
permission after reviewing the manuscript to publish this information for the
medical community. 1
Some editors and authors have commented that obtaining consent from iden-
tifiable patients is too burdens~rne.'~~~Askiig those who so argue to consider that
the identifiable person could be themselves or a close relative might help convey the
rationale for this requirement. Others have argued that the process of obtaining such
consent may be disturbing to the patient or the patient's faqdy members.35 However, .-
i
subsequent discovery ,of unauthorized publication of a patient's information that ;
results in identification or unwanted publicity would be even more d i s t ~ r b i n $ ~ ' ~\
and may also violate national privacy laws such as the US Health Insurance Por- * 1
[ability and Accountability Act (HIPAA)?" Moreover, the publication of unautho- \
rized identifiable paiient information could result in legal claims related to invasion
of privacy, allegations of professional misconduct, or criminal penaltie~.7.8.17s32
,,r !:
:.
. ) _

!,.
 5.8.2 Patients' Rights t o Privacy and Anonymity

Box. JAMA and Archives Journals Patient Permission Form

Consent for Publication of Identifying Material in JAMAIArchives Journals

Igive my permission for the following material to appear in the print, online, and
licensed versions ofJAMAIArchives ~ournalsand for JAMA/Archiues Journals to
grant pe.rmission to thiid parties to reproduce this material.
Title.or subject of article, photograph, or video:
i

I understand that my name will not be published but that complete anonymity
cannot be guaranteed.
Please check the appropt3ate box below afrer reading each statement.
I have read the manuscript or a general description of what the manuscript
contains and reviewed all photographs, illustrations, or video files in which I am
included that will be published.
or
I have been offered the opportunity to read the manuscript and to see all
photographs, illustrations, orvideo files in which I am included, but I waive my
right to do so.
t s~gnea .
-uate
,'...- Print name
If are granting permission for another person, what is your relationship to
.!. that person?

I
AtJAUA, whether a manuscript contains identifiable patient information is de-
termined on a case-by-case basis. In most cases, potentially identifiable data are
removed from the manuscript. However, if such details are required, the editors will
ik. assess the risk of identifiabmty after considering the type.and amount of detail that is
needed, circumstances surrounding the clinical situation or investigation, and, if

[L
applicable, relevant identifiable information contained in previously published re-
ports involving the same patient($ or news reports that have resulted in p~~l~licity.34
(~ote:Previous publication or news coverage does not eliminate a patient's right
to privacy and does not negate the need for patient permission.) If the editors
r' detirmini that the information could result in-recognition-ven if only by the
t patient-they will ask the author to delete icl&ntifiahledetails and material. This can
It be done with most manuscripts. However, if "deidentification" is not possible, the
editors will ask the author to obtain consent from the patient, which includes offering
(
1- the patient the opportunity to read the submitted manuscript. In this case, it' tl~r

F patient cannot be located or refuses to consent to pul,lication, t h e manuscript i\.ill nor

be published.
5 8 Protect~ngResearch Participants' and Patients' Rights in Scientific Publication

1
'. .
'+>
--.d
Rights in Pliblished Reports of Genetic Studies. The rules for ethical approval of :
studies and for obtaining informed consent also apply to genetic studies of family
pedigrees and population-based samples. However, obtaining written informed con-
sent from all members of a large pedigree (many of whom may be deceased or
unlware of the collection of family data) may be diicult or impossible. Proposals for
obtaining some form of group consent and for avoiding the publication of informa-
tion about identifiable family members who will not give their permission have been
considered. All such studies must be reviewed by an independent ethics review
committee or IRB, and if the individual members of the family.or population-based
sample are considered to be "human subjects" and identifiable, informed consent
may be required; otherwise a waiver may be granted.39140(See also 5.8.1, Ethical
Review of Studies and Informed Consent.) The "Methodsnsection of all reports of
genetic studies should include statements about ethics cornmittee/lRB review and I--
approval or vvdver and information about informed consent procedures or waivers. :
As with reports of other types of studies, nonessential identifying information Ii
should be removed from reports of genetic studies. However, data should not be
altered in an attempt to protect the identities of individuals or family members,
although relevant information may be masked. For example, in pedigree charts, .
triangles can be used instead of squares and circles if the sex of family members is not
essential to the report (eg, if the disease is known not to be sex-linked), or sections of
pedigrees may be excluded from pedigree charts or not desaibed in detail if ap-
propriate consent could not be obtained as long as such omissions are noted. (See
also "Pedigree" in 4.2.2, Visual Presentation of Data, Figures, Diagrams, and 15.6.6, - =
Nomenclature, Genetics, Pedigrees.)

Patients' Rights in Essays and News Reports in Biomedical Journals. In essays and
news stories in biomedical journals, descriptionsand photographs of individuals are
often included. However, if these descriptions or photographs depict patients or
anyone in an actual patientclinician encounter who is identifiable, the authors or
writers should be asked to "deidentify" those patients. Identifying details may be
omitted but may not be altered or falsified. If patients cannot be deidentified, their
written informed consent must be obtained. (See Box.) Fictionalized cases and re-
ports generally should not be presented except in rare cases and unless this is made
clear to readers (eg, a hypothetical case to explain a clinical scenario or a fictional
essay in which it is made clear to the readers that it is fictional). In news stories, third-
party photographs should not be used if they include identifiable patients, unless
consent for publication has been obtained. Appropriately credited stock or staged
photographs depicting patients or simulating a patientclinician encounter are acc-
eptable.
ACKNOWLEDGMENTS
Principal author: Annette Flanagin, RN,MA
I thank Catherine D. DeAngelis, MD, MPH, J A M and Archives Journals, and
Povl Riis, MD, University of Copenhagen, for reviewing and providing important I!
suggestions to improve the manuscript; the following for reviewing and providing I,
minor comments: Terri S. Carter, Archim of Sutgety; C. K. Gunsalus,JD, University
of Illinois, Charnpaign/Urbana; Trevor Lane, MA, DPhil, University of Hong Kong;
\
1
 5.8.4 Patients' Rights in Essays and News Reports in Biomedical Journals
6'

?.
it- Diana J. Mason, RN,PhD, American Journalof Nursing;Cheryl Smart, MBA; a n d Fio
Witte, MA, ELS, AdvancMed LLC; a n d Sandra R. Schefris and Yolanda Davis, JamesS.
! Todd Memorial Library, American Medical Association, Chicago, Illinois, for biblio-
I- graphic assistance. . '

REFERENCES
1. World Medical Association. Declaration of Helsinki: ethical principles for nledical
research involving human subjects. http://www.wma.net/e/policy/b3.htm. Updatecl
2004.Accessed October 25, 2005.
2. The Nuremberg Code. JM. 1996;276(20):1691.
3. World Medical Asmciition. Declaration of Geneva. http://w\~~v.wma.net/e/polic)-
/c8.hun. updated May 2 0 5 . Accessed October 25,2005.
4. National Commission for the Protection of Human Subjects of Biomedical and
Behavioral Research. The Belmont Report: ethical principles and guidelines for the
protection of human subjects of research. April 18,1979. http://ohsr.od.nili.go\.
. /guidelines/belmont.html.Accessed September 9, 2006.
5. US Department of Health and ~ u k Services.
n Regulations for the Protection of
Human Subjects (45 CFR 46). http://www.hhs.gov/ohrp/humansubjects/gi~idanc.e
/45dr46.htm. Revised June 23,2005.Accessed October 25,2005.
6.National Institutes of Health. Guidelines for the conduct of research involving 1ii1rn;m
subjects at the National Institutes of Health. http://ohsr.od.nih.~ov/guidelinch
/graybook.html. Augua 2004. Accessed October 25,2005.
. 7. US Department of Health and Human Services. Office for Civil Rights--HIPAA:
medical privacy--national standards to pmtea the privacy of personal he;~ltliin-
formation. http://www..hhs.gov/oa/hipaa. Accessed September 9, 2006.
8. Office for Civil Rights. Standards for privacy of individually identifiable he;~ltliin-
formation; final rule. August 14, 2002. 45 CFR parts 160 and 164.
9. UK General Medical Council. Publishing case studies. Confidentiality: protecting ;11irl
providing information. http://www..gmc-uk.or~guidanceAibrary/confidentk~lity~f;~c~
.asp. Accessed September 9, 20%.
10. Council for International Organizations of Media11 Science. 1ntern:ltional crhicll
guidelines for biomedical research involving human subjects. l~ttp://nw.cio~i~s.ch
/guidelines_nov-2002-blurb.htm. 2002.Accessed November 3, 2005.
11. Office for Human Research Protections, US Department of Health and Human Ser-
vices. International Compilation of Human Subject Research P~vtections.2nd ed.
October 1, 2005. http://www.hhs.gov/ohrp/international/HS~Compi~ation.pdf.
Accessed November 3, 2005.
12.Council of Europe. Additional Protocol to the Convention on Human Rights and
Biomedicine, Concerning Biomedical Research. Strasbourg, France. h t t p : / / w .
.Conventions.coe.int/treaty/en1Treaties/HVl9.ii.January 25,2005.Accessed
January 8,2007.
13. UNESCO. Universal Declaration on Bioethics and Hiunan Rights. Paris, France:
UNESCO. 2005. http://unesdoc.unesco.org/ini;1ges/0014/001461/146180~.pdf.
Accessed September 9, 2006.
14 Inrernntlonal Committee of Medical Journal Eciitors. tlniform Requirements for
Manuscrlp~5Submined to Blomrvlical Journals: Writing and Editing for Bionledical
Puhllatlon hrtp //www Icmr org Updated Frl,n~;~ry 2006. Accessed Septeml~er9.
L(XX>
5.8 Protecttng Research Part~clpants'and Pat~entJ'R~ghtrIn k t e n t ~ Publrcat!On
t~

15. \I 01ltl A . \ u ~ i ~ [ r o01-n 5lc.dtc~lEditon Wh\tE rr-c.t,t~lmencl;ll~onson pubitciition of

~thlcz~x>lic.tcs for nlcdtc~liouml5. http://ulsv u~amc.org/resourcrs/public31ion
-c~i~tcs-policics-for-111edic-~l-pum;~ls. A c c r r d January 5, 2007.
16. Comtnittee on Publication Ethics. A code of conduct for editors of biomedical journals.
l~ttp://w~.publicationeti~ics,org.uk/guidelines/code. Accessed September 9, 2006.
17. Kirsch J. Kinch's Handlwok of Publishing Law. 2nd i d . Los Angeles, CA: Acrobat
Ilooks; IY)5.
18. N:ition:~l Inslitiitcs ol' I Ic:ilt11, Ol'lice of Lalmr~toryAninla1 Welfare. Public Health
Services policy on humane care and use of laboratory animals. http://grants.nih
.gov/grants/olaw/references/phspol.htm. Amended August 2002. Accessed
Novcll~ber13, 2005.
19. Yank V, Rennie D. Reporting of informed consent and ethics committee approval in
clinical trials. J A M . 2002;287(21):2835-2838.
20. Weil E, Nelson RM,' Ross LF. Are research standards satisfied in pediatric journal
publications? Pediatrics. 2002;110(2, pt 1):364-370.
21. Myles PS, Tan N. Reporting of ethical approval and informed consent in clinical re-
search in leading anesthesia journals. Anesthesiology. 2003;99(5):1209-1213.
22. Botkih JR, McMahon WM; Smith KR, Nash JE.Privacy and confidentiality in the
publication of pedigrees: a survey of investigators and biomedical journals. JAMA.
1998;279(22):1808-1812.
23. Kent DM, Mwarnburi DM, Bennish ML, Kupelnick B, loannidisJPA. Clinical trials in
sub-Saharan Africa and established standards of care: a systematic review of HN, .
tuberculosis, and malaria trids. J M .2004;292(2):237-242.
24. Aagaard-Hansen J, Johansen MV, Riis P. Research ethical challenges in cross-
disciplinary and cross-cultural health research: the diversity of codes. Dan Med Bull.
2004;51(1):117-120.
25. Beecher HIS. Ethics and cliical research. N Engl J Med. 1966;274(24):1354-1360.
26. Beauchamp TL,Childress JF. Principles ofBiomedical Ethics. 5th ed. New York, NY:
Oxford University Preb; 2001.
27. Slue WE Jr. Unmasking the Lone Ranger. NEngl JMed. 1989;321(8):550-551.
28. Riis P, Nylenna M. Patients have a right-to privacy and anonymity in medical pub-
lication. JAMA. 1991;265(20):2720.
29. Nylenna M, Riis P.Identification of patients in medical publications: need for informed
consent. BMJ. 1991;302(6786):1182.
30. Smith J. Keeping confidence in published papers: d o more to protect patient's rights to
anonymity. BMJ. 1991;302(6786):1168.
31. Pitkin RM,Scott JR. Privacy and publication. Obstet Gynecol. 2001;98(2):198.
32. Court C. GMC finds doctors not guilty in consent case. BMJ. I995;311(7015):1245-1246.
33. Borg GJ. More about parkinsonism after taking ecstasy. N Engl J Med. 1399;
341(18):1400-1401.
34. Fontanarosa PB, Glass 'RM. Informed consent for publication. J A M . 1997;278(8):
682-683.
35. Snider DE. Patient consent for publication and the health of the public.JAMA. 1997;278(8):
624-626.
36. Clever LH. Obtain infornled consent before publishing information about patients.
JAMA. 1997;278(8):628-629.
37. Tierney E. Consent for publication o f a case report. Anaesthesia. 2004;59(8):822.
 5.9 Defamation, Libel

38. Ghai B, Saxena AK. Patient's consent for publication. Anaesfhmia. 2005;60(.3):289.
39. BotkinJR. Protecting the privacy of family members in survey and pedigree rcse;~rc.l\.
J A M . 2001;285(2):207-211.
! 40. Beskow LM,Burke W, Merzp et al. Informed consent for population-based rese:~rcir
I involving genetics. J M .2001;286(18):2315-2321.

Tmtb is generally the best oindication against

slandb.
Abraham ~incoln'

Defamation, Libel. ~efamahonis the act of harming another's reputation by I i l x l

or slander and thereby exposing that person to public hatred, contempt, ridicule, or
financial loss.*-'~ibelis false and negligent or malicious publication involving words.
picams, or signs.2C Technically and historically, libel has differed from slander in
that slander was definedas defamation by oral expressions or gestures and libel was
defined as defamation in print. With both libel and slander, resultifig liability de-
pends on a third party reading or hearing the defamatory words. With the advent of
modem forms of communication, the distinction between these terms has become
blurred because of the niix of print, audio, and video content in multiple forms of
media.M5.01),6Cp131> ,

Truth is considered a defense against libel in most case^.^^^^*) However, the

context of the alleged libelous communication, effect of the communication on the
so-called average reader, intentions and actions of the author/writer, editor, and
publisher, and location of the publication can each influence l i a b i ~ i t ~ . ~For* ~ex-
~*'
ample, a statement may be truthFul in isolation, but coupled with other statements or
placed in a different context, the same statement could result in an overall false
. impression, which could result in d e f a m a t i ~ n . ~On ~ ' other hand, ? statement
~ . ~the
with minor inaccuracies or omission of inconsequential details could still be con-
sidered "substantially truenand thus not be determined to be d e f a r n a t o ~ y . ~In
' ~US
~~~~'
courts, most libcl cases are difficult for plaintiffs to win. ?his is not necessarily the
case in other countries. For example, the United Kingdom is known for libel laws that
are more favorable to plaintiffs? Libel law is complex, and it is difficult for an author,
editor, or publisher to know with certainty whether the text of a specific manuscript
could be defended successfully in a libel s ~ i t . ~ ' ~Editors
' ~ ~ ' and publishers should
consult lawyers with expertise in media law when concerned about risks of libel and
should also carry liability insurance that covers claims for libel (see also 5.9.7, De-
fense Against ~i&l,and 5.9.8, Minimizing the Risk of Libel).
In the United States, libel law generally requires courts to balance 2 competing '
values: freedom of expression vs protection of personal reputation? Freedom of
expression has its foundation in the First Amendment of the US Constitution,and this
freedom has been largely assured in instances involving public officials governed by
US law since a landmark Supreme Court dccbion in 13(d.'" In IVcw Yo& Times Co v
~ullivan,'~ an elected official in Alabama sued tile New York Times for publishing an
advertisement that included statements, some of which were inaccurate, about police
actions against students who participated in a civil rights demonstration; the elected
5.9 Defamation. Libel

official had supcn.i.wn rr.~~x~n~ibility over the police force alwut wh1c.h thc .sure-
ments were nlade. Aftcr J wries of decisions on this case in which ir W;LI demon-
strated that some of thc pul)lisllcd statements were false, the US Supreme Court
detennined that a public official could not recover damages for publication of a false
statement relating to his or her official conduct unless it is proven that the defendant
published the statement knowing it was false or with reckless disregard of whether it
was False (ie, actual malice). This decision established important protections for the
press against libel claims based on First Amendment protections to ensure that de-
bate on public issues remains "uninhibited, robust, and wide open,"6<P131)~10 but
more recent decisions in US courts have not always resulted in such favorable pro-
tections for the
Libel threats and suits have been used to silence those with opposing viewpoints
arid censor the free flow of information. Lawsuits, referred to as SLAPP suits (the .. '
acronym for strategic lawsuit against public participation), have been used in an .
attempt to intimidate those who wish to publish criticism or information that could ,

expose wrongdoing on the part of a particular industry or corporation. Even if the ,'
suit is groundless and the plaintiff eventually loses the case, a protracted and ex- I
pensive legal battle may be damaging to an author, editor, publisher, or journal. For i '

example, in 1984, Immuno AG, a multinational pharmaceutical company based in ;

Austria, brought a $4 million libel suit against an unpaid editor of the Journal of .! .
Medical Plimatology,Jan Moor-Jankowski, and the journal's The lawsuit .

.I,
followed publication of a letter from an author who raised questions aibout Immuno's
plans to conduct hepatitis research in Sierra Leone, West Africa,using chimpanzees- .- -., .
I
caught in the wild. Prior to publication of the letter, Moor-Jankowski had sent the
letter to Immuno AG for review and requested comments and a reply to be published
along with the letter. The company rejected the opportunity to reply and threatened . i
litigation. Moor-Jankowski suggested that Immuno AG contact the author for further !
information, but after no response was received from the company, the Journal of
Medical Primatology published the letter. After extensive and costly legal proceed- . b.
ings (the publisher was uninsured), the Appellate Division of the Supreme Court of . I-
New York ruled that the statements contained in the letter were either opinion or i.
factual statements that Immuno AG had failed to prove false. Immuno petitioned for j ...,.

hearing by the US Supreme Court, but that petition was denied in 1991.12
. ~this
Publication is an essential element for a legal action of ~ i b e l . " ~ In ~ ' context, ' . '

publication means that the alleged libelouscomrnunicationwas transmitted to a third

party who read, saw, or heard the alleged libelous c o r n r n ~ n i c a t i o n . ~ ~ . ~ ~ )
Courts have distinguished between those who publish third-party information
(ie, publishers) and those who provide facilities to third parties to transmit information
(ie, online service providers). Editors and publishers of scientificjournals, whether pub-
lishing information in print, online, or in both media, generally review, edit, and control
the information that is transmitted and deliiered, while online service providers may
not provide such oversight and control of third-party postings.6(p132)In Stratton Oak-
mont, Znc v Pmdigy Skm'ces~ 0 :the ' ~court held that even an online service provider !
could be held liable for a subscriber's defamatory statement because the online service
provider exercised "sufficient control over its computer bulletin boards to render it a i, :
publisher with the same responsibilitiesas a newspaper." Thus, scientific journals are .,
more vulnerable to libel suits than are online service providers because of the editorial ';
i
control their editors typicany exercise.
A publication is considered defamatory when it includes each of the following3-': 11
 5.9.2 Public and Private Figures

m A substantially false statement concerning another

Publication to a third party (Note: there are exceptions here, such as in publication
of testimony made during judicial or legislative proceedings; see also 5.9.6, Re-
publication and News Reporting)
a Fault amounting to at least "negligence" if involving a private individual (ie,
failing to meet the minimum standards that a reasonable person would have been
expected to meet in researching, fact checking, writing, reviewing, and publishing
the statement) or "actual malice" if involving a public figure (ie, publishing with
knowledge that the statement is false or with reckless disregard for the truth of the
statement)

Living Persons and Existing Entities. A statement generally cannot be libelous unless
it is "of and concerningna living person or existing entity (eg, corporation, institution,
or organization).2s317According to a 1992 case, Gugliuzza u K M C , Inc, "once a
person is dead, there is not extant reputation to injure or for the law to protect."14
Even when the living person or entity is not named in the statement, if the person's or
corporation's identity can be determined from other published facts, a case for libel
can be ~nade.~~'~'')

Public and Private Figures. A public figure is a person who assumes a role of prom-
inence in society, such as an elected official, a celebrity, or an infamous criminal. In
cases of alleged libel, public figures are afforded less legal protection than private
In a 1964 case, Nau York Times Co v ~ u l l i u a nthe, ~ US
~ Supreme Coun
determined that for a public official to prove defamation, the official must demon-
strate that the alleged defamatory statement was made with "actual malice" (ie, witk
knowledge that the statement was false or with disregard for the truth of the state.
ment) (see also 5.9, Defamation, Libel). A private figure is defined in the negative
someone who is not a public figure? In contrast, a private individual need not provt
malice, only negligence, to be successful in a libel ~ u i t . ~ : ' ~ ~ , ~
In legal settings, biomedical authors or researchers who publish might be con
sidered "limited-purpose" public figures, for example, if they publish articles in a1
attempt to influence a matter of substantial public interest, a governmental agenc
decision, or ~ e ~ i s l a t i o n . In
~ ~some
. ~ " ~cases,
~ an author who publishes might b
considered a limited-purpose public figure among the community represented b
the readers of a specific publication (eg, journ;il, bulletin board, cl~rrtroo~n)."'~''~
Answers to the following questions may aid in determining public figure stat[
of an individual and vulnerability to a claim of defamation when a personal statemel
about an'individual is pub~ished3s4.7:
Is the person described someone who has assumed a role of pronlinence 1

notoriety?
a Does the content of the statement pertain to a matter of public contro\.er\tr
public concern?
m If the statement refers to a public figure. t l w s it conraln rcfcrcnce\ 10tllv 1111
vidual's public figure status (eg. the ind~bIO~J.II'\ lo)>prf1)r111:111cc
o r ~ I I I ) I I C1
havior)?
5.9 Defamation, Libel

If the statement refers to a public figure, will the connection between such ref-
erences and the individual's public status be evident to a reasonable reader?
R If the reference is peripheral to the person's public figure status or responsibilities,
does it involve nonrelevant, highly intimate, or embarrassing facts?
8 .

Groups of Individuals. Defamatory statements about groups of individuals are usu-

ally not 1-:gaily actionable if the group is so large that no individual can be identified
in the For example, broad statements about specific groups (eg, phy-
sicians) or entities (eg, the pharmaceutical industry) are not at risk for libel actions
because no single individual or company is identifiable.

Statements of Opinion. Statements that contain pure opinion (ie, purely subjective
. judgment without assertion of fact) are not legally actionable because opinions can- i
not be proven true or However, an opinion that includes, asserts, or i
- implies facts that are false and defamatory could result in liability." As noted pre-
viously, publication of an expression of opinion about a public figure maybe pro- !
i
tected under the "fair comment" doctrine (see also 5.9.2, public and private ~ i ~ u r e s ) . ~ . ~
Fischer et alKS5.m)offer the following questions to help distinguish statements of fact
from statements of opinion:
r Can the statement be proved w e or false? . .
i
I
i
. .
n Are the facts' on which the opinion is based fully disclosed to the reader? . . " C
' ..
m If not, are the facts on which the opinion is based obvious to a reasonable reader
or readily available to the reader from other sources?
Are both the disclosed and undisclosed facts on which the opinion is based
substantially true?
B Does the context of the op&n suggest to a reasonable reader that it represents
opinion and not fact?
.nHave the statements that contain opinions been published in a manner that in- , 1
forms readers that they deal with opinion, commentary, or criticism (eg, a dearly
identified editorial or opinion page)? . .
Editorials, Letters, and Reviews. '1n some publications, such as newspapers and
popular magazines, editorials, correspondence, and critical reviews tend to alert the
reader that the content is opinion. This is not always the case for scientific journals.
No matter where the material is pbblished, malicious criticism of an individual or
entity could be considered defamatory, especially if it is demonstrated that such
criticism was not based -on facts?"' However, criticism of a public figure or public
institution or commercial entity may not be actionable if such criticism is scholarly
and supported by evidence and documentation. Similarly, scholarly criticism of an
- I
individual's research, theory, opinion, or previous publication,that is supported by 1
eviderce and documentation may not be actionable for 1n any case, editors '
\ 'i
:ind publishers should be cautious about statements chtical of individuals or com- I
i t
nlercial entities made in editorials, letters, and reviews. Use of-suchphrases as "in my
opinion" or "I believe" will not shield an author against an action for libel? whenever i..

> I.
a . .
.? i ,
'.
I..:
 -- ..

5.9.6 Republication and News Reporting

possible, authors of letters, editorials, and reviews in biomedical publications should

support opinions, assertions, and interpretations with documentation and/or formal
references, and editors/publishers should review all such material and require au-
thors to provide appropriate documentation and references. Editors and publishers
should consider obtaining legal review of material being considered for publication
that contains potentially libelous statements. In addition, publishers should have
liability insurance that covers the costs of defending against suits for libel. (See also
5.9.7, Defense Against Libel, and 5.9.8, Minimizing the Risk of Libel.)

Book Reviews. For reviews of books and other media (eg, CDs, videos, journals, and
Web sites), welldocumented critical comments about the book, media, or the work
of an author, producer, editor, or publisher are generally acceptable, but critical
comments about the author, producer, editor, or publisher should be avoided. In
Moldea v New York i7mes ~ 0 , the ' ~ author of a book that received a disparaging
review in the New Yo& Z?msued the paper for libel after trying and failing to get
the Nau Yo& Z?mto publish his rebuttal letter. The book review included a nutnber
of critical comments, including a statement that the book contained "too much
sloppy journalism to trust the bulk of this book's 512 pages."9 6 i s comment was
suppoited with specific examples of misspellings and allegations of mischacicteri-
zation of events? After an initial decision in favor of the New ~ o r Times,
k an ;\ppc;~l
that favored the author's claim,and an unusual reversal by the appeals court, the Ii1)t.l
suit was dismissed. The final decision in this case reaffirmed impunity from lihel suits
for opinion pieces and provided a "workable test for analyzing allegedly def;~~~xlton
statements of opinionn9(see the beginning of this section).

-Works of Fiction. Fictional accounts are not actionable for defamation unless a
reasonable reader believes that the story is depicting factual events and'can identify
the person bringing suit in the story.97 Humor, satire, and parody may be exempt
from defarhation suits as long as they are clearly works of fi~tion.~.' .
Republicationand News Reporting. A publisher caw Ix held li:lble for repuI>lisliin~
a
defamatory statement. For example, if a publisher reprinted a defamatory statemenr
about a public figure knowing that the statement was false, the publisher coultl be
held liable. Similarly, if the republished false statement was about a private figure, the
publisher could be held liahle for clefi~n~ation even if the statement w:w puhlishetl
I without knowledge of its falsity (ie, through negligence). Under the privilege of "fair
reporting," an author can repeat a previously published defamatory statement if it is
part of official proceedings (eg, a congressional debate or press conference) as long
as the account is fair and ac~urate.".~ Under the privilege of "neutral reporting," an.
author may repeat a previously published defamatory statement as long as the sec-'
ond account is a neutral or balanced report of a public controversy or maKer of
legitimate public concern (see also 5.9.4, Statements of Opinion). Publishers, editors,
and writers who rely on confident'ial sources for potenti:llly clefamatory statements
are at increasing risk for libel action. For ex:l~llplc,in I lnircd St;~tcs.shicltl I:~ws,
intended to protect news reporters from being legally forcecl to reveal identities of
sources, vary by state, and their application has been challenged in a number of
recent cases.a5.03'
Defense Agalnst Libel. In tllc linltrd States, truth is a defense against claimsof libel in
IIIO.I XT aim j.9,Defamation, Libel). Aside from consideration of truth of
c1.11n.rg111g
st.wnients. some jurisdictions also consider whether damaging statements
\vL'~c.made with intent to h a r n ~ . ~ ~ As ' ~ a. ~result,
) . ~ editors should query authors
alx~utany statements that criticize or imply criticism of individuals or corporate enti-
tics and ask the authors to provide evidence or documentation to support such
statements. If an editor is concerned about the risk vs benefit of publishing such
statements, obtaining a legal review as part of the process of peer review is recom-
menclecl. The legal review should be performed by an attorney with experience in
media law. Even though legal review may result in delay and several requests for
revision, it nlay help protect the editor and publisher from a libel claim. In addition,
offering those criticized an opportunity to review the material before publication, if
deemed appropriate by the editor, or to respond to the criticism after publication
m:ly reduce the risk of a successful claim.
Threats of litigation and fear of libel suits have kept some editors from meeting
their ethical duties to authors, readers, and the public. For example, during the 1980s
a number of medical journals declined to reprint retractions of articles by 2 separate
rese~rchels,Robert Slutsky and Stephen Breuning (even though the articles had been
proven to be fraudulent and even after Breuning's federal indictment), because of
fear that the journals would be liable for publishing statements impugning the work
of Slutsky and ~reuning." Such defensive editorial practices should be avoided
because they may impair the integrity of the journal and allow fraudulent research to .
continue to be read and cited. For example, allowing Slutsky and Breuning's fraud-
ulent articles to remain in the literature without retraction was an injustice to the
readers of those arti~les.~'Biomedical editors and publishers should follow the
statement on retractions from the International Committee of Medical Journal Edi-
tors2' (see 5.4.4, Scientific Misconduct, Editorial Policy for Detecting and Handling
Allegations of Scientific Misconduct).
Another case in biomedical publication involving a claim against the Journal of
Alcohol Studies demonstrates the need for an editor's awareness of the risks of libel
and the need for legal review of potentially defamatory material before abceptance
for p~blication.~~ In this case, an author sued the Journal ofAkoho1 Studies claiming
breach of contract after the journal did not publish an "accepted" manuscript. The
editor had determined the manuscript to be libelous after acceptance but before
publication. The journal decided to publish the manuscript following an agreement
with the plaintiff/author that he would drop his lawsuit. The editor said he had no
choice in light of the mounting legal fees. Ironically, a libel suit was never filed after
publication of the article because the person about whom the potentially libelous
statements were made believed that readers could determine that the statements
made about him were not truthful.23

Minimizing the Risk of Libel. The suggestions in this section are offered to help
authors, editors, and publishers redke the risk of libel in biomedical publication. All
statements of fact about individuals or commercial entities should be supported or
documented and verified to be accurate in the context in which they were and are
made. Similarly, statements of opinion should be supported, or based on documented
facts, and should not be malicious. In addition, authors should disclose any conflicts of
interest or concerns about the potential reactions'ofthose criticized to the editor so that
the editor and author work tpgether to ensure responsible publication (see also 5.5,
 5.9.10 Other Liability Concerns

Conflicts of Interest). Editors should consider offering those who are criticized in :I
submitted manuscript an opportunity to review the material of concern hcforc. puh-
, lication, or to respond to the criticism after publication, or both. In addition, editors
should consult experienced medii attorneys when necessary, and publishers shoultl
have insurance covering claims for l i i . None of these suggestions will ensure that
a lawsuit--even if frivolous or g r o u n d l ~ w i lnot
l be made, but they should help
editors, authors, and publishers avoid situations in which such claims have merit.

Demands to Correct, Retract or Remove Libelous Information. Demands to correct

or retract allegedly libelous material should be handled carefully. Removal of libel-
ous informationin print is not possible, and the standard course of action has been to
print corrections or retractioni in an expeditious and prominent Online
archives,which are considered part of the original publication in the United States
(but not in other counuiesl, may be corrected, edited, or removed, and continued
posting of defamatory material in an online archive may increase the risk of liability
for the author, editor, and publisher.6 However, demands to remove libelous ma-
terial must be carefully balanced against the need to preserve the integrity of the
scientific record, and corrrction and retraction are always preferred over removal of
content."'25 Editors should consider consultinga lawyer with expertise in media law
to deterrnine the best course of action.
If an allegation of defamation or threat to take legal action because of alleged
defamation is determined to be frivolous or groundless, the editor should inform the
person making the allegation that there is no merit to the allegationlthreat and no
further action should be taken. If the allegation is considered to have merit, the editor
may wish to consider publishing a letter from the person or representative of the
entity criticized and ask the author to provide for publication a letter of explanation
or apology; or the editor may choose to publish a correctiqn or a retraction. In each
case, reaprocal l i i g should be established between any published letters, cor-
rection, or retraction and the original article. Irk rare and truly &ordinary cir-
cumstances, the editor may choose to remove or obscure the libelous material from
an article or other online posting provided that a brief explanation of why the
material has been removed or obscured is included and is made easily accessible. If
the libelous material is so inextricably embedded in the context of an article that it
cannot be partially removed or obscured, an entire article may need to be removed
from the online archive provided that the bibliographic citation to the article remains
intact and a brief explanation of why the article has been removed is included with or
linked from the citation. In each of these cases, correction or retraction is highly
preferred to changing or removal of
In addition, republication (eg, reprints, e-prints, book collections) of articles :
containing defamatory material must be avoided, as these are not part of the original
publication and republication of known libelous material may result in additional
liability and damage c~aims.~
I
-1) Other Liability Concerns. There are other sourcesof legal problems for publishers and
editors that are beyond the scope of thii manual. Perle and Williams on Publishing
I.ad and Law of the Web:A Field ~uideto~ntemet ~ u b l k b i are
n ~good
~ resources for
information that address many of these problems, including issues related to copyright,
patent, and trademark (see 5.6, Intellectual Property: Ownership, Access, Rights, and
Management), privacy (see 5.8, Protecting Research Participants' and Patients' Rights in
r
5.9 Defamation, Libel I
Scientific I'ubliatiun). ~clvcrtihingand liability ( x c 5.12, Advt.rrixn~cn~\.
Adv~non;lls.
Sponsorship, Supplemcn~~. Hcprints, and E-prints), circuhion audts, sutxcnpuon IM
fraud, taxation and accounting issues. and employment issue.
ACKNOWLEDGMENTS
Principal author: Annette Flanagin, RN, MA
I thank Wayne G. Hoppe, JD, and Maggie Mills, JAMA and Archim Journals, for
reviewing and providing important suggestions for improvement of the manuscript;
the following for reviewing and providing minor comments: Catherine D. DeAngelis,
MD, MPH,J A M and Archives Journals; Diana J. Mason, RN,PhD, Amen'can Journal
of Nursing;and Povl Riis, MD, University of Copenhagen; and Sandra R. Schefris and
Yolanda Davis, James S. Todd Memorial Library, American Medical Association,
Chicago, Illinois, for bibliographic assistance.

REFERENCES
1. Lincoln A. Letter to Secretary Stanton, refusing to dismiss Postmaster General Mont-
gomery Blair, July 18, 1864. In: Bartlett J. Familiar Quotations. 15th ed. Boston, MA:
Little Brown & Co h c ; 1980:523.
2. Gfis SH. luw Dictionary. 5th ed. Hauppauge, NY: Barrons Educational Services Inc;
2003.
3. Fischer MA, Perle EG, WilliamsJT.Perk and Willianzs on Publishing Law. 3rd ed. Vol
1. New York, NY: Aspen Publishers; 2005.
4. Kirsch J. Kirsch's Handbook of Publishing Law. Los Angeles, CA:Acrobat Books; 1995.
5. Stubbs SE, Boyce WJ.The risks of libel in medical publishing. Ann Al-, 1994;72(2):
101-103.
6. Hart JD. Law oftbe Web:A Field Guide to Internet Publisbing. Denver, CO: Bradford
Publishing Co; 2003.
7. A P Stylebook 2005. New York, NY: Associated Press;2005. http://www.apstylebook
.corn. Accessed December 1,2005.
8. Chepesiuk R. Libel tourism chills investigative journalism: fear of libel suits deters
some publishers from publishing books in Britain. ZPZ Global Joumalfst. http://www
. g l o b a l j o u m a l i s t . o r g / m a g a z i n e / 2 0 0 4 2 / l i b . Second quarter 2004.
Accessed January 21,2006.
9. Hershey J. Casenote: if you can't say something nice, can you say anything at all?
Moldea v New York Times Co and the importance of context in Fist Amendment law.
67 U Colo L Rev 705 (Summer 1996).
lo. Neu York Times Co v Sullivan, 376 US 254, 280 (1964).
11. Immuno AG v Moor-Jankowski,74 NY 2d 548, 556 (1989).
12. Inzmuno AG v Moor-Jankowski,77 NY 2d 235 (1991).
13. Stratton Oakmont, Inc v Prodigy Sedces Co, No. 31063/94, NY Sup Ct (1995).
14. Gugliuzza v KCNG Inc, 606 So2d 790, 20' Media La Rptr 1866 (La 1992).
15. Swartz BE. Defamation law: implications for medical authors. Plast Reconstr Sutg.
2003;111(1):498-499.
16. Ezraikon v Robrich, 09-01-038-CV, 17 TLCS 1075 (2001).
17. Gertz v Robert Welch Inc, 418 US 323,347 (1974).
18. Milkovich v Lorain Journal Co, 497 US 1 (1990).
19. Moldea u New York Times Co, 793 F Supp 335, 337 (DDC 1992); Moldea I, supra note
12; Moldea 11, supra note 12.
 5.10 Editorial Freedom and Integrity

20. LaFollette MC. Stealing Into Print: Fraud, Plagiarism, and Misconduct in Scienlijic
Publishing. Los Angeles: University of California Press; 1992.
21. Whitely WP,Rennie D, Hafner AW. The scientific community's response to evidence
of fraudulent publication; the Robert Slutsky case. J A M . 1334;272(21:170-173.
22. International Committee of Medical Journal Editors. Uniform Requirements for
Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical
Publication. http:/wmv.icmje.org. Updated February 2006. Accessed September 10,
2006.
23. MacDonald KA. Rutgers journal forced to publish paper despite threats of libel suit.
Cbtvnicle Higher Educ. September 13,1989A5.
24. International &sodation of Scientific,Technical, and Medical Publishers. Preservation
of the objective record of science:an STM guideline. http://www.stm-assoc.org
/documents-statements-publica.March 2006. Accessed September 10, 2006.
25. International Federation of Library Associations and Institutions. W I P A Joint
Statement on Removal of Articles From Databases. http://www.ifla.orgNv4/admin
/joint-iflajpa-statementJuly2006.htm.Accessed October 27, 2006:

7bejkedom of thepress is one of tbegreatest

bulwarks of libmty.
George aso on'
Editorial Freedom and lnteghty. EditoriaILf~edornimplies a range of indepen-
dence, from complete absence of external restraint and coercion to merely a sense of
not being unduly hampered or f r u s ~ a t e dIntegrity
.~ is the state of honesty, credibility,
incorruptibility, and acco~ntabilit~.~ A biomedical journal has editorial integrity if it
adheres to these values, but different journals have different levels of editorial free-
dom. The First Amendment of the US Constitution affirms several freedoms, includ-
ing the Freedom of the press.3 Thus, communication through the US press or other
media is a right that should not be interfered with by the government, other insti-
tutions, or individuals? Many countries guarantee similar freedoms of the press.5
Freedom of the press is a foundation for editorial independence, "which is the distinct
right of the editor to publish any material that passes defined criteri:~for c1u;llity :~ntl
that fitswithin the mission of the publication, without suffering undue interference
from ~ t h e r s . " ~
A journal's editorial independence must be balanced against the need for ap-
propriate authority, responsibility, and account:d~ility;IS well :IS tnlst I>ct\\~cnthc
editor and the journal's many stakeholders: readers, authors, reviewers, pul>lishers:
owners, subscribers, advertisers, and others6(see also 5.11, Editorial Responsibilities.
Roles, Procedures, and Policies). The level of editorial freedom differs among tlif-
ferent biomedical journals, from maximum independence for those peel--revit.\vccl
journals in which the editor hascomplete authority and responsibility for the journal.
its content (including all editorial and advertising content), reuse of its content. :ind
use of the journal name/logo, to no independence for those journals tll;~t arc. not
peer reviewed and in which all authority and responsibility rests completely \\Ah
others (eg, publrshers or ownem). Journals th:rr .I~L. pul>lisl~culprim:lrily tc) hcl-\le
business, political. or a h e r concerns of their owners an: known 3s 'I~ouworg:ln\."'
For some b~ornedicaljournals and editors, the level of tditori;~lf r d o m 11i:l). IWIwxr
5.10 Editorial Freedom and Integrity

described as somewhere between complete ed~tonal~ndepndenceand no In-

dependence. Furthermore, editorial freedom may be assumed to exist by an ed~tor.
and the journal's readers, until and unless a major conflict occun A 1999 survey of
the editors of 33 peer-reviewed medical journals owned by professional socieues
(10 journals represented in the International Committee of Medical Journal Editors
and a random sample of 23 specialty journals with high impact factors) found that 23
(70%) of the 33 editors reported that they had complete editorial freedom, and the
remainder reported that they had a high level of freedom? However, many of these
editors reported having received at least some pressure in recent years over editorial
content from the professional society's leadership (42%), senior staff (30%), or rank-
and-file members (33%)?
There are numerous examples of editors and journals battling incursions from
interpersonal, social, political, and economicforces. Editors have been dismissed from
their posts and joumals have ceased publication after a mere "stroke of the editorial :

pen."s In one case, the I d b Medical Journal was voted out of existence in 1987 after
the editor published an editorial against physician strikes that angered some influ- I
ential members of the Irish Medical ~ r ~ a n i s a t i o n . ~ ' ~ I
During the last 10 years, editors of several leading general medical journals have
been unwillingly removed from their positions after publishing articles that were
considered inappropriate by various external forces (eg, owners, publishers) and for
having disagreements with owners or publishers about the editor's level of autonomy i
and authority over the journal's content and the journal's name and brand.(eg, 1
logo).'G26 In each of these cases, long-term struggles between the editors and the_- ,
owners of the journals resulted in loss of trust between the parties, and because of a
lack of effective protective oversight and governance and apparent lack of an ef-
fective system for conflict resolution, precipitate decisions to remove the editors
resulted in widespread criticism of the owners and threats to the integrity and con-
tinued existence of the journals. (See 5.10.1, Maintaining Editorial Freedom: Cases of ,
Editorial Interference and the Rationale for Mission, Trust, and Effective Oversight .
and Governance.)
An earlier example of a medical- editor credited for his struggles to maintain
editorial freedom is Hugh Clegg, editor of the BMJfrom 1944 to 1965. In 1956,Clegg
wrote an unsigned editorial entitled "The Gold-headed Cane," in which he castigated
the president of the Royal College of Physicians for taking office for the seventh
successive year. He also admonished the college for its failure to recognize the
modem welfare state and its lack of attention to postgraduate medical education?^^
With much difficulty, Clegg kept his editorial position and freedom and purposely
published a reply from the president that rebutted all of Clegg's criticisms. Clegg ,
believed that medical editors are the protectors of the conscience of the profession,
and he is well known for his assertion that editors who maintain this ideal will often
find themselves in trouble. This trouble may come in the form of incursions into
editorial freedom, which editors must be able to defend.
Editors of biomedical joumals that have editorial freedom must have complete
authority for determining all editorial content of their publications.6'2B33(Note: Un- 1,
less otherwise dictated by a journal's specific mission, this may not be the case for\
journals that are house organs or that have minimal editorial freedom.) While many\
stakeholders may offer useful input and advice, editorial decisions must be free from \
restraint or interference from the publication's owner, publisher, advertisers, spon- . -
 5.10 Editorial Freedom and Integrity

sors, subscribers, authors, editorial board or publication comminee members, re-

viewers, and readers. Owners, publishers, boards, and publication comn~itteesmay
have the right to select, hire, evaluate, and dismiss the editor, but they shoi~ldnot
interfere with day-to-day editorial decisions and policies.".'5vL"3'3'
Without a clear delineation of editorial freedom and the authority to maintain it,
an editor might not be able to ensure the integrity of the publication. Thus, owners.
publishers, and editors must have a clear and mutually understood definition of the
editor's level of editorial freedom, authority, responsibility, and acco~ntabilit~."~~~'
Editors of journals with complete editorial freedom should not comply with esternnl
pressure from any party-includixig owners, publishers, advertisers, sponsors. au-
thors, reviewers, and readers-that may compromise their autonomy or their jour-
nal's integrity.29pwExamples of such inappropriate pressures include, I ~ u aret not
limited to, the following: .
Pressure from an owner or a politically pwerful or motivated indivicIu:~lor gnwp
on the editor to avoid publishing certain types of articles or to puhlisll a specific
article
w Pressure or requirement of an editor by a publisher or owner to modify or sup-
press specific content before publication
1 Demand from an owner or publisher to. censor or remove publishecl content
deemed controversial or contrary to the owner's position or that of an anolhcr
organization or entity allied with owner
Demand from an owner or publisher or external person or organization to ha\.c
access to confidential editorial or peer review records (see also 5.7.1. Con-
fidentiality, ConfidentialityDuring Editorial Evaluation and Peer Review and After
Publication)
Demand from an author or group of authors to bypass the journal's standarcl
editorial and peer review processes and publish their manuscript without review
or revision (eg, a society demanding acceptance and publication without re-
view or revision of its meeting abstracts, proceedings, or papers)
ra ~ t t e kby
~ tan author or peer reviewer to have an editorial decision reversed by
threatening the journal's editor or owner
The use or repurposing of the journal's content or name by the publisher without
the editor's consent or in a manner that could ham1 the journal's integrity
~equestby an advertiser to insert an advertisement next to an article about or
related to. the advertised product or a threat to withdraw advertising support be-
cause of publication of a specific article (see also 5.12, Advertisements, Adver-
torial~,and Sponsored Supplements)
m An advertiser or publisher's attempt to publish an advertisement or sponsored
content disguised as editorial content (advertorial) (see also 5.12, Acivertisements,
Advertorials, Sponsorship, SuppIc~nc.nts,Itc'prili~s.;111d1'-prints)
m A publisher demanding information about ;rcctlptcd or pending editorial content
in advance of publication to sell that information to advertisers/sponoors or ftx
other commercial purposes
5.10 Editorial Freedom and Integrity

. -.
S
I A sponwr attempting to exert influence over editorial decisions or selectingspecific a

content for publication (eg, sponsored supplements) (see also 5.12, Advertise- '
ments, Advertorials, Sponsorship, Supplements, Reprints, and E-prints)
sl A publisher demanding publication of an advertisement that the editor deems
inappropriate (see 5.12, Advertisements, Advertorials, Sponsorship, Supplements,
Reprints, and E-prints)
w Request from a company to an editor to purchase reprints of an article under
consideration but not yet accepted for publication
Demands by a commercial entity or governmental agency to publish or censor
specific content
compliance with governmental or other external policy to not consider manu- -.
scripts from authors'based on their nationality, ethnidty, race, political beliefs, or
religion (see 5.11, Editorial Responsibilities, Roles, Procedures, and Policies)
Pressure from a news organization or journalist to publish information about a jour-
i
nal article before the news embargo is lifted (see also 5.13.3, Release of Infor-
mation to the Public and Journal/Author Relations With the News Media, 1
Embargo)
Editors may need to educate and remind the journal's various stakeholdersabout the
fundamentals of editorial freedoni and its direct relation to the publication's integrity.
1:
iI

.
-
,

c--?,
Maintaining Editorial Freedom: Cases of Editorial Interference and the Rationale
.
for Mission, Trust, and Effective Oversight and Governance. Interference with ed-
itorial freedom has affected several prominent medical journals and has been well
documerited in the biomedical literature and the press. However, many other cases
of such interference have not been made public or are discussed only anecdotally,
privately, or via restricted electronic mailing lists. The experiences of JAMA, the
New England Journal of Medicine, and the Canadian Medical AssociationJournal
( W J ) are presented here for the folIowing reasons: there is sufficient literature
documenting the relevant events; effectiveprotective oversight mechanisms ancl gov-
ernance plans were lacking or insufficient at the time; and the mechanisms for '
'
protection of editorial freedom that were developed as a result of these events are
informative and may be helpful for other journals, editors, publishers, and owners.

The Case of JAMA. Since 1982,George D. Lundberg, MD,had served as editor in chief I
of J A M , a weekly, peer-reviewed, general medical journal, and the Archives spe- I

cialty journals that are owned and published by the American Medical Association ,
I
(AMA). JAMA had operated under a set of goals and objectives that were developed i
by Lundberg and the journal's editorial staff and that were approved by the journal's I
editorial board and A h a management.34These goals and objectives had protected I!
the editor on several occasions £;om external pressures to restrict the journal's edi-
torial freedom, and in 1993 the AMA House of Delegates (the policy-setting and
governing body of the association) passed a resolution reaffirming editorial in-
dependence for all of its scientific journals.35AlthoughJAMA had a defined mission ',
that included editorial freedom that had been publicly supported by its owner, it did \
not have sufficient oversight and a governance plan in place to help promote a trust

.v 1 -
. .
! ;
 5.10.1 Maintaining Editorial Freedom

relationship between the editor and AMA leadership, facilitate resolution of conflicts,
and help prevent interference and threats against editorial freedom and authority.
During Lundberg's editorship, there had been tension between him and rep-
resentatives of the AMA leadership and executive staff related to editorials and articles
that were published in J A M that were controversial or contrary to AMA positions. In
1999, Lundberg was abruptly fired by the AMA after he accelerated the publication of
an article in JIM.IA (after peer review and acceptance) that reported the results of
d e g e students' attitudes toward sex to coincide with the impeachment hearings
of President Clinton. According to the AMA's executive vice president, the publication
of that artide was an act of "inappropriatelyand inexcusably interjecting [JAMAI into a
major political debate th2t has nothing to do with science or medi~ine."'~~"~~' At the
time, Je had as 2.of its objectives "to foster responsible and balanced debate on
controversial issues that affed medicine and health care" and "to inform readers about
nonclinical aspects of medicine and public health, including the political, philosophic,
ethical, legal, environmental, economic, historical, and cultural."* In addition, the
j d had a long history of publishing articles that were pertinent to ongoing national
and international political disamions, that were directly or indirectly related to medi-
cine or public health, and that were released at a specific time to influence those
discussions.
The AMA was widely criticized for the firing, which was considered interference
with the journal's editorial independence and which damaged the reputation of the
journal and the AMA and harmedJAUA's previously demonstrated i n t e g ~ i t y . ' ~ - ~ ~ . ~ ' . ~ ~
Immediately after Lundberg's firing, the journal's remaining editors, led by 2 interim
coeditors, and the editorial board published an editorial in protest.16 The senior
editorial staff considered resignation but decided to stay on to support the journal.
However, 2 members of the journal's editorial board and some members of the AMA
resigned, and some readers cancelled subscriptions to the journal. Many authors
threatened to withhold manuscript submissions to JAW, and others threatened not
to serve as reviewers.
The AMA appointed an independent 9-member search cornmiftee, chaired by a
member of the JAUA editorial board who was also an editor of one of the Architres
Journals. Other members of the committee included leaders in academia and re-
search who were independent of the AMA,other journal editors, and aJ A M deputy
editor; it did not include AMA executive staff or officers. The search committee's
objectives were to identify a new editor, review the journal editor's job description
and reporting relationships, determine how to evaluate the editor's performance, and
review existing practices and develop safeguards to ensure the journal's editorial
independepce, integrity, and re~~onsibility.~'.~
Before the search committee had completed its work, the JAM editorial board
(which included 10 editors of the AMA-owned Archives Journals) met with the re-
maining editors, other editorial staff, publisher and publishing staff, and AMA senior
management during its regularly scheduled annual meeting. During that meeting, an
executive session was called that incIuded the editorial board members and senior
editorial staff, but excluded representatives of AMA senior management and the
journals' publishing staff. The editorial board voted unanimously to resign en masse
if the journal's complete editorial freedom and a new governance plan to repair the
journal's integrity was not accepted by the AMA leadership.
M e r multiple discussions and negotiations between the se;trch committee and
AMA leadership, a new governance structure for.lA,1,4 and the ~ r r h i w Journ:~I~
.~ \\..I.
 ----- .,

5.10 Ed~torialfreedom and Integrity

I ..*
developed by the search committee, AMA senior management, and the AMA Board
'.
of Trustees to "insure editorial freedom and independence for JAMA, the Archives
Journals, and their ~ditor-in-chief."".38This governance structure was set in place
before Catherine D. DeAngelis, MD, MPH, became editor in chief of J A M and the
Archives Journals in January 2000, and it was a condition of her acceptance of the
position. The governance plan was subsequently reaffirmed by AMA leadership.j9
The governance plan is republished here as a model for other peer-reviewed
journals, editors, publishers, and owners to consider (see Box 1 and Figure). This
governance structure supports the editor in chief's editorial independence, facilitates
access of the editor in chief to the decision-makingbody and top management of the
AMA, and provides mechanisms for review of the editor in chief's performance and
conflict resolution. For all editorial responsibilities, the editor in chief reports to the
Journal Oversight Committee, which in turn reports to the AMA Board of Trustees.
For business responsibilities (including editorial finances and budget), the editor in .'

chief reports to the AMA executive vice president (the top management position), ;
'

who reports to the AMA Board of Trustees. The journal's publisher reports through
an administrative channel simiiar to that of the editor in chief for business and does
not havesupervisory or other authority over the editor in chief. The editor in chief
and publisher work as a t&m.

The Case of the New England Journal of Medicine. Since 1991, Jerome P. Kassirer,
MD, had served as editor in chief of the New EnglandJoumal @Medicine, a weeMy,
peer-reviewed, general medical journal that is owned and published by the Massa-
chusetts Medical Society. In 1999, Kassirer was dismissed as editor in chief of the
New England J o u m l of Medicine after a struggle over authority with leaders of
the Massachusetts Medical Society could not be r e s ~ l v e d . ' ~Kassirer
- ~ ~ ~ objected
~ to
the society's plans for reuse of the journal's content and co-branding of the journal
name with other information providers over which he had no control or authority.19
He also objected to plans to move the journal's editorial staff from its academically
affiliated location at Harvard University to the publisher's commercial offices because
he believed that these plans threatened-the journal's credibility and autonomy.lg
According to W i r e r , the decision to dismiss him was made by the Massachusetts
Medical Society's Committee on Administration and Management, which did so
without input from the society's trustees or the Committee on ~ublications.'~ Ac-
cording to the society's bylaws, the Committee on Publications was responsible for
the publication of the journal and was the authority to which the editor in chief had
reported for decades.
In response to the firing of Kassirer, there was much criticism from the interna-
tional medical community as well as resignations of members of the Committee on
Publications, the journal's editorial board, and members of the Massachusetts Medical
~ o c i e t y . " .In
~ ~addition,
~ ~ ~ the journal's remaining editors discussed a plan for mass
resignation in response.20Deciding that such an action could irreversibly damage the
journal, the remaining editors dikussed and negotiated with the Massachusetts Med-
ical Society a set of principles to maintain the journal's editorial independence and the
editor's authority and responsibility for all content, editorial policies, use of the jour-
nal's content, name, and logo, and location of the editorial office.20With these as-
surances, Marcia Angell, MD, then the journal's executive editor, agreed to serve as
editor in chief until a search committeewith representation of the editorial staff and the
wider academic community could identify a new editor in chief for the journal. In May
Box 1. Editorial Governance Plan for J A M A ~ * , ~ ~

1. There will be a seven (7) member Journal Oversight Commiuee (JOC).

This committee will function and be recognized not only as a system to
evaluate the Editor in Chief but also as a buffer between the Editor in Chief
and AMA management and a system to foster objective considemtion of the
inevitable issues that arise between a journal and its parent body.
2. The JOC will prepare an annual evaluation of the Editor in Chief, which will
be reported to the AMA executive vice president (EVP) ind to the Board of
Trustees of the AMA. The Committee will have the charge to evaluate the
performance of the Editor in Chief on the basis of objective criteria, and
deliver that evaluation on an annual basis to the EVP and Board of Trustees
of the AMA.The JOC will be responsible for determining the criteria for
evaluation of the Editor in Chief. These aiteria will be established in writing
and made available to each member of the JOC, theJAMA Editorial Board,
the Editor in Chief, and the EVP and approved by the B m of Trustees of
the AUA.TheJAMA Editorial Board will be soliated for input to the eval-
uation process by the Committee. Correspondence abgut the performance
of the Editor in Chief or J A M received from constituent groups will be
shared with the Committee. The Editor in Chief will be offered a 5-year
contraa If the Editor in Chief is dismissed during the term of the employ-
ment contract, other than for cause, the contract will be paid in full. Should
such dismissal occur in year 5 of the contract, the minimum payment to the
Editor in Chief shall be 12 months' salary.
3. The JOC wili be charged, in addition, with reviewing and, if necessary,
making additional recommendations to the AMA EVP and Board concerning
governance and structural reforms necessary to ensure the A M A Joi~mals'
editorial independence. For this purpose the Editor in Chief and Vice
President for Publishing will serve as advisors to the committee. Tkis
function will be ongoing.
4. The,7 members of the JOC will include 1 member of AMA senior m n -
agement, 1 member from outside the AMA with publishing business
experience, and 5 members representing the scientific, editorial, pecr-
reviewer, contributor, and medical communities. The Committee n~en~l>c.rs
shall serve 3-year staggered terms. A Committee member may serve no more
than 2 terms.
5. No member of the JOC may be an AMA employee except for the meml>cr
from AMA Senior Management. No AMA employee may be Chair of the
committee, who shall be elected by the JOC.
6. Nominations for the first set of JOC members will be forwarded to the M , l A
Board by the Editor Search Committee, which will also recommend the
initial term of each member.
7. JOC members are to be selected by the AMA Board only from a list of
recommended persons submitted by the JOC. Three names per position will
5.10 E d ~ t o r l a lf r e e d o m a n d l n t e g r ~ t y

- - - - - --- . --

I Box 1. Edltorol Governance Plan for JAMA% '' ( c o w

be recommended by the JOC. In the event that [he Board selects none of the
three, additional names would be recommended by the JOC, as necessary.
Members of the JOC can only be appointed or removed by a two-thirds
supermajority vote of the AMA Board of Trustees in the exercise of its
oversight function.
8. Any proposal to dismiss the Editor in Chief for any reason shall be brought
before the JOC for evaluation and a formal vote. The recommendations and
views of the JOC shall be presented to the AMA Board along with the rec-
ommendation and views of the EVP. A supermajority (two-thirds) vote of
the AMA Board would be required for dismissal of the Editor in Chief.
9. The Editor in Chief will continue to report to the EVP only for business and
financial operations. The Editor in Chief will not report to management
for any aspect of the editorial content of J A M or the Archives Journals or
o+,'lerAMA publications under hisher jurisdiction. Editorial independence of
the Editor in Chief will be absolutely protected and respected by AMA
management. In order to exercise its evaluative functions, the JOCwill have
full access to financial information including revenue and expense state-
ments, budgets, and actual results. In order to have access to this proprietary
information, each member of the JOC who receives it will execute the AMA's '

standard Confidentiality and Conflict of Interest Agreements.

10. The Editor in Chief will have total responsibiity for the editorial content of
JAUA and responsibiity for the performance of the At.chives Editors and
other AMA publications under hisher jurisdiction. AMA management rec-
ognizes and fully accept3 the necessity of editorial independence for the
Editor in Chief at all times.

EDITORIAL RESPONSIBILITY

I Oversight Cornmlttee to the Executive

he AMA Board of T~SteesIs one of
Journal's progress and performance.
server inan advisory capacity to the

i
Figure. Reporting structure for IAMA's Editor in Chief. Reprinted from JAMA. 2004;291(1):109.~~ \ 1
-
%.

5.10.1 Maintaining Editorial Freedom

2000,Jeffrey M. Drazen, MD,wasappointed editor in chief, and it das reportcd th;~ctlw

editorial freedoms negotiated previously by Angel1 would remain?"

The Case of the Canadian Medical Association Journal (CMAJ). Since 1996, John
Hoey, MD, had served as editor in chief of the mJ, a weekly, peer-reviewed general
medical journal owned by the Canadian Medical Association. In 2006, the ChlA
abruptly fired Hoey and the journal's senior deputy editor, Anne Marie ~ o d k i l l . ~ ~ - ~ "
Initial public reasons from the publisher and CMA leadership for the dismissals were
to "freshen" the CMAJand because of "irreconcilabledifferences" between the editor
in chief and t!e CMA, but no specific differences were While the CMA
denied that the dedsions had anything to do with editorial independence, Hoey,
other editors, editorial board members, and members of the journal's oversight
committee have all desuibecl several examples of censorship and interference with
the <;IMAJ by CMA leaders and executives dating back to 2001 or earlier.25m26m4143
In 2001, CMAJ published an editorial supporting medical use of marijuana,
which contradicted the CMAJsposition and for which the CMA's general counsel
complained to ~ o e y . ~ In' 2002, the CUAJ published an editorial criticizing Quebec
physicians for not properly staffing an emergency department after a patient with a
myocardial infarction died while beiig transported from an emergency department
that had closed at midnight to a second open emergency d e p a r ~ n e n tMembers .~~
of the CMA board called the editorial irrespokible, and the CMA president called
for the editorial to be retracted.The GUJeditorial board responded that the CMA
was threatening the CiW!,Js' editorial independence.2sv42 Following these incidents, a
journal oversight committee was established in 2002. However, the oversight com-
mittee's roles and functions were unclear andainterpreted differently by the CMA
leadership, the editor in chief, and even the chair of the committee.2s
In late 2004, the CMA had reorganized its publishing services and placed the
ownership and direction of the W J u n d e r a subsidiary, CMA Holdings I ~ CThis . ~
change reduced the editor in chief's contact with the CMA and increase$ his inter-
actions with the holding company and publisher, whose primary objective was
profit.41143However, this change didmot decrease the CMA's attempts to influence
the editorial direction and decisions of the journal. In late 2005 and early 2006, 2
other incidents of interference and censorship by CMA leadership and executives
o c c ~ r r e d . ~In~one
.~~ case,
,~~ a CUllJnews story reported on the difficulty Canadian
women had in obtaining nonprescription emergency contraception (Illan 13) froln
Canadian pharmacists. Apparently, the Canadian Pharmacists Association com-
plained to the CMA's chief executive officer and objected to CMAJ's plan to run this
news story after one of the CMAJ reporters interviewed an executive with the as-
sociation. The ~ h 'chief s executive officer took the objections to the CMAJ pub- ,
lisher, who told Hoey not to run the news story. Faced with what was thought to be
an unreasonable demand and to avoid a crisis, the editors and reporters then
modified the news story to address some of the objections and a revised article was
published.25.26.41 An unsigned editorial w:~ssul,scqucntly published in the CMAJ to
alert readers to the incident of editorial interference and to "set in motion a process to
ensure the future editorial independence of the journal."45
The second case of such interference involved a CMAJ news story that was
cnrial of a Canadian public health official. The news story was published in the
online vetston of GCtAJon February 7,2006,and was .\ul,?;equenrlyremoved from the
Web site." On February 20, Hoey and Todkll were fired. and 2 days later, a revised
 ..
5.10 Editorial Freedom and lntegrlty

version of the original story posted onl~nethat was less cntlc-dl of the hcrlth
official and more supportive of and t>t.ncficial to the CMA.'~
During this time, Hwy l~adlost confidence in the journal's oven~ghtconlrnltrcx
and asked an ad hoc committee to review these events.25s26 The ad hoc committee
faulted the editors for modifying the news story on Plan B before it was published
and for failing to follow the appropriate channel for conflicts (ie, the journal's
oversight ~ommittee).~' However, the ad hoc committee found more serious fault
with the CMA for "blatant interference with the publication of a legitimate report" and
concluded that the " M J ' s editorial autonomy is to an important degree illusory."41
Following the abrupt dismissals of Hoey and Todkill, the remaining editors, led
by acting editor Stephen Choi, MD, published an editorial in protest of the firings.46
Choi and colleagues drafted a proposal that included editorial independence for the
CMAJand aimed to ensure that the CMA and the publisher would not make decisions
about editorial content.25The CMA did not agree to the proposal, and Choi and
another editor reslgned." Otller eclitors and most of the editorial board also re-
signed, and there were calls from academic leaders not to send papers or serve as
peer reviewers for the The journal's former editor in chief, Bruce P.
Squires, MD,was asked to serve as acting editor, but under pressure from editors of
other journals, he too w.u unable to .serve unless the CMA would agree to the
journal's editorial independence.j5
Like the events at JAMA and the New EnglandJournal of Medicine, the abrupt
firing of M J ' s editors and the refusal of the CMA to recognize the journal's editorial
independence resulted in widespread news coverage of the conflicts, and a number
of other leading journals published articles in support of the editors.^^'^^'^^'^^ In
the wake of such criticism, in March 2006 the CMA announced the establishment of
a panel to assess the journal's governance and management and agreed to an interim
plan granting the editor in chief total responsibility for editorial content. With this
plan in place, Noni MacDonald, MD, agreed to serve as interim editor and Squires
agreed to serve as editor emeritus. The CMAJ governance review panel released
its final report on July 14, 2006.~~ The report contained 25 recommendations, all
of which were accepted by the C M A . ~ ~The ' ~ recommendations included the fol-
lowing:
re Assurance that the editor in chief would have editorial independence
B Amendment of the W J ' s mission statement to enshrine the "principle of edi-
torial integrity, independent of any special interests"
Confirmation that the CMA has no right to alter any editorial content, but should
.be given the same advance notice of potentially controversial content that is given
to the news media (see also 5.13.3,Release of Information to the Public and
Journal/Author Relations With the News Media, Embargo)
s Proposal that the CMA take back direct ownership of the G"/LAJ from its for-profit
holding conlpany
*: Proposal that the CMAjeditor in chief have separate and discrete reporting struc-
tures for editorial and business matters (ie, the editor in chief has access to the
ChlA Board of Directors if needed to defend or explain editorial positions or other
concerns that cannot be resolved through administrative mechanisms such as the
journal's oversight committee; and the editor in chief reports directly to an officer
 5.10.2 Ensuring a Trust Relationship Between Journal Editors, Publishers and Owners

of the CMA rather than to the publisher about the journal's business matters, and
the publisher reports to the same officer)
I
! a A recommendation for a reconstituted journal oversight committee that permits it
to more effectively help resolve potential disputes between the journal's owner,
publisher, and editor in chief
For more details on the makeup and responsibilities of the CMAJ's oversight conl-
mittee and the panel's other recommendations, see the CMA/ Governance Review
Panel's final report.44In January 2007, Paul C. ~ 6 b e iMD,
, was appointed editor in
chief of the mJ with assurance of the journal's independence as outlined in the
CjiMAJ Governance Review Panel's report.53

Ensuring a Trust elations ship Between Journal Editors, publishers, and Owners.
As describedby ~ a v i eand s ~ennie,6 the relationship between editors and publishers/
owners is interdependent and must be based on mutual trust. However, there are
bound to be uncertainties, concerns, and oc&ional conflicts that could threaten the
trust relationship! To maintain trust,,a formal agreementbetween the editor and
o-er-should specify each party's expectations and the mission of the journal (for
example, keJAMAns govemance and Key and Critical objectivess4 repro- ,
duced in Box 2). If these expectations are not formalized in a. govemance plan or
other document, are not mutually understood, or are intentionally disregarded (as
, happened in the cases described above), either party (but usually the owner) "may
seek new (and possibly costly) mechanisms .of accountabiity, reassurance, and con-
trol," which would result in loss of trust and potentially serious damage to the
integrity, credibility, and reputation of both the journal and the owner.
Uncertainty, concern, and disputes are best resolved informally through re-
ciprocally open communication between the editor and publisher/owner and by
maintaining a trust relationship. However, formal procedures for conflict resolution
must be in place in the event that a dispute cannot be resolved informally! These
, procedures should rely on the journal's mission and objectives to direct the assess-
ment of the dispute, should require measured consideration of the facts involved
(with appropiate evidence), and s.r~ot~ld not result in hasty decisions that do not
consider the outcomes of such decisions for the editor, ownkr, and journal (see, for
example, JAM'S governance plan). In the cases described in the previous section,
the continued existence of each journal was suddenly and severely put at risk be-
cause there was no effective, independent mechanism to help achieve resolution of
conflict, or, if resolution proved impossible, allow time for an orderly and dignifiecl
change of editors. Such an orderly system and buffer and, if all else fails, such
an orderly transition best serves the interests of journals, owners, publishers. ancl
editors!
The following recommendations, many of which are supported by the lntkr-
national Committee of Medical Journal ~ d i t o r sWorld
, ~ ~ Association of Medical I'd-
it or^,^' Council of Science ~ditors,~' and UK Comnlittee on Publication ~tliics,~.!
may help editors, publishers. and owners develop policies for maintaining etlitori:ll
freedom for their publications. Such policies should Ix. rc.gul;lrlg reviewcrl ;lncl m:~tlc.
publicly available to the extent possible. For example. an individu;rl editor's contl;Ic.t
would ncfi k made public, bur 3 genec~ldescription of the ediror's level o f ;~urIiority.
msponsihiljty. and ~cwuntahilityc l n Ix. pt11,lishc~tl;llong \ritl~t11c ~ n l r l i ; ~ l ' ?1l1is5io11
;

253
 . -. -
5.10 Editorial Freedom and Integrity

Box 2. JAMA's Key and Critical objectives"

Key Objective
To promote the science and an of medicine and the betterment of the public
health.
Critical objectives

1,To maintain the highest standards of editorial integrity independent of any

special interests
2. To publish original, important, welldocumented, peer-reviewed articles on
a diverse range of medical topics
3. To provide physicians with continuing education in basic and clinical
science to support informed clinical decisions
4. To enable physicians to remain informed in multiple areas of medicine,
including developments in fields other than their own
5. To improve health and health care internationallyby elevating the quality of
medical care, disease prevention, and research
6. To foster responsible and balanced debate on issues that affect medicine
and health care
7. To anticipate important issues and trends in medicine and health care
8. To inform readers about nonclinical aspects of medicine and public health,
including the political, philosophic, ethical, legal, environmental,
economic, historical, and cultural
9. To recognize that, in addition to these specific objectives, the journal has a
social responsibility to improve the totd human condition and to promote
the integrity of science
10. To achieve the highest level of ethical medipl journalism and to produce a
publication that is timely, credible, and enjoyable to read

in an editorial, on the journal's masthead, or elsewhere (eg, see the governance plans
forJ A M A and ~ ~the~ C~M~A J ~ ~
These
) . recommendations are offered to help joumals
protect agsinst threats to editorial freedom and integrity, but even if all of these
recommendations are followed, they will not provide absolute immunity from such
threats.
I
Complete editorial freedom is recommended for all peer-reviewed biomedical
I
joumals because it ensures the highest level of editorial quality, credibility, and in-
tegrity. However, it is recognized that not all journals operate under complete editorial
I
freedom, and achieving all of the elements necessary for complete independence
may not be possible or desirable for some journals. Thus, these recommendations are ,
provided for peer-reviewed journals with complete editorial freedom (highly pre-
ferred) and those journals with limited editorial freedom.
!

6 The editoi should have a written contract or job description that clearly defines \,
the editor's duties, rights, level of authority, responsibility, accountability, term . :
of appointment, relationship to the publication's owner, reporting relationship,
 5.10.2 Ensuring a Trust Relationship B h n Journal Editors, Publishers, and Owners

oversight and governance plan, objective criteria for evaluating the performance
of the editor and journal, rights if removed from the position before term ex-
piration, and procedures for conflict resolution. An explicit and mutually accepted
definition of the editor's authority, responsibility, and accountability before the
editor accepts the position will enable the ,editor to make an informed decision
about accepting the position. Editors should carefully consider the ramifications
of signing any nondisclosure agreements that would prevent them from speaking
publicly if unwillingly removed from their positions.
H A:governance plan should be in place that defines oversight and evaluation pol-
icies and procedures-for the editor, conflict resolution mechanisms for the editor
and owner of the journal, and the level of editorial freedom provided the edi-
tor and the journal. This plan should be published or otherwise made pi~blicly
available.
H Ideally, as in journals with complete editorial freedom, the editor should have
direct access to the highest level of management in the organization or company
that owns the publication. If this is not possible, as in journals with limited edi-
torial freedom, the editor's line of authority and reporting relationship should I x
specified in a formal agreement.
w All journals should have a published and easily accessible mission statement that
clearly defines the journal's goals and objectives; for journals with editorial freedom,
the mission statement should include explicit reference to editorial freedom. The
mission statement should serve as guide for the editorial direction of the journal and
should be relied on by the editor, editorial board, and members of the oversight or
governance body when conflicts or disputes arise; it should be reviewed regularly
by the editor and editorial board.
H An independent editorial oversight committee may help the editor establish and
maintain the specified level of editorial freedom and resolve conflicts. To be
independent, this committee's chair should not be a representative of the owner's
employed, appointed, or elected leadership, and representation of the owner's eni-
ployed, appointed, or elected leadership on the oversight committee should be
limited (ideally to a single individual), or at most should have fewer voting po-
sitions on the committee than would constitute a majority. While this may require
a dierent appointment procedure for some societies, the importance of an in-
dependent oversight committee for helping to maintain the journal's integrity and
manage contentious conflicts cannot be overstated. Note: An oversight committee
d i e m from, an editorial board, which serves to advise the editor on editorial
content and policies (see 5.11.10, Editorial Responsibilities, Roles, Procedures,
and Policies, Role of the Editorial Board).
In journals with complete editorial freedom, editors should have complete authority
to hire, evaluate, and dismiss all editorial staff as well as the authority to appoint,
evaluate,and dismiss editorialboard memlxrs and peer reviewers (see 5.11, Editori:~l
Responsibilities,Roles, Procedures, and Policies). If this arrangement is not possible
for all editorial staff (eg, manuscript editors or other editbrial staff employed, pro-
vided, or outsourced by the publisher), editors should at a minimum Ix able to
review and evaluate their performance. For journals with limited editorial fwc~lo~ii
in which the owner may make recommendations ;11~)ut cclitorial Iw);~rilrilc.mlxc.rsor
5.10 Editorial Freedom and Integrity

peer reviewers, the editor should have final authority to approve their appointment,
evaluate their performance, and terminate their appointment.
n The editor should have the opportunity to interview and comment on candidates for
a new publisher being considered during the editor's term. The publisher should
have the opportunity to interview and comment on candidatesfor a new editor being
considered by the journal owner and/or search committee. For society-owned
journals using outside publishers, editors should be involved in the selection and
performance review of the publisher and other external commercial companies or
vendors (eg, advertising, marketing, and research agencies; printers; suppliers of
editorial systems; and online vendors/hosts) as well as decisions to renew or ter-
minate publishing agreements.
In journals with complete editorial freedom, editors should have complete au-
thority over use and reuse of the name, logo, and content of the jouryial in print,
. online, and other media. Content includes editorial content, covers, mastheads,,
design, formatting, online features and linking, and approval of advertising and
sponsorship. While the editor must not be involved in the business (ie, selling) of
advertisements and sponsorship, the editor should have authority over policies
on appropriate types of advertisements and their placement and over policies on
sponsorship activities (see also 5.12, Advertisements, Advertorials, Sponsorship,
Supplements, Reprints, and E-prints). At a minimum, for journals with limited.
editorial freedom, the editor's level of authority and responsib'llty for content
should be specified in a governance plan, contqct, or other formal document.
Owners and publishers should not interfere in the evaluation, review, selection,
or editing of editorial content that is under the authority of the editor. For journals
with complete editorial freedom, this 'pertains to all content. All changes and
corrections made to content during production and publishing and after pub-
lication should be reviewed and approved by the editor or the editorial team
reporting to the editor and production staff involved in producing the content, but
not the journal's owner, publisher, or sales and marketing staff.
Editors and owners should establish mutually understood policies and proce-
dures that guard against the influence of external commercial and political inter-
ests as well as personal self-interest on editorial decisions (see also 5.5, Conflicts
of Interest).
Editors should be accountable for their editorial decisions, which should be based
on the validity and credibility of the content and its relevance and importance to
readers, not the commercial success of the journal or political interests of owners
or other groups. Editors' decisions and communicationswith stakeholders should
be based on competence, fairness, confidentiality, expeditiousness, and courtesy
(see also 5.11, Editorial Responsibilities, Roles, Procedures, and Policies). How-
ever, editors need to understand the requirements for financial management and
viability of their journals and should publish content that attracts readers, authors,
peer reviewers, subscribers, advertisers, and other stakeholders. Note: This does
not mean that stakeholders should determine specific editorial content to publish
or not to publish. For journals to maintain editorial freedom and integrity, editors
should be free to express critical but responsible views without fear of retribution,
i. 5.10.2 Ensuring a Trust Relationship Between Journal Editors, Publishers, and Owners

\
5
even if these views are controversial or conflict with the commercial goals of the
1
publisher or the policies, positions, or objectives of the owner or external forces.
For journals with complete editorial freedom, the journal should publish a state-
ment about its editorial independence and a prominently placed disclaimer that
identifies and separates a publication's owner and sponsor from the editorial staff
and content. For example, JAMA regularly publishes its objectivd3 (which in-
clude "to maintain the highest standards of editorial integrity independent of any
special interestsn) and a statement that it is editorially independent of its owner
and publisher, and 2 disclaimers that differentiate the journal from its owner. The
following appears in the Table of Contents of each issue:
All articles published, &cluding editorials, letters, and book reviews, rep-
resent the opinions of the authors and do not reflect the official po!icy of the
American Medical Assodation or the institutions with which the author is
affiliated, unless this is clearly specified.
In addition, the following notice appears on the editorial opinion page:
Editorials represent the ophions .of the authors and J A M and not those of
the American Medical Association.
For journals that have limited or no editorial authority over specific types or sec-
tions of content (eg, pages reserved for the owning society/association or other
content stipulated to be out of the editor's control), authority and responsibility for
such content should be made clear to readers.
m Owners have the right to hire and fire editors. However, except for provisions
contractually stipulated (eg, term Limits or contract expiration), owners should di-
miss editors only for substantial reasons that are incompatible with a position of
trust, such as editorial mismanagement, scientific misconduct, fiscal malfeasance,
undisclosedconflictsof interestthat result in biased editorial decisions, unhpported
changes to the long-term editorial direction or stated mission of the journal, criminal
behavior, or specific activities that violate terms of a formal agreement.
Editors should inform editorial board members, advisory committee members,
owners, publishers, and editorial and publishing staff of the journal's policies on
editorial freedom.
Editors should publish articles on editorial freedom when appropriate and should
alert readers a?d the wider international community to major transgressions
against editorial freedom.

ACKNOWLEDGMENTS
Principal author: Annette Flanagin, RN, MA
I thank the following for reviewing and providing substantial comments to im-
prove the manuscript: Catherine D. DeAngelis, MD, MPH, JAMA and Archives
Journals; John Hoey, MD; and Drummond Rennie, MD,JAMA; and the following for
reviewing and providing minor comments: Michael Callaham, MD, University of
California, San Francisco; Tem S. Carter, Archiway of Surgery; Wayne G. Hoppe, JD,
JAMA and ~rcbives Journals; Trevor Lane, MA, Dl'hil, University of Hong Kong; and
June Robinson, MD, Archim of Dcrmatok~gy.
5.10 t d ~ t o r ~ a
Freedom
l and Integr~ty

REFERENCES
1. 11.1u)ni; \ J I ~ I I I I L II ~ I / / K I X ~MIL-!^ 12. Iune 12. 1776.
2. . l i c ~ r n t r r ~ r - \ l t ~ l0~1r1 tL~l rr~ t . . ~ ~ ~ t ~ . / / u u w . m
Accessed
- ~ v . ~February
. 26, 2006.
3. Thc US Consrirution Online. htrp://ww.u.sconstitution.net/const.ht~l.
Accessed Fc.l)ru;~r)26. 2006.
;tnrl ctwrcion. In: Reich TW, ed. Encyclopedia of
4. F.dw:~rds1t11. Erclc. EL. I:reedo~i~
Biwthics. \'ol 2. New York, NY: Macmillan Publishing Co; 1995:883.
j. Reporters Without Borders. Worldwide Press Freedom Index.
http://www.rsf.org/rubrique.pl~p3?iddrubrique=54. Accessed February 26, 2006.
6. Davies HTO, Hennic D. Independence, governance, and ws; redefining the re-
lationship between jAMA and the AMA. J A M . 1=,281(24):2344-2346.
7. Davis RM,Mullner M. Editorial independence at medical journals owned by profes-
sional associations: a survey of editors. Sci Eng Ethics. 2002;8(4):513-528.
8. Death of a journaI. Lancel. 1987;2(8573):1442.
9. O'Brien E. Closure of the Irish Medical Journal. 11 MedJ 1987;80(5):247-248.
10. Goldsmith MF. George D. Lundberg ousted as JAMA editor. JAMA. 1939,281(5):403.
11. Tanne JH. J A M ' S editor fired over sex article. BMJ. 1999,318(7178):213.
12. ~ m i R.h The firing of brother George. w.
11939,318(7178):210.
13. Horton R. The sacking of J M . Lancet. 1999;353(9149):252-253.
14. Davidoff F. The making and unmaking of a journal. Ann Intern Med. 1999;130(9):
774-775.
15. Kassirer JP. Editorial independence. N Engl J Med. 1999,%O(21):1671-1672.
16.JM Editors, AMA Archives Journals Editors, J A M Editorial Board Members. JAMA
and editorial independence. JAM. 1999;281(5):460.
17. Horton R. An unwilling exit from the mJM. Luncet. 1999;354@176):358.
18. Kassirer JP. Goodbye, for now. NEngl JMed. 11999,341(9):686.
19. Kassirer JP. The departure of Jerome P. W i r e r . N Engl JMed. 1999;341(17):1313.
20. Angel1 M. The Journal and its owner--resolving the crisis. N ~ nJ ~~ e ld1999, .
341(10):752.
21. Bloom FE. Scruples or squabbles? Science. lW,285W31):1207.
22. Sacking of OMAJ editors is deeply troubling. Lancet. 2006;367@512):704.
23. Spurgeon D. Owner fails to guarantee editorial independence. BMJ. 2006;332(7541):
565.
24. Spurgeon D. CMA draws criticism for sacking editors. w.
22006;332(7540):503.
2j.Shuchman M, Redelmeier DA. Politics and independence--the collapse of the
Catzadiaiz Medical Association Journal. N Engl J Med. 2006;354(13):1337-1339.
26. Hoey J. Editorial independence and the Canadian Medical Association Journal.
N Engl J Med. 2006;354(19)1982-1383.
27. The gold-headed cane. BMJ. 1956;1(4970):791-793.
28. Booth CC. The British Medical journal and the twentieth-century consultant. In: By-
nun1 \ , , Lock S, Porter R, eds. Medical Journals and Medical Knowledge. New York,
NY:Routledge Chapman Hall Inc; 1992:259-260.
29. International Committee of Medical Journal Editors. Uniform Requirements for
Manuscripts Submitted to Biomedical Journals. http://www.icmje.org. Updated Feb-
ruary 2006. ~ccessedFebruary 26, 2006.
30. World Association of Medical Editors. The relationship between journal editors-
in-chief and owners (formerly titled Editorial independence). http://nww.wame.org
I '
5.10.2 Ensuring a Trust.Relationship Between Journal Editors, Publishers, and Owners
!

/resources/policies#independence.Modified version posted May 15,2006. Accessed

January 5, 2007.
31. Council of Science Editors. Relations between editors and publishers, sponsoring
societies, or journal owners. h t t p : / / w w w . c o u n c i l s c i e n c e e d i t o r s . o r g / ~ s
/white-paper.cfm. Accessed January 5, 2007.
32.Committee on Publication Ethics. A code of conduct for editors of biomedical
journals. http://www.publicationethics.org.uk/guideliies/ce. Accessed February
26,2006.
33. Smith R. Editorial independence and the BMJ. m J . .2004;329(7205):272.
34. Lundberg GD. Goals for THEJOURNAL. JM.1982;248(5):553.
35. Lundberg GD. House of Delegates reaffirms editorial independence for AMA's
scientific journals. JAMA. 1993;270(10):1248-1249.
36. Kassirer J. Should medical journals try to influence political debates? N Engl J Med.
1999;340(6):466-467.
37. Rosenberg RN, Anderson ER Jr. Editorial governance of the Journal of the American
Medical Association: a report. JAMA. 1999,281(23):2239-2240.
38. Editorial governance for JAMA.JAMA 1999,281(23):2240-2242.
39. DeAnge1'i CD, Maves MD. Update of the Editorial Governance Pi- for JAMA. JAMA.
2004;291(1):109.
40.Johanna..I N m Engkmd Journal of Medicine appoints Drazen as editor in chief. Wall
Street Journal. May 12,2000;l.
41. W i r e r JP,Davidoff F, O'Hara K, Redelmeier DA. Editorial autonomy of CMAJ. mJ.
2006;174(n945-950.
42.Armstrong PW, Cashman NR, Cook DJ, et al. A letter frdm -J's editorial bbard to
the CMA. CUA]. 2~2;167(11):1230.
43. Kuehn BM. M J governance overhauled: fi*gs, resigkons, compromised
independence cited. J M . 2006;296(11):1337-1338.
44. M J Governance Review Panel: final report. http://www.cmaj.ca/pdfs
/C;overnanceReviewPanel.pdf. July 14, 2006.Accessed Januay 5,2007.
45.The editorial autonomy of CMA/[published online ahead of prht Decemkr 12,20051.
M J . 2006;174(1):9. doi:10.1593/anaj.051608.
46. Choi S, Flegel K, Kendall C. A catalyst for change. WJ.22006;174(n901, 903
47. Spurgeon D. Most of mJeditorial board resigns. BMJ. 22006;332:687.
48.Webster P. Canadian researchers respond to CMAj crisis. Luncet. 2006:367(9517):
1133-1134.
49. Ncayiyana DJ. Journal ownership versus editorial independence tug-0'-war. SA/r. ,lid
J. 2006;96(6):470-471.
50. CI.IAJ. W J a n d editorial autonomy. WJ. 2006;175(4):339.
51.MacDonald h, Squires B, Hawkins D. Editorial independence for GIIAJ:signposts
along the road. CMAJ. 2006;175(5):453. . -
52.Sullivan P.CMA accepts all recommendations from panel reviewing CMAJ's structure.
http://www.cma.ca/index.cfm?ci~id/=10035293&la~id=I. July 14,2006. Accessed
October 14, 2006.
53.HCbert PC. A new year and new opportunities. C'MAJ. 2007;176(1):9.
54.JA,%I's key and critical objectives. http://jama.arna-assn.org/misc/al.outjan~~.dtl.
~ c c e s w dMarch 11, 2006.
5.1 1 Ed~torlalRerponstbtltt~er.Roles. Procedure. and Policler

IDc./rc.iu. rbc~cdlror u rht~pnmaty source for c ~ b ~ c u l

1vsp01~srbili1-y atjlotlg pmjkssiotlal publicalrota.
George D. Lundberg, MD'

Editorial Responsibilities, Roles, Procedures, and Policies. Coupled with the

I
autonomy and authority that come with editorial freedom are responsibility and
accountability (see also 5.10, Editorial Freedom and ~ntegrity).~-' Editors are respon-
sible for determining the journal's content, ensuring the quality of the journal, dir-
i
ecting editorial staff and board members, developing and maintaining procedures,
and creating and enforcing policies that allow the publication to meet its mission and iI
goals effectively, efficiently, and ethically and in a fiscally responsible
This section focuses primarily on decision-making editors (ie, editors in chief and
other edito~s,such as deputy, associate, assistant, contributing, section, and guest
editors) who make decisionsto review, reject, request revision of, and accept content
for publication.

The Editol's Responsibilities. An editor's primary responsibilities are to inform and

educate readers and to maintain the quality and integrity of the journal.53 Thus, editors
are obliged to make rational and consistent editorial decisions, select papers for pub- i
lication that are appropriate for their readers, ensure that the content of their journal /
is of high quality, and maintain standards to ensure the journal's integri$3S10 (see :.-a,
also 5.10, Editorial Freedom and Integrity). The editor's duty to readers often out-
weighs obligations to others with vested interest in the publication and may require i
actions that may not appear fair or suitable to authors, reviewers, owners, publishers, .t I

1.
advertisers, or other stakeholders.
Editors' roles may be major public positions with broad, ethically based, pro-
fessional and social responsibility (eg, editors in chief of major medical or scientific
journals),247.8 whereas other editors' responsibilities are more limited (eg, other !
decision-making editors), more focused-(eg, assistant editors or section editors), or I
i I
procedural or technical (eg, manuscript editors, managing editors, production edi-
tors). These responsibilities, regardless of their scope, should be clearly delineated in I'
i
the editor's position description and supported by the publication's editorial mission
statement (see 5.10, Editorial Freedom and Integrity).
. '!
i
~ i s h o ~ , organ,"
" ' ~ identified 5 additional requisites of an edi-
and ~ i i s have
tor: competence, fairness, conlidentiallty,expeditiousness, and courtesy (described in I

greater detail below). I

Competence. Editors must possess a general scientific knowledge of the fields cov-
ered in their publications and be skilled in the arts of writing, editing, critical
assessment, negotiation, and diplomacy. In addition, editors should consider join-
ing professional societies in theit respective scientific fields as well as professional
organizations for editors (eg, Council of Science Editors, European Association of
Science Editors, World Association of Medical Editors, American Medical Writers
Association, European Medical Writers Association [see 25.11, Resources, Profes-
'
sional Scientific Writing, Editing, and Communications Organizations and Groups]).
These societies have Web sites, and publications, policjr statements and other re-
sources, conferences. and courses and workshops for new editors. Editors who
 5.1 1.1 The Editofs Responribilitier

publish original research, or reviews or interpretationsof research, should be fami1i;lr

with the scientific methods used, including the general principles of statistics."
Editors should also rely on the expertise of others (eg, editorial board members. peer
reviewers, statistical consultants, legal advisers) for advice and guidance, with the
recognition that the editor has the ultimate authority for all editorial decisions. A
competent editor will make rational editorial decisions, within a reasonable period of
time, and communicate these decisions to authors in a clear and consistent man-
ner. '48' ' A competent editor (whether editor in chief or manuscript editor) will
also be skilled in the art of rhetcric13 to recognize the tools of linguistic persuasion
and identify and remove hyperbole, inconsistent arguments, and unsupported as-
sertions and conclusions from manuscripts. Finally, as ~ i s h o ~suggests,
" a sense of
humor should not be regarded as a trivial characteristic for an editor, as a bit of
humor can often avoid, or at least soften, potential conflicts between editors and
authors, reviewers, owners, publishers, other stakeholders, and other editors.

Fairness. Editors must act impartially and h ~ n e s t l ~ Because

. ~ . ~ . ~editors
~ are human,
they cannot avoid the influence of all biases. Using peer review and consulting other
editors during the editorial process may help control some personal biases? Editors
of peer-reviewed journals a& responsible for maintaining the integrity of the peer
review process, for developing policies regarding the peer review process, and for
ensuring that editorialstaff are properly trained in the procedures Editors
should document factors relevant to editorial decisions and maintain records of
decisions and reviewers' recommendations and comments for a defined period so
they will be prepared to deal with appeals or complaints. (See also "Record Retention
Policies for Journalsn in 5.6.1, Intellectual Property: Ownership, Access, Rights, and
Management, Ownership and Conuol of Data.) .

Appeals. Journals should develop and maintain policies for handling appeals of de-
cisi~ns.?.~The Luncet has published a useful review of its appeals policy and pro-
cedures.14In 1996,the Luncet established an independent editorial ombudsman who
is assigned to review unresolved allegdons of editorial mi~mana~ement.'~ This in-
dividual may also be called on to handle appeals of editorial decisions not considered
satisfactorily resolved by the journal's initial response. The ombudsman publishes
annual reports summarizing these disputcs and their rcsolutions.'~nresolving dis-
putes, editors should consider all sides of an issue and avoid favoritism toward friends
and colleagues or allowing editorial decisions to be influenced by powerful or
threatening external forces (see 5.10, Editorial Freedom and Integrity). Note: Editors
and journals shoujd not keep copies of rejected manuscripts for longer than. neces-
sary to deal with appropriate appeals of decisions, and journals should have record- ;
retention policies to direct how long decision letters and reviewer recommendations
and comments should be kept (see also "Record Retention Policies for Journals" in
5.6.1, Intellectual Property: Ownership, Access, Rights, and Management, Ownership
and Control of Data, and 5.11.5, Editorial Responsibility for Rejection).

Conflicts of Interest Editors should not have financial interests in any entity that
(.see 5.5, Conflicts of Interest).
might influence editorial evaluations and deci~ions'.~-~
Editors with other types of conflicts of interest with a specific manuscript or author
that could impair objective decision making should recuse themselves from in-
volvement with such papers and should delegate rcqxx-isihility of the review and
I
 --
5.1 1 Editorial ~esponsibilities,Roles, Procedures, and Policies

. .
decision of such papers to another editor or editorial board member.23For example,
the Archives of General Psychiatry does not permit an editor who collaborates with
an author or who is employed by the same institution as an author to make decisions
about that author's manuscript; the review and decision-making authority is dele-
gated to an editorial board member without such a relationship.'' Some journals will
not consider manuscripts from authors who also serve as editors for the journal
(clearly, this does not apply to editorials). Other journals will consider such sub-
missions, but reviews of and decisions about manuscripts for which an editor is an
author or coauthor are managed independentlyby another editor who has complete
. decision-making authority (including the ability to reject a manuscript in which the
editor in chief is an author). For example, the Archives of Pediatrics C Adolescent
Medicine delegates the review and decision of such papers to an associate editor and I

an editorial board member,'' and the N w England Journal of Medicine has an

independent editor at large who is assigned to handle all original research papers
that are submitted by editors.19
I
Confidentiality. Editors must ensure that information about a submitted manuscript is
not discIosed to anyone outside the editorial office, other than the peer reviewers and
authors invited to write an editorialcommentingon an accepted but not yet published
manuscript (see 5.7, ~onfidentialit~).~'~ Editors should create and maintain policies
about confidentiality and ensure that all current and new staff (editorial and pro-
duction), reviewers, and editorial board members are sufliaently educated about the
,
1
I
I

journal's principles of confidentiality. The following statement may be useful when . ,

handling inquiries abouf manuscripts under consideration or previously rejected:
We can neither confirm nor deny the existence of any manuscript unless and
until such manuscript is published.
Editors should also establish policies and procedures to handle breaches of con-
fidentiality by authors, .peer reviewers, and editorial staff (see 5.7, Confidentiality).

Expeditiousness. Although the length of time it takes to evaluate a manuscript de-

pends on many factors (eg, number of submitted manuscripts, resources of the
editorial office, time allocated for peer review, and availabilityof efficient submission
*
and review systems, such as Web-based systems), an author has a right to expect to
receive a decision within a reasonable ~ournalsshould publish an audit or
otherwise make available to prospective authors turnaround times for manuscript
decisions, peer review, and publication.2 See, for example, the annual audit pub-
lished by JAMA" and 5.11.12, Editorial Audits and Research. If the review and eval-
uation are delayed significantly beyond the journal's standard turnaround times for
any reason, notifying the author of the reason for the delay is appropriate. Authors
have a right to contact the editorial office to inquire about the status of their manu-
scripts. Many journals that use Web-based manuscript submission and review systems
offer authors the opportunity to ;heck the progress of their submission online.
Editors should plan to accept papers with knowledge of the number of accepted
manuscripts awaiting publication, the approximate number of pages and/or articles
that can be published during a year, and the resources available to publish additional
I
material online, if applicable. ~ o r ~ a nhas " commented that a journal that accepts
more p:ipers than it can publish within the time span observed by other journals in
1l1c wine field 15 suppressing, not disseminating, information.
 5.1 1.3 Editorial Responsibility for Manuscript Assessment

On occasion, an editor will receive a request from ;In author or a suggestion from
a reviewer to expedite publication of a specific manuscript. The quickened pace of
scientific discovery and heightened competition among scientists and journals have
fostered an increase in requests for rapid review and publication, and technologic
advances have facilitated the ability to do so." A number of journals have proce-
dures for fast-track consideration. For example,JAMA has a procedure for expedited
peer review and editorial considerationof manuscripts of high-quality evidence (usu-
ally randomized controlled trials) that have immediate clinical and/or public health
importance." Some biomedical journals routinely publish accepted papers online
ahead of print publication. Such online ahead of print publication should include
appropriate procedures for editorial review, editing, and proofing before posting, as
well as for proper identification of any versions (eg, online ahead of print version vs
print version). This is especially important for journals that publish information that
can affect clinical decisions and patient care. For journals that d o not routinely
publish all content online ahead of print, a policy should be developed to allow for
rapid considemtion and early online publication of appropriate accepted manu-
scripts (eg, those with important and urgent implications for public health) that does
not compromise the peer-review and editorial decision processes or the integrity of
the journal and that does not result in the premature publication of an incomplete or
inaccurate article (see also 5.13, Release of Information to the Public and Journal/
Author Relations With the News Media).

Courtesy. ore than a mere extension of etiquette and convention, editorial po-
liteness requires editors and all editorial staff to deal with authors and reviewers in a
respectful, fair, professional, and courteous Diplomacy, tact, empathy,
and negotiation skills will help editors maintain positive relationships with'authors,
even those whose work the editor rejects.
Note: Sections5.11.2 through 5.11.7 focus on the editor's responsibilityfor manuscript
processing, assessment, and decisions (see also 6.0, Editorial Assessfpent and Pro-
cessing).

Acknowledging Manuscript Receipt .Journals should send a notice to authors to

acknowledge receipt of their manuscripts and provide names and contact infornia-
tion of relevant editorial staff. For journals with Web-lx~sedlllnnuscript sul~mission
systems, acknowledgment letters may be sent automatically, usually after an author
has viewed the submission and confirined that it is complete.

Editorial ~esponsibilityfor Manuscript Assessment. The editor should cst;~l>lish

;tnrl
maintain procedures and policies for appropriate editorial assessment and rlecisions
to accept, request revision of, and reject mansucripts (see also 6.0, Editorial ~ss;ss-
ment and processing)? The editor also establishes whether such decisions \\.ill I>c.
made unilaterally or by other editors (eg deputy, associate. assist:~nt.conlril>ur-
ing, section, or guest editor) or in collaboration. klctors i~sctlto dcternlinc rlcc.isic 1114
should be made available to authors and reviewen. For ex;unple,JAIM cclitor3 [I\<.
the followinggeneral criteria to evaluate manuscripts: m;~teri;llis origin;~l.\vri~irjgi-
clear, study methods are appropriate, data are valid, conclusions an. rca.u~n;~l>lt.
and supported by the data, information is import;~nt,and topic h;~sgc-~lc.~.;~l I I ~ V ~. III C
interesteZ2Through instructions for autl~orsand rc\.ic\\'er for~ll*. .lA.~l:l ; I ~ I I I Ir\
~ I : I , I ~I

263
 --
5.1 1 Editorial Responsibilities, Roles, Procedures, and Policies

revicwcl.4arc inlormctl [hat thcsc lx~hiccriteria are used to assess a paper's ellgil~ility
for publication.
Depending on the nature of a journal's editorial resources and the number of
manuscripts received, the editor may rely on a triage system to evaluate all manu-
scripts before peer review. Not all manuscripts will be appropriate for the journal,
and after an initial assessment the editor may decide to reject some papers without
sending them for external peer review. For example,J A M editors reject more than
50% of the approximately 6000 major manuscripts received annually without ob- I
taining external peer review." In such cases, the editor's duty to provide a detailed I
review to the author of each paper is outweighed by the dutp to reviewers (by not I
i
requesting their time to review a manuscript that has no chance of publication), to I
owners (by not consuming resources needlessly), and to other authors who have 1
submitted papers to the joumal (by maintaining efficient processes) (see also 6.0,
Mitorial Assessment and Processing). In addition, the author may be best served by a
prompt notification of a decision indicating rejection if the manuscript is unlikely to
i
make it through the journal's review process and be considered for acceptance,
thereby allowing the author to submit the manuscript to another journal without
additional delay.
j
For manuscripts determined to be eligible for external review and additional
consideration, all components of the submission should receive proper review and
editorial assessment; this includes the manuscript text, tables, figures, and references, ,
as well as relevant supplementary materials, documents, and video and audio files.
- --y-
I
i
I
Editorial Responsibility for Peer Review. Decisions about manuscripts are made by '?
editors, not peer reviewers. Reviewers offer valuable advice, serve as consultants to
the editor, and may make recommendations about a paper's vitabiity for publica- I
tion, but all editorial decisions should be made by the editors. Editors are obliged to !
be courteous to peer reviewers, provide them with guidance and explicit instruct- i
ions, assign only those papers that are appropriate to specific reviewers (in terms of ;
reviewer expertise and interest), maintain confidentiality if using blind or anon-
ymous review, provide reviewers with sufficient time to conduct their review, and
avoid overworking them.'14 Editors should ask reviewers in advance whether they I .

are available for and interested in reviewing a specificminuscript, unless theyhave a I

prior agreement to assign manuscripts to reviewers without advanced consent. . ,
Many journals publish lists ofreviewers' names to acknowledge,credit, and thank
them publicly for their work. Some journals offer qualifying reviewers continuing
education credit, a letter of co~ilmer~dationthat can be shared with supervisorsor pro-
motion committees, or subscriptions to the journal. Pew journals offer financial
compensation to peer reviewers, except perhaps those who may review a substantial
number of papers or perform specialized reviews (eg, statistics). Editors should pro-
vide feedback to reviewers, such as notifying reviewers of the manuscript's final dis-
position, sharing copies of other reviewer comments of the same manuscript, and

'-
providing regular assessments df the quality of the reviewer's
Editors should not share a specific review of a manuscript with anyone outside
the editorial office, other than the authors and other reviewers, unless the journal
operates an open peer-review system that includes of reviewer recom- \
mendations and comments and reviewers are informed of this in advance. Editors \-
should develop a specific policy regarding who has access to copies of a review, and
this policy should be clearly communicated to all persons involved in the review

264 ,r '. ,

1,
 5.11.5 Editorial Responsibility for Rejection

i
i
process (see 6.0, Editorial Assessment and Processing, and 5.7.1, Confidentiality,
Confidentiality During Editorial Evaluation and Peer Review and After Publication).
Many joumals develop databases of reviewers, including their addresses and
affdiations, areas of expertise, turnaround. times, and quality ratings for each manu-
saipt review. Editors and publishers are obliged not to make secondary use of the
information in the database without the prior consent of the reviewers and shoukl
never exploit it for personal use, benefit, or profit (eg, selling a list of peer reviewers'
names and contact information for promotional purposes).
1
j Editorial Responsibilityfor Rejection. Rejecting manuscripts may be one of the il-ros~
important responsibilities of an editor. By rejecting papers appropriately, an editor
b sets standardsand defines the editorial content for the journal.'? Decisions to reject :I
manuscript may be based on a wide range of factors, such as lack of originality. 1;ick
of importance or relevance to the journal's readers, poor writing, flawed method.s.
scientificweakness,invalid dam, b i d interpretationsand/or conclusions, timeliness.
or the specif~cpublishing priorities of the j~urnal.~ A rejection letter must Ix cxrefiilly
worded to avoid offending the author and should express regret for the outcome. hit
also must not raise false hopes about the merits of an unsuitable paper. Many editors
avoid use of the word rejection in any letters, opting instead for phrases such as "\\re
are unable to accept" or "your paper is not acceptable for publication." However,
editors should be certain that the intent of a letter of rejection is clear. If the letter
scunds too much like a request for revision, the author may subsequently resubmit an
inwacably flawed manuscript; or worse, the author may resubmit a rejected tnanu-
script, essentially unchanged,with the hope that the editor will not notice."
An editor should determine on'a case-by-case basis whether a standard rejection
letter (form letter) or an individualized letter explaining the specificdeficiencies of the
I
manuscript should be sent to the author. Some editors argue that for a paper rejected
for "reasons of editorial choice (usually without outside editorial peer review), the
editor has no obligation to give the author any explanation beyond the statement that
the manuscript was not considered appropriate."8 Other editors suggest that all au-
thors be provided a specific reason for rejection of their manuscript.4 However, a
standardized (form) rejection letter that includes an explanation for rejection based
on editorial priority (especially for large journals that receive large numbers of sub-
missions and/or that have very low acceptance rates) or that is accompanied by
copies of detailed reviewer comments is sufficient for many papers that are rejected.
Editors should develop specific policies for the rejection process, including how
to handle p~eviouslyrejected manuscripts resubmitted with an appeal for reconsid-
eration (see also the "Appeals" section under "Fairness" in 5.11.1, The Editor's Re-
sponsibiiities).2~4If the author's appeal provides reasonable justification, the iditor
should carefully consider the appeal (see also 6.1.8, Editorial Assessment and Pro-
cessing, Editorial Assessment, Appealing a Rejection).
Once a common act of courtesy, the practice of returning all copies of rejected .
manuscripts has become obsolete. However, original illustrations, photographs,
slides, and other artwork should be returned if requested by the author, as should
any manuscripts an author specifically requests be returned. Because journals do not
own unpublished works (ie, copyright is typic;~llytr;tnsferred in the event of pul~li-
cation), journal offices should not keep print or electronic copies of rejected manu-
scripts for any ~eriodlonger than that required to deal with appeals of decisions. tliey
should be destroyed or deleted. See also "Record Retention I'olicics for Joirrn.ll\" 111
 ..

5.1 1 Ed~tor~al Rolcr. Procedure%,and Policies

Responwb~llt~cl.
I

I
5.6.1. O\vncrship and Control of Data, and 5.6.5, Copyright Assignment or License,
both in 5.6. Intellecrual Property: Ownership, Access, Rights, and Management.

Editorial Responsibility for .Revision. The editor's impartial focus on improving a

manuscript faciliates the process of revision. According to ~ o r ~ a n ,"in" letters re-
questing revision the editor should use an impersonal tone in criticizing." All such
communication is best if the tone is objective and constructive. Editors should clearly
communicate to authors what is expected in a revision; it may be helpful for editors
to request that authors submit revised. manuscripts with changes, additions, and
deletions indicated and a cover letter itemizing the changes made in response to the
editor's and reviewers' comments and suggestions.
Editors are obligated to use sound editorial reasoning in requesting a revision. .-
Editors must be skilled in arbitrating reviewer disagreements and reconciling contra- PI

dictory recommendations, which may result from reviewers having diverse back-
grounds, different expectations of the journal, and variable levels of expertise, ,
diligence, or interest in the subject of the manuscript." Authors object to receiving
inconsisient or contradictory comments from reviewers and editors and may object to ,
new and different criticisms of the revised manuscript submitted in response to the
initial review. Although editors can never be certain that new issues will not surface at
the time of resubmission, they are obliged to evaluate all reviewer comments, address
any inconsistencies or unreasonable criticisms, censor any inappropriate criticisms,
and guide authors in preparing their revisions.48 Editors who make decisons about - =
publication should never relegate themselves to the role of manuscript traffic con-
trollers by simply passing on reviewer comments without direction for the revision or
by permitting reviewers' recommendations to serve as the editor's decision.
Some editors feel uncomfortable asking an author to revise a manuscript if there
is a possibility that the revision will not be published. However, a revision may be
needed to permit an author to provide missing data or information or to more clearly 1
describe the study or work being reported so that the editor can properly evaluate
the manuscript. The revision may also =-pose an important weakness, limitation, or
flaw that was not apparent in the original submission and that necessitates a decision
to reject. Alternatively, a revision may introduce new issues or concerns or simply
may not be satisfactory. In each of these cases, the editor's responsibility to readers
outweighs any obligation to publish the author's revised manuscript. Edirors should
develop specific policies regarding requests for revisions, and the revision letter
should state explicitly whether the author should or should not expect publication of
a satisfactorily revised manuscript.4 For example, JAMA editors include language
similar to the following in their revision letters:
If you decide to revise your paper along these lines, there is no guarantee that
it will be accepted for publication. That decision will be based on our editorial
priorities at the time, the quality of your revision, and perhaps additional peer
review.
'
The rejection of a revised manuscript is probably best handled with a personal letter
tactfully explaining why the revision was not acceptable. Although editors may need ,
to ask for multiple revisions of a paper, such requests should include a detailed j
; ,
explanation to the authors. In most cases, these efforts serve to give the authors the II
best chance for their paper to reach a level of quality that is appropriate for accep-
tance and publication.
I ( . I
/
 5.1 1.7 Editorial Responsibility for Acceptance

Editorial Responsibility for Acceptance

Acceptance. Editors should follow consistent procedures to evaluate papers and make
decisions regarding acceptance (see 5.11.3, Editorial Responsibility for Manuscript
Assessment). Editors should inform authors of acceptance of their manuscripts in
a letter that describes the subsequent process of publication, including substantive
editing and any remaining queries, editing of the manuscript, tables, and figures for
accuracy, consistency, clarity, style, grammar, and formatting; and what material the
author will be expected to review and approve before publication. Editors may also
provide an approximatetimetable for the publication process. If authors are given an
expected date of publication, they should be informed of the likelihood of the date
changing. The acceptance letter should also remind authors of any policies regarding
duplicate publication, disclosure of conflicts of interest, and restrictions on prepub-
lication release of information to the public or the news media (see also 5.3, Duplicate
Publication; 5.5, Conflicts of Intetesc; and 5.13, Release of Information to the Public
and Joumal/Author Relations With the News Media).
Authors should avoid making substantial changes to the, manuscript after
acceptance, unless correcting an error, answering an editor's request for missing
information, responding to an editor's or a proofreader's query, or providing an
essential update. Likewise, editors should review manuscripts before acceptance and
avoid asking authors for substantial changes after final acceptance.
If circumstances (eg, an unanticipated decrease in the number of pages allotted
for publication or clustering of certain papers for a special issue) cause a delay in
publishing a n accepted manuscript beyond the typical time between acceptance
and publication, editors should inform the corresponding author of the reason for
the delay.
Editors should not reverse decisions to accept papers after the authors have been
notified unless serious problems are subsequently identified with the content of the
manuscript (eg, flawed methods, inconsistent or invalid data, allegations of mis-
conduct) or the author has failed to meet the journal's publication requirements (eg,
transfer of copyright, disclosure of duplicate submissions or publications, disclosure
of conflicts of intere~t).~An example of editorial discourtesy in handling accepted
manuscripts occurred when an editor "unaccepted" a paper that his journal had
accepted unconditionally 20 months earlier. The reason provided to the authors for
this change of decision was that the journal's inventory of accepted papers had
grown too large.23However, if a new editor inherits from the journal's previous
editor a large inventory of accepted manuscripts deemed outdated or inappropriate,
the new editor may have to find ways to deal with these papers appropriately. In
such a case, the editor may request a one-time or temporary increase in journal pages
from the publisher. If this is not a viable option, for financial or other reasons, the
editor may choose to contact the authors of accepted manuscripts that have not yet
been scheduled for publication and explain hat too many papers had been accepted
to be able to publish them in a reasonable period. The editor may offer the authors
options to withdraw their manuscript and send it to another joumal, reduce the
length of their manuscript to allow it and others to be published in the limited
number of pages allocated to the print journal, or publish their manuscript online
only. However, any decisions not to publish previously accepted papers should be
made carefully and pertups with the consultation of the journal's editorial board or
legal adviser.
5 . 1 1 Editorla1 Responslbillt~m.Roler, Procedurm, and Policlo

Provisional Acceptance. k ) m c editors will grmt authors a 'provisional acceptance,"

offering to publish thc~rpapers if ccrtlln conditions or minor requirements are met.
Sonlc journals use provisional or conditional acceptance for revision requests when
they are fairly certain that the revision will be accepted for publication. However, use
of a provisional acceptance as a request for revision can cause problems if the revised
manuscript is not suitable for publication. To avoid such problems, provisional ac-
ccpt:ulcc decision lcttcrs sl~ouldclearly communicate that acceptance is contingent
on specific conditions that are clearly described for the author. If a new editorial
policy requires a new condition for publication to be met by authors who submitted
,papers before the policy took effect, a provisional acceptance can be used to permit
.these papers to move forward without unnecessary delay.

Correspondence (Letters to the Editor). A biomedical journal should provide a fo-

.um for readers and authors to participate in postpublication peer review and sci-
entific dialogue and to exchange important information, especially with regard to
articles published in the journal?s3s24A common forum for such exchange is the
correspqndence, or letters to the editor, column (see also 1.6, Types of Articles, Cor-
respondence). Such letters become part of the published record and, like articles,
are indexed by bibliographic databases. In the correspondence column, joumal
readers have the opportunity to offer relevant comments, query authors, and provide
objective and scholarly criticism of published articles. Authors of articles to which t&e
letters pertain should always be given the opportunity to respond. Whenever pos-
sible, the letter author's comments and criticisms and the author's reply should be
published in the same issue to enable readers to evaluate the arguments presented. If
an author chooses not to submit a reply for publication, the journal may publish a
statement indicating that the author declined to comment. Follow-up or later work
that clarifies or amplifies a previous publication (other than a correction of an error or
omission or retraction of fraud) may also be considered for publication as a letter4
(see also, 5.11.9, Corrections [Errata], and 5.4, Scientific Misconduct)
Editors should establish policies and procedures .for processing and evaluating
letters just as they have done for handlixig manuscripts, and these should be pub-
lished in the journal's instructions for authors or as part of the regular correspon-
dence column. L i e authors of manuscripts, authors of letters are expected to follow
the same policies and procedures for authorship responsibility, disclosure of du-
plicate publication and submissions, disclosure -of conflicts of interest, copyright
or publication license transfer, research ethics, and protection of patients' rights to
privacy in publication.
Journals prefer to publish letters that objectively comment on or critically assess
previously published articles, offer scholarly opinion or commentary on journal
content or the journal itself, or include important announcements or other infor-
mation relevant to the journal's readers (although journals may have separate sec-
tions for announcements, meetings, and events). Letters that merely praise authors,
the editor, or the journal rarely provide any meaningful or useful information.
Likewise, ad horninem attacks should not be published?4 Some journals also publish
short reports (eg, less than 500 words) of original research, technical comments, or
novel case reports in the correspondence column. These reports should be handled
as regular manuscripts, with peer review and revision, as necessary.
Many journals set limits on the length of letters that will be considered for
publication (eg, 500 words or less and no more than 5 references). Some journals will
 5.1 1.8 Correspondence (Letten to the Editor)

publish small tables or figures in letters, space permitting. To maintain timeliness,

some journals also set a limit on the amount of time in which a letter sent in response
to a published article must be received. For example,J A M and the Archives Journals
generally allow readers 4 weeks to submit a letter in response to a published article.
Journals with time limits may allow exceptions for important letters that are sub-
mitted after the recommended deadline, especially for letters that identify important
errors. Journals with space and time limits have, been criticized for stifling post-
publication scientific exchangeand but such criticism does not recognize
'the resource limitations of journals and their editorial and production staff or the
practical concerns associated with gathering all relevant submitted letters on a spe-
dfic article and sending them to the author for a reply and publishing these in a
timely manner. Some journals have addressed this criticism by permitting online-only
correspondence to be posted without such restrictions on length and timeliness. In
1998,the BWbegan an experiment with an unrestricted policy for online-only letters
that included no limitations on length, h e l i n e s , or number of online po~tings.~' By
2002, the 20000 online letters represented one-third of the journal's total online
~ontent.~' After posting the 50000th online-only letter in 2005, the BMJ recognized
that the quality of some of these responses was low and commented that "the bores
are threatening to take over. Some respondents feel the urge to opine on any given
topic, and pile in early and often, despite having little of interest to say."mAs a result.
the BMJadded a maximum length requirement and raised the bar for acceptance o f
online-only letters for those that contribute "substantially to the topic ilnder dis-
cu~sion.~~~
Typically, a submitted letter undergoes an initial assessment, at which point it
may be rejected, revised, or accepted. Some letters may be sent for peer re\.ic.\v o r
accepted without external peer review. Letters on the same topic or in responsc t o
the same article should be grouped, sent to the author of the orfgiml article for reply
Ci necessary), and published in the same issue under one general title. Journals
should cross-reference, and reciprocally link online, the original article :lnd rc1:ltccl
letters to allow readers to identify and read the original articles and all rel:~tedlcttcrs.
Authors of letters accepted for publication should sign statements o f :~i~thorsl~ip
responsibility, financial disclosure, and copyright or publication license t::~n.sli.r.
Journals may edit accepted letters for content, length, cl;lrity. gr;lmm;lr. stylr*.;111tl
format. Authors should approve changes that alter the substance or tone of a Icttcr c )r
response.24
For joumals that publish rapid-response sections for online-only letters. these
postings should be reviewed to verify that they meet the journal's guidelines :ind
requiremefits for such postings, to determine that they contribute substantinlly to the
previous publication and/or the discussion under way, and to check for lilxl, krror.
and gratuitousness. If accepted, these postings require minimal editing. The A~rbirvs
of PediaMcs G Adolescent Medicine and other Archives Journals that puhlish onlinc-
only letters under a Readers Reply section include the following instructions'":
Instructions: Only replies that have not been published or posted elsewhere
should be submitted. Replies will be selected for posting by the editors:
those that are selected may be edited. By submitting this Readers Reply, ~ O L I
attest to being the sole author. You ~ ~ n . s fcopyright
cr to A\lA if your lleply is
posted on the JAMA 6 Arcbirps Journals Wch site. Indicate any financial
disclosures (eg, employment. mnst~ltanc~cs. honoraria, stock ownership or
5.1 1 Editorial Responsibilities. Roles, Procedures, and Policies

options, expert testimony, grants received, pdtenrs rrc.c~\.~-d or pending, or

royalties relevant to the topic discussed) in the texr held. 1f you have none,
indicate "No relevant financial interests" in the text field. This information
inay be posted with your response.
However, these online-only letters may not be indexed by bibliographic databases,
and whether they fulfill the need for an official record of postpublication peer review
is subject to del~ate.~"

Corrections (Errata). Journals should publish corrections (or errata) following errors
or inlportant omissions made by authors or introduced by editors, manuscript edi-
tors, production staff, or According to the International Committee of
MedicalJournal Editors, journal editors have a duty to publish corrections in a timely
however, the age of the original article in which the error was made
should not be used as a reason not to publish & correction. Corrections to print
publications should be published on a numbered editorial page and listed in the II
journal's table of contents. It is preferable to publish corrections in a consistent place'
in the journal, such as at the end of the correspondencecolumn. If this is not possib!e '
or if corrections are routinely published in available white space in print versions ~f
journals, these should still be listed on the journal's table of contents. If easily i d e p
tified, corrections will then be included in literature databases, such as MEDLI ,
and appended to online citations to the original article that contains the error?'
Corrections made to online-only content and publications should aLso be properly -
I'Y i
j
I

'
labeled and identified (eg, listed in the online table of contents) and reciprocally
linked to the original content. On occasion, an error may be so serious (eg, error in
drug dosage) or important to the author (eg, misspelling of author's name) to warrant
immediate correction online. In this case, it should be made clear in the online article
that a correction has been made, and a print correction should follow. ,
In online publications and versions of print journals, corrections should re- ..
ciprocally link to and from the original article. Corrections should also be appended
to all derivative publications (eg, reprints). If major errors arecorrected in derivative ,
publications, a note should be included indicating that a correction has been made
and/or linking to a correction.
IsI I

Corrections (or errata) should not be used for retractions of fraudulent articlee
resulting from fabrication, falsification, or plagiarism (see also 5.4.5, Scientific Mis-
conduct, Retractions, Expressions of Concern).

Role of the Editorial ~oard.Editorial boards comprise leaders and experts in the
subject area(s) represented by a journal. Editorial board members provide various
functions, including representation of the journal and outreach to the community of . -'

readers and authors.served by the journal; advising the editor on policies, editorial
content, and editorial.direction of the journal; serving as peer reviewers; writing and
recruiting manuscripts;and/or assisting the editor on editorial decisions (ie, handling ,
nlanuscripts with which the editor has a conflict, seriing as guest editor, or serving as I
section editor or editor for specific types of manuscripts). Some journals use editorial :
board members as decision-making editors who conduct initial triage of the quality I
and suitability of manuscripts or assign papers to peer reviewers. Journals without
independent oversight committees may wish to position the editorial board with the
I
I
 5.11.10 Role of the Editorial Board

c
j ability to help maintain the editorial freedom and integrity of the ed~tor;tncl iourt~.tl
(see also 5.10, Editorial Freedom and Integrity). Editorial boards should Ix. \vorktng.
functionalboards, with specific roles, responsibilities, direction, a clear reporting rcla-
. ~ ~ nonworking figurehead Imards may hclp tllc
tionship, and term l i ~ n i t s . ' ~While
image or marketing of a journal, they will not provide reliable and consistent ;~cl\.icc
and assistance to the editor.
i
An editorial board should be independent of the publisher, owner, or othcr
external forces, and the journal's editor in chief should serve as the chair of the
editorial board. Editorial board members should be selected and appointed by the
journal's editor, not the publisher or the owner.1° However, if the editor has an
agreement with the publisher or owner that permits an external group (eg, profes-
sional society that owns or has a formal relationship with the journal) to nominate
board members, the editor should have the final authority to appoint these individuals
and to review their performance, and the number of editorial board members iden-
tifred by the owner or an external group should be limited to a minority of the total
board membership. Editors should maintain confidentialityand fairnesswhen making
decisions to renew or not renew a specific board member's appointment.
Editors should develop, review, and update as necessary an editorial board mem-
ber position description that clearly lists roles, responsibilities, requirements, and
term limits. For example, see the position description for an editorial board member
forJAMA (Box 1).
A conflict of interest policy should also be established for editorial board mem-
bers (see also 5.5.7, Conflicts of Interest, Requirements for Editors and Editorial

Box 1. Editorial Board Member Position Description

1.Attends annual meeting of the editorial board.
2. Permits name to be placed on masthead of the journal.
3. Reports to the editor in chief and serves as a source of editorla1 advice.
4. Serves as peer reviewer and consultant, reviewing manuscript9 promptly
and thoroughly.
5. Represents the journal to peers in member's scientific, clinical, and aca-
demic disciplines.
6. Assists in recruiting authors, manuscripts, and reviewers for the journal.
7. Writes editorials, commentaries, and other articles as requested.
8. Reviews each issue of the journal and provides feedback to the editor in
chief. ,
9. Makes the comments and impressions of colleagues regarding the journal
available to the editor in chief.
10. Promotes readership of the journal by calling it to the attention of col-
leagues and using it in educational settings, as appropriate.
11. Is appointed for 2-year terms, with a general tenure of 10 years.
12. Does not serve as editor or editorial board memher of a competing
journal.
13. Discloses all relevant financial conflicts of interest to the editor in chief
annually.
14. Performs other duties as requested.
--
I
I
 -._ _
5.11 Editorial ~esponsibilities.Roles, Procedures, and policies

Board Members). Editorial board members should disclose all relevant conflicts of
interest (financial and nonfinancial) to the editor; they should not participate in the
review of or decisions on any manuscripts in which they may have a conflict of
interest; and they should never use information obtained during the review process,
editorial consultation, or an editorialboard meeting for personal or professional gain.
Editorial board members may be asked to serve multiple journals; this may pose a
conflict of interest, especially for journals that represent a small community or the
same field or specialty. The following questions, developed by the Archives of Oph-
thalmology, may help editorial board members and editors decide whether positions
with 2 journals pose a conflict of interest: Are both journals competing for the same
readership, subject matter, and authors? Are the editorial positions and responsibil-
ities similar?Can the editorial board member meet this journal's requirements as listed
in the position description? I

Journal editors should hold regular meerkgs of the editorial board at least an-
nuallylo or, if resources are limited, conduct regular meetings via conference call ,
and/or the Web. In any case, the editor should communicate frequently with the
editoriq board members, ensure that. board members understand their responsi-
bilities and terms, and review the performance of each board member on a regular
basis and before renewing a term.

Disclosure of Editorial Practices, Procedures, and Policies. Underlying the ethics of

editorialresponsibilityis the need for disclasure of editorial procedures and policiesto
authors, reviewers, and readers. Typically, these are listed, and explained as neces- - *- i

sary, in the publication's instructions for authors, which should be published and
readily available on the journal's Web site (if published online). Items that should
be considered for inclusion in a biomedical journal's instructions for authors are
listed in Box 2.
When an important editorial policy is first created or undergoes a major revision,
it should be announced to prospective authors, reviewers, and readers. The easiest
way to accomplish this is to publish an editorial note or an editorial. Editors should
also draw attention to major changes hi policy and procedures in the journal's in-
structions for authors and correspondence with authors.
Editors should also ensure that all individuals responsible for contributing to the
publication are properly identified, typically in the masthead (eg, editorial and,
.
publishing staff, editorial board members, advisers, oversight bodies or publication
committees, and owners). Other items that should be disclosed include any sources
of financial support or other sponsorship that supports the publication.

Editorial Audits and Research. Many journals conduct internal assessments, audits,
and research into various aspects of the editorial process. For example, a journal may
produce monthly or annual reports from its database of manuscripts, authors, and
peer reviewers to track inventq, workflow, and efficiency metric^.^ Trends from
these reports can help editors determine the number and types of papers to accept
for publication, assess staffing needs, track reviewer performance, and determine
when to institute corrective action. For example,JAMA publishes an annual editorial -,
audit that includes the number of manuscripts received the previous year, accep-
j
I

tance rates, and the turnaround time foc manuscripts that are reviewed, accepted or I
I'I ,
I
Box 2. Items That Should Be Considered for Inclusion in a Biomedical Journal's
Instructions for Authors

Information About the Journal

Name, address, telephone and fax numbers, e-mail address, and URLs
(uniform resource locators) of the journal's Web site and online submission
system (if available)
Journal's mission, goals, and objectives
Policies and procedures on editorial assessment, review, and proc6ssing
(eg, turnaround times forreviews and decisions, type of peer review pro-
cess, acknowledgingreceipt of submissions, editing and review of accepted
manuscripts) .
Types of manusaipts 'yitable for .submission
Requirementsfor Manuscript Submission
Name, address, telephone and fax numbers, and e-mail address of corre-
sponding author; list of all coauthors with their relevant academic degrees
and institutional afliliations .
Methods and requirements for submitting manuscripts, tables, and figures;
cover letters; and supplementary materials, including audio or video files if
acceptable (ie, via Web site, e-mail, or other means)
If accepting submissions by mail, number of copies of manuscripts, tables,
and artwork required
Style and format of manuscript text, tables, figures, references,. abstracts,
and supplementary material
Specific requirements for categories of manuscripts (eg, reports of original
research, reviews, letters, editorials, or journal-specific features)
Manuscript submission checklist
Requirementsfor Manuscript Consideration and Publication
Policies on authorship, contributions of authors, access to data, and ac-
knowledging assistance
Policy on submission of duplicate or redundant manuscripts
Policy on disclosure of conflicts of interest
Policy on disclosure of funding and the role of the sponsor
Policies for deposition of data in public repositories and registration of ,

clinical trials
For experimental investigations involving human or animal subjects, policy I
on approval by ethics committee or institutional review board and infornicrl
consent or appropriate animal care and use
Policy on including identifiable descriptions or photographs of patients
Policies on obtaining permission for reprinting or adapting previoi~sly
published material
Policies on transfer of copyright or publication license ancl open ;ICCC*%
Payment responsibility for open access journals with nurhor-pay n i c ~ l c(l1 1~
journals with other forms of public;~tion(p;lgc o r color) c11;lrgc.s
5 1 1 Edrtorldl Responsibilities. Roles. Procedures, and Policies

relcctcd, and published.20The Archives Journals publish dates of acceptance with

each article.
In addition, some journals systematically analyze information from submitted
n~anuscriptsas part of research to improve the quality of the editorial or peer
review processes. All identifying information should remain confidential during such
assessments, and any research conducted should not interfere with the review
process or the ultimate editorial decision. For example,JAMA's instructions for au-
thors inform prospective authors that information related to their submissions may
be subject to such analysis and that confidentialitywill be maintained. If a research
project involves change in the journal's usual review process (eg, random assignment
to a different review procedure), authors should be informed and given the o p
portunity to choose whether they want their manuscripts to be included in the study.
Their decision to participate or not should not adversely affect the editorial con-
sideration of their manuscript in any way.

Editorial Quality Review. A final editorial procedure that should be a part of every
journal's operation is quality review. After publication, editorial and production staff
and advisers should review each issue for content errors (which, if detected, should
be considered for publication as corrections), problems in presentation and format,
and general appearance. All editorial and publishing staff should have the oppor-
tunity to participate in the quality review process, and all errors, problems, ant! :
suggestionsfor improvement should be communicated to the editor as well as those -
directly involved in editing and producing the publication.

ACKNOWLEDGMENTS
Principal author. Annette Flanagin, RN,MA
I thank the following for. reviewing and providing helpful comments on this
manuscript: Catherine D. ~ e ~ n ~ eMD, l k MPH,
, JAUA and Archives Journals; C. K.
Gunsalus,JD, University of Illiiois, UrbanaIChampaign; and Terri S. Carter, Amhives
of Suqery.

REFERENCES
1. Lundberg GD. Perspective from the editor of JM,l%e Jouml of the American
Medical Association. Bull Med Libr Assoc. 1992;80(2):110-114.
2. Council of Science Editors. Editor roles and responsibilities. In: CSE's white paper on
promoting integrity in scientific journal publications. http://wvm-.coun~ilscienceedit~rs
.org/services/draft_approved.cfm.September 13, 2006. Accessed January 5, 2007.
3. World Association of Medical Editors. WAME recommendations on publication ethics
policies for medical journals. http://www.wame.org/resources/publication-ethics
-policies-for-medical-journals. Accessed January 5, 2007.
4. Utiger RD; for the Education Committee, World Association of Medical Editors. A
syllabus for prospective and newly appointed editors. http://www.wame.org
/resources/editor-s-syllabus. Posted October 26, 2001. Accessed January 5, 2007.
5. Committee on Publication Ethics. A code of conduct for editors of biomedical journals. i
I
http://www.publicationethics.org.uk/guidelines/code. ~ccessedApril 10, 2006.
6. Behlmer GK. Ernest Hart and the social thrust of Victorian medicine. BMJ. 1990; \
301(6754):711-713.
 . ---.
.

5.1 1.13 Editorial Quality Review

7. Lundberg GD. The s ~ c i aresponsibility

l of medical journal editing. J Gen Intern Med.
1987;2(6):415419.
8. Relman AS. Publishing biomedical research: role and responsibilities. Hastings Cent
Rep. May/June 195023-27.
9. Schiederrnayer DL, Siegler M. Believing what you read: responsibilities of medical
authors and editors. A d Intern Med. 1986;146(10):2043-2044.
10. Bishop CT.How to Edit a ScienNficJountal. Philadelphia, PA: IS1 Press; 1984.
11. Morgan P. An Insider's Gufdefor Medical Authors and Editors. Philadelphia, IJA: IS1
Press, 1986.
12. Riis P. The ethics of sdentific publication. In: European Association of Editors. Sciet~ce
Editors' Handbook. West Clandon, United Kingdom: EASE; January 1994. Reissued
June 2003.
13. Horton R. The rhetoric of research. BMJ. 11995;310(6985):985-987.
14. Sperschneider T, Kleinert S, Horton R Appealing to editors?hncer. 2003;361(9373):
1926.
15. Horton R The Luncet's ombudsman. Lancet 1996;348(9019):6.
16. Carter R Ombudsman's eighth repoh Lance! 2004;364(9432):402..
17. Instructions for authors. Arcb Gen Psycbiahy. http://archpsyc.ama-assn.org/misr
/ifora.dtl. Updated November 2006. Accessed January 5, 2007.
18. Instructions For authors. Arcb Pediatr Adokc Med. http://archpedi.arna-assn.org
/misc/ifora.dtl. Accessed April 22, 2006.
19. Curfman GD, DrazenJM. Too dose to call. NEngl JMed. 2001;345(11):832.
20. DeAngelis CD,Fontanarr>sa PB. Thank you, JAM peer reviewers and authors. JAMA.
2006;295(10):1171-1172.
21. Roberts L. The rush to publish. Sdence. 1199;251(4991):260-263.
22. Instructions for authors. JAUA. h~p://m.ama-assn.orS/midifora.dtl. Accessed
January 3, 2007.
23. Chusid MJ, Casper JT,Camitta BM. Editors have ethical responsibilities, too. lV EnglJ
Med. 1984;311(15):990-991..
24. International Committee of Medical Journal Editors. Unifonn Requirements for
Manuscripts Submitted to Biomedical Journals. http://www.icmje.org. Updated Feb-
ruary 2006. Accessed April 10, 2006.
25. Altman DG. Poorquality medical research: what can journals do?J M 2002; .
287(21):27652767.
26. Altrnan DG. Unjustified restrictions on letters to the editor. PLoS Med. May 2005;
2(5):e126.
27. Crossan L. Letters to the editor: the new order. BMJ. 1998;316(7142):14oG-1410.
28. Delamothe T, Smith R. Twenty thousand conversations. BMJ.22002;324(7347):1171-1172.
29. Davies S. Revitalising rapid responses: we're raising the bar for publication. BMJ. :
2005;330(7503):12&f.
30. Readers Reply submission instructions. Arcb Pediatr Adolesc Med. http://archpedi
.ama-assn.org/cgi/eletter-submit/160/4/402Accessed April 22, 2006.
I:!ti;'
;.
I%>:

1:':
31. National Library of Medicine. Fact sheets: errata, retraction, duplicate publication, F:i
11
:
comment, update and patient summary policy for MEDLINE. January 21, 2005. I..
http://www.nlm.nih.gov/pubs/factsheets/errata.html. Accessed April 22. 2006.
32 Marcovitch H, Williamson A. 1.1.3: Editorial boards. In: European Association of
Ed~rotsScience Editon' Handbook. West Clandon, United Kingdom: EASE; June 2003.
 Advertor-l~ Sponronh~p.Supplemenu, Reprints, and E-prints
5.12 ~dwrt~rernents.

The ~irtcetlainronlance between scholarlyjoumaki

rind the dnrg industry has long been like a maniage
of corrvenience between partnm who became
fh'etzds ullirnufely,no1 becuuse t h q were m y fond
of each other originully, but because they needed
each other.
Robert H. Moser, MD'

Advertisements, Advertorials, Sponsorship, Supplements. Reprints, and

E-prints. Commercial activities, such as advertising, sponsorship, reprints, and
e-prints provide a major source of revenue for many scientific publications. With this
revenue, publications can offset some of the costs of journal operations, production,
and distribution; may be able to set lower subscription rates than would othenyise be
possible; and can serve as a source of income for the journal's owner. Thus,editors
and readers often consider advertising an unfortunate necessity. A cynic might say
that generating revenue is the ultimate goal of advertisers, publishers, and editor*
advertisers want to sell more products, publishers want to increase journal revenue, '
and editorswant their journals to remain financially viable and sustainable. However, ;
editors have a larger ethical responsibility to their readers, who must be able to rely j
-
on the editor to ensure that the journal's integrity remains intact and that the infor- - . :

mation contained in the publication is vatid and objective. This includesensuring that
advertising does not influence editorial decisions or content and having policies and
procedures in place that prevent such influence.
Thus, editors should have ultimate responsibility for all content published in
their journals, including advertisements and sponsored content (see also 5.10, Edi-
torial Freedom and Integrity, and 5.11, Editorial Responsibities, Roles, Procedures,
and Policies). The International Committee of Medical Journal Editors (ICMJE) rec-
ommends that editors "have full and final authority for approving advertisements
and enforcing advertising policy.n2 The American Society of Magazine Editors
(ASME) recommends that "every effort must be made to show all advertising pages,
sections and their placement to the editor far enough in advance to allow for nec- .
essary changes" and to permit the editor to monitor compliance with advertising
g~idelines.~ However, some editors may not be able to review and approve specific
ads because of limited resources (personnel and time). Nevertheless, all editors
should oe involved in the development, enforcement, and evaluation of formal
advertising policies for print and online versions of their journals. For example,
principles for advertising in print and online are developed jointly by editorial and
publishing staff for JM and the ~rchives ~ournals.~These principles are used by
both publishing and editorial staff to determine the suitability of advertising. Al-
though editorial and publishing s'taff regularly review and discuss these policies and
their applicability in specific situations, the JAMA and Archives Journals editor in
chief has final authority over all advertisements. I
According to the ICMJE, advertising must not be allowed to influence editorial !
decisions? All editorial decisions must be based solely on the quality and suitability
of the editorial content and should not be influenced by potential revenue, or loss
1I
of revenue, from advertising, sponsorship, sales of reprintsle-prints, o r related I

i
 5.12.1 Advertisements

commercial activities, or the influence of ad'sales and marketing representatives. This

policy is also supported by the World Association of Medical ~ditors'and the UK

i
--
!
Committee on Publication ~thic.5.~ Complete separation of the roles and functions
that determine editorial decisions and advertising sales is critical. Thus, editorial staff
must not be involved in the promotion or sale of any advertisements, and the
publishing staff who sell ads and sponsorship (including reprints) shpuld not be
permitted access to editorial content until it is published. Editors should have policies
and procedures in place to address reader and online user complaints, ~ e s s m e nof t
such complaints, and appropriate remedy or action. The ICMJE recommends that
editors consider publishing letters that raise important concerns about advertising
content, in the same way that they publish critical letters about articlesy2including
asking the advertiser to submit a reply.

Advertisements. Mvertisements appear in print and online journals, e-mail alerts,

other online information products and services, and other types of media (such as
podcasts and blogs). For biomedical publications, advertisements typically include
the following:
Advertisementsthat promote professional or trade-related products (primarily phar-
maceuticals and medical equipment in biomedical publications), services, educa-
tional opportunities or products, or announcements (see a l h 5.12.3, Advertorials).
These are typically called dfsplayaduertisementsin pr&t; online, they may include
banners, popup windows, or text-based ads (such as in e-mail alerts or other online
communicatio& of information) (see also 5.12.6, Advertising and Sponsorship in
Online Publications).
Display advertisements that promote products and services not specifically related
to a profession or trade (such as an ad for an automobile or an airline in a medical
journal).
I
I Classified or recruitment advertisements (listings of employment ?pportunities,
educational courses, workshops, announcements, or oth& services).
I In most cases, advertisers pafto place advertisementsfor their products and services
in publications. Those advertisements for which a publisher does not typically
charge a fee include public service announcements, ads for nonprofit organizations
or charities, and "house ads," which promote a product or service provided by the
owner of the publication.
Important considerations for editors and publishers are whether paid advertise-
ments and sppnsorship invite potential infringements on editorial independence and
whether they represent important revenue opportunities for journals in increasingly
competitive rnarket~?~ The keys to maintaining editorial integrity are to achiev~a
balance between these seemingly opposing forces, to maintain a recognizable se-
paration between the functions and decisions of editorial and advertising departments,
and to have consistent and publicly available policies on advertising and sponsor-
ship.29
Although the primary function of most journals is to educate and inform in a
neutral manner and that of advertisements is to educate and inform in a promotional
manner, advertisers and editors share a common goal--to influence the behavior of
readers.'' Obvious differences b m e e n editorial text and advertising copy exist. In
biomedical publication. editorial material typically comprises text composed in a
5.12 Advertisements, Advertorials, Sponsorship. Supplements. Reprints, and E-prints

consistent scholarly format w~thd;ltd-t)as~tdtabla and figures, whereas 3dven1.x-

ments typically contaln bold, colorful statements and eye-catching gnphlcs Schol-
arly editorial material is generally intended to be objective, whereas advenlsements
are generally intended to be preferential, selective, and persuasive. Problems arise
when the means to achieve the common goal--of influencing behavior-fall outside
expected norms or violate specific regulations and standards.
In many countries, advertisers must meet specific criteria established by national
regulatory agencies. For example, drug ads are required to follow the regulations of
-the Food and Drug Administration in the United states," the Association of the
British Pharmaceutical Industry in the United ~ i n ~ d o m , 'and
* the Pharmaceutical
Advertising Advisory Board in ~anada." The International Federation of Pharma-
ceutical Manufacturers Associations has regularly updated guidelines for pharma-
ceutical marketing practices that may be helpful for countries without well-defined
regulations.14 However, each of these regulatory agencies has been criticized for not
enforcing its regulations.15.16 I
i
Crit~riafor Advertisements Directed to Physicians and Other Health Care Profes-
I
sionals. The editorial and publishing staff of JAMA and the A ~ b i u e Journals
s have
developed general eligibility requirements and guidelines for advertising copy to
ensure that advertisements published in these journals are appropriate (see Tables 1
and 21.4 The ASME also has developed a guide for print-based advertisements3 I
I i
The following criteria for print pharmaceutical ads are adapted from the guide- '
lines prepared by the World Health Organizationl' and the International ~ederation' -
of Pharmaceutical Manufacturers tio on^^^:
1. Advertising text should be presented legibly.
2. Pharmaceutical ads in print journals must include the following (in online
ads, this information may be included on a Web site to which the ad links):
Name of the product, typically the trade (brand) name
The active ingredients, using either the international nonpropriemy
names or the approved generic name of the drug
Name and address of the manufacturer or distributor
Date of production of the advertisement
Abbreviated prescribing information, which should include an approved
indication or indications for use together with the dosage and method of
use and a succinct statement of the contraindications, precautios, and
adverse effects
For a "reminder"advertisement(a "short advertisementcontaining no more
than the name of the product and a simple statement of indications to
designate the therapeutic category of the product"5), the abbreviated
prescribing information may be omitted. (See also 5.12.3, Advertorials.)
, .
3. When published studies are cited in promotional material, standard re- ,
trievable references with complete bibliographic information should be in- ,'
cluded (see also 3.0, References). Information in advertisements and other
promotional material, such as excerpts from the medical literature or quo- I

tations from personal communications, must not change or distort the in-
tended meaning of the authods) or the significance of the relevant work or 'i I
Table 1. Eligibility Requirementst o Advertise in Journals Publishedby the American Medical Association

1. The AMA, in its sole'dixretion, reserves the right to dedine any submitted advertisement or to discontinue
'
publication of any advertisement previously accepted.
2. Produds or se~ceseligible for advertising in the scientific publications shall be germane to and useful
in (a) the practice of medicine, (b) medical education, or (c) health care delivery, and should-
be commercially available.
3. In'addition to the a h , products and sewic6s that are offered by responsible advertisers and that are
of interest t o physicians, other health professionak, and consumers are also eligible for advertising.
4. Pharmaceuticalproducts for which approval of a new drug application by the Food and Drug
Administration (FDA) is a prerequisite for marketing must comply with FDA regulations regarding
advertising and promotion.
5. Institutional advertising germane to the practice of medicine and public sewice messages of interest to -
physicians may be considered for indusion in all AMA publications.

1.
i
6. Alcoholic beverages and tobacco products may not be advertised. :j

7. Equipment Insbuments, and Devices: The AMA determines the eligibility of advertising for products
intended for preventive, diagnostic, or therapeutic purposes. Complete xientific and technical data
concerning the product's safety, operation, and usefulness may be required. These data may be either I -
published or unpublished. Samples of equipment, devices, or instruments should not be submitted. The
AMA reserves the right to dedine advertising for any product that is involved in rigation with a !:
governmental agency with respect to claims made in the marketing of the product. j:,
8. Food Products
A General-purpose foods, such as bread, meats, fruits, and vegetables, are eligible.
0. Specialgurpme foods (eg, foods for carbohydraterestricteddiets and other therapeutic diets)
are eligible when their uses are supported by acceptable data.
' C. Dietary programs: Only diet programs prescribed and controlled by physicians are eligible.

9. Dietary Supplements Advertisements for nutritional supplements and vitamin preparations are not
eligible unles the safety and efficacy of the product have been reviewed and approved by the FDA for a
disease daim.
10. Books: A book may be requested for review to determine its eligibility.
11. Insurance Coverage: Claims made in advertisements for insurance coverage must conform w ~ t hthe
following specific aiteria:
A. Claims relating to policy benefits. losses covered, or premiums must be complete and truthful.
B. Claims made shall include full dixlosure of exclusions and limitations affecting the basic
provisions of policy.
C. Claims incorporatingquoted testimonials must meet the same standards as other claims.
D. Each advertisement for insurance products and services must include a statement indicating either
the states in Wkh the products or services are available or the states in which the products or
s e ~ c e sare not available.
12. CME Programs: Advertisementsfor continuing medical education (CME) programs are not eligible unless
the CME sponsor is accredited by the Accreditation Council for Continuing M e d ~ aEducation
l and is
an accredited medical school (or hospital affiliated with such a school). a state or county medical society.
a national medical specialty society, or other organization affiliated with the American Board of
Medical Specialties member boards.
13. Miscellaneous Products and Services: Products or services not ~nthe abovt chswfcatmr may be
eligible for advertising if they satisfy the general principles governing ehgblrv fgr adveRr~ng~nAMA
publications.
- -- - - -

'These guidelines are intended for advertknents lor USbaed c a n p a n e . poducts. md u n ~ e skc r e f w e w e 1 2
to 14 for examples of relevant g u ' k k h ~ 0th~ counnrr
 ,*

5.12 Advertisements, Advertorials, Sponsorship, Supplements, Reprints, and E - p r ~ n a

Table 2. Guidelines for Advertising Copy in Journals Published by the AmerKan Medtcal Association
(AM4

1. The advertisement should clearly identify the advertiser of the product or services offered. In the case of
drug advertisements, the full generic name of each active ingredient shall appear. [This requirement
applies to print ads; for online ads, the active ingredient may appear on the company or manufacturer's
Web site to which the ad links.]
2. Layout, artwork, and format shall be such as to be readily distinguishable from editorial content and to
avoid confusion with the editorial content of the publication. The word Advertuerner~tmay be required.
3. Unfair comparisons or unwarranted disparagements of a competitor's products or je~iceswill not
be allowed.
4. Advertisements will not be acceptable if they conflict with the Principles of Medical Ethia of the American
Medical Association or the advertising guidelines in Cunent Opinions of the Council on Ethical and
Judicial Affairs of the American MedicalAssociation.
5. It is the responsibilityof the manufacturer to comply with the laws and regulations applicable to
marketing and sale of its products. Acceptance of advertising in AMA publicationsshould not be construed
as a guarantee that the manufacturer complies with such laws and regulations.
6. Advertisements may not be deceptive or misleading.
'
7. Advertisements will not be accepted if they are offensive in either text or artwork, or contain attacks
of a personal, racial. sexual, or religious nature, or are demeaning or d i i m i n a t i i g toward an individual
or group on the basis of age, sex, race, ethnicity, religion, physical appearance, or disability.

study. Prepublication peer review and editorial evaluation of articles help to

reduce problems associated with misleading or inappropriate information
from published articles, but ads do not typically undergo the same level of
evaluation before publication. Several studies have documented problems
with advertisements in medical journals, including promotional statements
not being accurately supported by references, references cited to support
promotional statements that are not retrievable (eg, "data on file'?, and
numerical distortion of data presented in tables and graphs.ls2' Thus;some
editors have instituted formal review processes to assess the validity of claims
made in ads.23124
4. According to the Internatibnal Federation of Pharmaceutical Manufacturers .
~ssociations,'~ the same req&ernents that apply to printed matc,ials should
also apply to electronic promotional materials, including audiovisuals. Spe-
cifically, in the case of pharmaceutical product-related Web sites, the identity of
the pharmaceutical company and of the intended audience should be readily
apparent, the content and presentation should be appropriate for the intended
audience, and country-specificinformation should comply with local laws and
regulations.14(See also 5.22.6, Advertising and Sponsorship in Online Publi- . ,I
cations.)Typically,an onlineadvertisementlinkstoa company's Website, where
the details about the prescribing information as listed above are provided.
Five issues should be addressed in any journal's policy on advertising: !' 1
1. Advertising-to-editorial content ratio
I
2. Advertising interspersion
I
 5.12.2 Criteria for Advertisements Directed to Physicians and Other Health Care Professionals

, 3. Advertising-editorial juxtaposition (adjacency)

4. Editorial calendars
5. Appropriate advertising content

mAdvertising-to-Editorial Content Ratio. For print publications that have an abun-

dance of advertising, setting an ad-editorial page ratio (ie, limiting the advertising
content to no more than a certain proportion of total annual pages) may help protect
the perceived integrity of the publication.25The ICMJE recommends that journals not
be dominated by advertising and that they avoid publishing advertisements from
only 1or 2 advertisers; otherwise readers may perceive that the journal is sponsored
by 1 or 2 advertisers and that these advertisers have influenced the editor and the
editorial ~ o n t e n tFor
. ~ print journals, compliance with relevant postal regulations in
some countries may also need to be considered if the number of ad pages exceeds
the number of editorial pages. The ratio of editorial to advertising on Web versions of
journals should also follow these general principles.

Advertising Interspersion. Placing advertisements between articles and interleaving

them within articles may attract advertisers, but such practices may also diminish the
perceived credibility of the publication-especially if the ads create dimculty for the
reader in reading or finding editorial ~ontent.~'~' For scholarly biomedical journals,
ads should not be interleaved within a scientificor clinical article in print or online.
- Many print publications group, or stack, their ads in the front and back of their
joumals, leaving an editorial "well" in the middle of the publication for major articles
that are not interspersed with ads. stacking ads can cause some advertisers to go
elsewherebecause they want their ads to be placed next to editorial material. For that
reason, some journals place popular editorial features (such as news articles) in the
front and back of the journal to allow for ad interspersion of those sections and
maintain an ad-free editorial well for the original research and other major articles.
Ads should not appear on the journal's front cover. For discussion of advertising
interspersion on the Web, see also 5.12.6, Advertising and Sponsorship in Online
Publications.

Advertising-Editorial juxtaposition (Adjacency). Advertisers may request pl:~ce~nent

of their ads next to related editorial content to help promote their products. Although
common in consumer publishing, this practice is discouraged by the ICMJE and the
AS ME.^.^ Ad adjacency, like ad interspersion, may be an impediment to readers and
may diminish tHe perceived integrity of a scholarly pub~ication.~.'~ To avoid the
occurrence of adjacent ads and editorial content on the same topic, even by chance,
the editorial staff of JAUA and the Archives Journals review the entire makeup
(imposition) of the journal after the ad deadlines have closed and before the journal
is printed. If an ad is scheduled to appear adjacent to an article on the same or a
closely related topic, the editors ask the production staff to move the ad or may
decide to move the article. For those journals that permit online ads on pages with
editorial content, ad adjacency policies should be developed that maintain the
journal's editorial integrity. (See also 5.12.6, Advertising and Sponsorship in Online
Publications, for additional discussion of advertising-editorid adjacency in online
publications.)
5.12 Advertisements, Advertorials, Sponsorship, Supplements, Reprints, and E-prints

Editorial Calendars. Providing advertising sales representatives with editorial cal-

endars that include specific content scheduled for upcoming issues invites pressure
for advertising-editorial adjacency and other attempts from industry to interfere with
editorial decisions. The ICMJE states that advertising should not be sold on the
condition that it will appear in the same issue as a particular arti~le.~~ournaleditors
and publishers can respond to industry pressure by reminding advertisers of the
importance of the journal's integrity. Advertisers understand this issue, because
without integrity, a publication will have few readers, and without readers, the ad-
vertiser cannot sell products. For this reason, advertising sales staff should not have
access to the journal contents until after publication. However, sales staff may know
about general editorial plans, such as plans for theme issues,proceedings, symposia,
or sponsored supplements (see 5.12.4, Sponsored Supplements).

Appropriate Advertising Content Appropriate ads must meet the following re-
quirements4.13.16.17.26.

No false claims
No implied false claims
m Ability to substantiate claims
R No omissions of important facts
No distortion of data
Good taste (although this is diEcult to define objectively)
a Clear identification of the advertiser of the or services being offered
m~ Layout, artwork, and format that differ from those of the editorial content so that
readers can clearly distinguish the advertising and editorial content
Biomedical journals typically publish a disclaimer statement to separate the claims
made by advertisers from the views of the jownals' owners. For example, the fol-
lowing statement appears in each issue of JAMA:
ADVERTISING PRINCIPLES-Advertisements in this issue have been re-
viewed to comply with the principles governing advertising inJ A M and the
Archives Journals. A copy of these principles is available on request and
online at www.jama.com. Thz appearance of advertising in J A M is not an
AMA guarantee or endorsement of the product or the claims made for the
product by the manufacturer.

Advertorials. An advertorial is an ad that imitates editorial content or presents con-

tent in an editorial-like format, such as using text, tables, or figures in a manner
similar to the journal's editorial content. During the early 1 9 9 0 ~
following
~ a decline
in the biomedical advertising market, advertorialsbecame more common. The ASME
developed guidelines for special advertising sections," which may help a publica-
tion maintain its integrity if it publishes advertorials (see Table 3).
Companies may submit advertisements that provide information on a topic
pertaining to a product the company markets (or plans to market) but that do not
nilme any commercial product. It is essential that such ads are clearly labeled "Ad-
\,cniwment,"have a different format from the journal's editorial content, and include
 ., .. ..

5.12.4 Sponsored Supplements

Table 3. ASME Guidelines for Special Advertising Section?

I. Each page of special advertising mud be clearly and conspicuously identified as a message paid for by
advertisers.
2. To identify special advertising sections dearly and conspicuously:
A. The words adkrtking, aderthrnent or special advertising seaion should appear prominently at
or near the top of every page of such sections containing text, i n type at least equal in size
and weight to the publication's normal editorial body typeface. (The word advertorialshould not
be used.) -
B..The layout, design, and type of such sections should be distinctly different from the publication's
normal layout. design, and typefaces.
C. Special advertiw'ng sectionsshould not be slugged on the publication's cover or included in the -
editorial table of contents.
D. tf the sponsor or organizer of thesection is not the publisher, the sponsor should be clearly identified.
I
# -

3. The editon' names and tides should not appear on, or be associated with, special advertising sections,
!
nor should the names and titles of any.other staff members or of regular contributors to the publication
appear or be awiated with special advertising sedons. The publication's name or logo should not :
appear as any part of the headlines or text of such section$. ,
4. ~diit& qnd other ediotial staff m&benshould not prepare advertising sections for their own publication.
for other publicaths in their field, & f& advertisen'inthe fields they cover.
5. For the publication's chief editor to have the opportunity to monitor compliance with these guidelines,
material for special adwrtising s&om should be made available to the publication's editor in ample time
to review and recommend necessary changes. Monitoringwould indude reading the text of special I
advertising sectiw beZwe p u W i for problems of fact, interpretation, and M e and for compliance
with any relevant laws.
1;
6. To avoid'potkntialconflii or werlaps with editorial cqntent, publishersshould notify editors well in
advance of their plans to run special advertising d o n s .
1
7. The size and number of Special advertising sections within a single issue should not be out of balance
with the size and nature of the magazine. .

'Adapted and reprintedwith penn'kion f&

.

the ~ r n e r b n
Society of bIag&ine ~ d i i r s . ~ ~
j:
j
.... , j '.
i.
% . .
j
a prominent display of the company name and/or logo so that readers can quickly !I
I.
ascertain that the information is an advertisement from the company and is not part j
1

of the journal's editorial content.

I

i
Sponsored Supplements. Sponsored supplements are collections of articles, usually ;
on a single topic, and are published as an extra edition or a separate section of a
. .
journal, often after a meeting or symposium'. A study of 58 highly cited and read
medical j o u d found that the number of supplements published by these journals ! ..

had increased &fold from 1966 to 1989.~'Forty-two percent (262 of 625) of these
supplements were single-sponsored (ie, sponsored by 1 pharmaceutical company)
and, compared with supplements funded by other types of sponsors, were less likely
to have been formally peer reviewed and more likely to have promotional attributes,
such as misleading titles, focus on a single-drug topic, and use of brand names
only.28Because of the promotional and biased quality of such industry-sponsored
supplements,JAUA and the Archives Journals will not publish them. In addition. the
US National Library of Medicine will not index articles in sponsored supplements
unless certain disclosure conditions are met.29

283
5-12 Advertlsemnts, Advertorialr, Sponsorship, Supplements, Reprints, and E-prints
. .
I
lio\vever, supplements can serve useful educational purposes, provided that the
content is objective, balanced, independent, and scientifically rigorous?*30Spon-
sored supplements also may provide additional reverlue to publishers. Recognizing
this, the ICMJEdeveloped a set of principles to guide editors when considering the
publication of sponsored supplements.2These principles should help avoid bias in
the selection of content for inclusion in industry-sponsored publications2:
1. The journal editor must take full responsibility for the policies, practices, and
content of supplements, including complete control of the decision to publish
all portions of the supplement. Editing by the funding organization should not
I
be permitted.
2. The journal editor must retain the authority to send supplement manuscripts for :
.. I

external peer review and to reject manuscripts submitted for the supplement.
j
i
These conditio'ns should be made known to authors and external supplement
,.
editors before beginning editorial work on the supplement.
3. The journal editor must approve the appointment df any external editor of the I
supplement and take responsibility for the work of the external editor. I
;

I
4. The sources of funding for the research, publication, and the products the
funding source make that are considered in the supplement should be clearly . '

stated and prominently located in the supplement, preferably on each page. . i.

Whenever possible, funding should come from more than 1 sponsor. .- -.c

5. Advertising in supplements should follow a e same policies as those of the rest :

of the journal.
6. Journal editors must enable readers to' distinguish readily between ordinary
editorial pages and supplement pages.
7. Journal editors and supplement editors must not accept persdnal favors or
personal remuneration from sponsors of supplements.
8. Secondary publication in supplements (republication of papers previously
published elsewhere) should be clearly identified by the citation of the original
paper. Supplements should avoid redundant or duplicate publication. Supple- .
ments should not republish research results, but the republication of guidelines
or other material in the public interest might be appropriate.
9. The principles of autiiorship and conflict of interest disclosure should apply to
supplements.
. .

Other Forms of Sponsorship. Other forms of sponsorship include sales of bulk sub-
scriptions to commercial entities for distribution to individuals, noncommercial spon-
sorship or grants to supportspecificeditorial sections, and grants to support publication
of journals in corrimunities. With each type of sponsorship, the funding --- .
source should be clearly indicated to recipients and readers/users, and all editorial 1'1
content should be under the complete authority of the editor, should undergo the
journal's usual editorial evaluation and peer review, and should not be influenced by , 1
the sponsods). \ 1
i
i. 5.12.6 Advertising and Sponsorship in Online Publications

'mAdvertising and Sponsorship in Online Publications. Online a& are not restricted by
the physical limits of a printed page. For example, a user can increase the type size of
the prescribing information that appears in small type in print pham~aceutical:~ds.
A d s can rotate, expand, be animated, or pop up on a screen without the i~sttr's
request. An ad for a particular drug, product, or service can be hyperlinked to the
manufacturer or provider's Web site. In addition, ads can be targeted for specific
users or a specific user experience. ?he standards for protecting editorial integrity of
print publications apply to advertising in online publications and other electronic
products, such as CDs, DVDs, Web sites, e-mail, audio and video casts, and online
databases, especially for publications in clinical and health-related fields. For exam-
ple, just as a print reader can choose to read an ad or skip over it, an online user
should have the same choice; online ads should not interfere with the reading and
use of editorial content and should not dominate the online content; and online ads
should not appear adjacent to editorial content on the same or a closely related topic.
As stated by the ASME, Whiie linking and other technologies can greatly enh:lncc
the user experience, the distinction between independent editorial content and paid
promotional information should remain clear."31 i

Privacy Concerns. Privacy rights of online joumal users and visitors must be main-
tained. If any specific or personal information about users is to be collected and
specifically distributed or sold to third parties (such as advertisers), users should be
informed in advance and given the opportunity to not have their information shared
with others. Aggregate demographic information about numbers and types of users
may be provided to advertisers to guide decisions about placing advertisements in
specific journals in the same manner that circulation numbers are provided to ad-
vertisers and used for decisions to place print ads. This information may also be used
I by publishers to set advertisement rates and fees. Data on overall. numbers of users,

i
I
impressions (ie, number of times an advertisement has been viewed), and click rates
(percentage of impressions that account for'a click through to an advertiser's Web
site) are acceptable to share with advertisers provided that the journal advertising
policy and use of such information are made clear to users.

Guidelines for Online Advertising and Sponsorship. As the technology advances, .

online advertising will provide additional opportunities and ethical dilemmas for
publishers and editors. Accordingly, guidelines for online advextising and sponsor-
ship will also continue to evolve. The following guidelines, which gre based on some
of those developed for use in online versions of JAMA and the ~ r c h i v e ~ournals?
s
provide guiance for advertising in online publications.

Online ~dvertising
m Policies and procedures for online advertising should be jointly developed, re-
viewed, and approved by editorial ant1 publisl~ingstaff. Similar principles should
apply to print and online ad guidelines.
Journals that have policies for editorial review and approval of print ads should
apply similar policies for review and approval of online ads.
8 Online advertising niay appear on journal Wcl, sites, journal-rtrlatecl e-mail mes-
sages (eg. e-mail alerts of new content or tal3les of contena that users Ila\~e
 D
5.12 Advert~rementr.Advenortals. Sponwrrhlp. Supplements. Repr~nts.and E-prints

registered to receive), other communications of puma1 infomution. and other

media (such as pdcasts).
Online advertisements must be readily distinguishable from editorial content; ads
should be labeled with the word Aduettiment (ie, placed above or below the ad).
Online advertisements may appear as text, fixed or rotating banners, or pop-up
windows. Online advertising should not interfere with a user's ability to read, use,
navigate within, search, or interact with editorial content. Users should have the
ability to easily navigate away from such advertisements (eg, close a pop-up
advertisement).
m Online advertisements should not be juxtaposed with, appear in line. with, or
appear adjacent to editorial content on the same or a closely related topic, or be
I
linked with editorial content on the same topic. However, just as advertising may I
appear across from the print table of contents, ads may appear adjacent to online I
tables of contents or similar listings of article titles (eg, a journal or publisher's
home page).
1
I

w 0 n l d advertising may appear on screen with specific types of articles as long as *'

the separation between. editorial and advertising content is made clear and juxta- I
position of editorial and advertisements on the same or a closely related topic does j
not occur. It is preferred that such ads not appear on editorial pages of scholarly, I
peer-reviewed articles and be reserved for other types of articles, such as news
sections.
a Logos of journals or journal owners may not appear on commercial Web sites as
logos or in any other form without prior written approval.
w Advertisements may link from the journal to an off-site commercial Web site,
provided that viewers are clearly informed that they are viewing an advertisement
by means of the word Advertisement placed above, below, or in the ad. The Web
site to which the ad links should be reviewed in advance. The linked page must
include the following elements:
Company sponsoring the Web site is clearly displayed.
Claims on the online advertisement and the landing page of the Web site are
reasonable and substantiated. .
No registration requiring personal heormation is required before reaching the
Web site. For journals that permit facilitation of the gathering of such personal
information (eg, promotional leads), privacy policies and procedures should be
followed (see also "Privacy Concerns" above).
a Non-journal-affiliated Web sites should not frame a journal's Web site content
without express permission; should not prevent the viewer from returning to the
journal's Web site or other previously viewed screens, such as by disabling
the viewer's Back button; and should not redirect the viewer to a Web site that the
viewer did not intend to visit.
a E-mail alerts and other forms of online information dissemina.tion may have text
or HTML ads embedded in the e-mail (top and/or bottom) provided that the
relevant guidelines herein are followed.
 b'.
5.12.7 Reprints and E-prints

.i 8 Journals should not permit their content to be used on an advertiser's site. How-
ever, journals may sell e-prints to advertisers who then link to the journal's article
from the Web site. In such cases, the advertiser's Web site should not imply any
relationship with the journal (see also 5.12.7, Reprints and E-prints).
.,
L - 8 Ads should not be linked to editorial content Search terms. Journal search engines
should not include the ability to search content from advertisements unless the
results of such searches clearly indicate the difference between editorial.and ad-
vertising content. Advertisers or sponsors should not receive preferential treatment
in search programs and search results.

Online Sponsorship
Editorial content of any sponsored product (eg, online publications, CDs, DVDs,
Web sites, e-mail, audio and video casts, and online databases) should be de-
termined by the standard editorial process:The sponsor should have no influence
over the editorial content of any sponsored product. -

a Sponsorship policies should be clearly noted, either in text accompanying the

product or on a disclosure page, and should clarify that the sponsor had no input
into or influence over the content.
a All fhmcial or material support for sponsored content should be acknowledged
and clearly indicated (eg, on the home or landing page as well as on any pack-
aging and collateral material included).
These acknowledgmentsshould not make any claim for any supporting company
product(s1. The final wording and positioning of the acknowledgment should be
1,- . determined by the journal, with review and approval by the editor. The wording
could be.sirnilar to "Produced by uoumal Name1 with support from [Company
Nmel.'!
The acknowledgment of the sponsor's support may be linked to the sponsor's
Web site.
a Journal names and logos should not appear on the sponsoring company Web site
without prior written approval by the joumal.
rn Journal search engines should not include content from sponsors unless the re-
sults of such searches clearly indicate the difference between sponsored and non-
sponsored content. Sponsors should not receive preferential treatment in search
programs and search results.
See also 5.12.4, Sponsored Supplements.

Reprints and E-prints. Publishers of journals may sell reprints and e-prints of journal
articles as a source of revenue. Reprints and e-prints may be purchased by authors for
personal use, by others for educational purposes, or by commercial entities for
promotional purposes. In biomedical journal publish~ng,a m p r i ~ r rIS the republica-
tion of an article or collection of anicles in which the content is unch:lngcd fronl t l l ~
original publication (except perhaps for the inclusion of postput~licark~n correc-
tions). An e-print is a digital reproduction of o r :In onllnc- link t o :In .~nlc.lcc,r c ~ l -
I lection of articles, usually PDF files(s). For cs~nlplc.~ ~ u l ) l ~ ~ol'./.4.l!~
l l c r \ . t r l ~ l IIIC
!
5.12 Advertisements, Advertorials, Sponsorship, S u p p l e ~ ~ t ReprlntJ.
J, and ~-printJ

Archives Journals sell reprints to authors (at relatively low cost) as a x n i c c f o r

authors and to the pharmaceutial industry as a source of revenue. JA4L-l ~ n thc d
Archives Journals also provide authors with conlplimentary access to their aniclcs
as e-prints and sell access to e-prints to commercial entities. Some journals permit au-
thors to post e-prints of their articles (usually PDF files) on personal or other archival/
institutional Web sites (see also 5.6.2, Intellectual Property: Ownership, Access, Rights,
and Management, Open-Access Publication and ScientificJournals), and some journals
permit commercial entities to purchase and post copies of e-prints on their Web sites.
Note: Reprints and e-prints differ f r o m p ~ ~ n which
t s , are print and online versions of
articles/manuscripts made formally available to others before publication in a peer-
reviewed journal.
Journals should establish and follow consistent policies and procedures on the
production, sale, review/approval, and distribution/dissemination of reprints and
e-prints. For an example of such standards, see those developed for J A M and the
Archives Journals in 5.6.10, Intellecti~alProperty: Ownership, Access, Rights, and
Management, Standards for Commercial Reprints and E-prints. Editorial decisions
must be free of any influence from the potential for sale of reprints and e-prints, and
all such a l e s must not be permitted to occur until after publication of the original
article. Reprinted articles should not be abridged or altered by the purchaser and
should not include an advertisement or the advertiser's logo or other commercial
content. A publisher may incorporate or append a qmection to a previously pub-
'
lished article in a reprint/e-print as long this is noted in the reprintle-print.
-..
ACKNOWLEDGMENTS
Principal author: Annette Flanagin, RN,MA
I thank the following for reviewing and providing useful comments on the
manuscript: Geoffrey Flick, American Medical Association, Periodic Publishing &
Business; Trevor Lane, MA, DPhil, University of Hong Kong; and June Robinson, MD,
Archives of Dermatology.
REFERENCES
1. Moser RH.Advertisements and our journal. Ann Intern Med. 1977,87(1):114115.
2.International Committee of Medical Journal Editors. Uniform Requirements for Manu-
scripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publi-
cation. http://www..icmje.org. Updated Febmary 2006.Accessed July 22,2006.
3. American Society of Magazine Editors. ASME Guidelinesfor Editors and Publ&hers.
13th ed. New York, NY: American Society of Magazine Editors; 2006.http://www
. .magazine.org/Editorial/Guidelines. Accessed June 11, 2006.
4. American Medical Association. Principles governing advertising in publications of the
American Medical Association. Chicago, IL: American Medical Association. http://pubs
.amna-assn.org/misc/adprinciples.pdf.Revised October 2006.Accessed January 5,
2007.
5. Utiger R; for the Education Committee of the World Association of Medical Editors. A
syllabus for prospective and newly appointed editors. http://www.wame.org
/resources/editor-s-syllabus. Posted October 26,2001.Accessed January 5, 2007.
6. Committee for Publication Ethics. COPE Code of Conduct for Editors. http://www I
I.
.pul~licationethics.org.uk/reports/2005/code. Accessed July 16, 2006.
 5.12.7 Reprints and E-prints

7. Fletcher RH.Adverts in medical journals: caveat lector. funcet. 2003;361(3351):10-11.

8. Tsai AC. Conflicts between commercial and scientific interests in pharmaceutical ad-
K vertising for medical journals. Znt J Health Seru. 2003;33(4):751-768.
9. Callaham M. Journal policy on ethics in scientific publication. Ann E m q Med.

\
?-!
2003;41(1):82-89.
10. Dixon T. Pharmaceutical advertising: information or influence? Can Fam Phys.
1993;39:129&1300.
11. US Food and Drug Administration. Title 21: Food and Drugs. Chapter 1: Food and
Drug Administration, Department of Health and Human Services. Subchapter C:
Drugs: General. 21CFR 202.1. http://www.fda.gov. Revised April 1, 2005. Accessed
July 16, 2006.
12. Asxiation of the British Pharmaceutical Industry. Code of practice for the pharrna-
ceutical industry 2006. http://www.abpi.org.uk/links/assoc/PMCPA/code06use.pdf.
Accessed July 16, 2006.
13. Pharmaceutical Advertising Advisory Board. Code of advertising acceptance. http:I,'
www.paab.ca/ideqen.html. Updated April 1, 2005. Accessed July 16, 2006.
14. InternationalFederation of Pharmaceutical Manufacturers Associations. ZFPMA Code of
Pharmaceutical Macketing Practices. 2006 Rev. http://www.ifpma.org/pdf/IFPM~
-TheCode-FinalVersion-30May2006-EN.pdf. Accessed June 11,2006.
15. Kessler DA. Addressing the problem of misleading advertising. Ann ~ n t e m Med.
1992;116(11):9SO-951.
16. Lexchin J, Holbmok k Methodologic quality and relevance of references in phar-
maceutical advertisements in a Canadian medical journal. &J. 194>51(1):47-54.
17. World Health Organization. +tbical Criten.afor Medicinal Drug Pmmotion. Genev;~,
Switzerland: World Health Organization; 1988.
18. Vianueva P, Peiro A, Liberos J, Immaculada P. Accuracy of pharmaceutical advcr-
tisements in medical journals. Lancet. 2003;361(9351):27-32.
19. Wilkes MS,Doblin BH, Shapiro MF.Pharmaceutical advertising in leading mrdicxl
journals: experts' assessments. Ann Intern Med. 192;116(11):912-919.
20. van Winkelen P, van DenderenJS, Vossen CY,Huiziinga TW,Dekker FW.Bow evidence-
based ate adveltisements in journals tegardiig the subspecialty of rheumatology?
Rheumatobgy (word)2006;45(9):11%1157.
.
21. Cooper RJ, Schriger DL. The availability of references and the sponsorship of original
research cited in pharmaceutical advertisements. CMAJ. 2005;172(4):487-491.
22. Cooper RJ, Schriger DL; Wallace RC, Mikulich VJ,Wilkes MS. The quantity and quality
of scientific graphs in pharmaceutical advertisements.J Gen Intern Med. 2003;18(4):
294-297.
23. Pitkin RM. Advertising in medical journals. Obstet Gynecol. 1989;74(4):667-679.
24. Wilkes MS, Kravitz RL. Policies, practices, and attitildes of Nonh American lnedicll
journal editors. J Gen Intern Med. 195;10(8):443-450.
25. Remie D, Bero LA. Throw it away, Sam: the controlled circulation journals. CBE Vieus.
1990;13(13):31-35.
26. Parmley WW. Has Madison Avenue become Medicine Avenue?J Am Coll Card01
1994;23(7):1726-1727.
27. American Society of Magazine Editors. GuidelinesJorS p u l Adrlerlisrtrg S e c ~ t o ~Rrh
~s
ed. New York, NY: American Society of Magazine Editors, July 1996
28. Bero LA, Galbraith A, Rennie D. The publication of spclnsurcc! s y m p i u m s in ~nrvlical
journals. N Engl J Med. 1992;327(16):1135-1140
5.13 Release of lnformation to the Public and Journal/Author Relations With the News Media

29. US National Library of Medicine. Fact sheet: response to inquiries about journal
selection for indexing at NLM. http://www.nlrn.nih.gov/pubs/factsheets/jq
.htrnl. Last updated October 13, 2006. Accessed January 5, 2007.
30. Kessler DA. Drug promotion and scientific exchange: the role of the clinical in-
vestigator. N Engl JMed. 1991;325(3):201-203.
31. American Society of Magazine Editors. Best practices for digital media. http://www
Jor-Digital-Media. Accessed July
.rnagazine.org/Editorial/Guidelines/BesttPractices ,

16, 2006.
!
I

Most people understand science and technology less

through direct experience than througb thefilter of
journalism. .. .Journalists are, in effect, bmkets,
framing sxial reality a,.d shaping the public
consciousness about science.
Dorothy elk in'

Release of lnformationto the Public and Journal/Author Relations With the '
News Media. Public interest in matters of health and in news about medicine and'
health is substantial. A telephone survey of 1250 US adults concluded that the ma{
jority of citizens consider news coverage of science to be as important as coverage of
crime, the economy, politics, sports, and entertainmenL2Many factors affect sciencd - ,,-
journalism and the communication of scientific information to the public, including
poor science literacy among the public; the increase in costs for print publication and I
I
distribution; a concomitant decline in print newspaper circulation and the decline of . I'
newspaper sections dedicated to health and science; a dearth of investigative jow-
nalists trained as scientists and more coverage of science news by reporters who
do not understand science; the rise of online news systems and ondemand news
delivered to niche markets; news and topic-specific e-mail lists and blogs; tabloid
journalism; sponsored infotainment, infomerdals, and Web sites masquerading as
I
r
1
credible and objective providers of science and health information; and the .increas- I.
ingly competitive nature of the businesses of news delivery and scientificjournals.39
The responsible dissemination of the results of new scientific research and in-
formation to the public is critical. Unfortunately, amid the burgeoning means of
conveying such information, ac&racy and reliability in science news coverage in the :
news media are not increasing proportionateh. To gain a competitive edge in the
information chain, news organizations may exchange complexity, analysis, back-
\
ground, and perspective for immediacy and sensationalism.1° Thus, the need for ,
journal editors to develop and maintain viable and ethical relationships with news i
journalists-for all types of media-has become even more important.
Scientific journal editors have several responsibilities regarding communicating ,
scientific information to the public and their relationship with the news media:
iI
Publish appropriate, accurate, reliable, timely, and accountable scientific informa- i

tion. , i
P Inform authors and journalists about journal policies regarding release of information \, '

in manuscripts under consideration or accepted prior to publication and journal

E

1i 5.13.1 Release of Information to the Public

embargoes prohibiting news media coverage of articles before publication (.we

I
I\
5.13.1, Release of Information to the Public).
Assist the news media to prepare accurate stories of the information about to Ilc
I
! published by providing news releases, answering questions, facilitating equzil
- .\ .
advanced access to the journal articles in a controlled and consistent manner, and
providing access to authors or other experts as needed (see 5.13.1, .Release of
Information to the Public).
. Evaluate the quality of news coverage of information published in the journal. For
example, if a news organization has published an inaccurate report of a partici~lar
journal article, the journal editor should consider notifying the journalist and/or
news editor to identify the errors in the report."
Studies have documented that reporting of science, biomedicine, and health in the lay
media is often inaccurate, incomplete, or without adequatec~ntext.'"'~~ournaleditors
and news journalists share a common obligation-to ensure that the public receives
accurate information and is not This obligation becomes particularly
importdnt when information about risk is communicated to the public For example,
failureto desaibe health risksaccurately and in proper perspective may be misleading,
can create unnecessary concern, A d may result in loss of pGblic trust in reporters,
editors, and scientists. Tensions between journalists, editors, and scienths-often
driven by self-interests--can do much to confuse the public. These tensions should be
recognized and mitigated,19and journals should seek an appropriatebalance between
their duties to the community of readers they serve, the integrity of the scientific
literature, and public entitlement to access to important scientific information without
unreasonable delay.20
' Release of Information to the Public. In many ways, biomedical journals and their
editors act as gatekeepers for the release of scientific information to their readers as
well as to the public. However, conflicts often arise between journal editors (who
have aq ethical duty to ensure that the information they publish has been appro-
priately peer reviewed and assessed for quality) and scientists (who want to dis-
seminate their findings as widely and quickly as possible) and between editors and
news reporters (who want to deliver information about new scientific developments
to their readers as quickly as possible).'9 The announcement of "scientific break-
throughs" at press conferences or through press releases before the data that sup-
port the supposed advance have been evaluated and published in a peer-reviewed
journal may cause confusion for the public (who may be given misleading or inac-
curate information), news media (who may give undue attention to an inaccurate qr
incomplete claim), journal editors (who may have a policy that discourages publl-
cation of data that have already been reported in the press), and investigators (who
may forfeit their chance for publication in a reputable peer-reviewed journal by
choosing to publish by press conference or through press rclense~).~'-~"
Journal editors have developed 2 policies to discourage premature release of
information to the public. The first policy, based on the "Ingelfingerrule" (developed
in 1969 by Franz Ingelfinger, MD, then editor of the New Englandjournal of Med-
icine), is an understanding between authors and editors that a manuscript will be
considered for publication on the condition that it has not been submitted or re-
ported elsewhere 24 (see also 5.3, Duplicate Publication). The seconcl policy 1s a
5.13 Release of Information t o the Public and Journal/Author Relations With the News Media

news embargo, which is an agreement between journalists and editors that prohibits
news coverage of a journal article until it is published (see 5.13.3, Embargo). Al-
though some authors and journalists misunderstand or disagree with the intent of the
Ingelfinger rule and the news e ~ n b a r ~ o ,many
~ ~ . 'journals
~ have found that both, if
applied consistently and fairly, effectively serve'all communities interested in dis-
seminating quality scientific inforrnation to the public (with exceptions made in cases
of urgent public need for information or to coincide with presentations at scientific
meetings).
The International Committee of Medical Journal Editors (ICMJE) and the World
Association of Medical Editors WAME) recommend that journals develop and follow
policies for orderly, controlled, and consistent release of inforrnation to the public,
including the use of embargoes.M*n There are 4 general exceptions to a journal
policy that precludes prepublication release of information to thepublic: presenta-
tion of information during scientific or clinical meetings, release of information that is
determined to'be of urgent public need, testimony before government agencies, and,
in rare instances, release of inforrnation that is in the public domain.22 -

Presentation of Information During Scientific or Clinical Meetings. Presentation of

findings during scientific or clinical meetings (via oral presentation or poster pre-
sentation) does not preclude consideration of a manuscript reporting the complete
findingsfor publication.20*-~uthors may include abstracts of their findings in print
and/or online proceedings published for these meetings. However, authors should
refrain from disseminating or publishing details in proceedings that are not included -
in the meeting abstractor presentation. Authors should not include a complete report
of their findings (ie, a mansucript that they plan to submit to a journal) or disuibute
copies of their detailed findings or tables and figures to meeting attendees or jour-
nalists. Authors are encouraged to participate in discussion and the usual exchange
with meeting attendees during their presentation Audiocasts and videocasts of
meeting presentations also do not preclude consideration of the full manuscript for
publication provided these are intended for meeting participants.
Authors may also answer questions from journalists about their meeting pre-
sentations, but they should limit their discussion to explaining and clarifying the
findings presented during the meeting and should not discuss any related manu-
scripts under consideration by a journal or accepted but not yet published. In the
event that an author is presenting findings at a meeting that are also included in a
manuscript that is under consideration or has been accepted by a journal but not yet
published, the author should limit her or his remarks to the findings as presented
at the meeting. In this case, the author should inform the editor of plans to present
the work at a meeting before the meeting occurs and should discuss options with the
editor (see also 5.13.3, Embargo, and 5.13.4, Suggestionsfor Authors InteractingWith
the News Media). News media coverage (based on these interactions) about manu-
scripts that are accepted but not yet published or that are under consideration by a
journal occurring before the journal embargo is lifted and without prior approval of
the editor may be grounds for rejection of the manuscript by some journals.
Authors of papers under consideration by a journal or accepted but not yet
published, as well as authors' institutions and funders, should not participate in press
conferences before publication of the peer-reviewed article. Thus, authors should
,
not participate in press conferences at meetings separate from their scientific pre-
 5.13.1 Release of lnformation to the Public

sentation unless they have prior approval from the journal to which the full paper has
been submitted.
On occasion, the journal and the author may plan to publish the complete manu-
I
script online before the article appears in print (after peer review and revision) on the
same date of the presentation of the findings during a scientific meeting (eg, with a
late-breaking trial that is likely to have a practice-changing effect). In these cases,
news releases prepared by an author's institution or funder that summarize in-
formation to be published in a journal should be coordinated with the journal (see
also 5.13.5, News Releases). Proper planning is needed among all parties (journal,
author, and meeting organizer) to ensure that findings are released in an orderly
manner that does not confuse journalists or the public.

Release of infonnation Determined to Be of Urgent Public Need. Contrary to what

many authors and news reporters believe, few findings from scientific and medical
research have such signiticant and urgently.important implications for the public that
the informationshould be released to the public before it has been peer reviewed,
revised, and published in a joumal (online or in print). Calling such circumstances
"exceptional," the ICMJE recommends that public health authorities should make
such decisions and should be responsible for disseminating such information to
health professionals and the news media.20 However, an editor may recognize the
public health urgency of releasing information contained in a manuscript under
consideration without prompting from the authors or relevant authorities. In such a
case, the editor should ask the author to notify the appropriate authority to consider
advance dissemination of the infonnation, and this diemination should be co-
ordinated between the responsible authority or agency and the journal. In situations
in which there is an immediate public health need for the information, there should
be no delay in its release even if this release antedates publication in the print
journal." ~ournakshould expedite the editorial and peer review proces! and speed
. .. the publication process to permit online publication as quickly as possible. If such
I online publication occurs before print publication of the article, care should be taken
that this is conducted in an orderly and consistent manner so as not to confuse
journalists and the public.
. /

Testimony Before Government Agencies. An author's testimony before a govern-

mental agency or institution (eg, the US Congress or Food and Drug Administration)
.-
that includes information not yet published should not preclude consideration of that
information in a manuscript under consideration or subsequently submitted for
publication.22~uthorsand editors should discuss whether consideration and pub-
limtion of a manuscript with information relevant to such testimony can be ex-'
pedited to coincide with or be published before the testimony on a case-by-case
basis.

Information in the Public Domain. Reports of important infomation fro111national

government or international agencies published in print and widely diswminaterl o r
published online (eg, an urgent health alert or Web posting from the US N;~tion:~l
Institutes of Health or the World Health Organi7~ion)shoul~ltx. considered wlcc-
tively for publication in a peer-reviewed jor~rnalon a ~ : ~ ~ c - t , y - r . ;ha3is." ~hc In 3uc.11 ;I
case, the editor needs to determine if the ~nfnrnlation\\.r,~lldtx LIW-fulrc) tllc. iot~rn;il'\
readers, there isdemonstrate(l ncc.(l f o r :In . ~ t i t l ~ r ~ t r nrc-lw>rr
;ll fcs,q. . ~ ~ I t f ~ ~I Il~oI ~n) ;I -~
I . lI I I [
5.13 Release of Information to the public and Journal Authw Relat~on,Wtth the Newr Media

dCr;iils o r follow-up infom1;ltlon is avalLl>lc). and d he ln~tlala1t.n did not already

inc.lilclc the con~plcrert.In)n.

Expedited Publication and Release of Information Early Online. Many journals have
policies to expedite the evaluation and publication of manuscripts deemed worthy of
accelerated dissemination, including release of an article online ahead of its print
p~blication.~~ Editors should use consistent and orderly policies and procedures to
identify manuscripts containing such information, expedite the editorialfpeer review
and publication process, and, if feasible, notify and provide controlled advance
access to journalists.

Embargo. A news embargo is an agreement between journals and news reporters

and their organizations not to report information contained in a manuscript that has -
been accepted but'not yet published until a specified date and time in exchange for
advance access to the information. Among medical journals, the embzgo system
may have been initiated by Morris Fishbein, MD,editor o f J M between 1924 and
1949.~~
,kan example, the standard embargo date and time forJAMA is 3 PM central time
on the day before the journal's cover date (issue publication date). Qualified jour-
nalists are given early access to the journal online via a password-protected Web sitel
for the news media (usually 5 days before issue publication date). D l l ~ this
g time,
the embargo is intended to provide competitive news reporters an equal amount of
access and time to research and prepare their news stories. However, those news - .
reports cancot be released until the embargo has lifted.J A M is printed and mailed in
advance of the cover date, so that physicians can read pertinent journal articles
before they are reported in the news media and before patients begin asking them
questions after reading or viewing the news coverage.'*
The news embargo has been criticized for being overly restrictive, delaying
public access to information, and serving the self-interest of j0urna1.s.~~
However, the
embargo system is intended to create a level playing field for journalists to prepare
accurate and complete news stories and to maintain consistency in the timing of
release of scientific information to the public and help prevent confusion that may
result from sporadic reporting on the same study at different dates and &es. Ac-
cording to the ICMJE,such consistency of timing helps to minimize economic chaos
surrounding those articles that contain information that may influence financial
markets.20
On occasion, a news reporter or organization may break an embargo and report
on information from a peer-reviewed journal article before the embargo is lifted,
either unintentionally (owing to miscommunication or misunderstanding) or inten-
tionally, to scoop corn petit or^.^^.^^ The rare intentional embargo break is a serious
breach of trust and can result in the journal applying sanctions against the reporter
and the news organization. Such sanctions may include barring the reporter, and
perhaps the news organization, from receiving news releases and advance access to
journal content and declining requests for interviews, access to authors, or other
assistance. \
Suggestions for Authors Interacting With the News Media. The following rec-'\,
ommendations -are provided for interactions between authors and the news.
media.12.18.20.22
 5.13.4 Suggestions for Authon Interacting Wnh the News Media

Authors should abide by agreements with journals not to publicize their work
while their manuscript describing their work is under consideration or awaiting
publication by a journal. If authors have any questions about prior release of such
information, they should contact the journal's editorial
Authors presenting research at clinical and. scientific meetings may discuss their
presentations with reporters but should refrain from distributing copies of their
presentations, data, tables, or figures (see 5.3, Duplicate ~ublication).*~-~~
w Authors should inform editors of previous news coverage of their work at the time
of manuscript submission (see 5.3, Duplicate ~ublication).~~
Authors of manuscripts under consideration by a journal or accepted but not yet
published should not participate in press conferences before publication of their
findings in the journal unless this is an approved exception by the journal editor
and this is done in coordination with the
w Authors who receive telephone calls or other conlrnunications from ioilrnalists
about their research or other work reported in manuscripts that are under con-
sideration but not yet accepted by a journal may indicate that the manuscript is
under consideration but should not provide details on the name of the journal if
and until the manusaipt is accepted. (See also 5.7.1, Confidentiality, Confiden-
tiality During Editorial Evaluation and Peer Review and After Publication.)
w Authors should establish an understanding with a reporter before an interview
about the journal's embargo policy, comments made "on and off the record." and
the opportunity to review direct quotations.'2 Note: Authors should be cautious
about making comments "off the record."
w For accepted manuscripts about to be published and those just published, authors
should be as accessible to the news media as their schedules permit, keeping
reporters' deadlines in mind and setting aside time to prepare for and give in-
terview~.'~
During an interview, authors should avoid use of medical/scientific jargon, ac-
ronyms, and too many statistics; explain commonly used jargon and acronyms
and provide easily understood statistics; avoid answering hypothetical questions:
and avoid responding with "no comment" (provide an explanation for not being
able to answer a specific question).''
Authors should inform reporters and news organizations of errors in news stories
and request published corrections if necessary.12
Authors who expect to be interviewed frequently by the news media should
consider having training in providing informative and accurate interviews.12 '
In addition, journal editors should inform authors of accepted manuscripts of the
journal's policies regarding release of information prior to publication and relations
with the news media. For example,JAMA reminds authors of its policies on duplicate
publication and news embargoes in acceptance letters, noting that authors and the
news media should not release any information about the author's accepted article
until the specified embargo date and time. This embargo does not preclude authors
from participating in interviews with reporters who are preparing stories; it is meant
5.13 Release of Information t o the Public and Journal/Author Relations With the N e w s Mtdla

to remlnd authors that any news stones resulting from such intewlcws should not
precede publlat~onof the authon' articles in the )ournal.
Some journals notlfy authors of projected publlcatlon dates In their acceptance
letters, and some journals include a notice of the publication date on the edited
manuscript or page proof sent to authors for approval before publication. Editorial
and publishing staff may also receive calls from authors requesting information about
expected dates of publication. Staff and authors should not assume that such dates or
their corresponding embargo dates are definite or final. Editors may rearrange the
editorial content schedules of specific issues; thus, publication dates may change.
When informing authors of the expected dates of publication for their accepted
articles, editors should remind authors that these dates may change.
If authors want to coordinate news coverage of their published articles through
a press conference or press release, they should first contact the journal editor to
asce;:ain the exact date of publication. The ICMJE suggests that editors and pub- r
,-
lishers may want to help authors and representatives from their organizations co- I
ordinate press conferences and releases with the simultaneous publication of their
articles." Editors and publishers can also help the news media prepare accurate
reporis by providing news releases, answering questions, providing access to the , I
authors and other experts, and providing advanced access to journal articles. This
assistance should be contingent on agreemept with and cooperation of the news '
media in timing their release of stories to coincide with the publication of the article.
Press releases, advance copies of journals, and journal articles released onlirie in
advance should indicate the date and time of the news embargo and be restricted t o - - c ,.
qualified news journalists and agencies that agree to honor the journal's embargo
policy. f
I
News Releases. Many journals issue news releases on selected articles determined by
the editors to be of interest to the public. For JM and the Arcbim Journals,
experienced science writers prepare the news releases, which are reviewed by the .
editors to ensure accuracy and objectivity. News releases of journal content should
be urder the authority of the editor, not the journal's publisher or owner (see also
5.10, Editorial Freedom and Integrity).
News editors, writers, and producers receive hundreds of news releases a week. .
Thus, a news release must attract attention, but it also must conform to a familiar
format and style (see Box). Journalists are taught to present facts accurately, but they
may not know how to interpret biomedical statistics or understand the specific
context of new scientific information. In news releases and news stories, research
findings and statistics are often cited inaccurately or out of context to support an
exaggerated medical ~ l a i m . ' ~ * ' ~To
* " .help
~ ~ prevent exaggerated or misleading
claims, news releases must include accurate and clearly stated statistics33(see 20.1,
Study Design and Statistics,The Manuscript: Presenting Study Design, Rationale, and
Statistical Analysis). In addition, research findings must be placed in proper context
and should include important background, summary of study methods, limitations of 4

the methods, and informationon study sponsorship and relevant conflicts of interests
of authors (see 5.5, Conflicts of Interest). Care should be taken to provide balance
(eg, citing a related editorial) and to avoid sensationalism (eg, use of terms , ,
1 I
I
 5.13.5 News Releases

Box. Guide for News Release Format

Printed releases should be double-spaced and printed legibly with an
identifying logo or letterhead.
The name, address, telephone and fax numbers, and e-mail address and
URL (uniform resource locator), if available, of the releasing organization
should be listed under the title "News Release" at the top of the page.
The name, address, telephone and fax numbers, and e-mail address of the
release contact person should be clearly identifiable.
The release should be no longer than 200 to 600 words (1-2 pages in print).
For print releases that exceed 1page, the word more should appear at the
bottom of the first page.
The time and date of the release and the embargo should appear prom-
inently at the top of the release.
An easily identifiable headline (eg, boldface or underlined) that provides
the essence of the release should also appear at the top of the release.
Before the lead sentence, the location of the release should appear in
capital letters.
The lead sentence should contain the most important information. Details
should be given in later paragraphs. The name of the journal in which the
article appeared should be included in the lead sentence to help facilitate
mention of the journal in the story as a source of the information.
Authors of the article should be clearly identified with complete names,
academic degrees, affiliations, and relevant conflicts of interest. All sources
of funding for the research/work should be identified.
Releases should contain simple, declarative sentences and should avoid
jargon and undefined abbreviations. All medical terms should be explained.
All statistics and numbers should be properly explained and put in the
proper context.
See also "Common Problems to Avoid in News Releases" below.

like hakthmugh). Examples of common problems to avoid in news releases are

listed below: ,

Common Problems to Avoid in News Releases i

Unfamiliar mathematical and statistical terms and numbers that are difficult to in-
terpret should be avoided; do not confuse association and correlation with cau-
sa!lon
Results should be reponed In context, including locations and dates of the study,
representativeness of the sample, and lim~tationsof the study. Risks of events
should be acknowledged to be common (cg. common cold) or rare (eg, being hit
b\ I~ghtn~ng) ''

297
 --_
5.13 Release of Information to the Public and Journal/Author Relations With the News Media

H If the results of a survey are reported, the response rate should be provided along
with a caveat that the results may not be generalizable if the response rate is low.
If a news release mentions a specific sample that was studied or a specific number
of cases, whether the number is large or small, information about the size of the
total population from which the sample or cases were drawn should be included.
Statements about statistical significance should not be quoted from an article out
of context or without an explanation. Reporters and readers do not necessarily
know the difference between statistical significance and clinical significance. For
example, quoting a statement that there was a trend toward a statistically sig-
nificant association between treatment X and outcome Y may give undue im-
portance to a treatment that has no real clinical value.
PI Absolute event rates should be reported. Care should be taken to avoid confusing
absolute and relative risks because relative risks are often erroneously translated
to specific risks. For example, a decrease from 2.5% to 2.@! should not be re-
ported as a 20% reduction in risk, but could be reported as a 0.5% absolute risk
reduction and 20% relative risk reduction. It is also helpful to report excess or
decreased risk in terms of numbers per 1000 or 10 000.
Avoid reporting odds ratios, especially for common outcomes, which may over-
state a relative risk.''
s If reporting the results of a study about an intervention, event rates for benefits
I
and harms should be reported equally and in a balanced manner.''
Before news releases are distributed, they should be proofread and the content
should be reviewed by a professional familiar with the article or report covered in the
release. or by the editor.

ACKNOWLEDGMENTS 1..
Principal author: Annette Flanagin, RN,MA
I
I thank Joan Stephenson, PhD, J& Medical News & Perspectives, and Jann
Ingmire, JAM and Archives Journals Media Relations, for reyiewing and providing
important suggestions to improve the manuscript; -and the following for reviewing
and providing minor comments: Terri S. Carter, Archives of Surgv, Catherine D.
DeAngelis, MD, MPH, JAMA and Archives Joumals; Robert M . Golub, MD, JAM;
Wayne G. Hoppe, JD, J A M and Archives Journals; Trevor Lane, i.lA, DPhil, Uni-
versity of Hong Kong; and Povl Riis, MD, Lniversity of Copenhagen.

REFERENCES
1. Nelkin D. Journalism and science: the creative tension. In: Health Risks and the Press.
Washington, DC: Media Institute; 198953-71.
2. Science news: what does theIpublic want: a survey by Lou Harris commissioned by
SIPI. SIPISCO~~.1993;20(2):1-10.
3. Hume E. Tabloids, Talk Radio, and the Future of News: Technology's Impact on
Joumalis~n.Washington, DC: Annenberg Washington Program; 1995.
4. Hard times hit science sections. SIPlsope. 1992;'20(1):1-4.
5. Ethiel N, ed. Medicine and the Media: A Changing Relationship. Chicago, IL: Robert R
i
hlcCor~nickTribune Foundation; 1995.
 - - --

5.13.5 News Releases

6. Levi R. Medical Joumlimt: Erposing Fact, Fiction, Fraud. Lund, Sweden: Stu-
dentlitteratur; 2000.
7. Schwitzer G, Mudur G, Henry D, et al. What are the roles and responsibilities of the

\ media disseminating health information?PI.& Med. 2005;2(7):e215:0576-0582.

8. Ankney RN, Moore RA, Heilman P. Newspaljer cpverage of medicine: a survey of
editors and cardiac surgeons. M W A J. 2001;16(1):23-32.
9. Erickson A, McKenna J, Romano R. Past lessons and new uses of the mass media in
reducing tobacco consumption. Public Health ~ e p .1990,1050:239-24.
'
10. Garrett L. Reporting epidemics: real and unreal. Paper presented at: Institute of
~edid'i~ Annual
e Meeting: Emerging and Reemerging Infections; October 16, 1995;
Washington, DC.
11. Freischlag J. "Wrong" surgeq is rare occurrence. USA Today. April 26, 2006:A12.
12. Rubin R, Rogers HI.Jr. Under the Microscope: ZBe Relationship Bet= Physicians
and the Naus Media. Nashville, TN: Freedom Forum; 1993.
13. Smith DE, Wilson AJ, Henry DA; on behalf of the Media Doctor Study Group. Monitoring
the quality of medical news reporting: early experience with Media ~ o c t o rMed . JAurt.
2005;i8~(4):i90-193.
14. Moynihan R, Bero L, Ross-Degnan D, et al. Coverage by the news media of the
benefits and risks of medications. N ~ nJ ~~e dl22000,342(22):1645-1650.
.
15. Schwartt LM,Woloshin S. News media coverage of screening mammography for
women in their 40s and tamoxifen for primary prevention of breast cancer. J A M .
2002;287(23):3136-3142.
16. Voss M. Checking the pulse: midwestern reporters' opinions on their ability to report
health care news. Am J Public Health. 2002;92(7):1158-1160.
17. Mot1 SE, T i p e EM, Eichner SF. Evaluation of accuracy of health studies reported in
mass media. J Am Phann Assoc. 2005;45(6):720-725.
-_ 18. Stamm K, WilliamsJW, Noel PH, Rubin R. Helping journalists get it right: a physician's
guide to improving health care reporting. J Gm Intern Med. 2003;18<2):13&145.
19. Glass RM,Flanagin A. Communication, biomedical 11. scientific publication. In: Reich
WT, ed. Encyclopedia of Bioethics.2nd ed. New York, W. Macmillan Publishing Co;
1995:42&435.
20. International Committee of Medical Journal Editors. uniform ~ e ~ u i r e m e nfor ts
Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedia~l
Publication. http:#www.icmje,og. Updated Febn~ary2006. Acces.sed April 30, 2006.
21. Butler D. "Yublication by press conference" under fire. Nulrlrv. 1993;306(0350):0.
22. Fontanarosa PB, Flanagin A, DeAngelis CD. THEJOURNAL'S policy regarding re1e:lst. of'
.information to the public. J A M . 2000;284(22):2929-2931.
23. Schwartz LM,'Woloshin S, Baaek L. Media coverage of scientificmeetings: too much.
too soon?jAMA. 2002;287(21):2859-2863.
24. Kassirer JP, Angel1 M. The Ingelfinger rule revisited. NE12gl.I Med, 1991;325(19):1371-
1373.
25. Altman L. The Ingelfinger rule, eml>argocs,;lntl jou~.n;~l peer review, pan I . krrrc.c,t.
1996;347(9012):1382-1386.
26. Who's responsible to whom-and for what. In: Ethiel N, ed. .ll~>liicir~c rrrrd th(,. I / c ~ I ( I
A Changing Relationship. Chicago, IL: Roben K hlcCorn~ick'I'ril~unt.1'ound;llic~n.
1994:16-47.
27. tiger RD;for the Education Committee, Worltl A.<wr.i;~rioi> of hlcdic.;ll Iltlilor\ ,\
for prospective ;tnd newly aplwbin~cllrtli~t,r\ I I I I ~//~ \\.\\w \\ .1111%.1 wc
syll;~l,i~s
I'oslerl O C I~~l x 20.
/resources/eclitor-s-syll;~I>~~s. r 21M 1 1 ,\t cxw.d I.tnu:~ni.Lt 1'
 . .. .....

5 1 3 ReIeaw of lnforrnaflon to the Public and JournaljAuthor Relations With the News Media

. .
r i I.~~ndIxr):GI). Glass RM,Joyce LE. Policy of AMA journals regarding release of in-
l'or~narionro the public. JAMA. 1991;265(3):400.
29. Sracy J. The press embargo-friend or foe?J A M . 1985254(14):1965-1966.
30. Fontanarosa PB, DeAngelis CD. The importance of the journal embargo. J A M .
2002;288(6):748-750.
31. Hough GA. News Writing. 3rd ed. Boston, MA: Houghton Mifflin Co; 1984.
32. Cohn V, Cope L. News and Numbers: A Guide to Reporting Statistical Ckzims and
Cortrtv~miesin Hcul~hatul Reluted Fields. 2nd ed. Ames, IA: Blackwell Publishing
Professional; 2001.
33. Woloshin S, Schwartz IJd.Press releases: translating reseaich into news. JAMA. 2002;
287(21):2856-2858.
 Editorial Assessment and Processing

6.2
Editorial Assessment Editorial Processing
6.1.1 Editorial Decisions 6.2.1 Manuscript Editing
6.1.2 Assessment Criteria 6.2.2 Composition, Page Makeup, and Web
. 6.1.3 Peer Review Content .
6.1.4 ,Selection of Reviewers 6.2.3 Proofreading
6.1.5 Statistical Review 6.2.4 Advertising
6.1.6 Concealing of Author and Reviewer 6.2.5 ' Issue Makeup and Review
6.2.6 Reprints
6.1.7 Revision 6.2.7 Corrections
6.1.8 Appealing a Rejection 6.2.8 Index
6.1.9 Postpublication Review

'

The principal goals of editing biomedical publications are to select, improve, and
disseminate information that will advance the art and science of the discipline cov-
ered by the publication. For example, biomedical publications are a major source of
informationfor the improvement of medical care. In addition to initial transmission to
readers at the time of publication, information from journal articles is often carried by
the public media. Published articles influence educators and opinion leaders, \vho
m m i t the information to many persons who do not read the original publications.
Medical j o d articles can also be subsequently accessed by clinicians and re-
searchers seeking information about particular topics. Such searches are facilitated by
online search engines (see 25.0, Resources) and provide the information essential to .
practicing evidence-based medicine,' in which patient-care decisions &e infonned
by acquiring and assessing the relevant medical literature. These myriad uses of
biomedical literature indicate the importance of the procedures to improve quality
involved in editorial assessment and processing.

Editorial Assessment. The assessment process (Figure 1) consists of 2 phases:

editorial review and peer review. In editorial review, editors first assess submissions
for their 'overall quality and appropriateness for the publication's readership. Some
manuscripts are,rejected on the basis of this editorial "triage." Manuscripts that pass
this initial step go on to the peer review phase. Peer review (see 6.1.3, Peer Revie:
W) involves evaluation by experts who are "peers" of the authors with regard to ::;::
I....

knowledge about the topic of the submission, and may also include evaluation by
expert statistical reviewers (see 6.1.5,Statistical Review). The integrity of the edito-
rial assessment process requires strict confidcniiqlity(see 5.7.1,Ethical ;lnd I.cg:~lCon-
siderations, Confidentiality, Confidentiality Iluring I:clitori:~l I:v;~lu:~tion,
I'ccr Itcvicw,
and After Publication) and attention to possil~lcI)i;lscs :~ntlc-onllic:~~ of' inlcrc..~~.

sutxnittcd manuscripts arc cilllcr rc:j(.c.l(,(lor rc.l~~rrtc.(l 11, ; I I I I ~ I JI',

I will1 -.I ~ i j i j r - . t~r ,II.. 18,I

improvc~ncnttllroi~gt~rcvisio~). I I I I I ~ ~ ;I; l~l .I ~ l ~ l l -11,t

A I I I I I ( J ~ S S I I ~ I r1*;1Jiz13 , ~ ~,.vI.,II ,I,, I , ,, .,
 PREACCEPTANCE
EDITORIAL ASSESSMENT

OPOSTACCEPTANCE
EDITORIAL PROCESSING

WEB
START
v

g POSTPRINT
PRODUCTION

A
END

Figure 1. JAMA manuscript (MS) workflow: editorial assessment and processing. -- ....
-.-. -..-. , ...
,
..- ,;'.-;; ;,;,) 1 ,

_ . _ _ . _ ----.
_ .--.- . . . . . , .. _. _ _^ _
_. . .. .. -. . ---....-
.. ,. .--

%.
 6.1.2 Assessment Criteria

not guarantee acceptance, because revised manuscripts are subject to editorial review
and may also have additional peer review. Several rounds of review and revision m;~y
occur before a final decision is reached. Acceptance of manuscripts expressing view-
points, perspectives, or opinions may be based solely on editorial review, but reports
of original data and other major alricles almost always undergo peer review, statistical
review, and revision before acceptance for publication (see 1.0, Types of Articles).
Journals with more than 1editor may hold meetings during which submitted man-
uscripts and their reviews, and also revised manuscripts, are presented and discussed
before decisions are reached regarding revision or acceptance for publication.
The decisions for rejection, revision, and acceptance all belong to the editor, not
the peer reviewers. The term mfme, meaning a person to whom a paper is referred
for review, is sometimes used sykonymously with peer reviewer. However, in the
Onited States eferee can be misleading because that term often implies one who has
authority for decisions, particularly in sports events. In biomedical publishing, editors
have that decision responsibility. Peer reviewers have an important and helpful but
advisory role, essentially serving as consultants to editors.

Assessment Criteria. Two major criteria are central to the evaluation of manuscripts
submitted for publication: importance and quality. Importance involves an assess-
ment of whether the work
Represents a scientific advance (recognizing that individual articles
usually convey only small advances)
Has clinical relevance (if the journal is to be read and the
information used by practicing clinicians)
Presents new information
Will be of interest to readers
An additional component of importance is editorialpriority, a composite judgment
made by the editor regarding the value of a particular submission relitive to other
submissions under evaluation at .the same time, weighed in the context of the
articles that joumal has recently published and has scheduled for publication. The
reality of limited space may also be a consideration,.even in the era of electronic
publication. Cyberspace may appear infinite, but the attention span and patience of
readers are not. Furthermore, the editorial processing requirements (see 6.2, Edi-
torial Processing) for material to be published electronically may be very similar to
those for print publication. Hence, concise submissions may be given higher priority
than long ones (other factors being equal) because they take up a smaller pro-
portion of a jo'urnal's resources and total space allotment.
Evaluation of quality involves an assessment of how well a paper treats Its
topic, including how well the topic and the methods used to deal with that topic are
described. For original research reports, assessment of quality involves consider-
ation of whether
The design and methods are appropriate to answer the stated research
questions
The research questions and the methods used to answer them are
well described and rigorously conducted
The data analysis is appropriate
6.1 Editorial Assessment

The conclusions are supported by the results

Patients or research participants were treated ethically ( x e 5.8. Ethical
I
and Legal Considerations, Protecting Research Participants' and Patients'
Rights in Scientific Publication)
The quality of the writing may be a major factor in the assessment of editorials,
commentaries, and other nonresearch submissions where the elegance and impact
of the writing itself may constitute major reasons for publication. For research and
review articles (see 1.0, Types of Articles), writing quality (especially clarity) may
affect the reactions of editors and peer reviewers even though the importance and
quality of the research should be the main focus for assessment. Writing quality can
be improved by manuscript editing (see 6.2.1, Manuscript Editing), but only if the
research is described with sufficient clarity to permit basic understanding.
The specific nature or direction of results should not be an issue in quality :'
assessment. If a paper addresses an important question and uses highquality meth-
ods to answer it, the result.. are worth publishing no matter what they are. Publication i
I~iasthat results from a tendency for investigators not to submit, or editors not to :
accept; papers that do not report statistically significant "positive" results should be ;
eliminated.' A w e l l d o n e ' s t ~ dthat
~ shows that a particular intervention is ineffective
is usually just as important as a study that reports a "positivenresult. .

Peer Review. Peer review was fist used for biomedical publications by the Royal !
Societies of London and Edinburgh in the 18th century, but it evolved haphazardly
and was not used consistently until after World War 11.~'The essence of peer re-
view consists of asking experts "How important and how good is this paper, and how
can it be improved?" (see 6.1.2, Assessment Criteria). The use of expert consultants
to advise editors about the selection and improvement of papers has become a stan-
dard quality-assessment measure in biomedical publication. Yet the process and ef-
fectiveness of peer review have come under scientific scrutinyonly since the 1980s.'-~
Experts in the topic of a paper are needed to assess importance and quality.
However, peer review .hasbeen criticized for its reliance on human judgments that
are subject t o biases and conflicts of interest, and there have been few empirical
documentationsof the efficacy of the peer review process.B13 Empirical research on
editorial peer review has begun to address some of the deficiencies in knowledge
about it. See the March 9,1990; July 13,1994;July 15,1998; and June 5,2002, issues
of JAMA for articles from the first 4 International Congresses on Peer Review in
Biomedical Publication.
Peer reviewers should assess all components of a manuscript, including online-
only supplementary material, and are usually asked to provide comments for the
authors regarding the strengths and weaknesses of a paper, including suggestions
for improvement. Reviewers also make recoinmendations to the editor, usually on a
form provided by the journal (Figure 2), but specific criticisms and suggestions are
much more valuable than summary judgments. It is remarkable that the peer review :,'

process depends largely on the efforts of peer reviewers who donate their time-
sometimes large amounts of it14-in the interest of the quality of publications in
their field. The speed and efficiency of the peer review process has been improved
\
by the availability of electronic or Internet-based peer review systems. Using such 'i ,
systems, which are often combined with electronic or Internet-based manuscript
submission, peer reviewers can be queried regarding their availability, receive or
Figure 2. JAMA peer
reviewer comments form. N;A
indicates not applicable.
 -.

6.1 Editorial Assessment .._

;:- -
download a copy of the submission for review, and send their review and recorn:,
mendations electronically, eliminating the time previously required for telephone
contacts and mailing or faxing of paper copies.

Selection of Reviewers. The selection of peer reviewers and the number of reviewers
for a particular submission are matters of editorial judgment. Peer reviewers are
,, .
usuaHy experts who are not part of the journal staff. However, editorial staff members I

may serve as peer reviewers in areas oftheir expertise. Reviewers may be members of [
the journal's editorial board, or a peer review panel, or they miy have no other as- I
sociation with the journal. The editor's knowledge of experts in a particular field often I
1
determines reviewer selection. Many journals maintain a database of reviewers in- I
dexed by areas of expertise and including information on review quality and turn-
around time. A paper's reference list can be useful in indicating contributors to the I-
literature on the same topic. A literature search b ; ~the editor can also be helpful in f

identifying potential reviewers. I

Authors sometimes suggest names of possible reviewers and also may indicate
persons they believe should not review their paper, usually because of perceived
bias. ~ditorsshould cohsider such information, but the selectionof reviewers belong?
to the editor, who must use judgment in distinguishing a reviewer's valid praise o{
criticism from unwarranted bias for or against a particular submission. In an obser:
vational study at 10 biomedical journals,15 reviewers suggested by authors did nqt
differ in the quality of their reviews compared with reviewers selected by editors; but ,
author-suggested reviewers tended to make more favorable recommendations for- -'1
publication. Reviewersshould disclose to the editor any conflicts of interest they may
have regarding a topic or an author (see 5.5.6, Ethical and Legal Considerations,
Conflicts of Interest, Requirements for Peer Reviewers).

Statistical Review. Reviewers with expertise in statistics Cincluding the assessment of

study design and research methods) are essential to evaluate the quality of original
research reports. Such reviewers may serve as paid consultants to a journal. Empir-
ical studies have shown that statistical review can be very helpful in selecting and
improving scientific reports for Unfortunately, many published re-
search articles are flawed by weaknesses in study design and methods that should
have been detected by review or, far better, prevented by appropriate statistical
consultation in planning the research before the manuscript was written.

Concealing of Author and Reviewer Identities. Among the unsettled issues in peer ;
review are efforts 'to conceal the identities of authors (and their affiliations) from i
'reviewers,and the question of whether the identities of reviewers should be revealed 1
to authors. Biomedical journals commonly use a "single-blind" (single-masked) re- i
view process in which authors' identities are revealed to reviewers, but the names of !
reviewers are not revealed to authors (see 5.7.1, Ethical and Legal Considerations,
Confidentiality, Confidentiality During Editorial Evaluation and Peer Review and "
After Publication). This process recognizes the difficulty of concealing author identi- :
ties, makes it easier for reviewers to detect attempts at duplicate publication by the \
same authors, and may encourage more candid reviews because the reviewers know \
they are anonymous to the authors, who may be their professional colleagues.
Flowever, this single-blind tradition is controversial. Reviewers might be influ-
cnced by the identities and reputations of authors or their affiliations and thus not
.I ': . .
306 ... . ..
!::,
 6.1.7 Revision

judge a manuscript solely on quality and importance. Furthermore, some critics Ix-
lieve that authors ought to know who is evaluating their work and that rcvie\vcrs
should stand by their critiques by signing them, a process sometimes called "open
peer re vie^."^^^^ ~ournalpolicies vary regarding concealing or revealing author anrl
reviewer identities, and these practices should be indicated in the inan~ctionsfor
authors (see 5.11.4, Ethical and Legal Considerations, Editorial Responsibilities. Kolcs,
Procedures, and Policies, Editorial Responsibility for peer Review). In sonie tlisci-
p l i e s (eg, nursing and psychology), "double-blind review, in which neither author
nor reviewer identities are revealed, is common. Authors who submit a paper to a
journal that attempts to conceal author identities should remove identifying infor-
mation from all pam of the manuscript. Author names, affiliations, and acknowl-
edgments (including funding sources) should be submitted separately.
A few empirical studies of these issues have been published. One relevant
finding is that attemptsto conceal author identitiesare often not successful due to xlf-
references in the paper or reviewer knowledge of the authors' work. The latter is not
surprising because the reviewers are experts in the authors' fields. Thus, "blind"
review is often unblinded. A multijournal randomized controlled tria1l9 found that
masking of author identities was successful for only 68% of nianuscripts overall, and
that author mas)dng tended to be less successful for reviewers with more research
experience and for well-known authors, but was unrelated to a journal policy of
masking." ~ v e moren important,masking of author identities, wheiher it was success-
ful or not, did not improve the quality of reviews as assessed by editors or author^.'^
.These findings were si& to the results of trials of masking of author identities
undertaken at single journa~s.~'-~~ In a large-scale "field trial," the C a d i a n Medical
AssocfationJoumal (GWAJ)in 1984 switched to concealing author identities but
reversed this practice in 1990 after concluding that the time-consuming efforts
to conceal author identities were often unsuccessful and did not improve the re-
view process.z4
Less empirical information is available on the effects of ide~tifyingpeer re-
viewers to authors (open peer review) vs keeping them anonymous. A randomized
trialz5 performed at the BMJ concluded that asking reviewers to consent to being
identified to authors had n~ important effects on quality of reviews, recommenda-
tions regarding publication, or the time taken to review, but it increased the likeli-
, hood of reviewers declining to review. Positions in favor of open peer review are
usually taken on the grounds of ethics and acc~untabilit~.~
Whatever its problems may be, it is clear that peer review "has been indispens-
able for the progress of biomedical sciencen2' and that no better alternative has
emerged for the assessment and improvement of submissions to biomedical and
scientific journals." ~ e n n i e ~has
~ ' observed,
~' "It is therefore no surprise that as the
evidence of its flawsand inefficienciesaccumulates, peer review, far from found&ring
as it hits iceberg after iceberg, shrugs them off and sails proudly on."

Revision. If an editorial decision is made to request revision of a submitted ni:inu-

script, the author should receive specific recominendations from the editor almut
how to improve the paper, in addition to receiving the comments of the peer re-
viewers. Guidance from the editor is particularly imponant if recommendations from
the peer reviewers are discordant. The revision process is n1.y the appropriate tlme
b for the editor to make suggestionsregarding contlcnvng ~ i l m;lnirwrlpt
c ancl rculue<\
for additional data or analyses, and to ol,tatn rc-clutrt~lxttllorall~p.funding. ant1
c . u n l l ~ cof~ interest statements. Authors are usually requested to submit a list of the '

rcvlslons completed and the reasons for any suggested revisions not undertaken
\\.hen they return the revised manuscript. As previously noted (see 6.1.1, Editorial
Decisions), the editor should make it clear that a revision will require editorial eval-
uation and possibly additional peer review, s o no promise of acceptance for publi-
cation can be made in advance of that assessment. Unless there is a compelling reason -
for the revised paper to be evaluated by a new reviewer, peer review of a revision (if it
is necessary in the editor's judgment) should usually be done by the original peer
reviewers, who, along with the reviewing editor, are in the best position to evaluate
the success of the revision process.

Appealing a Rejection. If a paper is rejected, authors occasionally ask for reconsid- -.

eration, usually because they believe the reviewers or the editor have misjudged the i
importance and quality of the submission. Thii situation can be viewed in 2 different :
ways. On the one hand, peer review and editorial decisions are based on fallible :
human judgments. Mistakes can be made, so perhaps the rejected manuscript merits
reconsideration. On the other hand, heeding appeals for reconsideration may fulfill .
the adage "The squeaky wheel gets the grease," Reconsideration of papers solely on :
the basis of author complaints could be unfair to authors who have equally legitimate :
grounds for reconsideration but who do not appeal. Thus,some journals take the i- .
position that rejections are final. Other journals reconsider rejected submissions. at : '

the discretion of the editor who made the initial decision. Such discretion usually ; .lbc
would include consideration of whether the authors provide objective grounds for
reconsideration of the original decision, particularly if they can provide new data or
new analyses, as opposed to diierences of opinion about editorial priority (see 6.1.2,
Assessment Criteria, and 5.11.5, Ethical and Legal ~onsidektions,Editorial Respon-
sibilities, Rules, Procedures, and Policies, Editorial Responsibility for Rejection).

~ost~ublication ~eview.Evaluation does not end with publication. Postpublication

review includes letters to the editor that identify flaws or additional implications,
rapid online responses to published articles, efforts to replicate the work, and the
experience of clinicians in applying the information in practice. Such evaluations are
at least as important as prepublication review. Electronic journals should link from .
articles to the letters related to them to facilitate retrieval. Editors should also per-
form a quality review of each published issue of their journal, looking for problems
in content and format that can be corrected or improved in subsequent issues (see
5.11.13, Ethical and Legal Considerations, Editorial Responsibilities, Rules, Proce-
dures, and Policies, Editorial Quality Review).

Editorial Processing. Editorial processing-refersto the processing of manuscripts

after acceptance in preparation for publication (Figure 1). With the development of
electrcbilic document processing, the term manuscript has moved increasingly far ...

from its handwritten origins to refer to a prepublication document, whether it hap- ',

pens to be a hard-copy typescript or an electronic file. Manuscript submission, peer i,

\
review, editing, processing, and tracking are now commonly performed electron- !
ically. A major technical issue for many publishers is the need to efficiently process I
content for multiple publication outputs, such as print, Web, reprints, and personal I
digital assistants (PDAs). The use of electronic markup languages such as XML or
 6.2.3 Proofreading

SGML to provide coding for each content element facilitates the conversions neces-
sary for such multiple outputs.

Manuscript Editing. After acceptance for publication, a manuscript undergoes copy

editing, now often referred to as manuscript editingz8 Extensive editing for clarity,
accuracy, and internal consistency may be necessary for .some manuscripts. The
manuscript editor coordinates communication between the editor, author, and pro-
duction staff. Manuscript editors incorporate suggestions of the reviewing editor;
correct grammar, spelling, and usage; querjr ambiguities and inconsistencies;venfy
mathematical calculations;verify reference citations; and edit to journal style. Tables,
boxes, and figures are also edited for style (see 4.0, Visual Presentation of Data),
accuracy, and consistency with the text. Original figures may be created by a graphics
specialist in consultationwith the author and reviewing editor. The manuscript editor
sends the edited manuscript, including online-only content, with proposed additions
and deletions clearly iridicated (see 23.0; Manuscript Editing and Proofreading), as
well as queries, alongwith a cover letter and the edited art and tables, to the reviewing
editor and the author for approval.'~fter.theauthor responds, the manuscript editor
incorporates the authois changes. Any substantive changes requested by the author
(eg, inclusion of additional data or analyses, requests for addition of figures or tables)
Id be discussed with and approved by the reviewing editor.

Composition. Page Makeup, and Web content. Once the author's and reviewing
editor's changes have been made i n the manuscript file, the document is ready
to be composed, or made into pages. Before the widespread use of electronic page
makeup systems, galley proofs of typeset text in long columns were produced.
A layout served as the model for the page, Showing breaks (if any) in the title, type
sizes and spacing in the text, and placement of tables, figures, and headings. The
galley proofs were then ait and pasted along with the tables and art to make page

In an electronic composition system, codesmust be inserted for each element (eg,

title, authors, abstract, headers) of an article according to journal style. An electronic
composition operator then pulls the text, tables, and art together in the electronic
composition system and arranges these elements into pages according to design and
typographic specifications. These pages can be printed as page proofs, or can be sent
electronically, for review and approval. For print publication, the pages can be trans-
mitted electronically to a printer. For ele.ctronicpublication, coded files are converted
to an appropriate language (eg, HTML) or forinat (eg, I'DF) for Web posting.

Proofreading.The page proofs are checked by a proofreader and by the manuscript

editor. In a traditional publishing process, the proofreader checks the m;lnuscript
copy word for word against the typeset copy, alerting the nlanuscript editor t o any
discrepancies (see 23.0, Manuscript Editing .and Proofreading). In an electtonic
processing system, the role of the proofre:~deihas changed. The proofre:lder m:l!,
look only for line breaks and problems that arose through improper cociinp cC$.
space problems or incorrect font) or page makeup (eg, misplaced blocks 01' ~ y p c01.
improper line justification). The manuscript editor, reviewing editor, ancl/or ;~ii[l,r )I.
may perform the word-for-word reading once done by a proofreader. I{cvi.;cd p;~gt.
proofs can be generated and checked again by a prooftc;rcler. Content f o r c.l~.c1 1 , , ! I N

309
.. ..
6.2 Ed~torialProcessing
.?
pilt)l~cat~on htlould JIX, Ix rrv~cwruiand compared with print content for errors and
rnlx.slrlg clcmttnts Lxfore release.

Advertising. At the same time as the manuscript editing and composition of articles
for an issue are proceeding, advertisements are scheduled for specific issues, and
possibly for specific positions in an issue (eg, back cover or facing the table of
contents). Advertising sales and placement should be administrativelyseparate from
all editorial functions to ensure that there is no influence by an advertiser on any
editorial decisions. As stated by the International Committee of MedicalJournal Edi-
t o r ~ , editors
*~ must have full and final authority for approving advertisements and
enforcing advertising policies. Staff members responsible for issue makeup should
ensure that there is no inadvertent link between advertisements and articles-for
instance, that no advertisement for an antihypertensionmedication appears next to a ,I-
research report on hypertension (see 5.12, Ethical and Legal Considerations, Adver- t

tisements, Advertorials, Sponsorship, Supplements, Reprints and e-Prints).

Issue Makeup and Review. For each journal issue, the production staff merges the '
e d i t o h and the advertising material, numbers the pages, prepares the table of con- .
tents, and produces an imposition(a list that shows the sequential order of pages with
placement of editorial and advertising content). The editorial content of each issue -
should be determined by the journal editor or managing editor, considering the,
balance of types of articles and thematic consistency (eg, there might be sevkral.- --q ,'

articles on related topics). The made-up issue is reviewed by editorial and production --
staff, and final changes are incorporated. When final pages have been created, the
electronic files can be telecommunicated to the printer. For print publication, proofs
for each page may be prepared and returned to the journal for final review. When all
pages have been approved, the issue is printed, bound, and mailed.

Reprints. Authors have the option to purchase reprints or e-prints of their articles.
Reprints may also be sold to individuals, organizations, or companies interested in
disseminating the article (see 5.6.10, Ethical and Legal Considerations, Intellectual
Property: Ownership, Access, Rights, and Management, Standards for commercial 1.
Reprints and E-prints).' I
Corrections. Errors are an inevitable part of the publishing process. Fortunately,
I
authors or readers commonly call them to the journal's attention, or they are found
during the internal quality-review process, and corrections can be published. In
JAMA, corrections are printed at the end of the Letters to the Editor section and are
listed in the Table of Contents. Correctionsshould be indexed, with a cross-reference
to the original article. This will enable online database services (such as MEDLINE) to
link indexed articles with published corrections (see 5.11.8, Ethical and Legal Con-
siderations, Editorial ResponsiI$lities, Roles, Procedures, and Policies, Correspon-
dence [Leaers to the Editor], and 5.11.9, Legal and Ethical Considerations, Editorial
Responsibilities, Roles, Procedures, and Policies, Corrections [Errata]). Corrections
should also be linked from the article to the correction on the journal's Web site and
appended to the article PDF. If online-only corrections are made or corrections are !
made online before appearing in print, the change and date should be indicated in the
electronic file.
 6.2.8 Index

Index. Indexes organized by subject and author's surname are published regularly in
most medical journals. Some journals publish indexes only online and not with their
print version. Indexes may be created by indexing specialists or by indexing soft-
ware that searches articles for key words.
. .

ACKNOWLEDGMENTS
Principal author: Richard M. Glass, MD

. Karen Adams-Taylor, MS, J A M and Archives Journals, reviewed the section on

editorial processing. Kathy Schneider, Harmony Communications & Design, Inc.
Downers Grove, Illiiois, provided the figures.

REFERENCES
1. Guyaa GI Rennie D, eds. Usets' Guides to the Medical Literutzire: A A.lrrrrrrrr1 JLr
Em.dence-Based Clinical Practice. Chicago, IL: AMA Press; 2002.
2. Chalrners TC, Frank CS, Reitman D. Minimizing the three stages of publication 1)i;ls.
J A M . 1990,263(10):1392-1395. '

4. Burnham JC. The evolution of editorial peer review. JAMA. 19$;263(10): 1323-1.329.
5. Rennie D. Editorial peer review: its development and rationale. In: Godlee F. Jcffcrson
T, eds. Peer Reviau in Healtb ~ci&es, London, England: BMJ Books; 199%3- 13.
6. Lock S. A DiJkdtBalance: Edirorial Peer Review in Medicine. Philadelphia. I ' k IS1
Press; 1988.
7. Remie D. Editorial peer review in biomedical publication: the First International
Congress. J M .1990,263(10):1317.
8. Godlee F, Jefferson T, eds: Peer Review in Health Sciences. London, England: BhIJ
Books; 1999.
9. Weller AC. Editorial PeaReview: Its Stmgtbs and Weaktzeses.Mdfortl, NJ: Alneric;ln
Society for Information Science and Technology; 200 1.
10. Goodman SN, Berlin J, Retclier SW, 1:letcher Rtl. M:~ni~script qir~lirybefore anrl alic:?
peer review and editing at Annak of Irttcimal Mrtlicirre. Anr? Intenr Med.
1394;121(1):11-21.
11. Ixxk S. Dtws cditorkll pcrmrrc.vic.w work? Arrrr 1rr1~~r.11 Akrl. 100~~;171( 1 ):60-01.
12. Pierie J-PEN, Walvoort HC, Overbeke AJI'M. Readers' evaluation of effect of peer
review and editing on quality of articles in the Nederla~zckTijdschnp voor Genees-
kunde. hncet. 19%;348(9040):1480-1483.
13. Jefferson T,Alderson P, Wager E, Davidoff F. Effeas of editorial peer review: a
systematic review. JAMA. 2002;287(21):2784-2786.
14. Yankauer A. Who are the peer reviewers and how much do they review?JAMA.
1330;263(10):1338-1340.
15. Schroter S, Tite L. Hutchings A. 13l;lc.k N. 1)ifrcrcncc.s in review clu;llity ;rntl rcc.oln-
mendations for public=ltion Ixtwccn peer ~~cviewcrs si~ggcstcclI)y a ~ ~ t l ~or
o rIly
s
editors. J&. 2006;295(3):314-317.
16. Altman DG,Schulz KF. Statistical peer review. In: Godlee F, Jefferson T, eds. Peer
Xm'ew in Health Sciences. London, England: 13ooks: 1999:157-171.
17. Altman DG.I'oorquality n~cdicalresearch: wll:~~ c;u~journals cltPJAMA. 2002:287(2 1):
2765-2767.
18. Fabiato A. Anonymity of reviewers. C'urdiorxi.~~ I+.<. 1')94:2X(H):1134-1139.

311
6.2 Editorial Processing

19. Justice AC, Cho MK, Winker MA, Uerlin JA. ~ e n n j eD; and PEER Invesrigotors. Docs
masking author identity improve peer review quality? a nndomized controlled tnal.
J A M . 1998;280(3):240-242.
20. Cho MK, Justice AC, Winker MA, et al. Masking author identity in peer review: what
factors influence masking success?JAMA. 1998;2800):243245.
21. McNutt RA, Evans AT, Fletcher RH, Fletcher SW. The effects of blinding on the quality
of peer review: a randomized trial.JAMA. 1930;263(10):1371-1376.
22. Yankauer A. How blind is blind review? Am J Public Health. 1991;81(7):843-845.
23. van Rooyen S, Godlee F, Evans S, Smith R, Black N. Effect of blinding and unmasking
on the quality of peer review: a randomized trial. J A M . 1998;280(3):234-237.
24. Squires B. Editor's page: blinding the reviewers. WJ. 11930;142(4):279.
25. Rooyen S, Godlee F, Evans S, Black N, Smith R. E f k t of open peer review on quality of
reviews and on reviewers' recommendations: a randomized trial. BMJ. 11999;318(7175):
23-27.
26. Kassirer JP, Campion EW. Peer review: crude and understudied, but indispensable.
JAMA. 1994;272(2):96-97.
27. Godlee F, Jefferson T. Introduction. In: Godlee F, Jefferson TI eds. Peer Review in
Healtb Sciences. London, England: BMJ Books; 1999:xi-xv.
..
28. Iverson C. "Copy editor" vs ".manuscript editor" vs . :venturing onto the minefield of
titles. Sci Editor. 2004;27(2):39-41.
29. International Committee of Medical Journal Editors. Advertising. In: Uniform Re-
quirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for
Biomedical Publicatidn. http://www.icrnje.org. Updated February 2006. Accessed
December 15, 2006.
 7.1.1 . Modifiers (Noun.Strings)
7.1.2 . Modifying Gerunds 7.7
7.1.3 Subject-Complement Agreement Parallel Construction
7.7.1 Correlative Conjunctions
7.7.2 Elliptical Comparlsons
7.7.3 Series or Comparisons
7.2.1 Personal Pronouns 7.7.4 Lists
7.2.2 Relative Pronouns
7.2.3 Indefinite Pronouns 7.8
Subject-Verb Agreement
7.8.1 Intervening Phrase
7.8.2 False Singulars
7.3.1 Voice 7.8.3 False Plurals
7.3.2 Mood 7.8.4 Parenthetical Plurals
7.3.3 Tense 7.8.5 Collective Nouns
7.3.4 Double Negatives 7.8.6 Compound Subject
7.3.5 Split Infinitives and Verb Phrases 7.8.7 Shift in Number of Subject and Resultant
7.3.6 Contractions Subject-Verb Disagreement
7.8.8 Subject and Predicate Noun Differ
in Number
Modifiers 7.8.9 Every and Many a
7.4.1 Misplaced Modifiers 7.8.1.0 .One o f Those
7.4.2 Verbal Phrase Danglers 7.8.1 1 Number

7.5.1 Homonyms
7.5.2 Idioms, Coiloquialisms, and Slang
7.5.3 Euphemisms
7.5.4 ClichQs ...

7;bediJference between the almost right word and the

rkht word is nu fly a l a e c rnattcv-ii s: rbc d{J?v-c.r~ce

. A clear understanding of grammar is basic to good writing. Many excellent g ~ u n n i ; ~ r

books provide a detailed discussion of specific principles (see 25.3, Hesourccs.
Gener~lStyle and Usage). In this section, the li)cus is on ho\v to avoicl conillion
grammatical ancl writing errors. 'l'llc COIIIL~III 01' 111i.s( . l ~ ; ~ l ) l iis~ ro r ~ : ~ l i i %l'ro111
~ ' d 1111'
smallest parts of speech (eg, nouns and pronounh) 10 1.11gc.r\trrlc.turc\ (L.K. scnlcnccz
and paragraphs).

N O U ~ S . Noi11>s(wor'ls I I ~ ; I I 11;11111~ .I IH'1,1111. 1,1.1( 1.. 1 1 1 1 1 1 ~ . 111 1 1 1 ~ . . 1 1 I I I ; I ) 4<.1-\.1. . I \

subjects or ol~jects.

315
7.1 Nouns

P Modifiers (Noun Strings). Although in English nouns can be used as

overuse of noun modifiers can lead to a lack of clarity. Purists may
rules on usage, but, as with the use of nouns as verbs (see 11.3, Correct and preferred .I,,
Usage, Back-formations), the process of linguistic change is inevitable, and gram:.. '
matical rigor must be tempered by judgment and common sense. -* ..

diabetes patient patient with diabetes, diabetic patient

depression episode depressive episode, episode of depression
elderly over-the-counter elderly users of over-the-counter drugs
drug users
In.me Careful Writer,~ernsteidadvises the use of no more than 2 polysyllabic noun
modifiers per noun for the sake of clarity. However,long noun strings are sometimes dif- !-.
ficult to avoid. If several of the attributive nouns are read as a unit, the use of more than i
2 may not compromiseclarity,especially in scientificor technical communications.Thus, i
noun strings may be more acceptable, for 'thesake of brevity, if the terms have been ;
previously defined without noun strings. Some acceptable examples appear below: .'

cornmunit hospital program nicotine replacement program .

i
physician provider organization placebo.pain medication !
risk factor surveillance system ' proficiency testing program . .

baseline CD4 cell counts cliical research organization

sudden infant death syndrome community outreach groups

If there is a possibility of ambiguity, hyphens may be added for clarity (large-vessel

dissection) (see Temporary Compounds in 8.3.1, Punctuation, Hyphens and Dashes,
Hyphen).

Modifying Gerunds. When a noun or pronoun precedes a gerund (a verb form

ending in -ing that is used as a noun), the noun or pronoun is possessive. (See also
8.7, Punctuation, Apostrophe.)
The toxicity of the drug was not a factor in the patient's dying so suddenly.
The award recognized the.researcher's planning & well as his performance.
Present participles (used adjectivally) should not be co-?fused with gerunds. In the
sentence below, the objective case (them) is correct.
I watched them gathering in the auditorium.
If the possessive their were used instead of the objective them, the emphasis would
be on the action (gathen'ng).
!
Subject-Complement ~greement.Subjects and complements should agree in num-
ber. i
The child can take off his own shoes. \i 1
We asked trial participants to return their pill dispensers. \ 1
However, when the complement is shared by all constituents of the plural sudject, it
rcnl;~inssingular. I
 7.2.2 Relative Pronouns

The authors were asked to revise their paper.

All study sites obtained approval from their institutional review board.
Investigators inserted a catheter into the study participants' pulmonary artery.

Pronouns. Pronouns replace nouns. In this replacement, the antecedent 111ustI,t.

clear and the pronoun must agree with the antecedent in number and gender.
Avoid: The authors unravel the process of gathering information
about diethylstilbestrol and dis~minatingit. [Antecedent
unclear; does it refer to information or to diethylstilbestrol?l
Correct: The authors unravel the process of gathering and
disseminating information about diethylstilbemol.
Avoid: A questionnaire was given to each medical student and their
spouses. [Disagreement of pronoun with referent in number;
the referent is eacb medical sfudent (singular), but the
pronoun used is plural (their spozses).l
Bettec A questionnaire was given to the medical students and
their spouses.
or
A questionnaire was given to each medical student and his
or her spouse.
Note: The possessive pronoun its should not be confused with the contraction it's
(see also 8.7.2, Punctuation. Apostrophe, Possessive Pronouns).

Personal Pronouns. Care must be taken to use the correct case of personal pronouns:
subjective (the pronoun is the subject of the phrase or clause) or objective (the
pronoun is the object of the phrase or clause).
She was assigned to the active intervention group. (She is the subject.)
Collect all the samples and give them to her. (Her is the object.)
Your decision affects him and me. (Both him and me are objects.)
Do not substitute a reflexive pronoun, ending in -selfor -selves, for a simple personal
pronoun.
Avoid: , George, Patricia, and myself attended the lecture.
The author replied to the editor, illustrator, and myself. i

Correct: George, Patricia, and I attended the lecture.

. The author replied to the editor, illustrator, and me.

duce a qualifying clause.

Who vs Whom, who is used as a subject and whom .IS ;in oblecr The u.inlples below
illustrate correct usage.

317
 --- _
7 . 2 Pronounr

GIVC(hC award 10 whomever you prefer. [Objective case: whomever is the

o\,jec~of [he verb preJer.1

Give thc :iwsrd to whoever will benefit most. [Subjectivecase: whoever is the
subject of will beizeJit.1
Whom did you consult? [Objective case: whom is the object of consult.]
Who was the consultant on this case? [Sbbjectivecase: who is the subject of
the sentence.]
He is one of the patients whom Dr Rundle is treating. [Objective case: whom
is the object of is treating.]
He is one of the patients who are receiving the placebo. [Subjective case:
who is the subject of are receiving.]

That vs Which. Relative pronouns may be used in subordinate clauses to refer to

previous nouns. The word that introducesa restrictive clause, one that is essential to the
meaning of the noun it describes. The word which introduces a nonrestrictive clause,
one that adds more information but is not essential to the meaning. Clauses that begin
with which are preceded by commas. Two examples of correct usage follow.
A study on the impact of depression on US labor costs was published in the
2003JAMA theme issue on depression, which &mains articles on a range of.
similar topics. Wonrestn'ctiv~there was only one theme issue on depression in -.. ,
2003.1
The issue ofJAMA that contained the article on the impact of depression on
US labor costs was the 2003 depression theme issue. [Restrictive; there are
thousands of issues of JAMA.1
Following are examples of ambiguous or incorrect usage that highlight this gram-
matical problem.
Incorrect: The high of antibodies to the 3 Bartonella
'
species, which were examined in the present study,
indicates that health care workers should be alert to
possible infection with any of these organisms when
treating intravenous drug users. [There are more than 3
species of Bartonella. Hence, the correct form here would
be " . . .the 3 Bartonella species that were examined.. .."I
Ambiguous: Many reports have been based on series of patients from
urology practices that may not fully reflect the entire
spectrum of illness. [Do the patients or the practices not fully
reflect the entire spectrum of illness? Also, do the reports
involve a11 or only some urology practices?]
Reworded: Many reports have been based on patients in urology
practices, which may not fully reflect the entire spectrum of
illness. [Urology practices in general do not capture the
range of the disease.] I
 7.2.3 Indefinite Pronouns

Many reports have been based on data from urology practices

that may not fully reflect the entire spectrum of illness. [Some
particular urology practices do not capture the range of the
disease, but others might.1

Note: The omission of that to introduce a clause may cause difficulty in compre-

Avoid. This morning he revealed evidence that calls the study's integrity
into question has been verified.
Better: This morning he revealed that evidence that calls the study's
integrity into question has been verified.

The addition of that after m a l e d frees the reader from backtracking to uncover the
meaning of the sentence above. The use of that ta introduce a clause is particularly
helpful when the second verb appears long after the first has been introduced
(above, the interval between revealed and has been verrijied).

lndefinite Pronouns. Indefinite pronouns refer to nonspecific persons or things.

Most indefinite pronouns express the idea of quantity and share properties of col-
lective nouns (see 7i8.5,Subject-Verb Agreement, Collective Nouns).

6Pronoun-VerbAgreement Some indefinite pronouns (eg, each, eithet; neither, one,

no one, eoeryone,someone, anybody, nobody, somebody) always take singular verbs;
some (eg, several,fau, both, many) always take the plural; and some (eg, some, any,
none, all, and most) may take either the singular or the plural, depending on the
referents. In the last case, usually the best choice is to use the singular verb when the
pronoun refers to a singular word and the plural verb when the pronoun refers to a
plural word, even when the noun is omitted.
Singular eferent: Some of her improvement is due to the increase in
dosage.
Plural referent: Some of his calculations are difficult to follow.
Singular r e f m t : Most of the manuscript was typed with a justified
right-hand margin.
Plural r e f m t : Most of the manuscripts are edited electronically.
.
Singular referent: Some of the manuscripts had merit, but none was
of the caliber of last year's award winner.
Plural m f m t : None of the demographic variables examined were;
found to be significant risk factors.

Pronoun-Pronoun ~greement.The use of.;in indefinite pronoun as the antcccdc.l~\oI'

another pronoun .can create confusion. some writers try to avoid bias l ~ y
using their or he/she with plural indefinite pronouns (eg, Everyone shoulcl cite fll~cir
sources.). Grammatically, the use of a plural pronoun is not correct, and construc-
tions such as s/he are distracting. He or she should be used consistently :lnrl tlic
writer should keep the context in mind when making these decisions. Ilcttcr still.
when possible use the plural throughout3 (eg, All authors should cite their sonrccz. ).
(See also 11.10.1, Correct and Preferred Usage, ~nc]usi\~e Ianguagc. Scs/Gcnclc.l..

319
7 . 3 Verbs

Verbs. \fert>sexprcs.\ a n ;Itrlon. an occurrence, or 3 n l d c of being. T h r y tuve vo~cc.

mood, nnd ten.%.

Voice. In the active voice, the subject does the acting; in the passive voice, the subject
is acted on. In general, authors should use the active voice, except in instances in
which the actor is unknown or the interest focuses on what is aaed on (as in the
following exanlplt. of p~ssivevoice).
He was shot in the abdomen and within 10 minutes was brought to the
emergency department.
If the actor is mentioned in the sentence, the active voice is preferred over the passive
voice.
Passive: -Datawere collected from 5000 patients by physicians.
Active (better): Physicians collected data from 5000 patients.
Passive: The definition of bullying used in the survey was taken
from previous studies.
Active (bet~er): The authors.used previous definitions of bullying in
the survey.

Mood. Verbs may have 1of 3 moods: (1) the indicative (the most common; used for
ordinary objective statements), (2) the imperative (used for requesting or com-
manding), and O the subjunctive. '

Subjunctive verbs cause the most difficulty;they are used primarily for expressing
.
a wish (I wish it were possible), a supposition (If I were to accept the position. .I, or
a condition that is uncertain or contrary to fact (If that were m e . . .; If I were
.
younger. .). The subjunctive occurs in fairly formal situations axid usually involves
past (were) or present (be) forms.
P a s fonn: If we were to begin treatment immediately, the patient's
prognosis would be excellent.
Present fonn: The patient insisted that she be treated immediately.
The subjunctive is sometimes used incorrectly, eg, where matters of fact-not
supposition-are discussed. In the following examples, the indicative, not the sub-
junctive, is correct.
Therefore, we determined whether there had been [not the subjunctive,
were1 deviation from the prescribed regimen.
W'e investigated whether the fracture had been [not the subjunctive, were1 set
incorrectly.

Tense. Tense indicates the time relation of a verb: present (lam), past (Iwas), future
(Iwill be), present perfect ( I have been), past perfect (Ihad been), and future perfect
( I will bave been). It is imporrant to choose the verb that expresses the time that is
intended. It is equally important to maintain consistency of tense.
The present tense is used to express a general truth, a statement of fact, or
something continuingly true.
r.
r
I'
i
s

He discovered enzyme~--~RNA y copy [not copied1

polymerases-that direc~l
7.3.3 Tense

the messages encoded in DNA.

ti For this reason, the present tense is often used to refer to recently published work.
1.
. indicating that it is still valid.
Kilgallen's assay results demonstrate the highest recorded sensitivity ;~nrl
specificity to date.
The present perfect tense illustratesactions completed in the past but connected \vitll
the present2 or those stil! ongoing. It may be used to refer to a report published in tllc
recent past that continues to have importance.

5, Kaplan and Rose have described this phenomenon.

The past tense refers to a completed action. In a biomedical article the past tense is
usually used to refer to the methods and.results of the study being descril~etl:
We measured each patient's blood pressure.
Group 1had a seropositivity rate of 50%.
The past tense is also used to refer to an article published months or years ago that
is now primarily of historical value. Frequently a date will be used in such a refer-
ence.4
In their 1985 article, Northrup and Miller reported a high rate of mortality
among children younger than 5 years.
In general, tense must be used consistently:
Incorrect: There we& no adverse events reported in the control group,
but there are 3 in the intervention group.
Correct: There were no adverse events reported in the control group,
but there were 3 in the intervention group.

However, tense may vary within a single sentence, as dictated by context and judg-
ment.
We determined which medications are used most frequently by this popu-
lation.
Alternatively, the past tense and the present tense may be used in the same sentence
to place 2 things in temporal contela:
Although the previous report demonstrated a significant response, the;
follow-up study does not.
Even when tenses are mixed, however, consistency is still the rule:
Incorrect: I found it difficultto accept Dr Smith's contention in chapter 3
that the new agonist has superior pharmacokinetics and was
therefore more widely used.
Comxt: I found it difficult to accept Dr Smith's contention in chapter 3
that the new agonist has superior pharmacokinetics and is
therefore more widely usctl.
7.4 Modifiers

Double Negatives. Two negatives used together in a sentence constitute a dout)lc

negative. The use of a double negative to express a positive is acceptable, although it
yields a weaker affirmative than the simpler positive and may be confusing:
Our results are not inconsistent with the prior hypothesis.
More direct incentives have produced substantial changes in behavior in the
past, although not without adverse consequences.
Rheurnatologic symptoms were not uncommon in both groups.
However, it is not grammatically acceptable to use a double negative to emphasize
the negative. In the following example, the double negative conveys the opposite of
what is intended.
The authors cannut barely contain their enthusiasm.
A double negative is best avoided in scientific writing because it often causes the .
reader to go back and reread the sentence to make sure of the meaning.

Split Infinitives and Verb Phrases. Although some authorities may still advise the
avoidance of split infinitives, this proscription-a holdover from Latin grammar,
wherein the infinitive is a single word and cannot be split-has been relaxed. In.
some cases, moreover, clarity is better served by the split Witive.
Ambiguous: The authors planned to promote exercising vigorously. [Is it
the exercising or the promotion of exercising that is vigorous?]
Cleam The authors planned to vigorously promote exercising.
or
The authors planned to promote vigorous exercise.

=w Contractions. A contraction consists of 2 words combined by omitting 1 or more

letters (eg, can't, aren't). An apostrophe shows where the omission has occurred.
Contractions are usually avoided in formal writing.

Modifiers. A modifier describes another word or word group. Words, phrases

(groups of words without a subject or predicate, usually introduced by a preposition
or conjunction), and clauses (groups of words with a subject and verb within a
compound or complex sentence) may all be modifiers. An adjective modifies a noun
or a pronoun. An adverb modifies a verb, an adjective, another adverb, or a clause.
Clauses or phrases may serve as adjectives or adverbs.

Misplaced Modifiers. Misplaced modifiers result from failure to make clear what is
being modified. Illogical or ambigups placement of a word or phrase can usually be
avoided by placing the modifying word or phrase appropriately close to the word it
modifies.
Unclear: Dr Young treated the patients using antidepressants. [Who
used the antidepressants?Ambiguity makes 2 meanings
possible.]
 7.4.2 Verbal Phrase Danglers

Better: Dr Young treated the patients with antidepressants.

or
[alternative meaning]: Dr Young treated the patients who were
using antidepressants.
Unclear: The patient was referred to a specialist with severe bipolar
disorder. [Who had the bipolar disorder?] .
Better: The patient with severe bipolar disorder was referred to a
specialist.

Likewise, sometimes it is necessary for clarity to place an adverb within a verb phrase.
' Note the shift in meaning when the adverb is moved outside of the verb phrase.
He had just called me.
He had called just me.
Use of the word only as a modifier poses particular problems. It must be placed
immediately before the word or phrase it modifies for the meaning to be clear. Note
the different meanings achieved depending on placement in the examples below.
Only medication can ease the pain.
Medication can only ease the pain.
Medication can ease only the pain,

Verbal Phrase Danglers. A participle is a verb form used as an adjective..A dangling

. . partiaple implies an actor but fails to indicate correctlywho or what that actor is. The
following examples of dangling participles illustrate the problem.
Amid. Working quickly, the study was completed early by my
research team. m e participle appears to refer to "the study";
however, it is. the m a r c h team that was working quickly.]
Berm My research team worked quickly and completed the study early.
or
The study was completed early because my research team
worked quickly.
Avoid: Based on our experience, educational interventions are needed
to foster higherquality end-of-life care. [Are the educational
. interventions based on the authors' experience? No-it is the
statement about the need for higher-quality end-of-life care that
is based on the authors' experience.]
Better We have found that educational interventions are needed to
foster higherquality end-of-life care.
or
Experience has shown t11:1t edu~~tional inrewentions ;lrc ncctlctl
to foster higherquality end-of-lifca r c .

A gerund is a verb form used as a noun (.* 7 1 2. Noun.;. hltnlifyinfi C;c.n~nclx), 1.1hv
the dangling participle, rhe thngllnp gcnlntl i1nplic.3;III ;rc.tcbr t l c ~ 4no1 \IX.C I I

323
7.5 Diction
..
who o r what that actor is and sometimes may be confused with a participle modi-
fying the wrong entity,
Avoid: Dietary therapy slows the return of hypertension after stopping
long-term medical therapy. [This states that dietary therapy not
only slows the return of hypertension but also stops medical
therapy.]
Better Dietary therapy slows the return of hypertension after cessation
of long-term medical therapy.
or .
After patients discontinue long-term medical therapy, dietary
therapy slows the return of hypertension.
Avoid: Before initiating an exercise program or engaging in heavy I-
physical lab.? after a myocardial infarction, a physician should
review the exercise program carefully. ["A physician" is errone-
ously implied to be the actor, the one initiating an exercise
program or engaging in heavy physical labor.]
Better: Anyone about to initiate an exercise program or engage in heavy
physical labor after a myocardial infirction should consult his or !
her physician. i. .

k @ f
Diction. Diction, or word choice, is important for any writing to be understood by its L .G-.~:
intended audience. In scientific writing, concrete and specific language is preferred
over the abstract and general.
Avoid-
Better:
Avoid-
The area under study provides new evidence for a solution.
Immunology provides new evidence for a solution.
An individual with a medical degree should examine this lesion.
I1.
Bern A physician should examine this lesion.

Homonyms. Homonyms are words that sound alike but are spelled dierenrly and
have different meanings. They are easily confused, and computer spell-check pro-
grams are unable to diierentiate them. Common examples include affectleffect,
.
accept/except, altar/alter,mistance/mistants, cite/site/sigbt, council/counsel, i d
it%,patiencelpatients, peacelpiece, peak/pek/pique, phral/plural, princtpc!/
principle, and your/you 're. (See also 11.1, Correct and Preferred Usage, Correct and
Preferred Usage of Common Words and Phrases.)

Idioms, Colloquialisms, and Slang. Some language is best avoided in material written
for a professional or academic audience.
Idioms are fixed expre~sions~that cannot be understood literally (kick the bucket,
on a roll, put up with, pay attention).In addition, some may have multiple meanings
that can be understood only in context (pass out, standfor). Idioms are not governed
by any rules and each stands on its own. Be wary of using idioms, particularly for
ri~~diences that include readers whose first language is not English.
Colloc~i~idisms (or casualisms2) are characteristic of informal, casual communi-
cat ion (ain'1, utzpuys, cold turkey,flat line, OK, shell-shocked, tax hike).
 . . . ... .
. .

7.7.1 Correlative Conjunctions

Slang includes informal, nonstandard terms whose meanings are not readily
understood by all speakers of a language. Sometimes slang words are newly coined
(hick, rinky-dink, FAQ) and sometimes they are created by applying new meanings
to existing words (bad, cool, awesome, random, killer).
Colloquialisms and slang should be avoided except in special situations, such as
"flavorful" prose or direct quotations.
My sense is that part of the reason why Claude is able to survive is denial. He
. .
just says, flat out, "This ain't happening." .
The technical terminology specific to various disciplines is considered jargon and
should be avoided (see 11.4, Correct and Preferred Usage, Jargon).

Euphemisms. Euphemisms (from the Greek eu, "good," and pheme, "voice") are
indirect terms used to express something unpleasant. Although such language is often
necessary in social situations ("He passed away.'?, directness is better in scientific
writing ("The patient died."). (See also 11.4, Correct and Preferred Usage, Jargon.)

Cliches. Cliches are worn-out expre&ions (sleep like a log, -deadps a doornail, Jirst
andforemost, crystal clear). At one time they were clever metaphors, but overuse has
left them lifeless, unable to conjure in the reader's mind the original image. Avoid
cliches like the plague.

Sentence Fragments. A sentence must have at minimum a subject and a verb; it

also usually contains m d e r s . Sentence fragments, which lack a subject or a verb,
should not be used in scientific or technical writing (except within the stnlctured
abstract; see 2.5, Manuscript Preparation,.Abstract). Occasionally, writers of prose
and poetry use sentence fragments intentionally, for effect.
Her affect signaled depression. Utter depression.
In scientific writing, these fragments are likely to be unintentional and are definitely
inappropriate.
Incomck The clinical spectrum of disease varying accoding to the
population and age group under study.
Comct: - The clinical spectrum of disease varies according to the
population and age group under study.

Parallel Construction. Parallel constnlction can be used to build a senten5c or

emphasize a point.

. Correlative Conjunctions. Parallelism may rely on accepted cues (eitherlor, &i-

therlnor, notonly/butafso, bothland). All elements of the parallelism that appear on
one side of the coordinating conjunction should match corresponding elements on
the other side.
Avoid: The compleat physician h;ls not only ~n;~stcr~tl tllc science
of medicine but also its an.
Correct: The complear physici:ln h.15 ni;r\tered nor only tllc wiericc
of n~eclicincl,ur ;ilso ir5 . ~ n

325
7.7 Parallel Construction

Better: The compleat physician has mastered both the science and
the art of medicine.
Avoid: Poor drug efficacy may be caused by either lack of
absorption or by increased clearance.
Comct: Poor drug efficacy may be caused either by lack of
absorption or by increased clearance.
Also comct: Poor drug efficacy may be caused by either lack of
absorption or increased clearance.
Amid Three patients either took their medication incorrectly or
not at all.
Comct: Three patients took their medication either incorrectly or
not at all.

Note: Eitherlor is used with only 2 comparators (use with more than 2 items is
considered nonstandard).
Zhcomt: This medication can be taken with either water, milk, or juice.
Correct: This medication can be taken with water, milk, or juice.

Elliptical Comparisons. The conjunction than often introduces an abridged expres-

sion (eg, "You are younger than I [am young])." Correct placement of tban is ini-
portant to avoid ambiguity:
Unclear: Women are more likely to take vitamins than men. [Are
women more likely to consume vitamins than men are, or
are women more likely to consume vitamins than they are to
consume men?]
Rewritten: Women are more likely than men to take vitamins.

Series or Comparisons. Parallel constniction may also present a series or make

comparisons. In these usages, the elements of the series or of the comparison should
be parallel structures, eg, nouns with nouns, prepositional phrases with preposi-
tional phrases.
.
Amid Surgery, radiation therapy, and to give chemotherapy are
possible therapeutic approaches.
Correct: Surgery, radiation therapy, and chemotherapy are possible
therapeutic approaches.
Avoid..

c"orrec~:
When an operation is designed to improve Function rather than
extirpation of an organ, surgical technique dictates outcome.
When an operation is designed to improve the function of an
I
organ rather than to extirpate the organ, surgical technique
dictates outcome.
Amid: There was a long delay between the purchase of a scanner and I
when it started to be widely used.

326
 7.8.1 lnterven~ngPhrase

Correct: There was a long delay between the purchase of a scanner ancl its
widespread use.
Note: Avoid the use of nor when the first negative is expressed by not or no.
Fetuses with congenital diaphragmatic hernia who were stillborn would not
have been included in this study or [not no4 in many previously published
studies.
But: Fetuses with congenital diaphragmatic hernia who were stillborn would
not have been included in this study, nor would they have been included In
other trials. Nor is acceptable in noncorrelative constructions containing a
negative in the firsf

Lists. Parallel construction is also important in lists, whether run in or set off by
bullets or some other device (see Enumerations in 8.2.2,Punctuation, Comma, Semi-
colon, Colon, Semicolon, and 19.5, Numbers and Percentages, Enumerations).
After completing this CME exercise, readers should be able to .
identify the causal mechanism of the disease;
describe the most common symptoms;
understand the litations of pharrnacologic treatment.

Subject-Verb Agreement. The subject and verb must agree 51 number; use a
singular subject with a singular verb and a plural subject with a plural verb. Unfor-
tunately, this simple rule is often violated, especially in complex sentences.

Intervening Phrase. Plural nouns take plural verbs and singular nouns take singular
verbs, even if a phrase ending in a plural noun follows a singular subject or if a
phrase ending in a singular noun follows a plural subject.
Areview of all patients with grade 3 tumors was undertaken in the gniversity
hospital. [The subject in this sentence is review. Ignore aU modifying prep-
ositional phrases that follow a noun when determining verb agreement.]
Avoid: The patient, one of many study participants given access to state-
.
of-the-art medical care from the university's clinical researchers,
were followed up for more than a year. [The verb should be was
, followed up--the subject is patient.]
Sometimes the simplest solution is to rewrite it as 2 separate sentences: i
Better: The patient was followed up for more than a year. She was one of
many study participants given access to state-of-the-art medical
care from the university's clinical rcscarcl~crs.
If the intervening phrase is introduced by with, together with, as well as, along with,
in addition to, or similar constructions, the singular verb is preferred if the subject is
singular because the intervening phrase does not affect the singularity of the subject.
The editor, as well as the reviewers, believes that this article is ready for
acceptance.
1

327
7 8 Subject-Verb Agreement

Illc pawn[. ~c)gc~hc.r

W I I t~lcr phys~clrnand tlcr fanlily, nukes this decision.
The investiptor. in dddition lo 311 p3nicipanls, was expected to abide by the
institution's safety guidelines.
In these instances, recasting the sentence may eliminate confusion. . .
The patient, physician, and family members make this decision together.

tlt:k.-False Singulars. A few plural nouns are used so often in the singular that they are
often paired with a singular verb.
The agenda has been set for our next meeting.
Frequently treated erroneously in this way are the plurals bacteria, criteria, phe-
nometuz, and memoranda. The distinction between singular and plural, however,
should be retained; when the singular is intended, use bacterium, cntm'on, phe-
nomenon, and memorandum.
Also, many now consider acceptable the use of data as a singu~ar.~ In this usage,
data is thought of as a collective noun and, when considered as a unit rather than as
the individual items of data that compose it, it takes the singular verb. However,J A .
and the Arcbives Journals prefer to retain the use of the plural verb with data in all
situation^.^
Very few data were [ndt wry link data was1 available to support our hy-
- - .<..I
i
pothesis.
The word media in the sense of c o ~ u n i c a t i o nmedia
s is becoming acceptable in ;
this collective usage, although its use in this sense has not et reached the accept- . i
ability that agenda has gained and data is close to gaining?lgMost scientific journals
retain the distinction between singular and plural.
I
Singular Each news medium shapes journalism to its own constraints.
Plurak The media give mu.& attention to the managed care debate.
[Here media refers to all types of news coverage.]
1
In the sense of laboratory culture or contrast media, medium should be used for the
singular and media for the plural. i i

False Plurals. Some nouns, by virtue cT ending in a "plural" -s form, are mistakenly
taken to be plurals even though they should be treated as singular and take a singular
verb (eg, measles, mumps, mathematics, politics, genetics). (See 9.8, Plurals, False
Singulars.)

Parenthetical Plurals. When -s or -es is added parenthetically to a word to express the

possibility of a plural, the verb should be singular. However, in most instances it is
...
preferable to avoid this construction and use the plural noun instead.
Acceptable: The risk factor(s) for each study participant was not always
clear.
 . . .-
. .-

7.8.6 Compound Subject

Collective Nouns. A collective noun is one that names more than 1 person, place, or
thing. When the group is regarded as a unit, the singular verb is the appropriate
choice. (See also 9.2, Plurals, Collective Nouns.)
The couple has a practice in rural Montana. [Couple is considered a unit here
and so takes the singular verb.]
Twenty percent of her time is spent on administration. [Tuentypercent is
thought of as a unit, not as 20 individual units, and so takes the singular
verb.] (See also 18.3.3, Units of Measure, Format, Style, and Punctuation,
Subject-Verb Agreement.)
The paramedic crew responds to these emergency calls. [Creuris thought of
as a unit here and so takes the singular verb.]
When the individual members of the pair or group are emphasized, rather than the
group as a whole, the plural verb is correct.
The couple are both family physicians. [Couple is thought of as the 2 indi-
viduals who compose the couple, not as a unit, and so takes the plural verb.]
Ten percent of the staff work flexible hours. [Tenp e n t is thought of as
being composed of each individual staff member, not as a unit, and so takes
the plural verb.].
The surgical faculty were from all over the country. [Facultyhere refers to the
individual members of the faculty, rather than to the faculty a s a group, and
so takes the plural verb.]
The use of a phrase such a s "the members of" may make this last example less
jarring.
The members of the surgical faculty were from all over the country.

Compound Subject. When 2 words or 2 groups of words, usually joined by a n d or 01;

are the subject of the sentence, either the singular or plur.~lverl, form may I>e
appropriate, depending on whether the words joined are singular or plural nnd o n
the connectors used.

Compound Subject Joined by and. With and, a plural verb is usually correct.
' The nurse and the physician are discussing my case.
A singular verb should be used if the 2 elements are thought of as a unit:
Dilation and curettage was suggested.
or refer to the same person or thing:
The first author and principal investigator takes responsibility for the d;tt:t
analysis.

Compound Subject Joined by or or nor. With a compound subic-ct jotncrl I)!.o r . OI

nor, the plural verb is correct if both elements are plur;~l:if both t.lc.nient\ ;trc.
singular, the singular verb is correct. When one is singul:tr :tntl one i \ pl1lr:ll. rllc \ i . r l ,
should agree with the noun closer to the verh.

329
7.8 Subject-Verb Ayr,.ement

I I \~.i~lic.rt~ospi~:iI
st;tlT nor hn111y mc.mlxr\ \\.cn.In t h e
r(x)Ii1.

Uofhsirrgrrllrr: Neither a false-positive result nor a false-negative result

is definitive.
Mixed: Neither the physicians nor the hospital was responsible
for the loss.

Shift in Number of Subject and Resultant subject-verb Disagreement. In elliptical

constructions involving the verb (ie, the second verb is omitted because it is under-
stood), if the number of the subject changes, the construction is incorrect.
Incorrect: Her tests were run and her chart updated.
Correct: Her tests were run and her chart was updated.
Incorrect: The diagnosis was made and physical therapy sessions begun. 1

Correct: The diagnosis was made and physical therapy sessions were
begun.
or
The diagnosis was made and physical therapy begun.

Subject and Predicate Noun Differ in Number. The predicate noun is the comple-.
ment of a subject, it identifies, describes, or renames the subject. When the subject- --q
and predicate noun diier in number, follow the number of the subject in selecting
the singular or plural verb form.
Incorrect: The most s i d c a n t factor that affected the study results were
interhospital variations in severity of illness.
Correct: The most significant factor that affected the study results was
interhospital variations in severity of illness.

Avoid this by rephrasing:

I
Study results were most affected by interhospital variations in severity of
illness. . I
Every and Many a. When every or many a is used before a word or series of words,
use the singular verb form.
Many a clinician does not understand statistics. (But, betteryet: Many clini-
cians do not understand statistics.)
Every issue profiles a leader in medicine.

One of Those. In clauses that 6followone of those, the plural verb form is always
I
correct.
Dl.Cotter is one of those researchers who prefer the library to the laboratory.
I
Number. l%e n~rnlberis singular and a number of is plural (see also
Nouns).
I,
7.8.1 1 Number

The number that responded was surprising.

A number of respondents were concerned about adverse effects.
'i
The same is true for the total and a total oJ
.. ..
The Paragraph. A paragraph is a cohesive group of sentences. It presents a thought
or several related thoughts. Each paragraph should be long enough to stand alone
but short enough to hold the reader's attention and then direct that attention to the
next thought. Too many short paragraphs are ja-g to the reader, whereas too m;lny
long paragraphs strain the reader's attention. Sentences within a single p a c ~ g c ~ p h
should use parallel structure and consistent tense as much as possible.
Transitions are words or phrases that signal a connection among ideas. Trnnsi-
tions build bridges between paragraphs (and between sentences) and help the text
flow.6
To show addition: also, furthermore, in addition, moreover
To sbow contrast: however, yet, conversely, nevertheless, although
To sbow comparison: similarly, likewise
To show m l t s : therefore, thus, as a result, consequently
To show timesequence: first (second, third, etc), later, meanwhile,
subsequently, while
To summarize: hence, in summary, finally

ACKNOWLEDGMENT
Principal author: Stacy Christiansen, MA

REFERENCES
1. Platt S, ed. Respectjiully Quoted: A Dictionary of Quotations Requested Fmrn the
Congressional Researcb Setvice.Washington, DC: Library of Congress; 1989:entry 540.
2. Bernstein TM. i%e Careful Writer A Modern Guide to English Usage. New York,
NY: Free Press; 1998.
3. Crews F, Schor S, Hemessy M. 7be Borzoi Handbook for Writers. 3rd ed. New York,
NY: McGraw-Hill Inc; 1993.
4. Huth EJ. Writing and Publishing in Medicine. 3rd ed. Baltimore, MD: Williams Sr
Wilkins; 1999.
5. Burchfield RW. m e New Fowler's Modem English Usage. Rev 3rd ed. Oxford,
England: Oxford University 1'res.s; 2000.
6. Ibe American Heritage Dictionary of the English Langzrage. 4th ed. Boston, MA:
Houghton Mimin Co; 2000.

ADDITIONAL READINGS AND GENERAL REFERENCES

m e Chicago Manual of Style: m e ESsential Guidefor IVriters, Editon, arid P~rblishers.
15th ed. Chicago, IL: University of Chicago Press; 2003.
Copy Edito~Language News for the PublLFhing Ptvfe.csiona1. New York.iW:
.\lc.\lurr)'
Newsletters. http://www.copyeditor.com. Accessetl Scprc~nl,cr27. 2006
 ... .
-.
7.9 The Paragraph

Editorial Eye. Alexandria, VA: Editorial Experts Inc. http://www.eeicornmunications

.com/eye/. Accessed September 27, 2006.
Follett W. Modem AmeriGan Usage:A Guide. Wensberg E, ed.New York, NY:Hill & Wang;
1998.
Gordon KE. The Delluce Transitive Vampire: B e Lntimate Handbook of Grammarfor
[he Innocent, the Eager, and the Doomed. New York, NY: Pantheon Books; 1933.
Kilpatrick JJ. B e Writer'sArt. Kansas City, KS: Andrews McMeel& Parker Inc; 1985.
Merriam-Webster's Dictionaty of English Usage. Springfield, MA. Meniam-Webster; 1994.
Strunk W Jr, White EB. Elements of Style. 3rd ed. New York, NY: Maanillan Publishing CO
Inc; 1934.
Walsh B. Lapsing Into a Comma: A Curmudgeon's Guide to tbe Many 'Ibings m a t Can
Go Wrong in Prink-and How to Avoid 'Ibem.Lincolnwood, IL: Contemporary Books;
2000.
 8.1 Placement
Period, Question Mark, Exclamation Point Omission of Opening or
8.1.1 Period Closing Quotation Marks
8.1.2 Question Mark Coined Words. Slang
8.1.3 Exclamation Point Apologetic Quotation Marks
So-called .
8.2 Common Words Used in a Technical Sense
Comma, Semicolon, Colon Definition or Translation of Non-English-
8.2.1 Comma Language Words
8.22 Semicolon Titles of Works
8.2.3 Colon Indirect Discourse, Discussions
Block Quotations
83
Hyphens and Dashes 8.7
-8.3.1 Hyphen Apostrophe
8.3.2 Dashes 8.7.1 To Show Posse$sion
8.7.2 Possessive Pronouns
8.4 8.7.3 Possessive of Compound Terms
Forward Slash (Vlqule, Solidus) 8.7.4 Joint Possession
8.4.1 Used t o Express Equivalence or Duality 8.7.5 Using Apostrophes to Form Plurals
8.42 Used t o Mean per 8.7.6 Units of Time and Money as Possessive
8.43 In Dates Adjectives
8.4.4 In Equations 8.7.7 Prime
8.4.5 In Ratios
8.4.6 In Phonetics, Poetry 8.8
$-.- Ellipses
8.5 8.8.1 Omission Within a Sentence
Parentheses and Brackets 8.8.2 Omission at the End of a Sentence or
8.5.1 Pgrentheses Between Complete Senteqces
8.5.2 Brackets Grammatically Incomplete Expressions
Omissions in Verse
8.6 Omissions Between or at the Stan of
Quotation Marks Paragraphs
8.6.1 Quotations Change in Capitalization
8.6.2 Dialogue Omission of Ellipses
8.6.3 Titles Ellipses in Tables
8.6.4 Single Quotation Marks

.. .afterjourneying through the world ofpunctua-

tion, and seeing what it can do, I am all the more
convinced that we shouldfight like tigers topreserue
ourpunctuation and we should start now.
Lynne ~ r u s s '

Period, Question Mark, Exclamation Point. Periocls, question marks, and excl;~-
mation points are the 3 end-of-sentence punctuation marks.
 I ,
8.1 Period, Question Mark, Exclamation Point 'i .->..,2,
.
,i.
..
I::
- I

\:<.: '. '

Period. Periods are the most common end-of-sentence punctuation marks.
period at the end of a declarative or imperative sentence and at the end of each table
footnote and each figure legend.
US&.^::.
.I I
I
Advances in medical technology have saved many lives.
I:. .
Always listen carefully. .

Also use a period after a rhetorical question (one not requiring an answer).
Where, indeed, is the Osler of today.
!
. ;":.':$:Zd Placement. The period precedes ending quotation marks and reference citations. I

, .
The child is rated in 7 areas, such as "accepts responsibility" and "interacts ,.

appropriately with peers." !

I

We followed the methods of Wilkes et al.'

I
The period follows a closing apostrophe:
Their data were inconsistent with their associates'.
I
I

Enumerations. Use a period after the arabic numeral when enumerating paragraphed
items. - z

The signed authorship form required by the journal included the followin&-.
sections:
.i
1. Authorship responsibility, criteria, and conuibutions
2. Data access and responsibility
3. Financial disclosure
4. Acknowledgment statement
(See also 19.5, Numbers and Percentages, Enumerations, and the Enumerations (
section in 8.2.2, Semicolon, for kxamples of ways to handle enumerations that are
run into the text or that are setoff with bullets.) .! -
. I

Decimals. Use the period as.a decimal indicator. (See 19.7.1, Numbers and Percent- ,

ages, Forms of Numbers, Decimals.)

r = 0.75 .32 'caliber
0.1% P < .05 .

Multiplication. The period in raised position indicates multiplication. (See also 18.2.2,
Units of Measure, Expressing Unit Names and Symbols, Products and Quotients of
Unit Symbols, and 21.6, Idathematical Composition, Expressing Multiplication and ,
Division.) !

. .. When Not to Use a Period. J A M and the Archives Journals do not use periods yith 1 ' I

honorifics (courtesy titles), scientific terms, and abbreviations (exceptions: No. for
"number" and St. when it is of a person's name, although no period is used with .
St in a city name, eg, St Louis, Missouri) (see'2.1, Manuscript Preparation, Titles and
 .. . ---

8.1.2 Question Mark

Subtitles; 2.2, Manuscript Preparation, Bylines and End-of-Text Signatures; and 14.0,
Abbreviations).
Dr Hussey JAM
George Hussey, MD NIH
George R. Hussey, MD ie
E coli eg

-
Question Mark. The primary use of the question mark is to end interrogative sen-
tences.

I. When did he go into private practice?

If this article were a work of the 1930s, not the 1990s, would we view it
differently?And should we?

/n Dates. Use the question mark to show doubt about specific data.

-1. Hippocrates (460?-375 se) is often referred to as the ath her of ~edicine.

-Placement Place the question mark inside the end quotation mark (see 8.6.5.
Quotation Marks,Placement), the closing parenthesis, or the end bracket when thc
question mark is part of the quoted or parenthetical material.

I. The patient asked her physician of 25 years, "Why are you retiring, DoctoC

I. The chapter on interpretation asks the question "Can I be wrong?"

The mandate for health reform (can we agree on this?) will change practice
as we know it.
In declarative sentences that contain a question, place the question mark at the end
of the interrogative statement.
Why did I bother to attend this conference?she wondered.
The first section of the book, "What Medical Advances Made Open Heart
Surgery Possible?" is certain to interest medical historians.
The investigators asked the question "Have you ever injected drugs?" of
every study participant.
(Note: The question mark, like the exclamation point [see 8.1.3, Exclamation Point,
Placement], is never combined with another question mark, exclamation point,
period, semicolon, or comma; thus, the need for a comma is obviated in the 3 ex-
amples above. This usage is sometimes referred to as "dueling punctuation marks,"
' p
[j?.
and in this duel, the stronger mark wins.)
Rhetorical questions (those not requiring an answer) d o not require a question
j:
mark. (See R 1.1, Period.)
What is gained by recounting past 1osx.s when we have a chance to start
afrcch in our cffons to provide health care to the r~ninsured.
8.2 Comma, Sem~colon.Colon

111~l1rccr
o r rr-pc)ntd yx.~u.h11s)does not require a question mark.
Shc uondcrrd why thcrr were no illustrations in the article.

Exclamation Point. Exclamation points indicate emotion, an outcry, or a forceful

cornment. Try to avoid their use except in direct quotations and in rare and special
circumstances. They are not appropriate in scientific manuscripts and are more com-
mon in less formal articles, such as book reviews, editorials, and informal essays,
where added emphasis nlay be appropriate. If they are used, limit their use to one.
Beware!
Although it nlay be refemed to as the gold stapdard, nothing is perfect!
I had almost given up hope of his recovery. He was terribly sick!

Placement. When it completes the emphasized material, the exclamation point goes :
inside the end quotation mark, parenthesis, or bracket. (The exclamation point, like
the question mark [see 8.1.2,Question Mark, Placement], is never combined with
another exclamation point, question mark, period, semicolon, or comma; thus, there
is no cDmnm in the first exarnple below.)
"Let the reader beware!" the editor warned.
The frightened child cried, "I don't want my tonsils taken out!"

Factorial. In mathematical expressions, the exclamation point is used to indicate a

factorial. (See 21.6,Mathematical Composition, Expressing ~ u l t i ~ l i c a t i oand
n Divi-
sion.)

r:krdgaComma, Semicolon, Colon. Commas, semicolons, and colons can be used to in-
dicate a break or pause in thought, to set off material, or to introduce a new but
connected thought. Each has specific uses, and the strength of the break in~hought
determines which mark is appropriate.

Comma. Commas are the least forceful of the 3 marks. There are definite rules for
using comnas; however, usage is often subjective. Some writers and editors use the
comma frequently to indicate what they see as a natural pause in the flow of words,
but commas can be overused. The trend is to use them sparingly. Follow the ac-
cepted rules and use commas only when breaks are needed for sense or readability
or to avoid confusion or misinterpretation.

-, ,i*.~:2;2,$f Separating Groups of Words. The comma is used to separate phrases, clauses, and
groups of words and to c 1 a r ~ ' t h grammatical
e structure and the intended meaning.
Use a comma after opening dependent clauses (whether restrictive or not) or
long opening adverbial phrases.
If the infection recurs within 2 weeks, an additional course of antibiotics
should be given.
I
.8- -. ..... . . . ..

8.2.1 Comma

When you have to pay for your own health care, does your consunlption
really become more efficient?
A comma is not essential if the introductory p h r ~ s eis short.
In some patients midazolam produces paradoxic agitation.
Use commas to set off nonrestrictive subordinate clauses (see 7.2.2, Grammar, Pro-
nouns, Relative Pronouns) or nonrestrictive participial phrases.
Ms Frederick, who had been waiting on hold for more than an hour, aban-
doned all hope of having her questions answered.
The numbness, which had been apparent for 3 days, disappeared after drug
therapy.
The delegates, attaining consensus, passed the resolution.
But avoid setting a phrase off with commas where it would make the meaning am-
biguous.
Avoid: Although numerous investigators have called for measures to
improve sight in nursing home residents, to our knowledge,
none have attempted a study of the effect of a vision restoration-
rehabitation program on function and quality in this population.
In the example above, it is not clear whether the phrase "to our knowledge" applies
to what precedes it or what follows it. Removing the comma after "to our knowledge"
makes the meaning clear.
Better: - Although numerous investigators have called for measures to
improve sight in nursing home residents, to our knowledge none
have attempted a study of the effect of a vision restoration-
rehabilitation program on function and quality in this population.
Use a comma to avoid ambiguous or awkward juxt&osition of words. '

Outside, the ambulance siren shrieked.

Still, noting the trends and highlighting the lack of funding for achieving
world health goals does not translate into more positive actions.
Use commas to set off appositives. (Note: Commas precede and follow the apposi-
tion.)
Two colleagues,John Smith and Perry White, worked with me on this study.
The battered-chiid syndrome, a clinical condition in young children who ;
have experienced serious physical abuse, is a frequent cause of permanent
injury or even death.

Series. In a simple coordinate series of 3 or more terms, separate the elements by

commas. (See 7.1.1, Gnmmar, Nouns, Modifiers [Noun Strings].)
Each patient was asked to complete a 21-itc1ii.7-point, self-administered
questionnaire.
82 Comma. Sem~colon,Colon

Use 2 conlrna before the coniunction t t u t precedes the last term in a wries to prevent
anil,iguity (this is often referred to as a xrial comma).
Outcomes result from a complex interaction of medical care and genetic,
environmental, and behavioral factors.
The physician, the nurse, and the family could not convince the patient to
take his medication daily.
While in the hospital, these patients required neuroleptics, maximal ob-
servation, and seclusion.
i
However, a series of 3 or more modifiers should not be separated by commas when I
the modifiers are seen as 1 term or entity:
The patient has chronic progressive multiple sclerosis. i
Gray matter magnetic resonance imaging was used to predict longitudinal
brain atrophy.
~udgmentand common sense are required in the interpretation of this rule. If the.
order of the adjectives can be rearranged without loss of meaning or clarity, use the'
comma. I
The studies selected for inclusion were English-language, mndornized,
double-blind, controlled trials of newer atypical antipsychotic medications.
Data from several large, multicenter, administrative databases were ana-
lyzed.
.-
!

I,I
Note: When fewer than 3 modifiers are used, avoid adding a comma if the modifiers
and the noun are read as one entity:
We conducted a randomized placebo-controlled trial.
I
Data from multicenter administrative databases were analyzed.

Names of Organizations. When an enumeration occurs in the name of a company or

I . . ,

organization, the comma is usually omitted before the ampersand. However, follow
the punctuation used by the individual firm, except in references. (See 3.12.9, Ref-
erences, References to Print Books, Publishers.)
Farrar, Straus & Giroux Inc Little, Brown & Co
GlaxoSrnithKline Pharmaceuticals Mayer, Brown, Rowe & Maw
Houghton Mifflin Co Sidley Austin Brown & Wood

Setting Off ie, eg, viz. Use commas to set off ie, eg, and
equivalents, that is, for &ample, and namely.
viz and the expanded

The use of standardized scores, eg, z scores, has no effect on statistical

comparisons.
I 1

The most important tests, that is, the white blood cell and platelet counts, .
were unduly delayed. .-

.---- A
-. _ __ . - - -- - - .
 8.2.1 Comma

I ;
Note: If an independent clause follows these terms or their equivalents, precede the
clause with a semicolon.
Our double-blind study compared continuous with cyclic estrogen treat-
ment; ie, estrogens for 4 weeks were compared with estrogens for 3 weeks
followed by placebo for 1 week.

Separating Clauses Joined by Conjunctions. Use commas to separate main clauses

joined by coordinating conjunctions (and,but, or, nor, for).
Plasma lipid and lipoprotein concentrations were unchanged after low-
intensity training, but high-intensity training resulted in a reduction in tri-
glyceride levels.
No subgroup of responders could be identified, and differences between
centers were so great that no real comparison was possible.
I If both clauses are short, punctuation can be omitted.

I The test may be useful or it may be harmful.

I I have read the article and I am concerned about the data collection methods.
Be careful not to confuse the coordinating conjunction used between independent
clauses with a coordinating conjunction used to link a compound predicate. .
These facilities are beginning to resemble "minihospitals" and they are losing
their identity as freestanding ambulatory surgery centers. ,

I
Clauses introduced by yet and so and subordinating conjunctions (eg, while, where,
aper, whereas) are preceded by a comma. (See 11.1, Correct and Preferred Usage,
'

Correct and Preferred Usage of Common Words and Phrases.)

.- .-

He taught medical students, performed careful research, and wrote thbught-

ful articles, yet was denied tenure.
The United States spends more than $1000 per capita per year on papenvork
related to health care, whereas Canada spends only about $300 per capita.
One recent study found that low litcr:~cyw:w associ:~tctlwith worse nic.nr;~l
health, whereas another concluded that literacy was not associ:ltcd \\.it11
depiession.

II If such conjunctioils appear at the beginning of a sentence, however, the comm;t

following the conjunction may not be necessary.
I have seen many cases of vertigo. Yet this one was particularly troubling.

Setting Off Parenthetical Expressions. Use commas to set off parenthetical \vords,
phrases, questions, and other expressions' that interrupt the continuity of a sentence.
eg, therefore, moreover, on the other hand, of course, nevertheless, after all, conscJ-
quently, however. (See 8.8.1, Ellipses, Omission Within a Sentence.)

I The real issue, after all, was how to Fund the next stydy.
Therefore, we were disappointed that the article did not include con-
sideration of medical schools ant1 their influcncc on the culri~rcof nlctlic.inc..
8.2 Comma, Semicolon, Colon

What is needed, then, is collective empowerment of pr-ctitionen, guidcd by

accountability to the public.
Note: In some cases, removal of the commas: around parenthetical expressions
changes the ,meaning of the sentence. In the example immediately above, then
suggests a summing-up. Without these commas, then suggests time, ie, what comes
.. .
next.

Setting Off Degrees and Titles. Academic degrees and m e s are set off by commas '

when they follow the name of a person. Although it is not incorrect to setJrand Sroff i
by commas when they follow the name of a person,JAMA and the Archives Journals
are now deleting these commas.
Berton Smith Jr, MD, and Priscilla Armstrong, MD, PhD, interpreted the;- 1
radiographic findings in this study.
i
Joyce Fredrickson-Smith, MD, PhD, vice-chancellor, attended the con-
ference on health system reform.

Addresses. In running text and in aflliation footnotes, use commas to separateithe

elements in an address. Use commas after the city and before and after the state or
country name. (Note: In US and Canadian addresses, commas are not used before the
zip or the postal code.)
. 1
If -

This year, the editorial board meeting will be held in conjunction with the ' 1
Academy meeting at the Westin Bonaventure Hotel and Suites, 404 S Fig-
ueroa St, Los Angeles, CA 90071.
The study was conducted at The Wilrner Institute, Baltimore, Maryland, in
2004.
:,
i .
Dates. In dates and similar expressions of time, use commas according to the fol- !

lowing examples. Commas are norused when the month and year are given without ;
the day, or between a holiday and its year.
The first issue of J A M was published on Saturday,July 14, 1883.
The patient's rhinoplasty was scheduled for August 19, 2002, at Strong
Memorial Hospital, with postoperative evaluation on August 30.
The terrorist attack in London, England, in July 2005 led to further ex-
amination of major disaster preparedness.
The publication offices were closed on New Year's Day 2005.

Numbers. In accordance with SI convention, separate digits with a thin space, not a
comma, to indicate place values beyond thousands. (See 18.4.3, Units of Measure,
Use of Numerals With Units, Number Spacing.)

\
A comma may be used to separate adjacent unrelated numerals if neither can be ex-
pressed easily in words, but it is preferable to reword the sentence or spell out 1of
the numbers.
6 '

- -. .., -- .-. - .
- <
r.

1
 ,-
. -

8.2.2 Se.micolon

By December 2003,929985 cases of AIDS had been reported in the Unitecl

States.
Bettetz By December 2003, a total of 929 985 cases of AIDS had Ixen
reported in the United States.

Units of Measure. Do not use a comma between 2 or more measures whose units arc
the same dimension.
3 years 4 months 2 days old 31b 402

Placement. The comma is placed inside quotation marks (see 8.6.5, Quotation Marks,
Placement) and before superscript citation of references and footnote sytnbols.
a result of the "back-to-sleep campaigns," a call has been issued for a
"back-to-the-bench" campaign. .
These missed opportunities have been shown to occur during office visits:9
healthdepartment and h~s~italizations:'~
i .
To Indicate 0miss;on. The comma is used to indicate omission or to avoid repeating a
word when the sense is clear. (See 7.8.7, Grammar, Subject-Verb Agreement, Shift in
Number of Subject and Resultant Subject-Verb Disagreement.)
Three' patients could not be studied: in 1, duration of treatment was too
short; in 2, too long.
A plus indicates present; a minus, absent.

Dialogue. Commas are often used before direct dialogue or conversation is in-
troduced. (See also 8.2.3, Colon,.Introducing Quotations' or Enumerations.)
In the middle of the laboratory examination, a'student asked,G o u l d it be ,
OK to take a break?" - ..
Semicolon. Semicolons represent a more definite break in thought than commas.
Generally, semicolons are used to separate 2 independent clauses. Often a comma
will suffice if sentences are short; but when the main clauses are long and joined by
coordinating conjunctions or conjunctive adverbs, especially if 1 of the clauses has
internal punctuation, use a semicolon.

Separating Independent Clauses. Use a semicolon to separate independent clauses ,in

. a compound sentence when no connective word is used. In most instances it'is
equally correct to use a period and create 2 sentences.
The conditions of 52% of the patients improved greatly; 4% of the patients
withdrew from the study.
However, if clauses are short and similar in form, use a comma.
Seventy grafts were patent, 5 were occluded.
Use a semicolon between main clauses joined by a conjunctive adverb (eg, also,
i
besides, furthermore, then, however, tht~s,hence, ittcieed, yc.t ) or ;I co(xdinat i ng z,
9

341
'
8.2 Comma, Semicolon, Colon \

conjunction (and, but, or, for, nor) if 1 of the clauses has internal punctuation or is (

considerably long.
The patient's fever had subsided; however, his condition was still critical.
The word normal is often used loosely;'indeed, it is not easily defined. I
Introduction to the knowledge, skills, and attitudes relevant to safety should
begin in medical and nursing school; eg, the first 2yeBrs of medical school may
Se the most appropriate to learn error science and of leadership.

Enumerations. For clarity, use semicolons between items in a complex or lengthy

enumeration within a sentence or in an enumeration that contains serial commas in
at least 1of the itenis listed. (In a simple series with little or no internal punctuation,
even with multiword elements; use comas.)
A number of questions remain unresolved: (1) whether beverages that con- ,

tain caffeine are an important factor in amhythmogenesis; (2) whether such

beverages can vigger arrhjlthmias de novo; and (3) whether their arrhyth-
mogenic tendency is enhanced by the presence and extent of myocardial
impairment.
The photomicrographic illustrations of the grdss and microscopic features of /
normal skin, Spitz congenital and dysplastic nevi, lentigines, and melanoma ..i . - <
demonstrated the complexity of pigmented lesions.
In less formal writing and where the last element of a series is also a series, commas
are acceptable provided that clarity is preserved. .
The statistician addressed limitations in case-control studies, cohort studies,
and randomized, double-blind, controlled trials.
I
Colon. The colon is the strongest of the 3 marks used to indicate a decided pause or 1
I
break in thought. It separates 2 main clauses in which the second clause amplifies or
explains the first.
This dictum is often believed to be in the Hippocratic Oath: First, do no i
harm.

. .. When Not to Use a Colon. Do not use a colon if the sentence is continuous without it. I
You will need enthusiasm, organization, and a commitment to your beliefs.
Not: You will need: enthusiasm, organization, and a commitment to your
I
beliefs.
Avoid using a colon to separate a preposition from its object or to separate a verb
(including to be in all of its manifestations) from its object or predicate nominative.
I~rcorrect: The point is: do not insert the czitheter at this time.
.!?c.~ier The point is not to insert the catheter at this time. 6

\
I >(,not 1 1 . s ~;i colon after because or forms of the verb include.
 8.2.3 Colon

introducing Quotations or Enumerations. Use a colon to introduce a formal or ex-

tended quotation. (If the sentence to follow is in quotation marks, the first word is

Harold Johnson, MD, chair of the committee, summarized: "The problems

we face in developing a new vaccine are numerous, but foremost is isolating
the antigen,"
Use a colon to introduce an enumeration, especially after anticipatory phrasing such
as thuz, asfollows, thefollowing.
The solution included the following components: phosphate buffer, double-
distilled water, and a chelating agent.
Laboratory studies yielded the following values: hemoglobin, 11.9 g/dL;
erythrocytesedimentation, 104 mm/h; calcium, 16.9 mg/dL; phosphorus, 5.6
mg/dL; and aeatinine, 3 mg/dL.
Phytoestrogens are subdivided into 3 main classes: isoflavones, lignans, and
curnestram.
If 2 or more grammatically independent statements follow the colon, they may be
treated as complete sentencesseparated by periods, and the initial words may or may
not be capitalized.
The following procedure has been established for updating the journal's
instructions for authors: (1) Update and review the Word He. <2) Style the
Word document according to guidelines and send to the electronic media
staff. O Insert links.(4) Proofread final version. (5) Code and post on the
Web.

Numbers. Use a colon to separate chapter and verse numbers in biblical'references,

hours and minutes in expressions of time, and the elements of ratios when they are
expressed as numbers or abbreviations. For ratios expressed as words, use the word
to rather than a colon, unless the term conventionally takes a hyphen (eg, "cost-
benefit ration). In that case, follow the conventional usage and use a hyphen.

R The first Old Testament mention of leprosy is in Exodus 4:6.

It Medication was given twice a day, at 830 m and at 8:30 PM.

1 The chemicals were mixed in a 4:3 ratio.

I The controls and study subjects were randomized in a 2:l ratio.

I.
[I
The ACTH:TSH ratio was elevated when the patient was first examined.
The ratio of albumin to globulin was one of the outcome mc:rsures in the
study.
The student to insrnrctor ratio was 7 to 1.

References. In references, use :a colon (1) txrwcen title ;lncl sbl>title:(2) for pcriotl-
i d \ . Iwmeen issue nilmlwr ;lntl paye n~~nllxr\; ;~ncl(-1) for 17ooks. bet\vccn p\ll,-
I~shcr'sIwarion ;and name. ( S r r ; t l w 3 0. References.)

343
8 3 Hyphens and Dashes

.. I
Hyphens and Dashes. Hyphens and dashes are internal punctuation marks used
for l~nkageand clarity of expression. i
Hyphen. The hyphen is a connector; it may join "what is similar and also what is i
disjunctive. . . .it divides as well as marries."* The hyphen connects words, prefixes,
and suffixes permanently or temporarily. Certain compound words always contain
i,.:
8.

i
..
hyphens. Such hyphens are called orthographic. Examples are merry-go-round, free- .
for-all, and mother-in-law. For temporary connections, hyphens help prevent am- ;
biguity, clarify meaning, and indicate word breaks at the end.of a line. i .
In general, when not otherwise specified, I?yphensshould be used only as an aid i
to the readefs understanding, primarily to avoid ambiguity. For capitalization of hy- 1.
phenated c6mpounds in titles, subtitles, subheads, and table heads, see 10.2.2, Cap-
italization, Titles and Headings, Hyphenated Compounds. . . 1
Temporaw Compounds. Hyphenate temporary compounds according to current
dictionary usage and the following rules:
Hyphenate a compound that contains a noun or an adverb (except for adverbs
e n k g in -ly; see below, When Not to Use Hyphens) and a participle that together
serve as an adjective modifying the noun they precede. Do not use the hyphen if t$e
compound follows $e noun.
decision-making methods (But: methods d decision makin& . i I
1 '.
most-read work in the collection (Buk The work was the most read in the:;-?-.l
collection.) !
I
It was a placebo-controlled trial. (Buk The trial was placebo controlled.) i
This is a well-edited volume. (But: This volume is well edited.) i
i
The rash was a treatment-related adverse event. (But: The adverse event was
treatment related.) I .
!.

Hyphenate a compound adjectival phrase when it precedes the noun it m a e s but I'
not when it follows the noun. . I '1 . ..
side-by-side placement (But: placed side by side) . .
Hyphenate an adjective-noun compound when it precedes and modifies another
noun but not when it follows the noun.
low-quality suture material (But: suture material of low quality)
highestquality printing (But: printing of highest quality)
low-density resolution (But: resolution of low density)
lowdensity nerve fibers (But: nerve fibers of low density)
high-altitude sickness (But: sickness at high altitude)
very low-birth-weight children (But: children of very low birth weight) .,

low-molecular-weight heparin (But: heparin of low molecular weight) j

i
very low-density lipoprotein (But: lipoprotein of very low density) !
I
 8.3.1 Hyphen

i
!:
Note: In most instances middle-, high-, and low- adjectival compounds are hyphen-
ated.
For compound adjectival phrases, adverb-participle compounds, and adjective-
noun compounds that have become comqonplace and familiar in everyday usage,
hyphenate these phrases or compounds whether they precede or follow the noun
they modify. (Follow 'Ibe Chicago Manual of Style, 15th edition, to verify.)
long-term therapy
the commitment was long-term
up-to-date vaccinations
the vaccinations were up-to-date
state-of-the-art equipment
equipment that was state-of-the-art
Hyphenate a combination of 2 or more nouns used coordinately as a unit modifier
when preceding the noun but not when following.
the Biet-Simon test (But: the test of Binet and Simon)
Beer-Lambert law (But: the law of Beer and Lambert)
Charcot-Marie-Tooth disease (But: the disease described by Charcot, Marie.
and Tooth)
Hosmer-Lemeshow goodness-of-fit test (But: the goodness-of-fit test of
Hosmer and Lemeshow)
1
the physician-patient relationship (But: the relationship between the phy- -
1
sician and the patient)
Presentation of ratios as numbers or abbreviations is an exception to this rule. In
ratios presented as numbers or abbreviations, use a colon (see 8.2:3, Colon). For
ratios presented as words, use the word to or, if the word combination has become
accepted as a single term, such as cost-benefit analysis, a hyphen.
Hyphenate a combination of 2 nouns of equal participation used as a single
noun. (See also 8.4.1, Forward Slash [Virgule, Solidusl, Used to Express Equivalence
or Duality.)
William Carlos Williams was a physician-poet.
W. So.merset Maugham is considered a great physician-writer.
She is an obstetrician-gynecologist. i

Provide the best health care for all, says the citizen-patient; but don't allow
costs to rise, says the citizen-taxpayer.
The physician-patient may Ixcome impatient with treatment.
The study involved 1000 patient-years.
I-lyphenate most compound nouns that contain n preposition. Follow the latest
Collqtate D i c f i o ~ t a ~ .
eclition of hfeniarn-IVeb~terf
8.3 Hyphens and Darhes

tic-in be-up follow-up hand-me-down go-between

(Bur: onlooker, passerby, handout, workup, makeup)
Hyphenate a conlpound in which a number is the first element and the compound
precedes the noun it modifies.
18-factor blood chemistry analysis
7-fold increase
2-way street
ninth-grade reading level
1-cm increments
Hyphenate 2 or more adjectives used coordinately or as conflicting terms whether
they precede the noun or follow as a predicate adjective.
The false-positive test results were noted.
The test results were false-positive.
We performed a double-blind study.
The test we used was double-blind.
The author provided black-and-white il1"strations.
The author's illustrations were black-and-white.
Hyphenate color terms in which the 2 elements are of equal weight.
blue-gray eyes
blue-black lesions (lesions were blue-black)
(But: bluish gray lesions)
Hyphenate compounds formed with the prefixes all-, self, and ex- whether they
precede or follow the noun.
self-reported intake one's self-respect
all-powerful ruler . the patient's ex-husband
(hbte: With the prehv vice, follow the latest edition of Memiam- Webster's Collegiate
Dictionary, eg, vice-chancellor, vice-consul, but vice president, vice admiral.)
Hyphenate compounds made up of the suffixes -type, -elect, and -designate.
Hodgkin-type lymphoma president-elect
Valsalva-type maneuver secretary-designate
chair-elect
Hyphenate most contemporary adjectival cross- compounds (consult the latest edi-
,
tion of Mem'am-Webster's Collegiate Dictionary for absolute accuracy; there are
exceptions, eg, crossbred, crosshatched, crossover, crossrnatch, cross section).
I
cross-reactive cross-discipline training
cross-contamination cross-coherence analysis
cross-tolerance reaction cross-reference citation
 8.3.1 Hyphen

Hyphenate adjectiual compounds with qzrusi.

quasi-legislative group quasi-analytic model
quasi-diplomatic efforts quasi-expcri111entaI design

I
Most nouns that begin with quasi are not hyphenated but instead are set open (eg,
quasi diplomat), although some are closed up (eg,,quasicrysval, quasiparticle): Fol-
low the latest edition of Meniam- Webster's Collegiate Dictionary.
Hyphenate some compounds in which the first element is a possessive. Consult
the latest edition of Merriam- Webster's Collegiate Dictio17ary.
bird's-eye view bull's-eye
crow's-feet bird's-nest filter
, Hyphenate all prefixes that precede a proper noun, a capitalized word, a number, or
an abbreviation.
pro-~fhcaninitiatives
pre-AIDS era
post-2005 ruling
Note: There is growing recognition and acceptance of the use of a stand-alone prefix
with a hyphen when an alternative unhyphenated prefix follows.
We found a need for pre- and postoperative examination.
Patients were categorized as hyper- or hypotensive.
This could be an in- or outpatient procedure.
J A M and the Archives Journals choose not to follow this trend and instead would
use the following:
We found a need for preoperative and postoperative examination.
Patients were categorized as hypertensive or hypotensive.
This could be an inpatient or outpatient procedure.
When 2 or more hyphenated compounds have a common base, omit the base in all
but the last. In unhyphenated compounds written as 1 word, repeat the base.
first-, second-, and third-grade students
10- and ,l5-year-old boys
anterolateral and posterolateral aspects i
Hyphenate compound numbers from 21 to 99 (cardinal and ordinal) when written
out, as at the beginning of a sentence. (See 19.1, Numbers and Percentages, Use of
Numerals.)
Thirty-six patients were examined.
Twenty-fifth through 75th percentile rankings were shown.
. .
One hundred thirty-two people were killed in the plane crash.
8.3 Hyphens a n d Dashes

Hyphenate fractions used as nouns or adjectives.

A two-thirds majority was needed.
The flask was three-fourths Full.
Three-fourths of the questionnaires were returned.

Bz?j$-flClarity. Use hyphens to avoid ambiguity. If a term could be misleading without a

hyphen, hyphenate it. As with the use of commas to indicate pauses, the use of the
hyphen to provide clarity nyay be subjective. What is clear to one person may be a
source of ambiguity to another. Use the following guidelines and a healthy dose of
common sense.
a small-bowel constriction (constriction of the small bowel)
a small bowel constriction (a small constriction of the bowel)
(a
a single-specialty center center devoted to a single specialty)
a single specialty center (1 center devoted to a specialty)
a large-l,owel resection (resection of the large bowel) (Bettm: a colon
resection)
a large bowel resection (a large resection of the bowel)
a solid-organ tmnsplantation program (a program for transplantation of solid '
'
organs)
a solid organ transplantation program (a program for organ transplantation
that is solid, ie, well established) (Better: a well-established transplantation
progmm)
Use a hyphen afier a prefix when the unhyphenated word would have a different
meaning.
re-treat re-formation
re-creation un-ionized .
Note: Do not hyphenate other forms of these words for which no ambiguity exists:
retreatment, recreational.
Occasionally, a hyphen is used after a prefix or before a suffix to avoid an awk-
ward combination of letters, such as 2 of the same vowel or 3 of the same consonant
(with exceptions noted below, When Not to Use Hyphens). Follow the latest edition
of Merriam-Webster's Collegiate LEctionary or Dorhnd's or Stedman's medical dic-
tionary.
semi-independent intra-abdominal
hull-less bell-like
ultra-atomic anti-inflammatory
de-emphasize

(Some exceptions to this rule include microorganism, cooperation, reenter [see be-
low, When Not to Use Hyphens].)
In conlplex modifying phrases that include suffixes or prefixes, hyphens and en
dashes are sometimes usecl to avoid ambiguity. (See also 8.3.2,Dashes, En Dash.)
 8.3.1 Hyphen

non-self-governing non-English-language journals

non-group-specific blood non-Q-wave myocardial infarction
I non-brain-injured subjects

Expressing Ranges and Dimensions. When expressing ranges or dimensions used as

modifiers, use hyphens and spacing in accordance with the following examples in
the left-hand column. The alternatives in the right-hand column give the expression
of dimensions when not used as modifiers.
As M o d z ~ Alternative
in a 10- to 14-day period 10 to 14 days' duration
a 3 x h strip a strip measuring 3 x4 cm
a 5- to 10-mg dose a dose of 5 to 10 mg
in a 5-, 10-,or 15-mg dose in a dose of 5, 10, or 15 mg
a 3-cmdiimeter tube .a tube 3 cm in diameter
5-mm-thick lesion a lesion 5 mm thick
In the text, d o not use hyphens to express ranges. (See 19.4, Numbers and Percent-
ages, Use of Digit Spans and Hyphens.)
1I' The adverse events were experienced by 5% to 1% of the group.
The exceptions to this rule about ranges are for (1) ranges expressing fiscal years,
academic years, life spa?, or study spansand (2) ranges given inSparentheses.
! We present results from the 2002-2004 Renal Study Group.

I The patients' median age.was 56 years (range, 31-92 years).

I Note that no hyphens are needed in the following cases:

I a 3 to 4 ratio
a case of mild to moderate pruritus

Word Division. Use hyphens to indicate division of a word at the end of a line (folio\\,
i the latest edition of Merriam-Webster's Collegiate Dictionary or Stedman's or Ilor-
! land's medical dictionary).
I

When Not to Use Hyphens. Rules also exist for when not to use hyphens.
The following common prefixes are not joined by hyphens except when they
precede a proper noun, a capitalized word, or an abbreviation: aute-, a)?fi-,bi-. co-.
contra-, counter-, de-, extra-, infra-, inter-, intra-, miclo-, mid-, non-, over-, prc-.
post-, pm-, pseudo-, re-, semi-, sub-, super-, suprm, trans-, tri, I L ~ I ~un-,
L I -rrruler-.
,
antimicrobial nonresident
coauthor overproduction
codirects overrepresented
coexistence overtreatment
coitlcnlity [>osltr:li~~n:~I
ic
8.3 Hyphens and Dashes

coworker preexisting
deidentify reevaluation
interrater repossess
midaxillary transsacral
midbrow ultramicrotome
multicenter underrepresented
nonnegotiable
Retain the hyphen if needed to avoid ambiguity or awkward spelling that could
interfere with readability: co-opt, co-payment, co-twin, intra-aortic.
Retain the hyphen when the term after the prefixes anti-, neo-, pre-, post-, and
mid- is a proper noun or a number (see also above, Temporary Compounds), eg;
mid-1900s, mid-Atlantic crossing.
The following suffixes are joined without a hyphen, with exceptions if the clarity
woulcl be obscured (see Temporary Con~poundsabove): -hood, -less, -like, -wise.
womanhood shoeless
manhood insulinlike
catatoniclike probandwise concordance
Some combinations of words are commonly read together as a unit. As such.com-
binations come into common use, the hyphen tends to be omitted without a sacrifice
of clarity. Use the latest editions of Merriam-Webster's Colkgiate Dictionary and
Dorland's and Stedman's medical dictionaries as guides to common usage (eg,
broad-spectrum antibiotics is hyphenated in Dorland's; open heart sutgety, deep
venous thrombosis, and small cell carcinoma are not). For terms not found in these
sources, use a reader's perspective and the context as guides (eg, JAMA and the
Archives Journals hyphenate sof-tissue, as in sofl-tissue mass, to avoid confusion).
When no confusion is likely, leave 'open. If there is a possibility of confusion, hy-
phenate. A short list of examples that can usually be presented without hyphens is
givm below.
amino acid levels medical school students
birth control methods natural killer cell
bone marrow biopsy . open heart surgery
deep venous thrombosis peer review process
foreign body infiltrate primary care physician
health care system public health official
inner ear disorder small cell carcinoma
lower extremity amputation tertiary care center
Do not hyphenate names of disease entities used as modifiers.
basal cell carcinoma connective tissue tumor
.I
hyaline membrane disease sickle cell trait
:.
clam diggers' itch grand ma1 seizures

, ,
.-'
..
3 50 . . .
' ;:i

. . .? .
. - .
,~ .__ _ _-
.-_=. -c-l - .

-' 2:
... -
-. . -.
. ... -.
 8.3.1 Hyphen

Do not use a hyphen after an adverb that ends in -1' even when used in a compound
modifier preceding the word modified; in these cases, ambiguity is unlikely and the
hyphen can be dispensed with.
the clearly stated purpose biologically mediated therapy
a highly developed species previously published recotnniendations
clinically derived databases clinically relevant variables

I. Do not hyphenate names of chemical compounds used as adjectives.

II sodium chloride solution

tamic acid test
Most combmations of proper adjectives derived from geographic entities are not
hyphenated when used as noun or adjective formations.
Central Americans Pacific Rim countries
Southeast Asian countries Central American customs
African American ~ a t i rAmericans
i
Mexican American
(But:Scotch-Irish ancestry. Here the hyphen is used to indicate 2 countries of
origin.)
Do not hyphenate Latin expressions or non-English-language phrases used in an
adjectival sense. Most of these are treated as separate words; a few are joined without
! a hyphen. Follow the latest edition of Merriam-Webster's Collegiate Dictiona y.
an a priori argument an ex officio member
per diem employees antebellum South
prima facie evidence in vivo specimens
postmortem examination carcinoma in situ
cafe au lait spots post hoc testing
Note that when post is used as a combining adjectival form, as in postmoltenz ex-
!
amination, it is set closed up. When it is used as an adverb, as in post hoc testing, it is
.
I set as 2 separate words. This distinction is apparent in the examples below:
postpartum depression
depression occurring post partum
Do not hyphenate modifiers in which a letter or number is the second element.
i

I grade A eggs
study 1 protocol
t y p 1 di3hte~ mellitus
. I
I

Compound Official Titles. tiyphenarc combin:rtion posittonz OI

o f f i ~ l>ut
~ , r i o t cotii-
pound dczrgn:r~rons;I*follo~vh:
8 3 hfphcns and Dashes

acting secretary
honorary chair
(But: past vice president, executive vice president, past president)

Special Combinations. Special combinations may or may not necessitate the use of
hyphens. Consult Stedman's, Dorland's, and the latest edition of Merriam-Webstw's
Collegiate Dictionary. (See 15.0, Nomenclature, and 17.0, Greek Letters.)
B cell Mann-Whitney test
graft-vs-host disease T-shirt
T tube face-lift
B-cell helper prostate-specific antigen
I beam (I-shaped beam) Z-piasty
T wave forehead-lift
kblocker T square
J curve y-globulin
T-cell marker t test
brow-lift

Dashes. Dashes as another form of internal punctuation convey a particular meaning - - ,

or emphasize and clarify a certain section of material within a sentence. Compared
with parentheses, dashes may convey a less formal or more emphatic "aside."
There are 4 types of dashes that differ in length: the em dash, the most common;
the en dash; the 2-em dash; and the 3-em dash. When preparing a manuscript, if
symbols for various dashes are not available in the word-processing program, use 2
hyphens to indicate an em dash (--)and 1for an en dash (-1.

Em Dash. Em dashes are used to indicate a marked or pronounced interruption or

break in thought. It is best to use this mode sparingly; do not use an em dash when
another punctuation mark will suffice, for instance, the comma or the colon, or to
imply namely, that is, or in other words, when an explanation follows.
All of these factorsage; severity of symptoms, psychic preparation, and
choice of anesthetic agent--determine the patient's reaction.
An em dash may be used to separate a referent from a pronoun that is the subject of
a n ending clause.
Osler, Billings, Apgar-these were the physicians she tried to emulate.

En Dash. The en dash is longer than a hyphen but half the length of the em dash. The
I
en dash shows relational distinction in a hyphenated or compound modifier, 1
element of which consists of 2 words or a hyphenated word, or when the word being
modified is a compound.
Winston-Salem-oriented group
physician-lawyer-directed section
post-World War I
multiple sclerosis-like symptoms
'I
.-.
 8.4.1 Used to Express Equivalence or Duality

anti-Norwalk virus decision tree-based analysis

phosphotungstic acid-hematoxylin non-small cell carcinomd

2-Em Dash. The 2-em dash is used to indicate missing letters in a word.
The study was conducted at N- Hospital, noted for its low autopsy rate.

3-Em -Dash. The 3em dash is used to show missing words.

Each subject was asked to fill in the blank in the following statement: "I
usually sleep -
hours per day."
I admire Dr -too much to expose him in this anecdote,
Forward Slash (Virgule, Solidus). The forbard slash is used to representpel; and,
or or and to divide material Ceg, numerator and denominator in fractions; month, day,
and year in dates [only in tables and figures]; lines of poetry). It may also be used in.
URIs (see 2.0, Manuscript Preparation).

Used to Express ~~uivalence

or Duality. When 2 terms are of equal weight in an
expression and and is implied between them to express this equivalence, the for-
ward slash can be retained.
The diagnosis and initial treatment/diagnostic planning were recorded.
If the approval process raises concerns among the researchers or the ethics
committeeARB members, the author may want to explain the resolution of
these issues.
When the question of duality arises in the he/she construction, chang? the slash
construction when the gender is to be specified; substitute the word or for the
forward slash or, preferably, rephrase to be gender neutral.
Dr Kate Wolf and Dr Rob Cox agreed to serve on the nomenclature com-
mittee. Now I need to know whether he or she [not he/sliel will lead the
subcommittee on genetic nomenclature.

I\ Better: Now I need to know which of them will lead the subcommittrc.

I. If the sex is unspecified and does not matter, retain the slash construction.
This aspiration technique is one th;rt any pllysician c;ln 1n:lster ,\\:hc~licr01.
not he/she has surgical expertise.
Note: The trend today is toward rephrasing such sentcnccs and using the p l u ~ to ~l
avoid sexist language; eg, "This aspiration tcchniqi~rcan I>cm:~srcrctl.!,I pl~ysic.i;ins
whether or not they have surgical expcrti.;~."(See 1 1 . 1 0 . (:c>r.rc.r.[ ;~nrlI'rc.l;.r~xl
Usage, Inclusive L~ngungc..)
Although the fonvard sl;csh <;in I w u-ccl to lncf~c;lrc; I ~ I ~ I - I I . I cI I (11.
~ c . o ~ i i l > i n ~ zr.ut.\
.(l
in the same person, st~cli;IS Jckyll;l Iytlc ~ ~ c r \ o r ~ ; ~11l I,~ rIlnl>c,n.irir
y. rl1;1r 110 ; I I I ~ ~ ) I ~ I I I ~ \
11e introdi~cetl.i f 1 1 i ~ ~ Ir\ c:In!.
~ I ~ k c l ~ t i 01'
~ ~. nI Il I I ~ ? I ~r ~ I .I.<.IIICIICC.
li~ ~!. . t i o 1 1 1 ~ \ IR,I ( .
8.4 Forward Slash ( V ~ r g u l t So11dd\)
.

! ' . .

Used to Mean per. In 111c..jx.r" construction, use a forward slash only when (1) the
c . o n > l n ~ i ~ i c in\.olvc>
>n unirs of measure (including time) a n d (2) at least 1 element
includes a specific numerical quantity a n d (3) the element immediately adjacent on
each side is either a specific numerical quantity or a unit of measure. In such cases,
the units of measure should be abbreviated in accordance with 14.12, Abbrevia-
tions, Units of Measure. (See also 19.7.3, Numbers and Percentages, Forms of Nurn-
bers, Reporting Proportions and Percentages.)
The hemoglobin level was 14 g/dL.
The cD4+ cell count was 200/pL.
Blood volume was 89 mL/kg of body weight.
Respirations were 6O/min; pulse rate was 98/min.
- I
The drug dosage was 30 mg/d.
! i
Do not use the forward slash in a "per" construction (1)when a prepositional phrase I
intervenes between the 2 units of measure, (2) when n o specific numerical quantity is
expressed, or (3) in nontechnical expressions.
1
I i
4.5 rnEq of potassium per liter II
(Avoid: 4.5 mEq/L of potassium; instead reword: a potassium concentration 1;-
of 4.5 mEq/L.) . I I

expressed in milliliters per minute

I
1
.

Lri,.
.
4 I

i days per year

./
In Dates. Use the forward slash in dates only in tables and figures to save space ;
(month/day/year) (see 4.1.5, Visual Presentation of Data, Tables, Punctuation). Avoid.
this presentation of dates in the text.

In Equations. In equations that are set on line and run into the text rather' than :
i
centered and set off (see 21.3, Mathematical Composition, Stacked vs Unstacked),
use the forward slash to separate numerator and denominator.
The "stacked fraction y =-is written as y = (rl+ rd/(pl -p3.
Pl-P2

Note that when the slash is used for this purpose, parentheses and brackets must
often be added to avoid ambiguity.

In Ratios. Although a forward slash may be used to express a ratio (eg, rhk male/
female [WF] ratio was 2/1), J A M and the Archives Journals recommend use of a
colon to express ratios involving numbers or abbreviations, (the Apo B:Apo A-I ratio
was 2:l) and the word to to express ratios involving words (the male to female ratio).
(See 8.2.3, Colon, Numbers.)

In Phonetics, Poetry. The forward slash is also used to set off phonemes and phonetic
transcription and to divide run-in lines of poetry.

/d/ as in dog 1 I:
. . . cold-breathed earthlearth of the slumbering and liquid treedearth of the !
mountains misty-topped.
t
 - . . _- . .... ,

8.5.1 Parenthese

Parentheses and Brackets. Parentheses and brackets are internal punctuntion

marks used to set off material that is nonrestrictive or, as in the case of mnthen~ntiml
and chemical expressions, to alert the reader to the special functions occurring

Supplementary Expressions. Use parentheses to indicate supplementary explana-

tions, identification, direction to the reader, or translation. (See also 8.3.2, Dashes.
and 8.5.2, Brackets.)

1. A known volume of fluid (100 rnL) was injected.

The differences were not significant (P > .05).
One of us (B.O.G.) saw the patient in 2006.
Asymmetry of the upper part of the rib cage (patient 5) and pseudarthrosis of
the first and second ribs (patient 8) were incidental anomalies (Table 3).
Of the 761 hospitalized patients, 171 (22.5%) were infants (younger than 1
year).
In this issue of J A M (p 1037), a successful transplant is reported.
The 3 cusps of the aortic valve (the "Mercedes-Benz sign'? were clearly
shown on the echocardiogram.
If there is a close relationship between the parenthetical material and the rest of the
sentence, commas are preferred to parentheses.
The hemoglobin level, although in the normal range, was lower than ex-
pected.
If the relationship in thought after the expressions namely (viz), that 13Cie), andfor
example (eg) is incidental, use parentheses instead of commas.
He weighed the advice of several committee members (namely,Jones, Burke,
and Easton) before making hi proposal.

Punctuation Marks With Parentheses. Use no punctuation before the opening pa-
renthesiS except in enumerations (see Enumerations below).
Any punctu,ation mark can follow a closing parenthesis, but only the 3 end marks
(the period, the question mark, and the exclamation point) may precede it when the
parenthetical material interrupt. the sentence. If a complete sentence is contained
within parentheses, it is not necessary to have punctuation within the parentheses if it
would noticeably interrupt the flow of the sentence. Note that with complete sen-
tences, the initial letter of the first word is capitalized.
The discussion on informed consent lasted 2 hours. (A finai draft has yet to
be written.) The discussion failed to resolve the question.
The discussion on informed consent lasted 2 hours (;I final draft h;~syer 10 k
written) and did not resolve the question.
8.5 Parentheses and Brackets

--
After what seemed an ctrmity (11 took 2 hours!), the discussion o n ~nfom~ecl
consent ended.
When the parenthetical material includes special punctuation, such as an esclama-
tion point or a question mark, or several statements, terminal punctuation is placed
inside the closing parenthesis.

Oscar Wilde once said (When? Where? Who knows? But I read it in a book
once upon a time, hence it must be true.) that "anyone who has never
written a book is very ~earned."~

[dentifying Numbers or Letters. When an item identified by letter or number is re-

ferred to later by that letter or number only, enclose the letter or number in pa-
rentheses.

You then follow (31, (51, and (6) to solve the puzzle.
If the category name is used instead, parentheses may be dropped.
steps 1, 2, and 3 must be done slowly.

Enumerations. For division of a short enumeration that is run in and indicated by

numerals or lowercase italic letters, enclose the numerals or letters in parentheses.
(See also 19.5, Numbers and Percentages, Enumerations.)

The patient is to bring (1) all pill bottles, (2) past medical records, and (3) our
questionnaire to the first office visit.

References in Text Use parentheses to enclose all or part of a reference given in the
text. (See also 3.3, References, References Given in Text.)

Two cases of invasive zygomycosis with a fatal outcome were reported in the
Archives of Dermdtology (2005;141[10]:1211-1213). . .

In Legends. In legends, use parentheses to identlfy a case or patient and parts of

a composite figure when appropriate. (See also 4.2.7, Visual Presentation of Data, .
Figures, Titles, Legends, and Labels.)
Figure 6. Facial paralysis on the right side (patient 3).
Figure 2. Fracture of the left femur (patient 7).
The date, if given, is similarly enclosed.
Figure 2. Frdcture of the left femur (patient 7, October 23, 2004).
For photomicrographs, give the magnification and the stain, if relevant, in paren-
theses (see also 4.2.7, Visual Presentation of Data, Figures, Titles, Legends, and
Labels).
Figure 3. Marrow aspiration 14 weeks after transplantation (Wright stain,
original magnification ~600).
 8.5 2 Brackets

Trade Names. If there is a reason to provide a trade name for a drug or for equipment.
enclose the trade name in parentheses immediately after the first use of the non-
proprietary name in the text and in the abstract. (See also 15.4.3, Nomenclature,
Drugs, Proprietary Names; and 15.5, Nomenclature, Equipment, Devices, and Re-

Treatment included oral administration of indomethacin (Indocin), 25 mg

3 times a day.

Abbreviations. If used in the text, specialized abbreviations (as specified in 14.11,

Abbreviations, Clinical, Technical, and Other Common Terms) are enclosed in pa-
rentheses immediately after first mention of the term, which is spelled out in full.

Explanatory Notes. Explanatory notes, when incorporated into the text, are placed -
within parentheses. In such instances, terminal punctuation is used before the
closing parenthesis, the sentence(s) within the parentheses being a complete thought
but only parenthetical to the text.
I
(Antirejection therapy included parenteral antithymocyte globulin [ATGAMI,
at a dosage of 15 mg/kg per day.)
But: In mathematical expressions, parentheses are placed insidebrackets.
See 8.5.2, Brackets, W~thinParentheses. P-

Parenthetical Plurals. Parentheses are sometimes used around the letters s or es to

express the possibility of a plural when singular or plural could be meant. (See also
7.8.4, Grammar, Subject-Verb Agreement, Parenthetical Plurals.)
The name(s) of the editor(s1 of the book in reference 2 is unknown.
Note: If this construction is used, the verb should be singular, because the s is par-
enthetical. In general, try to avoid this construction and use the plural noun instead
or rephrase the sentence:
We do not know the name(s) of the editods) of the book in reference 2.

. Brackets

quoted. (See also 8.6.1, Quotation Marks, Quotations; 8.8.6, Ellipses, Change in Capi-
talization; and 8.8.7, Ellipses, Omission of Ellipses.)
"Enough questions had arisen [these :~rcnot clcscrihedl lo warrant 111edic:ll
consultation."
'
Thompson stated, "Because of the patient's preferences, surgery was crt3.w-
lute& contraindicated [italics added]."
"The following year 119471 was a turning point "

357
 8.6 Quotation Marks

Note: Use sic (Latin for "thus" or "so") in brackets to indicate an error o r peculiarity in
the spelling or grammar of the preceding word in the original sourcc of the quota-
tion. As with apologetic quotation marks (see 8.6.8, Quotation Marks, Apologetic
Quotation Marks), use sic with discretion.
"The plural [sicl cavity was filled with fluid."
"Breathing of the gas is often followed by extraordinary fits of extacy [sicl."

-. Within Parentheses. Use brackets to indicate parenthetical expressions within par-

enthetical expressions.
A nitrogen mustard (mechlorethamine hydrochloride [Mustargenl) was one
of the drugs used.
In scientific text, one often encounters complex parenthetical constructions such as
consecutive parentheses and b n c ~ e t swithin parentheses.
Her platelet count was 100 000/mm3(100 x 109/L) (reference range, 150000
to 450000/mm3 [I50 to 450 x 1o9/L1).

In Formulas. In mathematical formulas, parentheses are generally used for the in-
nermost units, with parentheses changed to brackets when the formula is par-
enthetical. (See also 21.3, Mathematical Composition, Stacked vs Unstacked.) .

The equation suggested by this phenomenon (t = d[rl - r23)can be applied

in a variety of circumstances.
In chemical formulas, the current trend is to use only parentheses and brackets,
making sure that every parenthetical or bracketed expression has an opening and
closing parenthesis or bracket symbol. Consult the most recent edition of USP Dic-
tionary of USAN and International Drug Names for drug formulas and The Merck
Index for chemical compounds to verify 'the correct use of parentheses and brackets.
An experimental drug ( ~ [ ( 2 - h ~ d r o ~ - l - ( h ~ d r o ~ e t h ~ l ) e t h o ~ r n e ~
nine) was used to treat the cytomegalovirus retinopathy in patients with AIDS.
If the older style of parentheses, braces, and brackets has been used by the author,
retain it. The notation will be readily understood by the author's intended audience.
When a parenthetical or bracketed insertion in the text contains a mathematical
formula in which parentheses or brackets appear, the characters within the formula
should be left as given unless that would place 2 identical punctuation symbols (eg,
2 open parentheses) immediately adjacent to each other. To avoid adjacent identi-
cal characters, change parentheses to brackets or brackets to parentheses in the for-
mula as needed, working frpm inside out, starting with parentheses, to brackets, to
braces.
+
CV: = [ C V ~ (cv~/NR)]/Ns
Quotation Marks. Quotation marks are used to indicate material that is taken di-
rectly from another source.
 8.6.5 Placement

Quotations. Use quotation marks to enclose a direct quotation of no more thin 4

lines from textual material or speeches (for longer material, see also 8.6.14, Quota-
tion Marks, Block Quotations); When the quotation marks enclose conversational
dialogue, there is no limit to the length that may be set in run-on format.
In all quoted material, follow the wording, spelling, and punctuation of the
original exactly. The only time this rule does not apply is when,the quoted material,
although a complete sentence or part of a complete sentence in its original source, is
now,used as part OF another complete sentence. In this case, the capital letter in the
quoted sentence would be replaced by a lowercase letter in brackets.
Similarly, in legal material any change if: initial capital letters from quoted ma-
terial should be indicated by placing the change in brackets. (See 8.5.2, Brackets,
Insertions in Quotations.) '

To indicate an omission in quoted material, use ellipses. (See 8.8, Ellipses.)

To indicate editorial interpolation in quoted material, use brackets. (See 8.5.2,
Brackets, Iniertions in Quotations.) Use [sic] after a misspelled word or an incorrect
or apparently absurd statement in quoted material to indicate that this is an accurate
rendition of the original source. However, when quoting material from another er:!
that uses now obsolete spellings, use sic sparingly. Do not use sic with an excla-
mation point. (Note: The use of sic is not limited to quoted material; in other in-
stances, it means that any unusual or bizarre appearance in the preceding word is
intentional, not accidental.) (See 8.5.2, Urxkets, Insertions in Quotations.)
The author should always verify the quotation from the original source.

Dialogue. With conversational dialogue, enclose the opening word ancl the fin;11
word in quotation marks.
"Please don't schedule the surgery for a Tuesday."
"OK, if that's inconvenient for you, I won't."

Titles. Within titles (including titles of articles, references, ancl tables), centcrecl
heads, and run-in sideheads, use double qi~olationmarks.
The "Sense" of Humor

Single Quotation Marks. Use single quotation marks for quotations within quota-
tions.
He looked at us and said, ''As my patients always told me, 'Be a goocl
listener.'"
I

Placement. Place closing quotation marks outside commas and periods, inside co-
lons and semicolons. Place question marks, dashes, and exclamation points inside
quotation marks only when they are part of the quoted nmterial. If they apply to the
whole statement, place them outside the quotation marks.
\Vhy bother to perform autopsies at all if the main finding is invariably
"edema and congestion of the viscera"?
Tile cl!nlcian continues to ask, "Why clid he clic?"
8 6 Quotat~onMarks

"I'll lend you my stethoscope for clinic''-then she remembered the last time I-

she had lent it and said, "On second thought, I'll be needing it myself."
(Note: Commas are not always needed with quoted material. For example, in the
foltowing example commas are not necessary after "said" or to set off the quoted
1. '

material.)
He said he had had his "fill of it all" and was "content" to leave the meeting. 1
Omission of Opening or Closing Quotation Marks. The openkg quotation mark
should be omitted when an article beginning with a stand-up or dropped initial
capital ietter also begins with a quotation. It is best, however, to avoid this construc-
tion.
Doctors need some patients," a sage had said.
When excerpting long passages that consist of several paragraphs, use opening
B
double quotation marks before each paragraph and closing quotation marks only at
the end of the final paragraph. (See also 8.8, Ellipses, and 8.6.14, Block Quotations.).

Coined Words, Slang. Coined words, slang, nicknames, and words or phrases used 1
ironically or facetiously may be enclosed in quotation marks at first mention. There- ; .
after, omit quotation marks. (See also 22.5.4, Typography, Specific Uses of Fonts, j
Italics.)
We further hope that, above all, those who have been fed only "docufiction"
on this matter, as if it were truth, will cease to be misled.
Nelson Essentials of Pediatrics is not a .. .synopsis of or a companion to the
Nelson Textbook.of Pediatrics, although initially our associates dubbed it
"Baby Nelson," "Half Nelson," and "Junior el son."^
It has been said that shoes and latrines are the best "medicine" for ancy-
lostomiasis (hookworm disease). -
Do not use quotation marks when emphasizing a word, when using a non-English
word, when mentioning a term as a term, or when defining a term. In these instances,
italics is preferred. (See also 22.5.4, Typography, Specific Uses of Fonts, Italics.)
The page number is called the folio.
The eye associated with the greater reduction in hitting ability when dimmed
by a filter was termed the dominant eye for motion stereopsis.
Pulsus paradom is defined as an exaggeration of the phystologic in-
spiratory drop in systolic blood pressure.

Apologetic Quotation ~ a r k sQuotation

. marks are sometimes used around words
for special.effect or to indicate irony. In most instances, however, they are unnec-
essary.
Using their own finances and being informed about the economics of the
approach, some may opt for the "boutique class" of health care.
 8.6.14 Block Quotations

So-called. A word or phrase following so-called should not be enclosed in quotation

The so-called harm principle holds that competent adults should have
freedom of action unless they pose a risk to themselves or to the community.

-1 Common Words Used in a Technical Sense. Enclose in quotation marks a common

word used in a special technical sense when the context does not make the meaning
clear. (See also 8.6.11, Definition or Translation of Non-English-Language Words.)
In many publications, "running feet" on left-hand pages face the "gutter" at
the bottom of the page.
"Coma vigiln(akinetic mutism) may be confused with conscious states.

Definition or Translation of Non-English-Language Words. The literal translation

of a non-English-language word or phrase is usually enclosed in quotation marks if
it follows the word or phrase, whereas the simple definition of the word or phrase
is not. (See also 12.2, Non-English Words, Phrases, and Accent Marks, Accent Marks
[Diacritics].)
.Hysterical patients may exhibit an attitude termed la belle i n d i f f ' c e
("beautiful indifference"or total unconcern) toward their condition.

Titles of Works. In the text, use quotation marks to enclose titles of short poems, es-
says, lectures, radio and television programs, songs, the names of electronic files,
parts of published works (chapters, articles in a periodical), papers read at meetin-
gs, dissertations, theses, and parts of the same article (eg, the "Results" section). (See
also 10.5, Capitalization, Types and Sections of Articles, and 22.5.4, Typography,
Specific Uses of Fonts, Italics.)

Indirect Discourse, Discussions.After indirect discourse, do not use quotation marks.

The nurse said he would be discharged today.
Do not use quotation marks with yes or no.
His answer to the question was no.
In interview or discussion formats when the name of the speaker is set off, do not use
quotation marks.
Dr lack: Now let us review the slides of the bone marrow biopsy. i
Dr Smith: The first slide reveals complete absence of granulocytic pre-
cursors.

Block Quotations. If material quoted from texts or speeches is longer than 4 lines of
text. the material should be set off in a block, ie, in reduced type and without the
quotation marks Paragraph ~ndentsare generally not used unless the quoted mate-
rial IS known to begin a paragraph Fpnce ic often added both above and below these
longer quotations

P 361
6 7 -0r:rophe

I t rtlc t,lt~-kquotation appears in a section to be set in reduced type, do not reduce

r l ~ crypc size of the quored material further.
If another quotation appears within a block quote, use double quotation marks
I
around the contained quotation, rather than setting off in blocks, regardless of the
length. . .
Apostrophe

To Show Possession. Use the apostrophe to show the possessive case of proper
nouns in accordance with the following examples (see also 16.2, Eponyms, Non-
possessive Form):
Jones' bones (1 person named Jones)
the Joneses'.bones (2 or more people named Jones)
If a singular or plural word does not end in s, add 's to form the possessive.
a child's wants men's concerns
. women's health everyone's answer
If a proper noun or name ends in a silent s, z,or x; form the possessive by adding 2 ! I
Theroux's The Mosquito Coast
Jacqueline du Pres's recordings

Possessive Pronouns. Do not use s' with possessive pronouns: his, hers, ours, its,
yours, theirs, whose.
The idea was hers. 1
Give the book its due.
Note: Do not confuse the contraction of it is (it's) with the possessive its, eg, "It's an
excellent resource. I have not seen its equal."

Possessive of Compound Terms. Use 'safter only the last word of a compound term.
father-in-law's health
editor in chief's decision '
someone else's problem
secretary of health's ruling

Joint Possession. When joint possession is being shown with nouns, or witli an
organization's or business firm's name, use the possessive form only in the last word
of the noun or name.
Food and Drug Administration's policy
I- I

Farrar, Straus & Giroux's books

Centers for Disease Control and Prevention's Task Force
Hammond and Horn's study
When possession is individual, each noun takes the possessive form.
we matched.the infant's and mother's records.

362
. .-

.----.- '. ------..7

. . -. . .
... .:c .' . :.. .
. - ' I
 8.7.7 Prime

Note: When one of the nouns takes a possessive pronoun, the other nouns take the
possessive as well.
I presented the intern's and my workups.

IUsing Apostrophes to Form Plurals. Do not use an apostrophe to indicate the plural
of a name. Do not use an apostrophe in the name of an organization in which the
qualifying term is used as an adje&ve or an attributive rather than possessive. Of
course, always follow the official name.
The Chicago Cubs state parks rangers
Veterans Affairs musicians union
Rainbow Babies Hospital nurses station .

[I$. Use 's to indicate the plural of letters, signs, or symbols spoken as such, or words
I'.
referred-to as words when s alone would be confusing. Note the italics with inflec-
tional ending in roman type for words, letteys, and numbers but not for symbols and
?
signs.
He uses too many and's.
The punuscript editor was mindful of the list of do's and don't's.
Mind yourp's and 4s'.
There are 9 +'s o n the page.
His 1's looked like 7s.
Do not use an apostrophe to form the plural of an all-capital abbreviation or of
. numerals (including years). (See also 9.5, Plurals, Abbreviations.)
ECGs RBCs
EEGs a woman in her 40s .
IQs during the late 1990s

mUnits of Time and Money as PossessiveAdjectives. With units of time (minilte, llour.
day, month, year, etc) used as possessive adjectives, an 's is added. The same holds
true for monetary terms:
a day's wait a few hours' tin~e
an hour's delay 6 months' gestation
5 days' hard work ;I dollar's worth

Prime. Do not use an apostrophe where a prime sign is intended. Do not use ;I pt.in~c,
sign as a symbol of measurement. (See also 15.4.4, Nomenclature. Dnigs. Chcmic:~l
Names.)
The methyl group was in the 5' position.
8.8 Ellipses

arc. 3 sp;rced doh ( . . . ) gcner~llyused to indicate omiulon of 1 or

Ellipses. El11pw~
morc ,:ords. 11nt.s.p;rmgr~phs.or data from quoted nutcriai (this onllsslon being the
c.ll@sis).Excerpts from tlic foilowing paragraph will kx: u x d to demonstrate the use
of ellipses.

In Fruit Displayed on a Stand (cover), exhibited in 1882, Caillebotte depicts a

traditional subject in a manner far removed from the traditional cornucopian flow
of fruit. Instead, he shows a stark, rectangular grid lit by centers bf rounded forms,
brilliantly colored. Vivid oranges, reds, and purples, light greens, creamy violets,
and color-flecked gold are cupped within areas of crinkly blue-white paper, the
cooler shades in the center separating the hotter tones, preventing them from
spilling into each other.5

Omission Within a Sentence. If the ellipsis occurs within a sentence, ellipses rep-
resent the omission.
Instead, he shows a . . .grid lit by centers of rounded forms, brilliantly .
colored.
In some such instances, additional punctuation may be used on either side of the
.
. ..--
.,
ellipses if it helps the sense of the sentence or better shows the omission. t

Instead, he shows ,a stark, rectangular grid.. ., brilliantly colored.

If the quotation itselfcontahk ellipses, to make clear that the ellipses were part of the
original a note to this effect should be included in brackets.

Omission a t the End of a Sentence or Between Complete Sentences. If the ellipsis

occurs at the end of a complete sentence, or bemieen 2 complete sentences, ellipses
follow the final punctuation mark,the-finalpunctuation mark being set close to the
word preceding it, even when this word is not the final word in that sentence in the
original.
In Fmit Displayed on a Stand (cover), exhibited in 1882, Caillebotte depicts
a traditional subject in a manner far removed from the traditional. ...Instead,
he shows a stark, rectangular grid !it by centers of rounded forms, brilliantly
colored.

Grammatically Incomplete Expressions. The sentence within which an ellipsis oc-

curs should be a grammatically complete expression. However, ellipses and no
period may be used at the end of a sentence fragment to indicate that it is purposely
grammatically incomplete. '
Complete the sentence "When I retire, I plan to . . . " in 20 words or less.

Omissions in Verse. Use 1 line of em-spaced dots to indicate omission of a full line'or !
several consecutive lines of verse.
 :.-. .

8.8.7 Omission of Ellipses

Sometimes you say it's smaller. Today

. . . . . . .
you said it was a touch larger, and would change.
Marc Straus, ML), "AUI~IIIIII"

Omissions Between or at the Start of Paragraphs. Wit11 material in wllich sc.vcral

paragraphs arebeing quoted and omissions of full paragraphs occur, a pyriorl :~nrI
ellipses at the end of the paragraph preceding the omitted nlaterial are sitffir-icn~I( I
indicate this omission.
Indeed, it is no more than the just desert of Dr Theodore Schott and his late
brother to attribute to them the credit of having introduced and elaboratecl a
method capable of restoring most cases of heart disease to a state of com-
plete compensation, after the failure of other means, such as digitalis. . . .
If the initial word($ or the first sentence of the paragraph being quoted is omitted.
begin that paragraph with a paragraph indention and ellipses to indicate that this is
not the beginning of that parag-ph..
..
. it is no more than the just desert of Dr Theodore Schott and his late
brother to attribute to them the credit of having introduced and elaborated a
method capable of restoring most cases of heart disease to a state of com-
plete compensation, after the failure of other means, such as digitalis.. . .

. Change in Capitalization. The first word after the end punctuation mark and the
ellipses should use the original capitalization, particularly in legal and scholarly
documents. This facilitates finding the material in the original source and avoids any
change of meaning. If a change in the original capitalization is made, brackets should
be used around the letter in question. (See also 8.5.2, Brackets, Insertions in Quo-
tations, and 8.6.1, Quotation Marks, Quotations.)
m]e shows a stark, rectangular grid lit by centers of rounded for& brilliantly
colored.

I In the cover story, the artist is described as using "[vlivid oranges, reds, and
purples, light greens, creamy violets, and color-flecked gold to depict "a
traditional subject."

Omission of Ellipses. Ellipses are not necessary at the beginning and end of a quo-
tation if the quoted material is a complete sentence from the original.
L

In a 1985JAMA cover story, Martha Bier wrote, '.Instead, he shows a stark, ;

rectangular grid lit by centers of rounded forms, brilliantly colored."
Omit ellipseswithin a quotation when the omitted words occur at the same place as a
bracketed editorial insertion. (See also 8.5.2, Brackets, Insertions in Quot:~tions.)
"[Caillebottelshows a stark, rectangillar grid lit by centers of rounded forms.
brilliantly colored."
When a quoted phrase is an incomplete sentence, readers understand that something
precedes and follows; therefore, ellipses are not used.
8.8 Ellipses

In Place de LL'Eurcp on u Kai~iyf h j , Caillct>ottc docs not u.x "centrrs of I

rounded forms, brilliantly colored- t ~ u instcad

t uses muted gnys and purplrs I

to give the feel of the rain.

Ellipses are generally not needed when the first part of the sentence is deleted. ! I
Here Caillebotte "depicts a traditional subject in a manner far removed from
the traditional.. . . "

Ellipses in Tables. In tables, ellipses may be used, for example, to indicate that n o
data were available or that a specific category of data is not applicable. (See also
4.1.3, Visual Presentation of Data, Tables, Table Components.) An explanatory foot- I
note should always be included if it is not absolutely clear from the context what the
ellipses represent.
"Ellipses in&&-ateno test performed.

ACKNOWLEDGMENT
Principal author: Cheryl Iverson, MA

REFERENCES
1. Truss L. Eats, Shoots E. Leaves: The Zero Tolerance Approach to Punctuation. New
I
York, NY: Gotham Books; 2003:201.
2. Shields C. Invention. In: Dressing Upfor the Carnival. New York, W. Penguin Putnam -
Inc; 2000:151.
3. Ball P. m e Unauthorized Biography of a Local Doctor Or Fmm Infancy l%rough
Puberty and On to Senility. Hagerstown, MD: Exponent Publishers; 1993.
4. Behrman R, Kleigman R. Nelson's Essentials of Pediatrics. Philadelphia, PA: WB
Saunders; 1990.
5. Bier ML. The Cover. J A M . 1985;254(8):1000.
 9.5
How Plurals Are Formed Abbreviations

9.6
Plurals of Symbols, Letters. Numbers, and Years

9.7
Latin and Greek vs English When Not to Use Plurals

9.0
Microorganisms False Singulars

How Plurals Are Formed. The plurals of most nouns are formed by adding -s or -a.
Singukr Plural

church churches
decision decisions
11
disease diseases
/I
However, English is irregular enough that it pays to consult a dictioriary for most

Singular
-- Plural
woman women

tooth teeth
wolf wolves
child a children
5
Collective Nouns. Collective nouns may take either singular or plural verbs, de-
pending on whether the word refers to the group as a unit or to its n~enibersas
f
individuals. In American English, most nouns naming a group regarded as a unit :Ire
treated as singular. (See also 7.8.5, Grammar, Subject-Verb Agreement. Collective ,

Fifty percent of my time is spent on administration.

Fifty percent of all physicians do not exercise regularly.
The audience was enthralled.

367
9.4 Microorganisms

This gathering is beconling noisy.

At noon today the jury delivers its verdict.
I
For a unit of measure, use a singular verb.
I
Five nlilliliters was injected.
Two weeks of symptonls is common.
I.
Latin and Greek vs English. There is a trend toward using. English plurals rather
than the traditional Latin or Greek. However, in most cases the latest edition of
MCI-rinnz-Wcbster's Collegiate Dictionary or Dorland's or Stedman's medical dictio-
nary should be followed. Consistency within a manuscript is key.
Singtihr Preferred Plural
alg:~ :11gac
amoeba amoebas
appendix appendixes or appendices [consult dictionary
for specific usage]
cannula camUkis
condyloma acuminatum condylomata accuminata [with 2-word Latin
plurals, both parts become plural1
cranium crania
fistula fistulas .-
formula formulas
genus genera
index indices or indexes [consult dictionary for
specific usagel
maxilla maxill~s
orbit orbits
rhytid rhytids
sequela sequelae
vertebra vertebrae

Microorganisms. When referring to the common vernacular plural of a genus, use

roman lowercase letters. Consult the latest edition of Dorland's or Stedman's medical
dictionary. For organisms that do not have a common plural, add the word species or
organisms to the genus name to indicate a plural use (see also 15.14, Nomenclature,
Organisms and Pathogens).
Genus Plural Noun Form
Chlamydia chlamydiae
Eschen'chia Eschm'chia organisms
Mycobactenum mycobacteria
Pro1eli.s - Proteus species
l'scriclot~~o~rrrs pseudomonads
 9.8 False Singulars

F;
L
;.I
Salmonella
Staphylococcus
salmonellae
staphylococci
Slrepococctlr streptococci

Abbreviations. For most all-capital abbreqiations, the plural is formed by adding s.

CIS HMOs
EEGs ICUs
k
\ ORS RBCs

REFERRAL PATERNS IN MIDWESTERN HMOs

Plurals o f Symbols, Letters, Numbers. and Years. Use 's to.indicate the p l u r ~ol f

roman type for words, letters, and numbers but not for symbols and signs. (See alxo
8.7.5, Punctuation, Apostrophe, Using Apostrophes to Form Plurals.)
He uses too many and's.
All of the capital P's should be underlined.
Please use +'s to indicate a positive result.
Note: If the symbol can be easily expressed using words, this is preferred:
L
Please use plus signs to indicate positive results.
Do not use an apostrophe to form the plural of numerals (including years).

When Not t o Use Plurals. Beware of "plur~lizing"nouns that clnnot stand on their
own as plurals.
x n l m samples (not "sera")
urine tests (not "urines")

verb (eg, measles, mumps, mathem;ltics. genetics).

Measles is a deadly disease in unclcrdevelopecl countries.
A few nouns are usually used in the plural form; however, the distinction between
plur.~l;~ndsingular should he retained where appropriate. (See also 7.8.3, G~ininiar.
Sl!l,jcrr-VL.r\, ,\~rccliienl, ell^ I'luclls.)
 10.3.8 Tests
First Word of Sentences, Statements, Quotations, 10.3.9 Official Names
Titles, Subtitlar, and Table Headings 10.3.10 Titles and Degrees of Persons

10.4
Titles and Headings Designators
10.2.1 Titles of Medical Articles
10.2.2 -HyphenatedCompounds 10.5
. Types and Sections of Articles
Proper Nouns 10.6
10.3.1 Geographic Names Acronyms and Initialisms.
10.3.2 Sociocultural Designations
10.3.3 Events, Awards, and egislation 10.7
10.3.4 Eponyms and Words Derived Capitalized Computer Terms
From Proper Nouns
10.8
10.3.6 Organisms, "Intercapped" Compounds
10.3.7 Seasons, Deities, Holidays

First Word of Sentences, Statements, Quotations, Titles, Subtitles, and

j1:;.,
Table ~eadings.The first word of every complete sentence should be capitalized. ::
i;.

The following should also be capitalized:

II The first word of a formal statement that follows a colon

I- Our conclusions may be stated thus: More research is needed.

8 The first word of a direct quotation (but see 8.6.1, Punctuation, Quotation Marks,
Quotations)
The report noted: "A candidate may be admitted after completing 2 years of
medical school."
Kurt Vonnegut put it best when he said, "Writers can treat their mental
illnesses every day."
Note: If the quotation is run into the sentence, a lowercase letter on the first word i
may be preferable (see 8.6.1, Punctuation, Quotation Marks, Quotations).
The patient described her headache pairi as feeling like "needles behind the
eyes."
a Each major word in the title of a tahle (.see 10.2.1.Titles and Headings, Titles of
Medical Articles, and 4.1.3, Visual Presctntarion of I h a . Tables. T.~bleCompo-
nents). In column and row headings (table stulx), only [he initial word should bt.
capitalized. If a symbol, numeral, or lowerc;l.;r Greek Ierter begins thc stub, the
first word that follows should hc cnpit;~lizeci
10.2 Tlrles a n d Headlngl

-Titles and Headings. Gpir;~lizr.nl:r)or \ \ o r c L ~ 111 [r[lc\. sut,clric,. arrcl 1rr;ldings of

pt~l>lii.:r~ron~
mu>ical con~lwh~tio~lh. pldys ~ . \ [ ; I ~ C - . ~ n dx.rc-C-n), r d ~ oand television
pmgrJms, movies. paintings ancl other \vorks of an, x)it\varct programs, Web sites and
weblogs, electronic systems, tradem:lrks, and names of ships, airplanes, spacecraft,
a~vards,corporations. and monuments.
D o not capitalize :I coordinaring conjunction, an article, or a preposition of 3 or
fewer letters. escept \vlien i t is the first or last word in a title or subtitle. (For more o n
typeface rules when referring to \\,orlis ol' art, see 22.5.4, Typography, Specific Uses
of Fonts, Italics, and 8.6.3, I'i~ncti~ation, Quotation Marks, Titles.)

the Cochrane Database the Mo7zitor and the Menimac

the USS Cole My Man Godfrey
the space shuttle E~zrierlvor the New England Journal of
The Four Seusolu by Antonio Vivaldi Medicine
Lucian Freud's Girl W'ith a White Dog Oscar
~ ( i l d e nGlobe Award PubMed
Internet n e Sopranos
the Journal of tl'e American Medical Symphony No. 8, "Symphony of
Association a Thousand," by Gustav Mahler
the Kitty Hazttk the Tomb of the Unknown Soldier
The Lasker Award Windows
the Lincoln Mtt~norial Wordperfect
MEDLINE World Wide Web (the Web,
Web site)
MeSH [Medical Subject Headings]

A1ote:The may b e dropped from titles if the syntax of the sentence improves without it.

Titles of Medical Articles. Titles of articles take initial capitals when they are in'the
title position but not when they are in the reference position.
Title: Autonomic Response in Depersonalization Disorder
Reference: Sierra M, Senior C, Dalton J. Autonomic response in
depersonalization disorder. Arch Gen Psychiatry.
2002;59(8):100-103.
In titles and headings, capitalize 2-letter verbs, such as go, do, am, is, be. Note: In
infinitives, "to" is not capitalized. Do not capitalize a coordinating conjunction, ar-
ticlc. or preposition of 3 or fewer letters, except when it is the first word in the title or
sul)title.
\Vliat Is Sarcoma?
We 110 Need to Treat Mild Hypertension
\X/hcre the Worlcl \Vill L3e in the Year 2020
 .8 .

10.2.2 Hyphenated Compounds

Defining the Role of Computed Tomography in Injuries Resulting From

Blunt Abdominal Trauma
Cardiovascular Risk Factors in Patients With Type 2 Diabetes
Opportunities for Comprehensive Risk Management
In compound terms from languages other &an English, capitalize all parts of the
expression.
Fluorescence In Situ Hybridization in Surgical Specimens of Lung Cancer
'
Nephrectomy W~thConcomitant En Bloc Adrenalectomy
With a phrasal verb, such as "follow up," capitalize both parts in a title.
The Need to ~ o l l o ; ~
the~ Patient With E.sophagGl Cancer

Hyphenated Compounds. In titles, subtitles, table headings, and text headings, d o

not capitalize the second part of a hyphenated compound in the following instances:
If either part is a hyphenated prefix or suffm (see Temporary Compounds in 8.3.1,'
Punctuation, Hyphens and Dashes, Hyphen)
Nonsteroidal Anti-inflammatory Drugs
Self-referral to Psychiatrists [compound words with the prefix sey- are con-
sidered one word]
Intra-abdominal Surgery
If both parts together constitute a.single word (consult the current edition of
Merriam-Webster's Collegiate Dictionary or Stedman's or Dorland's medical dic-
tionary)
Long-term Treatment of Diabetes
Follow-up Studies of Patients With Leukemia
Part-time Nursing Staff
How to Interpret X-ray Films
However, in the case of a temporary compound, in which each part o f thc. hy-
phenated term carries equal weight, capitalize both \\lorcis.
Cost-Benefit Analysis
Low-Level Activity
Drug-Resistant Bacteria
B-Cell Lymphoma
obsessive-Compulsive Disorder
Age-Related Macular Degeneration
In titles, subtitles, table heads, text headings, and line ;in,capiralize the first Icr~cr01 ;I
word that follows a lowercase (but not a capital) Greek letter (see 17.2.Grct-k I.c*rr~-I.
Capitalitation Mter a Greek Letter), a numeral (escept \\.hen ;In al~l~rwiatc<l ilnlr o f

373
10.3 Proper Nouns

measure that never is capitalized follows), a symbol, or an italicized organic ct~crn-

ist~yprefix such as tram- and cis-.
Systemic Adverse Effects of Ophthalmic P-Blockers
Enhancement of A-aminolevulinic Acid Photodynamic Therapy
Effectiveness of Tilnolol at 10% Strength
High-Dose 308-nm Excimer Laser for the Treatment of Psoriasis
or,-Antitrypsin Inhibits Overexpressed Serine Proteinases During
Inflammation
Both genus and species should be capitalized in all-capital text headings.
HELICOBAClER PYLORI AND THE PATIE-w WITH ULCERS
However, they should be treated normally in mixed capital and lowercase headings
(see 10.3.6, Proper Nouns, Organisms, and 15.14.1, Nomenclature, Organisms and
Pathogens, Biological Nomenclature).
Heficobucterpylori and the Patient With Ulcers

Proper Nouns. Proper nouns are words used as names for unique individuals,
events, objects, or places.

Geographic Names. Capitalize names of cities, towns, counties, states, countries,

continents, islands, airports, peninsulas, bodies of water, mountains and mountain
ranges, streets, parks, forests, canyons, dams, and regions.
the Antarctic the Loop [Chicago]
Arabian Gulf Mexico City
the Bay Area Mississippi River
Central America New Hampshire
the 23rd Congressional District New York State [but:the state of
Cook County New Yorkl
Dismal Swamp Oman or Sultanate of Oman
[either is correct]
El Paso
Quebec City
the Florida Panhandle
Saudi Arabia or Kingdom of
Grand Canyon
Saudi Arabia [either is correct1
Hoover Dam
the Silk Route
the Iron Curtain
Third World
the Isle of Skye .
United Kingdom
Kennedy Expressway
Upstate New York
LaGuardia International Airport
the West Coast
Lake Placid
 10.3.2 Sociocultural Deugnations

If a common noun is capitalized in the singular, it is generally not capitalizecl in the

Atlantic and Pacific oceans

Kennedy and Eisenhower expressways.

Compass directions are not capitalized unless they are generally accepted temls for

There is a large time difference between Europe and the Far East.
Walk east until you arrive at the lake.
There is no party like a West Coast party because a West Coast party doesn't

He lives in northern Michigan.

The practice of meditation is finding followers in the Western world.

Sociocultural Designations. Capitalize names of languages, nationalities, qthnicities,

political parties, religions, and religious denominations. Do not capitalize political
doctrines (conservative, progressive). Do not capitalize white or black as a desig-
nation of race.
African American-
an Arab man
the Berbers
the Catholic Church (but: a Methodist church, First Methodist Church)
English language
Ethiopian food
the French
Hispanic population
Indian American community
of Italia? heritage
Latina girls I!,
1;:1
d!j
Native American
I>:.;
,\

;':
Protestant
Sanskrit
Although she has been a member of the Republican party for years, at one
time she was a Democrat.
This legislation endorses the principles of democracy in our republican form
of government.
 ---_.
10 3 Proper Noun%

Events. Awards, and Legislation. Capitalize the names of historical and special
c\,t.nrs, historicdl periods, and awards (but not common nouns that may follow the
1
nanlcs). Capitalize the official names of awards and specific parts of laws and bills,
but follow the official name (as in the lowercase w in Americans with Disabilities
Act).
Americans with Disabilities Act the Great Depression
Civil War Medicare
Civil War era Nobel Prize
Congressional Medal of Honor Physician's Recognition Award
Declaration of Helsinki Public Law 89-74
Equal Rights Amendment Purple Heart
Family and Medical Leave Act of 1993 Special Olympics
French Revoltltion Taste of Chicago
Geneva Convention Title M

Eponyms and Words Derived From Proper Nouns. With eponyms, capitalize the
proper name but not the common nouns that follow it.
Down syndrome Trendelenburg position
Rose-Waaler test Wada test

Most common words derived from proper nouns are not capitalized. In general,
follow the current edition of Menium-Webster's Collegiate Dictionary or Dorland's
Illustrated Medical Dictionary (for medical terms).
arabic numerals mendelian
brussels sprouts parkinsonism
candidiasis roman numerals
darwinian schiitosomiasis
india ink

Note: J A M and the Archives Journals d o not capitalize arabic and roman when
referring to numerals.

Proprietary Names. Capitalize trademarks and proprietary names of drugs and brand
names of manufactured products and equipment. Do not capitalize generic names or
descriptive terms.
The patient had swallowed 46 tablets of acetaminophen (Tylenol;Johnson &
Johnson, New Brunswick, New Jersey) and was treated for acetaminophen
overdose.
All references to exact brand names must be verified and include the city and state or
country of the manufacturer. (See also 15.5, Nomenclature, Equipment, Devices, and
lieagrnts.) The trademark and copyright symbols are not used in JAMA and Ar-
chiilcsJournals style.
 10.3.9 Official Names

Organisms. Capitalize the formal name of a genus when used in the singular, with or
without a species name. Capitalize formal genus names but not traditional plural
generic designations (eg, streptococci) or derived adjectives (streptococcal) (see also
9.4, Plurals, Microorganisms). Do not capitalize the name of a species, variety, or
subspecies. Do capitalize phylum, class, order, or family (see 15.14, Nomenclature,
Organisms and Pathogens). For capitalization of virus names, see 15.14.3, Nomen-
clature, Organisms and Pathogens, V i s and Prion Nomenclature.

Seasons, Deities, Holidays. Do not capitalize the names of the seasons. Do capitalize
the names of specific deities and manifestations.
Allah Jesus Christ
Ganesh Nature
God or Goddess (when used in a Shiva
monotheistic sense) Zeus
the goddess Athena
the Holy Spirit

I Capitalize recognized,holidays and calendar events.

Christmas New Year's Eve
Eid ul-Fitr Passover
Fourth of July Ramadan
Good Friday Rosh Hashanah
Kwanzaa Thanksgiving Day
Labor Day

Tests. The exact andcomplete titles of testsand subscalesof tests shouldbe capitalized.
The word test is not usually capitalized except when it is part of the official name
of the test. Always verify exact names of any tests with the author or with reference
sources.

Official Names. Capitalize the official titles of organizations,businesses, conferences,

congresses, institutions, and governmental agencies. Do not capitalize the conjunc-
tions, articles, or prepositions of 3 or fewer letters contained within these names. For
names of institutions, do not capitalize the unless it is part of the official title.
,

Chicago 13oarcl of Educ:~tion the Intcr~i;~tio~i;~l

Sul>c-o~n~nittcc.
on
the Communist Party Viral Nomenclature
Congress Knox College
Council of Science Editors Northwestern Memorial Hospital
the Fedcnl Bureau of Investigation The Ohio State uni~ersi9'
Hanwd University Quaker Oats Corporation
I4ou.w of Representatives Robert Wood Johnson Founclation
 I!IL.v r > . l i ~ . Tufts University School of Medicine

Suprclnc Coun ole: capitalize

Court only ~vlienreferring to the
Supreme Court)
B I I ~the
: board of trustees, the boards of health, the company, congressional
reports, a congresswoman, the federal government, the navy, US senators
Oiten when referring to themselves and their officers in abbreviated form, institu-
tions ancl :,rganiz:~tions use initial capitals for titles. We prefer lowercasing such
generic terms. For example,JAMA and the Archives Journals use the following des-
ign:ltions:
the American ~ k d i c a lAssociation the assnciation
the Board of Trustees the board or the trustees
the Council on Scientific Affairs the council
the House of Delegates the delegates
the president of the AMA the president

In running text, a singular form that is capitalized as part of the official name is
~rs~r;tlly
not c;~pitalizeclin the plurnl.
She is chair of the Department of Pediatrics at the University of Illinois,
Urbana.
Funding was received from the departments of pediatrics and neurology at
the University of Illinois, Urbana.
(See 3.3.3, Manuscript Preparation, Footnotes to Title Page, Author Affiliations, for an
es:implt. of capiralization of department titles in an affiliation footnote.)
. .

Titles and Degrees of Persons. Capitalize a person's title when it precedes the per-
son's name but not when it follows the name.
Committee Chair Lawrence Mandelbaum led the meeting.
At the meeting, Lawrence ~ a n d e l b a u mwas named committee chair.
Capitalize academic degrees when abbreviated but not when written out.
Irene Briggs, MA
Irene Briggs received her master's degree from the University of
Pennsylvania.

~ e s i ~ n a t o rWhen
s. used as specihc designations within a particular article, with or
without numerals, capitalize Table, Tables, Figure, and ~ i ~ h r e s .
summarized in Table 2
as seen in the Table
the middle third of the basilar artery (Figure 2)
 10.6 Acronyms and lnitialirmr

Do not capitalize the following words, even when used as specific designators. i~nlcss
used as part of a heading or title:
month

chromosome paragraph

edition schedule
experiment section

wave
method week
But: Step I diet, Schedule II drug, and Axis I of the Diagnostic and Stat&tical
~ a n hofMental
l Disordm, Fourth Edition

article, capitalize the first letter in the words of the category or section name.
The Letters to the Editor section of Archives of Netirology is a favorite of mine.

Acronyms and Initialisms. Do not capitalize the words from which an acronym or
initialism is derived (see 14.0, Abbreviations).
prostate-specific antigen (PSA)
enzyme-linked immunnsorbc.nl :rss;~y(ELISA)
Exception: When the word5 rtrirr form rtw acronym o r initi:ilis~nare propcr nilmes,
use capitals a s dcsritxd in I i l 3 9 . Prc>pc.~Soun.. Offici;~l5:rrnes
N:III~II:I~I ~ . \ [ I I L I [ C -o f fft:n[.rl I lc.~l[li1 X l 3 f l l \

379
10.8 "lntercapped" Compounds

When there has been a "stretch" to c.rc3te a study name or the name of a wr~tinggroup
that makes sense, is easy to say, and somehow relates to the name of the group, but
where the first letters of the major words do not match the acronym, do not use
unusual capitalization to indicate how the study name was derived. Ekpanded study
or group-authorship names use normal JAhU and the Archives Journals capitaliza-
tion style.
Evaluation of Platelet IIb/IIIa. Inhibitor for Stenting (EPISTEN??
Enhanced Suppression of the Platelet 1Ib/IIIa Receptor With Integrilin
Therapy (ESPRIT)
Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)
Clopidogrel in Unstable Angina to Prevent Recurreri; Events (CURE)
c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE)

Capitalized Computer Ternis. Use initial capitals with computer commands, func-
tions, or features.
Please d o not press the Back button on your browser until we have finished
processing your request.
Enter one or more search terms and click Go..
Items in the History folder will be deleted after 90 days.
The word e-mailtakes a lowercase letter injAMA and Archives Journals style except
when it starts a sentence.
Please send e-mail messages to my work address.
E-mail submissions are preferred.

"lntercapped" Compounds. JAMA and the Archives Journals capitalize trade

names according to the spelling of the legal trademarks, even if they begin with a
lowercase letter and contain a capitalized letter.
She sold her collection of vintage hats on eBay.
Data were processed in the field on iBook computers (Apple, Cupertino,
California).
Avoid starting a sentence with one of these trade names. It is almost always pref-
erable to reword the sentence so that it begins with a word that takes an initial capital
letter, while retaining the preferred spelling of the trade name.

ACKNOWLEDGMENT
Principzl author: Brenda Gregoline, EIS
11.1 11.6
Correct and Preferred Usage of Anatomy
Common Words and Phrases
11.7
112 Clock Referents
Redundant Expendable, and lncomparable
Words and Phrases 11.8
11.2.1 Redundant Words Laboratory Values
11.2.2 ExpendableWords and Circumlocution
11.2.3 lncomparable Words 11.9
Articles
11.3
Back-formations 11.10
Inclusive Language
11.4 11.10.1 ' SexfGender
Jargon 11.10.2 RacefEthnicity
11.10.3 Age
11.5 11.10.4 Disabilities
Age and Sex Referents 11.10.5 Sexual Orientation

What would become of us if the deleatur did not

aW, sighed thepy%ader.
Jos6 sararnagol
,
We not i n f r q w t l y are compelled to refuse
publication to an article which contains valuable
facts, but which is tuer'ghed down with so many
imwectiom as to discourage one-as does the
porcupine- fmm closer investigation.
JM=
Correct and Preferred Usage of Common Words and Phrases. The second
quote, from a 1904editoriai inJ M , certainly holds true today, but of course, editors
d o consider manuscripts that are poorly written but are of good science, although;
they may feel less confident about a paper's content if the presentation is sloppy.
Also, authors whose first language is not that of the journal should still he given
consideration. In particular, editors should not lose the author's voice, especially in
informal usage. Still, scientific writing should .be as precise as possible to avoid
misinterpretation. This section provides a selection of correct and preferred terms.
A note about the entries: All terms (and pairs of terms) are in alphabetical (not
preferential) order.
abnormal, normal; negative, positive: Examinations and laboratory tests and sti~dies
are not in themselves abnormal, normal, negative, or positive. ~ h e s adjectives
e apply
11.1 Correct and Preferred Usage of Common Words and Phrases

to observations, results, or findings (see also 20.0, Study Design and S~atistics)..\'ole:
Avoid the use of "normal" and "abnorn~al"to describe penom' health Garus.
Results of cultures and tests for microorganisms and sprclfic rrac.tions to tests
m a y be negative or positive. Other tests focus on a pattern of activity rather than a
single feature, and hence a range of normal and abnormal resulrs is possible. These
tests include electroencephalograms and electrocardiograms and modes of imaging
such as isoropic scans, radiographic studies, and tomography.
Incorrect: The physical examination was normal.
Correct: Findings from the physical examination were normal.
Incorrect: The throat culture was negative.
Correct: The throat culture was negative for P-hemolytic streptococci.
Incorrect: The electroencephalogram was positive.
~6rrect: The electroencephalograrn showed abnormalities in the
temporal regions.
Incorrect: Serologic tests for Treponemapallidurn hemagglutination,
which were previously negative, are now positive.
Correct: Serologic test results for Treponemapallidum
hemagglutination, which were previously negative, are
now positive.
Also correct: Serologic tests for Treponeina pallidurn hemagglutination,
the results of which were previously negative, showed
a titer of 1:80.
See also 11.8, Laboratory Values.
Exceptions: HIV-positive men
seronegative women
negative node -
abort, terminate: Abort means to stop a process prematurely. In pregnancy, abortion
means the premature expulsion-spontaneous (miscarriage) or induced-from
the uterus of the products of conception. Apregnancy may be aborted, not a fetus or
a woman. The synonym t e r m i n a t e ~ t obring to an ending o r a halt-may also be used.
accident, injury: According to the National Center for Injury Prevention and Control of
the US Centers for Disease Control and Prevention, accident should not be used to
refer to injuries from any cause. Although accident implies a random act that is
unpredictable and unavoidable, epidemiologic studies and injury control programs
indicate that injuries may be predictable and therefore preventable. The preferred
terms refer either to the external cause (eg, injury from falls, injury from motor vehicle
crashes, gunshot injury) or to the intentionality ("unintentional injury" for injuries
resulting from acts that were not intended to cause harm and "violence" for any act in
which harm was intended).3n4
In addition, accident (and accidental) is considered by the pubiic health com-
munity to be imprecise. The injury-causing event can be described as noted above or
with other terms, such as crash, shooting, drowning, collision, poisoning, or suffo-
cation.
 11.1 Correct and Preferred Usage of Common Words and Phrases

Note. Do not change accident if it is integral to the terminology being used, for
example, an established injury classificationsystem (eg, Fatal Accident Reporting Sys-
tem, International Classification of Diseases).
acute. chronic These terms are most often preferred for descriptions of symptoms,
conditions;or diseases; they refer to duration, not severity. Avoid the use of acute
and chronic to describe patients, parts of the body, treatment, or medication.
Avoid: chronic dialysis
chronic heroin users
acute administration of epinephrine
chronic diagnosis
chronic care
chronic aspirin therapy
Prefmed. long-term dialysis (also: maintenance dialysis [query author])
long-term heroin users
immediate administration of epinephrine
long-standing diagnosis of a chronic disease
long-term care [see note below1
long-term aspirin therapy
chronic obstructive pulmonary disease
acute renal failure
chronic arthritis
acute nephritis
Also: acute, severe cystitis
acute, mild pruritus
Erception: Acute abdomen is a specific medical condition.
A note on short- and long-term patient care: According to Kane and ~ a n e "actrte
?
care hosprsprkzl
is preferred to short-term care hospital. Long-term care has come to in-
clude both an acute component (sometimes called subacute care or postactlte care),
which effectivelyprovides the care formerly offered in hospitals, and the more tradi-
tional chronic component, which includes both medical and social services. As the
name implies, subacute care has a shorter time frame and serves patients who are
expected to recuperate or die, while the more chronic form provides more sustained :
supportive services."
adapt adopt: TOadapt means to modify to fit a particular circun~stanceor require-
ment. To adopt means to take and use as one's own.
As evidence-based medicine continues to evolve ancl to ;~tlapt,
it is useful to
refine the discussion of what it is and what it is nc,t.
Austnlia hec~rncithc first nation to forrn:tily : l t l o p r c.\.~clcnc.c.-l>:i\c.cI nlvtlic.inc
of i~.; hc;tl111bysrcllr.
;IS a kc): f r a t u r ~
 ..,

1 1 . 1 Correct and Preferred Usage of Common Words and Phrases

adherence, compliance: Although these terms are often used as synonyms, there are ..
differences.Adherence can be defined as the extent to which a patient's behavior (for
cs:~niple,taking medication, following a diet, modifying habits, or attending clinics)
coincides with nledical or health advice. Use of the term adherence is intended to be
nonjuclgmental, a statenlent of fact rather than of blame of the prescriber, patient, or
treatment.' Not.,co~l-lplianceconnotes a stigmatizing image of rule, enforcement,
ancl control; clominr~ncc:~nclsubmission; ancl deviance from expected social roles.
\Vhcther a patient chooses to adhere to a therapeutic regimen may depend on many
:~spcctsof liis or her experience with the disease and the medical encounter itself.'
AltI1oug11 incompletely characterized and understood, the association be-
[ween poor aclherence to drug therapy and virologic failure with resistance
has been clearly established in HIV infection.
Possihb exception: A patient with a severe mental illness may be required to comply
with court-ordered therr~py.
adverse effect, adverse event, adverse reaction, side effect: Side effect is a secondary
consequence of therapy (usually drug-based) that is implemented to correct a med-
ical condition. The tern1 is often used incorrectly when adverse effect, adverse event,
or adverse wuction is intended. Since a side effect can be either beneficial or harmful,
specific terminology should be used.
A recent study examined the incidence of serious and fatal advers; drug .
reactions-any harmful, unintended, or undesired effect of a drug-in hos-
pitalized patients.
A side effect of therapy wirh hydrochlorothiazide is improved bone mineral
density.
affect, effect Affect (a-'fekt), as a verb, means to have an influence on. Effect (i-'fekt),
as a verb, means to bring about or to cause. The 2 words cannot be used inter- . .
changeably.
1
Ingesting massive doses of ascorbic acid may affect his recovery [ i u e n c e
the recovery in some way].
Ingesting massive doses of ascorbic acid may effect his recovery [produce
the recovery].
Affect ('a-fekt), as a noun, refers to immediate expressions of emotion (in contrast to
mood, which refers to sustained emotional states). Affect is often used as part of
psychiatric diagnostic terminology. Effect (i-'fekt), as a noun, means result.
The patient's general lack of affect was considered to be an effect of recent
trauma.
age, aged, school-age, school-aged, teenage, teenaged: The adjectival form aged, not
the noun age, should be used to designate a person's age. Similarly, school-aged and
teenaged are preferred-to school-age and teenage. However, a precise age or age
range should be given whenever possible. See also 11.5, Age and Sex Referents.
The patient, aged 75 years, had symptoms of cognitive decline.

-. .---.. . .. .. . . . .. : .- - --
.. .- I

, iI -.- - ..- . -
 11.1 Correct and Preferred Usage of Common W'ords and Phrases

Alternativefom: The 75-year-old patient had symptoms of cognitive

decline.
Routine screening of sexually active teenaged girls during regular physician
visits is an effective way to detect Chlamydia trachomatis.
Note: In some expressions regarding age, it is redundant to add olage after the num-
ber of months or years, since it is implied in the adjectivesyounger and older.
Influenza vaccination is not recommended for infants younger than G
months.
See also 11.2.1, Redundant, Expendable, and Incomparable Words and Phrases,
Redundant Words.
aggravate, irritate: When an existing condition is made worse, more serious, or more
severe, it is aggravated (also, emcerbated), not irritated. Irritated indicates reaction,
i
I
often excessive (eg, inflammation), to a stimulus.
although, though: Although and though may be considered interchangeable. How-
ever, although is preferable as a complete conjunction, because though in this
consuuction is an "abbreviation" and thus may be less appropriate for formal prose. I
nough, as an adverb, meaning "however" or "nevertheless," is correct, as are the
b e d expressions "even though" and "as though." I

Although the analysis was done correctly, the fundamental terms of the
investigation were too narrow to be interesting. I
i
Basal cell carcinoma of the skin and melanoma are the subjects of an ex- 1
tensive literature. Squamous cell carcinoma, though, remains largely unre- I

ported and unstudied.

among, between: Among usually pertains to general collective relationspnd always in
a group of more than 2. Between pertains to the relation between 1 entity and 1 or
more other entities. For instance, a treaty may be made between 4 powers, since each
is defining a relationship with each of the others, but peace may exist among them.
The patients shared the library books among themselves.
Between you and me, we are certain to find the common factor among those
we have examined.
analog, analogue: Use analog when referring to items related to computers or elec-
tronic equipnient. Use analogue when "something similar to something else" is
meant or when referring to chemical compounds. Use visual analog scale (not visizal
analogue scale).
apt, liable, likely: When apt refers to volition or a habitual tendency, it should not be
used of an inanimate object. This restriction does not apply when apt means "suited
to a purpose." Liable connotes the possibility of risk or disadvantage to the subject
Likely merely implies probability and thus 1s morr ~nclus~vr than apt
Correct: A child LF apt 10 cry n h e n fr~i\rr.trccI
I~lcomcr A polyt.rllvlenc. r.lrhc.rcr I\ I(.,, .I,-,[ 10 I\,nh th.ln onc m.ltle t

of vlnvl

385
 ...-
1 1 . 1 C o r r e a and Preferred Usage of Common Words and Phrases

Correct: The team must decide on the most apt configuration before
the first incision is made.
Correct: Patients receiving immunosuppressant drugs are liable to
acquire fungal infections.
Correct: The computer system is likely to crash if it is overloaded.

article, manuscript, paper, typescript: An unpublished study, report, or essay-that

is,
the document itself-may be referred to as a manuscript, paper, or typescript. When
published, it is an article (also, a study).
The authors thank Frank J. Kobler, PhD, for statistical review of the manu-
script.
Nancy MacClean assisted with manuscript preparation.
The content of this article does no[ necessarily reflect the views or policies
of the US Department of Health and Human Services.
The article by Carrozza and Sillke addresses the therapeutic options for a
6$-year~ldwoman with disease- of the left main coronary artery.
as, because, since: As, because, and since can all be used when "for the reason that" is
meant. However, in this construction, as should be avoided when it could be con-
strued to mean while.
Ambiguous: She could not answer her page as she was examining a
criticaily ill patient.
Better She could not answer her page, as she was examining a
critically ill patient [comma used].
Prefd. She could not answer her page because she was examining
a critically ill patient.

Similarly, since should be avoided whenjt could be construed to mean "from the
time of" or "from the time that."
Ambiguous: She had not been able to answer her page since she
was in the clinic.
Prefd: She had not been able to answer her page because she
was in the clinic.

association, relationship: Association is a connection berween two variables in which

one' does not necessarily cause the other. Relationship implies cause and effect. See
20.9, Study Design and Statistics, Glossary of Statistical Terms.
assure, ensure, insure: ~ h & everbs are used synonymously in many contexts, but
there are distinctions. A m * means to provide positive information to a person or
persons and implies the removal of doubt and suspense (assure the study's partici-
pants that their test results will be held, in complete confidence). Ensure means to
make sure or certain (ensure the statistical power of the study). Insure means to take
precaution beforehand (insure his life).
The insurance company assured workers' families that their policies ensured
that workers .with few assets would get a decent (ie, permanent) burial.

386

.. .. . .- .
;s
, _- _ _-..-*,. --.- .. .
:r,
-
 11.1 Correct and Preferred Usage of Common Words and Phrases

By mandating that every relevant paper expressly state that an institutional

review board approved the study protocol, journal editors can assure
readers that the research itself was conducted ethically.'
attenuate, attenuation: In computed tomographic (Oimaging, attenuation refers to
the absorption of x-rays by the patient's body. The appearance of the patient's tissues
on the CT scan is dependent on the amount of x-rays absorbed (ie, attenuated)
by that tissue. LOUJattenuation (or hypoattenuation) refers to areas of blackness on
the a s c a n . High anmuation (or hyperattenuation) refers to areas of whiteness on the
scan.
because: see as, because, since
because of, caused by, due to, owing to: These phrases are not synonymous, but the
differences are subtle. Due to and caused by are adjectival phrases; owing to and
because of, adverbial phrases. The use of due to in both situations can sometimes
alter a sentence's meaning.
Survivors of child abuse tend to enter abusive relationships hue to intra-
psychic conflicts.,

Meaning: Survivors of child abuse tend to enter abusive relationships

that are ,caused by intrapsychic conflicts.
Because due to is adjectival, "intrapsychic conflictsn describes the relationships.
Caused by could be substituted for due to, and the meaning would be retained. That
aw could be inserted before due to without changing the sentence's meaning.
Survivors of child abuse tend to enter abusive relationships owing to intra-
psychic conflicts.
Meaning: Because of intrapsychic conflicts, survivors of child abuse
tend to' enter abusive relationships.
Because owing to is used adveibially, "intrapsychic conflicts" chac~cterizesthc cn-
trance into abusive relationships. Because of could be substituted for otoirlg lo, ;tncl
the meaning would be retained. However, if that are is inserted 5efore oluirzg lo, the
sentence's meaning changes.
Clue to usage: The phrase "coughs due to colds" is a good ex:mlple o f correct
usage of due to. If "because of" sounds right, use it or "owing to." If "c:tuscd by" is
intended, use it or "due to" (or possibly "attributal,le to" or "that result from").
between: s6e among, between
biopsy: Biopsy refers to the removal and examination (usually rnicro~co~icall~~)
of
tissue or cells from the living body. Use of biopsy as a verb was previously consiclcrccl
to be incorrect. However, such use has become common and accep~~ble.
Acceptable: The lung mass was biopsied.
A biopsy of the lung mass was performed.
Lesions believed to be malignant were biopsied.
' Observations are made of the biopsy specimen, not on the biopsy itself.
11.1 Correct and Preterred Urage of Common Words and Phraser

blinding, masking: Thc statistical tern1 bli)zding (or blitlded r r q p i m ~or nssestnent) is
the ev;iluation or categorization of an outcome in which the person assessing the
outconle is unaware of the treatment assignment; blinding is used to avoid bias.
The term is also used to refer to peer review, usually to represent cases in which the
author's name and affiliation are concealed from the reviewer. The equivalent term
(or nznskcl ussessment) is preferred by some investigators and journals,
?)zusU.lri~~g
p:trticularly those in ophthalmology. See also 20.9, Study Design and Statistics, Glos-
s:uy of Statistical Terms.
breastfeed, nurse: When referring to human lactation, use breastfeeding. This term is
more specific than ntrning and prevents any confusion with the profession of
nursing.
cadaver, donor: When describing the source of human organs and tissues used for
transplantation, avoid cadaver (or dead body). Correct usage is deceased donor (or
oqazi and !issue donors).
recovere~lfrom clc~ccus~~cl
When referring to a deceased person whose body is to be used for anatomical .
dissection, cadaver is correct (cadaveric as adjective).
. .

can, may: Referring to one meaning of can and may, ern stein^ in 7he Careful Writer
.
\
,
stated: "Whatever the interchangeability of these words in spoken or informal Eng- I
::
lish, the writer who is attentive to the proprieties will preserve the traditional dis-
tinction: can for ability or power~todo something, may for permission to do it."
A second meaning of may refers to likelihood or possibility:
Dehydration may have contributed to the early onset of shock.
The lesion may or may not resolve without treatment.
case, client, consumer, participant, patient, subject: In clinical research, a case is a
particular instance of a disease. Apatient is a particular person under medical care. A
research participant (preferred to subject; see below) is a person with a particular
characteristic or behavior, or a person who undergoes an intervention as part of a
scientific investigation,usually a case-control study or randomized controlled trial. A
controlparticipant is a person who does not have at least some of the characteristics
under study, or does not receive the intervention, but provides a basis of comparison
with the case patient (see 20.0, Study Design and Statistics). In case-control studies, it
is appropriate to refer to cases, patients in the case group, or case patients; and
controls, participants in the control group, or controlpatients.
Some consider subject (as in study subject) to be impersonal, even derogatory, as
if the person in the study were in a subservient role. Similarly, the use of case is
dehumanizing when referring to a specific person. For example:
Avoid: A 63-year-old case of type 2 diabetes.. .
Prefemed: A 63-year-old man with type 2 diabetes.. .

Note: Make the distinction between person and patient

Many personsin the United States have type 2 diabetes [persons with type 2
diabetes regardless of care].
3
11.1 Correct and Preferred Usage of Common Words and Phrases
b

Many patients in the United States have type 2 diabetes [only persons unclcr
medical care].
A case is evaluated, documented, and reported. A patient is esaniined. unclcr~oc~
testing, and is treated. A mearchparticipant is recruited, selected, somc.tirnc.4sul)-
jected to experimental conditions, and observed. (See diagnose, evaluate, examine,
J identi@, and follow, follow up, observe.)
Note: In general, patients should not be referred to as clients or corrsrrtrrc,rs.
However, persons enrolled in substance abuse treatment programs, for esvi~ple.or
persons undergoing treatment at a dialysis center are sometimes referred to as c1ic~trt.v.
Cl-t may also be used by social workers or psychologists and in some research
settings where patient or-participant is inappropriate. C o n s u m e r = n ewho con-
sumes goods or services-has worked its way into the medical lexicon and may Ix
appropriate in certain discussions. For instance, in the follonring example, prrtietrl
would not fit the context:
The Internet has become an important mass medium for consumers seeking
heal* information and health care services online.
case-fatality rate, fataliw morbidity, morbidity rate; mortality, mortality rate: See 20.9,
Study Design and Statistics, Glossary of Statistical Terms.
catatonic, manic, psychotic,schizophrenic These adjectives refer to severe psychiatric
disorders. It is inappropriate to trivialize the disorders by using these terms to de-
scribe normal variations of individual or group behavior, for which suitable descrip-
tors are available. For example, in common trivial uses of these terms, contradictory
can usually be substituted for schizophmic; strange, disorganized, or senseless for
pgxhotic (depending on the context); w a c t i u e for manic; and motionless for
catatonic.
Note: It is dehumanizing to refer to a patient as "a schizophrenic." Use "the
patient with schizophrenia" or "the schizophrenic patient." See also 11.10.4, Inclu-
sive Language, Disabilities.
causd by: see because of, caused by, due to, owing to
cesarean delivery, cesarean section: According to h e American College of Obstetri-
cians and Gynecologists, the preferred terms are cesarean delivery (or cesarean
birth) or abdominal delimy (to differentiate it from vaginal delivery). Cesarean
section is incorrect, as are the spellings Caesarean and caesarean.
chief complaint chief concern: Chief complaint has been traditionally used by phy-
sicians when taking a patient's history. However, chief concenz niay be a beltter
.description because complaint may be construed as pejorative and confrontational.
chronic see acute, chronic
classic classical: In most scientific writing, the adjective classic generally means
authentic, authoritative, or typical (the classic symptoms of myocardial infarction
include angina, dyspnea, nausea, and diaphoresis). In contrast, classical refers to the
humanities or the fine or historical arts (the elements of classical architecture can be
applied in radically different architectural contexts than those for which they were
developed).
1 1 . 1 Correct and Preferred Usage of Common Words and Phrases

tlo\\,ever, some disciplines ( c . ~gcnctlcs.

, ~ln~nunology)
ubc clrw-iccrl f o r y x c ~ f i c
[eslns:
Classical lissencephaly nlay I
x caused by mutations of genes in chromosome
bands 17~13.3 and Xq22.3-q23.
The classical and alternative p:ithways of complement components are de-
scribed in 15.8.3,Nomenclature, Immunology, Complement.
The authors,suggest how to present results of data analysis under each of
3 statistical paradigms: classical frequentist, information-theoretic, and
Bayesian.
client: see case, client, consumer, participant, patient, subject

clinician. practitioner: Depending on context, these terms can be used to describe .

persons in the clinical practice of the health fields of medicine, nursing, psychology,
dentistry, optomeuy, and podiatry (as well as occupational and physical therapy and
veterinary medicine, for example), as distinguished from those specializing in lab-
oratory science, research, policy, theory, or writing and editing. When referring to a ;.
particular type of clinician or practitioner, it is preferable to use the more descriptive :
tern1 (eg, physician, nurse, dentist, optometrist). The plural forms of clinician and
practitioner may be appropriate to refer to a group of such professionals from dif-
ferent fields. See also provider.
compare to, compare with: One thing or person is usually compared with another
when the aim is to examine similarities or differences in detail. An entity is compared
to another when a single striking similarity (or dissimilarity) is observed, or when a
thing of one class is likened to one of another class, without analysis (ie, one entity is
comparable to another).
Compared with patients receiving only routine medical care, patients in both
active treatment groups had greater improvements from baseline in psy-
chosocial functioning and intermediate markers of cardiovascular risk.
Few medical discoveries can compare to the discovery of penicillin.
compliance: see adherence, compliance --

compose, comprise: Although these 2 oerbs are often used interchangeably, compose
is not synonynlous with comprise. Comprise means to be composed of or to include
(the pituitary gland comprises the adenohypophysis and the neurohypophysis).
Co7npose means to make u p or be a constituent of (the adenohypophysis and the
neurohypophysis compose the pituitary gland; the pituitary gland is composed of
the adenohypophysis and the neurohypophysis). The phrase comprised of is never
correct.
The chemotherapeutic reginleh is composed of several toxic ingredients.
The chemotherapeutic regimen comprises several toxic' ingredients.
consumer: see case, client, consumer, participant, patient, subject

continual, continuous: Cotztinual means to recur at regular and frequent intervals.

Co7zti7zuous means to gb on without pause or interruption.

.
- -
-
7-
-_.-
-
;
- .---
 11.1 Correct and Preferred Usage of Common Words and Phrases

The patient with emphysema coughed continually.

His labored breathing was eased by a continuous flow of oxygen through a
nasal cannula.

contrast contrast agent contrast material, contrast medium: Distinguish between

contrast (ie, blackness and whiteness on an image) and contrast material (or con-
trast agent, conlrast medium) (ie, a substance administered to enhance certain struc-
tures on an image).
A suspension of barium injected into the intestine was used as the contrast
agent for radiological examination.
criterion standard, gold standard: See 20.9, Study Design and Statistics,Glossary of Sta-
tistical Terms.
describe, report: Both patients and cases are'described; only cases are reported. (See
case, client, consumer, participant, patient, subject. management, treatment' diagnose,
evaluate, examine, identiQ.)
diabetes mellitus: The types of diabetes currently recognized by the American Dia-
betes Association are as follows:
Ok&r T m P t e f m d Terns
juvenile diabetes, juvenile-onset type 1 diabetes mellitus
diabetes, insuhdependent .
diabetes meIlitus
maturity-onset diabetes, type 2 diabetes mellitus
adult-onset diabetes, non-insulin-
dependent diabetes mellitus
chemical diabetes, borderline impaired glucose tolerance .
diabetes, latent diabetes (nondiagnostic fasting blood glucose
level, glucose tolerance abnormal)
. .. gestational diabetes mellitus

For other speciFic types, consult Table 1 ("Etiologic Classification of Diabetes Mel-
litus") in Diabetes care.1°
diagnose, evaluate, examine, identify: Diagnose, evaluate, and identify apply to con-
ditions, syndromes, and diseases. Patients themselves are not diagnosed but their
conditions may be'diagnosed. Patients are also examined. Patients may be evaluated ,

for the possibility of a condition (eg, The patient was evaluated for possible cardiac '

disease). (See also case, client consumer, participant, patient, subject; and manage-
ment treatment.)
Incorrect: The patient was diagnosed :IS schizoplirenir .i yc:lrs go
Corny1 The p;lrient's .schizophrenia was tli:~gno\ctl.i !rS;lrs fin.

die from. die of: Persons die o/, not front. specific disc*;lsrs o r disordcr~.

H c died of complications of tli?;wmi~i;~~ctl

i n ~ r : ~ \ ~. 1;.~1 1v- 1 I 1.1gt11.1tlr
In
11.1 Correct and preferred Usage of Common Words and Phrases

dilate, dilation, dilatation: Acccording to the American College of Obstetricians and

~ ~ n e c o l o ~ i s t dilate
s , " is a verb meaning to expand or open. Dilation means the act
of dilating. Dilatation means the condition of being stretched or expanded.
The patient's cervix dilated over a period of 12 hours.
The patient was treated by dilation and curettage.
After 4 hours of labor, cervical dilatation was 3 an.
disc, disk: For ophthalmologic terms, use disc (eg, optic disc); for other anatomical
terms, use disk (eg, lumbar disk).
In discussions related to computers, use disk (eg, floppy disk, disk drive, dis-

.
kette) (exceptions: compact disc, videodisc). (See also 24.0, Glossary of Publishing
Terms.)
disinterested, uninterested: Although these 2 words are inaeasingly treated as syno-
nyms in written and spoken language, their differences in meaning are sufficiently
useful to'be worth preserving. To be disinterested is to be unbiased or impartial;
to be unintmtedis to be unconcerned, indifferent,or inattentive.A disinterested judge
is admirable; an uninterested judge is not. As with many "word pairs," context is key.
She was uninterested in a career in basic research.
He was a disinterested observer of the complex procedure.
doctor, physician: Doctor is a more general term thanphysician because it includes
persons who hold such degrees as PhD, DDS, EdD, DVM,and PharmD. Thus, the
term physician should be used when referring specificallyto a doctor of medicine or
osteopathy, ie, a person with an MD or a DO degree (also FRCP,MBBS,ScD, etc).
(See also clinician, practitioner; provider, and 11.4, Jargon.)
donor: see cadaver, donor

dosage, dose: A dose is the quantity to be administered at one time, or the total
quantity administered during a specified period. m a g i implies a regimen; it is the
regulated administration of individual doses and is usually expressed as a quantity
per unit of time.
The usual initial dosage of furosemide for adult hypertension is 80 mg/d,
typically divided into doses of 40 mg twice a day. Dosage should then be
adjusted according to the patient's response.
due to: see because of, caused by, due to, owing to

effective, effectiveness; efficacious, efficacy: Efficacy and @ficacious, used especially

in pharmacology and decision analysis, have to do with the ability of a medication or
intervention (procedure, regimen: service) to produce the desired or intended effect
under ideal conditions of use. The determination of efficacy is generally based on the
results of a randomized controlled trial.
Eflective and eflectiveness, however, describe a measure of the extent to which
an intervention produces the effect in average or routine conditions of use, or a
nie:lsure of the extent to which an intervention fulfills its objectives.
Svr 3lso 20.9. Srutly Design and Statistics, Glossary of Statistical Terms.
 11.1 Correct and Preferred Usage of Common Words and Phrases

eg, ie: Use eg (from the Latin exempfigratia:"for example") and ie (id est: "that is")
with care.
Persons in risk groups for endemic disease (eg, tuberculosisin immigrants or
homeless persons, histoplasmosis in residents of the Mississippi and Ohio
River valleys) warrant special consideration.
With 95% power and a 2-sided significance level of 5%, the study had sta-
tistical power to detect a significant odds ratio of 0.76 (ie, a 24% reduced risk)
for individuals in the highest quartile of intake.
endemic, epidemic, hyperendemic, pandemic: Endemic conditions or diseases are
prevalent in a particular- place or among a particular group of people. Epi&nlic
conditions occur abruptly in a defined area and are usually temporary. A h - t p ~ . ~ r t -
d m i c condition is one that hasa high prevalence. Apandernic condition is one that
is epidemic over a wide geographic area, even worldwide.
Cowpox is an orthopoxvirus infection endemic in European wild rodents
but with a wide host range, including human beings. .
Public health officials feared an. epidemic of infectious disease after Hurri-
canes Katrinq and Rita in 2005.
The researchers used remote sensing and geographic information system
technology to identify individual high-risk residences in Westchester County.
New York, where Lyme disease has been hyperendemic since 1982.
Internationally, between 20 million and 40 million people died in the 1918-
1919 influenza pandemic.
ensure: see assure, ensure, insure
epidemic: see endemic, epidemic, hyperendemic, pandemic .

erectile dysfunction, impotence: Erectile dysfunction is the inability to develop and

maintain an erection foi3atisfactory sexual intercourse or activity (in the absence of
I an ejaculatory disorder). Erectile dysJunction is the preferred term rather than the less
I
precise term impotence.
etc: Use etc (or and so on or and the like) with discretion. Such terms art. often
superfluous and are used simply to extend a list of examples. When, in other in-
stances, omission would be detrimental, sul~stitutemore specific phrasing such ;is
and other methocis or and otherfactors. Etc may he used in a noninclusive listing
when a complete list would be unwieldy and its content is obvious to the reader.
Gelatin is made from animal ligaments, tendons, bones, etc, that have been
boiled in watqr. It is often used in confectionery, ice cream, and other dairy
products.
Note: It is redundant to add "etc" the cnd of :I l i a ~introduced by "include" or "in-
cluding" or a list introduced by e9
ethnicity, race: These terms arc. ncu c.cli~iv:\l~nr5c.v 1 1 10.2. Inclu>ive languayc..
Race/Ethnicity, for 1 tfi.w~~.;.sion
oI' \ I . ; : I X ~

ii
i!
I! 393
 .

1 1.1 Correct and Preferred Usage of Common Words and Phrases

evaluate: see diagnose, evaluate, examine, identify

examine: see diagnose, evaluate, examine, identify

fasted, fasting: These derivatives of the verb fast are often used in the scientific
literature. Fasting may be a present participle (verbal adjective), as in "the fasting
mouse," or a gerund (verbal noun), as in "the effects of overnight fasting." Fasted
m:~yI>ethe simple past tense form of the verb, as in "patients who fasted regularly,"
or a past participle, as in "12 fasted rats." Either word, when associated with 1or more
ausiliary verbs, can form part of a compound verb: "she had fastkd since midnight,"
'*hehad been fasting since midnigh."

fatality: see case-fatality rate, fatality; morbidity, morbidity rate; mortality, mortality
rate
fever, temperature: Fever is a condition in which body temperature rises above that
defined as normal. It is incorrect to say a person has a temperature if "fever" is
intended. Everyone has a temperature, either normal or abnormal.
Incorrect: The patient has a fever of 39.5%.
Correct: The patient has a fever (temperature, 39.5"C).
Correct: The patient is febrile (temperature, 39.5"C).
Correct: The patient has an elevated temperature (395°C).

fewer, less: Fewer and less are not interchangeable. Usefaverfor number (individual
persons or things) and less for volume or mass (indicating degree or value).
Fewer interventions may not always mean less care.
The authors evaluated fewer than 100 studies yet still reported more support
for the conventionally prescribed therapy.
Note: spent less than $1000 (not: spent fewer than $1000)
reported fewer data (not: reported less data)

film, radiograph: These 2 terms are not interchangeable. In radiography, film is an

outdated term that refers to an image obtained when achial film is exposed to x-rays
(rather than when a digital technique is used). Film should be reserved to refer to
actual film that is exposed and then developed into a resultant image. When referring
to resultant images, use the specific name of the image, eg, arteriogram, marnmo-
gram, radiograph.
follow, follow up, observe: Cases arefollowed. Patients are not followed but observed.
However, either cases or may befollowed up (eg, the maintenance of contact
with or reexamination of a.person .or patient, especially after treatment). Their
clinical course may be followed.
In a study, case or control participants may be lost to follow-up (eg, the inves-
tigators were unable to locate them to complete documentation on paqicipants in the
initial study groups) or unavailableforfollow-up (eg, they could not be contacted or
the investigators were unable to persuade them to complete the study).

. .
:-,..;---,-
- -
---
-
. - .
...
., ,

: I

-. --- . . -
 11.1 Correct and Preferred Usage of Common Words and Phrases

Patients with retained intracranial fragments have been followed up, and the
sequelae of such fragments were analyzed; to date, 9 patients have been lost
to follow-up.
gender, sex: Sex is defined as the classification of living things as male or female
according to their reproductive organs and functions assigned by chromosomal
complement. Gender refers to a person's self-representation as man or woman, or
how that person is responded to by social institutions on the basis'of the person's
gender presentation. Gender is rooted in biology and shaped by environment and
' experience.''
In most instances, authors of articles in biomedical publications intend the word
sex.
The authors assessed whether shifts in the ratio of males to females born in
1950-1994 in Denmark and the Netherlands, defined as the sex ratio, con-
stitute a sentinel health event.'

Many studies indicate that women are less likely than men to undergo cardiac
procedures after an acute myocardial infarction.,which has raised concerns of
sexual b i i in clinical care. However, no data exist about the relationship
between patient sex, physician sex, and use of cardiac procedures.
Responses to pain and pain therapies differ between men and women.
Whether this difference is related to sex-based factors (physiological), gen-
der factors (psychosocial), or both has not been determined.
See also 11.5, Age and Sex Referents.
global, international: Global relates to or involves the entire world; an equivalent term
1 is worIdui& (a global system of communication, global climate change).
Tuberculosis is a global public health problem.
Znternationul affects 2 or more nations (international trade, international move-
ment).
t
Researchers conducted an international survey, with respondents selected
from Australia, China, France, Korea, and the United States.
But: global amnesia, global aphasia, global congnitive function, global pain
relief, Global Assessment of Functioning Scale
glycated hgmoglobin, glycosylated hemoglobin: .The preferred term is glycated he-
moglobin. Gfycobemoglobin is also a ~ c e ~ t a . b l e(David
'~ E. Bruns, MD, e-mai! com-
$ munication, May 17, 2006). See also 15.10.2, Nomenclature, Molecular ~ e d i c i n e ,
Molecular Terms: Considerations and Examples.
gold standard: see criterion standard, gold standard
health care: Express this term as 2 words. It is not necessary to hyphenate heulfh cure
in its adjectival form. See also 8.3, Punctuation, Hyphens and Dashes.
health care professionals
' Ions
health care organizqt'
health a r e insurance
and Preferred Usage of Common Words and Phrarer

historic. historical: Artlough [heir rnrslnrngh o\.srhp and they are often used inter-
changeably, hisforic and hisroriwl l u v r dltfermt usages. Historic means important
or influential in history (a hisroric discovery). HisroncaI is concerned with the events
in history (a histon'cal novel).
Brlf: A historical novel might have a historic impact.
This historical review of pain management gives particular emphasis to the
20th century and to chronic pain and cancer pain.
hyperendemic: see endemic, epidemic, hyperendemic, pandemic

hyperintense, hypointense: In magnetic resonance (MR) imaging, hyperintense refers

to areas of whiteness on an MR image. Hypointense refers to areas of blackness.
Synonyms include high intmity and low intensity and high signal intensity and low
signal inawsity.
-ic, -ical: Merriam- Webster's Collegiate, Stedman 3, Dorland's, and American Heritage
dictionaries are resources for determining the appropriate suffix for adjectives. In
some cases, the "-ical" form is more remote from the word root and may have a
meaning beyond that of the "-ic" form. Although, for example, "anatomic" may be
used in the same sense as "anatomical," the latter is preferred as the adjectival form.
The important guideline is that the use of terms must be consistent throughout an
article or chapter, and preferably throughout the entire'publication. Usually the "-al'!
may be omitted unless its absence changes the meaning of the word. Examples of
such differences in meaning include biologic, biological;.classic, classical; economic,
economical; empiric, empirical; historic, historical;periodic, periodical; physiologic,
physiological.
identify: see diagnose, evaluate, examine, identify

ie: see eg, ie

immunize, inoculate, vaccinate: Immunize means to induce or provide immunity by

giving a vaccine, toxoid, or preformed antibody. Inoculate means to introduce a
serum, a vaccine, or an antigenic substance. Vaccinate refers to the act of adminis-
tering a vaccine.
To immunize the newborn infant of an HBsAg-positive woman against
hepatitis B, the patient should be inoculated with both hepatitis B immuno-
globlin and vaccine.
All participants w&e inoculated intranasally with influenza A/Texas/36/
91(HlNl) virus.
Ten vaccinia-naive participants were vaccinated with undiluted smallpox
vaccine.
impaired, intoxicated: These related terms are used in the United States to define
impairment in driving performance attributable to the use of alcohol or other drugs.
For instance, in some jurisdictions, a blood or breath ethanol concentration of
0.08 g/dL is considered to be legal evidence of impairment for driving. By exten-
sion, some injury prevention researchers have considered this concentration of al-
cohol to be scientific evidence of impairment in other potentially hazardous
activities. However, cognitive and other functions may be impaired at even lower
! . . .. .
'.

11.1 Correct and Preferred Usage of Common Words and Phrases

concentrations of alcohol, particularly if other psychoactive drugs, including pre-

scription drugs, have been taken. No specific blood or breath concentration of al-
cohol may be considered to be scientific evidence of intoxication or impairment for
all persons in all settingsand activities. Authors should explain, justify, and define the
use of these terms, preferably in the "Methods"'section of the manuscript.
imply, infee To imply is to suggest or to indicate or express indirectly. To infer is to
conclude or to draw conclusions from facts, statements, or indications.
-Theseresults, though cross-sectional,.imply that physical fitness is related to
fewer coronary risk factors.
Our study relied on cross-sectional data, which restricts our ability to infer
the causal relations underlying the observed associations.
See also 20.9, Study Design and Statistics, Glossary of Statistical Terms (inference).
impotence: see erectile dysfunction, impotence
incidence, prevalence: See 20.9, Study Design and Statistics, Glossary of Statistical
Terms.
injecting, injection drug user;intravenous: The terms injecting dmg user and injection
dmg userare not necessarily the same as intravenousdrug user.Injecting or injection
drug users can inject drugs intravenously, intramuscularly, or subcutaneously. Do <
not substitute one term for the other. If intravenousis used, ascertain that the route of 5- 1

adminimation is through a vein. If injecting or injection drug user is used, specify the E- 'i
- I
type of injection (eg, intravenous, intradermal) at first mention, unless all types are i L
meant. C.

injury: see accident injury

I inoculate: see immunize, inoculate, vaccinate

in order to: In ordercan often be removed from the phrase in order to without chang-
ing its meaning (see also 11.2.1, Redundant, Expendable, and Incomparable Worcis
and Phrases, Redundant Words). However, in some cases such a deletion niay I,c
awkward, change the meaning, or create a dangling infinitive.
Our students must have the learning opportunities that they need in order to
acquire not just facts but true understanding..
If "in order" is removed, the syntax is disrupted ("need to acquire" would seem to
apply to "opportunities").
The sentence might be reworded as "to he able to acquire" instead of "in orcler t o
acquire."
insure: see assure, ensure, insure

international: see global, international

I
I
intoxicated: see impaired, intoxicated
i
irregardless, regardless: Imgardless--most likely a blend of irrespective and
regardless-is incorrect, regardless of context.
irritate: see aggravate, irritate
11.1 Correct and Preferred U u g e of Common Words and Phrase,

less: .WC fewer, less

liable: bee. a p t Irable, likely

likely: see a p t liable, likely

lucency, opacity: In radiography, lucency refers to areas of blackness on an image.

Opacity refers to areas of whiteness.
malignancy, malignant neoplasm, malignant tumor: When referring to a specific tu-
p o r , use malignant neoplus~nor malignant tumor rather than malignancy. Malig-
nancy refers to the quality of being malignant.
Avoid: Pancreatic cancer is a type of malignancy that eludes
early detection.
Preferred: Pancreatic cancer is a type of malignant neoplasm that eludes
early detection.

management, treatment: To avoid dehumanizing usage, it is generally preferable to

say that cases are managed and that patients are cared for or treated. However,
constructions such as "the clinical management of the seriously ill patient" and "the
management of patients with AIDS" are acceptable when used to refer to a general
treatment protocol. Management is especially applicable when the care of the pa-
tient does not involve specific interventions but may include, for example, watchful
waiting (eg, for prostate cancer). Management may also be used to refer to the. ,

monitoring or periodic evaluations of the patient.

manic see catatonic, manic, psychotic, schizophrenic

manuscript: see article, manuscript paper, typescript

masking: see blinding, masking

may: see can, may

militate, mitigate: These 2 words are not synonymous. Militate means to have weight
or effect and is usually used with against. Mitigate means to moderate, abate, or
alleviate.
The constraints of nationalism militate against state conformance with global
health norms.
Tests of sprinkler systems in full-scale simulated fires indicate that such
sprinklers can be expected to mitigate the risk of fatality in residential fires.
morbidity: see case-fatality rate, fatality; morbidity, morbidity rate; mortality, mortality
rate

mortality: see case-fatality rate, fatality; morbidity, morbidity rate; mortality, mortality
rate

negative: see abnormal, normal; negative, positive

normal: see abnormal, normal; negative, positive

nurse: see breastfeed, nurse

observe: see follow, follow up, observe

It
11.1 Correct and Preferred Usage of Common Words and Phrases

ology: This suffix, derived from the Greek logos, meaning "word," "itlea." o r
"thought," denotes science of or study of. Terms with this suffix, like p~zlbok~,q~:
\ morphology, hbtology, etiology, and symptomatology, are general and abstract nouns
!
and should not be used to describe concrete physical entities.
Avoid: The gradual decline of symptomatology paralleled the resolution
of pathology as seen in serial chest films.
Preferred: The gradual decline of symptoms paralleled the resolution of
pu!monary infiltrates as seen in serial chest films.
on, upon: In scientific articles, upon often simply means on and may be changed.
opacity see lucency, opacity'
operate, operate on: Surgeons operate on a patient or pe$omz a n operation on a
patient. Similarly, patients are not operated but are operated on.
Incorrect: The operated group recovered quickly.
Correct: The surgical group recovered quickly. -
Ako correct: The group that underwent surgery recovered quickly.
operation, surgical procedure, surgeries, surgery: Surgery can mean surgical care,
surgical treatment, or surgical therapy (ie, the care provided by a surgeon with the
help of nurses and other personnel from the first consultation and examination,
through the hospital stay, operation, and postoperative care, until the last follow-up
visit is complete).
An operation is what occurs between the induction of and the patient's emer-
gence from anesthesia-incision, dissection, excision, and closure-the surgical
pr~cedure.'~
An operation can also be performed with the patient given local anesthesia.
S u r g q is what a surgeon practices or a particular medical specialty. An oper-
ation is what a surgeon performs. In this context, there is no such word as sutge*es.
In the United Kingdom, sulgeries are physicians' or dentists' offices.15.
over, under: Correct usage of these words depends on context.
Time: Over may mean either more than or during (fora period of 1. In cases in which
ambiguity might arise, over should be avoided and more than used.
Ambiguous: The cases were followed up over 4 years.
Pefemd: The cases were followed up for more than 4 years.
Also: The cases were followed up for 4 years.
Age: When referring to age groups, over and under should be replaced by the more
precise older than and younger than (see also age, aged, school-age, ,school-aged,
teenage, teenaged).
Amid: All participants in the study were over 6 j years old.
Pwfmd; All participants in the study were older than 65 years.

iLbte:It is unnecessary and redundant to add of~d,qc:~ftt.r

thc nunher of years. When the
terms oldcr and yrrtlger are used, age is ~nlplicul.Scv 31%) 11.2.1, Rcdund:~nt,Es-
pendable, and Incompnr~bleWords and Phr.lw.s. Ht.tlund;~ntWords.
11.1 Correct and Preferred Usage o f Common Words and Phrases

owing to: see because of, caused by, due to, owing to

pandemic: see endemic, epidemic, hyperendemic, pandemic

paper: see article, manuscript, paper, typescript

participant: see case, client, consumer, participant, patient, subject

patient: see case, client, consumer, participant, patient, subject

percent, percentage, percentage point, percentile: See 19.7.2, Numbers and Percent-
ages, Forms of Numbers, Percentages.
physician: see doctor, physician

place on, put on: The phrase "to put [or to place1 a patient on a drug" is jargon and
should be avoided. ~edicationsare prescribed or patients are given medications;
therapy or therapeutic agents are started, administered, maintained, stopped, or
discontinued.
Incorrect: The patient with hypertension was put on hydrochlorothiazide
and metoprolol.
Correct: Hydrochlorothiazide and metoprolol were prescribed for the
patient with hypertension.
Correct: The patient with hypertension was given hydrochlorothiazide
and metoprolol.
Correct: A therapeutic regimen of hydrochlorothiazide, 25 mg/d, and
metoprolol, 50 mg/d, was begun.

positive: see abnormal, normal; negative, positive

practitioner: see clinician, practitioner

prevalence: see incidence, prevalence

preventative, preventive: As adjectives,preventive and its derivativepreventative are

equal in meaning. J A M and the Archives Journals preferpreventive.
prostitute, sex worker: Epidemiologic studies use the term sex mrker(or commercial
sex worker) to describe these persois of either sex, rather than the more derogatory
prostitute.

provider: The termprovider can mean a health care professional, a medical institution
or organization, or a third-party payer. If the usage refers to 1specific provider (eg,
physician, hospital), use the specific name or alternative name for that provider (eg,
pediatrician, tertiary care hospital, managed 'care organization), rather than the
general termpmvidw. If the term connotes several providers, it can be used to avoid
repeating lists of persons or institutions; however, the term($ should always be
defined at first mention.
Increasing pressures for cost control and the spread of managed care create
an urgent, shared need for information on health care quality among all
health care stakeholders: consumers, public and private purchasers, policy
makers, health' plans, and health a r e providers (eg, hospitals, physician
groups, and clinics).
 11.1 Correct and Preferred Usage of Common Words and Phrases

The phrase nonphysician provider should he avoided because it is similarly impre-

cise and can refer to numerous health care professionals licensed to provide a health
care service. It is better to specify the type of professional (eg, nurse, pharmacist) or
to use health care p 1 0 f ~ o n a lor clinician. If a phrase. is needed to describe re-
peatedly and succinctly the many health care professionals who are not physicians,
then physicians and other health careprofessionalsmay be acceptable as long as the
phrase is defined at first mention. This guideline also applies to other professions (eg,
nonnurses, nonpharmacists).
psychotic: see catatonic, manic, psychotic, schizophrenic
race: see ethnicity. race
radiograph: see film, radiograph
radiography, radiology: These 2 terms are not interchangeable. Radiography is an
imaging technique based on x-rays through tissue and emerging to "hit" film
on the other side. Radiology is thg medical specialty that uses imaging to diagnose
and sometimes treat disease.
regardless: see irregardless, regardless
regime, regimen: A regime is a form of government, a social system, or a period of
rule. A regimen is a systematic schedule (involving, for example, diet, exercise, er
medication) designed to improve or maintain the health of a patient. .

Resistant hypertension is defined as the failure to reach goal blood pressure

in patients who are adhering to full doses of an appropriate 3drug regimen
that includes a diuretic.
relationship: see association, relationship
reluctant, reticent: Reticent is becoming more commonly seen in infoqal usage as an
incorrect synonym for reluctant. Reticent means habitually silent or uncommunica-
tive. Reluctant means unwilli?g or disinclined.
repeat, repeated: Repeat is a noun or a verb and should not be used in place of the
adjective repeated. Repeated implies repetition. For precision and clarity, the exact
number should be given.
Incorrect: A repeat electrocardiogram was obtained.
Possible but misleading: A repeated electrocardiogram was obtained.
~refkd: A second electrocardiogram was obtained.
Preferred: The electrocardiogram was repeated.
Preferred: Two successive electrocardiograms showed no
abnormalities.

report: see describe, report

respective, respectively: The.= words indicate a one-to-one corrcsponclcncc t t i ; ~ c may
not othentise obvious between members of 2 serivs. \\'hen on\, I \c.rir\ r , l c i c ,nc
ar nil. is listd. the distinction is nielninglcss ant1 rhoulcl not I,cb ,I.~.(I
 -------.

11.1 Correct and Preferred Usage of Common Words and Phrases

Incorrect: The 2 patients are 12 and 14 years old, respectively.

Correct: Kate and Jake are 12 and 14 years old, respectively.
Incorrect: The 2 patients' respective ages are 12 and 14 years.
Correct: The 2 patients are 12 and 14 years old.
schizophrenic: see catatonic, manic, psychotic, schizophrenic

school-age, school-aged: see age, aged, school-age, school-aged, teenage, teenaged

section, slice: Use section to refer to a radiological image; use slice to refer'to a slice of
tissue (eg, for histological examination).
But: froze:;-section biopsy
sex: see gender, sex

sex worker: see prostitute, sex worker

side effect: see adverse effect adverse event, adverse reaction, side effect

since: see as, because, since

subject: see case, client consumer, participant, patient subject

suffer from, suffer with: See 11.10.4, Inclusive Language, Disabilities, for a discussion
of usage.
suggestive, suspicious: To be suggestive of is to give a suggestion or to evoke. To be
sqpicious is to tend to arouse suspicion. Thus, the 2 phrases are not synonymous, '
and care should be taken to avoid confusing them. A finding may be abnormal (ie,
suspicious) but may not indicate a specific diagnosis (ie, suggestive).
1nco;ect: The chest film was suspicious for tuberculosis.
Correct: The chest film was suggestive of tuberculosis.
Also correct: The chest film showed abnormalities suggestive of tuber&losis.
Also correct: The chest film showed a suspicious lesion, but its nature
was unclear;
. ..
surgical procedure: see operation, surgical procedure, surgeries, surgery

survivor, victim: In scientific publications, use of the word victim-when describing

persons who survive physical, domestic, sexual, or psychological violence or a
natural disaster-should be avoided. Similarly, avoid labeling (and thus equating)
people with a disability or disease as victims (eg, AIDS victim, stroke victim; see
11.10.4. Inclusive Language, Disabilities).
Victim may imply a state of-helplessness.'6 Characterizing a person who has - ,'

experienced abuse or other violence as a victim perpetuates the stereotype of a

passive person who cannot recover from the effects of the malady. In such cases
strruivor may be more appropriate (eg, rape survivor, tsunami survivor, survivor of
torture).
If :1 person whb experienced such trauma has died, referring-to him or her as
r bc :~ppropriute(victim of a land mine explosion). Victim may also be
r r c ~ i ~ r1u:1y
t15ctl i n tllc \~crn:~cul:~r
(~'ictirnof his own success).

-. -. - -- . --,.*- . .
:. j
 11.1 Correct and Preferred Usage of Common Words and Phrases

teenage, teenaged: see age, aged, school-age, school-aged, teenage, teenaged

temperature: see fever, temperature
terminate: see abort terminate
though: see although, though
titrate, titration: In clinical medicine as in analytical chemistry, titrate and titration
refer to making a series of small adjustments in the quantity or concentration of a
substance until a goal or end point is attained4 color change or precipitation in the
laboratory, control of symptoms or a therapeutic blood level in the patient. Drug
dosages are titrated; patients are not.
toxic, toxicity Taxic means pertaining to or caused by a poison or toxin. Tdcity is
the quality, state, or degree of being poisonous. A patient is not toxic. A patient does
not have toxicity.
Dactinomycin is a toxic antineoplastic drug of the actinomycin group.
The drug had a toxic effect on the patient.
The patient had a toxic reaction to the drug.
The patient had a toxic appearance.
The toxicity of the drug must be considered. <
f
transplant transplantation: Transplant is both a noun (typically meaning the surgical I
operation itself but also increasingly referring to the overall field) and a tnnsitive
verb. Use grafi (or allografl, aatografl, xenografi, and so on, depending on the level t

of precision needed) as the general noun for the organ or tissue that is transplanted,
or specify which organ or tissue (eg, liver, skin), rather than continue to use the noun
transplant in this context. Transplantation is traditionally the noun used to describe
the overall field. Never use the plural transplantations.
Incorrect: .The patient was transplanted.
The surgeon transplanted the patient.
The patient underwent a transplantation.
Fifteen transplantations were performed.
Correct: The patient underwent a tr~nsplant.
. The patient received a kidney allograft.
The transplanted intestine functionccl well.
The surgeon transplanted the deceased donor's heart into a
4-year-old girl.
Fifteen transplants were performed.
She performed the first successful heart-lung transplant at our
center.
Cyclosporine has been used as monotherapy in pediatric liver
transplantation [also, transplant].
11 1 Correct and Preferred Usage of Common Wordr and Phrases

tmn\pl3ntxlon [also, rrarsplrrnt] is now a clinical reality at

1\1c-1
our~nhti~ution.
The researchers collected transplantation data.

For the adjectival form, use transplaat, as well as pretrarcsplant and posttransplant
(not pre1tzr?isplar2IuIio11and posttra?zsplantation).
Arwid: The transplantation coordinator described the pretransplantation
and posttransplancation data from her transplantation program.
Preferred: The transplant coordinator described the pretransplant and
posttransplant data from her transplant program.

treatment: see management, treatment

typescript: see aiticle, manuhcript, paper, typescript

ultrasonography, ultrasound: These terms are not interchangeable.When referring to

the imaging procedure, use ultrasonography. Utrasound refers to the actual sound
waves that penetrate the body during ultrasonography.
uninterested: see disinterested, uninterested

upon: see on, upon

use, usage, utility, utilize: Use is almost always preferable to utilize, which has the
specific meaning "to find a profitable or practical use for," suggesting the discovery of
a new use for something. However, even where this meaning is intended, use would
be acceptable.
. During an in-flight emergency, the surgeon utilized a coat hanger as a
"trocar" during insertion of a chest tube.
Some urban survivors utilized plastic garbage cans as "lifeboats" to escape
flooding in the .aftermath of Humcane Katrina.
.
Exception: Utilization review and utilization rate are acceptable terminology.
Usage refers to an acceptable, customary, or habitual practice or procedure,
often linguistic in nature. For the broader sense in which there is no reference to a
standard of practice, use is the correct noun form.
The correct usage of regime vs regimen is discussed on page 401.
Who determines what is correct usage?
Some authors use the pretentious usage where use would be appropriate. As a rule of
thumb, avoid utilize and be wary of usage. Use use.
Note: Utilitpmeaning fitness for some purpose, or usefulness--should never
be changed to the noun use. Nor sh6uld the verb employ be routinely changed to use.
Use employ to mean hire.
vaccinate: see .immunize, inoculate, vaccinate

visual acuity, vision: Vision is a general term describing the overall ability of the eye
and brain to perceive .the environment. Visual acuity is a specific measurement of
one aspect of the sensation of vision assessed by an examiner.
 11.2.1 Redundant Words

A patient describing symptoms of his or her visual sensation would be describing

the overall visual performance of the eye($ and would use the term visiorr: '.My
vision is improved [or worse]."
A practitioner reporting the examination.findings at one specific time would
describe v(rua1acuity (20/30,20/15, etc). However, the practitioner might also refer
to the general visual function as W o n : "As the vitreous hemorrhage cleared, the
vision improved and visual acuity returned to 20120." It is possible to have normal
visual acuity despite marked vision impairment, eg, when the peripheral visual field
is abnormal.

Redundant, Expendable, and Incomparable Words and Phrases

It's dqii vu all over again.
YogiBerra (1925- )

Redundant Words. A redundancy is a term or phrase that unnecessarily repeats

words or meanhgs. Below are some common redundancies that can usually be
avoided (redundant words are italicized):
adequate enough general rule
advance planning herein we describe
aggregate together interval of time
brief in duration large [small, bulky1 in size
combine together lift up
completely full [empty] major breakthrough
consensus of opinion near to
contemporaneous in age out of [but:out.of bounds, out of place, out
count [divide] up of the question, out of the jurisdiction, out
covered over of the woods1 .

distinguish the d @ m c e of
each individuul person oval [square, round, lenticular] in shape
eliminate altogether own personal view

I empty out
enter into (exception:
past history
period of time, time period, point in time
enter into 'a contract) personal friend
equally as well as i
precedes in time
estimated at about predict in advance
fellow colieagues raised uj)
fewer in number reassessed again
filled to capacity red in color
fitst initiated rough [smooth] in texture
fuse together similar results were
fulure plans obtained also by
1 1 . 2 Redundant. Expendable, and Incomparable Wordr and Phrart-,

- ~ f [firm]
t in c o t u ' i s t ~ ~ ~ c ? ~ 2 h;ll\ cs

sour [sweet, bitter1 rusting 2 of 12 '

split up unrformly consistent

still continues whether or not [unless
sum total the intent is to give equal
tender to the touch emphasis to the alternative]
true fact younger [older] than 50 years of age
Expendable Words and Circumlocution. Some words and phrases can usually be
omitted without affecting meaning, and omitting them often improves the readability
of a sentence:
as already stated it was demonstrated that
in other words needless to say
it goes without saying take steps to
it is important [interesting] to note the fact that
it may be said that the field of
it stands to reason that to be sure
it was found that

Quite, very, and rather are often overused and misused and can be deleted in many
instances (see also 11.1, Correct and Preferred Usage of Common Words and Phrases).
Avoid roundabout and wordy expressions:
Avoid Better
in terms of in, of, for
an increased [decreased] number of more [fewer]
as the result of because of
during the time that while
at this [that] point in time now [then]
in close proximity to . near
in regard to, with regard to about, regarding
the majority of most
produce an inhibitory effect o n inhibit
commented to the effect that said, stated
draws to a close ends
file a lawsuit against sue
have an effect [impact] on affect
in the vicinity of near
in those areas where where
 1 1.2.3 Incomparable Words

carry out perfonn, conduct

look after, take care of watch, care for
fall off decline. decrease

Incomparable Words. An adjective denoting an absolute or extreme state or quality

does not logically admit of quantification or comparison. Thus, we do not, or should
not, say deadest, morepe$ect, or somewhat unique. It is generally acceptable, how-
eve:, to modify adjectives of this kind with adverbs such as almost, apparerztly,
fortunately, nearly,pbably, and regrettably. Listed below are words that should not
be used with a comparative (more, Jess), superlative (most,least), or quantifying
(quite, slightly, wry) modifier.
absolute omnipotent
ambiguous original
complete [but: almost or nearly perfect [but: almost or nearly
complete] perfect1
comprehensive preferable '
entire pregnant
equal supreme
eternal total
expert ultimate
fatal [buk almost or nearly fatal1 unanimous [buc almost or
final nearly unanimous]
full [but half full, nearly full] unique
infinite
Note: In general, superlatives should be avoided in scientific writing.

Back-formations. Back-formation is the creation of a new word in the mistaken

belief that it was the source of an existing word. Many back-formations are verbs,
some of them derived from abstract nouns (ambulate from ambulation, diagr?o.sc~
from diagnosis, dialyze from dialysis) and others from agent nouns, real or supposeti
(beg from beggar, peddle from pehdler, scavenge from scaveizger). These esamples of
back-formations have achieved acceptance; however, many of those pertaining t o
medical jargon have not, including adhese, cyanose, defmsce, diurese, !)KC, necrwsy,
pex (from orchidopexy), plege (from cardioplegia), and tom. h1edic:ll jiugon als0
includes many deviant singular forms of nouns derived by back-fonnntion tiom
plural forms (comedone from comedones, plural of comc.do; fomite from Ji)niitca.$.
plural of fomes) or supposed plural fonns (hiccp,forcep,puhis). Back-forniations not
recorded in dictionaries should be avoided in formal technical writing.
&Ick-/onnariotz: The patient was diuresecl.
Pwfcmd: ThC patient WIS given tlii~rerics[or ~ ~ n d e m e cliuresisl.
nt
11.4 Jargon

Many wora3 have fotlnd their way iuto n~edicul

vocabulaties with unusual nzeanings that are not
recognized even by medical dictionaries. Sucl!
writings may be characterized as medical jargon
or lnedical slang. W e n these words appear in
medical tnantlscripts or in medical conversation,
they are unintelligible to otherscientists,particularly
those offoreign countries; they are not translatable
and are the mark of the careless and uncultured
person.
Morris Fishbein, MD"

I have laboured to refine our languuge to gram-

matical purity, and to clear it from colloquial
barbariuns, licentiozrs idioms, and irregular
combinations.
Samuel Johnson (1709-1784)

Jargon. Words and phrases that can be understood in conversation but are vague, !
confusing, or depersonalizing are generally inappropriate in formal scientific writ- i

ing (see also 7.5, Grammar, Diction; 11.1, Correct and Preferred Usage of Com-
mon Words and Phrases; and 20.9, Study Design and Statistics, Glossary of Statistical
Terms).
Jargon Preferred Form
4+ albuminuria proteinuria (4+)
blood sugar blood glucose
cardiac diet - diet for a patient with cardiac disease
chart medical record
chief complaint chief concern
congenital heart congenital heart disease; congenital
cardiac anomaly
emergency room emergency department
. exam examination
gastrointestinal infection gastrointestinal tract infection or
infection of the gastrointestinal
tract
genitourinary infection ' genitourinary tract infection or
infection: of the genitourinary tract
heart attack myocardial infarction
hyperglycemia of 250 mg/dL hyperglycemia (blood glucose level
of 250 mg/.dL)

A,*...
.......
-:- i' .. - - . .
2
- - ' . 8
I
- I

i__.
I

11.4 Jargon

jugular ligation jugular vein ligation or ligation of

the jugular vein
lab laboratory
labs laboratory test results
left heart failure left ventricular failure [preferred. I>ut
query author]; left-sided heart failure
normal range reference range
Pap smear Papanicolaou test
the patient failed treatment treatment failed
preemie 'premature infant
l?repped . prepared
psychiatric floor psychiatric department, service,
unit, ward
respiratory infection respiratory tract infection or infection
of the respiratory tract
status post after; following
surgeries operations or surgical procedures
symptomatology symptoms [query authod
therapy of [a disease or condition1 therapy for
treatment for [a disease or'conditionl treatment of
urinary infection urinary tract infection or infection
of the urinary tract .
The following terms and euphemisms should be changed to preferred forms:
Avoid Use
expired, passed away, succumbed died
sacrificed killed; humanely killed [query author1

Avoid trivializing or dehumanizing disciplines or specialties. For example:

Osteopathicphysicianand osteopathic medicine, not osteopath and osteopathy
Cardiologic consultant or cardiology consultation, not cardiology [for the
person1 .
Ortbopedic surgeon, not orthopod
Colloquialisms, idioms, and vulgarisms should be avoided in formal scientific writ-
ing. Exceptions may be made in editorials, informal articles, and the like.
When the administration of drugs is tlescril,ctl, illtra-o)ticula~;itthzcardiac.
intramt~scular,intrathecal, it~trauenous,itttraw~ltriculrrr,i~rtravitreal,oral, paren-
teral. metal, subconjt~ncrival,subcutanmrrs, s~rhlirrglrol,topical, and rra~zsdermal
are acceptable terms when these are the usual or inrentlcd routes of ;idministration.
Except for systemic chemotherapy, however, dnlgs ;\rc uso:~Ily neither systemic nor
local bur are given for systemic or loc:ll cffecr.
11.6 Anatomy

Some topical corticosteroid ointments produce systemic effects.

Oral penicillin is often preferred to parenteral penicillin.
Intravenously injected heroin may be contaminated.
fixccptions: Local anesthetics are a class of drug. Techniques for delivering anesthesia
:ire general, local, and regional. Certain drugs may be inhaled.

Age and Sex Referents. Use specific terminology to refer to persons' age. See also
11.10.3, Inclusive Language, Age.
Neorzates or newborns are persons from birth to 1 month of age.
Infants are children aged 1 month to 1 year (12 months).
Children are persons aged 1to 12 years. Sometimes, chiZdren may be used more
broadly to encompass persons from birth to 12 years of age. These persons may also
be referred to as boys or girk.
Adolescents are persons aged 13 through 17 years. They may also be referred to
as teenagers or as adolescent boys or adolescent girk, depending on context.
Adulk are persons aged 18 years and older and should be referred to as m& or
women. Persons 18 to 24 years of age may also be referred to as young adults.
Note: If the age of an individual patient is given, it may be expressed as a mixed
fraction (eg, 6%years) or as "6 years G months." But when age is presented as a mean,
use the decimal form: 6.5 years. See also 20.0, Study Design and Statistics.
Whenever possible, a patient should be referred to as a man, woman, boy, girl,
or infant, not as a male or female. Occasionally, however, a study group may c0.m- .
prise children and adults of both sexes. Then, the use of male andfemale as nouns is
appropriate. Male andfemale are also appropiiate adjectives.

Anatomy. Authors often err in referring to anatomic regions or structures as the

"right heart," "left chest," "left neck," and "right brain." Generally these terms can be
corrected by inserting a phrase such as "part of the" or "side of the."
right side of the heart; right atrium;*rightventricle
left side of the chest; left hemithorax
left aspect of the neck
right hemisphere [query author]
ascending [not right1 and descending [not left] colon
Where appropriate, use specific anatomic descriptors:
proximal jejunum distal ureter
distal esophagus femoral neck ,

distal radius

The upper extremity comprises the arm (extending from the shoulder to the elbow),
the forearm (from the elbow to the wrist), and the hand. The lower extremity com-
prises the thigh (extending from the hip to the knee), the leg (from the knee to the
ankle), and the foot..Therefore, references to upper and lower arm and upper and
lower leg are often redundant or ambiguous. When such references appear in a
l la nu script, the author sl\oulJ hc. qi~erirci.
- --
I
I

11.8 Laboratory Values

/ Clock Referents. Occasionally, reference to a locus of insertion, position, or attitude

is given in terms of a clock-face orientation, as seen by the viewer (see also 19.1.3,
Numbers and Percentages, Use of Numerals, Measures of Time).
Ambiguous: The foreign body was observed in the patient's left eye
at 9 o'clock.
Use: The foreign body was observed in the patient's left eye
at the 9-o'clock position.
Note: The terms clockwise and counterclockwise can also be confusing. The point
of reference (eg, that of observer vs subject) should be specified if the usage is
ambiguous.

Laboratory Values. Usually, in reports of clinical or laboratory data, the sub-

stance per se is not reported; rather, a value is given that was obtained by measur-
ing a substance or some function or constituent of it. For example, one does not
report hemoglobin but hemoglobin level. Some other correct forms are as follows:
differential white blood cell count
agglutination titer
prothrombin time
pulse rate
erythrocyte sedimentation rate
total serum cholesterol value or level or concentration
increase in antibody leuel
creatinine level or clearance
serum phosphorus concentration
increase in bilirubin level
platelet count
24-hour urine output or volume
antinuclear antibody titer
mean corpuscular volume
hemagglutination inhibition titer
high-density lipoproteinfraction
urinary placental growth factor co17centmtion
urinary protein excretion
In reports of findings from clinical examinations or I;~l>ot.:~tor).
v;~ltlt.\.rI.lr.l I I ~ . I ! .

enumerated without repeating value, level, etc, in ;~ccortl:~nc~ \vitIi [ ~ I IC;)II( I rr<
)\\

example:
11.10 Inclusive Language

Laboratory studies disclosed the following values: alkaline phosphatase,

722 U/L; serum creatinine, 4 mg/dL; serum urea nitrogen, 148 mg/dL; y-
glutamyltransferase, 138 U/L; prothrombin time, 15.3 seconds; and partial
thromboplastin time, 48.8 seconds. Immunoglobulin concentrations were
normal except for IgA levels of 6.7 g/L and h chain concentrations of 383
mg/dL.

Articles. The article a is used before the aspirate h (eg, a historic. occasion) and
nonvocalic y (eg, a ubiquitous organism). Abbreviations and acronyms are preceded
by a or an according to the sound following (eg, a UN resolution, an HMO plan).
(See also 14.8, Abbreviations, Agencies and Organizations.)
a hypothesis [h sound1 a hernatocrit [h sound1
an ultraviolet source [u sound] an honorarium [o soundl
a WMA report [d sound1 an MD degree le sound1
a UV source [y sound1 an NIH grant [e sound1

Sexist language, racist language, theistic

language--all are typical of the policing languages
of mastety, and cannot, do not, permit new knowl-
edge or etzcourage the mutual exchange of ideas.
Toni ~orrison''

Inclusive Language.J A M and the Atchives Journals avoid the use of language that
imparts bias against persons or groups on the basis of sex, race or ethnicity, age,
physical or mental disability, or sexual orientation. The careful writer avoids gener-
alizations and stereotypes and is specific when choosing words to describe people.

SexIGender. Sex refers to the biological characteristics of males and females. Gender
includes more than sex and serves as a cultural indicator of a person's personal and
social identity. An important consideration when referring to sex is the level of
specificity required: speclfy sex when it is relevant. Choose sex-neutral terms that
avoid bias, suit the material under discussion, and do not intrude on the reader's
attention. See also 11.5, Age and Sex Referents.

LmmNouns
Avoid . Prefmed

chairman, chairwoman chair, chairperson [but: see note1

corpsman medical aide, corps member (corpsman is
used by the US Marine Corps and it may
refer to either a man or a woman)
fireman firefighter
forernan supervisor
 Amid Prefmd

housewife homemaker
layman layperson
mailman letter cakier, mail carrier
man, mankind people, human beings, humans, humanity,
humankind, the human race, human species
[but: see notel
manmade artificial, handmade, synthetic
manpower employees, human resources, personnel.
staffing, workforce
mothering parenting, nurturing, caregiving
policeman, policewoman police officer
spokesman, spokeswoman spokesperson
steward, stewardess flight attendant
Note: Use man or men when referring to a specific man or group of men, u w ~ ~ rorr ) ~
wonm when referring to a.specific woman or a group of women. Similarly, chair-
man or spokesman might be used if the person under discussion is a man, and
chainvoman or spokeswoman if the person is a woman. Any of these might be used
in an officialtitle, eg, ~ o r o t hJ.
y Tillman, alderman of the Third Ward, City of Chicago
(verify with the author).
Do not attempt to change all words with man to person (eg, manhole). If pos-
sible, choose a sex-neutral equivalent such as sauer hole or utility access hole.
Terms such asphysician, nurse, and sdentist are sex-neutral and do not require
modification (eg, female physician, male nurse) unless the sex of the person or
persons described is relevant to the discussion (eg, a study of only female physicians
or male nurses).
After completing her internship, the physician specialized in emergency
medicine and worked at several hospitals in California;she was selected as
an astronaut candidate by NASA in 2007.

Personal Pronouns. Avoid sex-specificpronouns in cases in which sex specificity is

irrelevant. Do not use common-gender "pronouns" (eg, %/he," "shem," "shim").
Reword the seqtence to use a singular or plural pronoun that is not sex-specific,a
neutral noun equivalent, or a change of voice; or use "he or she" ("him or her," "his
or herlsl," "they or theidsl'?. i

Amid.. The physician and his office staff can do much to alleviate a
patient's nervousness.
Preferred: Physicians and their office 'staff can do much to alleviate a
patient's nervousness. [plural]
The physician and the office staff a n do much to alleviate a
patient's nervousness. [neutral noun equivalent]
Armid: Everyone must alloclte [heir ti~nccffec~ivcly.
11.10 I n c l u s ~ v eLanguage

f'nyi.m.d Onc onc's rlrnc

mu31 ;~llix.;ltc c-ffrtl~\.cly[smgularl
Pcvple musr all(~-atet l ~ r - t~lrn x cffea~vcly.[plunll
Time must be allocated rtTectively. [change of voice]
Note: In an effort to avoid both xs-specific pronouns and awkward sentence struc-
ture, some writers use plural pronouns with singular indefinite antecedents (eg,
1:vcryonc allocates their time [notesingular verb and "their" instead of "his or her"]),
particul:irly in infonnal writing. Editors of J A M and the Archives Journals prefer
that agreement in number be maintained in formal scientific writing (see also 7.8,
Grammar, Subject-VerbAgreement).
Avoid: One must allocate their time.
Everyone must allocate their time.
Prefetred: One must allocate one's time.
O r One must allocate time.
O r Everyone must allocate time.

Race/Ethnicity. Race is defined as "a category of humankind that shares certain

distinctive physical traits."19 Ethnicity relates to "groups of people classed according
to common racial, national, tribal, religious, linguistic, or cultural origin or back:
ground.""'
Like gender, race and ethnicity are cultural constructs, but they can have bio-
logical implications. Caution must be used when the race concept is described in
health-related research. Some have argued that the race concept should be aban-
doned, on the basis of the scientific evidence that human races per se do not exist.
Others argue for retaining the term but limiting its application to the social, as op-
posed to the biological, realm.
A person's genetic heritage can convey certain biological and therefore medi-
cally related predispositions (eg, cystic fibrosis in persons of Northern European
descent, lactose intolerance in persons with Chinese or Japanese ancestry, Tay-Sachs
disease in persons with Jewish Eastern European ancestry, sickle cell disease seen
primarily in persons of West African descent).
Speceing persons' race or ethnicity can provide information about the
generalizability of the results of a specific study. However, because many people in
ethnically diverse countries such as the United States, Canada, and some European,
South American, and Asian nations have mixed heritage, a racial or ethnic distinc-
tion should not be considered absolute, and it is often based on a person's self-
designation.
JAMA and several of the Archives Journals indicate the following in their in-
structions for authors:
If race and/or ethnicity is reborted, indicate who classified individuals as to
race/ethnicity, the classifications, and whether the options were defined by
the investigator or the participant. Explain why race and/or ethnicity was
assessed in the study. See also Winker MA. Measuring race and ethnicity:
why and how?J A M . 2004;292(13):1612-1614.
 A manuscript's "Methodsn section is a good place in which to explain how persons
were classified according to race/ethnicity. Authors should explain and justify the
inclusion or exclusion of certain groups. oliow win^ are some examples from man-
i uscripts' "Methods* sections
METHODS
Categorization of ~ace/~thnicity
Individuals were categorized on the basis of self-reported race/ethnicity.
Individuals were categorized as non-Hispanic, non-Jewish white (white);
Ashkenazi Jewish (Jewishk African American; Nispanic; or Asian. Because
of the unique spectrum and frequency of BRCAl and BRCA2 mutations that
occur in Ashkenazijewish individuals, these persons'were analyzed sepa-
rately from other whites.
=ODs
S t u d y Participant.
Race or ethnicity was self-re'ported by the parents of the Children from a list
including non-Hispanic white, non-Hispanic black, Hispanic, Asian or Pa-
cific Islander, Native American (including Alaskan), biracial or multiracial
(specify), or other (SpeciFY).

Participants and Measures

Participants were asked to self-identify their race with the "Do you
consider yourself to be primarily white' or Caucasian, black or African
American, American Indian, Asian, Hispanic or Latino, or something else?"
We combined American Indian, Asian, and other categories into "other"
because of the small numbers in those categories. We considered all par-
ticipants to be Hispanic regardless of whether they also identified themselves
as white, black, or other.

Study Population
Race was determined by self-identification and for analysis was categorized
as African American or non-African American. Non-African American cases
were predominantly white but also included 14 women who reported their
race as Native American, Hispanic, Asian American, or multiracial. Infor-
mation on race was obtained because a primary goal of the study was to
better understand breast cancer in African American women.
i
When mention of race or ethnicity is relevant to an understanding of scientific in-
formation, be sensitive to the designations that individuals or groups prefer. Be
aware also that preferences may change and that individuals within a group may
disagree about the most appropriate designation. For terms such as zuhire, black, ancl
African Ametican, manuscript editors should follow author usage.
Exception: Despite the example given above, Caucasian is sometimes used to
indicare white but is technically specific to people from the Caucasus region in
Eurasia and thus should be avoided.
1
11.10 Inclusive Language

In the Unircd States, the ten11/Ijncu~rAnzericurz may tx preferred to blcrck(ncw.

however, that this term should be allowevi only for US citizens of N-ric-~ndescent). A
hyphen is not used in either the noun or adjectival form (see also When Not to U s e
Hyphens in 8.3.1, Punctuation, Hyphens and Dashes, Hyphen).
In reference to persons indigenous to North America (and their descendants),
American Indian is generally preferred to the broader term Native American, which
is also acceptable but includes (by US government designation) Hawaiian, Samoan,
Guamanian, and Alaskan natives. Whenever possible, spec^ the nation or peoples
(eg, Navajo, Nez I'erce, Iroquois, Inuit).
Hispanic and Latino are broad terms that may be used to designate Spanish-
speaking persons as well as those descended from the Spanish-speaking people of
Mexico, South and Central America, and the Caribbean. However, the terms are not
interchangeable, since Latino is understood by some to exclude those of Mexican or
Caribbean ancestry. In either case, these terms should not be used in noun form, and
when possible, a more specific term (eg, Mexican, Mexican American, Latin Ameri-
can, Cuban, Cuban American, Puerto Rican) should be used.
Similarly, Asian persons may wish to be described according to their country or
geographic area of origin, eg, Chinese; Indian,Japanese, Sri Lankan. Note that Asian
and Asian American (Chinese and Chinese American, and so on) are not equivalent
or interchangeable. Do not use Oriental or Orientak.
Note: Avoid using "non-" (eg, "white and nonwhite participants"), which is a .
nonspecific "convenience" grouping and label. Such a "category" may be oversim-
plified and misleading, even incorrect. Occasionally, however, one sees these cat-
egorizations used for comparison in data analysis. In such cases, the author should
be queried. Multiracial andpeople of color are sometimes used in part to address the
heterogeneous ethnic background of many people.

Age. Discriminationbased on age (young or old) is ag&rn..~ecausethe term elderly

connotes a stereotype, avoid using it as a noun. When referring to the entire popu-
lation of elderly persons, use of the elder& may be appropriate (as in the impact
of prescription drug costs on the elderly, for example). Otherwise,terms such as older
persons, olderpeople, elderlypatients, geriatric patients, older adults, olderpatients,
aging adults, persons 65y e a s a n d older, or the olderpopulation are preferred.
Note: In studies that involve human beings, age should always be given spe-
cifically. Researchers in geriatrics may use defined terms for older age groups, eg,
young-old (usually defined as 60 or 65 to 70 or so years) and old-old (80 years and
older). See also 11.5, Age and Sex Referents.
Adultism is a form of ageism in which children and adolescents are disc~unted.'~

Disabilities. According to the Americans with Disabilities Act (http://www.usdoj

.gov/crt/ada/), "a disability exists when an individual has any physical or psycho-
logical illness that 'substantially limiis' a major life activity, such as walking, learning,
breathing, working, or participating in community acti~ities."~'
Avoid labeling (and thus equating) people with their disabilities or diseases (eg,
the blind, schizophrenics, epileptics). Instead, put the person first. Avoid describing
persons as victi?n.sor with other emotional terms that suggest helplessness (afflicted
with, suffeel-ingfrom, stricken with, maimed). Avoid euphemistic descriptors such as
physically challenged or special.
 11.10.5 Sexual Orientation

Amid Peferred
the disabled, the handicapped persons with a disability
disabled child, mentally ill child with a disability, person with
person, retarded person mental illness, person with intellectual
disability, person with intellectual
disability (mental retardation)
diabetics persons with diabetes, study participants
in the diabetes group, diabetic patients
asthmatics children with asthma, asthma group,
asthmatic child
epileptic person affected by epilepsy, person
with epilepsy, epileptic patient
. .
AIDS victim, stroke victim . person with AIDS, person who has
had a stroke
crippled, lame, deformed physically disabled
the deaf . deaf persons, deaf adults, deaf culture
or community
confined (bound) to a wheelchair uses a wheelchair
Avoid metaphors that may be inappropriate and insensitive (blind to themth. deaf
to the request). For similar reasons, some publications avoid the term double-6litld
when referring to a study's methodology.
Note: Some manuscripts use certain phrases many times, and changing, for ex-
ample, "AIDS patients" to "persons with AIDS" at every occurrence may result in
awkward and stilted text. In such cases, the adjectival form may be used.

I Sexual Orientation. Sexual orientation should be indicated in'a manuscript only

when scientificallyrelevant. The term semurlpreferenceshould be avoidecl bec:ulsc it
implies a voluntary choice of sexual orientation not supported by the scientific
literature. In some contexts, reference to specific sexual behaviors (eg. tllerl rc.l~o
have sex with men) may be more relevant than sexual ork~zfutio~~.
The nouns lesbiarrs andgay men are preferred to the broader term hon~oso.\-rrctls
when referring to specificgroups of women and men, respectively. Avoicl itsin~ .yrge
or gays as a noun. Heterosexual and homosexual may be used as acljcctivc.5 (~.p.
heterosqual men).
A member of a heterosexual or homosexual couple may be referred to :i.s,sjtorrsc~.
companion, partner, or lye partner. Same-sex couple and same-scJx ~t~rrnhr~~c, :I re
appropriate terminology.

i ACKNOWLEDGMENTS
Principal author: Roxanne K. Young, ELS
t Special thanks to Thomas B. Cole, MD, Contributing Eclitor, JA~llrl;Jolln I I.
I Ilircku, MD, Dayton, Ohio; Mary E. Knarten~d,PhD. Department of Surger).. Uni-

i
verslry of Minnesota, Twin Likes; and Diane I+mcatll h n g , BS. Racliological Socict!.
of Sonh America, Oak Brook. Illinois.

417
E
11.10 Inclusive Language

REFERENCES
1. Saramago J. 73e Hlstory ofthe Siege of Lisbon. Pontiero G, trans-ed. New York, NY:
Harcourt Brace; 1997.
2. Why are scientists poor writers [Queries and Minor Notes]?JAMA. 1904;42(7):477.
3. Revised Framework of External Cause of Injury (E Code) Groupings for Presenting
Injury Mortality and Morbidity Data. http://www.cdc.gov/ncipc/whatsnew/matr~
.htm. Accessed February 18, 2005.
4. Satcher D. Injury: an overlooked global health concern [From the Surgeon General].
J A M . 2000;284(8):950.
5. Kane RL, Kane RA. Long-term care. J M .1995;273(21):1690-1691.
6. McDonald HP, Garg AX, Haynes RB. Interventions to enhance patient adherence to
medication prescriptions: scientific review. JAMA. 2002;288(22):2868-2879. .
7. Chrer. M. Doctor's orders: rethinking compliance in dermatology [editorial]. Arch
Dennatol. 2002;138(3):393-394.
8. Altobelli L, reporter. Ethics in medical research [annual meeting report]. Sci Editor.
2005;28(5): 153.
9. Bemstein TM. 73e Careful Writer A Modem Guide to Englkh Usage. New York, NY:
Free Press; 1998.
10. The Expert Cornn~itteeon the Diagnosis and Classification of Diabetes Mellitus. Report
of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.
Diabetes Care. 2003;26(suppl 1155-S20.
11. Publications Department, American College of Obstetricians and Gynecologists.
Publications Guidelines. Washington, DC: American College of Obstetricians and
Gynecologists; 1997:22-23.
12. Pinn W. Sex and gender factors in medical studies: implications for health and
clinical practice. JAMA. 2003;289(4):397-400.
13. Roth M. "Glycated hemoglobin," not "glycosylated hemoglobin." Clin Chem.
1983;29(11):1991.
14. Allen CA. Surgeries. Arch Surg. 1996;131(2):128.
15. Schur NW. British English A to Zed. New York, NY: Facts o n File Publicitions; 1987.
16. Flanagin A. Re: Violence and nursing netted. ~ P t v f w s i m lNU^ 2000;16(4):252.
17. Words and phrases. In: Fishbein M. Medical Writing: l'be Tecbnic and the Art. chi-
cago, IL: American Medical Assodation; 1938:46.
18. Morrison T. Nobel Prize in Literature Lecture, December 7, 1993. In: Allen S, ed. Nobel
Lectures, Literature 1991-1395.Singapore: World Scientific Publishing Co; 1997.
http://nobelprite.org/literature/laureates/l/moon-lere.h. Accessed Feb-
ruary 27, 2006.
19. Mem'am-Websy's Collegiate Dictionary. 11th ed. Springfield, MA: Memam-Webster
Inc; 2003.
20. Maggio R. Talking About People: A Guide to Fair and Accurate Lunguage. Phoenix,
AZ: Oryx Press; 1997.
21. Orentlicher D. Rationing and the Americans with Disabilities Act. J A M .
1994;271(4):308-314.

ADDITIONAL READINGS
Burchard EG, Ziv E, Coyle N, et al. The importance of race and ethnic background in
biomedical research and clinical practice. N Engl J Med. 2003;348(12):1170-1175.
 11.10.5 Sexual Orientation

Cooper RS,Kaufrnan JS, Ward R. Race and genomic.. ArEnglJ Med. 2003;348(12):
1166-1170.
Indigenous: to capitalize or not. World Association of Medical Editors Web site.
http://www.wame.org/indigenous.htrn. Published September 2-18, 2003. Accessed April
24,2006.
Kaplan JB, Bennett T. Use of race and ethnicity in biomedical publication..JhL4.
2003;283(20>:2709-2716.
Leonardi M, Bickenbach J, Ustun TB,Kostanjsek N, Chattej i S; the MHADIE Consortium.
The definition of disability: what is in a name? Lancet. 2006;368(9%3):1219-1221.
Office of Management and Budget, the Executive Office of the President. Standards for the
Classification of Federal Data on Race and Ethnicity. http://www.n-hitehouse.gov/on~l>
/fedreg/race-ethnicity.html.Accessed April 24, 2006.
Oumm SM,Ellison ETH. Improving the use of race and ethnicity in genetic research: a
survey of instructions to authors in genetics journals. Sci Editor. 2006;29(3):78-80.
Race and ethnicity: how do we describe people?World Association of Medical Editors Web
site. http: //www..wame.org/describe.htm.Published January 13, '2006. Accessed April 24,
2006.
Risch N. Dissecting racial and ethnic differences. N ~ n gJl ~ e d2@4%;354(4):408411.
.
Rivara FP, Fiberg L. Use of the terms race and ethnicity. Arch Pediatr Adolesc Med.
2001;155(2):119.
Schwartz RS. Racial profiling in medical research. N Engl j Med. 2001;344(18):1392-1393.
Wmker MA. Measuring race and ethnicity: why and how?J M .2004;292(13):1612-1614.
 , .. . . . - - - --

Non-English Words, Phrases,

and Accent Marks

12.1 122
NowEnglish Words, Phrases, and Titles Accent Marks (Diacritics)
12.1.1 Use of Italics
12.1.2 Translation of Titles
12.13 Capitalization and Punctuation

Non-English Words, Phrases, and Titles

Use of Italics. Some words and phrases derived from otherlanguages have become
part of standard English usage. Those that have not should be italicized (see 22.0,
Typography), and usually a definition should be given. Consult standard medical
dictionaries and the most recent edition of Merriam-Webster's Collegiate Dictionary
for guidance.
A public health investigation revealed that the source of lead exposure was
haigefm (clamshell powder), 1of the 36 ingredients of the Chinese herbal
medicine.
In Vitro Susceptibility Testing of Antfingal Agents
Medical information and advice abound on the Internet, but remember:
Caveat lector.
Lorenz .Bolder, the son of a carpenter, eventually became the praeceptor
traurnatologiae totus mundi (teacher of traummitologyin the whole world).
Non-English street addresses, names of buildings, and names of organizations shbuld
not be italicized.
Correspondence: W. Wayand, MD, Allgenleines offentliches Kmnkenliaus
der Stadt Linz, Krankenhausstrasse 9, 4020 Linz, Austria.
The Brazilian College of Surgeons (Coltgio Brasileiro de CirurgiBes) w:rs
foi~ndcclon July 30, 1929.

Translation of Titles. Non-English.titles mentioned in text may be translated or not, ;I[

the author's discretion. If the original title is used, an English translation sl~oulcl1w
given parenthetically, except in cases in 'which the work is considered well kno\vn.
Both the English translation of the title (if given) and the non-English title sliol~lcllw
italicized for books, journals, plays, works of art, television and radio progr;tlli>.Ic I ~ S
poems, films, and musical compositions.
StcndahllsLe tvuge el Ie n o i r ( n e &JL[ U I I ~~ h Black)
c is rrquirctl rr;liilng I , ,r
all third-year students.

42 1
12.2 Accent Marks ( D l a c r ~ t ~ u )

Andrclrs Vcs;ll~ub' Ihhcmrur). nlasrerpiece De Humani Cotporis Fabrica

( O n f l ~Strucflrre
e of the Hunmn Body) marked the resurgence of anatomy as
a discipline.
The rules for italicizing and translating non-English-language journal article titles are
slightly different (see 3.9.2, References, Titles, Non-English-Language Titles).

Capitalization and Punctuation. Non-English words should be capitalized and non-

English phrases punctuated according to that language's standard of correctness.
Follow language dictionaries and The Chicago Manual of Style.

Accent Marks (Diacritics). An accent mark (diacritic), when added to a letter,

indicates a phonetic value different from that of the unmarked letter. English words
once spelled with accent marks (eg, cooperate, preeminent) now are written 2nd
printed without them. Consult the most recent edition of Merriam-Webster's Colleg-
iate Dictionary to resolve questions about whether a word should retain its accent. In
general, English aords in common usage should be spelledwithout diacritical marks.
Accent marks should always be retained in the following instances:
Proper names
Dr Borneman is a Pew Scholar in the ~iomedi&lSciences.
a When it is desirable to show the correct spelling in the original language
Koln (Cologne)
In quotations
"M6vale pajaro en mano que cientos vo!andon ("a bird in the hand is worth
more than a hundred flying birdsn) is a Spanish proverb similar to the
English-language "A bird in the hand is worth two in the bush."
In terms in which accent marks are.retained in current use (consult dictionaries)
cafe au lait spots
garson
Mobius strip
voil2
e
To show pronunciation and syllabic emphasis
centime (san-tern)
gluteus (gluttus)
Accent marks should be clearly indicated on manuscript copy.
Accent Mark Example of Usage
acute MenCtrier
breve Gabdulla Tuqay
cedilla Beh~et
circumflex Le NBtre
 12.2 Accent Marks (Diacritics)

dot marle
giave Bibliotheque
mamn gignoskein
ring Angstrom
slash Kabenhavn
tilde manana
umlaut ~enoch-~chonlein
purpura
wedge VrapZe
Some languages are not supported by commonly used, word-processing programs
and Web browsers. page proofs including words in such languages should he re-
viewed thoroughly by aperson familiar with the language, and some letters or entire
words and phrases may need to be rendered online using images rather than HTAlL.
ACKNOWLEDGMENT
Prindpal author: Brenda ~ r e g o l k eELS
,
I

Medical Indexes

13.1 13.2.3 Generic Cross-references

Index Style 13.2.4 Double-postings
13.1.1 Alphabetization and Sorting 13.2.5 Inversions
13.1.2 Consistency 13.2.6 Subentry Levels
13.1.3 Letter-by-Lettervs Word-by-Word 13.2.7 Vocabulary Control
13.1.4 Capitalization of Main Entries
13.1.5 Abbreviations 13.3
13.1.6 Locators Periodical Indexing
13.1.7 Indented vs Run-in Style
13.4
13.2 Controlled Vocabulary Indexing
Features of Indexes
13.2.1 Types of lndex
13.2.2 Cross-references Online and Electronic Indexes

i%e indexer can help save lives and can contml

outcomes.
L. P. ~ ~ r n a n ' ( P ~ ~ )

Indexes are essential and highly valued components of medical textbooks and jour-,
nals. Publishers should hire professional indexers conversant with medical termi-
nology and allot sufficient time in the production schedule for a comprehensive
index to be prepared. "Space limitations on indexes should not apply to medical
books."'(pm Medical indexes should aim for "accuracy, thorough analysis (subheads
and cross-references), completeness/comprehensiveness [andl A
textbook index should "tie together" discussions throughout of the same or related
subject, eg, an infectious disease and its pathogen.2(p62)
General references on indexing include Indexing ~ o o k sthe
, ~ indexing chapter
, ~ Indexing Fmm A to z5which includes a section
in The ChicagoManual o f ~ t y l eand
on biomedical indexing. The American Society of Indexers Web site provides in-
dexing re~ources.~ Patton and Wyman's online guide includes information specific
to biomedical indexing? Biomedical indexing is covered in Indexing Specialties:
~edicine'and Indexing the Medical ~ciences?
The following are some considerations specific to medical indexing.

'Elndex Style.The style of terms in the index must be the same as the style in the text.4

Alphabetization and Sorting. Alphabetization in indexes begins with the first letter
of the term, eg,
G pe"0d
G ph3x
G protc~n
13.1 Index Style
I

Commas precede letters in sorting order (examples from ~homas').

cold, common
cold agglutinin disease
Vibrio, noncholera
Vibrio cholerae infection

Other punctuation is i g n ~ r e d . ~

Omsk hemorrhagic fever virus

O'nyong-nyong virus

For entries that are identical except for case, choose whether uppercase or lowercase
will take precedence in sorting and be consistent throughout the index.3
abll, 99, 106-110
pbll, 95, 100-103
Brcal, 112
BRCAI, 54, 804-809

When an identifier in parentheses is used to clanfy similar terms, the identifier e y ,

be included in sorting (follow house style). :-

Abll (mouse gene), 95, 100-103

Abll (mouse protein), 98-99, 106
abll (retroviral oncogene), 93,106-110
BRCAl (human gene), 54,804-809
Brcal (mouse gene), 112
In biomedical indexes, numeric prefixes and chemical prefixes (eg, B,L, keto-, N-),
are usually ignored for purposes of alphabetization and sorting of main entries
. .
(first set of examples adapted from horna as?.
dihydroxyacetone
1,25-dihydroxycholecalciferol
L-dihydroxyphenylsciine
6-keto prostaglandin Flu, 119
13,14-dihydro-15-ketoprostaglandin FZa, 120
prostaglandins, 98-112, 345-367
Note: A better arrangement of the latter set of entries might be as follows:
prostagla~dis,98-112, j45-367
6-keto prostaglandin Flu, 119
13,14-dihydro-15-ketoprostaglandin FZa, 120
For terms with other prefixes, use cross-references or double-postings (see 13.2.4,
Features of Indexes, Double-postings) if the text suggests that readers are likely to
seek the term under the main portion of the keyword.
 13.1.1 Alphabetization and Sorting

E-selectin. See under selectins

P-selectin. See under selectins
Terms with numbers appear in numerical order.
CDla
CD36
CD4
CD6
CD8
CDlO
Numbers within terms are-sorted ahead of letters, eg, CX3C precedes CXC.
chemokine subfamilies, 801-858
CC, 250,825-830
CX3C, 764, 820-825
CXC, 826840
CXCL1, 830-832
CXCL4,835-839
XC, 841-855
Numbers that are parts of formal names are alphabetized as though written out," for
instance, a study-group name in an author index:
Nilanont Y
903 Study Group
Nishiguchi S
For Greek letters, follow house style if specified.* Greek letters are usually treated as
though they were spelled out, eg, P is "beta," y is "gamma."
W A (y-amino butyric acid), 244, 350-366, 998
y-amino butyric acid. See GABA
y chain, 243. See also IgG
Alphanumeric combinations are sorted by letter (including Greek), then nunlber
(including subscripts).
a-adrenergic receptors
a2-adrehergicreceptors
:i:,
P-adrenergic receptors .,. .
>
:,.

.% ...
.
,
PI-adrenergic receptors
In long series of Greek-letter-affixed terms that are likely to be listed together. 31-
phabetizing according to the Greek 1e.trc.r a n d not its name spelled out in English is
preferable.
IFN-a
IFN-P
IFN-h

427
13.1 Index Style

Symbols are sorted as though written out. Consider using double-postings,a separate
!.
symbol index or goup,' cross-references, or a key to direct readers to symbol
entries.
@ ("at"), in gene symbols, 495-497
X2 (chi-squared), 206
Formal binomial organism names (see 15.14, Nomenclature, Organisms and Patho-
I
gens) used as index entries are not separated5:
Staphylococcus albus
Staphylococcus aurars '

Not:
Staphylococcus
albus
a u m

Consistency. A text may not be consistent in style for particul& terms, eg, italics or ' ,

hyphens, but the index should be stylistically consistent.' If no style predominates for
a given term used throughout the text, the indexer should check with the editor or
consult the publisher's stylebook for the form to be followed in the index. It is hoped
that authors will use, and publishers will recommend, official style when that is an
option (consult 15.0, Nomenclature), eg, italicizing gene symbols (BRCI11).

Letter-by-Letter vs Word-by-Word. These are 2 styles of alphabetization. Letter-by-

letter considers all letters of the entire entry, ignoring spaces between words. Word-
by-word sorts by the first word of an entry term, then the next word. Letter-by-letter
alphabetization is commonly used by scholarly publishers4 and is the familiar ar- .
rangement found in dictionaries and encyclopedias.3s4 word-by-word sorting might
result in more informative groupings of terms, especially multipart but in
medical indexes letter-by-letter sorting usually allows readers to locate terms equally
well. Consult indexing texts for detailed descriptions of these 2 methods of sorting.
The publisher may specify a sorting style. The following examples are adapted from
~homas~:
Letter-by-Letter Word-by-Word
heart heart
heart block heart block
heartburn heart disease
heart disease heart failure
heart failure heart murmur(s)
heart mumuds) heart rate
 13.1.5 Abbreviations

Letter-@-Letter Word-by- Word

heart rate heart sound(s)
heart sounds heartburn
heartworm infection heartworm infection
xanthohtosis X chromosome
X chromosome xanthomatosis

Capitalization of Main Entries. Although main entries have traditionally featured

ini>;alcapitals to distinguish them from subentries, i"be ChicagoManual of Style, 15th
edition, recommends lowercase, except when the entry term would begin with
a capital, eg, proper nouns.' This is especially worthwhile in biomedical publica-
tions, in which capitalization may be complex and may distinguish otherwise iden-
4
tical terms.

AFP. See a-fetoprotein

A&, 98
AFP, 103
Bnal, 112
BRCAI, 54,804-809
breast cancer, 50-57, 110-113,801-815

Haemophilus i n f r m a e Rd, 998

hepatitis, 1015-1028
Hindm, 698

LPL. See lipoprotein lipase

LPL, 1092
Staphylococcus aureus, 1056-1077. See also staphylococci

Abbreviations. Include only abbreviationsused in the text being indexed (ie, if a text
uses only an expanded form, eg, National Institutes of Health, but never the abbre-
viation, do not include "NIH" in the index).
Abbreviations are listed alphabetically among other entries (examples from
horn as^.'?.
catheterization
CAT scan. See computed tomography
cat-scratch disease
CEA (carcinoembryonic antigen)
cecum

ectopic ACTH syndrome, 106, 107, 109

ectopic kidney, 2226
ectopic pregnancy, 1947, 2055-2056

i
Idvnticnl abbreviations are sorted by case; be consistent throughout the index, eg,

I- 429
I
13.1 Index Style

t I<.\',2.32
t iifi', 330-33.1

Pao,, 464
I'Ao~, 251
Use cross-references and expansions with abbreviations, as in these examples (first
set from horna as^).
CAT scan. See computed tomography
computed tomography (CT, CAT scan), 2715-2716
CT. See computed tomography

mitral stenosis (MS), 497

MS. See mitral stenosis; multiple sclerosis
multiple sclerosis (MS), 503
The following example illustrates (1) a cross-referencewith an abbreviated organism
name and (2) use of roman cross-referenceterm (See) when entry terms are in italics.
E'coli infection. See Eschericbia coli infection
II
When an abbreviation is more familiar than the expansion, index under the abbre- :'

viationls2;include the expansion in parentheses, use a cross-reference to the ab- .

breviation from the expanded term, or both? Terms.in this manual for which it is i
specified that the abbreviation may be used without expansion (see chapter 14.0, ,
. .
Abbreviations, and chapter 15.0, Nomenclature) should probably be indexed under
the abbreviation. However, terms expanded at first mention, as recommended in this
manual, may nevertheless be more familiar in their abbreviated form. Usage in the
text being indexed is a guide to which form is more familiar.
deoxyribonucleic acid. See DNA .

DNA, 112, 334, 556-560

B Locators. Locators are the citationscoinmonly, page numbers in print indexes--

that follow the entry to indicate where the material about that enuy is found. Locators
may also be paragraph numbers, line numbers, section numbers, volume-page num- .
ber combinations, figure identifiers in atlases: h y p e r l i i in online indexes, etc.
American Society of Indexers guidelines recommend that no more than 5 to 7 loca-
tors per term be given. When more than 7 locators accumulate under one heading .
(ie, 7 "undifferentiated locators"), the indexer should consider breaking them down
under subheadings. This will produce a more usable index.''
Not:
SARS (severe acute respiratory syndrome), 18, 20, 75-79, 93,105, 117,
145-148, 167, 187-189, 235, 280, 357, 402
Prefeved:
SARS (severe acute respiratory syndrome), 75-79, 145-148
in China, 187-189
 13.2.1 Types of Index
.

antibiotics, 18, 20
corticosteroids, 357
interferon alfa, 402
etiology of, 93, 105, 117
quarantine for, 167, 235
in Toronto, 280
Typographic variations on locators include bold for main discussions, t for tables
(frequently used in medical indexes), f for figures, and others.
eczema, 24,275fj 290-295,294t
Explanatory notes are recommended when any typographic variation is used, for
example, "Locators in boldface indicate main discussions. Those followed by t or f
indicate tables and figures, respectively." Such notes are most useful for the reader
when they appear as running headers or footers (L. P. Wyman, e-mail communica-
tion, February 19, 2004).

Indented vs Run-in-Style.In indented style, main headings are followed by indented

subheadings, each on its own line. In run-in style, subheadings'appear continuously,
not on separate lines,and are separated by commas. . '

Zmhted.
SARS (severe acute respiratory syndrome), 75-79, 145-148
in China, 187-189
drug therapy for
antibiotics, 18, 20
corticosteroids, 357
interferon alfa, 402
etiology of, 93, 105, 117
quarantine for, 167, 235
in Toronto, 280

Run-in:
SARS (severe acute respiratory syndrome), 75-79, 145-148, in China, 187-189,
drug therapy for, 18,20,357,402, etiology of, 93,105, 117, quarantine for, 167,
235, in Toronto, 280
The indented style is better suited for medical indexes because complex terms in
subheadings are easier to read when set on separate lines. This style is "particularly
useful where sulkubentries are required.. . ."4('".25.p764' Note that in the above es-
amples, sub-subentries are used for specific drug therapies in the indented style. A:
mixed style-indented main entries and subentries, run-in sub-subentries--is not as
well suited for medical indexes, again because of the complexity of the terms.

Features of Indexes

Types of Index. A 'single index is the most convenient for the reader." f lo\\.c\.cr.
sepante a~lthorand s~lbjeaindexes are common in I~iornedic;~l publications. c . 3 ~ -
ci;~llyjournnls. Sepante indexes should be "visually dihtinct""~-~"and Ix tli41in-
guished typographically and by nlnning headers o r ftx)tcrs.'
13.2 Features of Indexes

Cross-references. Cross-rrfrrt.nc.c.\ Arc v;llu;lt,le for tcrnls that re~drr.;n111511t x c k In

different alphabetic Iwations (Idst r x a r n p l c from ~homas").

cDNA. See under DNA

dsDNA. See under DNA
mtDNA. See under DNA
DNA, 5, 300-310, 999
cDNA, 24, 356
dsDNA, 24-25, 356, 900
mtDNA, 660
DTH. See hypersensitivity reactions, type IV
DTH skin test, 1010-1022, 1012J; 1031'~

Cross-references are also used for synonyms:

pro3ccelerin. See factor V

Stuart factor. See factor X
T cell. See T lymphocyte

In the middle example, if Stuart factor were used in text concerning the history of
factor X, a see also reference might be more appropriate:

factor X, 410-425. See also Stuart factor

Stuart factor, 418, 563

Generic Cross-references. General classes, and specific members of a class, may

require generic cross-references, ie, a cross-reference to a group of entries rather
than to specific entries by name. The following examples are from Patton and
~~rnan.7

drugs
antihypertensive, 483
See ako specific drugs by name
medications. See drugs; specific medications
pharmaceuticals. SeepMducts by name
kidney, 18-43, 586-592. See akio under nephro- or renal transplantation,
551-578

Double-postings. Listing the same qitation under 2 or more entries, known as double-
posting, is helpful when readers might be expected to look equally frequently in
more than one place.
benign prostatic hyperplasia (BPH)
BPH (benign prostatic hyperplasia)
prostatic hypeiplasia, benign (BPH)
 13.2.6 Subentry Levels
I

cTnC, 246
TnC, 345
[cTnC is listed in both the c's and in the 1k.1
However, for entries that will also appear in a series of related subentries under a
main heading, cross-references to the'principal form of entry are to double-
posting.
Acceptable:
E-selectin, 550 .
P-selectin, 551
Selectins
E-selectin, 550
P-selectin, 551
Pwfmd.
E-selectin. See under selectins
P-selectin. See under selectins
Selectins
E-selectin, 550
P-selectin, 551

Inversions. An inverted f o m changes the order of a compound term, eg, "leukemia,

B-cell." Inversions are preferred when the indexer, depending on context and the
coverage of the book, believes that the reader is most likely to look up information
under the keyword, eg, under "leukemia" rather than under "B-cell~"Such inverted
forms of entry should be cross-referenced (or double-posted) from the uninverted
disease name. Avoid unnecessary inversions such as "fatigue syndrome, chronic"
that break up commonly used compound terms.
*
BS
ubentry Levels. ~ u l l a ?recommends using more main entries or first-level suben-
tries rather than going beyond a third level of subentry, as in this example, adapted
from ~ulla?:
-
Not:
cancer
treatment of
pharmacologic
cyclophosphamide for
adverse effects of
thrombocytopenia

Preferred:
cancer
treatment of
pharmacologic
See ako indicviirml dnqs
13.2 Features of Indexes

chemotherapy
adverse effects of
See also individual drugs
cyclophosphamide
adverse effects of
thrombocytopenia from
drug-induced disorders
from cyclophosphamide
thrombocytopenia
thrombocytopenia
from cyclopl~osphamide
drug-induced
Even when a main heading cites the entire page range of the discussion of a par-
ticular topic, it is useful to include subtopics as subentries so that the reader is aware
that the subtopic has been covered in that discussion, as well as elsewhere in the
text.* The following example is based on Blake et al?
neurological disorders, 210-281
diagnostic procedures, 210-224, 343-345

Vocabulary Control. An entity may be referred to by different names throughout a

text. Such variation is common in multiauthor works.3 Cross-references, double-.
postings, and parenthetical synonyms help the reader know that the entity sought in
the index is the same entity discussed under various names. Authors and editors
should use vocabulary consistently and note synonyms in the text. The indexer
should consult the book author or editor and the publisher's book editor for clarifi-
cation. The following example is adapted from Thomas9:.
auditory nerve. See ctanial nerve VlII
cranial nerves, VIII (auditory, vestibulocochlear), 7812,782,7822,7833, 18702
eighth nerve. See cranial nerves, VJII (auditory, vestibulocochlear)
;estibulocochlear nerve (cranial nerve WI), 781t, 782, 7823, 7832, 18702
Note that a reader who sought information under vestibulocochIearnerve would be
helped by finding citations of pages discussing cranial nerve VIII. But the reader will
fruitlessly skim the page for vestibulocochkarnerue, unless the term actually used on
the page, cranial nerue VII, is included in parentheses in the index entry.
The noneponymous name of a disease should be included in the index parenthet-
ically after the eponymous index entry if the noneponymous name is used in the
text2 (see also chapter 16, Eponyms). Indexers should be cognizant of disease terms
that are synonymous, are encompassing, or overlap,217eg, nephric and renal? sei-
zures and epilepsy.' The following example is adapted from ~ h o m a s ~ :
Crohn disease, 152-155
inflammatory bowel disease, 149-159
ulcerative colitis, 155-159
1. 13.4 Controlled Vocabulary Indexing

Tullar recommends, "Whenevera disorder is cited by more than one name,. . .opt for
the term used in the principal discussion and cross-reference from alternate terms.
Double-post folios for a single discussion rather than cro~s-reference."~(~~~'

, Periodical Indexing. Vocabulary control is of particular importance not only for

indexes compiled for multiauthor texts, but also for the indexes that appear at the
end of the volume year in medical journals. In genera1;the rules and guidelines that
apply to back-of-the-book indexes also apply to journal indexes. Where, in specialty
journals, nomenclature is in flux or variable, indexers should follow the style and,
- recommendations of their publishers or editors, cross-referencing to preferred terms
or forms of entry rather than double-posting.Journal indexes differ -from book in-
dexes in basing index en& largely on title and abstract information, which sum-
marize~an article's main topics, and usually do not include entries for subject matter
that is secondary or incidental withii the text of the article. Locators are given as an
article's beginning page or the article's page range and sometimes include issue
number or date. Publishers may specify, or indexers may choose to make, general
entries for the type of study ("Randomized Trial," "Review"), for the population
group studied CChild," "Men," "Women," Elderly"), and other entries for recurring
article types or topics. These enhies should be made consistently issue by issue
throughout the volume year. If, for example, "Adverse Reactions" is established'as an
general index entry, it should be entered for each article examining a specificreaction
regardless of whether the term a d m reuction appears in the title or abstract.

Controlled Vocabulary Indexing. In indexing journals offering broad coverage of

general medicine and specialties and in indexing sets of periodicals issued by di-
ferent publishers, indexers usually rely on the external authority of a controlled
vocabulary. Controlled vocabularies allow indexers to resolve variances in natural
language systematically. The vocabularies establish preferred terms with cross-
references from alternative forms of entry. Thus, all relevant references can be
gathered under a single heading. Controlled vocabularies also establish hierarchical
relationships among related terms. Such hierarchies most often take the form of a
thesaurus in which narrower terms are entered as subentries beneath the broader
terms to which they relate. The following example is abbreviated from the National
Library of Medicine's Medical Subject Headings (M~SH)'~(~:'*):
Intercellular Signaling Peptides and Proteins
Cytokines
Ghemokies
Growth Substances
Interleukins
Interferons
In using a controlled vocabulary, entry style should follow that of the vocabulary list
or thesaurus, not the text.13 Adapting controlled vocabularies too freely for local use
may result in indexing that will not be fully functional in electronic systems. In-
dexable terms not listed in the thesaurus (including proper nouns such as the nxnles
of people and institutions) may be added as informal identifiers either in a separiltc
field of a database record or appropriately tagged among the controlled vocnhul;~~?'
terms.13 For example, in an index based on the MeSH vocabulary, an article enrirlcrl
b "Effects of Bilateral Posteroventral Pallidotomy on Subjects With I'arkinson lliscazc. '

c
: 435
i
13.5 Online and Electronic Indexes

may be indexed under the non-MeSH term "Pallidotomy." This term, however,
should be separated from the controlled vocabulary descriptors in the index record
or tagged as a local term to distinguish it from MeSH descriptors. The inclusion of
local terms in this way allows for valid additional points of access without com-
promising the integriry of the formal vocabulary and its hierarchy.
Most indexing and abstracting services base their indexing on controlled vo-
cabularies. Controlled vocabularies are also used among descriptive elements called
meta-data, which allow digitized information to be networked in a variety of ap-
plications. MeSH is the most comprehensive controlled vocabulary in medicine
and is used to index MEDLINE. Other biomedical controlled vocabularies and the-
sauri include The National Cancer Institute Thesaurus (http:lnciterms.nci.nih.gov
/NCIBrowser/Dictionary.do) and the Nursing and Allied Health Subject Headings
used to index CINAHL (Cumulative Index to Nursing and Allied Health Literature)
(http://www.ciiahl.com/).
Even when indexing is based on the language of the text, as in back-of-the-book
indexing, MeSH and specialized thesauri may be consulted along with standard
medical dictionaries as sources of authority for forms of entry and cross-referencing
and as general guides to the language and organization of medicine and its related
fields. 'ihe MeSH is revised annually and is available both in printed volumes and ,
online from the National Library of ~ e d i c i n e . ' ~
A suggested reference on the subject of controlled vocabularies is Vocabulay
Controlfor Infomzation ~etrieval.'~ I
'
Online and Electronic Indexes. Although indexing services continue to index
scientific literature much as in the past, few any longer compile their indexing into
the printed monthly and annual cumulations such as I n k Medicus or Cbemical
Abstracts that once sat in long rows on university library shelves. The database prod-
ucts that have replaced cumulated print indexes nevertheless still depend on con-
trolled vocabulary indexing as a means of achieving acceptable degrees of relevancy
in retrieving citations from among millions of abstracts. To eliminate the many mar-
ginal "hits" that result from the unrnediated keyword searching of large databases,
search screens typically allow users to construct their searches by selecting from
thesaurus terms or employ built-in mechanisms that map natural language queries to '
assigned, thesaurus-based indexing terms. Taxonomies designed for the graphic
interfaces of the Web have been among the more popular means of providing
classified or topical access to document collections, most commonly to consumer
health information. However, informal taxonomies classifying articles by topics of
general interest to medical students, practitioners, and researchers have also been
employed by medical publishers to supplement keyword-based search engines at
their journals' Web sites. Scientific validity and consistency, rather than style, are of
primary concern in both database indexing and taxonomy classification. Embedded
i n d e ~ i n g , ' ~a"process
~ whereby the indexer embeds markers in passages of text at
which index entries should point, allows index terms to be compiled into both print r '
indexes to be included in the back of a book and electronic indexes in which
hyperlinks replace page locators. Embedded indexing, usually available in desktop \,
publishing packages, has been used mostly for technical manuals issued simulta-
neously in print and electronically and which may be updated frequently. Style con- .,
I
s~dcr;~t~ons are much the same as those for tnditional back-of-the-book indexes.
 & . -

13.5 Online and Electronic Indexes

ACKNOWLEDGMENTS
Principal authors: Bruce McGregor and Harriet S. Meyer, MD
L. Pilar Wyman, Wyman Indexing, Annapolis, MD, reviewed this chapter and
provided invaluable suggestions.

REFERENCES
1. Wyrnan LP, ed. Indexing Specialties: Medicine. Phoenix, AZ: American Society of
Indexers; Medford, NJ: Information Today; 1999.
2. Tullar IC. General medicine. In: Wyman LP, ed. Indexing Speialties: Medicine.
Phoenix, AZ: American Society of Indexers; Medford, NJ: Information Today; 1999:
47-66.
3. Mulvany NC. Indexfng Books. 2nd ed. Chicago, IL: University of Chicago Press; 2005
4. me Chicago Manual of Syle.15th ed. Chicago, IL: University of Chicago Press:
2003755-801. Also available as Indexes: A CbapterFmm The Chicago Manual of Style.
15th ed. Chicago, IL: University of Chicago Press; 2003.
5. Wellisch HH.Indexing Ftwn A to Z. 2nd ed. New York, NY: HW Wilson; 1996.
6. American Society of Indexers Web site. http://asindexing.org. Accessed April 20.2006.
7. Patton D, Wyman LP. How to develop an index style guide. http://xmvw.wymanindesing
.com (see under "Pilafs Info," then "Pilar's Presentations"). Accessed April 20.2006.
8. Blake D, Clarke M, McCarthy A, Morrison J. Indexing the Medical Sciences (Sociep
of In& Occasional Papers on Inakdng, No. 3). Sheffield, England: Society of
Indexers; 2002.
9. Thomas S. Index. In: Beers MH,Ponet RS,Jones TV,Kaplan JL, Berkwits M. The ~Merck
Manual of Diagnosis and 'Iherapy. 18th ed. Whitehouse Station, NJ: Merck Research
Laboratories; 2006:2787-2991.
10. Thomas S. Index. In: Beers MH, Berkow R, eds. 7%eMerck Manual of Diag)zosis
and Therapy. 17th ed. Whitehouse Station, NJ:Merck Research Laboratories; 1999:
2657-2833.
11. American Soci$ty of Indexers. Indexing evaluation checklist. http://www.asindexing
.org/site/checklist.shtml. Updated April 7, 2006. Accessed April 20. 2006.
12. National Library of Medicine Medical Subject Headings Web site. http://www.nlm
.nih.gov/mesh/meshhome.html. Accessed August 2, 2005.
13. McMaster M. Practical medical database indexing. In: \Vyman LP, ed. Indexing S p -
cialties: Medicine. Phoenix, AZ: American Society of Indexers; Medford, NJ: Infor-
mation Today; 195983-91.
14. Lancaster FW.Vocabulay Controlfor Information Retrieval. 2nd ed. Arlington, VA.
Informatiolt Resources Press; 1986.
15. Mauer P. Embedded indexing. In: Proceedings of 50th Annual Conference of Socien;
for Technical Communication. 2001. http://www.stc.org/5Ot11Conf/Session~Materia\s
/dataShow.asp?1D=230. Accessed April 20, 2006.
16. American Society of Indexers. Software tools for indexing. http://ww.asindexing
.org/site/softwareesIitnil.Llpdntetl March 20, 2006. Acccsscrl April 24, 2006
 Abbreviations

' Academic Degrees, Certifications, Agencies and Orga~izations

and Honors
14.9
14.2 Collaborative.Groups
US Milialy Services and Titlis
142.1 US Military Services
14.2.2 US Military Officer Titles (GradesIRanks) Namesof Journals

bays of the Week, Months, Eras

Common Terms

Local Addresses 14.12

Units of Measure

14.13 '

Possessions; Provinces: Countries Elements and Chemicals

14.6 14.14
Names and Titles o f persons Radioactive Isotopes

,Business Firms

The G e e b did not use abbreoiations'commonly;

thej?had no instinctfor abbrariating. W e n they
did abbreviate, it was by simple suspension (or
curtailment), usually self-intelligible. 7hepurpose
was ofen to save n u m m u s repeitions in one
document. . . .Gmek abbreviations were not stan-
dardized, but depended on the whim of the scribe.
Herbert Weir smythl

7he use of acronyms and abbreviations works

against clarity, and the confusion is all the gmater
when they varyfrom language to Iurzguage.
Rory watson2

Memam-Webster's Collqiate Dictiotluty defirles an abbreviation a s "a shortened

form of a written word or p h n s e used in place of the \vholcW'( e g . Dr for doctor. IJS
for United States, dB for decikl).
An acronym is "formed from the initial lettar or lerters of each of the successive
parts or major parts of a compound term"' (cg,,\NCOVf\ for analysis of r.ov;~rinncc.)
Acronyn~sarc pronounced as words.

44 1
14.1 Academic Degrees. Certifications, and Honors

An initialism is "an abbreviation formed from initial letters" and pronouncd~

either as a separate word3 (eg, PAHO for Pan American Health Organization) or as a -
-- '

set of consecutive initials (eg, NSF for National Science Foundation).

Overuse of abbreviations can be confusing and ambiguous for readers-
especially those whose first language is not English or those outside a specific spe-
cialty or discipline. However, since abbreviations save space, they may be acceptable
to use when the original word or words are repeated numerous times.
Instructions for authors published in medical and scientific journals may include
guidelines on the use of abbreviations, ranging from "limit of 4 per manuscript" to
"use only approved abbreviations." Authors, editors, manuscript editors, and others
involved in preparing manuscripts should use good judgment, flexibility, and com-
mon sense when considering the use of abbreviations. Abbreviations that some
consider universally known may be obscure to others. Author-invented abbrevia-
tions should be avoided. See specific entries in this section and 15.0, Nomenclature,
for further guidance in correct use of abbreviations.
Note: The expanded form of an abbreviation is given in lowercase letters, unless
the expansion contains a proper noun, is a formal name, or begins a sentence :

(capitalize first word only).

Style for abbreviations used inJAMA and the Archives Journals rarely calls for the:
use of periods. (Buk See 14.6, Names and Titles of Persons.)
, '
Academic Degrees, Certifications, and Honors. The following academic deS
grees are abbreviated in bylines and in the text when used with the full name of a.r;.,- '
person. (See also 14.6, Names and Titles of Persons.) In some circumstances, how-
ever, use of the abbreviation alone is acceptable (eg, Katharine is a doctor of med-
icine and also holds a PhD in biochemistry). (See also 9.5, Plurals, Abbreviations.)
Generally, US fellowship designations (eg, FACP, FAAN, FACS) and honorary
designations (eg, PhDtHon.) are not used in bylines. In contrast, non-US designations
such as the British FRCP and the Canadian PRCPC (attained through a series of
qualifying examinations) should be listed in bylines.
At J A M and the Anhives Journals, for exarnple,.iFan author holds both an FACP
and an FRCPC, the former would be deleted.
Degrees below the master's level (eg, BA, BS) are generally not listed bylines
'
or elsewhere. However, if a bachelor's degree is the highest degree held, it may be .
listed. Exceptions are also made for specialized degrees, licenses, certifications, and
credentials below the master's level in medical and health-related fields (included
below). Any unusual degrees should be verified with the author.
ART accredited record technician
BPharm bachelor of pharmacy
BS, BCh, BC, CB, bachelor of surgery
or ChB
BSN bachelor of science in nursing
CHES certified health education specialist
CIH certified industrial hygienist
!
CNM certified nurse midwife
CNMT certified nuclear medicine technologist
 14.1 Academic degree.^. Certifications, and Honors

certified orthomist
COMT certified ophthalmic medical technologist
CPET certified pulmonary function technologist
CRNA certified registered nurse anesthetist
CRTT certified respiratory therapy technician
m certified tumor registrar
DC doctor of chiropractic
DCh or ChD doctor of surgery
DDS doctor of dental surgery
DHL doctor of humane letters
DMD doctor of dental medicine
DME doctor of medical education
DMSc doctor of medical science
DNE doctor of nursing education
DNS or DNSc doctor of nursing science
DO or OD doctor of optometry
DO. doctor of osteopathy
DPH or DrPH doctor of public health; doctor of public hygiene
DPhann doctor of pharmacy
DPM doctor of pediatric medicine
DSW doctor of social work
DTM&H diploma in tropical medicine and hygiene
DTPH diploma in tropical pediatric hygiene
DVM, DMV, or VMD doctor of veterinary medicine
DVMS doctor of veterinary medicine and surgery
DVS or DVSc doctor of veterinary science
EdD doctor of education
ELS editor in the life sciences
EMT emergency medical technician
EMVP emergency medical technician-paramedic
FCGP fellow of the College of General ~ractitionkrs
FCPS fellow of the College of Physicians and Surgeons
FFA fellow of the Faculty of Anaesthetists
FFARCS fellow of the Faculty of Anaesthetists of the
Royal College of Surgeons
FNP family nurse practitioner
FRACP fellow of the Royal Australian College
of Physicians
14.1 Academic Degrees, Certifications, and Honors -
, .4
FRCGP fellow of the Royal College of General
Practitioners
'RCOG fellow of the Royal College of Obstetricians and
Gynaecologists
FRCP fellow of the Royal College of Physicians
FRCPath fellow of the Royal College of Pathologists
FRCPC fellow of the Royal College of Physicians
of Canada
FRCP(G1asg) fellow of the Royal College of Physicians and
Surgeons of Glasgow qua Physician
fellow of the Royal College of Physicians
of Edinburgh
FRCPI or ~RcP(1re) fellow of the Royal College of Physicians
of Ireland
. FRCR fellow of the Royal College of Radiologists
FRCS fellow of the Royal College of Surgeons
FRCSC fellow of the Royal College of Surgeons
of Canada
fellow of the Royal College of Surgeons .
of Edinburgh
fellow of the Royal College of Physicians and
Surgeons of Glasgow qua Surgeon
fellow of the Royal College of Surgeons
of Ireland
fellow of the Royal College of Veterinary
Surgeons
FRS fellow of the Royal Society
GNP gerontologic or gerianic nurse practitioner
1 '

JD
LLB
doctor of jurisprudence
bachelor of laws
II
LLD doctor of laws ' I
LLM master of laws
LPN licensed practical nurse
LVN licensed visiting nurse; licensed vocational nurse
M(ASCP) '
registered technologist in microbiology
(American Society of Clinical Pathologists) .

MA or AM master of arts
MR or BM bachelor of medicine
MBA master of business administration
>IBRS or ?*ID,BS bachelor of medicine, bachelor of surgery
311) o r 1)\1 doctor of medicine I
.
I
I <

pi
.
. 14.1 Academic Degrees, Certifications, and Honors
!.
MEd master of education
MEA master of fine arts
MHA master of hospital administration
MLS master of .library science
MMM master of medical management
MN master of nursing
MPA master of public administratim
MPH master of public health
MPharm master of pharmacy
MPhil niaster of philosophy
MPPA master of public policy administration
MRCP member of the Royal College of I'hysicians
MRCS member of the Royal College of Surgeons
MS, MSc, or SM master of science
MS, SM, MCh, or MSurg master of surgery
MSN master of science in nursing
MSPH master of science in public health
MStat master of statistics
MSW master of social welfare; master of social work
MT medical technologist
MTA medical technical assistant
MTWCP) registered medical technologist (hinerican
Society of Clinical Pathologists)
master in urban studies
naturopathic doctor
nurse practitioner
OT occupational therapist
om occupational therapist, registered
PA physician assistant
PA< physician assistant, certified
PharmD, DP, or PD doctor of pharmacy
PhD or DPhil doctor of philosophy
PhG graduate in pharmacy
PNP pediatric nurse practitioner
PsyD doctor of psychology
FT physical therapist
RD registered dietitian
RN registerccl nursc
1 4 . 2 US M ~ l ~ r a rServbcm
y and T ~ t l o

registered nurse anesthetist

1
registered nurse, certified

RPh
registered pulmonary function technologist
registered pharmacist
I
RPT registered physical therapist
RRL registered 'record librarian
RT radiologic technologist; respiratory therapist
RTR recreational therapist, registered
ScD, DSc, or DS doctor of science
STD doctor of systematic theology
ThD or DTh doctor of theology
I
Services and Titles. JAMA and the Archives Journals prefer that the
US M i l i t a r y
author's nonmilitary academic degree(s) be used in bylines, eg, Christopher Lee, m,
not Col Christopher Lee, USAF, MC. If used in the text, the abbreviation of a military
service follows a name; the abbreviation of a military title (also called grade or rank)
precedes a name (eg, 1LT Cornelia McNamara, AN, USAR). Military titles and abbre-
viations should be verified with the author (see also 2.2, Manuscript Preparation,
Bylines and End-of-Text Signatures; and 2.2.3, Manuscript Preparation, Bylines and
End-of-Text Signatures, Degrees).

US Military Services

US Army

MC, USA Medical Corps, US Army

ANC, USA Army Nurse Corps, US Army
SP, USA Specialist Corps, US Army
MSC, USA Medical Service Corps, US Anny
DC, USA Dental Corps, US Army
VC, USA Veterinary Corps, US Army

Note: All of the preceding designations also apply to the Army National Guard
(ARNG) and US Army Reserve (USAR).

US Air Force
USAF, MC' , Medical Corps, US Air Force
USAF, NC Nurse' Corps, US Air Force
USAF, MSC Medical Service Corps, US Air Force
USAF, DC Dental Corps, US Air Force
USAF, BSC Bio-Sciences Corps, US Air Force
I.
b. . 14.2.2 US Military Officer Titles (GradesIRanks)
t1
Note: All of the preceding designations also apply to the Air National Guard (ANG)
and US Air Force Reserve (USAFR). The US Air Force has no veterinary corps; vet-
erinarians are in the Bio-Sciences Corps.
I :
!
US Navy iI.
MC, USN Medical Corps, US Navy ii
MSC, USN
NC, USN
Medical Service Corps, US Navy
Nurse Corps, US Navy
(I.
DC, USN Dental Corps, US Navy
Note: AU of the preceding designations also apply to the US Naval Reserve (USNR).

US Military Officer Titles (GradesIRanks)

US Army

General GEN
Lieutenant General LTG
Major General MG
Brigadier General BG
Colonel COL
Lieutenant Colonel LTC
Major MAJ
Captain CPT
First Lieutenant 1LT
Second Lieutenant 2LT
Chief Warrant Officer CWO
Warrant Officer WO

US Navy and US Coast Guard

Admiral ADM
Vice Admiral VADM
Rear Admiral RADM
Captain CAPT
Commander CDR
Lieutenant Commander LCDR
Lieutenant LT
Lieutenant (Junior Grade) LTJG
Ensign ENS '

Chief Warrant Officer cwo

,Vole: All niedical professionals in the US Cox,! Gu:~rd(except physician assistants)
are comnlissioned officers in tllr US l'uhl~ctie.rl~hService (PHs). US Coast Guard
14.3 Days of the Week. Months, Eras

chief wamnt officers In medicine arc deslgmt~-dW O ( h 1 d ) . This also applies to the
US Coast Guard Hexntr.

US Air Force and US Marine Corps

General Gen
Lieutenant General Lt Gen
Major General Maj Gen
Brigadier General Brig Gen
Colonel Col
Lieutenant Colonel Lt Col
Major Maj
Captain Capt
First Lieutenant 1st Lt
Second Lieutenant 2nd Lt

Note: The US Marine Corps does not have its own medical organization. The medical
care of the US Marine Corps is provided by the US Navy.

Days of the Week, Months, Eras. Generally, days of the week and months are not
abbreviated.
The manuscript was received at JAMS editorial offices in late December
2004 and accepted for publication on January 5, 2005, after expedited peer
review, revision, and discussion among the editors. Because of the im-
portance of its topic, the article was published 3 weeks later, on Wednesday,
January 26,2005, as a JM-EXPRESS.
In tables and figures, the following 3-letter abbreviations for days of the weeks and
months may be used to conserve space (see 4.1, Visual Presentation of Data, Tables;
and 4.2, Visual PresenGtion of Data, Figures):
Monday Mon
Tuesday Tue
Wednesday Wed .

Thursday Thu
Friday Fri
Saturday Sat
Sunday Sun

January Jan
February Feb
March Mar
April AP~
May May
June Jun
July Jul
 14.4 Lacal Addresses

August *ug
September Sep
October Oct
November Nov
December Dec

Occasionally, scientific manuscripts may contain discussion of eras. Abbreviations

for eras are set in small capitals with no punctuation. Numerals are used for years and
words for the first through ninth centuries. The more commonly used era designa-
tions are AD (anno Domini, in the year of the Lord), ~c (before Christ), CE (common .
era), and BCE (before -the common era). CE and BCE are equivalent to AD and BC,
respectively. In formal usage, the abbreviation AD precedes the year number, and BC,
a , and BCE follow it.
William Withering was the first to report extensively, in the late 18th century,
on the use of foxglove (Digitalis purpurea) for the treatment of dropsy
(generalized edema).
Hippocrates, a prominent Greek medical practitioner and teacher of the
fourth century BCE, has come to personify the ideal physician.
I
The prevalence of tuberculosis is thought to have increased greatly during
the Middle Ages (roughly AD 500-1500), possibly because of the growth of
towns across Europe.
Cuneiform was probably invented by the Sumerians before 3000 BC.

LO-I~ddressekUse the following abbreviations when complete local addresses

are given:
The hospital was built on Eighth Street.
The hospital's address is 319 W Eighth St.
A In some cases, these designators may or may not be abbreviated, by convention:
Fort Saskatchewan Ft Lauderdale
Mount St Helens Saint Louis

Designator Abbreviation
Air Force Base AFB
Army Post Office APO . .

Avenue Ave
Boulevard Blvd
Building BItlg
Circle Cir
C0llrt Ct
Crescent Cres
Drive llr
E:wt E
14.4 Local Addresses

Fleet Post Office FPO

Fort Ft
Highway H ~ Y
Lane Ln
Mount Mt
North N
Northeast NE
Northwest NW
Parkway Pkwy
Place P1
Post Office PO
Road Rd
Route Rte '

Bural Free Delivery RFD

Rural Route RR
Saint St or Ste (eg, Sault Ste Marie [verify])
South S ..
Southeast SE .

Southwest sw
Square sq
Street ,St
Suite Ste
Terrace Terr
West W

Do not abbreviate non-English address terms (eg, boulevard, avenue, place, rue, via,
Strasse, PlaO. (Note; The translation of such terms can be derived via the ~ntemet.)
Query author for preference of English or non-English address terms.
When the plural form of an address designator is used, do not abbreviate it (eg,
Broadway and Spring streets). When a street number is not given, do not abbrevi-
ate (eg, National Hospital for Neurology and Neurosurgeq Queen Square, London
WClN 3BG, England).
Do not abbreviate room, department (except in references; see 3.13.2, Refer-
ences, Special Print Materials, Government or Agency Bulletins), or dimkion.
Do not use periods or commas with N,S, E, W, or their combinations.
There may be excep.tions to these rules. For example, "One IBM Plaza," "One
Magnificent Mile,'' and "One Gustave L. Levy Place" are not only addresses but also , -:
proper names of buildings or office centers. In these cases it is appropriate to spell
out address numbers that accompany designators suchas "Place." In such cases, the i,
editor or author should use common sense and venfy unusual addresses.
Note: Use e-mail addresses exactly as given. (See also 2.10.4, Manuscript Prep- \
aration, Acknowledgment Section, Correspondence Address, and 10.3.9, Capibli- 1
zation, Proper Nouns, Official Names.)

450

. .

- .. ,. -. - --
. . ... /.- .-..-... -.
. . -.
. - . '. 5: .*?.?
>*?> +v:-g. . ..
.-. .: . .<
'.- . -. .
/: :
. -
?.
, .-
-.. .a
. .-
y .
 14.5 Cities, states. Counties, Territories, Possessions; Provinces; Countries
! .'

,:
Cities. States, Counties, Territories, Possessions: Provinces; Countries. Ar
first mention, the name of a state, territory, possession, province, or country shot~ld
be spelled out when it follows the name of a city. (Because the majority of autl\ors
\, and readers of J A M and the Archives Journals are from the United States. tlirse
journals do not add "United States" after the name of a US city and state. Sirnilsr n~lcs
are followed by other journals. For example, the funcet does not add "United King-
dom" after the name of a UK city.)
Chicago, Illinois Reykjavik, Iceland
Abu Dhabi, United Arab Emirates London, England
Paris, France London, Ontario, Canada
Names of cities, states, counties, territories, possessions, provinces, and countries
should be spelled out in full when they stand alone.
Note Be aware that the names of some cities (and other geographic entities)
have changed (eg, Mumbai instead of Bombay, Chennai instead of Madras, Kolkata
instead of Calcutta, Kyiv instead.of Kiev). The author should be queried as to his or
her preference.
Abbreviations such as "US" and "UK"may be used as modifiers (ie, only when
they directly precede the word they modify) but should 'be expanded in all other
contexts.
The authors surveyed representative samples of urban populations in the
United States and United Kingdom according to US and UK census data.
Use 2-letter abbreviations for US state and Canadian province names in addresses
(with US zip codes and Canadian postal codes) and in reference lists (eg, location of
book publishers) but not in the text. The US state and Canadian province names may
also be abbreviated to save space in tables and figures,
JAMA/ArchivesJournals Editorial Office
515 N State St
Chiczgo, IL 60610
Whitfield JF, Chakravarthy B. Calcium: lie Grand-Master Cell Signaler.
Ottawa, ON: NRC Research Press National Research Council Canada; 2001.
ScottJR,Di Saia PJ, Hammond CB, Spellacy WN,eds. Danforth's Obstetrics &
Gynecology. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1993.
US Postal Service
US State, TTartory, Possession Abbtwiation
Alabama AL
Alaska AK
American Samoa AS
Arizona AZ
Arkansas AR
California CA
Colorado CO
14.5 Cities, States. Counties, Territories, Possessions; Provinces; Countries

Connecticut
Delaware
District of Columbia
Federated States of Micronesia
Florida
Georgia
Guam
Hawaii
Idaho
Illinois
Indiana
Iowa
Kansas
Keptucky
Louisiana
Maine
Marshall Islands
Maryland
Massachusetts
Michigan
Minnesota
Mississippi
Missouri
Montana
Nebraska
Nevada
New Hampshire
New Jersey
New Mexico
New York
North Carolina
North Dakota
Northern Marianas Islands
Ohio
Oklahoma
Oregon
Palau
Pennsylvania
Puerto Rico
 14.5 Cities. States, Counties, Territories. Possessions; Provinces; Countries

Rhode Island
South Carolina
South Dakota
Tennessee
Texas
Utah
Vermont
Virginia
Vigin Islands
Washington -
West Virginia
Wwonsin
Wyoming

Canadian city names should be followed by the provirice name in the text (eg,
London, Ontario, Canada).
1
Canada Post
Canadian Pmuince, Territory Abbreviation
Alberta AB
British Columbia
Manitoba
New Brunswick
Newfoundland and Labrador
Northwest Territories
Nova Scotia
Nunavut
Ontario
Prince Edward Island
. Quebec
Saskatchewan
Yukon

At first mention in the text, the name of the appropriate state or country! should
follow the name of a city whenever clarification of location is thought to be important
for the reader, as in the following examples:
In September 2003 Hurricane Isabel made landfall between Ocracoke ant1
Morehead City, North Carolina.
A new scientific conference created by the International AIDS Society r o c A
place in July 2001 in Buenos Aires, Argentina.
The province name may also be added for less well-known cities:
San Miguel, Hidalgo, Mexico
 -
14 5 Cltln, Stater. Count~er.Territories, possessions; Provinces; countries

I -.
I f the CIY,stare, or country is clear from the context, as in the following examples, do
not include it.
Studies were carried out at the University of Michigan Medical School, Ann
Arbor [unnecessary to add "Michigan"].
A cross-secrional survey assessing bicycle safety helmets was conducted in 3
Dutch primary schools in Breda, Maastricht, and Terneuzen [unnecessary to
add "the Netherlands"].
Illinois' Argonne National Laboratory, located about 50 km west of Chicago,
supports more than 200 research programs and capabilities, ranging from
analytical chemistry of long-lived radioisotopes, to x-ray beam system de-
sign, to global climate change research [unnecessary to repeat "Illinois" after
"Chicago"].
Do not pidvide the state or country name in cases in which the entity is well known
and such clarification is excessive, eg, Chicago White Sox, Philadelphia chromo-
some, Glasgow sign, Uppsala virus, Lyme disease, the Boston Globe.
Do not provide the location of an institution if it is clear that the location is not
important, eg, "Using the Centers for Disease Control and Prevention criteria for!
AIDS.. . " or "Following the World Health Organization guidelines.. . " .
What does it matter that she was born in Boston, or that after her parents had .
instilled in her the guiding principles of life, Harvard University had its turd
In addition to the city name, provide the name of the state or country name in the
author affiliation footnote and correspondence address.
Afiliation Footnote:
Department of Pediatrics, Vanderbilt University School of Medicine, Nash-
ville, Tennessee (Dr Poehling).
Autbor CorrespondenceA d d m :
Katherine A. Poehling, MD,MPH, Department of Pediatrics, Vanderbilt Uni-
versity School of Medicine, AA0216 Medical Center N, Nashville, TN
37232-2504 ([email protected]).
'
Special Case: "New York" may refer to either the city or the state. In the former case,
the state name must be added:.
New York State Psychiatric Institute, New York
New York University, New York, NY
When giving the location of an institution or organization whose formal name in-
cludes a city, do not insert the state or country within the name:
Correct: Stanford University School of Medicine in California
Also correct: Stanfbrd University School of Medicine, Stanford, California
Not: Stanford University School of Medicine (California)
And not: Stanford (California) University School of Medicine
 14.5 Cities, States, Counties, Territories, Possessions; Provinces; Countries

The style used in the foregoing correct examples may be applied in signature bylines:
Correct: Remy I. Smith, MD
stanford University School of Medicine
Stanford, California.
Not: Remy I. Smith, MD
Stanford (California) University School of Medicine

The following are examples of address style for many countries throughout the world
(see also 2.0, Manuscript Preparation, and 14.4, Local Addresses).
Andrzej Szczewi, PhD, Allergy and Immunology Clinic, Department of
Medicine, Jagellonian University School of Medicine, ul Skawinska 8, i
31-0666 Krakow, Poland. 1
Vivek Goal, Department of Health Administration, McMurrich Rldg. 12
Queen's Park Cres W, Toronto, ON M5S 1A8, Canada.
1
;

Alain F. Broccard, MD,Division des Soins Incensifs, Department de MCcle-

cine, BH10-92, University Hospital (CHUV), CH-1011 Lausanne, Switzerl;incl.
N. J. Bouwmeester, MR, Department of An;lesthesioiogy and 13ac.tliatrk.
Surgery, Sophia Children's ~ospital,University Hospital Hottert1;un. Ilr
Molewaterplein 60,3015 GJ Rotterdam, the Netherlands. i
Konstantinos I. Gourgoloulianis, Pulmonary Department, Medical School,
University of Thessaly, 22 Papakyriazi, Tarissa 41222, Greece.
Didier Blaise, MD,Unit6 de Transplantation et d e Therapie Cellulare, Institut
Paoli-Calmettes, 232 Bd Ste Marguerite, 13273 Marseille CEDEX 09, France.
1.
Ruben Terg, Unidad de Hepatologia, Hospital de Gastroenterologia Uo-
norino Udaondo, Escuela de Medicina, Universidad del ~aivador,Avenida
Caseros, 2061 (1264) Buenos Aires, Argentina.
Ditlev Fossen, Department of Obstetrics and Gynecology, County Hospital
of Oestfold (Sykenhuset Oestfold), 1603 Fredrikstad, Norway.
Hajime Fujimoto, MD, Third Department of Internal Medicine, Respiratory
Division, Mie University School of Medicine, Edobashi 2-174, Tsu City, Mie
514-8507, Japan.
K*ang Hyun Kim, MD, Department of Otola~yngology-Head and Neck
Surgery, Seoul National University, College of Medicine, 28 Tongon-Dong,
<.<
Chongno-Gu, Seoul 110-744, Korea. !r,:,
Colin L. Masters, MD, Department of Pathology, University of Melbourne,
Parkville, Victoria, Australia 3010.
Thomas Schwarz, Division of Vascular Medicine, Department of Internal
Medicine. University ~ospitalof Dresden kledical School, Fetscherstrasse 74,
01307 Dresden, Germany.
David M Fcrpuswn. Christchurch Hcalth and Development Study,
Chr~srct~~lrr
11 ';c hgu I ' l,.'licinch.1'0 I1(.s-i?..;i.
Cl~ristchurcll,N e ~ k Zealand.
.
14.6 Namer and T ~ t l e of
l Pcrconr

Jd),
~\ILII,J [)cp;lnnicnt of O~orhinolaryn~ology and Head and Neck Sur-
Unit 1, Christian M e d i a l College, Vellore 632 004, India.
~ C Q .

Neville K. Osborne, DSc, Nuffield Laboratory of Ophthalmology, Walton

Street, Oxford OX2 6AW, England.
Yasemin Giles, MD, Istanbul Tip Fakijltesi, Gene1 Cerrahi ABD, Capa;
Topkapi, Istanbul, Turkey 34390.
Shurong Zheng, Department of Obstetrics and Gynecology, Peking Uni-
versity First Hospital, Beijing 100034, China.
Alfred Cuschieri, MD, FRSE, Department of Surgery and Molecular Oncol-
ogy, Ninewells Hospital and Medical School, University of Dundee, Dundee
DD1 9SY, Scotland.
J. Skordis, Department of Public Health and Policy, London School of Hy-
giene and Tropical Medicine, Keppel Street, London WClE 7HT, England.
Gar-Yang Chau, MD, MPH, Division of General Surgery, Department of
Surgery, Taipei Veterans General Hospital, 201 Shih-Pai Rd, Section 2, Tai-
pei, Taiwan 11217.
Two- and three-letter IS0 (International Organization for Standardization) country
codes may also be used in addresses. These codes are updated regularly by the RIPE I
Network Coordination Centre, in coordination with the IS0 3166 Maintenance -
Agency, Berlin, Germany (list available at http://userpage.chernie.fu-berlin.de
/diverse/doc/IS0~166.html).

Names and Titles of Persons. Given names should not be abbreviated in the text
or in bylines except by using initials, when so indicated by the author. The editor
should verify the use of initials with the author. (Some publishers prefer to use
initials, instead of given names.)
Do not use Chas., Geo., Jas.,Wm.,-etc, except when such abbreviations are part
of the formal name of a company or organization that regularly uses such ab-
breviations (see 14.7, Business Firms). When an abbreviation is part of a person's
name, retain the period after the abbreviation, eg, Oliver St. John Gogarty, MD.
Initials used in the text to iridicate names of persons (eg, coauthors of an article)
should be followed by periods and set close within parentheses. Note: This is one of
the few instances in which a period is used with an abbreviation.
A method was devised to calklate familial risk (K.A.R., unpublished ob-
servations, 2006).
A person who is not an author may also be mentioned in the text, in which case the
I
full name and academic degree are used.
'

I
Although measurements of the various components were divided among 3
examiners (R.Z., D.O.M., and Norris T. Friedlin, MD), each examiner mea-
sured the same components at each annual session.
Senior and junior are abbreviated when they are part of a person's name. The ab-I'
breviation follows the surname and is followed by a comma only when the'
 14.6 Names and Titles of Persons

abbreviationprecedes another, such as an academic degree. (But See 19.7.5, Numbers ,

and Percentages, Forms of Numbers, Roman Numerals, and 3.7, References,Authors.)

Note: These abbreviations are used only with the full name (nalerDr Forsythe Jr).
Peter M. Forsythe Jr, MD, performed his landmark research in collaboration
with James Phiiips Sr, PhD, at the National Institutes of Health.
Names with roman numerals do not take a comma: Pope Benedict XVI, Marshall
Field N.
. Many titles of persons are abbreviated but only when they precede the full name
(given name or initials and surname). Spell titles out (except Dr, Mrs, etc) when (1)
used before a surname alone (except in some cases as described below), (2) used at
the beginning of a sentence, and 8 used after a name Ci this instance, the title
should not be capitalized). (But: See also 14.2, US Military Services and Titles.)
ColonelJonas
COL M i n d a Jonas, MC, USA
Dr Jonas, colonel in the army
Alderman Daley
Ald Vi Daley
Vi Daley, alderman of the 43rd Ward of Chicago
Father Doyle.
Fr Raymond G. Doyle
Raymond G. Doyle, SJ
Governor Blagojevich
Gov Rod ~lagojevich
Rod Blagojevich, governor of Illinois
Representative ~ c ~ e r m o t t
Rep Jim McDermott
Jim McDermott, MD, representative from the state of Washington
Senator Obama
Sen Barack Obama (D, Illinois)
Barack Obama, US senator from Illinois
Sister Monica
Sr Monica Sobieski
Monica Fbieski, SJC, mother superior
Superintendent Smith
Supt H. B. Smith
Henry B. Smith, EdD, superintendent of schools
the Reverend Katharine M. Burke
the Reverend Dr Burke
R w Katharine M. Burke

o r Rev is used only when the first name or initials are

Nore 7he R a w ~ z dRe~lerend,
,
gtvrn wrth the surname. When only the surname a gtvcn, use [he Ret~mtzdMr(or Ms
or Dr), .\ir ((jr .tfs or Dr), o r Father (Roman Carhol~cand wrne Pro[c.stant denorni-
natw>n\) Never use rhc Rmwend Brvr~m.Rmre~tdBmrt3n.or Rev Bmriln
14.8 Agencies and Organizations

Exception, Heads of Stare: &-idenr is nor abbrevbted. It is cxplralized when rr

precedes a name and is set lowercase when following a name (see also 10.3.10,
Capitalization, Proper Nouns, Titles and Degrees of Persons):
President John F. Kennedy
President and Mrs Kennedy
John F. Kennedy, president of the United States
the president
The following social titles are always abbreviated when preceding a surname,with or
without first name or initials: Dr, Mr, Messrs, Mrs, Mmes, Ms, and Mss. Note that in
most instances, the title Dr should be used only after the specific academic degree
has been mentioned and only with the surname.
Pirthur L. Rudnick, MD, PhD, gave the opening address. At the close of the
meeting, Dr Rudnick was named director of the committee on sports injuries.

Business Firms. In the text, use the name of a company exactly as the company uses
it, but omit the period after any abbreviations used, such as Co, Inc, Corp, and Dd. In
I
the text, do not abbreviate these terms if the company spells them out, eg, Sandoz
Pharmaceuticals Corporation. Note that in the text, periods are used with a company
namesake's initials.
However, to conserve space in references, abbreviate Company, Corporation,
Brothers, Incorporated, Limited, and and (using an ampersand [&I), without punc- .

Nation, even if the company expands them, and delete periods even with initials, in
accordance with the following examples; and delete 7be in publishers' names. (See
also 3.12.9, References, References to Print Books, Publishers; and 15.5, Nomen-
clature, Equipment, Devices, and Reagents.)
Text Styk Reference Style
Farrar, Straus & Giroux Farrar Straus & Giroux
B. C. Decker BC Decker
American Mensa, Ltd American Mensa Ltd
I
HarperCollins Publishers
The Free Press -
HarperCollins Publishers
Free Press
. II
Agencies and Organizations. Many organizations (eg, academies, associations,
government agencies, research institutes) are known by abbreviations or acronyms
rather than by their full names. Some of these organizations have identical abbrevi-
ations (eg, AHA for both American Heart Association and American Hospital Asso-
ciation). Therefore, to avoid confusion, the names of all organizations should be
expanded at first mention in the text and other major elements of the manuscript,
with the abbreviation following immediately in parentheses, in accordance with the
guidelines offered in 14.41, Clinical, Technical, and Other Common Terms.
The article the is often used with abbreviated forms of agencies and organiza-
tions (eg, the UN, the AMA, the FDA); however, an article is not necessary with forms
pronounced as words (eg, NASA, OSHA, WAME).
The following are associations and organizations commonly,cited injAMA and
the Archives Journals. This list is intended to show examples and is not all-inclusive.
 14.8 Agencies and Organizations

Because there are other expansions of some of the abbreviations, authors and editors
should venfy that the expansion is correct in such instances.
AAAAI
American Academy of Allergy, Asthma, and Immunology
AAAS
American Association for the Advancement of Science
AABB
American Association of Blood Banks
AAW .
American Academy of Child and Adolescent Psychiatry
AACC
American Association of Clinical Chemists
AACLA
American M a t i o n for Clinical Immunology and Nlergy
AACN
American Association of Colleges of Nursing
American Association of Critical-Care Nurses
AAD
American Academy of Dermatology
AAFP
American Academy of ~ a m iPhysicians
l~
AAFPRS
American Academy of Facial Plastic and Reconstructive Surgery
AAHSLD
Association of Academic Health Science Library Directors
AAI
American Assocfation of Immunologists
AAMC
Association of American Medical Colleges
AAMCH
American Association of Maternal and Child Health
AAN
American Academy of Neurology
American Academy of Neuropathologists
American Academy of Nursing
AANA
American Association of Nurse Anesthetists
AANP
American ~ c a d e m yof Nurse Practitioners
14.8 Agencies and Organizations

AANS
American Association of Neurological Surgroiu
AAO
American Academy of Ophthalmology
AAOHNS
American Academy of Otolaryngology-Head and Neck Surgery
AAOS
American Academy of Orthopaedic Surgeons
AAP
American Academy of Pediatrics
American Association of Pathologists
AAPA
American Academy of Physician Assistants
American Association of Pathologists' Assistants
pApHp
American Association of Public Health Physicians
AAPM
American Academy of Pain Medicine
American Association of Physicists in Medicine
AAPMR
American Academy of Physical ~ e d i c i n eand Rehabilitation
AAPS
American Association of Plastic Surgeons
AARP
American Association of Retired Persons
AATM
American Academy of Tropical Medicine
AATS
American Association for Thoracic Surgery
AAUP
American Association of University Professors
AAWR
American Association for Women Radiologists
ABA
American Bar Association;
ABMS
American Board of Medical Specialties
ACA
American College of Allergists
American College of Anesthetists
 14.8 Agencies and Organizations

ACAAI
American College of Allergy, Asthma, and I~n~nunology
ACC
American College of Cardiology
ACCME
Accreditation Council for Continuing Medical Education
ACCP
American College of Chest Physicians
ACEP
American College of Emergency Physicians
ACG
American College of Gastroenterology
ACGME
Accreditation Council for Graduate Medical Educati~n
ACHA
American College Health Association
ACHE
American College of Hospital Executives
AClP
Advisory Committee o n Immunization Practices
ACLM
American College of Legal Medicine
ACMQ
American College of Medical Quality
ACNM
American College of Nuclear Medicine
American College of Nurse-Midwives
ACNP
American College of Nuclear Physicians
ACOEM
American College of Occupational and Environmental Medicine
ACOG
American College of Obstetricians and Gynecologists
ACP
American College of Physicians
ACPE
American College of Physician Executives
ACPM
American College of Preventive Medicine
 .--

14.8 Agencies a n d Organizations

ACK
American College of Radiology
American College of Rheumatology
ACS
American Cancer Society
h ~ e r i c a nchemical Society
Amcican College of Surgeons
ACSM
American College of Sports Medicine
ADA
American Dental Association
American Dermatological Association
American Diabetes Association
American Dietetic Association
ADRDA
~lzheirner'sDisease and Related Disorders Association
AERS
Adverse Event Reporting System
(US Food and Drug Administration)
AES
American Epilepsy Society
AFAR
American Federation for Aging Research
AFCR
American Federation for Clinical Research
AFIP
Armed Forces Institute of Pathology
AFS
American Fertility Society
AGA
American Gastroenterological Association
AGPA
American Group Practice Association
AGS
American Geriatrics Society
AHA
knerican Heart Association
American Hospital Association
AHRA
American Healthcare Radiology Administrators
 -.
. . . . ..

14.8 Agencies and Organizations

AHRQ
Agency for Healthcare Research and Quality
AJCC
American Joint Committee on Cancer
ALA
American Library Association
American Lung Association
ALROS
American 'aryngological, Rhinological and Otological Society
AMA
Aerospace Medical Association
American Management Association
American Marketing Association
American Medical Association
Australian Medical Association
AMDA
American Medical Directors Association
AMPA
American Medical Publishers' Association
AMSA
American Medical Student Association
AMSUS
Association of Military Surgeons of the United States
AMWA
American Medical Women's Association
American Medical Writers Association
ANA
American Neurological Association
American Nurses Association
ANSI
American National Standarcls Institute
AOA
Alpha Omega Alpha
American Orthopaedic Association
American Osteopathic Association
AOMA
American Occupational Medicine Association
AONE
American Organization of Nurse Execi~tives
AORN
A%sociationof Operating Room Nurses
14.8 Agenc~erand O f g a n l Z d t i ~ n ~

:IOS
American Orologicai Society
AOWHN
American Organization of Women's Health Nurses
AIJA
Ambulatory Pediatrics Association
American Pharmaceutical Association
American Psychiatric Association
American Psychological Association
AF'HA
American Public Health Association
APM
Academy of Physical Medicine
APS
American Physical Society
American Physiological Society
American Psychological Society
ARA
American Rheumatism Association
ARC
American Red Cross
ARENA
Applied Research Ethics National Association
ARRS
American Roentgen Ray Society
ARVO
Association for Research in Vision and Ophthalmology
ASA
American Society of Anesthesiologists
ASAM
American Society of Addiction Medicine
ASCN
American Society of Clinical Nutrition
AS20
American Society of Clinical pncology
American Society of Clinical Ophthalmology
ASCP
American Society of Clinical Pathologists
American Society of Consultant Pharmacists
ASCI'T
American Stxicry of Clinic21 Pharmacology and Therapeutics
 14.8 Agencies and Organizations

ASCRS
American Society of Cataract and Refractive Surgery
American Society of Colon and Rectal Surgeons
ASDR
American Society of Diagnostic Radiology
ASDS
American Society for Dermatologic Surgery
ASG
American Society for Genetics
ASGE
American Society for Gastrointestinal Endoscopy
ASHG
American Society of Human Genetics
ASLME
American Society of Law, Medicine & Ethics
ASM
American Society for Microbiology
ASMT
'

American-Society of Medical Technologists

ASPRS
American Society of Plastic and Reconstructive Surgeohs
m o
Association of State and Territorial Health Officers
ASTMH
American Society of Tropical Medicine and Hygiene
A m 0
American Society for Therapeutic Radiology and Oncology
ASTS
American Society of Transplant Surgeons
ATA
American Thyroid Association
ATS
American Thoracic Society
AUA
American Urological Association
BMA
British Medical Asxxiation
8 Agencies and Organ~zatlons

CDC
Centers for D w a x Control and ~rmenriJn
ChZA
Canadian Medical Association
CMS
Centers for Medicare & Medicaid Services
CNS
Child Neurology Society
CSE
Council of Science Editors
DHHS
Department of Health and Human Services
EASE
European Association of Science Editors
ECDC'
European Centre for Disease Prevention and Control
ECFMG
Educational Commission for Foreign Medical Graduates
EEOC .
Equal Employment Opportunity Commission
EIS
Epidemic Intelligence Service
(US Centers for Disease Control and Prevention)
EPA
Environmental Protection Agency .
EU
European Union
FASEB
Federation of American societies for Experimental Biology
FCC
Federal Cornmupications Commission
FDA
Food and Drug Administration
FTC
Federal Trade Commission '

GLMA
Gay and Lesbian Medical Association
GSA
Gerontological Society of America
 14.8 Agencies and Organizations

IARC
International Agency for Research on Cancer
ICAAC
Interscience Conference on Antimicrobial Agents and Chemotherapy
ICMJE
Intemational committee of Medical Journal Editors
ICN
International Council of Nurses
ICRC
Intemational Committee of the Red Cross
ICS
International College of Surgeons
IDSA
Infectious Diseases Society of America
IEEE
Institute of Electrical and Electronics Engineers
IOM
Institute of Medicine
IPPNW
International Physicians for the Prevention of Nuclear War
ISBT
International Society of Blood Transfusion
IS0
Intemational Organization for Standardization
JWO
Joint Commission on Accreditation of Healthcare Organizations
MGMA
Medical Group Management Association
MLA
Medical Library Association
MRC'
Medical Research Council
MSF
MCdecins Sans Frontitres
NAME
National Association of Medical Exarn~ncr.,
NAMS
North American Menopause k ~ i r t !
8 Agencies and Organizations

NAS
National Academy of Sciences
NASA
National Aeronautics and Space Administration
NBME
National Board of Medical Examiners
NCBI
National Center for Biotechnology Information
NCCAM
National Center for Complementary and Alternative Medicine
NCHS
National Cezter for Health Statistics
NCI
National Cancer Institute
NCOA
National Committee o n Quality Assurance
NCRR
National Center for Research Resources
NEI
National Eye Institute
NHGIU
National Human ~ e n o m kResearch Institute
. NHLBI
National Heart, Lung, and Blood Institute
NHO
National Hospice Organization
NIA
National ~nstituteon Aging
NIAAA
National Institute on Alcohol Abuse and Alcoholism
. NIAID
National Institute of Allergy and Infectious Diseases
NIAMS
National Institute of Arthritis and Musculoskeletal and Skin Diseases
NIBIB
National Institute of Biomedical Imaging and Bioengineering
NICHD
National Institute of Child Health and Human Development
 14.8 Agencies and Organizations

MDA
National Institute on Drug Abuse
MDCD
National Institute on Deafness and Other Communication Disorders
NIDCR
National Institute of Dental and Craniofacial Research
MDDK
National Institute of .Diabetesand Digestive and Kidney Diseases
MEHS
National Institute of Environmental Health Sciences
MGMS
National Institute of General Medical Sciences
MH
National Institutes of Health
NIMH.
National Institute of Mental Health
NINDS r:

National Institute of Neurological Disorders and Stroke '.'

NINR
National Institute of Nursing Research
MOSH
National Institute for Occupational Safety and Health
NISO
National Information Standards Organization
NLM
National Library of Medicine
NLN
National League for Nursing
NMA
National Medical Association
NM~A
National Mental Health Association
mc
National Research Council
Nuclear Regulatory Commission
NRMP
National Resident Matching Program
NSF
National Science Foundation ,
.8 Agencies and Organizations

NSPB .
National Society for the Prevention of Blindness
OMAR
Office of Medical ;\pplications of Research
ONS
Oncology Nursing Society
OPRR
Office for Protection From Research Risks
ON
Office of Research Integrity
ORWH
Office of Research on Women's Health
OSHA
Occupational Safety and Health Administration
PAHO
Pan American Health organization
PHR
Physicians for Human Rights
PHs
Public Health Service
PSR
Physicians for Soda1 Responsibility
PSRO
Professional ~t&dardsReview Organization
RDCRN
Rare Diseases Clinical Research Network
RPB
Research to Prevent Blindness
RSNA
Radiological Society of North America
Rehabilitation Society of North America
SAMBA
Society for Ambulatory Anesthesia
SAMHSA
Substance Abuse and Mental Health Services Administration
SCCM
Society of Critical Care Medicine
SEC
Securities and Exchange Commission
 14.8 Agencies and Organizations

SID
Society for Investigative Dermatology
SMCAF
Society of Medical Consultants to the Armed Forces
SNM
Society of Nuclear Medicine
SSA
Social Security Administration
SSO
Society of Surgical Oncology
SSP
Society for Scholarly Publishing
STC
Society for Technical Communication
STS
Society of ~horacicSurgeons
UICC
Internationd Union Against Cancer (Union Internationale Contre le Cancer)
UN
United ~ a t i o k
UNHCR
United Nations High Commissioner for Refugees
UNICEF
United Nations Children's Fund
UNOS
United Network for Organ Sharing
USAN
United States Adopted Names [Council]
VA
Department of Veterans Affairs
w m
World Association of Medical Editors
WFP
World Food Program
WHO
World Health Organization
WIC
Special Supplemental Nutrition for Women, Infants, and Children
14 10 N a m e of Journals

U'hlA
World Medical Association
For more detailed listings of US and international agencies and associations, consult
the current editions of The Official American Board of Medical Specialties (ABMS)
Directory of Board Certified Medical Specialists, i%e United States Government Man-
.:I .
ual, Federal Yellow Book, Congressional Yellow Book, Encyclopedia of Associations,
Directory of European Medical Organisations, Directory of European Professional G
Learned Societies, Civil Senrice Yearbook, 7be Medical Registv,, and The World of
Learning.
There are thousands of directories of Web sites, ranging from the official (eg, US
Executive Branch Web Sites at hap://www.loc.gov/nr/news/fedgov.html) to com-
mercial, private, and nonprofit (eg, http://directory.google.com/).

Collaborative Groups. Collaborative groups include study groups, multicenter

trials, task forces, expert and ad hoc consensus groups, and periodic national and
internatio~alhealth surveys. Such an entity's full name should be provided in addi-
tion to its abbreviation, even if it appears only once in a manuscript. Because some of
these groups are often better recognized by their acronyms than by their hlI names,
the acronym may be placed first, with the expansion in parentheses, contrary to the
order usually recommended.
To save space in titles, however, the acronym may be used alone if its expansion.
is provided early in the manuscript, for example, in the abstract and in the text.
Alternatively, the acronym might be given in the manuscript's title and the expansion
in its subtitle; or, if space permits and both the expansion and the acronym convey
separate and essential concepts, both could be given in the title or subtitle. The
collaborative group name may be used as the byline. (See also 5.1.7,Ethical and
Legal Considerations, Authorship Responsibility, Group and Collaborative Author-
ship; 2.2, Manuscript Preparation, Bylines and End-of-Text Signatures; and 2.10.6,
Manuscript Preparation, Acknowledgment Section, List of Participants in a Group
Study.)
Title: Fluoxetine, Cognitive-Behavioral Therapy, and Their
Combination for Adolescents With Depression
Subtitle: Treatment for Adolescents With Depression Study (TADS)
Randomized Controlled Trial
Byline: Treatment for Adolescent. With Depression Study (TADS) Team
Consider the manuscript's context and audience, database searches, and ease of
comprehension when choosing the form in which collaborative group information is '

presented. Remember that many literature databases contain only the title and article
citation; some, but not all, also provide the abstract.

Names of Journals. In reference listings, abbreviate names of journals according to

the US National Library of Medicine's current Fact Sheet (Construction of National
Library of Medicine title abbreviations at http://www.nlm.nih.gov/pubs/factsheets
/constructitle.html). Journal names are italicized. In references, the journal-name
abbreviation is followed by a period, which denotes the close of the title group of
bibliographic (See also 3.11.2, References, References to Print Journals,
Names of Journals.)
 14.10 Names of Journals
1

The following commonly referenced journals and their abbreviations are in-
cluded in Abridged Index Medicus. Abridged Index Medicus is no longer published,
but it is a subset limit (Core Clinical Journals) within PubMed. In this list, the article
l%ehas been omitted in the expanded journal titles (as in 73eJournal of.. .1. Single-
word journal titles are not abbreviated. . I

Academic Medicine (formerly Journal of Medical Education, abbreviated

J Med Educ)
Acad Med
i:
A p American J~urnalof Roentgenology
AJR ~m J ~oen&nol
American ~ a r n i Physician
b
Am Fam physician
American Heart Journal
Am Heart J
American Journal of cardiology
Am] Cardiol
American Journal of Clinical Nutrition
Am j Clin Nutr
American Journal of Clinical Pathology
Am J Clin Pathol
American Journal of the Medical Sciences
Am J Med Sci
American Journal of Medicine
Am JMed
American Journal of Nutsing
Am J Nun
American Journal of Obstetrics G Gynecology
Am J Obstet Gynecol
American Journal of Ophthalmology
Am J Ophthalmol
American Journal of Pathology
Am jPathol
American Journal of Physical Medicine & Rehabilitation/Association
of Academic Physiarrists
Anz J Phys Med Rchabil
 ---
4 10 N a m e of Journals

.4nrmian jounrtrl uJh'~3p1rutory

utrd Critical Care Medicine
.iJ h'~3'plrCnl Care Med

Americat~Jounlrrl of Surgery
Anr J Surg
American Journal of Tropical Medicine and Hygiene
Anz J Trop Med Hyg
Anaesthesia
Atzaesthesia
Anesthesia and Analgesia
Anesth Analg
Anesthesiology
Anesthesiology
Annals of Emmency Medicine
Ann Emerg Med
~ n L l ofs Internal Medicine
Ann Intern Med
Annals of Otology, Rhinology, 6 Gtyngology
Ann Otol Rhino1 Latyngol
Annals of Surgery
Ann Surg
Annals of Thoracic Surgery
Ann n o r a c Surg
Archives of Dermatology
Arch Dennatol
Archives of Disease in Childhood .
Arch Dis Child
Archives of Disease in Childhood. Fetal and Neonatal Edition
Arch Dis Child Fetal Neonatal Ed
Archives of Environmental ~ e b l t h
Arch Environ Health
Archives of General Psychiatry
Arch Gen Psychiatry
Archives of Internal Medicine
Arch Intern Med
a .

Archives of Neurology
Arch Neurol
Archives of Ophthalmology
Arch Ophthalmol
 14.10 Names of Journals

Archives of Otolatyngology-Head E. Neck Surgery

Arch Otolaryngol Head Neck Surg
Archives of Pathology &LaboratoryMedicine
Arch Path01 Lab Med
Archiues of Pediatrics &AdolescentMedicine (formerly American jounzal
of Diseases of Children, abbreviated A m ] Dis Child)
Arch Pediatr Adolesc Med
Archives of Physical Medicine and Rehabilitation
Arch Phys Med Rehabil
Archives of Surgery
Arch Surg
Arthritis G Rheumatism
Arthritis Rheum
BJOG (continues British Journal of Obstetrics and Gynaecology)
BJOG
Blood
Blood
BMJ British Medical Association (formerly British MedicalJottrnal,
abbreviated Br MedJ)
BMJ
Brain; A Journal of Neumlogy
Brain
. British Journal of Radiology
BrJ Radio1
British Journal of Surgety
BrJ Surg
CA:A CancerJournalfor Clinicians
CA CancerJ Clin
Cancer
Cancer
Chest a

Chest
Circulation
Circulation
Clinical Orthopaedics and Rcln!~~l
Research
Clin Ofthop
14.10 Names of Journals

CMAj (formerly Canadian bfedical Arsociar~onJournuf,abbrrvurttd

Can Med Assoc J )
M J
Critical Care Medicine
Crit Care Med
Current Problems i n Surgety
Curr Probl Surg
Diabetes
Diabetes
Digestive Diseases and Sciences
Dig Dis Sci
Disease-a- on th
Dis Mon
Endocrinology
Endocrinology

Geriatrics
Geriatrics
Gut
Gut
Heart
Heart
Heart G Lung; TheJournal of Critical Care
Heart Lung
Hospitak 6 Health XVecworks/AHA (formerly~ o s p i f a k )
H w Health Netw
J M : i%eJournal of the Amenencan
Medical Association
J M
Joumal of Allergy and Clinical Immunology
J Allergy Clin Zmmunol
Joumal of the American College of Cardiology
J A m Coll Cardiol
Journal of the American Cdlege of Surgeons (formerlySurgety, GynecologyG
Obstetrics,abbreviated Surg Gynecol Obstet)
J Am Coll Surg
Journal of the Amm'can Dietetic Association
J Am Diet Assoc
Journal of Bone &Joint Surgety. American Volume
J Bone Joint Surg Am
I 14.10 Names of Journals

Journa 1 of Bone G Joint Surgery. British Volume

J Bone Joint Surg Br
Journal of Clinical Endocrinology &Metabolism
J CIin Endocrinol Metab
Journal of Clinical Investigation
J Clin Invest
Journal of Clinical Pathology
J Clin Path01
Journal of Family Practice
J Fam Pract
-Journalof Immunology
J Immunol
Journal of Infectious Diseases
J Infect LXs
Journal of Laboratory and Clinical Medicine
J Lub Clin Med
Journal of Latyngology G Otology
J Laryngol Otol
Journal of Nentous and Mental Msease
JNemMent DZs .
Journal of Neurancrgey
a JNeumurg
Journal of Nudng Administration
J Nuts Adm
Journal of Oral and Mamamllofacial
Surgery
J Oral Maxillofac Surg
Journal of Pediatrics
J Pediatr
Journal of i%oracic and Cardiovascular Sulge y
J i%orac Cardiovasc Surg
J o u m l of Toxicology. Clinical Toxicology
J Tmicol Clin Toxic01
Journal of Trauma
J Trauma
Journal of Urology
J Urol
Journals of Gerontology. Series A, Biological Sciences artd Medical Sciolcc~.\.
J Gmntol A Biol Sci Med Sci
I Names of Journals

Journals of Gerontology.Series 8,Psychological Sciences and Sxwl k ~ e t l ~ . t . s

J Gerontol B Psycho1 Sci Soc Sci
Lancet
Lancet
Mayo Clinic Proceedings
Mayo Clin Proc
Medical Clinics of North AmeriGa
Med Clin North Am
Medical Letter on Drugs and l%wapeutics
~ e Lett
d Drugs Tber
Medicine; Analytical RmeU2ews
of 5eneral Medicine, Neurology, Psychiatry,
Dermatology, and Pediatrics
Medicine (Baltimore)

New England Journal of Medicine

N Engl J Med
Nursing Clinics of North America
Nurs Clin North Am
Nursing Outlook
N u n Outlook
Nursing Research
N u n Res
Obstetrics G Gynecology
Obstet Gynecol
Urthopedic Clinics of North Arnm'ca
Orlhop Clin North Am
Pediatric Clinics of North America
Pediatr Clin North Am
Pediatrics
Pediatrics
Physical nerapy
Phys iSber
Plastic and Reconstructive Surgery
Plat Reconstr Surg
Postgraduate Medicine
Postgrad Med
Progress in Cardiov~cularDiseases
Prog Cardiouasc Dis
 14.10 Names of Journals

Public Health Reports

Public Health Rep
I
Radiologic Clinics of North America
Radio1 Clin North Am
Radiology
Radiology
Southern Medical Journal
South Med J
surgery
surgw
Surgical Clinics of North America
Surg Clin North Am
Urologic Clinics of North Amenenca
Urol Clin North Am
The National Library of Medicine's (NLM's) abbreviationsused in MEDLINE are based
on the American Nationul Standardfor Information Science+Abbreuiation of Titles
of Publications (ANSI 239.5) (1985), as well as abbreviations formulated under
earlier ANSI guidelines. Use the following guide to abbreviate or not abbreviate
words that may appear in journal titles. (Single-word journal titles are not abbrrvi-
ated.) Note that these words are capitalized and that articles, conjunctions, prepos-
itions, punctuation, and diacritical marks are omitted in the abbreviated title form.
The NLM's database can be searched by means of the journal title, the MEDLINE/
PubMed title abbreviation, the NLM ID (NLM's unique journal identifier), the IS0
(International Organization for Standardization) abbreviation, and the print and
electronic International Standard Serial Numbers (pISSNs and eISSNs).
The correct abbreviations of journal titles indexed in M E D L I I can
~ 'also be
located through PubMed ('IToumals") access.
Word Abbreviation or Word Used
Abnormal Abnorm
Abuse Abuse
Academia Acad
Academy Acad
Acoustical Acoust
Actions Actions
Acupuncture Acupunct
Acute Acute
Addiction Addict
hclclictions Addict
:\(i~!itives Addit
:!drn~nistrat~on Adm
:\<I\
,It.zcc.ncc Adnlcs( cncc
14.10 Names of Journals

Adolescent Adolesc
~dvanced Adv
Advancement Adv
Advances Adv
Adverse Adverse
Aesthetic Aesthetic
Affairs ,
Af f
Affective Affective
African Afr

Age Age
Ageing Ageing
Agents Agents
Aging
~ i r Air
Alabama Ala
Alaska Alaska
Alcohol Alcohol
Alcoholism ~lcohol
Allergy Allergy
Allied Allied .
America Am
American Am
Anaesthesia haesth
Anaesthetist haesthetist
Anaesth
Analgesia Analg
Anatomical Anat
Anatomy Anat
Andrology Androl
Anesthesia ~nesth
Anesthesiology hesthesiol
Angiology Angiol

Angle Angle
!. nimal
Anim
Ankle Ankle
Annals Ann
Annual Annu
Anthropology Anthropol
Antibiotics htibiot
 - .

14.10 Names of Journals

Anticancer. Anticancer
Antigens Antigens
Antimicrobial Antimicrob
Antiviral Antiviral
Apheresis Apheresis
Appetite Appetite
Applied APP~
Archives Xrch
Argentina Argent
I .
Arizona Ariz
Arkansas Ark
m y m y
Arteriosclerosis Arterioscl
Artery Artery
Arthritis Arthritis
Artificial Artif
Asian Asian
Assessment Assess
Association Assoc
Asthma Asthma
Audiology Audio1
Audiovisual Audiov
Auditory Aud
Australia Aust
Australian Aust
Autism Autism
Autonomic Auton
Avian Avian
Aviation Aviat
Bacteriology Bacteriol
Bangladesh Bangladesh
Basic Basic
Behavior Behav
Behavioral Behav
Behaviors Behav
Biochemical Biochem
Biochemistry Biochem
Biocommunications Bioconim
Biofeedback Biofeedback
14 1 0 N a m e of Journals

Biological Biol
Biology Biol
Biomaterials Biomater
~iomechanical Biomech
Biomedical Biomed
Biometrics Biometrics
Biophysical Biophys
Biophysics Biophys
Bioscience Biosci
Biosocial Biosoc
Biosystems Biosystems
Biotechnological Biotechnol
Biotechnology ~iotechnol
Birth Birth
Blood Blood
Bone Bone
.Brain Brain
Brazilian Braz
Breast Breast
British Br
Bulletin Bull
Bums Burns

Calcified Calcif
Calcium Calcium
Canadian Can
Cancer Cancer
Carbohydrate Carbohydr '

Carcinogenesis . Carcinog
Carcinogenic Carcinog
Cardiography Cardiogr
Cardiology Cardiol
Cardiovascular Cardiovasc
Care Care
Caries Caries
Catheterization Cathet
Cell Cell
Cells Cells
Cellular Cell
Central Cent
 -

14.10 Names of Journals

Cephalalgia Cephalalgia
Cerebral Cereb
Ceylon Ceylon
Chemical Chem
Chemicals Chem
Chemistry Chem
Chemists Chep
Chemotherapy Chemother
Chest Chest
Child Child
Childhood Child
Children Child
Childs Childs
. .
Chinese chin
Chromatographic Chromatogr
Chromatography Chromatogr
Chronic Chronic
Chronicle Chron
Circulation Circ
Circulatory Circ
Cleft Cleft
Cleveland Cleve
Clinic Clin
Clinical Clin
Clinics Clin
Cognition Cogn
Collagen Coll
~oliege Coll
Colon Colon
Colorado Colo
Communicable Commun
Communication Commun
Communications Comrnun
Community Community
Comparative Comp '

Complement Complement
Comprehensive Compr
Computerized Comput
Computers Comput
14.10 N a m e of Journals

(:onnectrcul G,nn
CunnecUvt. Connccl
Consulting Consult
Contact Contact
Contaminants Contam
Contamination Contam
Contemporary Contemp
Contributions Contrib
Control Control
controlled Control
Copenhagen Copenh
Cornea Cornea
CorneIl Cornell
Corps
Cprps
Cortex Cortex
Council Counc
~raniofacial Craniofac
Critical Crit
Cryobiology Cryobiol
Culture Cult
Current cum
Currents Curr
Cutaneous Cutan
Cutis Cutis
Cybernetics Cybern
Cyclic Cyclic
Cytogenetics Cytogenet
Cytology . Cytol
Cytometry Cytometry
Dairy Dairy
Danish Dan .

Deaf Deaf
Decision Decis
Defects Defects
Deficiency Defic
Delivery Deliv
Demography Demogr
Dental Dent
Dentistry Dent
 14.10 Names of Journals

Dependencies Dependencies
Dermatitis Dermatitis
Dermatological Dematol
Dermatology Dermatol
Dermatopathology Dermatopathol
Detection '
Detect
Development Dev
Devices Devices
Diabetes Diabetes
Diagnosis Diagn
Diagnostic Diagn
Dialysis Dial
Diarrhoea1
Dietetic Diet
Differentiation Differ
Digestion Digestion
Digestive Dig .
Dimensions Dimens
Directions Dir
Directors Dir
Discussions Discuss
Disease Dis
Diseases Dis
Disorders Disord
Disposition Dispos
DNA DNA
D'-"g Drug
Drugs Drugs
Ear Ear
Early Early
East African East Afr
Economic Econ
Ecotoxicology Ecotoxicol
Educational Educ
Egyptian
Egypt
Electrocardiology Electrocardiol
Electroenccphalognph): Electroencephalogr
I:.lectromyogr.~phy Electromyogr
Electron tlcc~ron
14.10 Names of Journals

~lectrotherapciurics Elearorher

Embryo Embryo
Embryology Embryo1
Emergency Emerg
Endocrine Endocr
~ndocrinological ~ndocrinol
Endocrinology ~ndocrinol
Endoscopy Endosc
Engineering Eng
Enteral Enteral
Entomology Entomol
~nvironmental Environ

Eyme Enzyme
Enzymology Enzymol
Epidemiologic ~pidemiol
Epidemiology Epidemiol
Ergology Ergo1
Ergonomics Ergonomics
Essays Essays
Ethics Ethics
Eugenics Eugen
European Eur
Evaluation Eva1
Exceptional Except ,

Exercise Exerc
Experimental EXP
Eye Eye
Factors Factors
Family Fam
Federation Fed
Fertility Fertil
Finnish Finn *

Fitness Fitness
Florida Fla
Food Food
Foot Foot
Forensic Forensic
Foundation Found
 14.10 Names of Journals

Function Funct
Fundamental Fundam
Gastroenterology Gastroenterol
Gastrointestinal Gastrointest
Gene Gene
General Gen
Genetic Genet
Genetics Genetics
Genitourinary Genitourin
Geographical Geogr
Georgia Ga
Geriatric Geriatr
Geriatrics Geriatr
Gerontologist Gerontologist
Gerontology Gerontol
Group Group
Groups Groups
Growth Growth
Gut Gut
Gynaecological Gynaecol
Gynaecology Gynaecol
Gynecologic Gynecol
Gynecology Gynecol
Haematology Haematol
Haemostasis Haemost
Hastings Center Hastings Cent
Hawaii Hawaii
Head Head
Headache Headache
Health Health
Hearing Hear
Heart Heart
Hematological Hematol
Hematology Hematol
Hemoglobin Hemoglobin
Hemostasis Hemost
Hepatology Hepatol
Heredity Hcretl
Hip Hip
14.10 Names of Journals

Histochemical Histochem
Histochemistry Histochem
Histology Histol
Histopathology Histopathol
History Hist
Homosexuality Homosex
Horizons Horiz
Hormone Horm
Hormones Horm
Hospital Hosp
Hospitals Hospitals
Human Hum
Humans Hum
Hybridoma Hybridoma
Hygiene H Y ~
Hypertension Hypertens
Hypnosis HYP~
Hypotheses Hypotheses
Imaging Imaging
Immunity Immun
Immunoassay Immunoassay
Irr~nunobiology Immunobiol
Immunogenetics Immunogenet
Immunological Irrimunol.
Immunology Immunol
Immunopharmacology Immunopharmacol
Immunotherapy Immunother
Implant Implant
Including Incl
India India
Indian Indian
Indiana Indiana
Industrial Ind
Infection Infect
Infectious Infect
Inflammation Inflamm
Informatics Inform
Information Inf
Inherited Inherited
Injury Inj
Inorganic Inorg
Inquiry Inquiry
Institutes Inst
Instrumentation Instrum
Insurance Insur
Intellectual Intellect
Intelligence Intel1
Intensive Intensive
Interactions Interact
Interferon Interferon
Internal Intern
International Int
Internist Internist
Interventional Intervent
Intervirology Intervirol
Intraocular Intraocul
Invasion Invasion
Invertebrate Invertebr
Investigation Invest
Investigational Investig
Investigations Invest
Investigative Invest
In Vitro In Vitro
In Vivo In Vivo
Iowa Iowa
Irish Ir
Isotopes Isot
Isozymes Isozymes
Israel Isr
Issues Issues
Istanbul Istanbul
Japanese J P ~
Joint Joint
Journal J
Kansas Kans
Kentucky KY
Kidney Kidney
Kinetics Kinet
0 Names of Journals

Laboratory Lab
Language Lang
Laparoendoscopic ~aparoendosc
Laryngolog); Laryngol
Larynx Larynx
Lasers Lasers
Law Law
Lectures Lect
Legal Leg
Leprosy LePr
Letters Lett
Leukocyte Leukoc
Leukotriene Leukouiene
Leukotrienes Leukotrienes
Library Libr
Life Life
Life-threatening Life Threat
Lipid Lipid
Lipids Lipids
Literature Lit
Louisiana La
Lung Lung
Lymphokine Lymphokine
Lymphology ~ymphol

Madagascar Madagascar
Magnesium Magnesium
Magnetic Magn
Main Main
Making Making
Malaysia Malaysia
Management Manage
Manipulative Manipulative
Marital Marital
Maritime Marit
Maryland Md
Mass Mass
Mathematical Math
Maxillofacial ~axillofac
Measurenlent hleas
 14.10 Names of Journals

Mechanisms Mech
Media Media
Medical Med
Medicinal Med
Medicine Med
Membrane Membr
Mental Ment
Metabolic Metab
Metabolism Metab
Metastasis Metastasis
Methods Methods
Mexico Mex
Michigan Mich
Microbial Microb
Microbiological Microbiol
Microbiology Microbiol
Microcirculation Microcirc
Microscopy Microsc
Mic~ovascular Microvasc
Microwave Microw
Military Milit
Mineral Miner
Minnesota Minn
Mississippi Miss
Missouri Mo
Modification Modif
Molecular Mol
Monographs Monogr
Morphology Morphol
Motility Motil
Muscle ' Muscle
Mutagenesis
Mutation
Mycobacterial
Narcotics Narc
National Natl
Natural Nat
Nature Nnr
Naval N:Iv
*--
'
14 10 Names of Journalr

Zcl~r
3cc.k
Negl
Nron;~~c
Ncpl~i.ol
Nephron
New
Kclvo~~s New
Netherlands Neth
Neur;~l Neural
Neurobehavioral Neurobehav
Neurobiology Neurobiol
Neurochemist~y ~eurochem
Neurocytology Neurocytol
Neuroendocrinology Neuroendocrinol
Neurogenetics Neurogenet
Neuroimmunology Neuroirnmunol .
Neurologic Neurol
Neurological Neurol
Neurology Neurol
Neuropathology Neuropathol
Neuropediatrics Neuropediatr
Neuropeptides Neuropeptides
Neuropharmacology Neuropharmacol
Neurophysiology Neurophysiol
Neuropsychobiology Neuropsychobiol
Neuropsychology Neuropsychol
Neuropsychopharmacology Neuropsychopharmacol
Neuroradiology Neuroradiol
Neuroscience Neurosci
Neurosurgery Neurosurg
Neurosurgical Neurosurg
Neurotoxicology Neurotoxic01
Neurotrauma Neurotrauma
New N
New England N Engl
New Jersey NJ
New 0rlr;lns New Orleans
h'c\v 'l'ork N Y
 14.10 Names of Journals

New Zealand
North America North Am
North Carolina NC
Nose Nose
Nuclear Nu'cl
Nucleotide Nucleotide
Nurse Nurse
Nursing Nurs
Nutrition Nu tr
Nutritional Nutr
Obesity Obes
Obstetric Obstet
Obstetrics Obstet
Occupational Occup
Ocular Ocul
Official Off
Ohio Ohio
Oklahoma Okla
Oncology Oncol
Ophthalmic Ophthalmic
Ophthalmological Ophthalmol
Ophthalmology Ophthalmol
Optical Opt
optics Opt
Optometric Optom
Optometry Optom
Oral Oral
Organization Organ
Organs Organs
Orthodontics Orthod
Orthodontist Orthod
Orthopaedic Orthop
Orthopsychiatry Orthopsychiatry
Orthotics Orthot
Osaka Osaka
Oslo Oslo
()\teopsrhtc
Orc~lar).npolog-y
14.10 Names of Journals

Protozoology Protozool
Psyche Psyche
Psychiatric Psychiatr
Psychiatry Psychiatry
Psychoactive Psychoactive
Psychoanalysis Psychoanal
Psychoanalytic Psychoanal
Psycholinguistic Psycholinguist
Psychdlogist Psychol
Psychology Psychol
~sychoneuroendocrinolog~ ~s~choneuroendocrin01
Psychopathology Psychopath01
~sychopharmacology ~sychopharmacol
.Psychophysiology psychophysiol
Psychosocial Psychosoc
Psychosomatic Psychosom
Psychosomatics Psychosom
Psychotherapy Psychother
Public Public
Puerto Rico PR

Quantitative Quant
Quarterly Q
Radiation Radiat
Radiography -Radiogr
Radioisotopes Radioisotopes
Radiologists Radiol
Radiology Radiol
Rational Ration
Reactions React
Recombinant Recomb
Reconstructive Reconstr
Record Rec
Rectum Rectum
Regional Reg
Regulation Regul
Regulatory Regul
Rehabilitation Rehabil
Renal Renal
Report Rep
 14.10 Names of Journals

Reports Rep
Reproduction Keprod
Reproductive Reprod
Research Res
Residue Residue
Resonance Reson
Respiration Respir
Respiratory Respir
Response Response
Resuscitation Resuscitation
Retardation Retard
Retina Retina
Review Rev
Reviews Rev
Rheumatic Rheum
Rheumatism Rheum
Rheumatology Rheumatol
Rhinology Rhino1
Rhode Island RI
Safety Safety
Scandinavian Scand
Scanning Scan
Schizophrenia Schizophr
School Sch
Science Sci
Sciences Sci
Scientific Sci
Scottish Scott
Security Secur
Sem!nars Semin
Series Ser
Service Serv
Sex Sex
Sexual Sex
Sexually Sex
Shock Shock
Singapore Singapore
Skeletal Skeletal
Slecp Slecp
14.10 Names of Journals

Social soc
Societies Soc
Society I
soc
Sociological Sociol
Sociology Sociol
Somatic Somatic
Somatosensory Somatosens
South African S Afr
South Carolina SC
South Dakota SD
Southeast Southeast
Southern South
Space Space
Spectrometry Spectrorn
Speech Speech
Spine Spine
Sports Sports
Stain Stain
Standardization Stand
Standards Stand '

Statistical Stat
Steroid Steroid
Steroids Steroids
Stockholm Stockh
Strabismus Strabismus
Stress Stress
Stroke Stroke
Structure . Struct
Studies Stud
Subcellular Subcell
Submicroscopi~ Submicrosc
Substance Subst
Suicide Suicide
Superior Super
Support support
Surgeon Surg
Surgeons Surg
Surgery Surg
 14.10 Names of Journals

Surgical Surg
Swedish Swed
Symposia SY~P
Symposium SY~P
System syst
Systems Syst
Technical Tech
Technology Techno1
Tennessee Tenn
Teratogenesis Teratogenesis
Teratology Teratol
Thailand Thai
Theoretical Theor
Therapeutics Ther
Therapies Ther
Therapy Ther
Thermal Them
Thoracic Thorac
Thorax Thorax
Throat Throat
Thrombosis Thromb
Thromboxane Thromboxane
Thymus Thymus
Tissue Tissue
Today Today
Tokyo Tokyo '
Tomography Tomogr
Topics TOP
Total Total
T?xicologic Toxicol
Toxicological Toxicol
Toxicology Toxicol
Traditional Tradit
Transactions Trans
Tnnsfer Transfer
Tr-nsfuslon Transfusion
Tmnsmixsion Tr;~n.;m
Tnnsrn~rred l.r.irj\~~~
14 10 N a m e of Journalr

Transplant
I'nnsplantation Transplantation
Traumatic Trauma
Tropical Trop
Tuberculosis Tuberc
Tumor Tumor
Tumour Tumour
Tunis Tunis
Turkish Turk
Ulster Ulster
Ul tramicroscopy Ultramicrosc
Ultrasonic Ultrason
Ultrasonics Ultrasonics
Ultrasound Ultrasound
uitrastructurai Ultrastruct
Ultrastructure Ultrastruct
Undersea Undersea
Union Union
Uremia Uremia
Vision Vis
Visual vis
Vital Vital
Vitamin Vitam
Vitaminology Vitamin01
Vitamins Vikm
Vitro Vitro
Vivo Vivo
Welfare Welfare
Western West
West Indian . West Indian
West Virginia W Va
Wildlife Wid1
Wisconsin Wis
Women . Women
Women's Womens
Zoology
Zoonoses Zoonoses
 14.1 1 Clintcal, Techn~cal,and Other Common Terms

Clinical, Technical, and Other Common Terms. This compilation of clinical,

technical, and other common terms and their abbreviations is not intended to be all-
encompassing but is provided as a short reference. There are many published listings
of abbreviations, acronyms, and initialisms.
Many entities share the same abbreviation (eg, American Heart Association,
American Hospital Association, American Historical Association, American Humanist
Association, American Hyperlexia Association, American Hydrogen Association).
Thus, preciseness takes precedence over abbreviating.
In addition, some abbreviations encompass more than one grammatical variant
(eg, ncun, adjective) of a term. For example, ECG represents both electrocardiogram
and electrocardiographic. It is unnecessary to redefine the abbreviation for each
variation in usage within a body of work. Similarly, terms that have singular and
plural forms (eg, WBC and WBCs) are defined once, whichever form is mentioned
first.
When the expanded form is possessive at first mention, the parenthetical ab-
breviation is also possessive at first mention:
The National Aeronautics and Space ~drninismtion's (NASA's) Imple-
mentation Plan for Space Shuttie Return to Space and Beyond was the NASA
response to the Columbia disaster in 2003.
Most terms should be expanded at first mention. However. considerations for which
this general rule might be set aside include comprehensibi1i~-.reco_gnirion.and space.
as well as avoidance of cumbersome expressions. Esceptions include using the
abbreviation instead of the expansion in a long title or subtitle, a letter to the editor,
or an informal essay.
Use common sense in deciding whether to abbreviate the terms in the follow-
ing list and other terms. For example, if "acute respiratory distress syndrome" ap-
pears only once or twice in an article, spell it out. If the article concerns acute
respiratory distress syndrome and the term is used several times, e x p n d the term at
first mention with the abbreviation immediatelyfollowing in parentheses. Abbreviate
it thereafter.
Note: Some terms may be known better in their abbreviated form (eg, HIPAA),
and abbreviating them at first mention (with the expanded form following in pa-
rentheses) may be appropriate.
Avoid using abbreviations at the beginning of a sentence unless the expansion is
cumbersome, eg, a collaborative group name or other :\cronym pronouncetl as ;I
word (ALLHAT, AIDS, CLIA, UNICEF) (see also 14.8, Agencies and Organizations,
and 14.9, Collaborative Groups).
Do not use an abbreviation as the sole term in a subheading. Also avoid in-
troducing an abbreviation in a subheading:
Avoid:
National Institutes of Health (NIH)
The NIH is the steward of rnedlcnl and l,eh.~v~or.ilresearch for [he Iln~lccl
States. It is an agency iindcr ~ h z1's I)~p.innir*n[of H e ~ l t hand fl{ini.in
Services

I
50 l
14.1 1 Clinical, Technical, and Other C o m r m Terms

National lnst~rurcsof iicalth

The: National Institute of Health (NIH) is the steward of medical and be-
havioral re.search for the United States. It is an agency under the US De-
parunent of Hedlth and Human Services.
Apply the foregoing concepts to each element of the manuscript. See also 14.0, Ab-
breviations, and 2.0, Manuscript Preparation, as well as specific nomenclature sec-
tions (15.0, Nomenclature), for additional guidelines for correct use of specialized
terms and their abbreviations. (See also 4.0, Visual Presentation of Data.)
Note: At a 2004 National Summit on Medical Abbreviations, the Joint Commission
on Accreditation of Healthcare Organizations (JCAHO) approved an official "do not
use" list of abbreviations. It is important to note that this list applies to all medical
orders and all medication-related documentation that are handwritten or on pre-
printed forms used in hospitals and other health care facilities. The JCAHO require-
ment does not apply to the use of abbreviations in the publication of articles in
scientific journals.
However, authors and editors should be mindful of the possibility of introducing
error in journal articles when using certain abbreviations and symbols. Other orga- ,
nizations (eg, see the Institute for Safe Medication Practices at http://www.ismp.orgl
have suggested the desirability of even more stringent initiatives against the use of ;
'
certain abbreviations and symbols, which are designed to protect patients from
potential harm.
Note: JAMA and the Archives Journals do not endorse any proprietary entities in
this list.
Abbreviation Erpanded Fonn
AAA abdominal aortic aneurysm
ABC avidin-biotin complex
AC alternating current
ACE angiotensinconverting enzyme
ACS acute coronary syndromes
A m Use cotticotmpin (formerly adrenocorticotropic hormone)
AD Alzheirner disease
ADH antidiuretic hormone
ADHD attention-deficit/hyperactivity 'disorder
ADL activities of daily living (but: 1 ADL, 6 ADh)
aDNA anaent DNA
ADP adenosine diphosphate
ADPase adenosine diphosphatase
AED automated external defibrillator
AF atrial fibrillation
AFP a-fetoprotein
AIDS* acquired immunodeficiency syndrome
 14.11 Clinical, Technical, and Other Common Terms

ALL acute lymphoblastic leukemia; acute lymphocytic leukemia

allo-SCT allogeneic stem cell transplantation
ALS amyotrophic lateral sclerosis
ALT alanine aminotransferase (previously SGPT)
AML acute monocytic leukemia; acute myeloblastic leukemia;
acute myelocytic leukemia
AMP adenosine monophosphate
ANA anthiuclear antibody
ANCOVA analysis of covariance
ANLI. acute nonlymphocytic leukemia
ANOVA analysis of variance
AOR adjusted odds ratio
APACHE Acute Physiology i d Chronic Health Evaluation
APB atrial preniature beat
APC atrial premature contraction
ARC Use symptomatic H W infection (formerly AIDS-related
complex)
ARDS acute respiratory distress syndrome
ARMD age-related macular degeneration
ARR absolute risk reduction
ART antiretroviral therapy
ASC adult stem cell
ASC-US atypical squamous cells of uncertain significance
ASD atrial septa1 defect; autistic spectrum disorder '
AST aspartate aminotransferase (previoidy SGOT)
ATP adenosine triphosphate
ATPase adenosine triphosphatase
AUC area under the curve
AUROC area under the receiver operdting characteristic curve

BAC blood alcohol concentration

BADL basic activities of daily living (use activities of daily livitzK)
BAER brainstem auditory evoked response
BCG bacille Calmette-Gukrin (but: do not expand as a d n ~ g :
BCG vaccine)
BDI Beck Depression Inventory
bid twice a day (do not abbreviate)
BMD bone mineral density
BMI body mass index
14.1 1 Clinical. Technical. a n d Other C o m m o n Terms

BMT bone n13rro~vtran-\p13rlt;lrlon

BP blood pressure
BPD bronchopulmonary dysplasia
BPH benign prostatic hyperplasia
BPRS Brief Psychiatric Rating Scale
BSA body surface area
BSE bovine spongiform encephalopathy; breast self-examination
BUN blood urea nitrogen (use serum urea nitrogen)

C complement (use with a number, eg, C1, C2,. . . C9;

see 15.8.3,Nomenclature, Immunology, Complement)
C, ~a circa (do not abbreviate)
CABG coronary artery bypass graft
CAD coronary artery disease
CAGE cut down, annoyed, guilty, eye opener (screening
questionnaire for potential alcoholism) I .

CAM complementary and alternative medicine i

!
;';
CAMP cyclic adenosine monophosphate I
. I
CARS compensatory anti-inflammatory response syndrome _. .'.. -..
CART combination antiretroviral therapy
CBC complete blood (add cell) count
ccu cardiac care unit; critical care unit
CD* clusters of differentiation (use with a number, eg, CD4 cell;
see 15.8.2,Nomenclature, Immunology, CD Cell Markers)
CD* compact disc
cDNA complementary DNA
CD-ROM* compact disc read-only memory
cEA carcinoembryonic antigen; cost-effective analysis
CEU continuing education unit
cf compare
CF cystic fibrosis
. CFS chronic fatigue syndrome
CFT complement fixation test
CFU colony-forming unit
cGMP cyclic guanosine monophosphate
CHD coronary heart disease
CHF congestive heart failure
CI confidence interval
CIN cervical intraepithelial neoplasia
CIS carcinoma in situ

----- --
-.
 14.11 Clinical, Technical, and Other Common Terms

CJD Creutzfeldt-Jakob disease

CK creatine kinase
CK-BB creatine kinase .BB (BB designates the isozyme)
CK-MB creatine kinase MB ,

CK-MM creatine kinase htM

CL confidence limit
CLIA Clinical Laboratory Improvement Amendments
CME continuing medical education (often used without
expansion when describing credit hours, eg, category
1CME credit)
CMI cell-mediated immunity
CML chronic myelocytic leukemia
CMV cytomegalovirus
CNS. central nervous system
CONSORT Cunsolidated Standards of Reporting Trials
COPD chronic obstructive pulmonary disease
COX-2 cyclooxygenase 2 .
CPAP continuous positive airway pressure
CPD continuing professional development
CPK Use matine kinuse
CPR cardiopulmonary resuscitation
CPT ' C u m €Procedural Terminology
CQI continuous quality improvement
CRF corticotropin-releasing factor
cRNA complementary RNA
CRP C-reactive protein
CSF cerebrospinal fluid; colony-stimulating factor
csr central standard time
CT computed tomographic; computed tomography
CUA cost-utility analysis
CVS . chorionic villus sampling

DALY disability-adjusted life-year

deoxyadenosine monophosphate (deoxyadenylate)
dilation and curettage
direct current
DCIS ductal carcinoma in situ
DDD defined daily dose
DDT dichlorodiphenyltrichloroethane (chlorophenothane)
DE dose equivalent

i.
14.1 1 Clinical, Technical, and Other Common Terms

DEV duck embryo vaccine

DFA direct fluorescence assay
dGMP deoxyguanosine monophosphate (deoxyguanylate)
DIC disseminated intravascular coagulation
DIF direct imrnunofluorescence
DNA' deoxyribonucleic acid
DNAR do not attempt resuscitation
DNase deoxyribonuclease
DNH d o not hospitalize
DNR d o not resuscitate
DOS* disk operating system
DOT cl;.cectlyobserved therapy
DOTS directly observed therapy, short course
dpi* dots per inch
DRE digital rectal examination
DRG diagnosis related group
DS duplex sonography
DSM-ID Diagnastic a n d Statistical Manual of Mental Disorden
(Third Edition)
DSM-UI-R Diagnostic a n d tati is tical Manual of Mental Disordm
(Third Edition Revised)
D i a g m 0 cand Statistical Manual of Mental Disorders
(Fourth Edition)
Diagnostic and Statistical Manual of Mental Disorders
(Fourth Edition, Text Revision)
DSMB data and safety monitoring board
DT delirium tremens
DTaP diphtheria and tetanus toxoids and acellular pertussis
[vaccine]
DTP diphtheria and tetanus toxoids and pertussis [vaccine]
DXA dual-energy x-ray absorptiometry

EBM evidence-based medicine

EBV Epstein-Barr virus
EC ejection click
ECA epidemiologic catchment area
ECG electrocardiogram; electrocardiographic
ECMO extracorporeal membrane oxygenation
ECT electroconvulsive therapy
ED effective dose; emergency department
ED50 median effective dose
 14.11 Clinical, Technical, and Other Common Terms

EDTA* ethylenediaminetetraacetic acid

EEE eastern equine encephalomyelitis
EEG electroencephalogram; electroencephalographic
eg' for example (from,the Latin exempli gratia; see 1 1 . 1 ,
Correct and Preferred Usage, Correct and Preferred Usage
of Common Words and Phrases)
EGD esophagogastroduodenoscopy
EIA enzyme irnmunoassay
ELISA enzyme-linked immunosorbent assay
EM electron microscope; electron microscopic; electron
microscopy
EMG electromyogram; electromyographic
EMIT enzyme-multiplied immunoassay technique
EMS electrical muscle stimulation; emergency medical services;
eosinophilia-myalgia syndrome
EMT emergency medical technician
ENG electronystagmogram; electronystagrnographic
EOG electro-oculogram, electro-oculographic
ERCP endoscopic retrograde cholangiopancreatography
ERG electroretinogram; electroretinographic
ESBC extended-spectrum plactamases
ESC embryonic stem cell
ESR erythrocyte sedimentation rate
ESRD end-stage renal disease
EST eastern standard time
ESWL extracoGoreal shock wave lithotripsy
etc* et cetera (and so forth) (see 11.1, Correct and Preferred
Usage, Correct and Preferred Usage of Common Words
and Phrases)
EVR evoked visual response .

F* French (add catheter, use only with a number, eg, 12F

catheter)
forced expiratory flow, midexpiratory phase (scc 1i.1(>.
Nomenclature, Pulmonary, Respiratory, and Ulootl Gas
Terminology)
FEV forced expiratory volulne
FEVl forced expiraton volume in rlie firs1 secontl of c.spir;~t~on
FIO~ fraction of inspired oxygen
FISH Iluorescencc in sltt~hytxitlicction
FLAIR
FSI j
14.1 1 Clinical, Technical, a n d O t h e r C o m m o n Terms

FTA fluorescent ueponemal antibody

FTA-ABS fluorescent treponemal antibody absorption (add test)
FUO fever of unknown origin
FVC forced vital capacity

GABA y-aminobutyric acid

GAD generalized anxiety disorder
GAF Global Assessment of Functioning [Scale]
GB* gigabyte
GCS Glasgow Coma Scale
G-CSF granulocyte colony-stimulating factor
GDP guanosine. &phosphate
GDS Geriatric Depression Scale
GED General Education Development
GERD gastr&ophageal reflux disease
GFR glomerular filtration rate
GH growth hormone
GI gastrointestinal
GIFT gamete intrafallopian transfer
GLC gas-liquid chromatography
GM-CSF granulocyte-macrophage colony-stimulating factor
GMP guanosine monophosphate (guanylate, guanylic add)
GMRI gated magnetic resonance imaging
GMT geometric mean titer
GMT Greenwich mean time
GnRH gonadotropin-releasing hormone (gonadorelin as
diagnostic agent)
GSC germline stem cell
GLT genitourinary
GUI g r a p h i d user interface
GVHD graft-vs-host disease

HAART highly active antiretroviral therapy

HALE health-adjusted life expectancy
mv hepatitis A virus (see 15.14.3, Nomenclature, Organisms
and Pathogens, Virus and Prion Nomenclature)
HbA,, hemoglobin A*,
Hbco carboxyhemoglobin
HBO hyperbaric oxygen
Hbo2 oxyhemoglobin; oxygenated hemoglobin
t4t)S x k l e cell hemoglobin
 14.1 1 Cl~n~cal,
Techn~tal.and Other Common Terms

hepatitis B surface antigen (see li.14.3. Nomenclature,

Organisms and Pathogens, Virus and Prion Komenclature)
HBSS Hanks balanced salt solution
HBV hepatitis B virus
hCG human chorionic gonadotropin (do not abbreviate when
used as a drug)
HCV hepatitis C virus (see 15.14.3, Nomenclature, Organisms
and Pathogens, Virus and Prion Nomenclature)
HDL high-density lipoprotein
HDL-C high-density lipoprotein cholesterol
HDRS Hamilton Depression Rating Scale
hGH human growth hormone
HHV human herpesvirus
Hib Haemophilus infuenzae type b [vaccine or disease1 (see
15.14.2, Nomenclature, Organisms and Pathogens, Bacteria:
Additional Terminology)
HIPAA Health Insurance Portability and Accountability Act
HIV human immunodeficiency virus
HL hearing level
HLA* human leukocyte antigen (use "HLA antigen"; see 15.8.5,
Nomenclature, Immunology, HLA/Major Histocompatibility
Complex)
HMO health maintenance organization
HPF high-power field
HPLC high-performance liquid chromatography
HPV human papillomavirus (add hyphen to abbreviation when
indicating type, eg, HPV-6)
HR hazard ratio
HRQOL health-related quality of life
HSC hematopoietic stem cell
HSIL high-grade squamous intraepithelial lesion
HSV herpes simplex &us
HT hormone therapy
5-HT Use serotonin (also 5-hydroxytryptamine)
'
HTLV human T-lymphotropic virus (use arabic numeral with
specific type, eg, HTLV-1)
HTML* hypertext markup language
http* hypertext transfer protocol
I-IUS hemolytic uremic syndrome

IADL instrumental activities 0 1 rl;iily livinl; (hrtl 1 I:\l)l.. 6 IAnl.\)

ICD implantable cardiovencr-cl~hI~r~ll~ror
14.11 Cl~n~cal.
Techn~cal,and O t k C o m m o n Terrm

111rrnwrrorwlCluu-@cationof Diseases, Ninth Reuision

l n ~ ~ ~ a a t i o Cksijicatiorz
nal of Diseases, Ninth Revision,
Clinical ,~fdtficatiora
ICD-I 0 Internatiorlal Classification of Diseases, Tenth Reuision
ICD- I 0-CM International Classification of Diseases, Tenth Reuision,
Clinical hfodification
ICU intensive care unit
ID infective dose
IDU injecting drug user; injection drug user
ie' that is (from the Latin id est; see 11.1, Correct and
Preferred Usage, Correct and Preferred Usage of Common
Words and Phrases)
IFN interferon (do not abbreviate when used as drug;
see 15.4.13, Nomenclature, Drugs, Nomenclature for
Biological Products)
immunoglobulin (abbreviate only with specification of
class, eg, IgA, IgG, IgM; see 15.8.6, Nomenclature,
Immunology, Immunoglobulins)
insulinlike growth factor 1
interleukin (abbreviate only when indicating a specific
protein factor, eg, n-2)(see 15.8.4, Nomenclature,
Immunology, Cytokines)
IM intramuscular; intramuscularly
IND investigational new drug
IM international normalized ratio
IOP intraocular pressure
IPA intimate partner abuse
IPV intimate partner violence
Q
'I intelligence quotient
IRB institutional review board
IRMA irnrnunoradiometric assay
ISBN* International Standard Book Number
ISG immune serum globulin
ISSN* International Standard Serial Number
In intratubal insemination.
ITP idiopathic thrombocytopenic purpura
I T intention to treat
IUD intrauterine device
IUGR intrauterine growth retardation
IUI intrauterine insemination
IV intravenous; intravenously
 14.1 1 Clinical, Technical, and Other Common Terms

in vitro fertilization
intravenous immunoglobulin
intravenous pyelogram

JPEG* Joint photographic Experts Group (computer file format

for digital images)

kilobyte
kidneys, ureter, bladder [plain abdominal radiograph]

LA left atrium
LAD left anterior descending coronary artery
LAO left anterior oblique coronary artery
LASEK laser epithelial keratomileusis
LASIK laser in situ keratomileusis
LAV lymphadenopathy-associated virus '
LBW low birth weight (but: low-birth-weight infant)
LCA left coronary artery
LCR locus control region
L a left circumflex coronary artery
LD lethal dose
LD50 median lethal dose
LDH lactate dehydrogenase
LDL lowdensity lipoprotein
DL-C low-density lipoprotein cholesterol
LGA large for gestational age
LH luteinizing hormone
LHRH luteinizing hormone-releasing hormone (gonadorelin as
diagnostic agent)
low molecular weight (usually refers to low-molecular-
weight heparin)
LOCF last observation carried forward
Lob logarithm of odds
logMAR logarithm of the minimum angle of resolution
LOS length of stay
LR likelihood ratio
LSD lysergic acid diethylamide
LSIL low-grade squamous intraepithelial lesion
LV left ventricle; left ventricular
LVEDV left ventricular end-diastolic volume
14 1 1 C l ~ n ~ c aTechnical,
l. and Other Common Terms

l.\TF left \ . c n t n ~ u l ~c)cc11on

r tr~c~~on
L\.Ol' left vt.nrncul;ir ourtlow. tmc't

r?l-' meta- (use only in chemical formulas or names)

MA01 monoamine oxidase inhibitor
MAPC n~ultipotentadult progenitor cell
MB* megabyte
MBC minimum bactericidal concentration
MCH mean corpuscular hemoglobin
MCHC mean corpuscular hemoglobin concentration
MCO managed care organization
MCV mean corpuscular volume
MD muscular dystrophy
MDR multidrug-resistant
MEC mean effective concentration
MEM minimal essential medium
MEN multiple endocrine neoplasia [type 1: MEN-1; type 2:
MEN-2, etcl
MeSH Medical.Subject Headings [of the US National Library of ..

Medicine]
MET metabolic equivalent task
MGUS monoclonal garnmopathy of uncertain significance
MHC major histocompatibility complex
MI mitral insufficiency; myocardial infarction
MIC minimum inhibitory concentration
MICU medical intensive -care unit
MMPI Minnesota Multiphasic Personality Inventory
MMR measles-mumps-rubella [vaccine]
MMSE Mini-Mental State Examination
MODS multiple-organ dysfunction syndrome
MOOSE Meta-analysis of Observational Studies in Epidemiology
MPS Mortality Probability Score
MRA magnetic resonance angiography
MRI magnetic resonance imaging
mRNA messenger RNA
MRSA methicillin-resistant Staphylococcus aureus
MS rnitral stenosis; multiple sclerosis
MSA metropolitan statistical area
MSC mesenchymal stem cell
MSET multistage exercise test
 14.11 Clinical, Technical, and Other Common Terms

MST mountain standard time

MVC motor vehicle crash

NAD nicotinarnide adenine dinucleotide

NADP nicotinamide adenine dinucleotide phosphate
nb' nota bene (note well)
NDA new drug application
Nd:YAG9 neodymium:yttrium-aluminum-garnet[laser]
NEC necrotizing enterocolitis
hF National Fonnulay
NICU neonatal intensive care unit
NK natural killer (add cells)
NMN nicotinamide mononucleotide
NNH number .needed to harm
NNS number needed to screen'
NNT number needed to treat
NOS not otherwise specified
"PO nothing by mouth (do not abbreviate)
NPV negative predictive value
. NS not significant (see 20.0, Study Design and Statistics)
NSAID nonsteroidal anti-inflammatory drug
NSC neural stem cell
NSTE non-ST-segment elevation

0-• ortho- (use only in chemical formulas)

OC oral contraceptive
OCD obsessive-compulsive disorder
OD* oculus dexter (right eye) (use only with a number, as in
a refraction)
oral glucose tolerance test
odds ratio
oculus sinister (left eye) (use only with a number, as in
a refraction)
0s opening snap
OSA obstructive sleep apnea
OU' oculus uniras (both eyes) or oculus uterque (each eye)
(use only with a number)

P' pan- (use only in chemical formulas or names)

I.:\ posteroanlerior; pulmonary artery
13:\C prr*narVlretrial contmction; plllmonary a ~ e r ;catheter
14.1 1 Clinical, Technical, and Other Common Terms

partial pressure of carbon dioxide, arterial ( x c 15.16,

Nomenclature, Pulmonary, Respiratory, and BLood Gas
Terminology)
Paoz* partial pressure of oxygen, arterial
PAO~ partial pressure of oxygen in the alveoli
PAD peripheral artery disease
PAS periodic acid-Schiff
PAT paroxysmal atrial tachycardia
PBS phosphate-buffered saline
PBSC peripheral blood stem cell
PC1 percutaneous coronary intervention
Pco2* partial pressure of carbon dioxide
PCP Pnarmocystisjimveci pneumonia (formerly Pneumocysti.
carinii pneumonia)
PCR polymerase chain reaction
PCT practical clinical trial; pragmatic clinical trial
PCW pulmonary capillary wedge [pressure]
PDA patent ductus arteriosus
PDA* personal digital assistant
PDF portable document format
PDR Physicians' Desk R e f m c e
PE pulmonary embolism
PEEP positive endexpiratory pressure
PEG percutaneous endoscopic gastrostomy;
pneumoencephalographic; pneumoencephalography
PEP postexposure prophylaxis
PET positron emission tomographic; positron emission
tomography
PFGE pulsed-field gel electrophoresis
PGF placental growth factor
pH* negative logarithm of hydrogen ion concentration
PICC peripherally inserted central catheter
PICU pediatric intensive care unit
PID pelvic inflammatory disease
PKU phenylketonuria
PMS premenstrual' syndrome
PO orally (do not abbreviate)
Po2* partial pressure of oxygen
POAG primary open-angle glaucoma
PPD .purified protein derivative (tuberculin)
 14.11 Clinical, Technical, and Other Common Terms

PPO preferred provider organization

PPROM preterm premature rupture of membranes
PPV positive predictive value
P" as needed (do not abbreviate)
PRO peer review organization; professional review organization
PROM premature rupture of membranes
PSA prostate-specific antigen
Psqoz subcutaneous tissue oxygen tension
PSRO professional standards review organization
PS'P Patific standard time
PSVT paroxysmal supraventricular tachycardia
PT physical therapy; prothrombin time
PTCA percutaneous transluminal coronary angioplasty
PTSD posttt.aurnatic stress disorder
P'IT partial thromboplastin time
PUPA polyunsaturated fatty acid
PUVA psoralen-UV-A
PVC premature ventricular contraction
PVR peripheral vascular resistance; pulmonary vascular resistance
PVS permanent vegetative state; persistent vegetative state -
QA , quality assurance
QALY quality-adjusted life-year
QC quality control
qd every day,(do not abbreviate)
QI quality improvement
qid 4 times a day (da not abbreviate)
qod every other day (do not abbreviate)
QOL quality of life
QUOROM Quality of Reporting of Meta-analyses

RA rheumatoid arthritis
RAM* random access memory
RAST radioallergosorbent test
RBC red blood cell
RBRVS resource-based relative value scale
RCA right coronary a n e v
Rcr randomized clinical trial; ranciom~zetlcontrolled trial
RDA recc,mniendcd d:lily alloiv:inc.c. rccomn~c-ntlctl
dicta9 ;~lloiv;~ncc
RDC Re.w3rch I>i;~pnOhtlC(:rllcri.i
 --_..
14 1 1 C l * n ~ c a lTechnical,
. and Other Common Terms

rDN A ribosomal DNA

RDS respiratory distress syndrome
REM rapid eye movement
RFLP restriction fragment length polymorphism
RFP radiofrequency pulse
rh recombinant human
Rh* rhesus (of, related to, or being an Rh antibody, blood
group, or factor)
rhNGF recombinant human nerve growth factor
RIA radioirnmunoassay
RIND reversible ischemic neurological deficit
RNA* ribonucleic acid
RNAi RNA interference
ROC receiver operating characteristic [curve]
ROM* read-only memory
ROP retinopathy of prematurity
RPR rapid plasma reagin
RR relative risk; risk ratio
RSV respiratory syncytial virus
RT-PCR reverse transaiption-polymerase chain reaction
RV right ventricle; right ventricular
RVEF right ventricular ejection fraction
RVOT right ventricular oufflow tract

SAD seasonal affective disorder

SADS Schedule for Affective Disorders and Schizophrenia
SAH subarachnoid hemorrhage
SAPS Simplified Acute Physiology Score
SARS severe acute respiratory syndrome
SAS* Statistical Analysis System
SCID severe combined immunodeficiency; Structured Clinical
Interview for DSM (use with DSM edition number)
standard deviation (abbreviate only when used with a
number, eg, 2 SDs; or in Mean [SDI construction in table
stubs and headings)
standard error.(abbreviate only when used with a number;
see SD)
SEM standard error of the mean (abbreviate only when used
with a number; see SD)
SEM scanning electron microscope; systolic ejection murmur
SF-36 36-Item Shon Form Health Survey
 14.1 1 Clinical, Technical, and Other Common Terms

SGA small for gestational age

SGML* standardized general markup language
SCOT Use aspartate aminotransferase (for serum
glutamic-oxaloacetic transaminase)
SGPT Use alanine aminotransferase (for serum
glutamic-pynivic transaminase)
SIADH syndrome of inappropriate secretion of antidiuretic
hormone
SICU surgical intensive care unit
SIDS sudden infant death syndrome
SIL squamous intraepithelial lesion
SIP Sickness Impact Profile
siRNA small interfering RNA
SIRS systemic inflammatory response syndrome
SLE St Louis encephalitis; systemic lupus erythematosus
SNP single-nucleotide polymorphism
SPECT single-photon emission computed tomography
SPF sun protection factor
SPSS* Statistical Product and Service Solutions (formerly
Statistical Package for the Social Sciences)
SSC somatic stem cell
SSC* standard saline citrate
S
Sm selective serotonin-norepinephrine reuptake inhibitor
SSPE* sodium chloride, sodium phosphate, EDTA [buffer]
SSPE subacute sclerosing panencephalitis
SSN selective serotonin reuptake inhibitor
STARD Standards for Reporting Diagnostic Accuracy
m seyally transmitted disease
STEM1 ST-segment elevation rnyocalrli:~link~rction
STI sexually tr~nsmittcdinfection; structurccl trcatmcnr
interruption
SUN serum urea nitrogen
SVR systemic vascular resistance

t1/2 half-life
T3 triiodothyronine
T4 thyroxine
TAHBSO total abdominal hysterectomy \\.irh I~il;~rer.~l
salpingo-oophorectomy
TAT Thematic Apperception Tesr
TB* terabyte
! 4 1 1 Cl~nbcal,Technlcsl, and Other Common Terms

113
Ti3I traumatic brain injury
mSA total body surface area
TCA tricyclic antidepressant
TCD5~ median tissue culture dose
TE echo time
THA total-hip arthroplasty
TI inversion time
TLA transient ischemic attack
TIBC total iron-binding capacity
tid twice a day (do not abbreviate)
TIFF* Tag(ged) Image File Format
TLC thin-layer chromatography; total lung capacity
TNF tumor necrosis factor
n;r~* tumor, node, metastasis (see 15.2.2, Nomenclature, Cancer,
The TNM Staging system)
PA tissue plasminogen activator
TPN total parented nutrition
TQM total quality management
-TR repetition time
TRH thyrotropin-releasing hormone (pmtirelin as
diagnostic agent)
tRNA transfer RNA
TRP tyrosine-related protein
TRUS transrectal ultrasonography
TSH Use thptmpPn(previously thyroid-stimulating
hormone).
TSS toxic shock syndrome; toxic "strep" [streptococcal]
syndrome .
thrombotic thrombocytopenic purpura
UHF ultrahigh frequency
ul* uniformly labeled (used within parentheses; see 15.9.5,
Nomenclature, Isotopes, Uniform Labeling)
URI* uniform resource identifier
URL* uniform resource locator .
URN* uniform resource name
URTI upper respiratory tract infection
us ultrasonography; ultrasound
USAN United States Adopted Names [Council]
USP United States Pharmacopeia
 14.12 Units of Measure

!
USSC unrestricted somatic stem cell
W ultraviolet
. .
UV-A* ultraviolet A
UV-B* ultraviolet B
I
UV-C* ultraviolet C

VAIN vaginal intraepithelial neoplasia

vCJD variant Creutzfeldt-Jakob disease
VDRL. Venereal Disease Research Laboratory (add test)
VEGF vascular endothelial growth factor
VEP visual evoked potential
VER visual evoked response
VHDL very highdensity lipoprotein
VHF very high frequency; viral hemorrhagic fever
VLBW very low birth weight (but very low-birth-weight infant)
W L very lowdensity lipoprotein
voz oxygen consumption per unit time
vo- maximum oxygen consumption
VPB ventricular premature beat
v/Q ventilation-perfusion [ratio or scan1
vs* versus (use v for legal references)
VSD ventricular septa1 defect
VT ventricular tachycardia; tidal volume
VZV varicella zoster virus

WAIS Wechsler Adult Intelligence Scale

WBC white blood cell
mE. western equine encephalomyelitis
WISC-R Wechsler Intelligence Scale for Children

XML* extensible markup language

YLD years living with disability
YPLL years of potential life lost

zip* Zone Improvement Plan (zip code)

This abbreviation may be used without expansion.

Units of Measure. J A M and the Archives Journals report quantitative values in

conventional units. A number of analytes, however, are dual reported in the Inter-
national System of Units (SI units, Systeme International dlUnitCs),with conventional
units first, followed by the SI conversion in parentheses. See 18.5, Units of Measure,
Conventional Units and SI Units in JAMA and the Archiucs Journals.
14.12 Units of Measure

Use the following abbreviations and qmbols with a numerical quantity in ac-
cordance with guidelines in 18.0. Units of hleasure. See especially 16.5. Unirs; of
Measure, Conventional Units and S1 Units injA4iA and the A ~ h i u e Journals;
s Table 2
in chapter 18, Selected Laboraton Tests, References Ranges with and Conversion
Factors; and 8.4, Punctuation, Forward Slash (Virgule, Solidus). Exceptiotz: The fol-
lowing example is an acceptable format in table footnotes or figure legends:
SI conversion factor: To convert creatinine value to mmol/L, multiply by
88.4.
Note: Do not capitalize abbreviated units of measure (unless the abbreviation itself is
always capitalized or contains capical letters).
acre acre
ampere
angstrom Convert to nanometers
(1 angstrom = 0.1 nm).
atmosphere, standard atm
. .
bar bar
barn b*
base pair bp*
becquerel Bq
billion electron volts GeV
Bodansky unit BU*
British thermal unit BTU

calorie cal
candela cd'
Celsius - C (Use closed up with degree
symbol, eg, 40°C.)
centigram cg
centimeter cm
centimeters of water cm H20
centimorgan cM
centipoise CP
coulomb C*
counts per minute cpm
counts per second CPS
cubic centimeter cm3 (Use milliliter for liquid and
gas measure.)
cubic foot cu ft
cubic inch
cubic meter
cubic micrometer
 14.12 Units of Meas~

cubic millimeter mm3 (Use microliter for liquid

and gas measure.)
cubic yard cu yd
curie Ci
t cycles per second Use hertz.

dalton Da
day d+
decibel dB
decigram Convert to grams.
deciliter dL
decimeter Convert to meters.
diopter D*
disintegrations per minute dpm'
disintegrations per second dps*
dyne dyne

electron volt eV
electrostatic unit ESU*
equivalent ES
equivalent roentgen equivalent roentgen

Fahrenheit F (Use closed up with degree

symbol, eg, 99°F.)
farad (electric capacitance) F
femtogram fg
ferntoliter fL
femtomole fmol
fluid ounce fl oz
foot ft (Convert to meters; query author.)

! gas volume gas volume

i
gauss G
i gigabyte GB

I grain
gram
gravity (2c.c.clcration rluc 10)
grain
R
,q (Ilsc- closctl up t o p r ~ c d i n l :
numl>cr,cg, 200,q.)
gr.1). Gy

hcnn I I*
hrn7 Fl z
14.12 Units of Measure

horsepower
hour
immunizing unit ImmU'
inch in
international benzoate unit IBU*
international unit IU

joule
katal kat*
kelvin K
kilobase kb*
kilobyte kL3
kilocalorie kc4
!+locurie kCi
kilodaiton kDa
kiloelectron volt keV
kilogram kg
kilohertz kHz
kilojoule kJ
kilometer ' krn
kilopascal kPa
kilovolt kV
kilovolt-ampere kVA
kilovolt (constant potential) kV(cpY
kilovolt (peak) kV(pY
kilowatt kW
King-Armstrong unit King-Armstrong unit
knot knot
liter
lumen lumen
lux lux
megabyte MB
megacurie MCi
megacycle Mc
megahertz MHz
megaunit MU
megawatt MW
meter m
 14.12 Units of Measure

metric ton metric ton

microampere PA
microcurie pCi
microfarad pF*
microgram Pg
microliter PL
micrometer Pm
micromicrocurie Use picocurie.
micromicrogram Use picogram.
micromicrometer' Use picometer.
micromolar w
micromole pmol
micron Use micrometer.
PN
microosmole pOsm
microunit PU
microvolt PV
microwatt PW
mile mile
. miles per hour mph
milliampere
rnillicurie
rnillicuries destroyed
milliequivalent
millifarad
milligram mg
milligram-element mg-el*
milli-international unit mIU
milliliter
milli,meter mm
millimeters of mercury mm Hg
millimeters of water nun H20
millimolar mM
millimole mmol
million electron volts MeV
milliosmole
millirem
milliroentgen
millisecond
14.12 Units of Measure

milliunit
millivolt
milliwatt
minute (time)
molar
mole rnol
lr~onth mot
morgan M*
mouse unit MU*
nano,curie
nanogram
nanometer
nanomolar
nanomole nmol
newton N
normal (solution) N
ohm
osmole osm
ounce 02
outflow (weight) C*
parts per million
pascal
picocurie
picogram
picometer
picomolar
picomole pmol
pint Pt
pound Ib (Convert to milligrams, kilograms,
or grams; query author.)
pounds per square inch psi
prism diopter PD, A'
quart qt
rad rad
radian radian
rat unit RU'
revolutions per minute
 14.12 Units of Measure

roentgen R
roentgen equivalents human rem
(or mammal)
roentgen equivalents physical rep

Saybolt seconds universal SSU*

second st
siemen siemen
sievert Sv
SP g specific gravity (Use with a
number, eg, sp g 13.6.)
square centimeter cm2
square foot sq ft
square inch sq in
square meter m2
square millimeter mm2
Svedberg flotation unit Sf'

tesla T
tom Use millimeters of mercury.
tuberculin unit TU
turbidity-reducing unit TRU*

unit U

volt v
volume vol
volume per volume vol/vol
volume percent vol%

watt W
week
weight
weight per volume
weight per weight

yard
year
'Expand at first mention, with the abbreviation immediately following in pnrenthe5es.
Abbreviate thereafter, except at the beginning of a sentence. (See also 18.3 4. [!nits o f
Measure, Format, Style, and Punctuation, Beginning of Sentence, Tirlc. Subrirle.)
+use the abbreviation only in a virgule construction :~nclin tables and line ;trc
14 and Chemicals
1 3 Ehem~.f~t>
I

Elements and Chemicals. In general, the names of chemical elements and com-
~ w i ~ n should
ds be expanded in the text at first mention and elsewhere in accordance
\\.~ththe guidelines for clinical and technical terms. (See also 15.4.4, Nomenclature,
Drugs, Chenlical Names, and 15.9, Nomenclature, Isotopes.) However, in some cir-
cumstances it may be helpful or necessary to provide the chemical syn~bolsor for- ,
mulas in addition to the expansion if the compound under discussion is new or
relatively unknown or if no nonproprietary term exists. For example:
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) is often referred to
as the most toxic synthetic chemical known. [Use TCDD or dioxin thereafter;
TCDD is more specific, because there is more than 1 form of dioxin.]
3,4-Methylenedioxymethamphetamine(MDMA, ecstasy, XTC), a synthetic
analogue of 3,4-merhylenedioxyamphetamine, has been the center of con- -- :
!
troversy over its potential for abuse vs its use as a psychotherapeutic agent.
[Use MDM, ecstasy, or XTC thereafter, depending on the article's context.] 1I
The following format may also be used: .

Isorhodeose (chemical name, 6-deoxy-D-glucose[CH3(CHOH)4CHOI) is a

sugar derived from Cinchona o#cinalis. [Use "isorhodeose" thereafter.]
Names such as "sodium lauryl sulfate" are easier to express and understand (and type-
I
set) than "CH3(CH2)IoCH20S03Na."Similarly, "oxygen" and "water" do not take up
much more space than "02"and "H20nand hence should remain expanded throughout-..- .
a manuscript, unless specific measurements (eg, gas exchange) are under discussion.

l
The venous C02 pressure is always greater than arterial C01 pressure; speci-
fically, ~ v c o ~ / P a cisogreater
~ than 1.0 except when Po2 plus Pco2 is mea-
sured. Nevertheless, the C02 levels should be carefully measured.
Near the earth's surface, the atmosphere has a welldefined chemical com-
position, consisting of molecular nitrogen, molecular oxygen, and argon. It
also contains small amounts of carbon dioxide and water vapor, along with
trace quantities of methane, &onia, nitrous oxide, hydrogen sulfide,
helium, neon, krypton, xenon, and various other gases.
In the following example, sodium and potassium are not abbreviated.
Repeated serum chernistxy studies confirmed a serum sodium level of 140
'. 1
mEq/L and a serum potassium level of 145 mEg/L.
In the text and elsewhere, the expansion of such symbols as ~ a or+ ca2+ can be
cumbersome, since these symbols have a specific meaning for the reader. Usage
should follow the context. For example, in nontechnical pieces, the flavor of the
writing might be lost if, For example, the editor arbitrarily changed "COT to "carbon
dioxide" ("What's the patient's COz?"). '

When chemical symbols and formulas are used, they must be carefully marked
for the printer, especially when chemical bonds are expressed. (See also 21.1,
Mathematical Composition, Copy Marking.) Three types of chemical bonds com- ,
monly seen in organic and biochemical compounds are single, double, and triple: i
 14.14 Radioactive Isotopes

When deciding whether to expand or abbreviate element and chemical names, the
editor and the author should consider guidelines for established terminology, the
i manuscript's subject matter, technical level, and audience, and the context in which
the term appears.

Radioactive Isotopes. In general, the expanded terms for radioactive isotopes are
used in J A M and the Archive. Journals, as described in 15.9, Nomenclature, Iso-
topes, with exceptions noted, for example, in radioactive pharmaceuticals and certain
chemical notations. The following table lists radioactive isotopes (and their symbols)
used in medical diagnosis and therapy (adapted from The Merck ~ndex~). (See also
15.9.2, Nomenclature, Isotopes, Radiopharrnaceuticals, and 15.9.3, Nomenclature,
Isotopes, Radiopharmaceiltical Compounds Without ~ p p r o v e dNames.)
Name Symbol
americium Am
calcium Ca
cesium
chromium
cobalt
copper
fluorine
gadolinium
gallium
gold
indium
iodine
iridium
iron
krypton
mercury
phosphorus
potassium
radium
radon
ruthenium
selenium
sodium .
strontium
sulfur
technetium
14.14 Rad~oacllveIwtorjcc

.V<Jl ? I t > S,-r11 ix,l

- - --
rtull~un~ TI
xcnon Se
ytterbium YI,
ACKNOWLEDGMENT
Principal author: Roxanne K. Young, ELS

REFERENCES
1 . Smyth H W ; Messing GM, rev ed. Greek Grammar. Cambridge, MA: Harvard University
Press; 1984104.
2. Watson R. Presented by Kinnock N. A journalist's view of clarity at the Commission.
Presented at: First Clear Writing Awards; July 12, 2001; Brussels, Belgium. http://
europa.eu.int/comm/translation/en/ftfog/clearwntinawardswaon.h. Ac-
cessed February 11, 2004.
3. Memiam-Webster's Collegiate Dictionary. 11th ed. Springfield, MA: Merriam-Webster
Inc; 2003.
4. p a h a s K National Libraty of Medicine Recommended Fonnats for Bibliographic i
Citation. Bethesda, MD: Reference Section, National Library of Medicine, National j
Institutes of Health, US Dept of Health and Human Services; 1991.

96-267.
6. O'Neil MJ,Smith A, Heckelman PE, eds. i%e Merck Index: Encyclopdia of Chemicals,
Drugs, 6 Biologicak. 13th ed. Whitehouse Station, NJ: Merck & Co Inc; 2001.

528

. .

s-
I,.
15.1 15.6
Blood Groups. Platelet Antigens, and Genetics
Granulocyte Antigens 15.6.1 Nucleic Acids and Amino Acids
15.1.1 Blood Groups 15.6.2 Human Gene Nomenclature
15.1.2 Platelet-SpecificAntigens 15.6.3 Oncogenes and Tumor Suppressor Genes
15.1.3 Granulocyte Antigens 15.6.4 Human Chromosomes
15.6.5 Nonhuman Genetic Terms
15.2 15.6.6 Pedigrees
Cancer
15.2.1 Cancer Stage 15.7
15.2.2 The TNM Staging System Hemostasis
15.23 Bethesda System 15.7.1 Primary Hemostasis
15.2.4 Multiple Endocrine Neoplasia 15.7.2 Endothelial Factors
15.2.5 Molecular Cancer Terminology 15.7.3 Secondary Hemostasis
15.7.4 Inhibition of Coagulation and
15.3 Fibrinolysis
Cardiology
15.3.1 Electrocardiographic Terms . 15.8
15.3.2 Electrograms Immunology
15.33 Heart Sounds 15.8.1 Chemokines
15.3.4 Murmurs 15.8.2 CD Cell Markers
15.3.5 Jugular Venous Pulse 15.8.3 Complement
15.3.6 Echocardiography 15.8.4 Cytokines
15.3.7 Pacemaker Codes 15.8.5 HLAJMajor Histocompatibility Complex
15.3.8 Implanted Cardioverter/Defibrillators 15.8.6 lmmunoglobulins
15.3.9 Pacemaker-Lead Code 15.8.7 Lymphocytes
15.3.10 Heart Disease Classifications
15.3.11 Coronary Artery Angiographic 15.9
Classifications Isotopes
15.3.12 Cellular and Molecular Cardiology 15.9.1 Elements
15.9.2 Radiopharmaceuticals
15.4 15.9.3 Radiopharmaceutical Compounds
Without Approved Names
15.4.1 The Drug Development and Approval 15.9.4 . Radiopharmaceutical Proprietary Names
Process 15.9.5 Uniform Labeling
15.4.2 Nonproprietary Names 15.9.6 Hydrogen lsotopes
15.4.3 Proprietary Names 15.9.7 Metastable lsotopes
15.4.4 Chemical Names
15.4.5 Code Designations 15.10
15.4.6 Trivial Names Molecular Medicine
15.4.7 ~ r d With
~ s Inactive Component?; 15.10.1 Molecular Terminology: Other Sections of
15.4.8 Stereoisomers Chapter 15
15.4.9 Combination Products 15.10.2 Molecular Terms: Considerations bnd
15.4.10 Drug Preparation Names That Include a Examples
Percentage 15.10.3 Enzyme Nomenclature
15.4.1 1 Multiple-Drug Regimens
15.4.12 Drug Abbreviations 15.11
15.4.13 Nomenclature for Biological Products Neurology
15.4.14 Vitamins and Related Compounds 15.11.1 Nerves
15 4 15 Herbals and Dietary Supplements 15.1 1.2 Electroencephalographic Terms
15.11.3 Evoked Potentials
15.5 15.11.4 Polysomnography and Sleep Stages
Equipment, rnvites. and Reigentr 15.11.5 Molecular Neuroscience
Nomenclature

15.12 15.16
Obstetric Terms Pulmonary, Rnpiratory. and Blood Gas
15.12.1 GPA T*nninology
15.12.2 TPAL 15.16.1 Symbols
15.12.3 Apgar Score 15.16.2 Abbreviations
15.16.3 Mechanical Ventilation
15.13
Ophthalmology Terms 15.17
Radiology Terms
15.14 15.17.1 Resources
Organisms and Pathogens 15.17.2 Terms
15.14.1 . Biological Nomenclature
15.14.2 Bacteria: Additional Terminology
15.14.3 Virus Nomenclature
15.14.4 Prions

15.15
Psychiatric Terminology
15.15.1 Diagnostic and Statistical Manual
o f Mental Disorders (DSM)
15.15.2 Other Psychiatric Terminology

A generally accepted and uniuetsally used system

of nomenclature is an essential tool in any area
of study.
Julia G . ~odmer'

.the Author o.,f this editorial thouaht nomenck?ture

w

was boring and went sight-seeing-a serious

misjudgment, in retmspect.
H. 2ola2

Evolution continues, in nomenclature a . in the real d

life which cannot be discussed and hence u.ndmtood
without it.
Richard V . ~ e l v i l l e ~

I am away from my desk. . . .Ifyou are in need

of immediate nomenclature assistance, please
contact. . .
Lois Maltais, Jackson Laboratory,
e-mail message
This chapter is devoted to nomenclature: systematically formulated names for spe- :
cific entities.
Biological nomenclature dates back at least to the 18th century. Since the mid-
20th century, many biomedical disciplines have established committees to develop

\
and promulgate official systems of nomenclature. I

Accelerating knowledge, particularly from molecular biology, necessitated the

official biomedical nomenclature systems, sometimes with dramatic results. For in-
stance, a single coagulation factor had been referred to by 14 different names.* An
 Nomenclature

investigator deemed the official coagulation nomenclature "one of the most sig-
nificant, even if only semantic, recent advances in the field."5'p1G'The results, proba-
bly true in other disciplinesas well, were that an "impenetrable confusionwas cleared
away, apparent disagreements were often shown to be conflicts of terminology, not
of fact, and a much freer exchange of information was made possible."5@'6)
In microbiology, with publication of the approved list of bacterial names in 1980,
the number of names of bacteria decreased by an order of magnitude, from around
30000 to around 2000~~'(now nearly 7500~).The CD (clusters of differentiation) no-
menclature is thought to have prevented mistakes in laboratory and clinical research?
Those are some indications of the compelling need for systematic nomenclature,
which requires the ongoing work of international groups. The development of
nomenclature, however, faces challenges besides multiplicity of names. There is
tradition-"the ruins of previous sy~terns"'~(P~-whichinvestigators are often re-
luctant to give up. When disciplines converge-for instance, when the genetics of
a physiologic system are delineated-preexisting systems of nomenclature may
operate in parallel, and names proliferate.11 For instance, concerning the homol-
ogous human J3.A and mouse H-2 tissue antigen systems, it has been observed:
The situation is perhaps similar to what one might have encountered in the
field of immunoglobulins had researchers working with immunoglobulins in
different species not realized relatively early that the classes of heavy chains
and light chains they were working with were homologous and been williig
to adopt a common nomenclature. We might then have separate names in
each species for IgM, IgG, IgA, kappa, lamb&, and so ~ n . ' ~ ~ ' * '
A system of nomenclature may face the test of sheer numbers. The count
of assigned gene symbols has increased from several hundred1'*'* to more than
~ more than 25 000 human genes anticipated.16*" The system was de-
with
23 0 0 0 , ~
vised with a foresight that has allowed transition from typescript tp print to online
database.ls2'
Another challenge is to remain flexible. Those who deal with nomenclature ac-
cept it as a c o n s u u ~ t and
~ ' ~have
~ ~ noted the need to reflect new k n o w ~ e d ~ e . ~ ~ . ~ ~
Biomedical classification is arbitrary and "artificial," created by No-
menclature needs to "evolve with new technology rather than be restrictive as
sometimes occurs when historica'l . ..systems are
Such flexibility, however, places a burden on clinicians, who must replace f:1-
miliar names with new ones.29Often, "colorful or descriptive n a r n e ~ , " ~ ~ '\vl~icl~ ~''"
are more easily retained?' give way to more efficient terms, such as the alpha-
numeric epithets of many systems.
Nomenclature systems may differ markedly in approach. Stability is an o\.cr-
riding principle of the codes of taxonomic nomenclature, which nvoitl n:\lw
changes." For instance, the bacteriologic code has a provision that a namc may Ix.
rejected "whose application is likely to lead to accidents endangering llealth or lifc ( , r
both or of serious economic c ~ n s e ~ u e n c e s . " ~ For
~ ' example,
~'~) the n:irne ) i v s r t , r t r
pseudotuberculosz3 S U ~ S Ppestis for the plague b;lc.illus \v;is reiccred i ~ n r ld l c n.llllt.
Yeniniapestis r e t a i r ~ e dbecause
~ ~ . ~ ~of concerns ;rbout public heal1h I~;~z:lrd.\ [ c~ I I I ~
to confusion of themame of the plague bacillus u.itI1 rhar of the less r ~ n l l ~ n)i.tsrtrrrr r
pseudotuber~~l~~@'35). In contrast, current)' :In ovcmding princ.~plcoI'rln.- (,l.fi~
is; 1.11

human gene nomenclature, with genes rc.nam~.~l re[lec~ ncn kno\vlc.rl~c.(01'r l r r

;
approximately 260 gene symbols in ,s !,f C,rnc . \ l . ~ r k r r h 1.f
fir,! (-.lfil\, rfrl!
e
Nomenclature

introduction of the current system of gene nomenclature, more than half have been
Yet the principles of stability and currency are not mutually exclusive;
for instance, the bacteriologic code requires name changes necessitated by revisions
of taxonomy, and the human gene nomenclature acknowledges former names and
aliases.
Nomenclature is "the means of channelling the outputs of systematic research
for general consumption"37 and aims for international scope (" '. . .Science should
unite Nations. . . ' "M'p'03. ~ i a n ~ r a n d e ~ "writes
~ ~ ' ~that
) international nomenclature
efforts in coagulation "provide[dl an outstanding early example of intemational col-
laboration to resolve a scientific problem. This sort of co-operation is now com-
monplace, but was certainly not typical in [the post-World War I11period." To facilitate
worldwide access to the latest temls, large computerized databases have been created.
But computerized databases require consistent use of nomenclature." Unique iden-
tifiers provide a home base for terms in large databases but are not practical for
referring to entities throughout published articles and textbook~~~-hence. names.
Our purpose in the nomenclature chapter is to explain not how names should be
devised (although we cite the sources of such iules) but rather which names should .
be used'and how they should be styled. Official systems of nomenclature are not
universally observed to the letter (literally or figuratively), but style that is consistent
with official guidelines and within publications reduces ambiguity. Editors have the
task of mediating between official systems and authors' actual usage. To that end, the
goals of this chapter are to present style for terrns and to explain terms in hopes that
they are more easily dealt with.
In medical nomenclature the stylistic trend has been toward typographic
simplicity, driven by computers. Terms lose hyphens, superscripts, subscripts, and
spaces. However, such features have not been eliminated completely, either within or
beyond these pages. In 1950 standardized terms in pulmonary-respiratory medicine
and physiology were put forth, and typographic features impossible on a typewriter
were expressly retained, seen as indispensable components of a systematic and en-
lightening n o m e n c l a t ~ r e .Computers
~~ are hcreasingIy capable of generating un-
usual characters, and typographic simplification and electronic sophistication may
cross paths before medical nomenclature loses its last defining flourishes.
An umbrella resource for biomedical terminology is the Unified Medical Lan-
guage System (UMLS), a project of the National Library of Medicine. The UMLS is
intended to provide integrated terrninology (including synonyms and relationships
among terms) for use in electronic applications, ie, computer systerns.41.42A major
component of the UMIS is the Metathesaurus, a comprehensive repository of bio-
medical terms and their relationships. The Metathesaurus is accessible online at the
UMLS Knowledge Source Server, http://umlsks.nlm.nih.gov. (Complimentary regis-
tration is required.) That site offers concept and term searches that can be useful to
medical authors and editors seeking explanations of particular terms, including their
relationships to other terms (eg, human gene, protein, condition, and animal coun-
terparts)?'

ACKNOWLEDGMENTS
Principal authors: Margaret A. Winker, MD, sections 15.4, 15.5, and 15.9;Richard M.
Glass, MD, section 15.15; Harriet S, Meyer, MD, remaining sections
The following individuals reviewed drafts and provided invaluable suggestions:
Blood Groups and Platelet Anfigerzsr Geoff Daniels, PhD. Bristol lnsritute for Trans-
 Nomenclature

fusion Sciences, Bristol, England; Cancer: Irvin D. Fleming, MD, Methocl~stHeiilth-

care, Memphis, Tennessee; Cardiology: Michael S . Lauer, MD, Cleveland Clinic Hmrr
\ Center, Cleveland, Ohio, JAMA/Archives Journals, Chicago, Illinois; Dntgs. StepIi:i-
nie C. Shubat, MS, Director, USAN Program, Chicago, Illinois; David S. Cooper, ~ I I ) .
Sinai Hospital of Baltimore,Johns Hopkins University School of Medicine, Daltiniorc.
Maryland,JAMAIArchivesJournals, Chicago, Illinois (hormones and insulin);Julie A.
Mares, PhD, University of Wisconsin-Madison (vitamins and related compoundb).
Genetics: Richard G. H . Cotton, PhD, DSc, University of Melbourne, Melbourne.
Australia; Stylianos E. Antonarakis, MD, DSc, Centre Medical Universitaire, Gencvc.
-
Switzerland; Dr Johan den Dunnen, Leiden University Medical Center, Leiden. t h ~ ,
Netherlands, Human Genome Variation Society; Daniel W. Nebert, MD, University of
Cincinnati Medical Center,Cincinnati, Obio (nucleic acids and amino acids; hunian .
genes); Hester Mary Wain, PhD, Galton Laboratory, University College, Lonclon.
England (human gene nomenclature); Boris Pasche, MD, PhD, Northwestern Uni-
versity Medical Center, JAUAIArchives Journals, Chicago, Illinois (oncogenes and
tumor suppressor genes); Dr Felix Mitelman, University Hospital, Lund, Sweden
(chromosomes); Lois J. Maltais, BS, The Jackson Laboratory,. Bar Harbor, Maine
(nonhuman genetic terms); Robin L. Bennett, MS, CGC, University of Washington
Medical Center, Seattle (pedigrees); Hemostasis: Leon W. Hoyer, MD, Annapolis.
Maryland; Immunology: Tristram G. Parslow, MD, PhD, Emory University, Atlanta,
Georgia, Howard M. Gebel, PhD, Emory University, Atlanta, Georgia, Robert A. Bray,
PhD, Emory University, Atlanta, Georgia; Steven G. E. Marsh, PhD, ARCS, Anthony
Nolan Research Institute, Royal Free Hospital, London, England;MolecularMedicine:
Boris Pasche, MD, PhD, Northwestern University Medical Center, Chicago, Illinois,
JAMAIArchiues Journals, Chicago, Illinois; Jeanette M. Smith, MD, JAMAIArchiucs
Journals, Chicago, Illinois; NeumIogy: ~ i c h a eJ.l Amiioff, MD, DSc, FRCP, Universjry
of California, San Francisco, School of Medicine; Ophthalmology: Neil M. Bressltxr,
MD, Johns Hopkins Medical Institutions, Baltimore, Maryland, Daniel M. Albert, MD,
University of Wisconsin Hospitals and Clinics, Madison; O t g a n h and Pathogem
Kevin C. Hazen, PhD, D(ABBM), University of Virginia, Charlottesville (biological
nomenclature); Pulmonay and Respiratory Twrilinology:John B. West, MD, PhD,
DSc, University of California, San Diego, La Jolla.
Cassio Lynm,JAMA, provided illustrations. Joanne Weiskopf,JAMA and Archzrm
Journals, adapted illustrations. Yolanda Davis-Ellis and Sandra Schefris, James S.
Todd Memorial Library, American Medical Association, Chicago, Illinois, assisted in
obtaining references.

REFERENCE5
1. Bodmer JG. Nomenclature 1991 foreword. Hzrm Immirnol. 1991;34(1):2-3.
2. Zola H. The CD nomenclature: a brief historical summary of the CD nomenclature,why
it exists and how CDs are defined.J Biol Regzil Homeost Agents. 1999;13(4): 226-228.
3. Melville RV. Towards Stability in the Names of Animals: A History of the Itztct~~a~zonnl
Commission on Zoological Nomenclature 1895-1395.London, England: Intern,~r~onal
Trust for ~oologicalNomenclature; 1995.
4. Abe T, Alexander B, Astmp T, et al; and the International Committee for tile No-
menclature of Blood Clotting Factors, Wright IS, chair. The nomenclature of blood
clotting factors.JAMA. 1962;180(9):733-735.
5. Biggs R, ed. Human Blood Coagzrblion, Hett~oslusisU ~ I 7hrombos~.
L ~ 2nd < .. :
England: Blackwell Scientific Publications; 1976:15-16
Nomenclature

6. Baron EJ, Weissfeld AS, Fuselier PA, Brenner DJ. Classification and identification of
bacteria. In: Murray PR, ed. Manual of Clinical Microbiology. 6th ed. Washington, DC:
ASM Press; 1995:249-264.
7. Brooks GF, Butel JS, Morsc SA.Jawetz, Melnick, and Adelberg's Medical Microbiology.
22nd ed. New York, NY: Lange Medical Books/McGraw-Hill; 2001:40.
8. DSMZ-Deutsche Sarnrnlung von Mikroorganismen und Zellkulturen GmBH,
Braunschweig, Germany. Microorganisms: bacterial nomenclature.
http://www.dsmz.de/microorganisms/main.php?conteneid=l4. Accessed April
20, 2006.
9. Singer NG, Todd RF, Fox DA. Structures on the cell surface: update from the Fifth
International workhop on Human Leukocyte Differentiation Antigens. Arthritis
Rheum. 1994;37(8):1245-124s.
10. Wildy P. Classification and Nomenclature of Viruses: Fint Repo?? of the International
Committee on ~okenclatureof Viruses. New York, NY: S Karger AG; 1971:l-26.
Melnick JL, ed. Monographs in Virology, vol 5.
11. Camrnack R. The biochemical nomenclature committees. II%BMBLife. 2000;50(3):159-
161.
12. Hansen TH, Carreno BM, Sachs DH. The major histocompatibility complex. In: Paul
WE, ed. Fundamental Immunology. 3rd ed. New York, NY: Raven Press; 1933:577-
628.
13. Shows TB,McAlpine PJ. The 1981 catalogue of assigned human genetic markers
.
and report of the nomenclature committee. Cytogenet Cell Genet. 1982;32(1-4):
221-,245.
14. Evans HJ, Hamerton JL,Klinger HP, McKusick VA. Human Gene Mapping 5: Edin-
burgh Conference (1979): Fifh Intemational Workshop on Human Gene Mapping.
Basel, Switzerland: S Karger AG; 1979.
15. HUGO Gene Nomenclature Committee Web site. http://www.gene.ucl.ac.uk
/nomenclature/. Updated March 29, 2006. Accessed April 20,2006.
16. Wain HM, ~ i f o r EA, d Lovering RC, Lush MJ, Wright M W , Povey S. Guidelines for
human gene nomenclature (2002). Genomics. 2002;79(4):464470. Also available at
h t t p : / / w w w . g e n e . u d . a c . u k / n o m e n c l a ~ r e / ~Updated
. April 20, 2006.
Accessed April 20,2006.
17. Reaney R. Hu- have fewer genes than previously thought.
h t t p : / / w w w . r e u t e r s . c o m / n e w s A r t i c l e . j h ~ = 6 5 6 2 8 6 . Posted
October 20, 2001. Accessed 0ctober 26, 2004.
18. Shows TB,Alper CA, Bootsma D, et al. Intemational system for human gene no-
menclature (1979). Cytogenet CeU Genet. 1979;25(1-4):96-116.
19. Ruddle FH, Kidd KK.The Human Gene Mapping Workshops in transition. Cytogenet
Cell Genet. 1989;51(1-4):l-2.
20. Progress in nomenclature and symbols for cytogenetics and somatic-cell genetics
[editorial]. Ann Intern Med. 1979;91(3):487-488.
21. Staley JT, Krieg NR. Bacterial classification, I: classification of procaryotic organisms:
an overview. In: Krieg NR, Holt JF, eds. Betgey's Manual of Systematic Bactm'ology.
Vol 1. Baltimore, MD: Williams & Wilkins; 1984:l-4.
22. Erzinclioglu YZ, Unwin DM. The stabiliry of zoological nomenclature [letter]. Nature.
1986;320(6064):687.
23. Lublin DM, Telen MJ. What is a blood group antigen [letter]? Tramf~csion. ,

1992;32(5):493.
 Nomenclature

24. Lublin DM, Telen MJ. More about use of the term Drb [letter]. Transfmion.
1993;33(2):182.
25. Pappenheimer JR, chairman; Comroe JH, Cournand A, ~ e r ~ u s JKW, o n et al. Stan-
dardization of definitions and symbols in respiratory physiology. Fed Proc. 1950;9:
602-605.
26. Madias JE. Killip and Forrester classifications: should they be abandoned, kept, re-
evaluated, or modifie& Chest. 2000;117(5):1223-1226.
27. Vandamme PAR. Taxonomy and classification of bacteria. In: Murray PR, Baron EJ,
Jorgensen JH, Pfaller MA, Yolken RH,eds. Manual of Clinical Microbiology. 8th ed.
Washington, DC: ASM Press; 2003271.
28. Shows TB,McAlpine PJ, Boucheix C, et al. Guidelines for human gene nomenclamre:
an international sistem for human gene nomenclature (ISGN, HGM9). Cytogmet Cell
Genet. 1987;46(1-4): 11-28.
29. Patterson PY, Sommers HM.A proposed change in bacterial nomenclature: a rose by
any other name. J Infect L%. 1981;144(1):85-86.
30. Flexner CW.In praise of descriptive nomenclature [letter]. Luncet. 1996;347(89!93):68.
31. Jeffrey C. Biological Nomenclature. 3rd ed. London, England: Edward Arnold; New
York, NY: Routledge Chapman & Hall; 1989.
32. Lapage SP, Sneath PHA, Lessel EF, Skerman VBD, Seeliger HPR, Clark WA; Sneath
PHA, ed. International Code of Nomenclature of Bacteria and Statutes of the Bac-
teriology and Applied Micmbiology Section of the International Union of M i m
biological Societies, 1990 Revision. Washington, DC: American Society for
Microbiology; 1992.
33. Euzeby JP.List of bacterial names with standing in nomenclature--genus Yersinia.
http://www.baaerio.cict.fr/xz/ye~~inia.h. Accessed April 20, -2006.
34. Williams JE.Proposal to reject the new combination Yeniniapseudotu~uIosrS subsp
pestis for violation of the first principles of the International Code of Nomenclature of
Bacteria: request for an opinion. Int J Syst Bacteriol. 19&1;34(2):268-269.
35. Judicial Commission of the International Committee on Systemafic Bacteriology. Re-
jection of the name Yasiniapseudotuberculosissubsp pestis (van Loghem) Bercovier
et al. 1981 and conservation of the name Yminiapestis (Lehma~lnand Neumann) van
Loghem 1944 for the plague bacillus. Int J Systmat Bacteriol. 1985;35(4):540.
36. Searchgenes. Human Gene Nomenclature Database Search ~ n g i n ehttp://www.gene
.
.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.p. Updated August 23, 2005. Accessed
August 23, 2005.
37. Greuter W, Hawksworth DL. Preface. In: Greuter W, McNeill J, Farrie FR, et al. Bz-
temational Code of Botanical Nomenclature (St Louis Code). International Association
for piant Taxonomy. 2000. http://w~w.bgbm.org/~APT/~on~encIamre/Code
/SaintLouis/0002Preface.htm.Updated February 12, 2001..Accessed April 20,;2006.
38. International Society for Microbiology founding brochure. Quoted in: Murray RGE.
Holt JG. The history of Bergey's Manual. In: Boone DR, Castenholtz KW,ecls. U o ~ c < ) , 3
Manual of Systematic BacterioIo,r:y.Val 1. 2nd ed. New York, NY: Springer-\'crl:~~:
2001:i-13.
39. Giangnnde PL. Six characters in search of an author: the history of the nomc.nc.l:~r~~rc
of coagul:ltion factors. Br J Haematol. 2003;121(j):70j-712.
.to nt.urler E. 3fcKusick VA, Motillsky AG, Scriver CR, Hutchinson F. Mutation nolncn-
c.l:~rclrr nickn;~nltl~.
systematic nanles, and uniq~leitlentifiers. If!lrrl .Ilrilcrr. 1000:
N .+).2f1.5-2(Xl
15 1 Blood Groups. Platelet Ant~gens.and G r a n u l ~ y l eAnt~gens

41. S;lrion~lL t ~ r a no f Slculic~nc L i n h d Skd1ca1 L n g u ~ g cSysrcm.

hrrp://uuu..nlrn nih.~ov/rt~~rch/umls/abwt~uds.huni. Published March 22, 2004.
Updxed July 19. 2001. Accessed April 20, 2006.
42. Bodenreidcr 0. The Unlfied bledical Language System (UMLS): integrating
biomedical terminology. ~VucleicAcids Res. 2004;32(database issue):D267-D270.
doi:10.1093/n3r/gkh061.

[Allthough erythrocytes have traditionally been

considered relatively inert cellular containers of
hemoglobin, they are in fact active in a variety
of physiologic processes.
L. Calhoun and L. D. ~ e t z ' ' ~ ' ~ ~ '

E
q
Blood Groups, Platelet Antigens, and Granulocyte Antigens

Blood ~roups.Blood groups are characterized by erythrocyte (red blood cell) anti- , ,
I
gens with common immunologic properties (eg, group A). Blood group systems are
series ef such antigens encoded by a single gene or by a cluster of 2 or 3 closely
linked homologous (eg, ABO system).
There are about 600 recognized erythrocyte antigens2The International Society :
of Blood Transfusion (ISBT) designates around 270 blood group antigens. Of these,
around 250 belong to 1of 29 systems?**(Other antigens remain in officially desig-
nated series or collections.) Some antigens are erythrocyte-specific; others appear
widely, but specifically, on cells of other organs and tissues.
The discoveryof blood group antigenswas prompted by hemolyticdisease of the
newborn and transfusion reactions, but many antigens have since been implicated in
infection and other disease processes'1s; whether fundamentally or incidentally is not
known6 Erythrocytes are estimated to contain millions of antigen sites.'

Traditional/Popular ~omendature?-loTraditional blood group system nomencla-

ture is typically used in.medical publications. It comprises several approaches, and,
therefore, sometimes the same entity (eg, a particular erythrocyte antigen) can be
expressed by more than 1term. Editors generally should follow author preference.
The principal elements named are blood group systems, antigens, phenotypes,
genes, and alleles.

Blood Group Systems. The following list shows the blood group system names and
symbols. (The column of derivations of names of blood group systems is provided
for background interest1'2*9 11-14 [also Geoff Daniels, .PhD, written communications,
May 13 and 17,20041.) .
System Name Symbol Derivation
ABO

without)
Chido/Rogers Ch/Rg Names of antibody .makers

536

. . .

-:: d.
4
 15.1.1 Blood Groups

System Name Derivation

Name of antibody maker
Cromer Cromer Name of antibody maker
Diego Di Name of antibody maker
Dombrock Do Name of antibody maker
Duffy FY Name of antibody maker
Gerbich Ge Name of antibody maker
Gill GIL Name of antibody maker
Globoside - GLOB Globoside synthetase
Hh H Concept C'heterogenetic")
I I Concept ("individuality")
Indian In Geographic
John Milton Hagen JMH Name of antibody maker
Kell K Name of antibody maker (Kelleher)
Kidd Jk Initials of infant child of antihorly
maker (K already in use)
Knops Name of antibody maker
Kx Association with Kell and
X chromosome
Lewis Le Name of antibody maker
Lutheran Lu Name of antibody maker (actually
uttera an^ or ~ u t e r a n ' ~ )
LW or Landsteiner/Wiener LW Names of investigators
MNSs MNS M, N: the word immune;S: location
(Sydney, Australia)
U (an antigen of the MNSs
system): universal
Ok OK Family name initials (Kobutso; letters
reversed because ''G was in use)
P P Alphabetical
Raph Raph Name of antibody maker
Rh Rh Rhesus monkeys (antigens were,
LW antigens)
Scianna Sc Rime of antibody rnaker
xg XR X chromosome and location (Grand
R:~pids,Michigan)
\r't or Cnnnrighr \it ..

The ISRT prrfer.; a n all-capik~lstylc for Idfxxl Krorlp \).itern syml~ols3

(see "ISUT
N31nr anti Krjmtx-r" in this .u~ction).
15.1 Blood Groups. Platelet kntlgens, a n d Granulocyte Antigenr

I'hc follo\ving are cs:imples of uwgc:

AI30 inco~np;~ril,ility
A cell
rype AB recipient
type 0 donor
Hemolytic disease of the newborn primarily occurs from incompatibilities of
the Rh, ABO, or Kell blood groups.

Antigens. Antigen terms use single or dual letters, often with a qualifier that is a letter
(usually superscript) or number (subscript or typeset on the line).
A, Al, A21 Ax, B
cr"
Ffl Fyb
Ee

Kpa, K ~Ku,~Jsa,,JS~
K11, K12, K13, K14, Krn
Lea, Leb, LebH, B L ~ ~
Lua, L U ~ \

The Rh system historically has used 3 alternative schemes: the,Rh-Hr nomenclature,

the CDE nomenclature, and the numerical nomenclature? Terms from the h s t , eg,
rh', hr", rhx, RhA, are appropriate in historical discussions, but otherwise, the CDE
and numerical nomenclatures are favored:
4, C, E, c, e, f
Ce, Cw, Cx . . .BARC
Of

Rhl, Rh2, Rh3, Rh4, Rh5, RH6

M 7 , RH8, M 9 . . :M52
The following are examples of antigen-term usage:
anti-Jka alloantibody
Rh(D) incompatibility
human monoclonal anti-D antibodies
 15.1.1 Blood Groups

Studies using anti-Ch and anti-Rg antisera have demonsuated Ch and Kg

determinants on complement component C4.

Phenotypes. In phenotypic expressions--terms that describe an individual's blood

group or type-the presence or absence of an antigen is often indicated by a plus or
minus sign:
Antigen: M
Phenotype: M+
M+N+S-s+ erythrocytes
M+N+S-s+ phenotype
Lowercase letters that were superscripts in the antigen terms are set on the line in
parentheses in phenotypic terms.
Antigen: L U ~
Phenotype: Lu(b+)
More than 98% of the Western population is Lu(b+).
If the numeiical terminology is used for the antigen, a colon is added in the phe-
notype.
Antigen: Scl
Phenotype: Sc:l
the Sc:l,-2,3 phenotype
Other sample phenotypic terms include the following:

thC silent phenotype Le(a-b-1

A superscript w can indicate a weak reaction:

The ABO system is an exception: its phenotypic terms clo not fr.;~ri~rc
plu3 o r nllnu\
signs; A (not A+) indicates A erythrocyte antigens; (1 (nor A-- 13-) indic.~~~...;
r t ~ ~
absence of A and B antigens:
15.1 Blood Groups, Platelet Antigens, and Granulocyte Antigens

Groups: 0, A, B, AB, Oh, ohA

Subgroups: Al, A2, AIB, A2B
ohAindividuals do not express the H determinant but do have the A allele.
Terms for Rh phenotypes, which do not feature plus and minus signs, are also in use:
D-positive (Rh positive)
I.
D-negative (Rh negative)
DccE, DCce
RH:1,2,3
Rhnull
Absence of C, c, E, and/or e antigens is indicated with 1 or 2 minus signs14:

Usage note: Terms such as O+ ("0positive"), A+, and AB- are common parlance as.
Shorthand for blood of the ABO system and its Rh specificity. However, in scientific.
articles, use standard terms that specifically indicate Rh status:
0 Rh-positive
0 Rh+
or more specific designations of phenotype:
group B, D-negative
I
group A, Rh D-positive
In a blood group profile, elements from diFferent systems may be separated by
commas, as above, or, for more complex specificities, with semicolons:
The patient's blood was group B,Rh positive, D+ C+ c+ E- e+; M+ N+ S-
t
s+; PI+; Le(a-b-1; K- k+; Fy(a-b+); Jk(a+b-1. 15@846)
Note that in phenotypic expressions commas do not appear within elements of the
same blood group system:
D+ C+ c+ E- e+
Not: D+, C+, c+, E-, e+
Commas may be dispensed with between different blood group systems in bri
expressions:
K+Fy(a+)

Genes. As with International standard Gene Nomenclature (the "HUGO" recorn-

mendations; see 15.6.2, Genetics, Human Gene Nomenclature), ISBT gene terms
italicized. Traditional blood-group gene symbols often mixed uppercase and 1
ercase. However, symbols recommended by ISBT, like those of HUGO, use all ca
letters.
The following list3~4.9n'6
shows gene symbols associated with blood g
systems.

540

- ---
- . -- . .
= &.-*"..-. . .-
 15..1.1 Blood Groups

Traditional ZSBT HUGO

qBd ABO ABO
Chl@ C4A, C4B C4A, C4B
Co AQPl AQP1 (was CO)
Cmmw DAF CD55 (was DAB
Di SLC4A1 SLC4A1
Do DO ART4 (was DO)
FY FY DARC (was FY)
Ge GWC GWC
IGILI 42'3 AQP3
[Globoside] B3GALB B3GALT3
Hh m 1 FUTl
111 GCNm GCNm
In CD44 CD44
fi SLC14AI SLC14A1
UMHl SEUA 7A SEUA 7A
K KEL K;EI.
Kn CRI CRI
Kjc XK XK
Lx? FLnJ m 3
Lu LU BCAM (was LU)
LW zcAM4 zCAM4
MNor MNSs GWA, GYPB, GWE GWA, GWB, GWE
Ok BSG BSG (previously OK, CD147)
-p' PI A4GALT
Raph CD151 (wasMER2) CD151
Rh RHCE, RHD RHCE, M D
sc ERMAP sc
XG, MIC2 XG
Yt , ACHE ACHE
Gene symbols expressed according to ISBVor H U G O ' ~are preferred to trndition:~l
symbols.
Parenthetic synonyms are helpful:
(formerly OK)
. BSG

ERMAP (also called SC)

The Lutheran inllil,itor gcnc is cxl>rcssctl;IS fi)llows:
In(Lu) [traditional]
lNLU [standard]
15.1 Blood Groups, Platelet Antigens, and Granulocyte Antigens

'
Do not confuse In with the traditional Indian blood group gene symbol, In (rec-
ommended gene symbol: CD44).

Alleles. The italicized blood group symbol-ABO, MNS, M,etc-is used for alleles ,:, ,
(which are also distinguished by an asterisk and number). In the following example, i
compare the gene symbol and an allele term from the same blood group:
I

SC'I [allele]
I
EIZlZlAP [gene symbol] I
Note that qualifiers that are subscripts in antigen terms are superscripts in allelic
terms, eg, Al antigen, A' allele). The following are examples of genotypic terms.
- I
M1y IW( NN, MSNs
DCe/DCe (R'R')
DcEldce ( l r )
d c d d c e (w)
D- -ID- -
LuuLua, L U ~ L UL ~U ,~ L U ~
LeIe, &Le, lele
FfFf. FF~F~, OFY
~k K ~ O K PJ~S," / .
JVJP, jk?kb, ]k"Jkb
ww,W a &?%
WY;
%Y
For expressing alleles, the ISBT gives an option, eg, either Ff or I;Y*I
propriate superscripts and italics). Miiring the 2 styles, however (eg, P A ) , is not
appropriate (Geoff Daniels, PhD, written communications, May 13 and 17, 2004).

lSBT Name and umber.^,^^",'^ In the 1980s the Working Party on Terminolo
Red Cell Surface Antigens of the ISBT developed an alphanumeric system of blood
group notation, intended to provide "a uniform nomenclature that is b
machine readable and in keeping with the genetic basis of blood
system does not replace traditional terminology; rather, its terms corresp
traditional terms. It is also used to assign new terms as needed. In the IS
nology, each blood group system has a symbol, usually of 1 to 3 capital letters, and a
system number of 3 digits.
System ' Antigen No. Within System
1 Name Symbol No.!
- 1001
- 002
- 003
-
ABO ' ABO 001 A B . A,B
MNS MNS 002 M N S s
Rh RH 004 D C E
Ks XK 019 Kx

- - = -
=-
I-.
 Sinistral (left-hand) zeros can be dropped from system ancl antigen terms. ancl s!.stc~n
letter symbols can be used as part of the alphanumeric tcrrii. Thc follo\\:ing. f o r
i instance, are all acceptable for blood type AB:
AB
AB0:1,2,3
001:1,2,3
The following are acceptable terms for the antigen A,B:

~ u t h o r smay use ISBT terms in parentheses following traditional terms:

The patient's red blood cells were negative for Cromer blood system anti-
gens C? (CROMI) and Tca (CROM2).
In notations that use plus and minus signs to express presence and absence of
particular antigens, phenotypic expressions in the numerical notation use a colon
and numbers in place of letters, as in these examples:
LE:-1,2 [for Ha-b+)l
FY:l,-2 [for FY(a+b-)I
Genotypic expressions are italicized:
FY 112.or F Y I 1 2 (for ~ ~ ~ ~ ~ t 3
Tables of blood group systems, symbols, antigens, and ISBT numbers are available at
the ISBT Committee on Terminology for Red Cell Surface Antigens Web site.4

Platelet-Specific Antigens. The current system of human platelet antigen (HPA)

nomenclature, adopted in 1390, is overseen by the Platelet Nomenclature Committee
of the ISBT and the International Society on Thrombosis and ~aemostasis.'~-~' As
with blood gfoups, there are platelet antigen systems and specific antigens within
those systems. The HPA nomenclature pertains to "all protein alloantigens expressed
on the platelet membrane, except those coded by genes of the major histocompat-
ibility complex ( M H C ) . " ~ ""~(See
~ ~ 15.8.5, Immunology, HLA/Major Histocompat-
ibility Complex.) Currently, there are 6 HPA systems: HPA-1, HPA-2, HPA-3, HPA-4,
HPA-5, and HPA-15."
Complete tables of HPA terms are available at the IPD-HPA Database, http://
u-n~~~.ebi.ac.~k/i~d/h~a/.~' Sample terms include the following:
Antigen system: HPA-1
I
~swxiatedglycoprotein: GpIIIa
i1. Cl) designation of glycoprotein: CD61
1 5 . 1 Blood Group%.Platrlc: Anl~gen%.
and Granulocyte Ant~gens

Former antigen names:

Gene:
Alleles:

Epitopes:

Locuslink ID:
Ref-Seq:
Swiss-Prot:
Nucleotide change:
For CD (clusters .of differentiation) nomenclature, see 15.8.7, Immunology, Lym-
phocytes. For gene and allele nomenclature, see 15.6.2, Genetics, Human Gene
Nomenclature. For database identifiers and nucleotide nomenclature, see 15.6.1
Genetics, Nucleic Acids and Amino Acids.

Granulocyte Antigens. The Granulocyte Antigen Working Party of the ISBT has
formulated rules for well-defined human neutrophil antigens (HNAS)?~ as presented
in the following tabulation, although at this writing they have not met with universal

Antigen Sytem Antigen Former Name Alleles

HNA-1 HNA-la NA1 FCGmB*I
HNA-lb
HNA-lc
HNA-2 HNA-2a
HNA-3 HNA-3a
HNA-4 HNA-4a
HNA-5 HNA-5a
See also 15.8.6, Immunology, Immunoglobulins, for Fc receptor terminology and
15.8.7, Immunology, Lymphocytes, for CD terminology.

REFERENCES
1. Calhoun L, Petz LD. Erythrocyte antigens and antibodies. In: Beutler E, Lichtrnan MA,
Coller BS, Kipps TJ, Seligsohn U, eds. Williams Hematology. 6th ed. New York, NY:
McGraw-Hill; 2001:1843-1857.
2. Schenkel-Brunner H. Human Blood Groups: Chemical and Biochemical Basis of
Antigen Specgcity. 2nd ed. New York, NY: Springer-Verlag;2000.
 15.1.3 Granulocyte Antigens

3. Daniels GL, Fletcher A, Garratty G, et al. Blood group terminology 2004: from the
International Society of Blood Transfusion Committee on Terminology for Red Cell
Surface Antigens. Vax Sarlg. 2004;87(4):304-316.
4. International Society for Blood Tnnsfusion Committee on Terminology for Red
Cell Surface Antigens Web site. http://blood.co.uk/1~~~~/1~~~/020~ages
/ 1 S B W o 2 0 T e r m i n o l o g y " / 0 2 0 P a g e s / T e r m i n o l o ~ 2 0 a g e h t m .Accessed '
September 9, 2006.
5. Dzieczkowski JS, Anderson KC. Transfusion biology and therapy. In: Kasper DL,
Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Haniso?z'sPrinc@les of
Internal Medicine. 16th ed. New York, NY:McGraw-Hill; 2005:662-667.
6. Webert KE, Chan HHW, Smith JW, Heddle NM, Kelton JG. Red cell, platelet, and
white cell antigens. 1n:'~reerJP, Foerster J, Lukens JN, Rodgers GM, Paraskevas F,
Glader B, eds. Winfrobe'sClinical Hematology. 11th ed. Philadelphia, PA: Lippincott
Williams & Willcins; 2004:791-829. -
7. Daniels GL, Anstee DJ, CartronJP, et ai. Blood group terminology 1995: ISBT Working
Party o n Terminology for Red Cell Surface Antigens. V w Sang. 1995;690):265-279.
8. Issitt PD, Crookston MC. Blood group terminology: current conventions. Transfusion.
1984;24(1):2-7.
9. Garratty G, Dzik W, Issitt PD, Lublin DM, Reid ME, Zelinski T. Terminology for blood
group antigens and genes--historical origins and guidelines in the new millennium.
Transfm'on. 2000;40(4):477-489.
10. Lewis M, Anstee DJ, Bird GWG, et al. Blood group terminology 1990: the ISBT
Working Party on Terminology for Red Cell Surface Antigens. Vox Sang. 1330;
58(2):152-169.
11. Daniels GL, Anstee DJ, Cartron JP, et al. Reports and guideliies: International Society
of Blood Transfusion working party on terminology for red cell surface antigens. Vox
Sang. 2001;800:193-196.
12. Daniels GL, Cartron JP, Fletcher A, et al. International Society of Blood Transfusion
Committee on Terminology for Red Cell Surface Antigens: Vancouver Report. Vox
Sang. 2003;84(3):244-247.
13. Serum, cells, and rare fluid exchange: ISBT human blood group systems. h:p://jove
.prohosting.com/-~8.rfex/blood/groups.htl. Accessed September 9, 2006.
14. Avent ND,Reid ME. The Rh blood group system: a review. Blood. 2000;95(2):375-387.
15. Whitsett CF, Hare W, Oxendine SM, I'ierce JA. Autologous and allogeneic recl cell
survival studies in tile presence o f auto;~nti-AnWj.7i~rrrrsJiaior1. l~Y)3;33(10):H-'15-8.17,
16. Searchgenes. HUGO Gene Nomenclature Committee. http://www.gene.i~cl.:~c.i~k
/cgi-l,in(nomenclari~re/searcligencs.pl. Acccssccl I:c-I>ri~;~ry I i . 200i.
17. Issitt PD, Moulds JJ. Blood group terminology suital>le fix ilse in elccrronic cl:~r;l
processing equipment. 7i.amfiiorr. 1992;32(7):677-682.
18. Daniels GL, Anstee DJ, Canron JP, et al. Terminology for red cell surk~ce:~ntigcns:
ISBT Working Party Oslo Report. Vox Sang. lY)3:77(1):52-57.
19. Metcalfe P,Watkins NA, 0uweh:lntl Wl I , et :II. Nolnencl:~turcof human ~>l;t~clcr :In-
tigens. Vox Sang. 2003;85(3):240-245.
20. von dem Bornc AEG. Dtcnr). F ICSllilSl%l'\Y'orklny I':I~I!. on l'l;~rcl~.~ \c.rt,log\ I I ~ , -
menclature of platelel-spcific :~ntigcn. l i ~ S(IIW . ~ I'Fkl 5Sc 2 1 :1 - 0
21. European Bioinfom31ics In>rlrutc.11'1 1.1 It1:\ I).t!.lt~.l~cIlrrp \\ \ \ \ \ ~.i71 .I\ t l h ~ l ) , i

/hpa/. Accessed ?kptc:mlwr Ii. ,'INK)

13 2 Cancer

22 13us J Sorrlcnchiurc 01 srjnul<x>~c ~lltunt:~r~ r \ U'oriiing Pany on Platelet and

13HT
Grrrnuloq-rrkrulogy. (;rrrnulcx-)~chnrigcn U'orklng Party: lntemrional Society of
B l t d Trrrnbfusion 7kurLl/iuron. 1!@9;396):662-663.
23. hlruri P. Nomrncl~turrof nctutrophil-spechc antigens. Transfiion.
2002;42(11):1396-1397.
24. Stroncek D, Sux J . Is it time to srandardize granulocyte alloantigen nomenclature?
Tra~tifuio?l.2002;42(4):393-395.

Cancer

Cancer Stage. Cancer stages are expressed with the use of capital roman numerals:

stage I
stage I1
::age 111
stage IV
The term "stage 0" usually indiates carcinoma in situ.
Histologic grades are expressed with arabic numerals, eg,' grade 2.
Letter and numerical suffixes, usually set on the line, may be added to subdivide
individual cancer stages, as in the following examples:
stage Oa
stage Ois
stage IA
stage IE
stage IB2
stage IIIE+S
stage IVA
stage IVB
(E indicates extralymphatic spread; S, splenic involvement [as seen in Hodgkin dis-
ease]; "is," in situ.)

The TNM Staging System. The TNM staging system'-9 is an internationally stan-
dardized system for the staging of cancer and is in its seventh decade of continuing
formulation. The TNM classification is put forth by the AmericanJoint Committee on
Cancer (AJCC) and the International Union Against Cancer (UICC; http://www.uicc
.or@.' The AJCC's Cancer Staging ~ a n u a ?and the UICC's EVM Clasnjication of
Malignant ~ u r n o u dpresent the stages of ca.nceras defined by TNM classifications.
The TNM definitions and stage groupings are based on prognostic outcome. Infor-
mation about TNM may be accessed at the UICC Web site, http://www.uicc.org
/index.php?id=508. The TNM symbols follow.
T: tumor (indicates size, extent, or depth of penetration of the primary tumor). T
is followed by numerical or other suffixes set on the line, eg:
TX: primary tumor cannot be assessed
TO: no evidence of a primary tumor
I. Tis: in situ carcinoma
15.2.2 The TNM Staging System

TI, T2, T3, T4: increasing size, extent, or other characteristics of the primary tumor
Note: The number following T does not refer to an absolute size. For example, for
one type of tumor, T1 may indicate size. of 2 cm or less, for another, a depth (or
thickness) of 0.75 mm or less, and for another, tumor confinement within the un-
derlying mucosa.
m N: node (indicates the absence or presence and extent of regional lymph node
involvement)
NX: regional lymph nodes cannot be assessed
NO: no regional lymph node metastasis
N1, N2, N3: increasing metastatic involvement of regional lymph nodes accorcling
to criteria that vary for different anatomic sites
M: metastasis (indicates absence or presence of distant metast'asis)
MX: extent of metastasis cannot be determined
MO: no metastasis
MI: distant metastasis
Site of metastasis may be indicated with parenthetic 3-letter abbreviations:
ADR adrenals
f BRA brain
HEP hepatic
LYM lymph nodes
MAR bone marrow
OSS OSS~OUS

OTH others
PER peritoneum
PLE pleura \
PUL pulmonary
SKI skin
Example: Ml(PUL>

The TNM ,System and Cancer Staging. Various combinations of the T, N, and M
categories are used to define cancer stages (consult the AJCC or UICC manuals for
specifics). For example, a TNM stage grouping that defines stage I for many tjpes of
cancer is
TlNOMO
The combinations that define individual stages differ among anatomic sites, f o r ex-
ample:
lung cancer, stage IIA: T l N l M O
pancreatic cancer, stage IIA: T3NOhlO
15.2 Cancer

More than one combination of the T, N,and hl categories nuy con>[itu[ethe dcf-
inition of a single stage: eg, in a given cancer, stage 111 may be defincd as TlNlS10 or
T2NlMO or T3NOMO or TSNlh10.

, .2-;~2Optional Descriptors. Additional descriptors, although not part of the TNM staging
b,x
i&,?
-7 L- 7.-..

system, may be used as adjuncts to the T, N, and M categories for defining the extent
of disease; these are indicated by capital letters as follows:
certainty factor (C-factor) C1, C2, C3, C4, C5
histopathologic grading GX, GI, G2, G3, G4
lymphatic vessel invasion LX, LO, L1
residual tumor RX, RO, R1, R2
venou: invasion VX, VO, V1, V2
C-factor terms may be used together with T, N, and M categories, eg, T3C2, N2C1,
MOC2 (example from Sobin and ~ i t t e k i n d ~ ' ~ ' ~ ? .
Lowercase prefixes to the T, N, M, and other symbols may be used to indicate the
mode of determining criteria for tumor description and staging or other attributes;
these are as follows:
a autopsy
c clinical
p pathologic
r recurrent tumor
y classification during or after multirnodality treatment
Examples: cTNM, pT3
The T, N, M, and other symbols used in cancer staging may be followed by suffixes in
addition to the common X, 0, and numerals, which further speclfy qualities such as
size, invasiveness, and extent of metastasis, eg:
Ta T2a Mla Nla pNla pNO
Tis T2(m) M2a N2a pNlmi pNO(i)
Tlb T2(5) ~ 2 bpNO(sn) pNO(i+)
Tlc T3a N2c pN3c pNO(mo1)
Tlal pNO(mol+)
(m indicates multiple primary tumors at a single site; mi, micrometastasis; sn, sentinel
node status; i, isolated tumor cells; mol, isolated tumor cells demonstrated by non-
morphologic [eg, molecular] techniques.)
Examples of such combined terms are

Usage. Terms such as "stage I cancer," "TNM staging system," and "TINlMO" are
widely recognized and may be used in articles without expansion. However, authors
should specify the clinical and/or pathologic criteria that define any stage (option3lly
but preferably citing the staging system of the AJCC or UlCC rn:~nurlls).
 15.2.3 Bethesda System

Use terms as follows (see also 11.1, Correct and Preferred Usage, Correct and
Preferred Usage of Common Words and Phrases [Case, Client, Consumer, Patient,
Subject]):
Correct Incorrect
T stage
N category N stage
M category M stage
stage 111 cancer, patient stage I11 patient
with stage I11 cancer
N1 lesions ' N1 patients
patients with TlNOMO TlNOMO patients
tumor, TlNOMO tumors,
TlNOMO cases
TXNOMO classification
For some sites, the histologic grade has been integrated into the staging system.

Other Staging Systems and the TNM System. The AJCC-UICC TNM classification and
stage grouping is not the only system used for staging cancer, and equivalency of the
same stage number among different systems cannot be assumed. However, 2 cancer
staging systems, the FIG0 (International Federation of Gynecology and Obstetrics;
http://www.figo.org) staging system for gynecologic and the Dukes
stage system for colon and rectal cancers,12p13have virtual equivalence with the
AJCC-UICC stage. The AJCC-UICC system contains subsets of TNM classilications
within stage groups that provide greater prognostic precision within each stage for
colorectal cancer than does the Dukes stern.'^.^^
FlGO stages are expressed similarly to TNM stages:
stage I stage IA . 'stage
-
IAl stage IB stage IB1 stage IC
stage I1 stage IIA stage IA2 stage IIB stage IB2 stage IIC
stage 111 stage IIIA stage 11113 stage IIIC
stage IV stage IVA stage IVB
Dukes stages are expressed with letters:
Dykes A or Dukes stage A
Dukes B or Dukes stage B
Dukes C or Dukes stage C
Dukes D or Dukes stage D

Bethesda System. The Bethesda System for Reporting Cervical Cytology, dating to
1988, is a standardized, systematic means of reporting Papanicolaou test results.'*
Resources are the published handbook (the "blue book")'%nd the Web site (http://
~.~~to~athology.or~/~~~).'~
Expand the following abbreviations at first mention. Punctuate as shown:
 ---..
15.2 Cancer

ansion
adenocarcinoma in situ AIS
of endocervix
American Society for ASCCP
Colposcopy and,Cervical Pathology
American Society of Cytopathology ASC
ASCUS/LSIL Triage Study ALTS
atypical glandular cells AGCs
atypical squamous cells Ascs
atypical squamous cells, ASC-H
cannot exclude high-grade
squamous intraepithelial lesion
atypical squamous cells of
undetermined significance
Bethesda Interobserver BIRP
Reproducibility Project
carcinoma in situ CIS
cervical intraepithelial neoplasia CIN
conventional preparation CP
endocervical/transformation zone EC/TZ
high-grade squamous HSIL
intraepithelial lesion
human papillomavirus
intrauterine device or
intrauterine contraceptive device
liquid-based preparation LBP
loop electrosurgical excision procedure LEEP
last menstrual period LMP
lower uterine segment LUS
low-grade squamous intraepithelial lesion ISIL
malignant mixed mesodermal tumor MMMT
National Cancer Institute, Bethhda, Maryland NCI
negative for intraepithelial lesion or malignancy m
not otherwise specified NOS
nuclear to cytoplasmic ratio N:C
small cell undifferentiated carcinoma scuc
squamous intraepithelial lesion SIL
the Bethesda System TBS
transitional cell carcinoma TCC
transformation zone T zone
vaginal intnepithelial neoplasia VAIN
 15.2.5 Molecular Cancer Terminology

In the following examples, unexpanded abbreviations are assumed to have been

previously defined in the text:
Low-grade squamous intraepithelial lesions (LSILs) have been described as
a benign cytologic consequence of active human papillomavirus (HPV)
replication. Several studies have reported that certain behavioral and bio-
logical risks exist for LSIL, suggesting that HPV alone is not sufficient for
the development of LSIL.

ASC-H (CP)

glandular cells post hysterectomy (CP)

G r ~ d e sare expressed ns fdlows:
CIN 1, CIN 2, CIN 3
VAIN 1, VAIN 2, VAIN 3

Multiple Endocrine Neoplasia. Abbreviations for types of multiple endcxrine nro-

MEN 1
MEN 2
MEN 2A
MEN 2B

Gene terms are italicized with spaces closed up (see 15.6.2, Genetics, I.lu~nanS c n c
Nomenclature):
MEN1

Molecular Cancer Terminology. See also 15.10, Molecular Medicine, The style for tlic,

,Phue Exl~ansionor Derivation

growth 1 or gap 1
S synthesis (of DNA)
Gz growth 2 or gap 2
M mitosis
Go quiescent state
J{ point restriction point
\llscell;lncous rnolzcul;lr terms are stylctl as shown in the following tal~ulation.(See
I 6 . (;~.r:ctic.s. Oncogenes :ind 'Tumor Suppressor Genes.)

551
 -. - -. .
15.2 Cancer

Variant
/'ITJ~C,I PI Lkriuutio~t
acr~nin rr-actinin

l3cl B-cell lymphoma

CAK cyclin-activaring bcl-X BCLX
enzyme
(= cyclinH/CDK7)
catenin
cdc2 cell division cycle CDC2
CDK cyclin-dependent
kinase
CDKI CDK inhibitor
cyclin/CDK . cyclin B/CDKl,
complex

G protein GTP-binding
regulatory protein
INK4 inhibitors of CDK4
~ 2 1 CDXNlA
~ 5 3
Rb protein retinoblastoma protein
TGF tumor (or transforming)
growth factor
tumor necrosis
factor (TNFi)

Human Gene Nomenclature).

REFERENCES

. eds. Cancer Staging Manual. 6th ed. New York, NY: Springer; 2002.

Classijication of Malignant Turnours. 6th ed. New York, NY: Wiley-Liss; 2002.
4. Wittekind C, Henson DE, Hutter RVP,Sobin LH, eds. liVM Supplement:A Commentaty
on Uniform Use. New York, NY: Wiey-Liss; 2001.

eds. Prognostic Facton in Cancer. 2nd ed. New York, NY: Wiey-Liss; 2001.
6. Sobin LH. TNM: principles, history, and relation to other prognostic factors. Cancer.
2001;91(~uppl):1589-1592.

552

.
: .> .
T
......
I
I
I

15.3.1 Electrocardiographic Terms

8. Gospodarowicz MK, Miller D, Groome PA, Greene FL, Logan PA, Sobin Lti; k,r [he
UICC TNM Project. The process for continuous improvement of the TNhl classific;~tion.
Cancer. 2004:100(1):1-5.
9. Sobin LH.TNM:evolution and relation to other prognostic factors. Sernin S11rx Ol~col.
2003;21(1):3-7.
10. Benedet JL, Bender H, Johnes H 111, Pecorelli S; for the FIGO Committee on Gyne-
cologic Oncology. FIGO staging classifications and clinical practice guidelines in the
management of gynecologic cancers. Int J Gynaecol Obstet. 2000;70(2):209-262.
11. International Federation of Gynecology and Obstetrics Web site. http://www.figo.org.
Accessed March 14, 2006.
12. Hutter RVP,Sobin LH. A universal staging system f o cancer
~ of the colon and rectum:
let there be light. Arch Patbol Lub Med. 1986;110(5):367-368.
13. Winawer SJ, Fletcher RH,Miller L,et al. Colore&l cancer screening: clinical guidelines
and rationale. Gastmentemlogy. 1997;112(2):594-642.
14. Solomon D, Nayar R, eds. 73e Bethesda Systemfor Reporting Cervical Cytology: Def-
initions, Criteria, and Explanatory Notes. 2nd ed. New York, NY:Springer-Verlag;
2004.
15. 2001 Terminology. NCI Bethesdi System 2001. http://bethesda2001.cancer.gov
/terminology.html. Accessed March 14, 2006.

Cardiology. Several areas of cardiology use simple letter terms and alphanumeric
terms that need not be expanded at first mention.

Electrocardiographic Terms. International standardization of electrocardiographic

nomenclature dates back to the mid-20th century.f4
The preferred abbreviation for electrocardiogram and electrocardiographic in
JAMA and the Archives Journals is ECG,not EKG. In the following examples of ECG
terms note the use of capitals, lowercase letters, subscripts, and hyphens.

Leads. Leads (recording electrodes) are designated as follows:

TyPes of Leads Names
Standard (bipolar) leads I, 11, 111
Augmented limb leadslunipolar a m , aVL, aVF
extremity leads (a, augmented;
V, voltage; R, right arm; L,
left arm;F, foot)
InJerted aVR lead -aVR
(Unipolar) precordial v ~v2,, v3, v4, v5, v6, v7, ve, v9
'
(chest) leads
Right precordial leads VIR, VzR, V$, V4R, V,R, VbR
Modified chest lead using V, MCL,

,,
~ \',-\;. or \'?<,I
Example: The abnormality appeared in lentl3 \', t l ~ r o u\~ lI71ot

Deflections. The main deflections of the ECC; (set f'~gurc1 ) art. n:lnlrd In ;~lpt~at>e-
tical sequence (P, Q, R, S. T. U), a tisnRc r h : ~ti.~rcs
~ tx~ckr r , rhc. ~n\.crltor.U'illcrn
~inthoven.' Other deflections w c . initill IcSttcr>of rl~crntlrv t w ~ tf~.w.r~l)c-tl
n~

553
Figure 1. Electrocardiographic deflections (schematic).

As a guide, hyphens usually d o not link deflection terms in the same PQRSTU
complex (eg, QT) but d o link deflections in dflerent waves (eg, R-R), with the
exception of ST-T. The following are examples of terms descriptive of deflections
and patterns in ECG tracings:
delta wave (preferred over A wave)
F wave (atrial flutter wave)
f wave (atrial fibrillation wave)
J point, J junction (junction of QRS complex and ST segment; do not con-
fuse with the J curve in hypertension)
J-ST axis, vector
P wave, axis, etc
PR interval, segment, etc (not P-R)
Q wave, q wave
qR complex
QR-type complex
QRS complex, configuration, axis, duration, etc
qrs complex, etc
QRS-T complex
QS wave, qs wave
QT interval, prolongation, etc (not Q-T)
QTc (corrected QT interval)
R wave, r wave, R1-wave,'I wave
R-on-T
R-R interval
rS, RS, Rs complex, configuration, etc
R/S (ratio)
rSR1 pattern
S wave, s wave
 15.3.1 Electrocardiographic Terms

S' wave, s' wave

ST segment, depression, axis, etc (not S-T)
ST-segment abnormality
ST-T segment, elevation, changes, axis, etc (not S-T-T)
T wave, axis, etc
Ta wave (atrial repolarization)
TQ segment
U wave
When terms such as the foregoing are used as modifiers, use a hyphen before the
modifying noun (see also 8.3, Punctuation, Hyphens and Dashes).
P-wave duration
Q-wave irregularity
non-Q-wave myocardial infarction
ST-segment depression (not S-T)
The following symbols are used in connection with paced ECGs:
A atrial stimulus
V ventricular stimulus
AV interval from atrial stimulus to succeeding ventricular stimulus
AR interval from atrial stimulus to conducted spontaneous ventricular
depolarization
PV interval from spontaneous atrial depolarization to succeeding
"atrial-synchronous" ventricular stimulus
Capital letters are used to describe generic ECG deflections.
Improper paper speed will spuriously alter the QRS confi&uration. L~zorqrs
configuration]
In reference to an individual ECG tracixlg, or in descriptions of some specific ECG
patterns, capitals may indicate larger waves and lowercase letters smaller \\.:~\.cs: in
practice, this most often applies to the Q, R, and S waves.
Pathologic Q waves occur in nlyocardial infarction.
The q wave in aVF and the Rr' pattern in lead V3 in this patient's I1CG \\.crc
considered normal findings.
An rSR1 complex in the anterior chest Icacls ancl ql<sit1 thc Icfi c l l c s ~ilc:~tls
may indicate right bundle-branch block.
Lead and tracing terms may l)e combined t o describe pattern a n d Ioc.;~\ic~n
\ r )yc~llr.~..

RaVI. It wave in aVI.

SIII S wave in Iracl 111
15.3 Cardiology

Tenn E~ph;luf~o;r -
RV3 R wave in V,
S1Q3T3pattern Prominence of S wave in lead I, Q wave in lead 111,
and T-wave inversion in lead 111
SVl + RV5 Sum of voltages of S wave in Vl and R wave in V5
The P axis, QRS axis, ST axis, and T axis are speched with a plus or minus sign
followed by the number of degrees in arabic numerals, eg, +60°, -30".

Electrograms. Electrogram (EGM) terms pertain to invasive electrophysiologic re-

cording of cardiac impulse conduction. Expand them at first mention.
Tenn Expamion
AH interval atrial-His interval
His His potential
HV interval His-ventricular interval

Heart Sounds. The 4 heart sounds and 4 components are commonly abbreviated in
discussions of cardiac auscultatory findings; numerical subscripts are used.
S1 first heart sound
MIrnitral valve component
T1 tricuspid valve component
S2 second heart sound
AZ aortic valve component
Pz pulrnonic valve component
S3 third heart sound
S4 fourth heart sound
Examples:
The presence of an audible S3 was consistent with the patient's ventricular
.aneurysm.
An audible S4 may be due to a varlety of cardiac and systemic conditions.
Sound names may be written out in full when discussed generically.
Third heart sounds are suggestive of congestive heart failure, but an S3gallop
may be a normal finding in children and young adults.

The Sj is suggestive of congestive heart failure, but an S3 gallop may be a

normal finding in children And young adults.
For plurals, follow the term with "sounds" or another noun.
S3 sounds [not S3s1 may be normal or pathologic.
S3 gallops may be a normal finding in children and young adults.
 15.3.6 Echocardiography

Murmurs. Murmurs are graded from soft (lower grade) to loud (higher grridc). hlilr-
mur grades are written in arabic numerals. Systolic murmurs may be gr,~dcclfro111I t o
6 (see Freeman and ~ e v i n eand
~ ) diastolic murnmurs from 1 to 4. Murmurs nxiy also I,c
presented by means of a virgule construction. Examples:
grade 2 systolic murmur
grade 1 diastolic murmur
grade 4/6 systolic murmur
grade 2/4 diastolic murmur
The patient had a grade 3 systolic murmur radiating to the axilla consisrcnt -
with the diagqosis of mitral valve regurgitation.

Jugular Venous Pulse. The jugular venous pulse contours are expressed with italic
single letters and roman words:
a wave (atrial)
x descent
z point
c wave
x' descent
v wave (ventricular)
y descent (or y trough)
h wave
Examples:
prominent a wave
giant a wave
steep x descent
increased v wave
abrupt y descent

Echocardiography. The names of major echocardiographic methods are listed be-

low. Expand any abbreviations at first mention, unless otherwise indicated.
Name Common Abbreviafion
w ~ ' ~ ' ~ ~ L & d i r n e n s iechocardiography
onal 2DE
3-dimensional echocardiography 3DE

adenosine stress echocarcliography

color Doppler e~hoc;~rdiogr;ipl~y
color flow 1)opplcr e ~ ~ t ~ ~ ~ ~ ; i r c I ~ o ~ r ~ ~ ~ ~ h y
contin~~o~~s-wavc 1)opplc.r C'\ I 1pp1t.r
)(

echoc;irdiogr;1r>I1!,
c.onir.ts~<:<Ivx : : r ~ I uy : , ~ l ! t ~ i
I 5.3 Cardiology

Name Common Abbreviation

dipyridamole stress echocardiography
dobutamine stress echocardiography
Doppier echocardiography
Doppler flow imaging
exercise echocardiography
intravascular ultrasono,gaphy
pharmacologic stress echocardiography
pulsed Doppler echocardiography
spectral Doppler echocardiography
stress echocardiography
transesophageal echocardiography TEE
The following commonly used echocardiographic indexes should also be expa
at first mention but are included here for ieference:
T m wa-
aortic valve area

/: FAC
ejection fraction
E point septal separation
fractional ar& change
FS .fractionalshortening
NS,IVST interventricular septal thickness
LVID left ventricular internal dimension
MVA mitral valve area
PHT pressure half-time
PW, P W posterior wall thickness
RVID right ventricular internal dimension
SAM systolic anterior motion of the m i d valve
d or e d end diastole
s or es end sysrole
Terms are combined as in the following examples:
IVSd
IVSs
LVIDd
LVIDed
LVIDes
LVIDs
LVPWd
LVF'\Vs
ItVI Dd

- - -. **. _ -.-
..
. - ..
i
 15.3.8 Implanted Cardioverter/Defibrillators
-
Ejection fraction is expressed as a percentage, eg, 60% (see also 19.0, Numbers and
Percentages).

Pacemaker Codes. The capabilities and operation of cardiac pacemakers are de-
scribed by 3- to 5-letter code~.~.'
DDIR pacing
VVI pacemaker

The code system for antibradycardia pacemakers endorsed by the North American
Society of Pacing and Electrophysiology and the British Pacirlg and Electro-
physiology Group is known as the NASPEIBPEG Generic Code or NBG Code. Al-
though the code need not be expanded when mentioned in passing, it is good
practice to describe pacing modes in prose at first mention, eg, "dual-chamber,
adaptive-rate (DDDR) pacing." The NBG Code was revised in 2001 to apply to
antibradycardia, adaptive-rate, and multisite p a ~ i p ~ . ' . ~
In Table 1, positions I through V refer to the first through fifth letters of the NBG
Code.The character for "None" is the letter 0,not the numeral 0.In practice, the first
3 positions are always given; the fourth and fifth are added when necessary to
provide additional information.

----- - - - - - - - - - -- -

Table 1. Revised NASPEIBPEG Generic Code for Antibradycardia Pacinga

Position I II 111 1V V . .

Category Chamber(s) Chambeds) Response to Rate Multisite

Paced Sensed Sensing Modulation Pacing
0 = none 0 = none 0 = none 0 = none 0 = none
A = atrium A = atrium T = triggered R = rate A = atrium
modulation
-- V = ventricle V = ventricle I = inhibited V = ventricle
D = dual D = dual D = dual D = dual
(A -tV) +
(A V) +
CF I) +
(A V)
Manufacturers' S = single 5 = single
designation (A or V) (A or V)
only
aReprinted,pith perrniuion,.from Bernstein et dl.'

Note: The principal changes from the previous (1987) code are the dropping of
classifications from position IV (P, simple programmatic; M, multiprogramin;~l,le:C.
communicating) and additions to position V (shown in the table) and deletions from
position V (P, pacing; S, shock). Position V, which formerly appl~ecllo a n [ ~ ( ; \ ~ ..llrn-
rhythmia functions, now applies to multisite pacing.

-1 mplanted cardioverter/DefibriIlators. A similar code. kncnvn ; I , I ~ C . lrlll'c ;

Defibrillator Code or NBD code," exists for i,jlr,l:rnrc.<l c.;ir~liocr.~r;.r t l ~ ~ f t l ~ t t l,:..
l.tt~
(ICDs), as defined in T;lble 2.
 Table 2. Defibrillator Codea

Position II Position 111 Position IV

Position I (Antitachycardia (Tachycardia (Antibradycardia
(Shock Chamber) Pacing Chamber) Detection) Pacing Chamber)

0 = none 0 = none E = electrocardiogram 0 = none

A = atrium A = atrium H = hernodynamic A = atrium
--
V = ventricle V = ventricle V = ventricle
D = dual (A + V) D = dual (A + V) D = dual (A + V)
a Reprinted from Bernstein et all0 by permission of Blackwell Publishing.

Examples are as follows:

DDH defibrillator
VOEO defibrillator
There is also a Short Foqn of the NBD Code intended only for use in conversation:
ICD-B: ICD with antibradycardia pacing as well as shock
ICD-T: ICD with antitachycardia pacing as well as shock and antibrady-
cardia pacing
ICD-S: ICD with shock capability only
The foregoing terms can each represent a variety of devices; for instance, ICD-S
could indicate VO, VOE, VOEO, DOH, or DOHV. The same devices may also be
represented by more than 1term, eg, ICD-B may also represent VO and VOE, among
other devices. Therefore, only the Long Form is used in writing. As in the case of the
NBG Code, at first mention of an ICD it is good practice to include a prose description
as well as the NBD Code designation.
For maximum conciseness and completeness in ICD labeling and record
keeping, the first 3 positions of the NBD Code are given, followed after a hyphen by
the first 4 positions of the NBG Code. Thus, "VAE-DDDR refers to an ICD providing
ventricular shock, atrial antitachycardia pacing, EGM sensing for tachycardia detec-
tion, and duai-chamber, adaptive-rate antibradycardia pacing.

Pacemaker-Lead Code. The NASPEIBPEG Pacemaker-Lead Code (NBL Code) is as

follows:
I II 111 N
(Electrode (Fixation (Insulation (Drug
CorzJguration) Mechanism) Material) Elution)
U = unipolar A-= active P = polyurethane S = steroid
B = bipolar P = passive S = silicone rubber N = nonsteroid
= multipolar 0 = none D = dual (P+S) 0 = none
(Reprinted from Bernstein and Parsonnet" by permission of Blackwell
l'ublishing.)
'I'ypic;~Ily.: i l l .i po..iitions are mentioned, eg, UPSO, BAPS.

560
 15.3.1 1 Coronary Artery Angiographic Classifications

Heart Disease Classifications. Several classifications pertaining to heart disease are in

use:
Applies to Classes Example
Unstable angina 1-111 Braunwald class I
IA-IIIC Braunwald
class IIIB
Canadian Exertional angina CCS class I1
Cardiovascular
Society (CCS)'~.'~
orr rester'^" Cardiac function after I-IV Forrester class I
myocardial infarction
cardiac status after I-IV Killip chss 1 Iic:117
myocardial infarction f:lilure
New York Cardiac disease and I-IV NYHA c l a s I
Heart functional capacity
Association (NYHA)''
The classes are assessed in various ways, for instance, by physical exnminarion
(Killip), hemodynamic measurement (Forrester), and patient history ( NY HA 1. '1'1 ic
detailed meanings of each class are beyond the scope of this book, but sever;~lstylc
points may be noted:
s ~ k v e r iincreases
t~ from lower to higher numbers and letters.
a There is n o automatic correspondence between classes (eg. Killip class I is not
equivalent to NYHA class I).
The numerals are designators and are not quantitative o r semiquantitative. l'hcrc-
fore, roman numerals are appropriate.
. Avoid: Forrester class >2
Acceptable equivalents: Forrester class above I1
class greater than Forrester I1
Forrester classes 111 and N
ei Authors should describe their classification criteria, for instance:
Killip class on admission was determined as the following: patients in class I
were free of rales and a third heart sound; patients in class I1 had rales up to
50% of each lung field regardless of the presence of the third heart sound. . ,
(adapted from Neskovic et a12').
We suggest that cases of unstable angina class IIIB now be subdivided into
troponin-positive and troponin-negative subgroups. . . (adapted from Hanlm
and ~ r a u n w a l d ~ ~ ' ~ ' ~ ~ ' ~ .

Coronary Artery Angiographic Classifications. Guidelines are availablt. for nomen-

clature o f coronary artery segments,23i~sedin coronary artery catheterization and
rliro1i1l)olysisin fnyocartlial infarction flow (TIMI flow).
'I'l~c.TIh11 flow i!; csprcssctl :ISg~.:ltl(.0. g r ; ~ ~ Il .c&r;~tlc
2, o r gl-:ltlc :.),f'ro~nIowcs~
( 1 4 n v ( o r S C I , ~ ~ lcsio~i)
~ S [ 1011igIic-SI
Ilo\~.'~
 Cardiac Musde. Thcw descriprive trrnls do not require expansion:
I
A band actin-myosin overlap
H band Hensen (discoverer) I
M line mesophragma
J/"/ T tubules rubulus transversus
Z line Zuckzttzg (German: "contraction")
Expand these terms at first mention: 1
Term Expansion Dm'vation
troponin C binds calcium
,
uoponin I inhibits actin-myosin interactions
. TnT troponin T binds to tropomyosin
I

cTnC uoponin C, cardiac form

I
cTnI troponin I, cardiac form
I..
cTnT moponin T, cardiac form
. ,

Miscellaneous Cellular and Molecular Terms. If an expansion is given, use at first

mention. Otherwise, t e r n may be used without expansion.
T m Erpansion Derivation/Explanation
athemELAM endothelial leukocyte
adhesion molecyle
involved in athkrosclerosis
CK-MB -tine kinase, -
myocardial
NOS nitric oxide synthase
NOS1 Named in order of discovery, .
also nNOS (neuronal NOS)
NOS2 Also iNOS (inducible NOS)
NOS3 Also eNOS, ecNOS
(endothelial constitutive
isoform of NOS)
P cell Nodal cells of the sinus node
tPA tissue plasminogen activator
Expand the following lipoproteins and related terms at first mention:
T m ~ m i o n Note
acyl CoA acyl coenzyme A
high-density lipoprotein
HDL variant
 15.3.12 Cellular and Molecular Cardiology

J Term Expansion Note

---
HDL2 HDL subfraction 2
HDL3 HDL subfraction 3
HDL-C HDL cholesterol ,

HDL-R HDL receptor

HMG CoA 3-hydroxy<-methylglutavl
coenzyme A
IDL intermediate-density
lipoprotein
IDL-C F L cholesterol
IDL-R IDL receptor
LDL low-density lipoprotein
LDL-C LDL cholesterol
LDL-R LDL receptor
LPL lipoprotein lipase , ~ e e ' a l s o15.6.2,Genetics,
gene Human Gene Nomenclature
LPLIES mutation in LPL See also 15.6.1,Genetics,
at codon 188 Nucleic Acids and Amino
Acids
LPLAsnlgSer substitution in LPL of
serine at asparagine residue 29
LP-X lipoprotein X
LRpl LDL-R-related protein
LRpz LDL-R-related protein 2
VHDL very high-density lipoprotein
VLDL-C VLDL cholesterol
VLDL-R VLDL receptor
Expand apo as apolzpopmtein at first mention of terms such as the following:
apo.AI apo B ~ x apo CI apo D apo E apo J
apo A11 apo HI,,, apo C11 apo E2
apo AIII 21poCIII apo E3
apo AIV

REFERENCES
1 Barnes AH. P:~rdeeHEB, Wllite I'D, Wilson FN, Wolfertll CC; for the Committee of the
.+n~cr~c;~n t lc:ln A\uxl;lllon fol. the Stancl:~rtliz:~rion
of Precordial Leads. Standardiza-
on (11. prcc-c>r<l~;~i
Ir~tl5<upplcment;rryreport. At?, Hea,? J. 1938;15:235-239.
! 5 3 Cardlology

1. 15:::ncb .AH. h;arz LX. lr\-inc. SA. P;rrdc-c tiiit%.U.tl:tc ['I>. W h n FN. Repon of the
C:c)n~rnlrrccot t l ~ cA l l r c n ~ ~iic;rn
n h w z , ~ t i ~ o, n tht- St;ln&rdiz;rtion of Electro-
cardiogmphic Sor~lcncla~urc. .4rrr I i t r r r f j IcHJ.25:5&534.
3. Barnes AR, Pardee 1-iEB, U'hire PD. K'ilson FN, Wolferrh CC. Second supplementary
rcpon by the Cornnlittrr of the A~ncricanHean Association for the Standardization of
Precordial Leads. A ~ r it l c v ~J.
f 1943;25:535-5%.
4. Wilson FN, Koss~nannCE, Burch GE, et al. Recommendations for standardization
of electrocardiographic and vectorcardiographic leads. Circulation. 1954;lO:
564-573.
5. Freeman AR, Levine SA. The clinical significance of the systolic murmur: a
study of 1000 consecutive "non-cardiac" cases. Ann Intern Mecl. 1933:6(11):
1371-1385.
6. Bernstein AD, Camm AJ, Fletcher RD, et al. The NASPE~BPEGGeneric Pacemaker
Code for antibradyarrhythmia and adaptive-rate pacing and antitachyarrhythmia de-
vices. Pacing Clin Electrophysiol. 1987;10(4):794-799.
7. Parsonnet V, Furinan S, Smyth NPD. Implantable cardiac pacemakers status
report and resource guideline: Pacemaker Study Group. Circulation. 1974;50(4):
A21-A35.
8. Bemstein AD, Daubert J-C, Fletcher RD, et al. The revised NASPEIBPEG generic
code for antibradycardia, adaptive-rate, and multisite pacing. PACE. 2202;25(2):
260-264.
9. Bernstein AD, Camm AJ, Furman S, Parsonnet V. The NASPEIBPEG codes: use, rnis- ,
use, and evolution. Pacing Clin Electrophysiol. 2001;24(5):787-788.
10. Bemstein AD, Camm AJ, Fisher JD, et al. North American Society of Pacing and
E!ectrophysiology Policy Statement: the NASPEIBPEG defibrillator code. Pacing Clin
Electmphysiol. 1993;16(9~:17761780.
11. Bemstein AD, Parsonnet V. The NASPE/BPEG pacemaker-lead code (NBL Code).
Pacing Clin Electrophysiol. 19!%;19(11): 1535-1536.
12. Braunwald E. Unstable angina: a classilication. Circulation. 1989;80(2):410-414.
13. Campeau L. Grading of angina pectoris Uetter]. Circulation. 1976;540:522-523.
14. Campeau L. The Canadian Cardiovascular Society grading of angina pectoris revisited
30 years later. Can J Cardwl. 2002;18(4):371-379.
15. Forrester JS, Diamond G, Chatterjee K, Swan HJC. Medical therapy of acute myocardial
infarction by application of hemodynamic subsets (first of two parts). N Engl J Med. '..

1976;295(24):1356-1362.
Ib.'Forrester JS, Diamond GA, Swan HJC. Correlative classification of clinical and
hemodynamic function after acute.myocardia1 infarction. Am J Cardiol. 1977;39(2):
13l-145.
17. Madias JE. Killip and Forrester classifications: should they be abandoned, kept, re-
evaluated, or modified [comment]?Chest. 2000;117(5):1223-1226.
18. Killip T, Kimball JT. Treatment of myocardial infarction in a coronary care unit: a two
year experience with 250 patients. Am J Cardiol. 1967;20(4):457-464.
19. Werns SW,-BatesER. The enduring value of Killip classification. Am Heart J.
1999;137(2):213-215.
20. criteria Committee of the New York Heart Association. Nomenclature and Criteriafor
Diagnosis of Diseases of the Heart and Blood Vessek. 9th ed. Boston, MA: Little Br
& Co; 1994:254.

. .. .
.
,
li'.
..,
..
 15.3.12 Cellular and Molecular Cardlology

21. Neskovic AN, Otasevic P, Bojic M, Popovic AD. Association of Kill~pclas on admis-
sion and left ventricular dilatation after myocardial inklrcrion: a closer look into :in old
clinical classification. Am Heart J. 19%,137(2):361-367.
22. Hamm CW, Braunwald E. A classification of unsrable angina revisited. Circtrlafion.
2000;102(1):118-122.
23. Scanlon PJ, Faxon DP, Audet AM, et al. ACC/AHA guidelines for coronary angiog-
raphy: a report of the Arnericxn College of Carcliology/American Heart Association
Task Force on Practice Guidelines (Committee on Coronary Angiography). J Atn Coil
Cardiol. 1999;33(6):1756-1824.
24. Jameson ;L, ed. Principles of Molecular Medicine. Totowa, NJ: Humana Press; 1998.
25. Braunwald E, Zipes DP, Libby P, eds. Heart Disease: A Textbook of Cardioudlzular
Medicine. 6th ed. Philadelphia, PA: WB Saunders Co; 2001.
26. Zipes DP, Libby P, Bonow RO, Braunwald E. Braunwald's Heart Disease: A Textbook
of CardiovascularMedicine. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005.

ISF1L.r Drugs. Physicians and other health care professionals, patients, researchers, man-
ufacturers, and the public may refer to drugs by several names, including the non-
proprietary name (often referred to as the generic name) and at least 1 proprietary
(brand) or trademark name selected by the manufacturer of the drug. Other drug
identifiers include chemical names, trivial (unofficial) names, and code designa-
t i o n ~ . ~ (However,
~ ~ ~ ~ -only
~ ~1) drug name, the nonproprietary name, is regulated
internationally to ensure consistent usage and no duplication with other drugs. Once
a drug has been assigned a nonproprietary name, the nonproprietary name should
always be used to refer to the drug. (See 15.4.2, Nonproprietary Names.)
The nonproprietary name is established through nomenclature agencies, such as
the United States Adopted Names (USAN) Council (http://www.ama-assn.org
/ama/pub/category/2956.html),which work with the World Health organization
07CrHO) to establish a single nonproprietary name. According to the WHO, "the
existence of an international nomenclature for pharmaceutical $ubstances, in the
form of INN [international nonproprietary name], is important for the clear identifi-
cation, safe prescription and dispensing of medicines to patients and for commu-
nication and exchange of information anlong health professionals and scientists
worldwide."*The nonproprietary names of drugs that are to be marketed within the
United States must be approved by the USAN Council. The nomenclature rilles
provided in 15.4.13, Nomenclature for Biological Products, are established by tlir
USAN Council.
The pharmaceutical naming system of the WHO has been in operation since
1953. When a drug is being considered for possible approval, the sponsoring m;rn-
ufacturer must file an INN application with the WHO'S Essential Drugs ;~nclh:lctlic.incs
team of Quality Safety and Medicines Policy (QSM),or with onc 01' the. ci1.11~ no-
menclature councils such as USAN or Japanese Adopted Names ( I A N ) . l'hc Ilritisl~
Approved Names (BAN) and D6nominations Communes Frai1~;riscs(\>(:I:) (:I n~n<-il>
have now been superceded by the European Union. \vhicli docs not Ii:~vt.;I 4cp;,v:11~
council but requires that the INN be used for clri~ghm;~rlictccl\\ i t l ~ i ~1111. i I ' ~ I I, ,~. < . . t r j
I Union. These organizations work in conjunc.rion \\.ill1 rlir \\'I 10 10 .~ly)icI \ 1. .I 1 1 8 111.
proprietary name identicdl to thc I N K . ' hl;~nl~l:~c ~ ( I ~ C ' Ii l. l c t I ~ I I ~ I\\I 1~
1 1 1C . . .I 1 1 , ~
1 ,111

menclature agency can ~f2qLlf2st ;In 1XS fro111 rtlt. \\'I I t ) LIIIVL~I!. c ~ .11q' r 1\ 111 .L L l ( i l ! i l \
that has a nomenclat\~rcagency I"': "
15:4 Drugs

The Drug Development and Approval Process. This brief summary of thr. drug
development process is provided to help define the origins of d~fferentnJlnt.5 1l~:c.d
to identify drugs.
Drugs intended for clinical use undergo several phases of developn~entbefore
they can be considered for human use. Animal studies are performed initially to
assess pharmacologic and toxicologic effects. While clinical studies are being con-
ducted, animal studies may continue to assess effects on reproduction, teratoge-
nic~ty,and
To perform clinical studies in the United States, the developer or manufacturer
must obtain an investigational new drug (IND) approval from the US Food and Drug
Administration (FDA).~'~'~) Once an IND application has been filed, the company
must apply to USAN for a nonproprietary name. Until a nonproprietary name has
been approved, the developers of a drug may refer to it by the code name. The code
designation is usually alphanumeric, with letters to refer to the institc:lon or man-
ufacturer that assigns the code designation for the drug and numbers to refer to the
chemical ~ o m ~ o u n d . ~ ( ~ ~ " ~ ~ )
Drug developers must adhere to the Declaration of Helsinki and obtain in-
stitutional review board approval and patient informed consent to perform drug
studies in humans. Phase 1 studies generally are conducted in healthy volunteers to
assess safety, biological effects, metabolism, kinetics, and drug interzctions.4<p60)
Phase 2 studies usually are conducted to establish the therapeutic efficacy of a drug
for its proposed indication and to study dose range, kinetics, and m e t a b ~ l i s r n . ~ ~ )
Phase 3 trials typically are randomized controlled trials that assess a drug's safety and
efficacy in a large sample of patients (generally 2000 to 3000)!(~~~)The patients
selected have the condition(s) for which the drug is thought to be effective and for
which the manufacturer wishes to obtain approval. The 3 phases of clinical testing
take from 2 to 10years (average, 5.6 years).4p60)~heFDA reviews drugs for approval
in less than 1 year and performs expedited reviews for drugs for life-threatening
illnesses!'~~~'
In the United States, a drug cannot-be marketed or prescribed (other than for
specific exceptions) until it has been approved by the FDA. The FDA approves
labeling for the drug for specific indications for which the FDA believes sufficient
evidence of effectiveness has been provided. Approved labeling defines the in-
dications for which the drug can be marketed. The FDA does not approve indications
for which a drug may be prescribed, since a company may not study all possible
conditions for which a drug may be effective. In what is known as off-lube1pre-
scribing, physicians may prescribe a marketed drug for indications for which it does
not have FDA approval for labeling or marketing. The approved labeling is included
in drug packaging, marketing materials, and the PhysicianslDak ~eference.~
Because the number of patients tested before a drug is approved is insufficient to
identlfy rare adverse events, some countries require physicians to report adverse
events experienced by their patients, and some manufacturers may be required to
systematically monitor drug adverse events after approval in a process known as
postmarketing surveillance. Physicians and other health care professionals in the
United States should report adverse drug events to the voluntary reporting system
MEDWATCH (http://www.fda.g~~/medwatch) or to the pharmaceutical manu-
facturer, which is obligated to file reports with the FDA. The United Kingdom, Can-
ada, New Zealand, Denmark, and Sweden have legally mandated adverse event
 15.4.2 Nonproprietary Names

reporting ~ ~ s t e m s . In
~ ' addition,
~ ~ ~ ' the WHO maintains the \ W O Collal~orating
Centre for International Drug Monitoring in Uppsala, .Sweden.'

Nonproprietary Names. The INN identifies a specific phannaceutical subst;~nceor

active pharmaceutical ingredient. The INN is in the public clomain and cln Ilc ~~sccl
without restriction. It is sometimes referred to colloquially as the getzel-ic t~rrttic..~
However. the terms generic and nonproprietary are not synonymous. Generic drugs
are nontrademarked formulations of a drug that can be manufactured once a drug is
.no longer under patent restrictions. Generic drugs should be referred to 11y their
nonproprietary name, just as are proprietary drugs.
The INN reflects the chemistry, pharrnacologic action, and therapeutic usc
through its stem. Herbals (see 15.4.15, Herbals and Dietary Supplements), liomco-
pathic products, mixtures, drugs in common use for decades (eg, niorpliinc. co-
deine), and those with trivial chemical names (eg, acetic acid) do not receive ISSs.
The committees involved in reviewing and selecting INNS agree to a n:lnie that is :

then published as a proposed INN. During a 4-month comment period, any pcrson
can comment on or object to the proposed INN. If no objecti~nis raised, the name is
published as a recommended INN. New INNsare published in WHO Dtttg It!for-
mation in English, French, and Spanish (http://www.who.int/druginforn~:~tion). A
cumulative INN l i t is published, which also includes INNS in Russian. More tli;~n
7000 INNS have been designated as of 2004; 120 to 150 are added each year."

Stems. In addition to having a distinct sound and spelling to avoid confusion with
'other names, the INN includes a "stem" that designates the drug as a n~enlbero f a
family of related drugs, indicating that the drug has similar pharmacologic proper-
ties2
The stem is usually a suffix common to a particular drug class that is incorporatecl
h t o new drug names to indicate a chemical and/or pharmacologic relationship to
older drugs? For example:
~ ~ - r e c e ~antagonists:
tor cimetidine, racitidine, lupitidine (-tidine is the
stem)
Tyrosine kinase inhibitors: canertinib, imatinib, mubritinib (-tinib is the
stem)
P-Blockers: propranolol, timolol, atenolol (-0101 is the stem)
Combined a- and 0-blockers: labetalol, medroxalol (-a101 is the stem)
For some classes of drugs, the position of the stem varies within the drug name. For
the group of antiviral drugs (not necessarily having common pharmacologic, prop-
erties), the stem may be vir-, -vir-, or -vitl
ganciclovir, enviradene, viroxime, alvircept, delavirdinc
Approved stems are providecl on the USAN Web site7 and in the I I S P Diclio-
nary.l[ppl22&1232)
The goal of the WHO INN system is to have a single INN for each tlnrg LI\CCI
throughout the world. However, if the substance w:u in existence Ixforc tllr L.O-
ordination of nomenclature by WHO, nonproprietary namcs nl;ly t1ifit.r IW~.~\YC.VII
countries. For example, acetaminophen is the USAN for the salnc drug 111.1:11.1. !I!:.
BAN and DCF namepamcelamof. l'he USAN alh~llet.r,l h;ls a JI\S ,I ~ c l i h r ~ t ~I ~r i i~,I t , ~ , ;
(
 -*
--
15.4 Drugs

to be confused with sulmeterol, a longer-acting 0-adrenergic agonist).1(P44'Some

other names are more similar, such as cyclobarbitone (BAN) and cycloburbitol
(USAN). For these few drugs for which nonproprietary names differ by country, the
nonproprietary name used depends on the primary audience, although the Euro-
pean union has required that nonproprietary names that differ from the INN will be
phased out over time. In cases in which international recognition is essential (such as
adverse drug reactions), both names should be given at first mention.
Acetaminophen (paracetamol) was recommended as an initial treatment for
pain in the practice guidelines.
The existence of more than 1 nonproprietary name is also important when per-
forming searches on drugs in journals or databases; all nonproprietary names for a
particular drug should be used for a complete search. The USP ~ictionaryllists the
Y?TN and nonproprietary names by nomenclature agency, if they differ.

Orphan Drugs. Drugs that may be used to treat relatively rare diseases but that
otheryise are believed to have limited marketability are termed orphan drugs.8 I
When a drug is designated an orphan drug by the FDA, the name it receives is not
necessarily the name it will receive if it is approved for A listing of ;
orphan drugs is available at http://www.fda.gov/orphan.

Changes in Nonpropriebry Names. Nonproprietary names may be changed if they

are believed to be confusiig or could result in medication errors, or if they are
proven to infringe on trademark. For example, the antineoplastic compound mi-
thramycin became plicamydn to avoid confusing mithmmycin with the similar-
sounding antineoplastic rnitomyc,in and its proprietary name Mutamycin. The
nomenclature committees have procedures for applying to change the nonproprie-
tary name. (USAN'S procedure is available .at http://www.ama-assn.org/ama/pub
/category/!2916.html.)

Proprietary Names. The manufacturefsname for a drug (or other product) is called a
proprietary name or brand nanze.'@15)Proprietary names use initial capitals, with a
few exceptions (eg, pHisoHex). J A M and the Archives Journals ,do not use the .
trademark symbol (ml or the registered trademark symbol(0) because capitalization
indicates the proprietary nature' of the name (see also 5.6.16, Legal and Ethical
Considerations, Intellectual Property: Ownership, Access, Rights, and Management,
Trademark). The International Trademark Association has information about specific
trademarks and may be reached at http://www.inta.org/ or International Trademark
Association, 1133 Avenue of the Americas, New York, NY 10036.
Proprietary names for drugs often differ between countries (for example, nifed-
ipine initially was marketed as Procardia in the United States and Adalat in Europe).
Most US proprietary names are listed in the Physicians' Desk ~eferenc$and
~ictionary'and are cross-referenced to their USAN name. Unlike the nonproprietary
name, the proprietary name does not undergo a coordinated international effo
provide consistent naming. One example is the proprietary name Bextra, which is
the brand name for both valdecoxib (a cyclooxygenase 2 inhibitor type of non-
steroidal anti-inflammatory drug) in the United States and bucindolol (a P-blocker
not approved in the United States) in ~ u r o ~ Even
e ? when the same brand name does
nor refer 10 different drugs in different countries, a drug is often marketed under

568

-- . --- a
 15.4.4 Chemical Names

different brand names in different countries. Therefore, because the medical litera-
ture is read internationally and confusion about the intended drug could lead to
patient harm, the nonproprietary name should always be used and the proprietary
name should almost never be used in the medical literature.
The exceptions to this rule are reportsof adverse events that might be unique to
a specific product formulation, or comparison of a generic formula!ion of a drug with
the drug that was first approved. When both the nonproprietary and proprietary
names are used in text, the nonproprietary name should appear first, with the pro-
prietary name capitalized and in parentheses. Because proprietary drugs and man-
ufacturers are listed in the Physicians' Desk Reference and other sources, the
manufacturer does not need to be listed after the proprietary name.
The lot of penicillin G potassium (Pentids) was inspected and found to meet
the industry production standards.
Proprietary names may be used in questionnaires when the individuals responding
may be unfamiliar with the nonproprietary name or when the specific proprietary
product is important; in these cases the exact wording of the question should be
maintained, but the nonproprietary name should still be provided.
Parents were asked, "Have you ever given your child Tylenol [acet-
aminophen, paracetamoll or products containing Tylenol?"
Herbals and "natural" products generally d o not have INNS. Whenever possible, the
nonproprieta,ry name (as listed in the USP Dictionary or the PDRfor Nonprescription
Drugs and Dietary ~upplements,for.example) should be used. For some proprietary
formulations that comprise a blend of ingredients, however, the proprietary name
may be the only way to refer to the formulation. (See also 15.415, Herbals and
Dietary Supplements.)
The authors used mass spectrometry to analyze samples from a bottle of
Niagra Actra-R, and a bottle of Actra-R, (Body Basics) for the presence of
sildenafil.

Chemical Names. The chemical name describes a drug in terms of its chemical
structure."^^) Chemical names are provided in the American Chemical Society's
Chemical Abstracts (information available at http:/,,www.cas.org/,PRINTED/printca
.htrnl) and can be listed in 1 of 2 ways; the first reflects the way in which Chemical
Abaracts indexes inverted chemical names:
hydrazinecahoxyimidamide, 2-[-(2,6-dichlorophenoxy)ethyll-,sulfate, (2:l)
The second is the uninverted form:
2-[-(2,6-dichlorophenoxy)ethyl]hydrazinecarboxyimidamide sulfate, (2:l)
Both forms follow the recommendations of the International Union of Pure and
Applied Chemistry and the International Union of Biochen~istryand hlolecular
131ology.Each chemical is also designated a registry number with the Chemical
Abstclct Society (information available :lt http://www.cas.org/EO/regsys.html=q2),
7 ' h l h number is included in the USP diction^^^' listing for the dnlg. Chemicril names
:Inti registv are rarely used in medical pi~blications,and nonproprietaq
l(ppl3.1i)
n:lrllc.i ;lrc prefc.rrctl.
15.4 Drugs

Code Designations. A code designation is a temporary designation assigned to a

~ x c d u c r11). thr ins~itutionor manufacturer and may be used to refer to a drug under
de~.eloprnenrbefore a nonproprietary name has been assigned. Codes may be nu-
meric, alphabetic, or alphanumeric; letters in alphanumeric codes designate the
institution or manufacturer assigning the code designation of the drug, and are
followed by numbers to designate the chemical compound.1~p*5)
Once a nonproprietary name has been assigned, code designations become
obsolete and are rarely used in medical publications. If both the code and the
nonproprietary name are provided, such as in discussion of the history of a drug, the
nonproprietary name should be used preferentially and the code name may be added
in parentheses.
Mifepristone (formerly known as RU 486) was approved by FDA on Sep-
tember 28,2000.
Zidovudine (BW A509U) first became known as azidothymidine (commonly
known as AZT) during testing and eventually was marketed as Retrovir.

TrivialSNames.Drugs occasionally become known by an unofficial trivial name. The

trivial name should be &ed in biomedical publications only to reproduce the exact ;
language used as part of a study (eg, in a questionnaire), for historical reasons, or .
rarely when readers may be unfamiliar with the nonproprietary name. When re
ducing the exact language used in a study, the nonpropietary name should be
vided in brackets after the term used in the study.
The participants were asked, "Have you ever taken AZT [zidovudinel or
ddI [didanosinel?" Participants who said they had taken zidovudke or di-
danosine were classified as having had prior exposure to antiretroviral
agents.
When names other than the nonproprietary name are used for historical reasons or
1,ecause readers are unfamiliar with the nonproprietary name, the nonproprietary .
name should be used preferentially and the alternative name provided in pa-
rentheses.
Semustine (NSC-95441) has been referred to in the scientific literature by
trivial name, methyl-CCNU, a contraction of its chemical name 1-(2-chlor-
oethyl)-3-(4-methylcycloh&l)-1-nitrosourea.

Drugs With Inactive Components. Drugs often contain a pharmacologically inactive

component, eg, a base, salt, or ester, that is not responsible for the drug's mechanism
of action but lends stability or other properties to the drug. Drugs with both an active. :
and inactive component generally require a Zpart name that provides the active and
inactive portion of the drug. Inorganic salts and simple organic acids are n
in the order cation-anion'(eg, sodium chloride, magnesium citrate). For more com- .,

plex organic compounds, the active component is named first (eg, oxacillin so-
diUm).'(~1224)
~harmacologicallyinactive components are salts, esters, and com-
plexes. Sodium, potassium, chloride, hydrochloride, sulfate, mesylate, and fumarate ;

are common components of salts.

570

-- -__..-.-1 - - -- ..- _. _
. -- - <-, .;$p.L:'t;2~-r.+r 2
- .-
b .. .
. .
.
>. :i
.;.
-.
-. .-. -
-.
-.,.;.:I'.
.

. '. .
?
. .V . '
.. .'
 15.4.7 Drugs With Inactive Components

acyclovir sodium
midazolam hydrochloride
benztropine mesylate
morphine sulfate
Quaternary ammonium salts usually are designated by a Zpart name and have the
suffix -ium on the first word of the name.
atracurium besylate
alcuronium chloride
octonium bromide-
Salts and esters are frequently designated by the ending -ate. Three-word names are
used for compounds that are both salts and esters.
clomegestone acetate [ested
hydrocortisone valerate [esterl
testosterone cypionate [esterl
methylprednisolone sodium phosphate [salt and ester]
roxatidine acetate hydrochloride [ester and salt]
If more than one pharmacologically inactive molecule interacts with the pli:~rnia-
cologically active component, the number of molecules is reflected in the n:uile. I f
the number ,knot designated, the number of molecules is assumed to be I."~"""
balsalazide disodium 12 sodium molecules1
gusperimus trihydrochloride [3 hydrochloride molecules]
besipirdine hydrochloride [I hydrochloride molecule1
Complexes of 2 or more components may include a term ending in 4x to inrlic:~tc.;I
complex.
bisacodyl tannex
nicotine polacrilex
codeine polystirex
Chemical names are often too complex for general use. In such c;~scs,sliortc-r
nonproprietary names m a y be created. For example, for the rlrug cr)'throni!.i.in
acistrate, acistrate refers to the 2'-acecate (ester) and octadecanxttl (salt). For ~ h c
drug erythromycin estolate, estolate refers to the double salt propanoate ancl clodec!rl
sulfate.l(pp1224-l225)
In tlic I-I:IS~,so1i1e*INNS i ~ ~ ~ ~ li~i:~(.livc*
~ ~ c l c(.ol1i[-Ir)livllls
~ ( ~ :IS I-I:I~I of ~ I i c - i rI ~ : I I I(c~g.
IC
Ic~votliyrosincsorlii1111). ' 1 ' 1 1 ~ \VI I ( ) 111oili1ic.d l11ispolicy so 111:11 1 1 1 ~ .IbiN r ~ k r 10 s o11Iy
111c. : I C ~ I V Ccoliy>oncn\ ol' 111cclr\jg (os:~t.iIli~~. ~ I N I I ~ ~ I x I c ) .' 1 ' 1 1 ~I ~ : I I I I C ll1:11 i~iclt~ilcs IIIC
5;1it (os:lcillin stxliu111.il>ul'.n;~c.> o c l i t l l l l l I.\ I - C ' ~ I . I . C ' C ~ l o ;IS tlie 1l10diJio~1 IIVIV ( I N N M ) .
IIo\\c\.cr. for clnrgs origln;~llyn . ~ l ~ i r ft ol r tllv f i l l 1 entity. such as le\.othyrosine so-
clitlnj, tlic .horter (;~c.ti\c cnrlr! o r i l v ) n.lmtB.vg. Ic\.othYrosine, is consitlerecl the
1\\\1-
\ S ' \ I V I ~;I t o .I. .I .~crlcr.ll(.llrg~~!-,
~ l r t I l ~rc.tc-rrrxl 1l1c. I S N for the <]rugc:tn he
\ ~ * c . ( l \\-11llot11 1\ro\.1~1111g
111~.
III.ICII\C' I:I(~I~.(\
15.4 Drugs

The P-t,l(* kcrs mc,q wlcelve t o r P-1 aaivity are bisoprolol and metoprolol;
~~ct,urolol. c;lncd~lol,and ncbivolol are somewhat selective. All lose their
.wlcc~lv~cy ~vhcngiven at higher doses.
I lo\vever, if a specific drug is discussed for a specific use, particularly when
than one formulation is available, the inactive moiety should be included with the
drug name.
The patient was administered erythromycin ethylsuccinate, 400 mg by
mouth every 6 hours.
The inactive component should not be used when referring to an organism's sen-
sitivity to an antibiotic or to allergic reactions to drugs.
The strain of Streptococcus pneumoniae isolated by the laboratory was
highly resistant to penicillin.
The patient's plasma lithium level at 8 AM was 2.0 mEq/L.
The woman developed urticaria after &king erythromycin.
The inactive component -may also be used with the proprietary name (see 15.4.3,
Proprietary Names).
Hydralazine hydrochloride was marketed as Apresoline Hydrochloride.
If both the nonproprietary name and the proprietary name are provided toge
inactive component is given only once.
The patient had been taking hydralazine (Apresoliine) hydrochloride in the
1980s but developed an urticarial papular rash.

Stereoisomers. Some chemical compounds may occur in more than 1optical ori
tation, referred to as stereoisomers, and they may have very different biological I
effects, such that most biological activity is exerted by 1stereoisomer. Stereoisomers ..

are designated as leuomfatory or decxnjmtatory; a mixture of the 1 is racemic

addition, chemical compounds may have different biological chirality (de
by mass spectrometry), referred to as-enantiomm.'0<pp1314)Enantiomers
nated as R(-) or S(+). Nonproprietary names for new chemical entities do not usually . ,,;
speclfy the stereoisometric form of the molecule. For example, carnitine and ibu- ::
profen are racernic mixtures, remoxiprideis a lev0 isomer, and butopamine is a .
dextro isomer. If a subsequent drug is another isometric form of the same chemical, a :
prefix may be used to designate the stereois~mer.'(~'*~~)
For the racemate, rac- or race- is added to the compound (eg, racepinephrine).
For the levorotatory form, the "S" isomer uses the leu- or levo- prefix (eg, levamisole,
levdobutamine), whereas the " R isomer uses the ar- prefix. For the dextrorota
form, the "S" isomer uses. the es- prefix, whereas the "R isomer uses the dm- or
dextro- prefix (eg, dexibuprofeni dextroamphetamine, dexamisole).

Combination Producti. For combination products (mixtures), the names of the active
ingredients should be provided. The proprietary name of the combination ma
given in parentheses if necessary to clarlfy the product to which the article refers.

572

,
.. .-
_.. .- .
-.. A.

[
..
 15.4.1 1 Multiple-Drug Regimens

pseudoephedrine hydrochloride and triprolidine hydrochloricle (Actil;.cl)

povidone and hydroxyethylcellulose (Adsorbotear)
I
\ If the list of active ingredients is too long to use when referring to the coml,inarion
product, the active ingredients should be listed at first mention and either a n at>-
breviation or the proprietary name used thereafter.
The patient reported having taken several doses of Vanex HD, a liqi~icl
suspension of hydrocodone bitartrate, 10 mg, phenylephrine hydrochlo-
ride, 30 mg, and chlorpheniramine maleate, 12 mg, per 30 mL, the previous
day.
The patient had been administered an artificial tear product containing
0.42% hydroxyethylcellulose and 1.67% povidone (Adsorbotear).
only the active ingredients must be listed. However, in some circumstances it may be
necessary to include all ingredients, including preservatives, if sensitivity to an in-
gredient may be important. ,

The patient had complained of red, itching eyes after using an artificial tear
product containing hydroxyethylcellulose and povidone with edetate diso-
dium and thimerosal preservatives (~dsorbotea;).
The USP may provide a pharmacy equivalent name PEN)''^'^' to refer to a com-
bination product, such as co-triamterzide for the combination of triamterene and
hydrochlorothiazide. However, PEN terms are not official USP titles and should be
used only if they are familiar and clear to readers. Because co-triamterzide is unlikely
to be familiar to most readers, the following approach can be used:
Participants were given a capsule containing a combination of 25 mg of
hydrochlorothiazide and 50 mg of triamterene each day at 8 AM. Those not
able to tolerate hydrochlorothiazide-triamterenewere given.50 mg of met-
oprolol at 8 AM.
Trimethoprirrcsulfamethoxazole (80 mg of trimethoprim and 400 mg of
sulfamethoxazole) administered once daily effectively prevented reinfection
in 93% of patients.

Drug Preparation Names That Include a Percentage. Some drug names, such as
those used in topical preparations, include the percentage of active clrug contained in
the preparation. In these cases the percentage should be listed after the drug name.
The patient was treated with adalapalenc gel, 1%.
Metronidazole lotion, 0.75%, was applied twice a day.

Multiple-Drug Regimens. Regimens that include inultiple drugs may be referred to

by an abbreviation after the nonproprietary names of the drugs have been provided
at first mention (see also 15.4.12, Drug Abbreviations, and 14.11. ~bbreviations.
Clinical, Technical and Other Common Terms). D n ~ greginlens 11scd in oncology
frequently are referred to by abbreviations of conlbinations of antincr)pln.;ric ilgcntz.
but often the abbreviations are not derived from tllc INNS For vs:\~nplt..the lertcr 0
,
i
b
! 573
I;
15.4 Drugs

in MOPP is derived from Oncovin, the proprietsr) namc for vlncrisrint. sulfate, and
the A in ABVD is derived from Adriamycin, thc proprietltr). name for doxorul)~crn
hydrochloride. When the abbreviation is expanded [he proprietary namrs I I U ~ be
provided after the nonproprietary names to clarify the origin of the abbreviation.
The MOPP (methotresate, vincristine sulfate [Oncovin], prednisone, and
procarbazine hydrochloride) regimen for advanced Hodgkin disease was
compared with MOPP alternating with ABVD (doxorubicin hydrochloride
[Adriamycinl, bleomycin sulfate, vinblastine sulfate, and dacarbazine).

Drug Abbreviations. Some drugs have commonly used abbreviations, such as INH
for isoniazid and TMP for trimethoprim. However, abbreviations may be used in-
consistently or confused with other terms or be unfamiliar to some readers. Because
of the potential for harm from erroneous interpretation of abbreviated drug names,
abbreviations should not be used except in rare ins:.:nces (eg, trimethoprim-sulfa-
methoxazole may not fit in a table heading and may need to be abbreviated, eg, TMP-
SMX; in that case the expansion should be provided in a table footnote).

Nomenclature for Biological Products. Several categories of drugs are identical to or

derived from biological products. Some hormones given as drugs, for example,
require special mention because the drug name differs from the name used for the
endogenous substance (please note that this is not a comprehensive list of such
drugs). Other categories of biologicals are derived from specific guidelines devel-
oped by USAN, outlimed below..
Using the appropriate name can help clarify that the substance referred to is a
drug, although for less familiar drug names it may be necessary to include the
endogenous hormone name in parentheses to clarify the action of the drug for
readers. (For more information on appropriate abbreviations for hormones, see
14.11, Abbreviations, Clinical, Technical,and Other Common Terms.) The following
information is based o n the USP ~ i c t i o n a ~ ' ~ ~ ' ~ ~ ~ ~ ~ ~ '

Hypothalamic Hormones. The suffix -relin denotes hypothalamic peptide hormones

that stimulate release of pituitary hormones and the suffix -mlk denotes hormones
that inhibit release.
Native Substance Diagnostic/l%erapeuticAgent
thyrotropin-releasing prdtirelin
hormone (TRH)
luteinizing hormone-releasing buserelin acetate, gonadorelin
hormone (LHRH) (or acetate (or hydrochloride),
gonadotropin-releasing histrelin, lutrelin acetate,
hormone [GnRHD nafarelin acetate
growth hormone-releasing somatorelin
factor (GHRF)
growth hormone release-inhibiting detirelix acetate
factor (somatostatin, GHRIF)
 15.4.13 Nomenclature for B~ologicalProducts
1
I

-
Example:
After venipuncture, protirelin (synthetic thyrotropin-releasing liorrnonc)
was injected. .

Growth Hormone. The som- prefix is used for growth hormone derivatives.
Native Substance Diagnostic/ Therapeutic Agent
growth hormone somatrem (mettiionyl human growth
hormone)
somidobove, sometribove,
somagrebove (bovine
somatotropin derivatives)
somalapor, somenopor,
sometripor, somfasepor
(bovine somatotropin derivatives)

ThyroidHormones. Abbreviations for thyroxine and triiodothyronine are provided in

parentheses and may be used after the name is expanded at first mention.
Description Therapeutic Agent INN
levorotatory thyroxine (T4) levothyroxine sodium
//' ttiiodothyronine (Td liothyronine sodium
dextrorotatory triiodothyronine dextrothyroxine sodium
mixture of liothyronine and liotrix sodium
levothyroxine sodium

/nsulin. Insulin terminology can be a source of clinically important confusion. par-

ticularly with regard to insulin concentrations and types. Insulin concentrations :Ire
as follows (not necessary to'expand at first mention):
UlOO contains 100 U of insulin per milliliter (the most comtnot~lyuse-ti
concentration).
U40 contains 40 U of insulin per milliliter.
U500 contains 500 U of insulin per milliliter.
Insulin types include those that may Ile arlministerecl intravenously. sirl~cut;~n~~ousIy.
or intrarhuscularly (injections) and those that may be aclministcrccl onl!. stt11-
cutaneously or intraniuscularly (suspensions). Anothcr form of insulin 111;1y in-1 1 ~ 5

haled. !

Insulin is prepared with the use of recombinant DNA technology (rcfcrr~tlt o ;I.;
human insulin, since the source is human DNA) or as a synthetic mocliIir.:~tiorlof
porcine insulin. Proprietary names are provided below because they arc. oftc11~ I X Y I
to refer to the potentially confusing various types of insulin preparations. I:or ~.l;~rit!.
and conciseness, use of proprietary terms in addition to the nonproprict:~r!. Icsrl,.
may be necessary in some cases. The following lists are not c~mprehcnsi\-c.I ) ~ l t . I N .
intended to provide examples of the nonproprietary nanles that shoi~ltlIIC LI\I.CI ; ~ r l t l
their corresponding proprietary names.
15.4 Drugs

Injections

Preferred Temz Proprietary h'crtne

human insulin injection Humulin
insulin lispro injection Humalog
insulin aspa1-t injection Novolog

/ insulin gkargine injection Lantus

Suspensions

Preferred Term Proprietary Name

I
insulin zinc suspension, prompt Semilente
insulin zinc suspension Lente
. -. hunlan insulin extended zinc Ultralente
/" suspension
d
insulin isophane suspension NPH [neutral protamine
Hagedornl'
'NPH is the single exception to expressing drugs ;u: abbreviations and can be used in its
abbreviated fonn.

Insulin is available in combinations of injections and suspensions: - . ;

Prefened Tern Name

Pmpnpnetary
70% human isophane Humulii 70130
suspension/30% human
insulin injection
70% insulin aspart protarnine Novolog Mix 70130
suspension/300/o insulin
aspart injection
75% insulin lispro protamine- Humalog Mix 75/25
suspension/25% insulin
lispro injection
50% insulin isophane Humulin 50150
suspension/50% human insulin injection

Interferons. Interferon is defined as "the class name for a family of species-specific

. proteins (or glycoproteins) produced according to information encoded by species
of interferon genes and exert complex antineoplastic, antiviral, and irnrnuno-
modulating e f f e ~ t s . " ~ ' ~(See ~ ) 15.8, Immunology.)
' ~ ~also
The 3 main types used for therapy are as follows:
interferon alfa (formlrly leukocyte or lymphoblastoid interferon) [Thef is -.
used rather than ph to avoid the confusing ph in international usage.]
interferon beta (formerly fibroblast interferon)
interferon gamma (formerly immune interferon) \4
Subcategories are designated by a numeral and a lowercase lerter, l'hc lo\\ c . 1 ~: ~ s c
letter after the number differentiates one n~anuFdcturer'sinterferon from :inorlic.l-'s.
Examples of pure interferons are as follows:
interferon alfa-2a
interferon alfa-2b
interferon beta-la
interferon beta-lb
interferon gamma-la
For naturally occurring mixtures of interferons, a lowercase 17 prececles thc ~ ~ i ~ ~ n c r : ~ l :
interferon alfa-n 1
interferon alfa-n2

Interleukins. There are 12 interleukin derivatives. All except interleukin 3 rntl in -X?i~l
(eg, aldesleukin). Interleukin 3 is designated by the -plestim stem (eg. d:~niplc::.r ill; :,
and is a pleiotropic colony-stimulating factor (see also Colony-Stimulating F:IcIoI..:!.
Stem
interleukin 1 derivatives
interleukin l a derivativcs
interleukin l b derivatives
interleukin 2 derivatives
interleukin 4 derivatives
interleukin 5 derivatives
interleukin 6 derivatives
interleukin 7 derivatives
interleukin 8 derivatives
interleukin 9 derivatives
interleukin 10 derivatives
Linterleukin 11 derivatives
interleukin 12 derivatives

Colony-Stimulating Facton. Therapeutic recombinant colony-stimulating factors :ire

named according to the following guidelines"P""' (see also 15.8, Imn~unolog!~).
The suffix -grastim is used for granulocyte colony-stimulating factors (G-CSFs)

The suffix grarnoslim is usecl for gri~nulocyte-~~i:~cropI~dge

colony-stin~uliiringf x -
tors (Ghl-CSFs):
15.4 Drugs

The suffix -mostim is used for macrophage colony-stimulating factors (M-CSF):

mirimostim
I
, I

The suffix -plestim is used for interleukin 3 (IL-3) factors, which are classdied as -
I~L.'.
pleiotropic colony-stimulating factors:
muplestim
daniplestim
The suffix -distim is used for conjugates of 2 types of colony-stimulating factors: 1.
rnilodistim 1.
The suffix -cestim is used for stem cell-stimulating factors:
ancestim
I- 1
Erythropoietins. The word epoetin is used to describe erythropoietin preparatidns
that have an amino acid sequence that is identical to the endogenous cytokine. The
words alfa, beta, and gamma are added to designate prepaktions with different
composition and carbohydrate
epoetin alfa : I
epoetin beta . -
epoetin gamma

Monoclonal Antibodies. Therapeutic monoclonal antibodies and fragments are des-

ignated by the suffix -mab. Monoclonal antibodies are derived from animals as well
as from humans and the nomenclature is based on the source of the antibody
(mouse, rat, hamster, primate, or human) and the disease target or antibody subclass.
Some examples of monoclonal antibodies are abciximab, dacliximab, and satumo-
mab.1(p1225-1226)
The following letters are used to identlfy the source of the monoclonal antibody:
u human
e hamster
o mouse
i primate
a rat
xi chimera
zu humanized
These identifiers precede the -ma6 suffix stem, for example: I

-umab human
-omab mouse
, I
-ximab chimera
-zurnab humanized
.I.he general c1isc;lse state subclass is also incorporated into the name by use of a code.
s)~II:ll~lc..

I
I
1 .
. . --.--
 15.4.14 Vitamins and Related Compounds

-vir- viral
-bac- bacterial
-1im- immune
-1s- infectious lesions ,

-cir- cardiovascular
Monoclonal antibodies used to treat particular tumors are incorporated into the name
using the following syllables.
-col- colon
-mel- melanoma
-mar- mammary
-got- testicular
-got+ ovarian
-pr (0)- prostate .
-turn- miscellaneous
Key elements are combined in the following sequence:. the letters representing the
target disease state, the source of the product, and the monoclonal root -mab used
as a suffix (eg, bicimmab, satumomab). When a target or disease stem is combined
with the source stem for chimeric monoclonal antibody, the last consonant of the
targetldisease syllable is dropped to facilitate pronunciation:
Target Source
- - -mab Stem USAN
cir- -xi -ma6 abciximab
-1im- -zu -mab daclizumab

Radiolabeledor ConjugatedProducts. Some products are radiola6eled or conjugated

to other chemicals such as toxins. Such conjugates are identified by a separate,
second word or other chemical designation. For no no clonal antibodies conjug:tted
to a toxin, the "-to? stem indicates the toxin (eg, zolimomab aritox, in which the
designation aritox was selected to identify ricin A-chain). For radiolabeled products,
the isotope, element symbol, and isotope number precede the monoclonal anti-
(See also 15.9.2, Isotopes, Radiopharlnaceuticals.)
technetium Tc 99m biciromab
iidium In 111 altumomab pentetate
A separate term is also used to designate a linker or chelator that conjugiltes the
monoclonal antibody to a toxin or isotope, or for pegylated (having polyetl~ylene
glycol, or PEG, attached) monoclonal antil~oclies."~"~~"'

Vitamins and Related Compounds. 1-llc 1.i111111.11 ICIIC:~ I ~ . L I I ~01' ~ , 1110~1\ . i [ : ~ l i l i ~ l . qg~'11-
c.i.i!!i-rc.f(.r r o 1 1 1 ~ . \trlhl;irl~~c~ ; I \ I'ot111cI 111 I'(wK!.in<!in \ I \ < ) \\.;[I1 1111. c.sc.c.l>lio~~ 01
~ r . i t ~ i l r lA\ . I<. .111t\
1%c.011lplcs.lhc 1x5.. I'or \ l l . ~ i l l i f l \X I \ c.11 ~ l ) c . r . l ~ > c . t l [ i.IcII!- t1ilf.r 1'1.0111
L
1I)rlr lrl \,I\.() nlrmes. (To enhance clarity for readers, the equivalent vitamin name may
.IIWJ lx pro\iJcd.) Various types of carotenoids (alpha- and beta-carotene and beta-
~ - r ) . ~ ~ o s l r n tnuy
l ~ i nbe
) converted to vitamin A within the body, so the specific agent
that is administered should be provided. The native form of vitamin A is most often
supplied as retinol acetate. Other forms of vitamin A may be administered topically
(such as retinoic acid). Vitamin E refers to a group of tocopherol compounds, and
the specific chemical names should be provided (eg, alpha-tocopherol, gamma-
tocopherol, delta-tocopherol, or mixed tocopherols). The specific stereoisomers and
whether the product is natural or synthetic should be provided where relevant (eg,
DL-alphatocopherol acetate). For vitzamin B complex, the specific components in-
cluded in the B conlplex should be provided. (For additional information see the
Institute of Medicine texts listed under "Additional Readings and General References"
at the end of this section.) The following are examples of USAN drug names equiv-
alent to their vitamin n a m e ~ l ' p ~ ~ ~ ) :
Native Vitamin Drug Name
vitamin B1 . thiamine hydrochloride
vitamin B1 mononitrate thiamine mononitrate
vitamin B2 riboflavin
vitamin B6 pyridoxine hydrochloride
vitamin B8 ad.enosine phosphate
vitamin B12 cyanocobalamin
vitamin C ascorbic acid
vitamin D cholecalciferol
vitamin Dl dihydrotachysterol
vitamin D2 ergocalciferol
vitamin G riboflavin
vitamin K1 phytonadione
vitamin K2, menaquinone
vitad'~4 troxerutin

Herbals and Dietary Supplements..Herbals and dietary supplements do not receive

INNS, and they are not regulated as drugs in many countries, including the United
States (as mandated by the Dietary Supplement Health and Education Act, passed in
1994~9.
In the United States, Congress has defined a dietary supplement as
a product talten by mouth that contains a "dietary ingredient" intended to
supplement the diet. The "dietary ingredients" in these products may include:
vitamins, minerals, herbs or other botanicals, amino acids, and substances
such as enzymes, organ tissues, glandulars, and metabolites. Dietary sup-
plements can also be extracts or concentrates, and may be found in many
forms such as tablets, capsules, softgels, gelcaps, liquids, .or powders. They
can also be in other forms, such as a bar, but if they are, information on their 1'
label must not represent the product as a conventional food or a sole item of
a meal or diet. 'Whatever their form,may be, [Dietary Supplement Health and
 15.4.15 Herbals and Dietary Supplements
i
Education Act] places dietary supplements in a special category under the
general umbrella of "foods," not drugs, and requires that every supplement
he labeled a dietary supplement.'O~"
Components of dietary supplements may be pl~armacologicallya<tive, so :IC-
curate and specific nomenclature is essential. As noted above, dietary supplements
are often mixtures of several ingredients, and quantities of each may be proprietury.
Such a mixture makes standard nomenclature policy difficult to establish. \Vhencvcr
possible, a nonproprietary name should be used to refer to a dietary supplement.
However, if the dietary supplement is a mixture of many components, either XI
abbreviation derived from the components or the proprietary mame must I>c usctl.
(See also 15.4.9, Combination Products.)
Metabolife 356 (Metabolife International Inc, San Diego, California) is ;I
dietary supplement containing 19 labeled ingredients including ephcdra ;incl
caffeine (hereinafter abbreviated as DSEC).
The USP DictioruzyI1 Physicians' Desk Reference for Nonprescriptio~rDrrr,q.s trrrrl
Dietary ~upplements,'~ Physicians' Desk Reference for Herbal Medicir les." ancl ' I ~ c J
Complete German Commission E Monographs: i73erapetrtic Guide lo Hc~rl~trl .lltrl-
i c i n d 4 are useful resources for naming herbals and dietary supplemcnts. II' tllcsc
resources do not provide the necessary information, the Web can be helph~lin itlc-n-
tifyiig substances as well, although of course the accuracy of the source shoulcl iw
considered.
Herbal medicines generally can be named according to their bot;~nical~ c n u s
and species, although the lack of regulation in some countries again makcs con-
sistent nomenclature a challenge. A review of regulation of herlxl ~ileclicincs
worldwide has been completed by the WHO." Particularly in countries \vherc
botanicals are not regulated, the specific herlxl and manuh~cturer,\vhcrcvcr rcl-
evant, should be included, since different manufacturing techniques result in tlif-
ferent biological activity. According to WHO,
It is not unusual for a common came to be used for two or more different
species. Unless the names of herbal plants follow an international syste~n
of plant nomenclature, the potential for confusion when exchanging in-
formation is enormous. The information attached to a name is thus crucial.
As an example, because common names are often used, heliotrope (He-
liotmpium eumpaeum)-containing potent hepatotoxins-is often con-
fused with garden heliotrope (Valtfl.ana oficinalis), which is used as a
sedative and muscle relaxant. Identification of the herbal preparation by
the Latin binomial system, in addition to the common nzune, is ~herrfore
essential.16
Thus, whenever possible, herbals derived from a specific plant should be named
according to the botanical name (eg, Ginkgo biloba, Echinaceaptllplrrea) to ensure
that the correct entity is identified. When the plant itself is referred to, the genus and
species may be abbreviated after being spelled out at first mention:
The main pharmacologic substances with imrn~~nostimi~l;~nr :~cTi\.~r!. In C X -
perimental and clinical sti~dicsarc purifictl poIys:~cchariclcs111.11c . ~ nIN. c.s
tracted only in small quantity from pressctl Ec'chirlcrc-rw pit r p r r r t , i r
15.4 Drugs

One day prior to taking G i ~ ~ k Diloh

go or placetm and again at the end of the
6-week double-blind period (while still taking G biloba and within 3 days of
the end of the study), participants undenvent neuropsychological evaluation i
including :ests of learning, memory, attention and concentration, and ex-
pressive language. :
<

In some cases the vernacular name is nor the genus or species and should be pro-
vided as well to ensure that the reader understands which plant is intended. .j

Hypen'cutnperforatum (St John's wort) is a popular herbal product used to :

treat depression, but it has been implicated in drug interactions.
When referring to a specific product or formulation, as in a study, the specific pro- \
prietary name and manufacturer should be listed, because formulations vary by
manufacturing technique.
Participants were randomly assigned to 1 of 2 conditions: biloba
(Ginkoba; Boehringer Ingelheim Pharmaceuticals, Ingelhein mny) or
placebo control (1:l ratio). 1I7
A marketed enteric-coated preparation (Tegra; Hermes Arzneirnittel GmbH;
Grosshesselohe, Germany) containing 5 mg of steam-distilled garlic (Allium
sativum) oil bound to a matrix of beta cyclodextrin and matching placebos, -$
whose coating tasted like garlic, were used. f
Q

Guggulipid, which is an extract from the plant Commiphoramukul (guggul), j

contains numerous other substances besides the small amounts of guggul- 1
sterones purported to be the active ingredients. ?

REFERENCES
'
1. USP Dictionary of USAN and International Lhug Names. 41st ed. Rockviie, MD: US
Pharmacopoeia; 2005.
2. Guidance on INN. World Health Organization. http://www.who.int/medicines
/services/inn/innquidance/en/index.html.Accessed June 14, 2006.
3. International Nonproprietary IVk-nes. World Health Organization. http://www
.who.int/medicines/services/inn/en/.Accessed June 14, 2006.
4. Nies AS. Principles of therapeutics. In: Hardman JG, Limbird LE, eds. Goodman G
Gilman's The Pbannacological Basis of Therapeutics. 10th ed. New York, NY:
McGraw-Hill Book Co; 2001.
5. Physicians' Desk R e f i c e . 59th ed. Montvale, NJ: Medical Economics; 2005. 4
6. Safety, efficacy and utilization of medicines. World Health Organization.
http://www.who.int/m~dicines/areas/quality_safety/~afety~effi~acy/en/. Accessed
June 14, 2006.
7. Van Laan S. Approved stems. USAN. http://www.ama-assn.org/ama/pub/category
/4782.html. Updated July 20, 2006. Accessed September 22, 2006.
8. Orphan Drug Act, Pub L No. 97-414. http://w.fda.gov/orphan/oda.htrn. Accessed
June 14,2006.
 :'

., 15.4.1 5 Herbals and D~etarySupplements

9. Toyer D, Holquist C. Bextra: valdecoxib or bucindolol?[FDA Safen P . ~ g e ] . I l n ~7y)rc.s

g
January 6, 200354.
I
10. Dietary Supplement: Health and Education Act of 1994. I!S Food :rnd Drug Acl~nin-
istration, Center for Food Safety and Applied Nutrition. http:~vm.cfsan.lcla
.gov/-dms/dietsupp.html.December 1, 1995. Accessed September 22. 2006.
11. Overview of dietary supplen~ents.US F o a l and 1)rug Administration. http://\v\\.\\,
.cfsan.fda.gov/-dms/ds-oview.html.January 3, 2001. Accessed September 22. 2006.
12. Pbp'cians' Desk Reference for No?zprescnption Drugs and Dieta y Szipplenrerz/s. 25th
ed. Montvale, NJ: Medical Economics; 2004.
13. Pbysiciam' Desk Reference for Herbal Medicines. Montvale, NJ: Medical Economics;
1998.
14. American Botanicat Council; Blumenthal M, Busse WR, Klein S, et al, eds. %e Cotn-
plete Gaman Commission E Monographs: Therapeutic Guide to Herbal Medicines.
Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
15. Regulatory situation of herbal medicines: a worldwide review. World Health
Organization. http://whqlibdoc.who.int/hq/1998/WHO-TRM~8.1.pdf. Accessed
June 14, 2006.
16. General policy issues. W O Drug Inf: 1998;12(3)129-135. http://mw.who.int
/d1uginformation/voll2/12-3.pdf. Accessed June 14, 2006.

ADDITIONAL READINGS AND GENERAL REFERENCES

Billups NF, Billups SM, eds. American Drug Index. 40th ed. St Louis, MO: Facts and
Comparisons; 2004.
Dmg Facts and Comparisons [looseleaf with monthly updates]. St Louis, MO: Welters
Kluwer Health Inc. Available for purchase at http://www.factsandcomparisons.com
~/~roducts/index.aspx?id=l042. Accessed June 14, 2006.
F w d and Nutrition Board, Institute of Medicine. Dieta y Reference Intakesfor Vitamin C.
Vitamin E, Selenium, and Camtenoids. Washington, DC: National Academy Press; 2000.
Food and Nutrition Board, Institute of Medicine. Diela y Reference Intakes (DRl)for Vi-
tamin A, Vitamin K,A m i c , Boron, Chromium, Copper, Iodine, Iron, Maganese, Mo-
lybdenum, Nickel, Silicon, Vandadium, and Zinc. Washington, DC: National Academy
Press; 2000.
WHO Drug Informcrfion[published quarterly]. I~ttp://www.who.int/druginformation.
Ac-
cessed June 14, 2006.
I

Equipment, Devices, and Reagents. As with drugs and isotopes, nonproprietary

names o; descriptive phrasing is preferred to proprietary names for devices, equip-
ment, and reagents, particularly in the context of general statements and inter-
changeable items (eg, urinary catheters, intravenous catheters, pumps). However, if
several brands of the same product are being compared or if the use of proprietary
names is necessary for clarity or t o replicate the study, proprietary names should I)e
given at first mention along with the nonproprictary n;ume. In such cases inforni:ct~on
regarding the manufacturer or supplier and location also is important, and authors
should include this information in parentheses after the name or description. A~lthors
should provide this information for any reagents, antibod~es.enzymes. o r probes
used in investigations.
!
85
?'
58 3
15.6 Genetics

The following are examples wtwrc. specific ~nfomiat~ori

L< rrcquircd
;

The positron emission loniogmphy (1'W unit (4096 Plus; Ccnrril t.lt.c~r~c
., Systems, Milwaukee, Wisconsin) comprised 8 detector rings positioned in a
cylindrical array. Image processing and reconstruction were performed with
a VAX 4000-300 computer system and a VAX 3100 workstation (Digital
Equipment, Marlboro, Massachusetts).
All magnetic resonance angiography examinations were performed with
a 1.5-T whole-body imager (General Electric Medical Systems, Milwaukee,
Wisconsin).
The following are examples of general references:
I
Some hearing loss may result from use of a portable radio or cassette player
equipped with headphones (Walkman-style) played at high decibel levels. ,

Currently, treatment by Nd:YAG.laser is the accepted method to surgically

open the opacified posterior capsule.
As with drugs and isotopes, proprietary names should be capitalized; the registefed
trademark symbol is not used.
If a device is described as "modified," the modification should be explained or
an explanatory reference cited. If equipment or apparatus is provided free of charge
by the manufacturer, this fact should be included in the acknowledgment (see 2.1018;
Manuscript Preparation, Acknowledgment Section, Funding/Support; 5.2.1, Ethical
and Legal Considerations, Acknowledgments, Acknowledging Support, Assistance,
and Contributions of Those Who Are Not Authors; and 5.5.2, Ethical and Legal Con-
siderations, Conflicts of Interest, Reporting Funding and Other Support).

When new nommclature ispresenied, it ofien looks

odd to practising biochemists and is not alwa3js u p
preciated. Even systems such as the one-letter codes
for amino acids, which have been uniumally
adopted, met with some skepticism at fixst.
R. cammackl

Euey cell division involves the copying of 6 billion

base pain (bp) of DNA.
F . S . Collins and J. M. T.rent2

Genetics

Nucleic Acids and Amino Acids. Standards for molecular nomenclature are set jointly
by the International Union of Biochemistry and Molecular Biology (IUBMB) and th
International Union of Pure and Applied hem is try(^^^^^).' The recommendations iq e
this section are based on conventions put forth by the IUBMB-IUPACJoint Commission
on Biochemical Nomenclature and the Nomenclature Committee of the I L X ~ ~ I D . ~ . "
 15.6.1 Nuclei~Acids and Amino Acids

DNA. The nucleic acids DNA and RNA are nucleotide polymers. Deoxyribonucleic
acid, or DNA, is the embodiment of the genetic code and is contained in the chro-
mosomes of higher organisms. It is made up of (1) molecules called bases, (2) the
sugar 2-deoxyribose, and (3) phosphate groups. The bases fall into 2 classes: py-
rimidine and purine.
Structurally, DNA is a helical polymer of deoxyribose linked by phosphate
groups; 1of 4 bases projects from each sugar molecule of the sugar-phosphate chain.
A base-sugar unit is a nucleoside. A base-sugar-phosphate unit is a nucleotide
(Figure 2). The carbons in the sugar moiety are numbered with prime symbols (not
apostrophes), eg, 3'-carbon, 5'-carbon. The carbons and nitrogens of the bases are
numbered 1 through 6 (pyrimidines) or 1 through 9 (purines), and the carbons of
deoxyribose are designated by numbers with prime symbols, 1' through 5'.

Nucleoside Nucleotide

Phosphate

3'

Figure 2. Nucleosides and nucleotides: general structure.

This section presents nomenclature for nucleotides of DNA, especially nomen-

clature used for DNA sequences, ie, nucleotide polymers. For nomencl:iturc o f
nucleotides as DNA precursors and energy molecules, see the "Nucleotitles as I'rc-
cursors and Energy Molecules" section.
A 1-letter designation represents each base, nucleoside, or nucleotidc. Thc Icr-
ters are commonly used without expansion:

Abbreviation Base Residue in DNA ;I 1oIc~c.1/ / ( / I . (.Yc/.i.<

.

A adenine deoxyadenosine purine

C cytosine deoxycytidine pyri~i~icli~~c
G guanine deoxyguanosine purine
T. thymine deoxythyrnidine pyrimiclinc
The chemical structure of bases is illustrated in Figure 3. When a I~ase(or ni~clcc,sitl~
or nucleotide) is described that cannot be firmly identified zs A, C, G, or 1'. other
single-letter designators reflecting biochemical properties are used. U e c ~ i ~ rl-rcsc
sc
designations are not as well known as A, C, G, and T, it is best to definc them. :IS
shown below (table adapted by permission from ~ o s s l~ttp://\viv\\..chc~i~.c~tln\\.
, ~
.ac.uk!iubrnb/misc/n3~q9html, Nomenclat~~re for Inconlpletely Specifiecl I3;c.scs in
Nuclclc. Acid Scqucnccs, 5. Discussion, copyright IUBMB):
S)VIbtd .Sfi~r~li.x
j ~ r Dct-icv~tiot?
.
-

It G nr h purine
 15.6 Genetics

. i
Stands for Derivation I

A or C amino I
G or T
G or C strong interaction (3 hydrogen bonds)
AorT weak interaction (2 hydrogen bonds)
A or C or T not G (H follows G in the alphabet)
G or T or C not A (B follows A)
G or C or A not T (V follows T; U is not used
because it stands for uracil in RNA [see
"RNA" section])
not C (D follows C)
any base

7
Purines

Adenine (A)
H.
Bases

- Pyrimidines

Thymine O
I

1
i I

Guanine (G) Cytosine (C)

."

Figure 3. DNA bases: chemical structure.

Various forms of DNA are commonly abbreviated as follows; expand at first use:
bDNA branched DNA
cDNA complementary DNA, coding-DNA
dsDNA double-stranded DNA
gDNA genomic DNA
hn-cDNA. heteronuc1e;lr cDNA (heterogeneous nuclear cDNA)

586
 15.6.1 Nucleic Acids and Amino Acids

mtDNA mitochondria1 DNA

nDNA nuclear DNA
rDNA ribosomal DNA
scDNA single-copy DNA
ssDNA single-stranded DNA
There are several classes of DNA helixes, which differ in the direction o f rotation aticl
the tightness of the spiral (number of base pairs per turn): . -
A-DNA
B-DNA
C-DNA
D-DNA
Z-DNA (zigzag .,
In eukaryotic cells, DNA is bound with special proteins associated with chromo-
somes (see 15.6.4, Human Chromosomes). This ~ ~ ~ - ~ r complex G e i nis knon-n as
chromatin. DNA in chromatin is organized into structures called nucleosomes by
proteins known as histones. The 5 classes of histones are as follows:

H2A
H2B
H3
H4
Almost all native DNA exists in the form of a double helix, in which 2 DNA polymers
are paired, linked by hydrogen bonds between individual b a ~ e son each chain.
Because of the biochemical structure of the nucleotides, A always pairs with T and C
with G (Figure 4). Such pairs may be indicated as follows:

Mispairings (which may occur as a consequence of a mutation o r sequence variation)

may be shown in the same way:
C-T
Unpaired DNA sequences are quantified by means of the terms base, kb (kilo-
base), and Mb (megabase). Paired DNA sequences use the terms bp (base pairs). kb
(kilobase pairs), and Mb (megabase pairs). (Do not use "kbp" 01. "Mbp.") For example:
 SUgi
bacl

Figure 4. DNA double helix.

 15.6.1 Nucleic Acids and Amino Acids

Sometimes the number of nucleotides in a DNA molecule,is indicated using the suffix
"mer":
20mer (20 nucleotides)
24mer (24 nucleotides)
(This formation is based on the terms dime< [rimer, tetramer, etc.)
A DNA sequence might be depicted as follows:
GTCGACTG
Unknown bases may be depicted by using N (see previous table of symbols):
GNCGANNGX
Instead of N, a lowercase n or a hyphen may be used for visual clarity:
GnCGAnnG
or
G-CGA-G
A double-stranded sequence consisting of a strand of DNA and its complement
would be as follows:
GTCGACTG
CAGCTGAC
To show correct pairing bemeen the bases in the 2 strands, sequences need to be
.
aligned properly. In the sequence above, the first base pair is G C, the next is T A, -
etc. Note how the first G is directly above the first C, the first T above the first A, etc.
A codon is a sequence of 3 nucleotides in a DNA molecule that (ultimately)
codes for an amino acid (see below), biosynthetic message, ,or signal (eg, start
transcription, stop transcription). Codons are also referred to as codon triplets. Ex-
amples are as follows:
CAT ATC A?T
The genetic code--the complete list of each codon and its specific product-is
widely reproduced, eg, in medical dictionaries and textbooks and on the Internet.
Promoters are DNA sequences that promote transcription of DNA into RNA.
They include the following:
CAT box (CCAA??
CG island, CpG island (CG-rich sequence)
GC box (GGGCGGG consensus sequence)
5' UTR (5' untranslated region) (5' is defined below)
TATA box
Sequences of repeating single nucleotides are named as follows:
or, optionally, wirh lowercase d for deoxyribose:
poly(dT)
Repeating single-nucleotide pairs (in double-stranded DNA) are similarly named:
poly(dA-dT)
poly(dG-dC)
The phosphate groups linking the nucleotides are sometimes indicated with- a
lowercase p:
PGPAPAPTPTPC .
CpG island
Methylated bases may be shown with a superscript lowercase m, which refers to the
nucleotide residue to the right:

..-_I as
Sequences of repeating nucleotides, also known as tandem repeats, are indicated
follows (n stands for number of repeats):

Within a long sequence, the first repeat may be designated n, the next p, the next q, 'I.
and so on:
(TAGA),,ATGGATAGAT~A(GATG)+(TAGA),
The number of repeats may be specified: -
- I
The phosphates that join the DNA nucleotides link the 3'-carbon of one deoxy-
ribose to the 5' carbon of the next deoxyribose. The end of the DNA strand with an
unattached 5' carbon is known as the 5' end (or terminal), and the end with ari
unattached 3' carbon as the 3' end (or terminal) (Figure 4).
Sometimes chemical moieties are specified in connection with the 3' and 5' ends
of DNA: . .
3'-hydroxyl end (3'-OH end)
5'-phosphate (5'-P) end , il
5'-OH end
 15.6.1 Nucleic Acids and Amino Acids

By convention in printed sequences, for single strands, the 5' end is at the left
and the 3' end at the right; thus, a sequence a r h as the following:

would be assumed to have this directionality:

5'-CCCATCTCACITAGCTCCAATG-3'
The complementary strands of dsDNA have opposite directionality; by convention,
the top strand reads from the 5' end to the 3' end, while its complementary strand
appean below it with the 3' end on the left. The 5'-strand is the sense strand or
coding strand or positive strand. The 3'strand is the antisense strand or .tenpIatc
strand or negative strand. In the example:
CCCATCTCACTTAGCTCCAATG
GGGTAGAGTGAATCGAGGTTAC
this directionality is implied:
5'-CCCATCTCACTTAGCTCCMTG-3' (sense strind, coding str:~nci)
~I-GGGTAGAGTGAATCGAGGTTAC-5'(antisense strand, tm,pl;~testr.~nd)
Text should specify which strand, seh& or antisense, is displayed. T l ~ esensc stcind
'is the strand generally repofled in the scientific literature or in d;~wlnses..~~'~"~'
long sequences pose special typesetting problems. Such a q n m r r s S ~ O L I ~ C I
be depicted as separate figures, rather than within text or tables, ~vl~rnevcr p)s-
sible.
For DNA, it must be made clear whether the sequence is single-str:~ndcdo r
double-stranded. A double-stranded sequence such as that of the follo\\:ing es;~mdc:
CCCATCTCAC'ITAGCTCCAATG
GGGTAGAGTGAATCGAGGTTAC
might be mistaken for a single-stranded sequence and s s as such:
CCCATCTAC?TAGaCCAATGGGGTAGAGTGAATCGAGGTC
Conversely, mistaking a single-stranded sequence for a double-str:inde<lP(~UL,IIC.,
and typesetting accordingly should also be avoided.
- -.
Always maintain alignment in 2-stranded sequences-take care not t o h;nc 1l1is
CCCATCTCACTTAGCTCCAATG
GGGTAGAGTGAATCGAGGTTAC
become this:

Numlxring and s1);cing I ~ : I YI*. ua-d :ISvisu;~I:~icIsill l)rcscllling sc(lllcnccs, sl,;lcc

every 3 bases indicates the codon triplets:
. .GCA GAG GAC CTG CAG GTG GGG . .
15 6 Genet1c5

I)S:\ wqurnccs In mosr l-ukar)or~~ ~c11\conrJln twrt~cxonh (coding sequences of

tr~plcts)2nd inrronb (~ntcn,c.ning
nonccxi~ngsequences). An intron occurs within the
sequtrnctr (examples from ~oo~er"""-"):
intron: GTGAG . . . GGCAG
sequence in preceding example with intron included:
. . . GCA GAG GAC CTG CAG G GTGAG . . .GGCAG TG GGG . . .
Another way to display introns amid exons is to use lowercase letters for introns and
uppercase letters for exons. There is a space on either side of the intron, and the next
exon continues in the same frame or phase as before, to resume the correct codon
sequence:
. .. GCA GAG GAC CTG CAG G gtgag . . .ggcag TG GGG . . .
In larger DNA sequences, spaces every 5 or 10 bases are customary visual aids:
GAATT CCTGA CCTCA GGTGA TCTGC.CCGCC TCGGC (JTCCC AAAGT GCTGG

GAA'ITCCTGA CCTCAGGTGA TCTGCCCGCC TCGGCCTCCC AAAGTGCTGG

Several types of numbering are further aids: In the following

~ o o ~ e r ~"lowercase
' ~ ~ ~ ~letters
' ; indicate uncertainty in the base
the left specify the number of the first base on that line:
1 5'-GAAl'TCCTGA CCTCAGGTGA TaGCCCGCC
51 GATlTACAGG CATGAGGCAC CACACCTGGC
. 101 TC'ITA'ITTGC 'ITTACTTACA AAATGGAGAT ACAACCTTAT A
151 ACATATACTA GGmCCATG AACAGCAGCC
201 CCAGTGAG~ACCAATCTCA GGTAGCTGAT GATGGGCAAa
251 CTGATATGCC c N M G A C G AlTCGAGTGA
301 CTTTtCATCT tGATCTTCAC CACCCATGGg

Alternatively, numbers may appear above bases of special interest:

6 39
GAAlTCCTGA CCTCAGGTGA TCTGCCCGCC TCGGCCTCCC AAAGTGCTGG

When the base number is large, the right-most digit should be directly over the base
being designated:
21 857
21 831 ACATATACTA GGTITCCATG AACAGCAGCC AGATCKAAC

When a long sequence is run within text, use a hyphen at the right
line to indicate the bond linking successive nucleotides:
GA~ACAGGCATGAGGCACCACACCTGGCCAGT~G~AGCTCTCTAAGTC- ;
TTA?TGCTlTACITACAAAATGGAGATACAACClTATAGACA~CG
A hyphen is not necessary if spacing is used, as long as the break between groups
occurs at the end of the line:
. . . j'-CCT GGG
CAA AGC AAG GTA GG-3'

- ~.
- -,
---.-- -
-. -
I -

15.6.1 Nucleic Acids and Amino Acids :

Recognition sequences are seaions of a sequence recognized prc)rc.ins ?;ucll

as restriction enzymes that cleave DNA in specific locations (see thc "Si~clcic
Acid Technology" section). To indicate sites of cleavage, virgules or c:lrcts nla!. 1 ) ~ .
used:

single-stranded:
GT/MKAC
GG/CGCGCC
CATCGTG
.
- -
double-stranded ':
CGWCGA
AGC WGC
G RGCY/C
C/YCGR G
Other conventions should be defined, in parentheses for text or in legends for tables ..
and figures, eg7:
CACNNJNNGTG (1indicates cleavage at identical position in both strands)

Sequence Variations, Nucleotides. Recommendations for mutation nonlenclature

have been one of the major activities of the HUGO Mutation Database Initiative, now
the Human Genome Variation Society (HGVS)? Members devised the nomenclature
after extensive community disc~ssion."'~Authors should consult the Recommen-
dations page of the HGVS Web site (at www.hgvs.org [use the Recommendations
Including Nomenclature Guidelines link1 or www.kgvs.org/mutnomen) for the latest
recommendations8 Basic style points are as follows (see also the "Sequence Vari- - .
ations, Amino Acids" section):
pa For sequence variations described at the nucleotide level, the nucleotide number
precedes the capital-letter nucleotide abbreviation.
a Numbers at the end of the term, if any, do not stand for the nucleotide number
but rather indicate numbers of nucleotides involved in the change or, in the case
of repeated sequences, numbers of repeats.
1~ The symbol > is used for substitutions. The following abbreviations are used: . .

"ins," insertion; "del," deletion; "delins," deletion and insertion; "dup," duplica-
tion; "inv," inversion; "con," conversion; and "t," translocation.
i
M One set of brackets is used for 2 variations in a single allele, and 2 sets with a plus
sign are used for 2 variations in paired alleles. An underscore char~cterseparates
a range of affected nucleotide residues.
e The nucleotide numlxr ni:lv t,e preceded by g plus dot (g.) for gDNA (genomic)
or c plus dot ( c . )for c.l>NA (conlplcmentary or coding).
IP NUcIcoti(l~
nt1111lx*rs
rn:i!* tv ~5itivO
er negative.
15.6 Genetics

The HGVS recomn~cn&tiomnorc a prcfercncc for thc rcn11.5 S L ~ U O I L . ~ .I W T W ~ ~ I ,

squerzce ruricrrron, trlrc.rrrriotz,or allelic ~uriatrtover the trrrrb nrururtoti and/>o+
nzorphbm.
Note the following examples. In general medical publications, textual explanations
should accompany the shorthand terms at first mention.
T m Explanation
1691G>A G-to-A substitution at nucleotide 1691
253Y>N pyrimidine at position 253 replaced by
another base
[ 7 6 ~ > C83G>Cl
; 2 substitutions in single allele
[76A>CI+[87delGl substitution and deletion in paired all
[76A>C (+) 83G>C1 2 sequence changes in 1 individual, alleles
unknown
977insA A inserted at nucleotide 977
186187insC C inserted between nucleotides 186
and 187 . ;.

926insll insertion of 11 bases at position 926

185delAG deletion of A and G at positions 185 .
and 186
617delT deletion of T at position 617
188delll 11-bp deletion at nucleotide 188
1294de140 40-bp deletion at nucleotide 1234
c.5deI.A A deleted at position 5 (cDNA)
c.5-7delAGG AGG deleted at positions 5 through
7 .(cDNA)
g.5-123del 'nucleotides deleted from positions 5
through 123 (gDNA)
2316dupcCTGG~- duplicated sequence beginning at 2316
TGAGACGGTC
1007fs frameshift mutation at codon 1007

112-1 l7delinsTG '

These are all acceptable ways of indicating
112-1 17delAGGTCAinsTG a deletion from nucleotide 112 through
112_117>TG 117 and insertion of TG.
203jO6inv ' 304 nucleotides inverted from positions
203jOGinv304 203 through 506
167(GT)6-22 6 to 22 GT repeats starting at position
g. 167(GT)8 8 GT repeats starting at position
167 (gDNA)

594

-.
 15.6.1 Nucleic Acids and Amino Acids

Tenn &planation
f1263de155; 1326insTl variations in same allele indicated '

[c.l226A>G; c.l448T>C] by brackets

[76A>Cl+[76A>Cl changes in both alleles of same gene
or 76A>C/A>C (heteroallelic)
76A>C; 137C>G intra-allelic
c.827-XYZ:233del examplesRwith hypothetical gene
symbol XYZ incorporated (but not
italicized) (see 15.6.2, Human Gene
Nomenclature)
c.827-oXYZ:233del o: opposite (antisense) strand

When a gene symbol is used with a sequence variation term, only the gene symbol is
italicized (see 15.6.2, Human Gene Nomenclature).
ADRBl 1165C>G (not: ADRBI 1165C>G)
Note: Polymorphic variants are often indicated by using virgules, but this is not
recommended.14

Amid: 2417A/G
Pwfmd: . .2417A>G
In practice, means other than the symbol > are commonly used to inclicate sub-
stitutions:

h y symbol for substitution is better than no symbol; othenvise the expression 111;iy
be misinterpreted as indicating ;I dinucleotide at the site. For instance. 1691G)\ \\.ouItl
imply a change involving the dini~cleotirleGA (1691G and 1692A).
When genotype is'being expressed in ternis of nucleotitles (eg. ;I l>ol!.tnorl>hic
variant), italics and other punctuation for the nuclcotirles are not nectlc.tl (scbc;11so
15.6.2, Human Gene Nomenclature):
MiWFR 677 CC and +ITgenotypes
For nucleotide numbering of ;I cDNA rcferencc seqilence. nilc.leotitlc*+ I i \ 1 1 1 ~ .:\ 01'
the ATG initiator ccxion. The 5' nirclc~oticlc.o f the ATG initi;~torc-o~lonI \ - I 'l.llc.
nucIcoticic 3' of the trunsl~~t~orl4101) c.otio11 I \ '1 \:or intron\. tIit. f1r\1 r 1 , 1 1 1 1 1 > ~ . 1,1 1 1 ~ ~ .
posi:ion of rhc 1;lst nuclzoticlc of t l ~ cprr.c.~.clrn~
rsor; o r 111~.fir,: nt:\-l(.(\ri,\,-.1 ; \ I , . I r 11
Ion.lng cxon I:or cs.lnlpie
15.6 Genetics

c.77+2T cDNA, nucleotide 77 of prrcccl~ngc x o n , p)sitior~.! in inlron.

T residue
c.78-1G cDNA, nucleotide 78 of next exon, position 1 in intron, G residue
Nucleotide numbering of a gDNA reference sequence is arbitrary (ie, there is no
defined starting point as in cDNA). Therefore, authors should describe their num-
bering scheme. No plus signs or minus signs are used with gDNA reference se-
quences.
The recommendation to describe nucleotide variations with "IVS" (intervening
sequence, referring to an intron and its number)" has been withdrawns:
Preferred: c.88+2T>G
Replaces: c.NS2+2T>G
Promoter variants (promoter polymorphisrns) have been commonly expressed with
terms such as:
-765G>A
which' implies nucleotide numbering in terms of a cDNA reference sequence.
However, authors are advised to instead (or additionally) describe the variant in
relation to a gDNA reference sequence (see "Unique Identifiers" section) (J. den a
Dunnen, written communication, May 18, 2004):
L01531.1:g.l561C>T
Terms with a capital delfa have been used to indicate exonic deletions, eg:
A ex la-15
A ex la-12
A ex 3
However, HGVS strongly recommends an alternative form of expression
inclusion in sequence variation databases, eg:
c.32-?360+?del
See http://www.hgvs.org/mutnomen/disc.html~del?
(from which the abov
ample was taken) for further explanation.

Unique Identifiers. Official recomnlendations include mentioning a se

iant's unique identifier, for instance, a number assigned by a locus-specific curator or ..
the OMIM number.15 (See also 15.6.2, Human Gene Nomenclature.) For a
ldcus-specific database curators, see the Human Genome Variation Society
under Variation Databases and Related Sites'(http://www.hgvs.org). For example:
1311C>T (OMIM 305900.0018)
880C>T (OMIM 600681.0002)

Database Identifiers for Genornic Sequences. Several databases record ge

quence information:

596

,,--.....-..-. .
.... --i4;.. .
.-.-..
*

.'
. .

-:.
? I

,
 15.6.1 Nucleic Acids and Amino Acids

Nucleotides:
GenBank (http://www.ncbi.nlm.nih.gov/Genbank/index.l~t~ii~)
RefSeq (http://www.ncbi.nlm.nih.gov/RefSeq/)
EMBL (EuropeanMolecularBiology Laboratory)(http://n7vn~.eml~1-1lciclclIwr~
.de/)
DDBJ (DNA Data Bank of Japan) (http://www.ddbj.nig.ac.jp)
International HapMap Project (http://www.hapmap.org)

Proteins:
Swiss-Prot (http://www.expasy.ch/sprot/sprot-top.htn11)
PIR-PSD (~rcitkin Information Resource: Protein Sequence I >:,,a l,asc. )
(http:ljpir.georgetown.edu)
-
For a review of databases in molecular biology, including several of the foregoing.
see the 2005 Database Issue of the journal Nucleic A c i k ~eseal-ch.'"
Accession numbers are assigned when researchers submit unique secluCnc.e.s10
any one of the databases. 1n.published articles, accession numbers are i~~;ct'ulin
indicating specific sequences:
Founder effects were investigated using 2 previously undescribcd. Iiiglil!.
polymorphic microsatellite markers that flank presenilin 1. The first is a G'1'
repeat at position 33117 (GenBank accession No. AF109907). The second is a
CA repeat at position 23,000 of this same sequence."
Accession numbers should include tlle version (eg, .l, .2) if possiblex: -

'rhe following example shows vnriation expressecl with the :~ccessionnuml>crx:

Common formatting for nucleotide data was determined in 1988 by representatives

of GenBank, EMBL, and DDBJ, forming the International Nucleotide Sequence Da-
tabase Collaboration (http://w~w.ncl~i.nlm.nih.~ov/~rojects/c/).~*

RNA. Functionally associated with DNA is ribonucleic acid (RNA). It contains the 3
bases adenine (A), cytosine (C), and guanine (GI but differs from DNA in having the
base uracil (U)instead of thymine (TI and the sugar ribose rather than deoxyribose.
The corresponding nucleosides are adenosine, cytidine, guanosine, and uridine.
An example of an RNA sequence is as follows:

Examples of RNA codons are as follows:

CAU UUG AlJU
15.6 Genetics

Expand these common abbreviations at first use:

P
cRNA complementary RNA
dsRNA double-stranded RNA
gRNA genomic RNA
hnFNA heteronuclear RNA (heterogeneous RNA)
mRNA messenger RNA
miRNA microRNA
mtRNA mitochondria1 RNA
nRNA nuclear RNA
RNAi RNA interference
rRNA ribosomal RNA
siRNA short interfering RNA
snRNA small nuclear RNA
tRNA transfer RNA
~ ; ~ of
e tFNA
s may be further specified; follow typographic style closely (these nekd
not be expanded):
~ R N A ~ ~tRNA specific for methionine
M ~ ~ - ~ R Nmethionyl-tRNA
A ~ ~ ~
~ R N A ~ ~tRNA specific for formylmethionine

~ R N A ~ tRNA specific for alanine

~ R N A ~ ~ tRNA
~ specific for valine
The 3-dimensional structure of tRNA has several different arms, which allow it to
recognize a codon on mRNA and deliver the appropriate amino acid during protein
I
synthesis:
AA (amino acid) arm .

DHU (dihydrouridine) arm

anticodon arm
T$C arm ($ for the unusual base pseudouridine)

RNA Sequence Variations. Style for abbreviated sequence variation terms described at
the RNA level is essentially the same as for DNA (see the "Sequence Variations,
Nucleotides" section). The main exception is that the RNA nucleotide abbreviations
are lowercase. The prefix r.'is used to sign~fyRNA'~but is not required.
 15.6.1 Nucleic Acids and Amino Acids

RNA sequences are quantified by use of the same units as for DNA, ie, base, bp. kb,
and Mb:
240-bp &RNA
10-25 RNA bases
a 7.5-kb RNA probe

Nucleotides as Precursors and Energy Molecules. The nucleotides of DNA and RNA
are also important individually as the precursors of DNA and RNA and as energy
molecules. They may bind 1,2, or 3 phosphate molecules, giving rise to compounds
with the following abbreviations (see also 14.11, Abbreviations, Clinical, Technical,
and Other Common Terms) or alternative shorthand:

Ribonucleotides

Alternative
Abb.reviation Shorthand
adenosine monophosphate, adenyGc acid AMP
adenosine diphosphate ADP
adenosine triphosphate ATP
cytidine monophosphate, cytidylic acid CMP
cytidine diphosphate CDP
cytidine uiphosphate CTP
guanosine monophosphate, guanylic acid GMP
guanosine diphosphate GDP
guanosine triphosphate GTP
uridine monophosphate, uridylic acid UMP '

uridine diphosphate UDP PPU

uridine triphosphate UTP PPPU

Deoxyribonucleotides

Alternative
Tenn Abbreviation Short/~an&
deoxyadenosine monophosphate, dAMP PdA
deoxyadenylic acid
deoxyadenosine diphosphate
deoxyadenosine triphosphate
deoxycytidine monophosphate,
deoxycytidylic acid
deoxycytidine diphosphate
deoxycytidine triphosphate
deoxyguanosine monophosphate,
tleoxyguanylic ;icitl
15.6 Genetics

Alternative
Term Abbreviation Shorthand
deoxyguanosine diphosphate dGDP
deoxyguanosine triphosphate dGTP
deoxythymosine monophosphate, dTMP P ~ T
deoxythymidylic acid
deoxythymosine diphosphate dTDP
deoxythymosine triphosphate d?TP
Terms such as ppdA and pppdA are, by analogy with ribonucleotide shorthand, feasible
but not commonly found.

In the foregoing examples, monophosphates are assumed to be phosphorylated at

the 5' position, and the more specific term may be used:
5'-AMP
The additional phosphate groups of diphdsphates and triphosphates are li
quentially to the first phosphate group. Other phosphate positions and vari
may be specified as follows:
2'-UMP
3'-UMP Up
3'5'-ADP PAP
3',5'-AMP CAMP (cyclic AMP)
Note that the p follows the capital letter when 3'-phosphate is indicated.

Nucleic Acid Technology. Laboratory methods of analyzing DNA make use of

DNA sequences, which include the following:
RFLPs restriction fragment length polymorphisms
SWs single-nucleotide p o l y r n o r p h i ~
STRs short tandem repeats
STRPs ' STR polymorphism

STSs sequence tagged sites

VNTRs variable number of tandem repeats
Note: Satellite DNA repeats, microsatellite repeats (or markers), and minisatellite
repeats (or markers) are distinct types of tandem repeat sequences.
An SbP sequence may be preceded by rs (for reference SNP ID) or ss (for
submitted SNP ID), used for accession numbers assigned by the National Center for
Biotechnology Information:
rs1002138(-)
Methods of analysis include the following:
AS0 allele-specific oligonucleotide probes
DGGE denaturing gradient gel electrophoresis

. ~ - - .
- : A
 15.6.1 Nucleic Acids and Amino Acids

EMSA electrophoretic mobility shift assay

FISH fluorescence in situ hybridization
OSH oligonucleotide-specifichybridization
PCR polymerase chain reaction
PIT protein truncation test
RT-PCR reverse-transcriptase PCR
SKY spectral karyotyping, a type of FISH
SSCP single-stranded conformational polymorphism

Blotting. The first blotting technique, used for identifying specific DNA sequences in
genomic DNA isolated in vitro by means of nucleic acid probes, was named Southern
blotting for its originator, E. M. Southern. Similar techniques have since been namecl
(with droll intent) for compass directions and include Northern blotting ( U S A
identified; nucleic acid probe), Western blotting (protein identified; antibocly prohe).
Southwestern blotting (protein identified; DNA probe); and Far Western 1,lotting
(protein identified; protein probe).5
Recombinant DNA is DNA created by combining isolated DNA scquenccs 01.
interest. Among the tools used in this process'are cloning vectors, such as plasmids.
phages (see 15.14.3, Organisms and Pathogens, Virus Nomenclature), and hyl>ritls
of these, cosmids and phagemids. Additional tools are bacterial anifickil chrotno-
somes, or BACs, and yeast artificial chron~osomes,or YAG.
Basic explanations of these entities are available in medical diction:~ric.h;tnrl
textbooks. A few that present special nomenclatural problems are descrihccl here.

5.- Cloning Vectors. Plasmids are typically named with a lowercase p follo\vc.tlh!~:I Ic.ttcr
or alphanumeric designation; spacing may vary:
pBR322
b
pJS97
PUC
pUC18
pSPORT
I pSPORT 2
i
Phage cloning vectors are named for the phages, for example:
phage 1:IgtlO, hgtll, h g t 2 2 ~
M13 phage: M13K07, Ml3mp

Restriction Enzymes. Restriction enzymes (or restriction endon~~cleases) are special

enzymes that cle:~veDNA at specific sites. They are named for the organism frorn which
t l ~ r y;1rcB isol:ited. il~t1311y3 hictcri;~lS~?CC.~C'.\ o r s[r;iin. An authoritative source of
tnfonn;ltlon is H E I ~ A S E .k~oripin;~lly
' proporc.d.l"~l~c~r n;lmes consist ofa 3-letter tenn,
~t;iirc~izr.d n n ~tx~innlnp
l tvlrfl :I c:rp11;11
Icltcr. t.rkcn I r o ~ nthe org;~nis~n
of origin. eg:
\

11 ~ l l ~ ~ ~ r c;1croln;ln
l nunirml, which is a series number, eg:
1 ipr l
Hyall

In some cases, the series number is preceded by a capital or lowercase letter (ro
not italic), an arabic numeral, or a number and letter combination, which refers to the
str:iin of I>actcrium;there are no spaces between any of these elements of the term:
EcoKI
Hi&
Sau96I
Sau3AI
Many variations in the form of the names of these enzymes have appeared, eg, Hin d
Iii, Hin dIII, Hind 111, Hind 111. It is currently recommended that italics and spacing
be given as noted in the preceding paragraph, to differentiate the species name,
strain designation, and enzyme series number. The following list gives examp
Enzyme Name Organism of Origin -
AccI Acinetobacter calcoaceticur
AluI Arthmbacter luteus
AlwM Acinetobacter lwcfi N
BamHI Bacillus amyloliquefaciens.H
Bcll Bacillus caldolytcus
BsLEI I Bacillus srearothemophilur ET
BstXI Bacillus stearothermophilus X
I-CacI Chlamydomonus eugametos.
@
nI' Streptococcus (diplococcus) pneumoniae M
EcoRI Eschmerrch;bcoli RY13
EcoRI I fichenenchiacoli R245
HaeII Haemophilus aegyptius
HincII Haemophilus injluenzae Rc
Hind111 Hmophilus injluenzae Rd
Hinfl Hmophilus i n . m z a e Rf
MseI Micrococcus species
MspI Moraxella species
PleI Pseudomom lemoignei
PmlI Ps+domonas maltophilia
PstI Providencia stuartii
Sau3AI Staphylococcus a u r a 3A
Sau96I Staphylococcus aureus PS96
Sma I Serratia tnarcescens

_ _ __ -Ma-.

. i
 1

15.6.1 Nucleic Acids and Amino Acids

' Enzyme Name Organism of Origin

Sstl Streptornycqs sta~zJord
Tag1 7 b e r - m aquutictfi
~~ YT-I
XhaI Xanthoiitonm hudlli
XhoI Xunlhontorza~holicolu

i Prefixes may further specify type of enzyme action, eg:

,I-CeuI I: intron-coded endonuclease Chlamydomonm etigarlzetos
-
,

J(' ,MMlyI M: methylase Micrococcus lylae

,NMlyI N: nicking enzyme
Restriction enzyme names are often seen as modifiers, eg:
a B > ~ H fragment
I
an EcoRI site
For information on recognition sequences, see the "DNA" section.

Modifying Enzymes. Enzymes exist that synthesize DNA and RNA (polymerases),
cleave DNA (nucleases), join nucleic acid fragments (ligases), methylate nucleotides
(methylases), and synthesize DNA from RNA (reverse transcriptases) (see also
15.10.3, Molecular Medicine, Enzyme Nomenclature). Those in laboratory use come
from living systems, often from the same organisms that furnish restriction enzymes.
Because the names may be similar, it is essential to speclfy the type of enzyme so that
there is no confusion, eg:
AluI methylase
Pfu DNA polymerase (Ppcoccusfuriosus)
TaqI methylase
Tag DNA ligase
Modifying enzyme names are often seen as qualifiers, eg:
a Tag1 RFLP
In the following enzyme terms, T plus numeral refers to the related phage (set
15.14.3, Organisms and Pathogens, Virus Nomenclature):
l7 DNA polymerase
. T4 DNA polymerase
T4 polynucleotide kinase
T4 RNA ligase

I DNA Families. Fanlilies of rlorlgcbncI)Sr\ ~ n c l t ~ c lrhe

c . rollon,ing.
 Colkcrirv T r n ~ tixurn*
-
USE.\ (long ~ n t c n p c r d L1 farnily (from LJNE 1 family)
nuclear elements)

Amino Acids. Twenty amino acids are ultimate products of the genetic code (se
"DNA" section) and constituents of proteins. Each has 1 or more distinct codons in
DNA, eg, GCU, GCC, GCA, and GCG code for alanine.
The following tablulation gives the amino acids of proteins and their pre
3- and single-letter symbols. Although these amino acids have systematic nam
alanine is Zaminopropanoic acid), the trivial names are the most widely recognized
and used. The single-letter symbols are usually used for longer sequences; otherwise, :

the 3-letter symbols are preferred. Do not mix single-letter and 3-letter amino acid
symbols. In general publications, it may be helpful to define the single-lette
bols, eg, in a key, and to expand the 3-lettcr symbols at first mention as well.
Amino Acid 3-Letter Symbol Single-Letter Symbol
alanine Ala A
arginine Arg
asparagine Asn . R
N
aspartic acid Asp D
asparagine or aspartic acid Asx B
cysteine CY~ C
glutamine Gln Q
glutamic acid Glu E
glutamic acid or glutarnine GLU Z
glycine GlY G
histidine His H
isoleucine Ile I
leucine Leu L
lysine LYs K
methionine . Met M
phenylalanine . Phe F
proline Pro P
serine Ser S
threonine Thr T
tryptophan T~P W
tyrosine . TY~ Y
valine Val V
unspecified amino acid Xaa X
The symbols Asp and Glu apply equally to the anions aspartate and glutamate,
respectively, the forms that exist under most physiological conditions.
The PE and PPE. bacterial gene and protein families are named for Pro-Glu and
Pro-Pro-Glu, sequence motifs in the proteins. The terms need not be expanded.

604

.. .. , -- . . <-.
. ...
 15.6.1 Nucleic Acids and Amino Acids

Other amino acids are also well known by their trivial names and have 3-letter
codes. These, however, should always be expanded, as the example of cystine,
whose 3-letter code is the same as that of cysteine, bears out:
citrulline Cit
cystine CYS
homocysteine H~Y
homoserine Hse
hydrokyproline Hyp
ornithine Om
.thyroxine - Tku
The side chains of amino acids are known as R groups, and the letter R is used in
molecular formulas when indicating a nonspecified side chain, as in this general
formula for an amino acid:
COOH
I
H2N-C-H
I
R

Do not confuse the R with the single-letter abbreviation for arginine (see tabluation
above).
I The carboxyl (COOH) group is referred to as the a-carboxyl group, which
contains the C-1 carbon. The amino (NH2) group (shown as H2N above to indicate
that C is linked with N) is referred to as the a-amino group, which contains the N-2
nitrogen. (The true structure is not neutral, as above, but rather contains NHs' and
COO-. However, the structure above is often used, as it is herein, for purposes of
discussion.)
Peptide bonds are bonds between the a-carboxyl group of one amigo acicl :~ncl
the a-amino group of the next. Long peptide sequences are the backl,one.s o f pro-
teins. A peptide sequence might be indicated as follows, with hypl~ensrepresenting
peptide bonds:

By convention in such a secluence, thc :umino end o f the pepticlr (the crltl \\.llosc
amino asid has a free amino group, also known as the N terminal) is o n tl~clclt ant1
the carboxyl end (the end whose amino acid has a free carboxyl group. ;ilso krlo\\.n
as the C terminal) is on the rigl!t. The symbols NH2 and COOH I>cinc.li~clcelin
the representation of the pepticlc sequence, as follows:
N H 2 - G l y - I l e - V : ~ I - G I ~ i - G l n - C y s - C y s - A l ~ - l r - OI 0 l
.I'IIL.s:1111cIcli-10-rig111i.o~ive.nlioll;~lq>lic.s l o sc.cltlc-nc.cossing si~iglc.Ic.rrc.l.\. 'I'l~c.
: I ~ I O \ - CX Y ~ L I V I I C . ~using
' siliglc Icrrcrs wot~ltlI)c
15.6 Genetic5

When the NH2 group appears on the right of a xqucncc, it has a nlcsning orhcr rhan
amino end. For instance, in the following sequence, \'al-Nit2 ~ndicatebthe arnide
derivative of valine:
His-Phe-Arg-Lys-Pro-Val-NH2
To indicate bonds other than the peptide bonds described above, lines, rather than .
hyphens, are used:

'I
Glu CYS-Gly Glu

- Or I cys-Gly

(oxytocin)
Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Lek-Gly-NH2
(Adapted by permission from Moss3 http://www.chem.qmw.ac.uk/iupac'
/AminoAcid/A1819,html, Nomenclature and Symbolism for Amino Acids and
(glutathione)

tide;, 3AA-19.1. Peptide Chains; copyright IUPAC and IUBMB.)

For a multiline peptide sequence in running text, use a hyphen at the right end o
one line to indicate a break and at the start of the next line to indicate the peptid
bond:
Ala-Ser-Tyr-Phe-Ser-
-Gly-Pro-Gly-TrpArg
or, in figures, use a line:

Ala-Ser-Tyr-Phe-Ser

c---3Gly-Pro-Gly-TrpArg I

(Adapted by permission from MOSS? 6ttp://www.chem.qmw.ac.uk/iupac

/AmiioAcid/A1819.html; 3AA-19.1. Peptide Chains, copyright IUPAC and I
In special cases, such as cyclic compounds, the bond from C-2 to N-2
shown with arrows, as follows:

Val +Om +Leu 4 ~ P h+

e Pro

C e Leu +- Om tVal
Pro t~ P h+ 2 (grarnicidin S)

e dpermission from Moss: http://www.chem.qmw.ac.uk/iupac

( ~ d a ~ t by
/Amino~cid/~1819.html; 3AA-19.5.1. Homodetic Cyclic Peptides, copyright
and IUBMB.)
As with nucleic acid sequences, alignment is important in protein sequences.
the following examples, the amino acid residues must.remain aligned with the n
cleic acid triplets:
Met S e r I leGlnHis Met-Ser-I le-Gln-Hi s
AGTATGAGTA'ITCAACAT or AGT ATG AGT ATT CAA CAT
TCATACTCATAAGTTGTA TCA TAC TCA TAA G'IT GTA

. .

.- * . --..- '3
., .-. - .
_.-
...
.a
.= .
-
, 7:,
.:.:
'. f- . . . id
.-
8.:
. - ..
 15.6.1 Nucleic Acids and Amino Acid! -
(Adapted from ~ o s shttp://www.chem.qmw.ac.uk/iupac/An~inoA~
,~
.html#AA198, 3AA-19.8. Alignment of Peptide and Nucleic-Acid Sequences.)
An amino acid term plus number refers to the amino acid hy cotlon ncllnl)r.
(when known) or by protein residue, eg:

SequencC Variations, Amino Acids. Recently, HGVS has expressed a prcli-rcnc.c 1.t 1
the 3-letter amino-acid abbreviation to be used in shorthand descriptions o f 's
quence variations in proteins, unless the change is very simple. Becu~sc.this 1,re1.~.1
ence is recent, the 1-letter style still has currency. For sequence variations tic.sc.ril~c
at the protein level, recommended style for abbreviated terms is similar to th:~tti
nucleotides. (See also the "Sequence Variations, Nucleotides" section and IJhenot)-1-
Terminology in 15.6.2, Human Gene Nomenclature). Note that the amino acid ;II
breviation begins the term, preceding the position number (in contrast to nucleoris
sequence variant terms, in which the residue number precedes the residue :,I
breviation). Explanation of such terms at first mention is recommendecl. Use of 11
prefix p. (protein) is another recent recommendation.
3-LetterStyle Single-Letter Style Explanation
Arg506Gln R506Q , arginine at residue 506 replaced
by glutaxnine (This amino acid
substitution is the result of the
G1691A subsiti~tion.'~)
Leu loins LlOins leucine inserted at position 10
Leul4ldel L14ldel leucine deleted at position 141
Gln318X or Q318X glutntnine at 318 changed to stop
Gln318ter codon (X or ter)
p.Trp2GCys p.W26C tryptophan ar residue 26 replaced
by cysteine
X is officially recommended as the symbol for the stop codon, but it can also be
single-letter abbreviation for unspecified or unknown amino acid. Therefore, wi
an amino acid sequence expressed with single letters that includes X is used, thl
should be explained in the text.
When an amino acid sequence variation is used with a gene syml~ol,italic
only the gene symbol:
a

ADRBl Arg389Gly (not -2 Atg389Gly)

(See also 15.6.2, Human Gene Nomenclature.) i

Note: Residue numbering begins at the translation initiator methionine, + I .
For further details on expressing sequence variations in proteins, consult
HGVS reconimentl:~tions.~

REFERENCES
15.6 Genetics

3. Moss GP. International Union of Biochemistry and Molecular Biology rr.comrnmd;l

tions on biochemical S: organic nomenclature, symbols & terminology etc. hr

London, England: International Union of Biochemistry and Molecular Biology/

Portland Press Ltd; 1992.
5. Nussbaum RL, McInnes RR, Willard HF. Thompson and 2;bompson Genetics in Medi-
cine. 6th rev reprint ed. Philadelphia, PA: Saunders; 2004.
6. Cooper NG. 2;be Human Genome Project: Deciphering the Blueprint of Heredity. Mill
Valley, CA: University Science Books; 1994.
7. Roberts RJ, Macelis D. REBASE: the Restriction Enzyme Database. http:(rebase.neb.co
/rebase/rebase.html. Accessed August 23, 2005.
8. Human Genome Variation Society Web site. http:(www.hgvs.org. Updated Jan
16, 2006. Accessed April 22, 2006.

describe complex mutations: a dis

16. Antonarakis SE; Nomenclature Working Group. Recommendations for a no
system for human 'gene mutations. Hum Mutat. 1998;11(1):1-3.
11. Beutler E, McKusick VA, Motulsky AG, Scriver CR, Hutchinson F. Mutatio

203-206.
12. Ad Hoc Committee on Mutation ~omenclature.Update on nomenclature
gene mutations. Hum Mutat. 1336;8(3):197-202.
13. Beaudet AL, Tsui L-C. A suggested nomenclature for designing mutations. Hum
1993;2(4):245-248. .
14. den Dumen JT,Antonarakis E. Nomenclature for the description of human se
variations. Hum Genet. 22001;109(1):121-124.
15. Online Mendelian Inheritance in Man (OMIM). National Center for Biotechnology
Information Web site. h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e $ q u e ~ ~ . .
Accessed April 22, 2006.
16. 2005 Database Issue. Nucleic Acids Res. http://nar.oxfordjoumals.org/conten
/suppl-11. Accessed April 22, 2006.
17. Athan ES,Williamson J, Ciappa A, et al. A founder mutation in presenilin 1 causing '
early-onset Alzheirner disease in unrelated Caribbean Hispanic families. JAMA.
2001;286(18):2257-2263.
18. Range1 P, GiovannettiJ. Getfo,mesand Databases on the Internet: A Practical Guide to
Functions and Applications. Norfolk, England: Horizon Scientific Press; 2002.

Human Gene Nomenclature. The International System for Human Gene Nomen-
clature (ISGN) was inaugurated in 19791'2and has b e e n continually updated. The':,
Human Gene Mapping Nomenclature Committee, which developed the ISGN, put
forth a "one human g e n o m m n e gene language" principle:
Certainly there exists a genetic and molecular basis for a single human
language without dialects. All human nuclear genes as we know
low the same genetic, molecular, and evolutionary principles. . . . Thu

' .
 15.6.2 Human Gene Nomenclature

reasonable and logical to develop a standard and consolidated gene no-

menclature system rather than have ;I human gene language based on dif-
ferent gene ~ ~ s t e m s . ~ P ' ~ '
The committee, known as the HUGO Gene Nomenclature Committee (HGNC).
is 1 of 7 committees of the HumanGenome Organisation (HUGO) and is "respon-
sible for gene name ~alidation."~(~"~'
Gene names and symbols are assigned by the
HGNC.'The human genome is estimate? to have approximately 30 000 genes, more
than 20 000 of which are represented by active symbols,\vith the remainder to I,e
named in a consistent fashion as genes are discovered. - -
Gene Symbok: A gene synibol is a short term, typically 3 to 7 characters long. that
conveys in abbreviated form the name or other attribute of a gene. Human gene
symbols usually consist of uppercase letters and may also contain (but never
begin with) numerals. Approved gene symbols do not contain Greek letters,
roman numerals, superscripts, or subscripts and usually contain no punctuation. -
In JAMA and the Archives Journals, gene symbols are italicized, per official rec-
ommendations? Italicizing is a useful way to make clear that a gene, and not a
similarly named entity such as a condition or product of the gene, is being dis-
cussed. Italics are not necessary in published catalogs of gene symbols.7For style
rules for gene symbols, see Table 3.
Approved symbols may represent other entities, such as chromosomal regions,
certain syndromes, genes whose existence is inferred (supported by linkage analysis
or association with known markers), cloned DNA segments, pseudogenes, and DNA
fragments.

Table 3. Style Rules for Gene Symbols (Examples)

Approved
Gene Description Gene Symbol Rule Illustrated

a-fetoprotein AFP Greek letter changed t o Latin letter (but not

moved to end of symbol: exception to recommendation)
PI-microglobulin B2M Greek letter changed to Latin letter; no
subscripts or punctuation
a-galactosidase GLA Greek letter changed to Latin letter and moved
to end of symbol
coagulition factor Vlll F8 roman numeral changed to arabic numeral
Pl-galactosidase GLBl Greek letter changed to Latin letter and &ved with
numeral to end of term; no subscripts or punctuation
heterogeneous nuclear HNRPA281 no punctuation marks or spaces
ribonucleoproteinA2/B1 -

MCF.2 cell line-derived MCF2 no punctuation marks

transforming sequence --- -. .- . - -. -

5'-nucleotidase, cytosolic NT5C number moved

-. -
from 1r.e r!ar: o! i.,vr;:.< . . r..:.c: . .'
55 RNA, cluster 1 RN5S1@
-- -flrsl chdra~lerI\ I r ~ l r . no:
. ...
nori.t)ce

thromboxane A2 receptor TBXAZR no %J~>IV~,I tq,t,, ,I, *,, ,: , . ;:,.

 --_ _
15.6 Genetics

Within larger terms, only the gene symbol is italicized:

ADRB2 46G>A (not:ADRB2 4GG>A)
r g ADRB2 GlylGArg)
RDRB2 ~ l y l G ~ (not:
(For an explanarion of 4 6 ~ and > ~Gly16Arg, see "Sequence Variations, Nucleo- ,

tides," and "Sequence Variations, Amino Acids," in 15.6.1, Nucleic Acids and Amino
Acids.)
Authors are encouraged to use the most up-to-date gene symbol, which may
be verified at the HGNC Web site in the Human Gene ~omenclatureDatabase
(Searchgenes feat~re),~.'.~or Entrez ~ e n e . "The records available in Searchgenes
contain "23 fields, with 14 links to other resources," such as Online Mendelian In-
heritance in Man (OMIM, see later in this section), LocusLik, and Swiss-Prot (
1.5.6.1, Nucleic Acids and Amino ~ c i d s ) Consistent
.~ use of the approved gene
symbol provides advantages when searchirg for information in multiple databases." ';
II Gene Names: Genes are usually named for the molecular product of the.
-
,.

function of the gene, or the condition associated with the gene if known. G
names are not italicized. As shown directly below, the approved gene na
available in the above mentioned databases, expand Greek letters and do no
subscripts, etc (so that, for instance, in using Searchgenes to find a gene
a, one would type in "alpha''). Descriptions based on the approved gene n
but styled according to the journal in question (eg, using Greek letters and sub-
scripts) or omitting some terms from the full name are permissible in general
medical journals.
approved gene name: the alpha-fetoprotein gene
description: the a-fetoprotein gene
approved gene name: the gene for beta-2-microglobulin
descriprion: the gene for flTniicroglobulin
A number of conventions are followed when gene symbols and names are . ,
officially designated. Related genes are often assigned symbols by seque
numbering a stem, the root symbol for the gene family:
ABC: root symbol
genes: ABCAI, ABCG4, etc

W F : root symbol
genes: W ,lhrFATP1, 17VFATP2,W e ,etc
Other conventions involve stereotypic abbreviations, eg, CR will often signlfy a
"chromosome region." (However, a given letter or letter combination does
ways signify a conventional usage. For instance, L at or near the end
often, but not always, indicates "like.") In Table 4, the conventions in col
reflect HGNC recommendations.' (Note: DNA sequences are available
Genome Database, http://gdbwww.gdb.org/gdb/.7)

610

5 *.-----
---
Table 4. Conventions for Gene Names and Gene Symbols (Examples)
- - - -

Gene Description Gene Symbol Convention Illustrated

Angelman syndrome ANCR CR: chromosome region

chromosome region
BRO11-associated ~rotein BRAP AP: associated ~ r o t e i n
bromodomain containins 1 BRDl D: domain-containino
-

chromosome I 1 open O& lowercase exception for

readina frame 10 "ooen readina frame"
calcium modulating lisand C4MLG LG: lisand
- - -

caspase 1, 2, 3, etc, apoptosis- W 1 , C4SP2, CASP3, etc stem (WP), sequentially

related cysteine protease numbered
. -
cyclin-dependent kinase CDKNlB N: inhibitor
inhibitor 1 6
- --

Cornelia de Lange syndrome 1 CDL 7 .named for condition; L at end ~n

this case does not signify "l~ke"
-- .- -.

carpal tunnel syndrome 1 CTS7 named for syndrome

cystic fibrosis transmembrane CFTR formerly CF; name modifled after
condudance regulator discovery of gene product
collagen (type VI, a,), overlapping COLOTl OT' overlapping transcr~pt
transcript 1
DNA.segment sequence Dl951!77E 0: DNA; 19: chromosome 19;
5: (unique DNA) segment;
E expressed
Down syndrome chromosome DCR CR: chromosome region
region
deafness. autosomal dominant 4 DFNA4 named ?or condition
ONA seament seauence DXS522E as above: X: X chromosome
-- - ~

DNA segment sequence DXYS155E as above; XY: sequence present at

homologous sites on
chromosomes X and Y
---- - --- --..-. ... .- -
family with sequence similarity 7, FAM7A1 FAM: family with sequence
member A1 similarity
- -
fragile site. aphidicolin type. FRA 1OG FRA: fragile site; 10: chromosome
common, fra(lO)(qll.2) (see also 10; G: series letter
15.6.4, Human Chromosomes)
fragile site, folic acid type, FR4XF X: X chromosome; final F: series
rare, fra(X)(q28) letter
glucose 6-phosphatase, catalytic G6PC C: catalytic
(glycogen storage disease type I,
von Gierke disease)
glucose-6-phosphate G6PD named for gene product
dehydrogenase
glucose-6-phosphate G6PDL L: "like" sequence
dehydrogenase-like
 15.6.2 Human Gene Nomenclature

When a gene name or symbol has been changed, both the new and for~ilern;lmt.s
(previous symbols) are available in gene datal~~ses."~'~
Authors should use the most
up-to-date term. The previous symbol may be included parenthetically at first
mention:
CYP2AG (formerly CYP2A3)
SOD1 (formerly ALS and ALSI)

Writing About Genes and italicizing Gene Symbols. Observing the rule of italicizing
gene symbols makes clear whether the writer is referring to a gene or to another
entity that might be confused with a gene.
In any discussion of a gene, it is recommended that the approved gene symbol
be mentioned at some point, preferably in the title and abstract if relevant. However,
. the gene symbol need not be mentioned every time the writer refers to the gene.
Authors may refer to genes (or gene loci) by their official gene names or other
descriptive expression. Any of these is acceptable, depending on context and syntax.
Of names, descriptions, and. symbols, only the gene symhol is italicized. Ex:mlples
are shown below:
Acceptable Expression Gene Description Gene Syrnbol
the breast and ovarian breast cancer 1, BRUI
.
cancer susceptibility gene . early-onset gene
the cystic fibrosis locus cystic fibrosis transmembrane ClTR
conductance regulator gene
the factor VIII locus coagulation factor VIII, F8
procoagulant component
(hemophilia A) gene
the hemophilia A locus coagulation factor WII, . F8
procoagulant component
(hemophilia A) gene
the gene for synapsin I synapsin I gene SYNl
the p53 gene tumor protein p53 (Li-Fraumeni 7P53
syndrome) gene
In the foregoing examples, the gene names and descriptions are readily distin-
guishable from the gene symbols. Sometimes, however, the gene symbol may be
easily confused wit11 the abbreviation for the product or condition associated with
the gent: unless the gene symbol is italicized; for instance:
Gene Potentially Confuing Nongene Tern
ABO ABO blood group system (see also 15.1,
Blood Groups, Platelet Antigens, and
Gr;~nulocyteAntigens)
11POL apoE (apolipoprotein El
13'0 erythropoietin (Epo)
(,h'//i.\' GRIFiN protein (galectin-rei:lted interfiber
protein)
 Confus~
ffL4...(. ffL4-8,crc HLA-A, HLA-B, etc (see also 15.8.5, f
Immunology, HLA/Major Histocompatibility ;
Complex) 1
his multiple sclerosis (MS)
many hormone genes, eg, hormone name abbreviations, eg, CRH,
CRH, GHRH, GNRHR, GHRH, GNRH receptor, PTH, TRH
m,l'ml
In some expressions, italics may be moot, for instance, if a gene is named for an
1e it produc:es:
T m Meaning
--
Ti57 gene gene for tyrosine hydroxylase
TH gene gene for tyrosine hydroxylase
In other expressions, italics distinguish different meanings:
-
HD gene for huntingtin (protein), Huntington
disease gene
HD Huntington disease
person with HD person with the HD gene, whether the
disease-causing or normal form
person with HD person with Huntington disease
prevalence of HD prevalence of the HD gene I
prevalence of HD prevalence of Huntington disease; not necessarily
equal to prevalence of the HD gene
i
W deficiency impaired functioning of the i'X gene
i]
TH deficiency deficiency of the enzyme TH i
:
Therefore, it is best to make clear by italicizing gene symbols and through context 3
 15.6.2 Human Gene Nomenclature

the retinal guanylate cyclase 2D (GUCY2D) gene, GUCY2D

the retinal guanylate cyclase 2D (RetGC1) gene, GUCY2D
Not: the guanylate cyclase 2D (GUCYZD) gene

the Huntington disease (HD) gene, HD

the tyrosine hydroxylase (TH)gene, Z
R

The cystic fibrosis (CF)transmembrane conductance regulator gene, C m ,

is implicated in CF.
In discussions of mutations, the gene symbol remains italicized; specific mutations,
however, are not italicized (see "Sequence Variations>Nucleotides,"and "Sequence
Variations, Amino Acids" in 15.6.1, Nucleic Acids and Amino Acids):
ADRB2 46G>A
mutation of the GUCY2D gene
mutation of GUCY2D
GUCX2D mutation
mutated GUCY2D gene
Objective: To describe the phenotype in 4 families with dominantly in-
herited cone-rod dystrophy, 1with an R838C mutation and 1 with an R838H
mutation in the guanylate cyclase 2D gene (GUCY2D) encoding retinal
guanylate cyclase-1.
valine substitution at codon 171 of the L W gene
LRP5v171:
In gene mapping, when the order of genes along the chromosome is known. the
genes are listed from short-arm end (pter) to the centromere (cen) or long-arm encl
(qter) (see 15.6.4, Human Chromosomes): .

When the order of genes along the chromosome is not known, the genes are listccl
alphabetically and parentheses are used:

Table 5 presents gene n;lmcs :~ntlsyml>ols Sro~nficlrls c*o\lc.rc.clclsc\\.llc.lr. in [Iiis

chapter.

Table 5. Gene Names and Symbols From Fields Covered Elsewhere in This Chapter
I
Gene Symbol Gene Description

15.1, Blood Groups, Platelet Antigens, and Granulocyte Antigens

A4GALT IP b!md qro.~p)

a-1.4-galactosyltransferase
-- .

A80 ABO blood group iIr,~r~:fc,,~:i. h I 1 ? PJ ~ c c . f y : g a l a < ~?o :n.l

~ :r.!-\!r.,.,.,+.
transterase f3, x.1 3.r1,81,)<I,.c;,~~~,,,~.,~~~,,,,.~~~
--
ACHE ;*: ~ ' , x x :c . ~ . , : ,
acelylchol~n~~fr~d:,'
- - -
 Table 5. Gene Names and Syrnb& F r o m F& C w e d Elsewhere In This Chapter (con0

Gene Symbol Gene M p t i o n

15.1, Blood Groups, Platelet Antigens, and Granulocyte Antigens

AQPl (was CO) aquaporin 1

ART4 (was DO) ADP ribosyltransferase4 (Dombrock blood group)
B U M (was LU basic cell adhesion molecule (Lutheran blood group)
BSG basigin (OK blood group)
C4A complement component 4A
C4B complement component 4B
CD44 CD44 antigen (homing function and Indian blood group system)
CD 151 (was MER2) antigen identified by monoclonal antibodies 1D12, 2F7
CR 1 complement component (3b/4b) receptor 1, including Knops blood grou
system
CD55 (has DAF) CD55, decay accelerating factor (DAF) for complement (Cromer bl
group system)
DARC (was N ) chemokine receptor (Duffy blood group)
ERMAP (was SC) erythroblast membrane-associated protein (Scianna blood group) .
FUTl fucosyltransferase 1
FUl3 fucosyltransferase 3
GYPA glycophorin A (includes MN blood group)
-
GYPB glycophorin B (indudes Ss blood group)
GYPC glycophorin C (Gerbich blood group)
GYPE g~ycophorinE
/CAM4 intercellular adhesion molecule 4, Landsteiner-Wiener blood group
KEL Kell blood group
PI P blood group (PI antigen)
RHCE Rh blood group, C C E ~antigens
RHD Rh blood group, D antigen
SLC4A I solute carrier family 4, anion exchanger, member 1 (erythrocyte memb
protein band 3. Diego blood group)
SLCl4A1 solute carrier family 14 (urea transporter), member 1 (Kidd blood group)
XG Xg blood group (pseudoautosomal boundary-dividedon the X
chromosome)
XK Kell blood group precursor (McLeod phenotype)

15.2, Cancer (See Also 15.6.3, Oncogenes and Tumor !kppressor Genes)
ACTN1 a,-actinin
ACTNZ a,-actinin
BCU B-cell/CLL lymphoma 2

616

. .

--. ...- . - . _-.. _ _ .. -

. -. .- 7.
:
-5'

-
Table 5. Gene Names and Symbols From Fields Covered Elsewhere in This Chapter fconr)

15.2, Cancer (See Also 15.6.3, Oncogenes and Tumor Suppressor Genes)

BCL7A B-cell/CLL lymphoma 7 A

. ..
CCNDl (formerly BCL1) cyclin D l
.- .. .

CDU cell division cycle 2. G, to S and G2 to M

-. .- .

CDK2 cyclin-dependent kinase 2

CDKNlA cyclin-dependent kinase inhibitor 1A (p21, Cipl)
---
CTNNB 1 PI-catenin
-
MEN1 multiole endocrine neoolasia 1
--

retinoblastoma 1 (includina osteosarcoma)

R/3 (formerly MEN2A, MEN2B) ret proto-oncogene (multiple endocrine neoplasia and medullary -
thyroid carcinoma 1. Hirschsoruna disease)
TGFA transforming growth factor a
TGFB1 transforming growth factor P1 (Camurati-Engelmann disease)
TNF tumor necrosis factor UNF superfamily, member 2)
TNFRSFlA M F receotor suoerfamilv. member 1A
TP53 tumor protein p53 (Li-Fraumeni syndrome)

15.3, Cardiology
ANK2 (formerly LQT4 ankyrin 2 (neuronal; formerly long QT syndrome 4) -
APOA 1 apolipoprotein Al
APOB apoliprotein B
APOU apoliprotein CII
APOD apoliprotein D
APOE apolipoprotein E
GPRl G protein-coupled receptor 1
HDLBP hioh-densitv liooorotein-bindina orotein (viailin)
- -

KCNH2 (formerly LOR) potassium voltage-gated channel, subfamily H

(eaa-related). member 2
KCNOl (formerlv LOTI) potassium voltage-qated channel. KQT-like subfamily, member 1
LDLR low-density lipoprotein receptor (familial hypercholesterolemia)
LPL lipoprotein lipase
NOS 1 nitric oxide synthase 1 (neuronal)
NOS2A nitric oxide synthase 2A (inducible. he~atowtes)
- -

NOS2B nltrlc oxlde synthase 2B

- --
NOS2C nltrlc oxlde synthase 2C
NOS3 nltrlc oxlde synthase 3 (endothel~alcell)
PLAT tlssue plasm~nogenacttvator -
 Table 5. Gene t i m e s and Symbols F r m Fleld~Covered Elsewhere in Thts CP4p:t.r (CMU

15.3, Cardiology

SCN5A (formerly LQT3) sodium channel, voltage-gated, type V, alpha polypeptide

-. (long QT syndrome 3)
TNNCl troponin C, slow
TNNC2 troponin C2, fast
TNNll troponin I . skeletal, slow
JNNl2 troponin I, skeletal, fast
JNN13 troponin I, cardiac
JNNJl troponin TI, skeletal, slow
TNNR troponin R,cardiac
JNN73 troponin T3, skeletal, fast
VLDLR very-low-density lipoprotein receptor

15.7, Hemostasis
A2M az-macroglobulin
C4LM1 calmodulin 1 (phosphorylase kinase, 6 subunit)
CCLS chemokine (C-C motif), ligand 5
. CLEUB (was TNA) C-type lectin domain family 3, member B
F2 coagulation factor II (thrombin)
RR coagulation factor II (thrombin) receptor
RRLl coagulation factor II (thrombin) receptoilike 1
i3 coagulation factor Ill (tissue factor, thromboplastin)
FS coagulation factor V
W coagulation factor VII .
F7R coagulation factor VII regulator
F8 coagulation factor VIII, procoagulant component (hemophilia A)
F8A 1 coagulation factor Vlll associated (intronic transcript) 1
F9 coagulation factor IX
F10 coagulation factor X
Fll coagulation factor XI
F12 coagulation factor XI1
F13Al coagulation factor XIII. A1 polypeptide
F13A2 coagu!ation factor XIII, A2 polypeptide
p-

F13B coagulation fakor XIII, B polypeptide

FGA fibrinogen A, a polypeptide
FGB fibrinogen B, p polypeptide
FGG fibrinogen, y polypeptide

618

..
.
- ._
- , ,
% I
 - -

Table 5. Gene Names and Symbols From Fields Covered Elsewhere in This Chapter (conr)

15.7, Hemostasis

fibrinoaenlike 1
FGU fibrinogenlike 2
GP5 glycoprotein V (platelet)
GP6 glycoprotein VI (platelet)
GP9 glycoprotein IX (platelet)
GPlBA glycoprotein Ib, (platelet), a-polypeptide
ICAM 1 intercellular adhesion molecule 1 (CD54)
/CAM2 intercellular adhesion molecule 2
ITGA 1 a,-integrin
ITGAZ a2-integrin
ITGAZB aZb-integrin(platelet glycoprotein [Gp] Ilb of llbf llla complex, antigen CD41B)
ITGA3 a3-intearin
ITGA6 asintegrin
ITGAV h-integrin (vitronectin receptor, a polypeptide, antigen CD51)'
ITGB 1 f$,-integrin (fibronectin receptor, f$ polypeptide, antigen CD29)
llGB3 intearin (platelet G~llla.antiaen CD61)
ITPK4 inositol 1.4.5-triphosphate (IPd A
KLKBl kallikrein B, plasma
KNGl kininogen 1
NOS3 nitric oxide synthase 3 (endothelial cell)
PDGFA platelet-derived growth factor a-polypeptide
PDGFC platelet-derived growth factor C
PDGFRA platilet-derived growth factor receptor, a-polypeptide
PDGFRh platelet-derived growth factor receptor-like
PECAM 1 olatelet/endothelial cell adhesion molecule (CD31 antiaen)
PLAT plasminoqen activator, tissue (tPA)
PLAU plasminogen activator, urokinase (uPA)
PLAUR uPA receptor --.-. . . ..

PLG plasminogen -. .- .. ..... ...

PLGLA 1 plasminoqenlike A1
PLGLBl plasminogenlike B1 - --

PPBP proplatelet basic proteins (includes 0-thromboglobulin) -

. -. ..

PROC protein C - .

PROS 1 protein 5 --- - .- .-.

P,~OSP protein 5 pseudogene --. .--. .- .

PROZ protein 2, vitamin.K-dependent plasma glycoprotein

- . . -. .
 - - -- - - --

Table 5. Gene Names and Symbols From Fields Covered Elsewhere in This Chapter (cont)

15.8, Immunology

CD46 (was MCP) complement regulatory protein, CD46

- .

CDSS (was DAF) CD 55, DAF for complement (Cromer blood group system)
CD6 CD6
---
CD79A CD79A. Igz
CD97 CD97
-
CR I complement receptor tvoe 1. CD35

/CAM3 intracellular adhesion molecule 3, CDSO

--.- -. .
MME membrane metalloendopeptidase, CD10, CALLA
---- -.

15.8.3. Cornolement
Cl QA Claa
C1QB C~SP
ClQBP Clqbp
.. ..-

C1QR 1 ClqRl
C1R Clr
--
CIS Cls

CSAR 1 CSaR1
C6 C6
c7 C7

CD55 (was OAF) CD 55. DAF for complement (Cromer blood system)
CFH com~lementfactor H
CFP complement factor properdin
15 8 4 Cytok~nes
-- - - - --
-
.-

CRLFI cytoklne receptorllke factor 1

--
C". ''6 -- cytok~nereceptorl~kefactor 2
<SF ' M-CSF
--
Table 5. Gene Names and Symt
1
15.8, Immunology 4
CSF2 GM-CSF

CSF3R G-CSF receptor

EPO erythropoiet~n(Epo)
EPOR Epo receptor i
i
GH 1 growth hormone (GH) 1 ,j
GH2 GH 2 1
_.I
GHR GH receptor
IFNA 1 IFN-al 3
'il
IFNA2 IFN-a2
IFNB 1 IFN-$1
IFNG lFNr f
lL l A IL-1a
lLlE IL-1p I

lLlRl IL-1RI -
iLlR2 IL-1RII
lLlRAP IL-1R accessory protein
lL 1RN IL-1 receptor antagopi* IIL-lral
P
I
U IL-2 i
LEP leptin ... 4
21
LEPR leptin receptor -;
t
PRL ~roladin

TGFA transforming growth factor a (TGF-a) .!

TGFE 1 TGF-PI (Camurati-Engelmanndisease)
.--,
THPO thrombopoietin +
.
i?!
TNF tumor necrosis factor CTNF suoerfamilv member 2)

15.8.5, HLA/Major Histocompatibility Complex -?I

9
HIA-A HLA-A .<
HIA-B HLA-B

HlA-DMA
HlA-DM8
HLA-DM a
HLA-DM B
.U
3
,$a
HLA-DOA HIA-DO a -3
 - -

Table 5. Gene Names and Symbols From Fields Covered Elsewhere in This Chapter ( o n t )

HLA-DOB HW-DO 0
HLA-DPA 1 HlA-DP a1
HLA-DOA 1 HLA-DO a1
HLA-DO8 I HLA-DO Dl

HLA-E HlA-E
HLA-F HLA-F
HLA-G HLA-G
HLA-H HlA-H (pseudogene)
HLA-J ' HLA-J (pseudogene) .
15.8 6, immunoglobulins
IGHA 1 ce1
IGHA2 c.2
IGHD CA -

IGHD 1- 1 D"1 subgroup member 1

IGHE cc

IGHGl Cy1
IGHG2 C,2
IGHG3 C73 I

IGHG4 C#
IGHJ 1 J H ~

IGHM IgM P CH
IGHV@ VH - - --- --
IGHVI-2 V H subgroup
~ member 2
IGHVI-18 VH1 subgroup member 18
IGKC CK
IGK/@ JK

IGU2 Jk2
IGKW V,
-
IGKV1-5 V,1 subgroup member 5
/GLC@ -- - - - -c-A --- -
IGLCl ---
c) 1 -

IGU@ - J.

IGU 1 -
1. 1

IGL V@ L
--
 - --

Table 5. Gene Names and Symbols From Fields Covered Elsewhere in This Chapter (cont)

15.10. Molecular Medicine

COX56 cytochrome c oxidase subunit Vb
CRP C-reactive protein, pentraxin-related
CYPlA2 cytochrome P450 l A 2 isozyme (CYPlA2)
DHFR dihvdrofolate reductase
DKK1 Dickkopf homolog 1
ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2.
n~uroblastoma-/glioblastoma-derivedoncogene homolog
(avian) (formerlv HER2Ineu)
fructose 1.6-bisphosphatase 1
FDX1 ferredoxin (Fa 1
FDH Fd 2
--
FHlT fragile histidine triad (Fhit) gene
GNA12 G protein Gmzl
- -
GNG2 GVZ
GALNTl GalNAc transferase .l
.

G6PD glucosedphosphate dehydrogenase

. --
B3GALT1 UDP-Gal:P-GlcNAc &1,3-galactosyltransferase, polypeptide 1
-... - .....
CDKN2A CDK4 inhibitor 2A
- .
GFll growth factor independent 1
-. --. - .
GRB2 growth factor receptor-bound protein 2
-. -
GRIN1 glutamate receptor, inotropic, N-methyl-baspartate (NMDA) 1
HBA 1 hemoglobin (Hb) a,
- .
HBB Hb k'
- -
HMGCSl 3-hydroxy-3-methylglutaryl CoA synthase 1
IGF1 insulinlike growth factor 1 (IGF-1)
IGFlR IGF-1 receptor (IGF-R1)
--
IKBKB IKB kinase I3 (IKKB)
lTPK.4 inositol 1,4,5-triphosphate (IP3) A
..

MNATl menage a trois 1 (CAK assembly factor)

MB myoglobin /Mb)
---.
.- -

MCM2 Mcm 2 minichromosome maintenance deficient 2, mitotin

(Saccharomyces cerevisiae)
.---- - ..

NMNATl nicotinamide nucleotide adenvltransferase 1

NPY neuropeptide
NPPA natriuretic peptide precursor A -.-- --

OGDH oxoglutarate (a-ketoglutarate)dehydrogenase (I~poarntde)

--- -. - .- -- ---- . -
PIB5PA phosphat~dyl~nos~tol
4.5-b~phosphate(PIP,) 5-phospharase A
-- -
Table 5. Gene Names and Symbols From Fields Covered Elsewhere in This Chapter (con!)

15.11, Neurology

KCNJ3 (formerly GIRKI) potasslum inwardly rectifying channel, subfamily 1, member 3

MAOA monoamine oxidase A
NGFB nerve growth factor p-polypeptide
NGFR newe growth factor receptor
NMB neuromedin B
NOS1 nitric oxide synthase 1 (neuronal)
NPY neuropeptide Y
NPYlR neuropeptide Y receptor Y 1
NRTN neurturin
N773 neurotrophin 3
MS neurotensin
MSR1 neurotensin receptor 1
OPRDl ooioid 6 rece~tor
- - - ---
OPRKl opioid K ieceptor
OPRMl opioid u
. receptor

OPRSl opi,oid receptor ol

KP2 Purkinje cell protein 2
SLCIA l(formerly W73) solute carrier family 1
SLCIBAI solute carrier family 18 (vbicular monoamine), member 1
SNAP25 synaptosomal-associated protein, 25 kDa
SNCA a-synuclein
TACl tachykinin. precursor 1 (substance K, substance P, neurokinin 1,
neurokinin 2, neuromedin L, neurokinin a, neuropeptide K,
neuropeptide y)
TAU tachykinin 3 (neuromedin K, neurokinin p)
TRPA 1 transient receptor potential cation channel, subfamily A, member 1
TSNAREl , domain containing 1 [see 15.1 1, Neurology, for expansion]
t-SNARE

VAMP1 vesicle-associated membrane protein 1 (synaptobrevin 1):

15:14.3 and 15.4.4, Virus and Prion Nomenclature

AAVSl adeno-associated virus integration site 2

BNIP1 ~~~2/adenovirus
E1B 19kDa interacting protein 1
-- .. ..-
CR2 complement component (3d/Epstein-Barr virus receptor 2 )
CXADR ~~xsackievirus
and adenovirus receptor -

-
cxa3s coxsackievirus 83 sensitivity -- - . .-- .
El15 echovirus (serotypes 4, 6, 11. 19). sensitivity.--.
-
€812 E~stein-Barrvirus-induced gene 2
-
. .- . . .
- . ... .--- --- -, --
 -

1
p~

Table 5. Gene Names and Svmbds From Fiekis C m e d Ebcwtwre ~nThn Chapter kmU

15.14.3 and 15.4.4. Virus and Prion Nomenclature

EBVM 1 Epstein-Barr virus modification slte 1 I! .

EBVS 1 Epstein-Barr virus insertion site 1
HAVCR 1 hepatitis A virus cellular receptor 1
HBXAP heoatitis B virus X-associated orotein
- ~

he~atitisB virus X-interactina rotei in I

HCVS human coronavirus sensitivitv I
HIVE 1 human immunodeficiencyvirus 1 (HIV-I) expression (elevated) 1 .A
HW6AI1 human papillomavirus type 6a integration site 1 I
HTLF human T-cell leukemia virus enhancer factor I
HVlS heroes simolex virus woe 1 sensitivitv I
- -

intercellularadhesion molecule 1 (CD54). human rhinovirus recepto; ' 1

MXl myxovirus (influenza virus) resistance 1 1 I
PVR poliovirus receptor i .. .
I
PRND prion protein 2 (dublet)
PRNP PrP27-30 (Creutzfeld-Jakob disease, Gerstrnann-Strausler-Scheinker - - ' 4
syndrome, fatal familial insomnia)
PRNPIP orion orotein interactino orotein
PRNT prion protein testis specific

Alleles. Alleles denote alternative forms of a gene. AIleIes are often characterized b
particular variant sequences (mutations). For variant sequence nomenclature
1,
"Sequence variations, Nucleotides, and Sequence Variations, Amino
15.6.1, Nucleic Acids and Amino Acids.
Because alleles are alternative forms of a particular gene, they are expressed bd
means of both the gene inme or symbol and an appendage that indicates the specifi
allele.
Classically, allele syinbols consist of the gene symbol plus an asterisk plus the
italicized allele designation; eg:
HBB*S S allele of the HBB gene
I.,I
As with gene terms, Greek letters are changed to Latin letters in allele terms:
I
APOE'E4 allele producing the ~4 type of apolipoprotein E
If clear in context, the allele symbol may be used in a shorthand foml that ornits
gene symbol and includes only the asterisk and the allele designation that
eg:
*s
'E4

-- . . - - --.
 15.6.2 Human Gene Nomenclature

In the case of alleles of the major histocompatibility locus, which are not italicized
(see 15.8.5, Immunology, HLA/Major Histocompatibility Complex), a portion of the
gene name is usually included in the shortened form:
Full Name Shortened Form
HLA-DRB1'0301 DRB1'0301
In practice, common or trivial names for alleles, which take various forms, are used.
The same allele is often expressed in different ways that diverge from the rec-
ommended nomenclature. For example:
s: short allele of serotonin transporter gene (SLCGA4)
1: long allele -of SLCGA~ a

As another example of common allele names, the following expressions are all ilsctl
for APOEaE4; follow author preference:
~4 allele
epsilon 4 allele
E4 allele
MOP4
apo e4
APOEE4
A system of nomenclature that takes evolutionary divergence .into account has heen
proposed for alleles.12 Stylistically, it is consistent with the above system of no-
menclature, ie, asterisk followed by italicized alphanumeric allele designator. Es-
amples (from ~ebert'?:

Genotype and Phenotype Terminology. The genotype comprises the set of alleles in
an individual. Because individuals almost always have 2 of each autosome (nonses
chromosome) (see 15.6.4, Human Chromosomes), individuals have 2 alleles (which
may be the same alleles or 2 different alleles) for each autosomal gene.
The simplest genotype term for an individual would describe 1 gene and consist
of the names of 2 alleles. Larger genotypes would contain 2 or more allele syqnbol
pairs.
As originally formulated in ISGN, allele groupings may be indicated by placement
above and below 2 horizontal line or on the line. As seen in the following examples
(from Shows et a ~ ' , ~such ) , placement, as well ;IS order, spacing, and punctuation
rni~rks(\.irgi~lesI/], semicolons, spilces, and commas), has specific meanings.
Alleles of the s;llne gene :irc intlic:~tccl1)): placement above 2nd below n hor-
I ~ I ~ L I line
I o r L V I ~ I I .I virg~11~.
15.6 Genetic S

In theoretical discussions when a single letter is substiturd for the allele syrnlml, the
line or virgule may be dispensed with:
AA
Aa
aa
SS

11
sl
Semicolons separate pairs of alleles at unlinked loci:
ADA'1
- ADHI*
- 1 AMYIaA
-
ADA*~' AD HI*^' AIIfYIaB
or
ADA*I/ADA*2;ADHl*I/ADHl*1;AMY1*A/AMYIaB
or
ADA*lp2; ADI-PII'I; AMYl*ApB
A single space separates alleles together on the same chromosome from all
gether on another chromosome (phase known):
AMYI'A PGMI *2
AMYlaB PGM1*1
or
AMYl*A PGM1*2/AMYIaBPGMI*I
Commas indicate that alleles above and below the line (or on eith
virgule) are on the same chromosome pair, but not on which chromosome o
specifically (phase unknown):
PGMI 1 AM YI *A
9-

PGM1*2 AMYlaB
or
PGMI*I I P G M I * AMYI*A/AMYI*B
~,
A special form for hemizygous males is
GGPDAI Y
When genotype is being.expreged in terms of nucleotides (eg, a po
italics and other punctuation are not needed (see also 15.6.1, Nucl
Amino Acids):
MiTiYFR 677 TT genotype
CC genotype

.
. -
4--7
I 15.6.2 Human Gene Nomenclature

the "1ong/shortn (SHTTZPR) polymorphism in SLC6A4

(LPR: length polymorphism region)
When the subject is being described in terms of the 2 possible amino acids at 1
position in the protein owing to a single nucleotide poly~norphism(nonsynonymous
mutation), the corresponding amino acids are separated by a virgule (see also 156.1,
Nucleic Acids and Amino Acids):
. Val/Val (homozygous)
Met/Val (heterozygous)
Met/Met (homozygous)
Such terms should be explained at first mention with the amino acid terms expanded:

I.
I
the common methionine/valine (Met/Val) polymorphism at codon 129
The virgule is not needed in expressions such as the following:

individuals with the ZZ phenotype

The phenotype is the collection of traits in an individual resulting from his or her
genotype. When phenotypes are expressed in terms of the specific alleles, the
phenotype term derives from the genotype term, but no italics are used, and, instead
of asterisks, spaces are used. Genotypes usually contain pairs of symbols, while
phenotypes contain single symbols. The following examples are from Shows et a13:
Genotype Phenotype
ADA* I/ADA* I ADA 1
ADAbI/ADAb2 ADA 1-2
C.?C/C.?QO C2 C,QO
HBRAIHBEPGv HBB A,S [traditional, Hb A/SI
ABOIAl/ABOIO ABO A1
ClTPN/CFlR'R C m N
GGPDA/ Y G6PD A
NAiT4/'4 rapid acetylator
CYP2D6'4A/'5 poor n~etabolizer

OMIM. Online Mendelian Inheritance in Man (OMIM) is a datnbase of genetic syn-

d r o m e ~ . 'The
~ site is located at http://www.ncbi.nl~~i.nil~.~ov/entrez/que~y.f~~i
?db=OMIM.
When a specific syndrome is mentioned, it is helpful to include the OblIM
number:
bronch~m~lacia(Online Mendelian 1nherit;lnce in \!;In l(~.\lI.\II
2 l l . r i c ~j
DiGeorge syndrome (OMIM *188400)
Explanation of symbols that precede m:my 0%11.\1 n\lnll,c.r. i t . =. ~ '. '! . I - 1 % f t i ! ~ c l! ! I
1
. ,
the OMIM frecluently quesrions .,lr. ll!li, \\ ;,, : ): ;:,I:, t \ ; i , ;dc ,.
,$,

/Omim/omimfaq.~tml#n~~~~~beringg~~~~~~~ll,; I I ~ ( I 1 1 ) I I . I ~ , :.-!;
. I.: .:: ' '
15.6 Genetics

REFERENCES
1. Klinger HP. Progress in nomenclature and symbols for cytogenetics and somatic-cell
genetics. Ann Intern Med. 1979;91(3):487-488.
2. Shows TB, Alper CA, Bootsma D, et al. International system for human gene no-
menclature (1979). Cytogenet Cell Genet. 1979;25(1-4):96-116.
3. Shows TB, McAlpine I'J, Boucheix C, et al. Guidelines for human gene nomenclature:
an international system for human gene nomenclature (ISGN, HGM9). Cytogenet Cell
Genet. 1987;46(1-4):ll-28.
4, Rangel P, Giovannetti J. Genome and Databases on the Internet: A Practical Guide
to Functions and Applications. Norfolk, England: Horizon Scientific Press; 2002.
5. HUGO Gene Nomenclature Committee Web site. http://www.gene.ucl.ac.uk
/nomenclature/. Updated March 29, 2006. Accessed April :21, 2006.
Searchgenes. H v Gene Nomenclature Database Search Engine. 'm .gen
.ucl.ac.uk/cgi-bi/nomenclature/searchgenes.pl. Updated .April 21, Acc sed
April 21, 2006.
7. Wain HM, Bruford EA, Lovering RC, Lush MJ, Wright M W , Povey S. Guidelines for
human gene nomenclature. ~&rnics. 2002;79(4):464-470. Also avalilable
h t t p ' : / / w w w . g e n e . u c l . a c . u k / n o m e n c l a t u r e / ~ .Updated April
Accessed April 21, 2006.
8. Wain HM, Lush M, Ducluzeau F, Povey S. Genew: the Human Gene Nomenclature
Database. Nucleic Acids Res. 2002;30(1):169-171.
9. Wain HM, Lush MJ,Ducluzeau F, Khodiyar VK, Povey S. Genew: the Human Gene
Nomenclature Database, 2004 updates. Nutleic Acids Res. 2004;32(database issue): 4
0255-D257. doi:lO.l093/nar/gkh072.
10. Entrez Gene. h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e ~ n eAccessed
April 21,2006.
11. HGNC FAQs. http://arww.gcne.ud.a~.uk/nomenclature/inf~mtion/FAQ~.html.
.
i
Updated April 20.2006. Accessed April 24,2006. #:

12. Nebert DW.Proposal for an allele nomenclature system based on the evolutionaxy 'i
divergence of haplotypes. Hum Mufat, 2002;20(6):463-472. '6
13. Hamosh A, Scott AF,Amberger JS,Bocchini CA, McKusick VA. Online Mendelian 4
Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. 4
Nucl Acids Res. 2005:33(database issue):D514-D517. doi:lO.l093/nar/~ki033.

Cancer is caused by an accumulation of genetic

alterations that confer a sum'ml advantage
to'the neoplastic cell.
J. L. Jameson l(p73)

Oncogenes and Tumor ~ u p ~ r e s s oGenes

r

Oncogenes: Oncogenes are "[glenes that normally play a role in growth but, when
overexpressed o r mutated, can foster the growth of cancer."' Oncogenes were dis-
covered and characterized in viruses and animal experimental systems. These genes
exist widely outside. the systems in which they were discovered, and their normal
cellular homologues are important in cell division and differentiation.
 15.6.3 Oncogenes and Tumor Suppressor Genes

Human oncogenes should be expressed according to style for human gene

symbols (see 15.6.2, Human Gene Nomenclature). Mouse oncogenes (and other
nonhuman oncogenes) should be expressed according to style for mouse gene
symbols (see 15.6.5,Nonhuman Genetic Terms). Retroviral oncogenes are expressed
in a style typical of microbial genes (see 15.6.5, Nonhuman Genetic Terms), namely,
3 letters, italicized, lowercase. The protein products of the oncogenes (oncoproteins).
typically use the same term as the oncogene but in roman type. In humans, the
protein is all capitals; in mice, the protein has an initial capital.
Human Pmtein
Human Gene Pmduct(s); Mouse
Homol~gue(s); Pmtein Pmduct(s);
Retmviral Mouse Gene Retmviral
Oncogenes Homologue(s) Oncopmtein Origin
abl ABLI, ABL2 ABLI, ABL2 Abelson murine
Abll, Ab12 Abll, Ab12 leukemia virus
abl
BCL2
Bc12
bcl
erb ERBB2, -3, ERBB2, ERBB3, avian erytliroblastic
ERBB4 ERBB4 leukemia
Erbb2, Erbb3, Erbb2,
Erbb4 Erbb3, Erbb4
erb
ets mi,~ 7 3 . 2 ETS1, ETS2 avian
Etsl, Ets2 Etsl, EtB erythroblastosis
ets
fa . FES FES feline sarcoma
Fes Fes
fes
fm CSFlR (formerly colony stimulating McDonough
FMS) factor 1 receptor feline s;~rcorna
Csflr (formerly (CSFIR)
Fms)
fos FOS, FOSB FOS, FOSB murine
Fos, Fosb Fos, Fosb ostcos~~rco~~~;~
fos
jun JUN, JUNB, JUND JUN, JUNB, JUND avian sarcoma
Jun, Junb, Jund Jun, Junb, Jund
jun
kit KIT KIT feline sarcomii
Kit Kit
kit
 Human Protein
Hu?na?zGene Product(s); Mouse
Homologue(s); Protein Product(s);
Herron'ral Mouse Gene Retroviral
Oncogenes Homologue(s) Oncoprotein
?nos MOS MOS
Mos Mos sarcoma virus
mos
MYB MYB avian

MYC

mYc
raf M I , RAE1, ARAF1, rnurine leukemia
BRAF BRAF
Rafl, Araf; Braf Rafl, Araf, Braf
raf
ras family with HRAsl,m, retrovirus-
many human RAB9A, . k 4 S , associated .
homologues, RRAS2 DNA sequence '

eg, HRAS, NRAS, Rab9a, Rras, Rras2,

RABgA, RRAS, Hras, Nras, Rab9
RRAs2 ras
Hrasl, Nras, Rab9,

sis PDGFB PDGFB simian sarcoma

(platelet-derived virus

Rous sarcoma virus

SZ Src
src
Examples of use are as follows:
ras activation and inactivation
The rus protein, ras, functions as a signaling molecule.

634
 15.6.3 Oncogenes and Tumor Suppressor Genes

HER2/neuis widely used and recognized, it may be included in parentheses ;~frc.rr l ~ c .

first mention of ERBB2:
ERBB2 (formerly HER2 or ~ ~ R 2 / n e u )
Commonly, the oncogene term contains a prefix that indicates the s o i ~ r co ~r
location of the gene: v- for virus or c- for the oncogene's cellular or chromosotii;~l
counterpart. The c- form is also known as a proto-oncogene and in standard penc
nomenclature (see -15.6.2,Human Gene Nomenclature) is given in all capitals. as
in'the human gene homologues column of the tabulation above and the following
examples:
c-abl (ABLI) c-mos (M0.9
v-abl v-mos
Editors should not substitute one type of term for another.
The protein product may be similarly prefixed:
c-abl c-mos
v-abl v-mos
Additional prefixes may further identify oncogenes. Expansions of some prefixes are
given below, but it should not be inferred that the gene in question is associated only
with the tumor it is named for:
Oncogene PrefixEqansion
B-1' B-cell lymphoma
L-myc small cell lung carcinoma
N-myc neuroblastoma
H-ras Harvey rat sarcoma
c-H-ras
V-H-zzs
K-ras Kirsten rat sarcoma
c-K-ras

N-ras neuroblastoma
For example:,
Hypothesis: The K-ras mutation assay is more sensitive than the conven-
tional histologic diagnosis in detecting minute cancer invasion around the
superior mesenteric artery.
Nu~nl~ers
or letters clesignate genes in a scries, eg:

Fusion Oncogenes and Oncoproteins. The result of fusion of an oncogene and another
s<-nr1.; kno\vn ;IS ;I firsion otICO.qcn!~c~.
Thc prtxluct of a fiision oncogene is a fusion
15 d Gener so

Fu-iorr Otrcogcv~e I.-wion Ot~copmtein lan nation

bcr-abl bcr-abl bcr: breakpoint cluster region
c-/os/c-jlcn c-fos/c-jun
gag-onc gag-onc general term for fusion
proteins of viral gag
(group-specific antigen)
gene and oncogene
gag-jun gag-jun
PML-RARA PML-RARa promyelocytic leukernia-
retinoic acid a

Tumor Suppressor Genes. Tumor suppressor genes are "[glenes that normally restrain
cell growth but, when missing or inactivated by mutation, allow cells t o grow un-
~onfrolled."~Examples are in the tabulation below:
Gene Gene Product Eqlanatwn
cyclindependent kinase
(CDK) inhibitor 1A
CDKNlB p27 CDK inhibitor 1B
CDK inhibitor 1C
DCC a transmembrane deleted in colorectal carcinoma
receptor protein
GLTSCR1 gliorna tumor suppressor candidate
region gene 1
hF1 neurofibromin 1
retinoblastoma 1
a 53kd protein
a zinc finger protein W i tumor 1

REFERENCES
1. Jameson JL.Oncogenes and tumor suppressor genes. In: Jarneson JL, Collins FS. .
Principles of Molecular Medicine. Totowa, NJ: Humana Press; 1998:73-82.
2. Terms and definitions (0). National Institutes of Health Office of Rare Diseases.
'
3. V-ERB-B2 avian erythroblastic leukemia viral oncogene homolog 2; ERBB2. OMIM.
h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / d i s p 0 ~ 8 7 0 . Updated January 30,
2006. Accessed April 21, 2006.

Accessed April 21, 2006.

636

.-. . - . .
 15.6.4 Human Chromosomes

6. Terms and definitions (TI.National Institutes of Health Office of Rare Diseases.

h t t p : ~ o r d . a s p e n s y s . c o m / a s p / r e s o u r c e s / g l o s - S T Accessed
. April 21, 2006.

Human Chromosomes. Chromosomes are dark-staining, threadlike structures in the

cell nucleus composed of DNA and chromatin that carry genetic information (defi-
nition after Nussbaum et all and Mueller and young2).
Formalized standard nomenclature for human chromosomes dates from 1960
and, since 1978, has been known as the International System for Human Cytogenetic
Nomenclature (ISCN).
Material in this section is based on recommendations in ISCN 2005.~ Earlier
reports44 have also been .consulted.
Human chromosomes'are numbered from largest to smallest1from 1to 22. There
are 2 additional chromosomes, X and Y. The numbered chromosomes are known as
autosomes, X and Y as the sex chromosomes. Chromosomes stained using tech-
niques that do not produce bands are grouped based on similar size and centromere
position, as follows:
Group Chromosomes
A 1-3
B 4, 5
C 6-12, X
D 13-15 .

E 16-18
F 19,ZO
G 21, 22, Y
A chromosome may be referred to by number or by group:
chromosome 14
a D group chromosome

Chromosome Bands. Chromosome bands are elicited by special staining methods;

terms in the left-hand column need not be expanded:
Banding Pattern Technique
-
Q-banding, Q l>ands qi~inncrinc
G-bariding, G bands Giemsa
R-banding, R bands reverse Giemsa
C-banding, C hands constitutive heterochromatin
'f-lx~ncling.1' IxlnJs ~clolllcric
NOR
13:lntling techniclue ctxlcs o f several lette~spro\.itl~more inforrn:~[ion;~lx,~rr rllc
bantling metl~txl.'These ;~l,brevinti()nsmllst hc c . x l ~ . ~ n ~ l cIc, ~l ,I [ [lie lcrtcrs in r l l ~ .1i.r
:iIw\,tb( Q , G , R. C:. T. KC)R) \vi[I~iri1110s~
I C * ~ I I I \I ~ C C 0,.
~ !A L~S~.IIICI~CI:
15.6 Genetics
 15.6.4 Human Chromosomes

Regions are determined by major chromoson~eband landmarks. Chromosorlie at-tns

contain 1 to 4 regions, numbered outward from the centromere. The region numl~er
follows the p or the q:
4q3 region 3 of long arm of chromosome 4
The regions are divided into bands, also numbered outward from the centrotlicrc.
Bands have subdivisions or subbands. The band number follows the region t~i~tnl>cr.
and the subband number follows a period after the band number. When a sul,l,:~ncl is
further subdivided, the sub-subband number follows the subband nun11,t.r \\:ithoi~~a
period or other intervening punctuation:
llq23 chromosome 11, long arm, band 23 (region 2, band 3)
11q23.3 band in above subdivided, resulting in subband 23.3
20~11.23 chromosome 20, short arm, sub-subband 11.23
(region 1, band 1, subband 2, sub-subband 3)
It is correct usage to refer to the above expressions as "band 1 lq23," "band 11~123.3."
and "band 20~11.23."
The centromere is designated band 10, as in the following:
p10 (portion of centromere facing short arm)
q10 (portion of centromere facing long arm)
Visualization of genomic information by chromosonle region in humans and otller
organisms is available at the National Center for Biotechnology 1nform:ltion !Ll:~p
viewer8

Karyotype. Karyogpe is the chromosome complenient of an individual, tissue, or cell

line. Karyotype is expressed as the n u ~ l ~ bof
e r chromosonies in a cell inclucling the
sex chromosomes, a description of the sex chromosome compositipn, and, when-
ever applicable, any chromosome abnormality.
The kayogram and the idiogram are graphic repr.esentation of karyotype. The
karyogram is "a systemized array of the chromosomes" that has been prepared using
methods such as photomicrography. An idiogram is "diagrammatic representation of
the k a r y ~ t ~ ~ e . " ~ ' ~ '
In karyotype expressions, the sex chromosonies, which should always be spec-
ified, are separated from the nurnber of chromosomes by a comma, as in the fol-
lowing examples:
46,)CjC 46 chromosomes (2 each of cluomosonies 1-22 and 2 X
chromosomes in human female karyotype)
46,XY 46 chromosomes (2 each of chromosomes 1-22, 1 X and 1 Y
in human male knryotype)
45,X 45 chromosomes, 1 X chrotiiosomc (Turner syritlt-onlc)
47,XXY 47 chromosomes, 2 X chromoson~es.1 Y (I<linclclter sy~iclro~i\~
47,XYY 47 chro~nosomes,1 X, 2 Y cht-ornoso~i~~.~
69,X.X 3 e:lcIi of chro~nosotncs1-22 ;~ncl
15.6 Genetics

A virgule is used to indicate more than 1 karyotype in an individual, tumor, cell line,
and so on:

Descriptions of autosomal chromosome abnormalities are presented after the sex

chromosomes and listed in numerical order irrespectiveof aberration type, separated
from the sex chromosomes by a comma. For instance, the karyotype of a person with
trisomy 21 (Down syndrome) with an extra chromosome 21 is specified as
47,XX,+21 (female)
47,XY,+21 (male)
I1
A karyotype description may contain both constitutional and acquired elements. For
instance, the karyotype of a tumor cell from a person with trisomy 21 could
both the constitutionalanomaly and an acquired neoplastic anomaly, eg, an acquired
extra chromosome 8, and would be expressed as

Tlie lowercase c specifies that the trisomy 21 is constitutional, as distinguished from

: .
the acquired uisomy 8.
A n individual with more than 1karyotypic done may.have a mosaic (singleicell
origin) karyotype or a chimera (multicell origin) karyotype, which should be s ec-
ified with a %letter abbreviation at first mention of the karyotype, eg: P' .. '

L,.r. . . L

mos 45,X/463Y
chi 46,XX/46,XY
Brackets indicate the number of cells observed in a clone:
chi 46~251/46JYtlOM
11
A double slant (virgule), used in chimeras resulting from bone marrow transplants,,
separates recipient and donor cell lines. Recipient karyotype precedes the doubIe
slant,donor karyotype followsthe double slant,and either or both may be specified,eg:
I.
'

For details on order in such expressions, consult ISCN 2005.

Meiotic karyotypes may begin with a term such as MI and contain a haploid
near-haploid number of chromosomes,and may or may not have a comma
X and Y:

Chromosome Rearrangements. The abbreviations and symbols in Table 6 are

descriptions of chromosomes, including chromosome rearrangements. The
adapted from 1 ~ ~ ~ 2 0Former
0 5 . designations
~ based on ISCN 1995 and ISCN 1
appear in parentheses. (A short online version of the information in Table
available through the Cancer Genome Anatomy project.?

640

.. - \
. . --
Table 6. Chromosome Rearrangement Abbreviations and Symbolsa

AbbreviationlSymbol Explanation

Al first meiotic anaphase

All second meiotic anaphase
ace acentric fragment
add additional material of unknown origin
arr array
b break
C constitutional anomaly
cen centromere
cgh comparative genomic hybridization
chi chimera
chr (a[1985]) chromosome
cht (ct [1985]) chromatid
CP composite karyotype
a complex chromatid interchanges
del deletion
der derivative
dia diakinesis
dic dicentric
dim diminished
dip diplotene
dir direct
dis distal
dit dictyotene
dmin double minute
dn (de novo [1995)) chromosome abnormality not inherited
dup duplication
e exchange
end endoreduplication
enh enhanced
fem female
fis fission
frc~giIe
\iIc

9 gap
h heterochromatin
hsr homogeneously staining reglo-
iso~hromosom~
 modal number

mos mosaic

neo neocentromere

nuc . nuclear

wm oogonial metaphase

or alternative interpretation
short arm
P
first meiotic prophase
pachytene
paternal origin
premature chromosome condensation
premature centromere division
proximal
satellited short arm
pseudo-
pulverization
long arm
quadruplication'
quadriradial
Table 6. Chromosome Rearrangement Abbreviations and Symbolsa (cont)

AbbreviationlSymbol Explanation

qs . satellited long arm

ring chromosome
reciprocal
rea rearrangement
rec recombinant chromosome
rev reverse
rob robertsonian translocation
roman numerals
' univalent
bivalent
trivalent
IV quadrivalent
S satellite
sce sister chromatid exchange
Sct secondary constriction
sdl sideline
SI stemline
spm sperniatogonial metaphase
stk ~ t e l l i t estalk
subtel subtelomeric region
t translocation
tan tandem
tas telomeric association
ter terminal end of chromosome or telomere (tel [ i 9951)
tr triradial
trc (tri [1985]) tricentric
trp triplication
upd uniparental disomy
var (v 119951, var [1985]) variant or variable region
xma chiasma(ta)
zyg zygotene
break
break and reunion
separates chromosomes and chromosome bands in
structural rearrangements involving 2 or more
chromosomes
 - - - ..
I

Table 6. Chromosome Rearrangement Abbreviations and Symbols"cont)

~bbreviationl~~mbol Explanation

+ from-to

+ gain
- loss
- intervals and boundaries in a chromosome segm
<> angle brackets for ploidy
I1 square brackets for number of cells
- number of chiasmata
x multiple copies
? questionable identification

/ separates clones
// . separates chimeric clones
'Adapted by permission of S Karger AG, Basel, Switzerland.

Single-letter abbreviations combined with other abbreviations are set closed

chte chromatid exchange
Three-letter symbols combined are set with a space:
cht del chromatid deletion
psu dic pseudodicentric
The symbols in the list of chromosomes from ISCN2005 are part of an
shorthand that describes the exact changes in a karyotype containing rearranged:
chromosomes. In publications that range beyond the field of cytogenetics, the
symbols should always be defined.
Chromosome rearrangement terms can be written using a "short system" or short
form. Complex abnormalities are designated by the more specific "detailed system"
or long form. The detailed form uses symbols such as arrows to describe individual
derivative chromosomes resulting from complex rearrangements (even the short
system can result in a complex expression), eg:
short:
46,XY,t(2;5)(q21;q31)
long:
46,XY,t(2;5)(2pter+2qil::5q31-,5qter;5pter-,5q31::2q21j2qter)
The complete nomenclature, formulated for consistency in the description of c
mosomal rearrangements, is detailed in 1 ~ ~ ~ 2 0The 0 5following
.~ sections con
terms that illustrate some of the basic principles of the ISCN. Terms such as tl
stand alone or may be part of longer expressions such as those above.

- ----C--. . -.
I
15.6.4 Human Chromoromer

Order. For aberrations involving more than 1 chroniosome, the sex chro~iiosorn~
appears first, then other chromosomes in numerical order (or, less commonly. in
I
group order if only group is specified).
t(X;13)(q27;q12) translocation involving b;tnds Xq27 mcl 13q12

For 2 breaks in the same chromosonle, the short arm precedes the long arm, ancl
there is no internal punctuation, eg:
inv(2)(p21q31) inversion in chromosome 2
Exceptions to numerical order convey special conditions; for example, when a piece
of one chromosome is inserted into another (3-break rearrangement), the recipient
chromosome precedes the donor:.
ins(5;2)(p14;q21q31) insertion of portion of long arm of
chromosome 2 into short arm of chromosome j

Plus and Minus Signs. A plus sign.peceding a chromosome indicates addition of the
entire chromosome:
+14 entire chromosome 14 gained
A plus sign following p or q a d the chromosome number indicates an addition to
that chromosome:
14p+ addition to 14p
Such a term is ambiguous; it might refer to one of many possible specific additions to
14p of an individual karyotype, to an unknown addition to 14p, or to additions to 14p
in general. A term like 14pf may be used after context has been provided. In the case
of kdryotype descriptions, this means using more specific terms incorporating
symbols such as add, der, and ins:
Shorter Term Kayotype Term
14p+ add(14)(p13)

For example:
the 14q+ cytogenetic abnormality was found to be add(14)(q32).
A minus sign preceding a chromosome signifies loss of the entire chromosome:
-5 all of chromosome 5 missing
A minus signfollowing a chromosome arm signifies lossfron2 that arm, but this should
be reserved for text, while more specific notation is used in karyotype descriptions, eg:
Text
- Karyo(@e
5q- dc1(5)(q13q31)
A dclc[jon of rhc cnrire long arnl of cllrornosr)mc sllot~lclnot IJC csprcssed in text
nirh :I mint13sign.
15.6 Genetlcs

Punctuation

L ~number
P O ~ I J I ~[fir L ~ : of the affected chromosonle followsrhe rearrangement
symbol in parentheses:
inv(2) inversion in chromosome 2

Details of the aberration follow in a second set of parentheses:

inv(2)(p13p24) inversion in chromosome 2 involving bands
13 and 24 of the short arm

a Semicolon: In rearrangements involving 2 or more chromosomes, a semicolon

is used:
t(2;5)(q21;q31) translocation involving breaks at 2q21 and 5q31

m Comma: Commas separate the number of chromosomes, sex chromosomes, and

each term describing an abnormality:
46,XQ-(18)(pllq22) female karyotype with ring chromosome 18
with ends joined at bands p l l and q22

Underlining. In different clones within the same karyotype, an under1

distinguishes homologous aberrations of the same chromosome:
46,XX,der(l)t(l;3)(p34;q21)/46JX,der(l)t(1;3Xp34;q21)
In manuscripts, authors should indicate that the underline is intehded, so
not be set as italics, per typographic convention, in the published version.

Or. This word indicates "alternative interpretations of an aberration

native results (for instance, breaks appearing in consecutive bands us
techniques):
add(19)(p13 or q13)
add(lOI(q22 or q23)

Spacing. As seen in previous examples, there is no spacingbetween

karyotype description (except following mos and chi, between 2 or
abbreviations [eg, cht del, rev ish enhl, and before and after "or").

Long Karyotypes. Multiline karyotypes carry over from 1line of text to the next
no punctuation other than that of the original expression (eg, no hyphen at the
of the first line), as in the following tumor karyotype:
46,XX,t(8;21)(q22;q22)[121/45,idem,-M191/46,idem,
-X,+8[51/47,idem, Y +8,+9[81

In Situ Hybridization. Style for terms describing karyotypes identified by

this technique alone or along with cytogenetic analysis (traditional ka
techniques) is similar to that described above (see also 15.6.1, Nucleic Acids and

646
 15.6.4 Human Chromosomes

Table 7. In Situ Hybridization Abbreviations and Symbolsa

AbbreviationlSymbol Explanation

amp amplified signal

arr array

cgh comparative genomic hybridization

con connected signals
dim diminished signal intensity
enh enhanced signal intensity
fib ish extended chromatin/DNA fiber in situ hybridization
FISH fluorescence in situ hybridization
ish in situ hybridization
nuc ish nuclear or interphase in situ hybridization

PCP partial chromosome paint

rev ish reverse in situ hybridization

sep separated signals

subtel subtelomeric

WCP whole chromosome paint

separates probes on different derivative chromosomes
[period] separates cytogenetic observations from results of in situ
hybridization or array-based cgh
+ present on a specific chromosome
duplication on a specific chromosome
absent on a specific chromosome
precedes number of signals seen

aAdaptedby permission of 5 Karger AG, Easel, Switzerland.

Amino Acids). Some symbol meanings may differ. T ~ b l e7 is adaptecl from I.Sc:\'
2005.
Examples are as follows:

(D22S75 refers to the probe for the DNA segment sequence D22.775: s c ~1i.(,.:.
Human Gene Nomenclature.)

Marker Chromosomes, Derivative Chromosomes, and the Philadelphia Chromosome.

A markerchromosome"is a structurally abnormal chromosome in n.hich n o IXIII (.;III
be identified""~~~)
and might he includecl in 21 k:~ryotypcas in
15.6 Genetics

A structurally abnormal chromosome in which any pan can be recognized is

sidered a derivative cbmmosome, defined as *a suucturally rttarangrd chromoso
generated by a rearrangement involving two or more chromosomes or by multipl
aberrations within a single chromosome."xp62'
A derivative chromosome is specified in parentheses, followed by th
.tions involved in the generation of the derivative chromosome. The abe
not separated by a comma. For instance:
deI(l)t(1;3)(p32;q21)t(l;ll)(q25;q13)
signifies a derivative chromosome 1generated by 2 translocations, one i
short a m with a breakpoint in lp32 and the other involving the lon
breakpoint in lq25.
PhiIadeIphia chromosome is the name given to a particular deriv
some found in chronic myelogenous leukemia and some types of acute leuke
The Philadrtphia chromosome can be abbreviated as "Ph chr
context, "Ph." Appendages, as in phl, Phl, Phi, or Ph', are not neces
the preferred form. The Ph chromosome is the derivative chromoso
from the translocation t(9;22)(q34;qll) and may be described as follows:
der(22)t@;22)(q%;q11.2)
ThePh chromosome is the result of a rearrangement that
ABL with the breakpoint cluster region gene BCR (see 15.6.2, H
menclature, and 15.6.3, Oncogenes and Tumor Suppressor Genes).. ,

REFERENCES
1. Nussbaum RL, McInnes RR, Willard HF. 220mpson G
6th rev reprint ed. Philadelphia, PA: Saunders; 2004.
2. Mueller RE, Young ID. Emery's Medical Genetics.New York, NY:
2001.
3. Shaffer LG, Tomrnerup N, eds. ISCN 2005: An International S'
genetic Nomenclature (2005). ~a&el, Switzerland: S Karger AG; 2005.
4. Mitelman F, ed. ISCN 1995: An International S'tem for Huma
clature 1995. Basel, Switzerland: S Karger AG, 1995.
5. Mitelman F, ed. ISCN (1991): Guidelinesfor Cancer Cytogenetics: Supplement to an '
IntenWimal S ' e m for Human Cytogenetic Nomencla
Karger AG; 1991.
6. Harnden DG, Klinger HP, eds. ISCN (1985):An ~ntemationai
togenetic Nom.enclature. Basel, Switzerland: S Karger AG; 1985. .
7. Qurnsiyeh MB, Y i z Y. Molecular biology of cancer: cytog
Hellman S, Rosenberg SA, eds. Cancm Principles and Pract
Philadelphia, PA: Lippincott Williams & W i ; 2005:34-43.
8. NCBI Map Viewer. http://www.ncbi.nlm.nih.gov/mapview/. Accessed April 21, 20
9. ISCN abbreviated terms and' symbols. The Cancer Genome Anatomy Project.
http://cgap.nci.nih.gov/Chromosomes/IS~s. Accessed April 21, 2006. ..

648

. ,- --..-
, -....
+-. ..
...
.*rh'<m.r."'
.. ._^. - _.-
 15.6.5 Nonhuman Genetic Terms

(T/heword mouse . . . comes originallyfrom the

Samkrit mush derived from a verb meaning to
steal. . . . Mice and rats, .through their voracious
activities in grain larders and as carriers of disease,
inficted considerable losses infood and lives upon
ancient civilizations.
H. C. Morse 111''~~'

A vey obviousgap in our undetstanding of human

genome evolution lies in the complete absence of any
mapping data from the euthaian o r d m most dis-
tantly related to man, particularly the edentates. We
would urge anyone m'th an interest in thegenetics of
the aardvark and the armadillo to consider a unique
mappingproject whicb will be at theforefront (al-
phabetically, at least) of the comparative mapping
effort. '

J. A. Marshall Graves et a12'p964)

Nonhuman Genetic Terms. Comparative genome analysis has shown that eukaryote
species share genes to a great e ~ t e n tTherefore,
.~ similar or identical names designate
the same gene across species whenever possible. Italicization of gene symbols is
uniformly observed. . -
Vertebrates. Animal gene symbols resemble human gene symbols (see 15.6.2, Hu-
man Gene Nomenclature, and below)?-5 However, unlike human gene symbols,
animal gene symbols typically use or include lowercase letters >nd punctuation
marks. Editors of medical publications may follow author style for animal gene
symbols.
Gene terminology for the laboratory mouse ( M u musculus domesticus) and
laboratory rat (Rattus norvegiclls), often seen in medical publications because of the
common use of those species in investigating diseases affecting humans, is proto-
typic of such style.

Mouse and Rat Gene Nomenclature. Mousc and nit gent: nomenclature gclidelines
were unified in 2003 by the International Committee on Standardized Genetic No- . .
'
menclature for Mice and the Rat Genome and Nomenclature ~otnmittce."
Mouse and rat gene symbols resemble human sy~iibolsin several respects."7
They are descriptive, short (prefcraliy 3 to 5 cli;~r:lctcrs),ancl italicizecl. Symbols
begin with letters, not numbers. They contain roman letters in place of Greek letters
and arabic numerals in place of roman numerals.
Mouse and rat gene symbols differ from human sy~ilbolsin using lowercase
letters. Symbols usually contain an initial capital. Capital letters within a mouse gene
symbol may indicate the laboratory code or code for another species/vector (see
below). A symbol with all lowercase letters (ie, no initla1 capital) inclicates a recessive
trait. Mouse ;ind mr gene synll~olsmay contain hyphens and other punct.uation.
Table 8. Stvle Rules for Mouse Gene Svmbols and Cornoarison With Human Gene Svmbols .a
,..,
(Examples)
'
Mouse Mouse Gene Human Gene Symbol
Gene Symbol Description Rule Illustrated w h e n Known) :

a nonaaouti lowercase initial ca~ital ASIP

because named for
1
mutant recessive trait

A fp a-fetoprotein initial capital, otherwise AfP

.p
;$
lowercase, Greek
letter chanaed to roman 2
.I<

B2rn . P2-microglobul~n no subscript B2M

Gla a-galactosidase Greek letter changed to GLA
roman and moved
to end of svmbol
G ~ ( R O S A ) ~ ~ S O ~gene trap, ROSA 26, parentheses may be used
Philiooe Soriano
Rn4.5~ 4.55 RNA period permissible
RnB 55 RNA symbol does not begin RNSSI@ (Q signifies
with number gene family; see 15.6.2,
Human Gene ~omenclatu;$
-.3
The central source for mouse gene terms is the Mouse Genome Database (http:1/
www.informatics.jax.org),8 and for rats, RatMap (http://ratmap.gen.gu.se) and ther
k t Genome Database (http://rgd.mcw.edu)? Gene names and symbols may be':'
verified by means of the search features at those sites.
Style rules and conventions for mouse and rat gene symboIs are shown in Tab;$$
-3
8 through 10. (Note: The gene descriptions in the tables that follow are based on but
not identical to the approved gene names available in the Mouse Genome Infor-
matics database, which are more comblete and do not use Greek letters and:]
other typographic variants. For instance; in searching for a term with a, one would
type in "alpha.") The ~ammalianOrthology Query Form (http://www.inforrnatici
.jax.org/searches/homology_form.shunl)allows comparative searches of 20 vea6
brate species. Note that a given letter or letter combination often but not always
signifies a conventional usage. For instance, l at or near the end of a symbol often, but
not always, indicates "like." - L'
Mouse Alleles. A mouse allele symbol consists of a mouse gene symbol often witha
'2
superscript. As with mouse gene symbols, mouse allele symbols are italicized. ..t.~
Allele symbols can be verified within the records of a mouse gene: $j
.'..7
Search for the gene symbol .at http://www.informatics.jax.org/javawi2/se~l
/WIFetch?page=markerQF
r Click on link for the gene symbol that has been located
Under Phenotypes, click on the numeric link after "all phenotypic alleles" .:
Allele searches are also available at http://www.informatics.jax.org/searches/all~
-form.shtm1.
 . . .,

15.6.5 Nonhuman Genetic Terms

- - - ~

Table 9. Conventions for Mouse Gene Symbols and Comparison With Human Gene Symbols
(Examples)

Mouse Mouse Gene Convention Human Gene Symbol

Gene Symbol Description Illustrated (When Available)

Brca 1 breast cancer 1 same as human symbol BRCA 1

except for case
Cafq 1 caffeine metabolism q: quantitative locus
QTL 1
C4bpps 1 complement component -ps: pseudogene
4 binding protein,
~seudoqene1 - - - -- - -- - -

D 1OMit 1 DNA segment, Chr 10, symbol for DNA segment

Massachusetts Institute of identified only in the mouse;
Technology 1 includes laboratory code (see
"Laboratory Codes")
D17H21556 DNA segment, Chr 17, HZ1 indicates DNA segment. D2 1556
human 021556 resides on human chromo-
some 21
G6pdx glucose4-phosphate similar but not identical to G6PD
dehydrogenase X-linked human gene symbol
Gna-rsl guanine binding protein, -1s: related sequence GNL 1
related sequence 1 ,

GtllO gene trap locus 10 Gt: gene trap

Gt(ROSA)26Sor gene trap ROSA 26. Philippe vector in parentheses;
Soriano laboratory code indicated (see
"Laboratory Codes" section)
HZ-Aa histocompatibility 2, class II HLA-DQAI
antiaen A. a
--
Hbb hemoglobin pihain complex same as human symbol HBB
exceDt for case
heterochromatin. Chr 9 Hc: heterochrornatin
Hras 1 Harvey rat sarcoma virus see a!so 15.6.3, Oncogenes HRAS
oncoqene 1 and Tumor Suppressor Genes
lghmbp2 immunoglobulin heavy chain name change with new lGHMBP2
(formerly nmd) ,cbinding protein 2 (formerly information about gene
neuromu~ulardegeneration)
--- . .- -
Il7Wis9 lethal, Chr 17. University of initial I:lethal
Wisconsin 9
Lambl-1 PI laminin. subunit 1 hyphen separates 2 LAMB 1
adjacent numbers
Up-5 P lysozyme structural - s structural
- -- .
mt Rnr 1 125 RNA m~rochondr~al mt mlIochondr~al MJ-RNRI
.--- - -. -- - - --
 15.6.5 Nonhuman Genet~cTerms

Table 10. Conventions for Mouse Gene Symbols Identified in Collaborative Sequencing Efforts
(Examples)" (cont)

Mouse Gene Mouse Gene Convention Human Gene Symbol

Symbol Description Illustrated (When Available)

P P ~ palmitoyl-protein thioesterase Genbank sequence ID PPT2

2, formerly -672937 and withdrawn when gene
061 W07M19Rik identified in other organism

'See also Database Identifiers for Genomic Sequences in 15.6.1, Nucleic Acids and Amino Acids.

Conventions and rules for mouse allele symbols are shown in Tahle 11.
In a phenotype expression, a superscript plus sign indicates wild-type. eg:
N ~ I ~ ~ ~ ~ ~ ~ / N ~ I +
which indicates a phenotype with a mutant neurofibromatosis allele (tilrgerecl 11111-
tation 1, Fredrick Cancer Research and Development Center) and the w i l d - t y p c
neurofibromatosis allele.

Table 11. Rules and Conventions for Mouse Allele Terms (Examples)

Allele Symbol Allele Name Convention o r kule Illustrated

abn abnormal recessive trait, thus begins with lowercase;

because there is no superscript indicating an
allelic term, use context to clarify
Dbf doublefoot dominant trait, thus begins with capital; because
there is no superscript indicating an allelic term,
use context to clarify
Dnahcl l N situs inversus viscerum allele of dynein, axon, allele superscript,designationi s lowercase
heavy chain 11 gene (recessive)
I~SP'~' Akita allele of insulin 2 gene allele superscript designation has initial capital
(dominant)
1amaflP2' . dystrophia muscularis allele, Jackson 2, of laboratory code included in superscript (see
a2-laminingene (second allele discovered at the "Laboratory Codes" section);
Jackson Laboraory) hyphens used
~ a t p ~ ~ underwhite
~ ' dominant brown alleles of multiple alleles separated by hyphen in
membrane-associatedtransporter protein gene superscript

Mouse Chromosomes. Chromosome n o m e n c l : ~ t u ~ . cis s i m i l a r for mice ancl h u m a n s

(see 15.6.4, H u m a n C h r o n i o s o ~ n ~ s Ilo\vc.vc.r.
). ill niic,c., r e : t r r ; ~ n g c ~ n c n ttcrrnb ;lrc
capitalizetl. T l i c folloa,ing libtinl: :ind s u l x r c l \ ~ c n r cs;~riil~le.s;\rc fro111 t h c 1nrcrn;l-
tion;iI <:ornn,ittcc on St;lnd;rrd17c.d <;cnrt~r. s o ~ ~ l ~ . l l c . l ; ~t'or-
t ~ hlic-cl".
~rc
 Df dcficienc-y
DP dupl~ca~~on
Hc pericenuic heterochromatin
1
Hsr homogeneous staining region ?

In inversion
Is insertion
MatDf maternal deficiency
MatDi maternal disomy
MatDp maternal duplication
Ms monosomy
Ns nullisomy
PatDf paternal deficiency
PatDi paternal disomy
PatDp paternal duplication
Rb robertsonian translocation
T translocation
Tc transchromosomal I : ;.

Tel telomere $4
Tet tetrasomy
Tg transgenic insertion ...:.
TP transposition
Ts trisomy
UpDf uniparental deficiency
UpDi uniparental disomy .
UpDp uniparental duplication
As with human chromosomes, lowercase p represents the short arm and lowercase q

Human chromosome 1 shows extensive homology to several mouse chro-

mosomes, especially Chromosome (Chr) 4 and Chr 1.

InSRk fifth inversion found by Rodericg

T37H 37th transl~cationfound at Harwell 4
I

Chromosome number appears in parentheses:

In(215Rk inversion in Chr 2
Semicolons separate numbers of chromosomes involved in translocations:
T(4;X)37H translocation involving Chr 4 and Chr X
 15.6.5 Nonhuman Genet~cTermr

Periods indicate the centromere in robertsonian translocations:

~b(9.19)163H robertsonian translocation involving Chr 9 and Chr 19

In insertions, the donor chromosome number comes first:

Is(7;1)40H insertion froni Chr 7 to Chr 1

For further rules and conventions for chromosomes, see the chromosome nomen-
clature section of the Mouse Genome Informatics Web site.''

Laboratory Codes. Laboratory registration codes appear as 1- to Cletter symbols in

animal genetic terminology, including chromosomal, DNA locus, and mouse strain
nomenclature (see below). Such codes help identlfy specific colonies, useful in
genetic studies that can extend over many generations. Laboratory codes are regis-
tered with the Institute of Laboratory Animal Resources at the National Academy of
Sciences in Washington, DC, and may be located at http://dels.nas.edu/ilar-n
/ilarhome.ll These codes uniquely identlfy an investigator, laboratory, or institution
that .breeds rodents or rabbits. Laboratory codes have initial capitals and appear
without exbansion. Examples are as follows:
Arb: Arthritis and Rheumatism Branch, National Institute of Arthritis and Mus-
culoskeletal and Skin Diseases
Ddd: University of Durham, Drug Dependence Group
J: The Jackson Laboratory
N: National Institutes of Health
Ty: Benjamin A. Taylor, The Jackson Laboratory
Wil: Jean Wilson, University of Texas

Mouse Strains. Mouse strain named2 are registered at the Mouse Genbme Informatics
Web site (http://www.infomtia.jax.org/mgihome/~~bmi~~ion~/~~bmi~~i~ll~~menu
.shtml). Mouse strain names are available at http://www.infomatia.jax.org/extemal
/festing/search-form.cgi. (Rat strain namesare registereciat the at ~enome~atabase.3)
Mouse strain names consist of capital letters or combinations of capital letters
and numbers:
A
BXH
CBA '
C57BL
FVB
HDA32
A few earlier strains have names that are entirely numeric, eg:

[I~c
A substrain is indicated by a term Sollowing lllc smin n;imc ;~licr;I vil.gi~le,i~sil;~lly
laboratory registration codes (see above), eg:
15.6 Genet~cs

1 ?I/]
A/J

atherosclerosis in CBA/J mice

m/h'mice used as controls
A serial number may precede the laboratory code, eg, the 10 before the J in this
example:
C57BL/lOJ
Exceptions to the initial capital after the virgule exist in the case of 2 we
strains (not substrains) of mouse:
BALB/C
C57BR/cd
Many standard laboratory mouse strains are derived from crosses dating back to the:
early 20th century or even older lines, and the names reflect abbreviations for'
characteristics:
A albino
BALB Bagg, albino
DBA dilute, brown, nonagouti
However, mouse strain names are not expanded.
Strain names may be abbreviated using approved abbreviations, eg:
B C57BL
C BALB/c
Note that some abbreviationsare the same as some names of different strains (eg, the
strain C and the abbreviationC), so Context must clarify. Additional abbrevi
available at http://mnv.informatics.ja~org/mgihome/nomen/strains.shtml.
Abbreviations and the letser X are used to indicate recombinant inbred s
(female parental strain first), eg:
CXB BALB/c x C57BL
Capital F followed by a number in parentheses may appear after a strain d
to .indicate the number of @bred generations:
a
F(20) 20 inbred generations
For further guidelines on mouse strain nomenclature, see the Mouse Geno
matics Web site at http://www.informatics.j&.org/mgihome/nomen/strai

Invertebrates

Drosophila melanogaster. Gene symbols for the fruiffly Dmsophila melan

generally capital and lowercase or all lowercase for recessive phenotypes. Th&
convention is also observed for gene names. Gene symbols may include punctua-
tion.l3.l4A source for background on Dmophila gene names is ~ 1 ~ ~ o r nNG.-e.l~
menclature rules and symbol search are available at FlY~ase.l3

. _-_
._.......-_
-. . _:
 15.6 5 Nonhuman Genet~cTerms

Gene Symbol Name

PP2' Preproinsulinlike
\ SmT Serotonin transporter
su(Hw) suppressor of Hairy wing
tRNA:ST23Ea transfer RNA:ser7:23Ea (ser7:
seventh isoform of serine; 23E:
map position)
As with mouse alleles, Drosophila alleles are indicated with superscripts:
Hnr, ~ n ' *(Henna gene, eye color-defective alleles)

Caenorhabditiselegans. The gene symbols for this nematode (roundworm) consist of

_< _ =--
3 lowercase letters, hyphen, arabic numeral (sometimes a decimal), and, somelimes.
a roman numeral after a space1*"':

Parentheses indicate mutation in the gene:

Mutation symbols consist of 1- or Zletter terms plus a number:

A characteristic of a mutation may be indicated by a 2-letter ending set in roni;lli

type:
hcl7ts (ts: temperature sensitive)

OMIA. Online Mendelian Inheritance in Animals is the counterpart to Online hlcn-

delian Inheritance in Man (OMIM; see 15.6.2, Human Gene ~omenclature).".~~

Microorganism Gene Nomenclature

$ Yeasts. Gene symhob for the fungus Sacchammn.yc~sccretlisim consist o f 3 c;tpit;d

letters plus a numl>er(or, occasionally, a numl)cr-leitcr) cncling'":
Gene Symbol Name
ACT1 actin
CDC25 adenylate cyclase regulatory protein
COX5A cytochrome c oxidase chain Va
This represents a change from earlier style in which all-lowercase symbols were
used for loci named for recessive mutations (the preponderance of symbols) ancl
 f
15.6 GeneticS

all-capital symbols for loci named for dominant mutations. Allele symbols ail1 follow
the case convention (ie, capital for dominant, lowercase for recessive).

Bacterial Gene Nomenclature. Gene terms typically consist of an italicized lowercase

3-letter abbreviation often with an uppercase locus designator. The phenotype or1
encoded entity (eg, enzyme) is in all roman letters with an initial capital.
Gene Symbol Phenotype (Explanation)
araA AraA (L-arabinose isomerase)
usr Asr (acid shock protein)
imp (formerly 0st.A) OstA (organic solvent intolerance; imp:
increased membrane permeability)
katE KatE (catalase)
so& SodA (superoxide dismutase, manganese)
sodB SodB (superoxide dismutase, iron1
A nuAber of bacterial genome databases are available on the Internet.
Center for Biotechnology Information sponsors Entrez Genome
.nlm.nih.gov/entrez: under Search,select Gene, then search for the
Alleles are designated with a number after the uppercase 1
a hyphen, when not assigned to a locus. Wild-type alleles are
superscript plus sign:
ara+
araA1
ara-23
sodAl

Retroviral Gene Nomenclature. Human immunodeficiency virus and other re-

viruses contain 3 main structural genes and a number of regulatory genes22(see also
15.6.3, Oncogenes and Tumor Suppressor Genes):
Strucrural:
env envelope gene
gag groupspecific core antigen gene
Pol polymerase gene
Regulatory:
nef negative factor
reu regidator of viral protein expression
tat transactivator of viral transcription
vif viral infectivity
Wr viral protein R
V ! . viral protein U
VPx viral protein X

. . -. .
.
_
- .. . _-:.
-.

.. ,
 15.6.5 Nonhuman Genetic Terms

Compare typographic style of gene names and their products (p stands For protein.
g p for glycoprotein):
Gene.Product Protein Products
Gene
- (Protein o r Pol'eptide) (Examples)
enu Env gp41, gp120
gag Gag P6, ~ 7~ , 1 7p24
,
Pol POI p12, p32, p66/51
nef Nef P27
rev Rev ~ 1 9
tat Tat - PI4

REFERENCES
1. Morse HC 111. The laboratory mouse-a historical perspective. In: Foster HL, Fox F,
eds. m e Mouse in Biomedical Research. Vol 1. Orlando, FL: Academic Press Inc;
1981:6-10.
2. Marshall Graves JA, Wakefield MJ, Peters J, Searle AG, Womack JE, O'Brien SJ.
Report of the Committee o n Comparative Gene Mapping. In: Guticchia AJ, ed.
Human Gene Mapping 1994:A Compendium. Baltimore, MD: Johns Hopkins
University Press; 1995962-1016.
3. Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat
Genet. 2000; 25(1):25-29. Also available at http://www.geneontology.org/GO-nature
_geneticsCS2000.pdf.Accessed April 21,2006.
4. ARKdb. http://www.thearkdb.org. Accessed April 21, 2006.
.-
5. RatMapGroup. RATMAP: the Rat Genome Database. http://ratmap.gen.gu.se/.
Accessed April 21, 2006.
6. International Committee on Standardized Genetic Nomenclature for Mice and Rat
Genome and Nomenclature Committee. Rules for nomenclature of genes, genetic
markers, alleles, and mutations in mouse and rat. http://www.informatics.jax.org
/mgihome/nomen/gene.shtml#genenom.Updated January 2005. Accessed April 21,
2006.
7. ~ a l d LJ,
s Blake JA, Chu T, Lutz CM, Eppig JT, Jackson 1. Rules and guidelines for
mouse gene, allele, and mutation non~enclature:a condensed version. ~enojnics.
2002;79(4):471-474. Also available at http://www.inforrnatics.jax.org/mgihome
/non~en/short_gene.shtml.Acccssetl April 21, 2006.
H. Jackson Lrlwratory. MGI: Mol~sc(;cnomc Infol.~l~;~lics. I~~~l~:~www.ink)r~~~;~~ics,j:~x
.org. Updated April 20. ?(k)(). A ~ c c ~ s c April
cl 21. LOO0
9. I1GI). Rnt Genome 1):lt;lt);lsc h~tp://rp,dmcn.etlu. I1ptl:~rcd hpr~l17. 2OCK. Accessed
April 21. 2006
10 l f i ~ ~ r r l . i f ~ o
( :n~. )~~
! l l l l l ~( 1 1I1l ~
I',,r norntmnc I.II~II-c.of ( ' ~ ~ ~ O I ~ ~ ( I :11*.rr:111o11,
' l l l l l , l , . / l 1 1 1 1 1 1 1 l l lllllll
~ ~ ) I H I :

c ,I
-
~tl' . ~ l ~ d . ~ <rVlC~I ~~C/I !c,\,~,111t.114
I
!:[1p \ \ \ , \ \
1 1 I
i :!I Ir,. f , !: \!I'
11111 ~ ! 1 ,11 1 1

2 . " .. .
\ ,.I\
I<~IIL~\
ore
 -. -.

15.6 Genetics

11. ILAR: Institute for Laboratory Animal Research. Laboratory Code Registry. http://
dels.nas.edu/ilar-nfilarhome.Accessed April 21, 2006.
12. International Committee on Standardized Genetic Nomenclature for Mice
Genome and Nomenclature Committee. Rules for nomenclature of
strains. http://www.infomati~~.jax.org/mgihome/nornen/sai.~h. Updated
January 2005.Accessed Appl 21, 2006.
13.FlyBase: a database of the Drosophila genome. http://flybase.net. Accessed April 21,
2006.
14. Stewart A, ed. 7i'G Generic Nomenclature Guide. Tanytown, NY: Elsevier Trends
Journals; 1995.
15.FlyNome: a database of Drosophila nomenclature; http://www.flynome.com. AC-
cessed April 21,2006.
16. Hodgkin J. ~ekommendedgenetic nomenclature for Caenorhabditis elegans. hap://
elegans.swrned.edu/Genorne/nomen.ht1nl.O1~10~25. Accessed April 21, 2006.
17. Nicholas FW. Online Mendelian Inherimce in Animals (OMIA). h t t p : / / m
.au/omia. Updated October 16,2003.Accessed April 21,2006.
18..Rangel P, GiovannettiJ. Genomes.andDatabases on the Internet: A Practical
Guide to Functions andApp1ications. Norfolk, England: Horizon Scie
2002.
19. SGD gene naming guidelines. http://www.yeastgenome.org/gene_guidel
Accessed April 21,2006.
20. Dernerec M, Adelberg EA, Clark AJ, Hartman PE. A proposal for a uniform nb- ,
menclature in bacterial genetics. Genetics. 1966;54(1):61-76.
21.Jounzal of Bacteriology 2006 instructions to authors. http://jb.asrn.org/misc/itoa.pdf
Accessed April 21, 2006.
22. Guatelli JC,Siliciano RF,Kuritzkes DR, Richman DD. Human immunodeficiency
virus. In: Richman DD, Whitley RJ, Hayden FD,eds. Clinicul Virology.
Washington, DC: ASM Press; 2002:685-729.

: Pedigrees. Pedigree format recomme~dationsare put forth by the pedigree

dardization Task Force of the National Society of Genetic ~ounse1ors.l(See
5.8.3,Legal and Ethical Considerations, Protecting Research Participants' and
ients' Rights in Scientific Publication, Rights in Published Reports of Genetic
dies.)
A square represents a male individual; a circle, a female individual; and a
mond, an individual whose sex is unknown:

00
Shading indicates an'affected individual. Partitions with different shadin
used for individuals with more than one condition. Define all shading in a legend
key.

. --.- .-
.
.
. -
C
.
--'-
.<
 15.6.6 Pedigrees

Condition I

Condition 2

Multiple individuals are indicated by a number inside the shape. For unknown
number, a roman n is preferred to a question mark:

A slash mark indicates a deceased individual:

An individual in gestation is ihdicated with a capital P inside the shape:

The proband ("first affected family member coming to medical att~nti~n""~'~"')

is
indicated by a capital P with arrow:

The consultand (person seel<ing~~icclir::~l

altcnrion ) is inclic:~tcciw it11 :In ; I I . S ~,\\.:
'I'CAI 11.11 ~ n l )cr n l ~ ! ~ oanp p . i r s below the individual symbol. Preferred order is agej
a
f
~ntc~ r l r u r l o n cvalulttion,
, and pedigree number:

Eu: uninformative evaluation. -4

An obligate carrier (ie, unaffected individualinferred by pedigree analysis to
trait) is indicated with a central dot:

1
A small triangle indicates an individual in a pregnancy not carried to term. Se
if known, is indicated with text. Shading is used as described above for affectt
individuals. "ECT" indicates ectopic pregnancy. A slash indicates termination !
pregnancy-

Female ECT /Male

6 wk

Stillborn individuals are represented by full-sized shapes with "SB" in the caption

ti
Partner relationships are indicated by a straight,horizontal line. It is preferred that the!
male partner be shown on the left. . '
I
 15.6.6 Pedigrees

Siblings should appear in order of birth (oldest to the left), connected by lines ;is
follows:

Offspring are indicated by vertical lines; a shorter line indicates a pregnancy not
carried to term:

An ended relationship is indicated by a double slash:

Consanguinity (''kinship because of common a n ~ e s t ~ " " ~is' ~indicated

~~) by a
double line:
 15.6.6 Pedigrees

In pedigrees that show relationships defined by assisted reproductive technologies,

D indicates donor (sperm or ovum) and S, surrogate carrier of the pregnancy.

Diagonal lines indicate other parental relationships:

Haplotypes may be indicated with shaded rectangles below the individual. Meaning
should be clarified by means of a key.

Key: [
B
Variant allele

I Normal allele

A sample complete pedigree follows (Figure 6):

15.6 Genetics

Figure 6. Pedigree showing 3 generations includes terminated relationship (double diagonal line:
.. . .. . - .,
2

condition commoln to father and 1 dizygotic twi~

n son (half-stladed boxes). and haplotype!
~

and anotherson (rectangles with numbers). RorIan numerals, indicate generations.

REFERENCES
1. Bennett RL, Steinhaus KA, Uhrich SB, et al. Recommendations for standardized h*
pedigree nomenclature. Am J Hum Genet. 1995;56(3):745752. AlSo published inJ
Genet Counseling. 1995;4(4):267-279. -I
2. Stedman's Medical Dictionary. 27th ed. Philadelphia, PA: Lippincott Williams & Will
. ----
Ins; ZUOU.

Thrombosis may be regarded as an accident of

nature that has not had time to adapt through the
lengthyprocess of evolution to the advances of
modern medicine, which allow patients to sunrive : <
. . E?
the hemostatic challenge of major s u e trry and
,

trauma but letzve them vulnerable to venous

thrombosb. -,
R. W. Colman et
 .. . :

15.7.1 Primary Hemostasis

. . .each milliliter of blood contaim enough clotting

material to clot all thejbrinogen in the body in 10 to

R. I. andi in^'"^^^'

Hemostasis. Hemostasis consists of platelet plug formation (primary hemosv~sis)

and blood coagulation (secondary hemostasis, coagulation, clotting). Hemost:~sis
lex interactions of more than 50 proco:lgul:lnts ancl
hemostatic processes depends on consistent llsc 01'
terms.

Primary Hemostasis. Note the typography of the following terms, which are h ~ o n di l l
descriptions of platelet hemostasis (use parenthetical abbreviated terms in iccor-
dance with 14.11, Abbreviations, Clinical, Technical, and Other Co~nlnonTernls):
Abbreviation
6-keto prostaglandin Flo, 6-keto I'GFk,

arachidonic acid AA
ATP P2X1 receptor P2X1
P-thromboglobulin PTG or BTG
calcium calrnodulin complex Ca-CaM or Ca-Ch.1
cyclooxygenase CO or COX
diacylglycerol DAG
G proteins (proteins that
hydrolyze guanosine
triphosphate; expansion not necessary)
glycoprotein Ia/IIa complex GpIa-IIa
glycoprotein 1b/IX complex GpIb-IX
glycoprotein Ib/M/V complex GpIb-IX-V
glycoprotein IIb/IIIa complex GpIIb-IIIa
glycoprotein IV (CD36; see also GpIV
15.8.7, Immunology, Lymphocytes)
glycoprotein VI G P ~
inositol triphospl~ate 11'3

myosin light chain MLC

myosin light chain kinase MLCK
myosin light chain, phosphorylated MLC-PO4
phosphatidylinositol 4,5-biphosphate I)IP2
phosphodiesterase 3A PDE3A
phospholipase Ar I'I.A2
phospholipase C 1' LC
platelet activating factor lJAF
15.7 Hemostasis

Term Abbreuiation
platelet-derived growth factor PDGF
platelet factor 3 PF3
platelet factor 4 PF4
platelet ADP P2T adenylate P2T~c
cyclase receptor
platelet ADP P2X1 receptor P2X1
platelet ADP P2Y1 receptor P2Y1
prostacyclin, prostaglandin I2 PG12
prostaglandin D2 PGD2
6-keto prostaglandin F1, 6-keto PGFI,
prostaglandin G2 PGG2
prostaglandin Hz PGH2
protein p47 P47
pi-otein p47, phosphorylated p47-PO4
protein kinase C PKC
thromboxane A2 TxAz
thromboxane BZ TIcBz
P-thromboglobulin PTG or BTG
von Willebrand factor (see also below) VW
See also 15.1.2, Blood Groups, Platelet Antigens, and Granulocyte
Specific Antigens. ,

Endothelial Factors. Structures and products of endothelial cells-the cells 1

blood vessel&maintain blood fluidity by preventing excessive clotting and prev
bleeding by promoting clotting. The following endothelium-associated terms
presented as a guide to style.
Class Term
cellular (or cell)
adhesion molecules
intercellular adhesion
molecule 1
intercellular 'adhesion
.molecule 2

platelet-endothelial CAM
vascular CAM 1
cytokines (see also
15.8.4, Immunology,
Cytokines)
gro (growth-stimulating factor)

. ... . . - .-. .- . _ .. -- - -TI

9 Ii--
 15.7.3 Secondary Hemostasis

Class Term Abbret?ation

RANTES (regulated on activation,
normal T-expressed, and
. presumably secreted3)
integrins
alPl integrin
a2P3integrin
a3& integrin
a6P1integrin
integrin
integrin
miscellaneous
nitric oxide NO
endothelial (or epithelial) eNOS
NO synthase (also NOS3)
endothelial-cell associated
ADPase
(CD39; see also 15.8.7,
Immunology, Lymphocytes)
prostacyclin, prostaglandin I2 PG12
E-selectin
L-selectin
P-selectin
tissue plasminogen tPA
activator (see 15.7.4, Inhibition .
of Coagulation and Fibrinolysis)
urokmase or urinary plasminogen ,,PA
activator (see 15.7.4, Inhibition
of Coagulation and Fibrinolysis)
Three glycoprotein complexes are synonymous with 3 integrins and take part in
hemostasis:
GpIa-IIa %PI
GpIc-IIa a601
GpIIb-IIIa aIIBP3

Secondaty Hemostasis. Blood coagulation is the phase of clot formation dependent

on plasma coagulation factors (also known as clotting factors).
I

1 Pathways. The laboratory evaluation of plasma factor-dependent coagulation has

1,c.c.n divided into 2 pathways (systems, phases). The following terms and synonyms
:Ire. tlicrf-

669
dSlS

7imn SPonUm
inrrinsic pathway contact system-initiated pathway
extrinsic pathway tissue factor-mediated or tissue
factor-dependent pathway

Clotting Factors. An international system of nomenclature, formulated from 195

through 1963,~t~ clarified clotting factor terminology and, as ~ i g g observed,
s~ su;
entific findings in coagulation, when factors identified and named independently b
different groups were shown to be the same.' A major update to the standard n
menclature was published by Blomback et in the early 1990s.
A number of clotting factors were named for the patients whose disorders led t
their discovery. Biggs considered this practice valuable in avoiding "'hypotheti
implication.'"5(~70"
Roman numerals are used id designate most of the major plasma coagulati
factors. These designations when formulated were seen as having advantages
eponyms and functional names for comprehension by readers of non-Western
guages.5 "The sequence of numbers in current terminology is ... based on the
torical order in which the coagulation factors were di~covered."~(~'~~)
The following tabulation gives roman numeral designations, descriptive nam
and synonyms for the plasma coagulation factors. Asterisks indicate preferr
Terms that are rarely used are enclosed in parentheses. If a term other
preferred term is used, the preferred term should be given in karentheses at the
mention of a factor. Common abbreviations-appearhere, but their use shoul
form to guidelines in 14.11, ~bbr*tions, Clinical, Technical, and Other Co
Terms. (The term "factor VI," originally designating activated factor V, is not use
Faltor No. Descn$tive Name Synonym(s)
(factor I ) fibrinogen* M

factor II prothrombin* prethrombii

(factor 111) tissue factor - thromboplastin
tissue thromboplastin
tissue extract
(factor IV) calcium* calcium ion
caZ+
factor V' proaccelerin (labile factor)
(accelerator globulin [AcGl)
(Ac globulin)
(thrombogen)
factor VII* proconvertin (stable factor)
(serum prothrombin conversion
accelerator [SPCAI)
(autoprothrombin I)
J
factor VIII* antihemophilic antihemophilic globulin (AHG)
factor (AHF) antihemophilic factor A
(platelet cofaaor 1)
(thromboplastinogen)

- - - -.-
.
--
....
.
. - .

: .?,. .-*
 15.7.3 Secondary Hemostasis

Factor No. Descriptive Name Sponym(s)

factor M* plasma thrombo- Christmas factor
plastin component antihemophilic factor B
(PTC) (autoprothrombin 111)
(platelet cofactor 2)
factor Y Stuart factor Prower factor
.Stuart- rower. facior
(autoprothrombin 111)
(thrombokinase)
factor XI* plasma thrombo- (antihemophilic factor C)
plastin antecedent
(FTA) /'
factor XII* Hageman factor contact factor
(glass factor)
factor Xm fibrin stabilizing plasma transglutaminase
factor (FSF); J fibrinoligase .
(Laki-Lorand factor [LLFI)
(fibrinase)
... prekallikrein* .Fletcher factor
prokallikrein
... high-mqlecular- Fitzgerald factor
weight kininogen Williams factor
(HMW k i o g e n , Flaujeac factor
I-@4WK, I-rK), (contact activation factor)
(Reid factor)
(Washington factor)
A lowercase a designates the activated form of a factor, eg, 1%. .
In diagrams of coagulation pathways, activation is indicated with a solid arrow:

and action on another factor, with a dashed arrow:

.I\tlditional terms relatccl to scconcl;~r)'Iic~nost:~sis

:ire ;IS Sollows:
Tenn ~ --
Ahhrc.uiutio?z
y-glutnmvl carbosylic acid rcsiduc3 Gla residues
.JSf%

Clotrrng Factor Variants. Specific variants or abnormal forms may be named

Itx;ltlons, as follows:

factor V Cambridge
factor V Leiden
factor X San Antonio
fibrinogen Paris
protein C Vermont
prothrombin Barcelona
prothrombin Himi I
prothrombin Himi I1
Clotting factor variants that have been characterized molecularly are s~ecified
means of terms that indicate the molecular change, ie, nucleotide o
a l t e r a t i ~ nThe
. ~ abbreviations ins (insertion), del (deletion), In (intron),
and ter (termination codon) are used within such terms9 See Sequence
~ucleotiies,and Sequence Variations, Amino Acids,, in..15.6.1, Genetics, Nu
Acids and Amino Acids, for a more detailed description of such notation. Examp
factor WI Arg1689Cys or VIII R1689C ,

factor VIII Glu1987ter or VIII G1987ter

'

factor VIII Ex24-25del

A shorthand expression is permissible after the term is first defined:
The factor I1 resulting from the 20210G4A variant (mutation) in the pro-
thrombi gene (factor II ~ ~ ' ~..' 4 .

Thrombin. The protein thrombin is the end resultof the coagulation factor casca
Related terms include the following: -
a-thrombi
P-thrombi
y-thrombin
thrombin A loop, B loop, C loop, E loop, y loop
P-thromboglobulin

Heniophilias and Thrombophilias.Hemophilias are bleeding disorders. H

is associated with factor VIII deficiency, hemophilia B with factor M
hemophilia C with factor XI deficiency, and von Willebrand disease w
ebrand factor deficiency. (Factor M was the originally named Christmas facto
patient's surname. That patient went on to become an influential advocate
blood supply.5 Hemophilia B, known as Christmas disease, was re
.Christmas 1952 issue of the British ~ e d i c a l ~ o u r n aExamples
l . ~ ~ ~ ) of subtypes inclu
hemophilia A, CRM(+) variant (CRM: cross-reacting material), hemophilia B Leyd
[sic],and hemophilia Bm.

.. - -- - --

I" e.
-. ?
;
.
.
;?,
 15.7.3 Secondary Hemostasis

Thrombophilias are excessive clot-fonning disorders. One variety occur!; \virh

factor V Leiden.
See "Clotting Factor Vgiants" above for molecularly based nomenclature.

Von Willebrand Factor. Because factor V I I I , involved in coagulation, ancl \.on \\;.111-
ebrand factor (vWF), involved in platelet adhesion, form a noncovalent I~imolecul:ir
complex, they were originally difficult to distinguish biochemically and imlnuno-
logically. Original nomenclature reflected this difficulty; for instance, what was first
referred to as factor VIII-related antigen (abbreviated VII1R:Ag) was found to \>ethe
factor that is deficient in von Willebrand disease.
Factor VIII and v'WF, although functionally associated, are physiologically. ge-
netically, and clinically distinct. In 1985 the International Committee on Coagulation
and Thrombosis put forth preferred terminology that was meant (1) to distinguish
VIII from vWF and (2) to clarify exactly which entityowasbeing specified (Table 12).
The committee noted that it is acceptable to use the term VIII-vWF for the biomo-
lecular complex but not for either single component.'0."
The terms in column 1 of Table 12 are not only preferred but also familiar exactly
as shown to those conversant with the field. However, for most audiences, authors
should clarify the preferred term by including the synonym or an explanation (eg,
column 4, "Meaning") at first mention.

Von Willebrand Disease. Variants of von Willebrand disease include the following:

Type Sample Molecular ~ariants'~

J type I vWF Arg854Gln, vWF Cys1149Arg

type IIB vWF Trp550Cys, vWE Arg545Cys

type 111 VWArg1659ter, VWArg2635ter
Normandy 1 v W Thr28Met

- - - - - - -

Table 12. Factor VII and von Willebrand Factor Terminology

Preferred Synonym Old (Avoid) Meaning

factor Vlll antihemophilic VIII:C factor Vlll proteln

factor (AHF)
VIII:Aq factor Vlll antigen VIII:CAg . factor Vlll antiqen :

VIII:c factor Vlll coagulant activity

vWF von Willebrand factor VIIIR:Ag von Willebrand factor prote~n
VIIIfvWF
AHF-like protein
- -
.- .
-.. . .

vWF:Ag VII1R:Aq von W~llebfandfactor aC.ll;r-

. .. . -

ristocetin cofactor (RCoF) VI1IR:RCoF ;ST W:ll~bfdn(?

t a ~ l n rI ; ; - r : . ~ ?
VII\ R RC 0 e ddT\
3 Jlr.?: ICT-;)';,'~.. ' -(j
VlllR vVJF , ,, ::,,. .. ::I .;;r ,- !L.; ,,..,..-,, ,.
15.7 Hemost

Nomenclature for sequence Valiants (mutations and polynlorphi: U) of

gene is indicated according to Sequence Varia~tions,Nuclleotide and
Variations, Amino Acids, in 15.6..1, Nucleic Acids and Amino Acids. S a h 1
the following exalnples13:

f
1234G>A adenine substituted for guanine at position 1234 in VWF
cDNA sequence
:j
g1234G>A as above, in complete VWF sequence
1234insN nucleotide insertion after nucleotide 1234 in lrWF
CDNA sequence
#
1
R123G glycine substitute for arginine at position 123 in pre-pro
VWF sequence .i?
R123del arginine deletion at position 123 in pre-pro WCrF sequence
1234A/G adeninelguanine polymorphism at position 1234 in
W T cDNA L

Inhibition of Coagulation and Fibrinolysis

Inhibition of Coagulation. The following sample terms are included for referenc
Expand at first mention in accordance with 14.11, Abbreviations, Clinical, Technic
and Other Common Terms.

AAT
AMG
antithrombin 111 A m
a-ATIII isofom ci-ATm i L

p-Am1
ATIII/heparin complex ...
C1 inhibitor C1 INH (see also 15.8.3,
Immunology, Complement)
heparin cofactor II ...
lupus coaplation inhibitor (also LC1
called lupus anticoagulant)
protein C ...
activated protein C APC
protein S ...
protein Z ...
serpin (serine protease inhibitor) ...
tissue factor pathway inhibitor TFPI i

B
Note: Protein C was named for an investigator's chromatographic fraction C in whid
it was discovered. The S in protein S refers to Seattle, where it was discovere3
Protein S is not the same as S protein; see also 15.8.3, Complement.
 15.7.4 Inhibition of Coagulation and Fibrinolysis

Fibrinolysis (Fibrin Degradation, Clot Degradation, Thrombolysis). The following

sample terms represent entities that take part in fibrinolysis or its inhibition. Expand
at first mention in accordance with 14.11, Abbreviations, Clinical, Technical, and
Other Common Terms:
Term Abbreviation
a2-plasmin inhibitor, a2-antiplasmin a2PI
aminocaproic acid (amicar) ACA
EACA
dirnerized plasmin fragment D D-dimer
fibrin degradation products or fibrin FDP or FSP
split products
Glu-plasminogen (see also "Amino Acids"
in 15.6.1, Genetics, Nucleic Acids and
Amino Acids)
Lys-plasminogen (see also "Amino
Acids" in 15.6.1, Genetics, Nucleic Acids and
A n k o Acids)
a plasminogen activator inhibitor PAI- 1
protein C inhibitor PAI-3
thrombin-activated fibrinolytic inhibitor TAFI
tissue plasminogen activator (when a @A
specific therapeutic formulation of tPA is
intended, use the USAN t e r n see 15.4,
Drugs)
tPA receptor
urokinase or urinary plasminogen
activator
uPA receptor uPAR

Tests of Coagulation. Two among several tests of coagulation are the prothrombin
time (PT)and the partial thromboplastin time (PTT). When the more common ac-
tivated partial thromhoplastin time (aP'IT) is used instead of the PTT,this shoultl I>c
specified.
~raditionally,the prothrombin ratio (PTR) had been reported as a ratio of the
patient's PT to the mean laboratory control PT. Reporting the PTR has been refinkd 1)s
use of a modified PTR, the international normalized ratio (INR).'~-"In accordance
with a 1985 policy statement of the 1nternation;ll Committee for Throtnl,osis ;ind
Hemostasis and the International Committee for Standarrlization in l-lcrn;~rolo~!..' '
;iuthors ;Ire encoilragccl 10 report the INR if ;it :ill possible. IJnlike conversions Iw-
tween conven[ion;il ;~ndSI units 18.1, Units o f Me;~sure,SI Units), thcrc is no
simple conversion f:rctor from t h I'~TR to the INR since the international sensiti\.ity
asis

inder; (IS11 of the thromboplastin used in the actual assay performed must be kno
The INR is calculated as shown:
INR = PTR'~'
Authors should speclfy the exact method by which their results were initial1
reported by the laboratory performing the assay and the method of conversion,
any, used o n the original results.

REFERENCES
1. Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ. Overview of
hemostasis. In: Colman RW, Hush J, Marder VJ,Clowes AW, George JN, eds.
Hemostasis and Z?Irombosis:Basic Principles and Clinical Practice. 5th ed. Phila
delphia, PA: ' ~ i ~ ~ i n cWilliams
ott & W i ; 200153-16.
2. Handin RI. Bleeding and thrombosis. In: Kasper DL, Braunwald E, Fauci AS, Hau
SL, Longo DL, Jameson JL,eds. Harrison's Principles of Internal Medicine. 16th e
New York, NY:McGraw-Hill; 2005337-343.
3. Stedman's Medical Dictionary. 27th ed. Baltimore, MD:Lipp
willcin s;2000.
4. Owen CA Jr. A Histoty of BIood Coagulation. Rochester, MN
Education and Research; 2001.
5. Giangrande PL. six chamcters in search of an author: the history of the nomenda
of coagulation factors. Br J Haematol. 2003;121(5):703-712.
6. Biggs R Human Blood Coagulation, H-&, and i%mmbosis. 2nd ed. 0
England: Blackwell Sdentific hblicationq 1976:15-16.
7. Blomback M, Abiidgaard U, van den Besselaar AM, et al. No
and units in thrombosis and haemostasis (recommendation 19
projea. of the Scientific and Standardization Committee of the
on Thrombosis and Haemostasis (ISTH/SSC) and the C
Quantities and Units (in Clinical Chemistry) of the Inte
Applied Chemistry-International Federation of Clinical
CQUCCD. Zbtvrnb Haemst. 1994;710:375-3%.
8. ISTH: The International Society on Thrombosis and Haemostasis Web site
GrouplLiaison Reports. http://wvm.med.unc.edu/isth/welcome. Accesse
16, 2006.
9. Peake I, Tuddenharn E. A standard nomenclature for factor VIII and fac
mutatioris and assoqhted amino acid
committee on Factor VII
' 10. Marder VJ,Mamucci PM, Firkin BG, Hoyer LW, M
factor VIII and von WiUebrand factor: a -rec
Committee on Thrombosis and Haemostasis. n m m b Haemat. 1985;54(4):87
11. Marder VJ, Roberts HR. Proposed symbols for factor VIII and von Willebrand
[letter]. Ann Intern Med. 1986;105(4):627.
12. OMIM. Online Mendelian Inheritance in M
/entrez/query.Pcgi?db=OMIM. Updated D
2006.
13. Goodeve AC, Eikenboom JCJ, Ginsburg Dl ei al. A standard nomenclature for
Willebrand factor gene mutations and pol
Factor Subcommittee of
International Society on Thrombosis an
. .

. .- -
 15.8.1 Chemokines

.edu/isth/SSC/communications/von~willebran/fnomen.pdf. Postrd Ocrc,l,c.r

30, 2000. Accessed March 16, 2006.
14. Loeliger EA. ICSH/IClX recommendations for reporting prothroi~~bin ri~nc.in c1r;tl
anticoagulant control. Tbromb Haemost. 1985;53:155-156.
15. Hirsh J, Dalen JE, ~ e i k i nD, pollei L. Oral anticoagulants: mechanism of acricln.
clinical effectiveness, and optimal therapeutic range. Cbest. 1392:102:312S-~ZO~.
16. Hirsh J, Poller L. The international normalized ratio: a guide to understancling ; I I I ~ ~
correcting its problems. Arch Intern Med. 1994;154(3):282-288.

Immunology

Chemokines. ~hemokinescomprise a family of about 40 low-molecular-weight cy-

tokines (see 15.8.4, Cytokines) with important roles in the immune system, as well :is
functions beyond The name chemokine,a contraction of "chemotactic cytokine."
reflects the common property, by which chemokines were originally identified, or
promoting leukocyte chemotaxis.
Chemokines are classified into 4 subfamilies, based on their cysteine (C) residues
and other amino-acid (XI residues (see 15.6.1, Genetics, Nucleic Acids and Amino
Acids):
Q[C 1 amino-acid residue between the 2 N-terminal cysteines
CC N-terminal cysteines adjacent
XC cysteines I and 3 not present
CX3C 3 amino'acids between the cysteine residues
Examples of specific chemokines, by subfamily, are shown below:
Subfamily
Name Synonym ~xampk? Receptors
1 -
Name anti' Abbreviation
CXC a class CXCLl growth-related on- CXCR2
cogene a (GRO-a),
melanoma growth
stirnulatory activity
protein (MGSA)
CXCL4 platelet factor 4 (see
15.7, Hemostasis)
CXCL5 epithelial cell- CXCRZ
derived neutrophil
attractant 78 (ENA-
78)
CXCI.6 granulc~ytc . CXCKI,
~lierno;~trr:~ct:int CXCR2
protibin 7 I(;CI'-.?)
15.8 Immunology

Subfamily
Name S'otzym &ample?
1 -
Name and Abbreviation
CXCL14 chemokine isolated
from breast and
kidney tissue
(BRAK), bolekine
CC p class CCLl inducible 309 (1-309) CCR8
CCL3 macrophage inflam- CCR1, CCR5 -
matory protein l a
or lct (MIP-la)

tion of normal T
cells expressed and calledCD195;
secreted ( W S ) see 15.8.2,

tactic) protein 3
(MCP-3)
CCL21 secondary lymphoid CCR7 (also
tissue chemokine called
(SLC), chemokine CDwl07;

y class XCLl - lymphotactin,

activation-induced,
T-cell-derived, and
chemokine-related

CX3C 6 class CX3CL1 fractalkine

Expanded common names of the chemokines are often unwieldy and uninformative
and so are rarely used, though use of the abbreviations persists. Terms such as those .
in the tabulation above for chemokine, chemokine subfamily, and chemokine re- \

the CXC chemokine family

the chemokine CXCLl
chemokine receptor CXCR2

678
 15.8.2 CD Cell Markers

A useful reference on chemokines is the Cytokine Family Dat:tbase (dl)CFC):

http://cytokine.medic.kumamoto-u.ac.jp.6

CD Cell Markers. Clusters of differentiation (CDs) are a system for identifying cellular
surface markers, a number of-which define lymphocyte subsets (see 15.8.7, Lym-
phocytes).7-'2 The system and its nomenclature were formalized in a 1982 internat-
ional workshop. Originally CD terms specified the tnonoclonal antibodies (mAl~s)
that clustered statistically in their reactivities to target cells. More recently, the CD
terms apply to the cellular molecules themselves. The CDs, which now number more
than 200 (and may eventually number in the thousands1'), are defined a; the Human
Cell Differentiation Molecules workshops (formerly Human Leukocyte Differentia-
tion Antigen Workshops). Workshops involve "multiple laboratories examining
coded panels of antibodies [with] multilaboratory blind analysis and statistical eval-
uation of the Although reactivity and cellular expression originally
were key in identify~ngCDs, gene-based molecular relatedness has become an im-
portant
See the Human Cell Differentiation Molecules Web site (http://www.hlda8.org)
for updates o n the most recent workshop and conference, including confirmed,
validated antibodies and newly assigned CDS.'~
Some CDs are Itnowri most commonly by their CD designation. Other molecules
have been assigned CD numbers retroactively; although they will be referred to by
their common names, it is useful for authors to include the CD designations." Terms
related to CDs do not need to be expanded. See the following examples.
CD T m Other ~arne(s)'~
CDla
CD3d CD3 complex
CD4 (see also 15.8.7, Lymphocytes)
CDb
CD8a (see also 15.8.7, Lymphocytes)
CALLA (common acute lympliohlastic leukenii:~antigen),
neprilysin;,enkephalinase;membr~nemctalloendopepti-
dase
FcyRIIIa (an Fc receptor; see also 15.8.6, Immunoglobulins)
C3b/C4h rcceplor; cotnplcmcnt receptor type 1 (Cltl; scc
also 15.8.3, Complement)
glycoprolcin IIh (scc :tlso 15.1.2, I'l;~tclct-Spccifc AnIigcnsJ
CD44 variant; CD44vl-10
membrane cofactor protein (MCP; see also the "Comple-
ment Regulators" section in 15.8.3, Complement)
intracellular adhesion molecule 3 (IChM-3)
delay accelerating factor (DAF; see also 15.8.3.
Complement)
P-selectin; granule men1br:tne protein-140 (GhlP-140)
Iga (see also 15.8.6, In~rnunog101~11lit~~). All3-1
i5 . 6 Inin>unology

<-',!I Pnrr\ Orht.r , ~ ~ ms~"

cf
CI>97 UL-KDD/FlZ
CD107a lysosornal-associated membrane protein 1 (LAMP-1)
CD l2Oa tumor necrosis factor receptor (TNFR) type 1;
TNFR p55
6~139
CD195 CCR5 (see 15.8.1, Chemokines)
CD213a2 IL-13Rr2 (see also the "Interleukins" section in 15.8.4,
Cytokines)
CD220 insulin receptor
CD235a glycophorin a
CD240CE Rh blood group, CcEe antigens (see also 15.1.1, Bloo
Groups)
A lowercase w (for "workshop") signifies a cluster (which is
become final, and have the w dropped, in an upcoming workshop1'):
CDw186
The new designation of CDw128A is CD181.
Complexesof more than 1CD molecule are indicated with a forward slash
CDlla/CD18 (leukocyte functional antigen 1 [LFA-11)
CDllb/CD18 (CR3 or C3bi receptor; see 15.8.3, Complement)
CD49qCD29
The CD nomenclature displaced previous terms, eg, CD8 for T8 or OKT8, CD4 for
or OKT4, CD5 for Leu-1, Lyt-1, CD5 for TI.
For therapeutic monoclonal antibody nomenclature, see 15.4, Drugs.

.s
It is estimated that one C3b dqmited on an organ-
ism can becomefour million in about 4 min.
M . K . Liszewski and J. P. ~ t k i n s o n ' ~ ~ ~ ~ ~ )

Complement. The term complement refers to a group of serum protein

sequentially and rapidly in a cascade that produces molecules providing resistance
The system was named in 1899 for its complementari
bodies in destroying microbes.''
Current nomenclature.derives largely from the 1968World Health
Bulletin "Nomenclature of ~ o r n ~ l e r n e n with
t , " ~subsequent
~ modifications as
anisrns of action were further elucidated.
Three complement activation pathways are recognized: the clas
(activation by antibody), the alternative pathway (despite the name, the more
logenetically ancient), and the lectin pathway. They culminate in a common t
pathway. Components of the classical and terminal pathways are designated
and a number, reflective of the order of discovery of the component

. .

?
,
---.
.- . .- -$Y
 15.8.3 Complement

reaction sequence. (The prime, as in C', has been discontinued.) Letters and ab-
breviations other than C typify the components of the other pathways. Complement
component terms need not be expanded:
Path way -. Components
classical C1, C4, C2
alternative factors D, B, P (P for properdin ["destruction-

Lectin or MBLectin mannose-binding lectin (MBL), MBL-

associated serine protease 1 (hL4SP-I),
MASP-2, MASP-3
terminal C5, C6, C7, C8,C9
C3 (common to all pathways)

Fragments. Appended lowercase letters indicate complement fragments. Usually, a

lowercase b indicates the larger, active (membrane-binding) fragment and a low-
ercase a, the smaller, release fragment (released on cleavage of the parent molecule).
However, C2 is inconsistent: C2a is the larger active fragment and C2b the smaller
release fragment. Other letters represent fragments of b fragments.
C3a C3b C3c C3d Cdg C3f
C4a C4b C4c C4d
C5a C5b .

Bb

Subunits. The subunits of C1 are as follows:

Clq Clr Cls
Various notations combining the C1 subunits convey the stoichiometry (relative
quantities of subunits) of the complex; all such styles are acceptable:

Isotypes of C4 have capital letters appended:

Protein chains have Greek letters appended:

<%a

OY
(:ja is the a chain of C3.
Cleavage of C3a produces C3a and C3b.

681
15.8 Immunology

An i signifies inactive f o m :

Complement components that form a complex are written in a series without spaces:
C4b2a3b
C4bC2
Sometimes a hyphen is used to indicate a series:
C5b67 or C5b-7
C5-9
An asterisk shows nascent or metastable state:

C5b-7' t:
>5l

Convertase complexes are linked complement fragments that activate other COG
plement components. For example, the conveqase that activates C3 is known as C3
convertase. As in the following examples, the convertases have different c ~ m p d ! . ~
tions, depending on which complement pathway generated them:

Pathway ~ l m n u t i v ePathwr
C3 convertase C4b2a C3bBb

C5 convertase C4b2a3b C3bBbC3b

(C3b)2Bb
(Note: Occasionally,authors have changed the designation of the activated moiety
C2 from C2a to C2b, to be consistent with other complement ~om~onents.'~~'~(P",'
tipoff to the change is the designation of classical pathway C3 convertase as C4b21
A bar over the suffix was' proposed in 1968 to designate activated compleme
eg: a

but this convention has fallen from use.

:$
Complement Regulators. Complement regulators include the following: :i
Name Other T m
C1 inhibitor (C1-INH) C1 esterase inhibitor, C1 esterase ;
INH L

C3 membrane' proteinases
 15.8.3 Complement

Name Other Terms

C4 binding protein (C4bp)
carboxypeptidases
CD59 me~nhraneinhibitor of reacri\/c
lysis (MIKL), membrane att:~ck
complex-inhibitory Factor (MACIF).
homologous restriction factor 20
(HRF20), P18, protectin
decorin
delay accelerating factor (DAF) CD55
factor H formerly PIH
factor I Detter I, not roman
numeral "one"]
factor H-Like protein (FHL-1)
membrane cofactor protein (MCP) CD46
S protein* vitronectin

PNot che same as protein S; see 15.7.4, Hemostasis, Inhibition of Coagulation and
Fibrinolysis.)

complement Receptors. Complement receptors include the following:

Name Other Temzs
-- --
complement receptor C3b receptor, CD35
type I (CR1)
C3d receptor, CD21, CD21S (shod
isoform). CD21L (long isoform)

cClQr collectin receptor; c prefix: collagen region of Clcl

gClQr g prefix: globulnr head portion of Clq
ClqK,
factor H receptor (fH-K)
 -.-.
15.8 Imn >logy

Cytokines. Cytokines are proteins or glycoproteins produced after stimulation (su

as activation of immune cells) that act at short distances in very low concentrations
produce various effects, such as immune and inflammatory reactions, repair pro-
cesses, and cell growth and differentiati~n.~.'~~~ Each cytokine has multiple effects
and overlaps with other cytokines, including structurally dissimilar ones, in those:
effects. The multiple effects (pleiotropy) are explained by th
receptors on a wide variety of cells, and the overlap (redu
similarities of the intracellular portions of cytokine receptors.
Cytokines were originally named by function. Because
overlapping fun~tions,'~ the interleukin n~menclature'"~~ was proposed to simplrfy
terminology of this major class of cytokines and, it was hoped, subsequent regulatory
immune system proteins. The more recent grouping of cytokines by receptor families
and signaling pathways, however, does not necessarily correspond to previous f
groupings; eg, the interleukins fall into more than one family. i1
E
Cytokine Families and Subfamilies. Molecular similarity of cytokine receptors has
resulted in their grouping into families and subfamiliesz6:
.
chemokine families (see 15.8.1, Chemokines)
interleukin l/toll-like receptors (a-l/TLR)
platelet-derived growth factor family (PDGF)
receptor tyrosine kinases
transforming growth factor CTGF-j3) receptor serine kinase family
tumor necrosis factor 0
type 1 (hematopietins)
PC-utilizing(common cytokine receptor j3 chain)
y,-utilizing (common cytokine receptor y chain)
gpl30-utilizing
heterodimeric
homodimeric
type 2 (interferons; IT.-10 family receptors)
heterodimeric
Cytokine signaling pathways are assodated with the families and subfamilies. .
Cytokine Signaling Expansion or Origin Associated Cytokine ,
Pathways &~enn
caspases TNF ;.I
FADD Fas-associated death domain TNF
-3
.,
FAST- 1 forkhead activin signal trans-
ducer kinase family
IRAK IL-1 receptor-associated ILl/TLR .. .-.
:. .
..

kinase
Jakl Janus kinase 1 type 1
Jak2 Janus kinase 2 type 1
Jak3 Janus kinase 3
 15.8.4 Cytokines

Cytokine Signaling Expansion or Origin Associated Cytokine

Path ways of Tern Family
MyD88 myeloid dfierentiation IL- 1/TLR
marker ,

NF-KB nuclear factor KB IL-I/TLR

Ras/Raf/MAPK ras protein, raf protein (see type 1, receptor
also 15.6.3, Oncogenes and tyrosine kinases
Tumor Suppressor Genes),
mitogen-activated protein
kinases
SARA SMAD anchor for receptor TGF-P receptor serine
activation kinase family
SMADs mothers against decapenta- TGF-P receptor serine
plegic (dpp) signaling (MAD) kinase family
in Dmsophila and Sma genes
from CaenorhabditZselegatd9 '

STAT1 signa? transducer and activator type 1

of transcription 1
STAT2 type 1
STAT3 type 1

STAT6 VPe !
TAKl TGF-P-associated kinase TGF-'p receptor serine
kinase fazily
TRADD TNF receptor-associated death R\IF
domain
TRAFs TNF-a receptor-associated TNF
factors.

Tyk2 tyrosine kinase 2 type 1

The pathway terms need not be expanded, but context should I,e clear ai first
mention, eg:
the Jakl signaling pathway ,

Chemokines. See 15.8.1, Chemokines.

Colony-Stimulating Factors. C ~ ~ ~ n y - s t i m u l ;facrors

~ r i n ~ (CSFs) 3t1rnl1l.11~ ,crcl\\~l:. I I I ( \
differentiation of 1 or more blood cell types (ncr~trol,I~iI\. r . o \ l n o l ~ l ~ ~111,
l \ . )no( \ I ( . ,
rnacrophages).~erlnsoftenindude the Ic.rrcr\ $1:. 1 , 1 1 1 not . I ! \ \ - . I \ \ , c.: I I I I C . I ~ L . I I \ ~ I ~ I . <. I
xnd 5-IL-3, IL-4, 1~-'j-wtlich :Ire : I ~ O( ~ I : . JI ~ ~ ~ . I I I (( 51-
I I C ~ I I I. I, I I'II\I I I I C , I I I I , ~ , I
 granulocyte-macrophagecolony-st~mulatingfactor GM-CSF , ,4
11
'r
granulocyte colony-stimulating factor G-CSF I

macrophage colony-stimulating factor M-CSF I

Hormones. These hormones are also considered cytokines:

I
erythropoietin Epo
growth hormone GH _I;
..:t
leptin I>
<
prolactin PrL l::.T-, dI
, ;S$
thrombopoietin Tpo

Interleukin cytokines arere designated as interleukins in 1978 for "the

ability to act as communication signals between different populations of leukoq 7 -

t e ~ . ~The ~ interleukins
~ ~ ( ~ have
~ ~other
~ ~biological
) effects as well. Their nome?;
clature was formalized in 1991.'~Thev are designated by number in order pf
discovery, eg, interle m 1, interlei
structural Ior function .elationship
efp:
recognized as members of larger &okine families, they retain their original d 'i.
nations. Specific interleukins are mentioned most commonly in their abbremat+
form (note hyphen): 1;
IL-1 Q
IL-18
IL-29
i

The IL-1 family includes 2 forms of IL-1:

IL-la
4
- b

IL-1p , a&
and the IL-1 receptor antagonist:

Receptors for interleukins are designated, at minimum, with the interleukin nar
plus a capital R, eg:
K-2R
IL4R
Receptor names designating subtypes may be even more specific:

-1
Greek letters are used for subunits (chains) of the same receptor:
iq
. IL-2Ra IL-2RP .3,
 15.8.4 Cytokines

Terms for interleukins from different species should be expanded ar ti I-stmention:

human IL-2 hIL-2
mouse IL-4 mIL-4
viral IL-10 vIL-10
For terminology for therapeutic interleukins, see 15.4.13, Drugs, Nomcnclat~~rc.
for
Biological Products.

Interferons. Interferons (IFNs) are another group of cytokines, origin:~llydi.sco\~c.~.c.cl

(and named) because of their interference with viral replication.
The type I IFNs, also known as antiuira[ interfemm, are as follo\vs:

Type I1 IFN, also known as' immune interfemn, is

For terminology for therapeutic interferons, see 15.4.13, Drugs, Nomenclature for
Biological Products.

Other ~'tokines. Other cytokines include the following:

cardiotrophin 1 a-
I
ciliary neurotrophic factor CNTF
endothelial growth factor EGF
FLT-3/FLT-2 ligantl I:I.
high mobility group I,ox 1 IMCil3- 1
ch'romosomal protein 1
leukemia inhibitory factor 1.1 1:
lymphotoxin a I ,'l.u
oncostatin M OSM
receptor activated nuclear RANKL
factor-KBligand
stem cell factor SCF, c-kit ligand
tansforming growth hctor P 'I'GFB, TGFP1, TGFP2, TGFP3
tumor necrosis factor u TN 1:-sr
tillnor necrosis factor p TNF-P
15 8 Immunology

B
111ri rrrr?uphtrrurion,Hisrocon~paribilityLeads to
Acceptat~ce;in anthropology, Human populations
are Located by Allelic variation; in disease, HLA
alleles in Linhge d&equilibriumAccount for dis-
ease... .
Julia G. ~ o d r n e l ~ ~ ( ~ ' )

as red blood cell antigens determine blood type (see 15.1, Blood Groups,
Antigens, and Granulocyte Antigens), HLA antigens determine tissue type.
HLA antigens were discbvered to be determinants of the success o
transplantation (histocompatibility, h&to- meaning "relating to tissue?. The
subsequently found to be critical for activating many immune responses, and
HLA antigens are associated with particular diseases. Because of the great
ambng individuals in .these antigens (polymorphism), they have been use
rensic identification.

cially named by 2005.~' The magnitude of this polymorphism distinguishes'

system from other gene families and has resulted in a detailed system for

these alleles consistent with the International System for Human Gene N

688
 15 8.5 HLA Major Htstocompat~b~ltty
Complex

HLA applies both to the antigens on cells and to the loci (klHC) on the hum:ln
genome responsible for those antigens. The tern1 Mhc is used ir. nonhuman a n i n ~ ~ l s '
(see the "Animals" section below).

HLA Class I Antigens (Class 1-MHC Antigens). The chss I antigens art. as follo\vs:

classical: HLA-A HLA-U HLA-C

nonclassical HLA-E HJA-F HJA-G
(or class Ib):
The components of a class I MHC nlolecule include the following:
a chain or heavy chain (coded in the MHC) doinains: a,, a,, a3
P2 chain (PZ microglobulin; coded on chromosome 15, not on the MHC)
HLA Class I1 Antigens (Class I1 MHC Antigens). The class I1 antigens are as follows:
classical: HLA-DR HLA-DQ HLA-DP
nonclassical: HLA-DO HLA-DM
(DR originally signified "D-related"; the others were named alphabetically,)
The components of a class I1 MHC molecule include the following:
a chain domains: al,a2
p chain domains: Dl,P2
(Note:The a and P chains of class I and class I1 molecules are not identical, despite the
similar naming convention, but rather are distinct proteins.)

Serologically Defined HLA Antigens. Antigen specificities of the major HLA loci are
'
indicated with numbers following the major locus letter(s), eg:
HLA-A1 HLALC27 HLA-DR1
A w (for "workshop") is used for 2 specificity groups:
HU-C (to distinguish the C antigens from complement), eg, HLA-Cwl
HLA-Bw4 and Bw6
Parenthetical numbers indicate subtypes or "splits" of a given serologically defined
antigen: .
HLA-A23(9) (A23 is a split of AS))
HLA-A24(9) (A24 is a split of A9)
HLA-B49(21) 0349 is a split of B21)
HW-CW~(W~) (Cw9 is :I splitof Cw3)
t-11~-~~14(6) (DR14 is a split of DR6)
t-l~\-DQ7(3) (DQ7 is a split of DQ3)
1ology

The term cross-reactive group (CREG) refers to xrologically related groups of

gens. The abbreviation should be expanded at first mention. Note the folio
sample terms:
the HIA-A1 cross-reactive group (CREG)
the HIA-A2 CREG
the B5 cross-reactive group HLA-B51, B52, and B53
B7 CREG
Phrases such as the following may be used:
HLA-A, HLA-B, and HLA-C associations
possible associations with HLA-B18 and HLA-A2, and HLA-DQB1
testing fo; HLA-A (A2, A 2 0 and HLA-B (B35, B44)
high prevalence of HLA-A1 (63%) and HLA-B8 (42%)
frequencies of HLA-A2 and A29

HLA Haplotypes. The HLA haplotype is theset of HLA alleles on 1chromo

person possesses 2 such haplotypes, 1from each parent, and thus has 2 HLA
determined by each major locus, ie, 2 HLA-A antigens, 2
HLA typing is performed serologically, antigen specificities of the indiv
. .
norype are presented as follows:
Phenotype . Not& ..

A3, A23, B51, B7, Cw2, Cw5, all antigens listed colle
DR7, DRll
A23, B7, Cw5, DR7/A3, B51, virgule separates anti
Cw2,.DR11 chromosome from
chromosome
A3, A23, B51, B7, Cw2, ~ w 5 , hyphen indicates undeterinined
DR11,- antigen
Al, B8, Cw4, DR17(3)/A2, DR for this haplotype not typed
B27, Cw5,- -. or untypable
Al, B8,Cw4, DR17(3)/A2, 2 identical DR specificities
B27, Cw5, DR170
Shorter haplotype expressions are shown below:
HLA-Cw6-bearing haplotype
the Al-B8-DR3 haplotypes
DRB1, DQA1; and DQBl haplotypes
A25 B18 BFS DRll haplotype

Other Histocompatibility Loci. HLA antigens represent only so

the MHC. Others, also important in immunity, are as follows:

-. . --- . .. *. - ..-.--
 15.8.5 HLA/Major Histocompatibility Complex

Class I loci
MIC (MHC class I-related chain)
specificities: MICA, MICB, MICC, MICD, MICE

C f m I1 loci
TAP (transporter associated with antigen processing)
specificities: TAPI, TAP2
PSMB (proteosome-related sequence)
specificities: PSMB8 (formerly LMP7), PSMB9 (formerly LMP2)

Class IZI loci (loci for 4 components of complement; see also 15.8.3,
Complement):
C2
C4 - ?
Bf (B factor, properdim)
A haplotype of complement types is called a complotype, eg:
BfS, C2C, C4AQ0, C4B1
(QO designates a deficiency.)

Genetic and Allele Nomenclature. Use italics to distinguish HLA genes or gene loci
from protein products, eg, HLA-A, HLA-DRBI (see also 15.6.2, Genetics, Human
Gene Nomenclature). HLA alleles are distinguished from HLA antigens by their
names, eg, the HLA-A1 antigen is coded by the HLA-A'0101 allele. The hyphen is
retained in HLA gene expressions, an exception permitted in officjal gene nomen-
clature. Terms with asterisks indicate that HLA typing has been performed by mo-
lecular techniques. Terms with 2 digits (eg, A'02) indicate antigen typing with known
serologic equivalent. Terms with 4 digits (eg, A'0201) represent alleles. In contrast to
other alleles, HLA alleles are usually not italicized. Authors should make clear from
context whether the gene or its product is being discussed.
The following tabulation, adapted from ~ a r s h , summarizes
~' nomenclature for
HLA designations:
Change Fmw!
Previous Nomen- Former Term
Tern Indicates cfatrrre(If Any) (If Any)
HLA HLA region, prefix
for HLA gene
HLA-DKB1 or a particular HLA
n ~l n locus. ic, D R U l (13
refers to the P-chain
locrls. \tard~rrc-rl\
I>clon t.ll>r~l;~t~on
\
15.8 Immunology

Cbatige Fmnr
PreYious h'omrti-
Term Indicates clature (If Any)
HLA-DRB1.13 a group of alleles at
the DRBl locus that .
encode the DR13
antigen (antigen
conferring DR13
specificity)
HLA-DRB1'1301 a specific HLA allele,
ie, DRBla1301
HLA- a null (N) allele
DRB1'1301N
HLA- 5th and 6th digits 5th digit only (2)
DRB1*130102 (02) indicate-synon- for synonymous
yrnous mutation mutation
HLA- allele with mdtation
DRB1*13010102 outsideadingregion
HLA- null allele with .
DRB1'13010102N mutation outside the
coding region
HLA- low expression (L)
A'24020102L
HLA- secreted (S) new as of 2002
B'44020102S report
cytoplasm (C) new as of 2002
report
aberrant (A) new as of 2002
expression report
HLA-Aa3211Q unconfirmed, ie,
questionable (Q)
effect of allele with
mutation
sHLA-G'0101 soluble (s) form
I I I H L A - G * ~ ~ ~ ~membrane-bound
(m) form
For the HLA-D region, the gene name includes a letter for the cha
codes for (A for a, I3 forP),
often followed by a number for the cha
domain number, as described in the previous section on class I and
cules). For instance,
DRBl gene for first DR P chain
DQAl gene for first DQ a chain
The HLA prefix (including the hyphen) may be dropped from allele
:.pries after first mention, eg:

- -.-. -. . - _.- .. .. <.. ," a

. -.
 15.8.5 HLA/Major Histocompatibility Complex

comparative frequencies of HLA-DKl31'14, DQA1'03, DQA1.05, DQ~1.01,

DQB1806
(not: HLA-DRB1'14, -DQA1103, -DQA1805, -DQA1801, -DQBI*O~)
The conjunction a n d may be used to separate haplotypes but is not used before the
final element in any single haplotype:
HLA-B38, DRB1'0402, DRB4'0101, DQB1*0201, DQB180302 [not and
DQB1'03021
HLA-B38, DR13180402, DRB4*0101, DQB180201, DQB110302 and HLA-B80702,
DRB1'1601, DIU35'02, DQB180502 haplotypes
The portion of the tirm before the asterisk may be dropped in a series, provided it
would be the same in each term:

Commas signify and, and virgules (forward slashes) signify or.39 Thus, commas
indicate correspsnding alleles from chromosome pairs (see the "Haplotypes" section
above), eg:
Donor: A'01, 02; B'08, 44; DRB1'01, 03; DRB3.
Recipient: A802, 11; B*40, 15; DRB1'09, 11; DRB3, DRB4
Virgules (forward slashes) indicate an ambiguous result ib HLA typing, eg:
Tern Meaning
-
A*0201/0203/0205 A'0201 or A'0203
(also A'0201/03/05) or A'0205 is present

Serologically defined antigens and the corresponding alleles may or may n o t he

.structurally similar and therefore may or may not be numeri~allysimilar.'- Also.
alleles not defined serologically way have no known associated antigenic spec-ilicity:
Spcijicity Allele Name --
A203 A80203
B78 B87801, B8780201, B'780202'
B65(14) B81402
B50(21) B'5001
DR53 DRB4 (various, eg, DIiU4'0102. '010303)
none the E alleles (E80101, 0102, etc)
none the F allele PO101
none the C alleles (G'010101, 010102, etc)
HLA pseudogenes (see also 15.6.2, Genetics, tlul~lanGene N i ~ r n c n r ~ I ; ~ rJurrcr , c ~ ~,Ic.
~l
and are located near the HLA loci but are not transcribed to proclilr,~-I ~ I I III C OILI~

products. The class I pseudogenes entl in letters after G. and the cl;15.; II IN.IICI~ ,s~,l>~-.

end in numbers after I:

 HLA-DRB2 HLA-DRBG HLA-DRBG HLA-DRB8 HLA-Dm
HLA-DQA2 HLA-DQBZ HLA-DQB3 HLA-DPA2 HLA-DPBZ

Animals. In animals, major histocompatibili~locus is abbreviated Mhc, using U$

percase and lowercase.
The names for the Mhc in other animals4' usually correspond to the expression
HLA for humans (but not always, eg, the protovpical mouse locus, H-2). In this
convention, the name is based on a common name or species name combined with
LA (leukocyte antigen):
cat FLA
dog DLA
domestic cattle BOLA
domestic fowl B
guinea pig GPLA
.horse EqLA
mole rat Srnh
mouse H-2
Pig SLA
rabbit RLA
rat RT1
Primate researchers use an alternative style based on the genus and species
(see 15.14, Organism and Pathogens), which substitutes Mhc for LA.& Note the
following examples:
Common Animal
Name Species Designation Mhc T m
chimpanzee Pan troglodytes MhcPatr
gorilla Gorilla gorilla MhcGogo GoLA
orangutan Pongo pygmaars MhcPopy
rhesus macaque Macaca mulatta MhcMamu RhLA

B.
. . . the antibody in serum b a mixture of perhaps
100 million slight@d f l m n t types of molecule . . .
.
J. H. L. Playfair and B. M. Chain41Cp38)

Plasma cells can release up to 2000 antibody mole-

cules per second . . .'
41Cp43)
J. H. L. Playfair and B. M. Chain

You are the antibody.

Smash Mouth

,. .. . -- . . .." "
..
Immunoglobulins. Immunoglobulins are the glycoproteins that constitutt. :unrilx)tl-
ies. They were first recognized by serum electrophoresis ;mi, I>ecausc rllc.!. \\.c.rr
localized to the electrophoretic gamma zone, were originally referrccl ro ;la
y-glob~lins.4247
The term immunoglobulin and terminology for immunoglobulin c.las..;c..;\\.c>rc.
put forth in the 1960s.~"~'The use of the abbreviation Ig (pronouncecl Ieyc-gcc.l'.' ) in
preference to y was suggested to avoid confusion with tlie IgG heavy chain, y;' (see
the "Heavy Chainsn section below). The class of immunoglobulin molecules most
abundant in serum was named IgG, the G deriving from the electrophoretic g;lllilna
mobility. The M in IgM originates in an earlier designation as a niacroglol>ulin.
The 5 classes of immunoglobulins, from most to least abundant, are as follo\\.s:
Class
- Oiigin of ~ a m e ~ ~ . ~ ~
IgG gamma electrophoretic mobility
I@ from PZA-globulin,later a-immunoglobulin
IgM macroglobulin
IgD ' "process of e~imination""'~': B reserved for mice,
C had no Greek equivalent
IgE E-reactive antibody associated with erythema of allergy
Each can b e found either on a cell surface (where it serves as an antigen receptor) or
-intissue fluids such as blood (where it serves as a protective antibody).
Figure 7 shows schematically the basic structural unit of all immunoglobulin
molecules, including many components defined herein. An immunoglobulin cah be
composed of 1 such unit (monomer) or more.

Figure 7. Basic structural unit of

immunoglobulin molecules. Adapted jrom
Haynes and Fauci by permission of THe
McGraw-Hill C~mpanies.'~

I:,nzymc clcav;~g~;lncl ;~nliln)tlycngitii.erin~~.c.sultin I'~:tg~ncnrs

01' llic. itii~lluno-
glol,ulin niolecule with specific n:Inies. I<xpansion01' tlicsc terms is not necessary:
kt\> :~ntigc.n-l>incling
Sr;~glll~n~
Fab' Fab with part of hinge
F(ab1I2 2 linked Pah' f r n g l l ~ e ~ ~ t ~
 Fc crystallizable fragment
F'c
DFC'
Fd
Fv variable part of Fab
scFv single-chain Fv 3
E ~ c himmunoglobulin monomer contains 2 heavy chains and 2 light chains, ab-
breviated as follows:

k c h H chain and L chain in turn contains both constant and variable regions, ab- -1
breviated as follows:

Regions of the Ig molecule may be indicated as follows:

VH variable region of heavy chain
variable region of light chain . 9

VL i.

CH constant region of heavy chain

CL constant region of light chain
have 3 or 4 CH domains, depending on isotype,
~mmuno~lobulins viatt
follows:
CHI CH2 CH3 CH4
*

p Heawy Chains. The type of heavy chain identifies the class (isotype) of immuno- ,
globulin. Heavy chains are nanned with the Greek letter that correspc the
of immunoglobulin:
Heavv-Chain Name Immunodobulin Clrass :.J
Y IgG
a IgA
P IgM
6 I@
3
E IgE
;1
IgG and IgA subclasses and corresponding heavy chains are as follows:
Heavy-Chain Name Immunonlobulin Subclass
 15.8.6 lmmunoglobulinr

Hea y-Chain Name Immunoglobulin Subclass

Y3 IgG3

CH domains may be specified according to isotype:

Light Chains. There are 2 types of light chain (named for initials of the discoverers'
surnames55):

Both types of light chain are associated with all 5 immunoglobulin classes; that is, an
immunoglobulin molecule of any type might have K or h light chains (but not both
types in the- same?nolecule). 1n humans, there are G classes (Gotypes) of h chain:

CLand VL regions may be specified by light chain type, as follows:

C, Cx
v, vx
The 3 specific hypervariable regions within the variable regions of an imrnuno-
globulin H or L chain are known as complementarity-determiningregions (CDRs)
and are named as follows:
;I
- CDRl CDR2 CDR3
. a

Heavy- and light-chain CDRs are termed HCDRI, etc, and LCDRI,etc, respectively.
The 4 framework regions (relatively invariable regions between hypervariable
regions) are designated as follows:

Ig Prefixes. The following are examples of terms combining Ig and a single-letter

prefix. It is best to expand tl~csctcrlns at first mcntion (cspcscially thosc witii thc
letters m or s, each of which has more than 1 meaning):
mIgM monomeric IgM
mIgM membrane-bound IgM
I-)& polynicric immunoglobulin
pIgA ~wly~\\c.l.izctl
IRA

I-)&R receptor for polylneric immunoglol~ulin

dg surface in~munoglobulin
slghl surfacc Ip31
dg.4 secreron. IgA
i
t
i. 697
15.8 Immunology

Other Immunoglobulin Components. Thc secretory forms of I&\! and I@ m n w n rn

additional polyppr~dt.,the J chain (not to be confuxd wtth thc pining or J segments
of the imnlunoglohul~ngene loci; .see the 'Immunoglobulin Genetics" -Tion below).
Secreted I@ also contains a secretory component, SC.

Molecular Formulas. These indicate the number of polypeptide chains that constitute
an immunoglobulin molecule:
YzLz IgG monomer wirh 2 y chains and 2 light chains
a2L2 IgA monomer with 2 a chains and 2 light chains
(IL?L~)~SCJ I@ dimer with 4 a chains, 4 light chains, an SC, and a J
chain
(pzLd5 IgM pentamer with 10 ,u chains and 10 light chains
(~2Ldd IgM pentamer with 10 ,u chains, 10 light chains, and a J
chain
82~2 IgD monomer with 2 6 chains and 2 K light chains
&?A2 IgE monomer with 2 E chains and 2 1 light chains

Fc Fragments and Fc Receptors. Fc fragments may be specified by the heavy-chain

class from which they arise5':
Fcyl Fcy2 Fq3 Fq4
Fcul Fcu2

Receptors for the Fc portion of immunoglobulin molecules are named as follows

(cell surface marker identities, if applicable, are shown in parentheses; see 15.8.2, CD
Cell Markers):
IgG receptors:

ZgA receptor:
FcuR (CD89)

IgM receptor
FcpR
IgE receptors:
FcsRI
 The 2 transmembrane accessory proteins associateti with surface immunoglobulins
on some immune cells should not be confused with terms for immunoglobulin
classes or heavy chains:

Igu (immunoglobulin-associateda; CD79a; this is not IgA or

the a heavy chain)
Igp (immunoglobulin-associated P; CD79b)
Serologic markers associated with some heavy and light chains are indicated with
roman letters and a lowercase m:
Marker Associated Chain
Glm - .rl

Immunoglobulin Genetics. Each immunoglobulin light chain gene is made up of a

variable (V), joining U), and constant (C) gene segment. Each imn~unoglo1,ulin
heavy chain is made u p of V, J, C, and D (diversity) gene segments. These segnients
can be referred to as follows:
VH VL JH JL CH CL DH
- or, more specifically, as in the following (subscript numbers refer to the cl;iss of I#): -

Subgroups (various nonallelic forms) of V, D, J, and C gene segments are spc.c.iliccl

numerically (subscript numbers refer to the class of Ig, numhers set on the linc*r c . I r
to the subgroup), as in:

A superscript plus sign may IK. ilsecl to inclicalc cxprcssion of ;I specific ..;cgnlc.nt.cg.
by a particular B lymphocyte (see 15.8.7,Lympliocytcs):
v,3+
The V, D, and J gene segments are brought together by DNA rearranpelnent. I)c- I

scriptive terms for this process includc t h e following:

\'/,I vxon. segrncnl. rcxion. X(.nc.. 11) I.-C.~I:IIII ~C.IICY
I
I
I rcc~o~~il~iri:~~~o~~ i
15.8 Immunology

VD], V/D/J, V-D-J, variable- alternative ter~ns

diversity-joining

A leader segment (L), which'codes for a leader (L) peptide, precedes each V segment.
Note the following potential sources of confusion:
V, D, and J segments code for the variable (V) region of an immunoglobulin
protein.
J segment does not refer to the J chain of the secretory forms of IgA and IgM
(see the "Other Immunoglobulin Components" section above).
18
L (leader) gene segment and L (light) immunoglobulin chain are different
entities. (Subscript L's, as in various terms in this section, typically refer to the
light chain.)

_ Official Gene Tsrminology. Official gene symbols for specific genes of the types :/
discussed above are presented in the following table (see 15.6.2, Genetics, Human
Gene Nomenclature). Follow author usaee.
0$cial Gene Symbol Immunogenetic T m
IGHAl Gal
1
IGHD Cs
IGHDI -1 member of DH1 subgroup . !
t
IGHE ce
IGHGl %I
IGHJl JH~
IGrn VH
IGNVI-2 member of VH1 subgroup
IGKC CK
IGKJ@ h
IGKJ2 Jr2
I G m vx
IGKVl-5 member of VK1subgroup I

IGLC@ CX i
IGLCl
!
CAI 4
IGLJ@ JA *3
1
IGLJl Jxl ,rl
a
IGL V@ VA 4
ZGLVI-36 member of Vxl subgroup

Alleles. Alleles are indicated with an asterisk and number following the gene name: .

J ~~mi*oi
3
IGHD'02 - ri
 15.8.7 Lymphocytes

For more detailed molecular information about immunoglobulin genetics, consult

the International IrnMunoGeneTics database (http://irngt.cines.fr).59

The normal adult human body contains on the or-

derof a trillion (10'') lymphocytes. . . . Together, the
thymus and marrow p&duce approximately 10'
mature lymphocytes each day, which are then
released into the cirhlation.
Tristram G. ~ a r s l o w ~ ~ ~ * " "

Lymphocytes. Lymphocytes are the cells that carry out antigen-specific immune
responses.w2 The 2 main types are the T lymphocyte and the B lymphocyte, also
called the T cell and the B cell. A hyphen does not appear in these terms, unless they
are used adjectivally.
T lymphocyte T cell T-cell lymphoma
B lymphocyte B cell B-cell signaling
Historically, the letters T and B reflected the anatomic sites of maturation of the 2
groups of cells, the thymus and the bursa of Fabricius, respectively. (The bursa of
Fabricius is an organ of birds.) Because in human adults B cells mature in the bone
marrow, the letter B is sometimes taken as signifying bone marrow.
A third group of lymphocytes is known as natural killer cells, abbreviated NK
cells.

B Lymphocytes. In the context of B-lymphocyte development, the prefixes pre- and

pro- are encountered; note hyphenation:
pro-B cell
pre-B cell
B-cell subsets are named in various ways, eg:
C D ~ +B cells
B1 B cells
B-cell antigen receptors (BCRs) are membrane colnplexes of membrane irnmuno-
globulins and the molecules Iga and IgP (see 15.8.6, Immunoglobulins).

I
T Lymphocytes. The main types of T Iymphocytc are as follows (esp;lncl ;Ir fir-.I
mention):
15.8 Immunology

helper T cells: TH cells

cytotoxic T cells: Tc cells, also called cytotoxic lymphocytes ( C X )
Most helper T cells express the cell marker CD4, and most cytotoxic T cells express
I
the cell marker CD8 (see 15.8.2, CD Cell Markers), giving rise to the following terms:
CD4 cells CD8 cells
When presence or absence of a marker on a T cell is emphasized, superscript plus or
minus signs are used. Presence and absence of the CD4 and CD8 markers are often
indicated by the terms positive and negative (eg, "double-positive lymphocyte"), as
below:
CD~+
%D4-
CD~+CD~' single positive a CD4 cell
CD4- C D ~ + single positive a CD8 cell
CD4- CD8- double negative
C D ~ + C D ~CD8-
- double negative
CD4+CD8+ double positive
.CD~+CD~+CD~- single positive a CD4 cell
C D ~ + C D ~CD8+
- single positive ' a CD8 cell
CD~+CD~+CD~- single positive a CD4 cell
CD~+CD~-CD~+ single positive a CD8 cell

Because other cells, eg, monocytes, may express CD4;authors should use terms more
specific than 'CD4 cells," unless context has made clear which cells are referre
CD4 lymphocyte count (not CD4 cell count)
Subtypes of helper T cells are as follows:
T H ~ T H ~T H ~

The theoretical helper T precursor to these subtypes is abbreviated:

T H ~

T-cell Receptors. T-cell receptors C'ICRs) are protein complexes on the su

The T-cell receptor-CD3 complex (abbreviated TCR-CD3) is a s
.recognizes antigen. Its subunits, or chains, are designated by Greek letters:
a chain
p chain
y chain
G chain
Echain
<chain
q chain .

702

. .
.,-. . - -.
/ '
'. .<.
.. $
.,
 15.8.7 Lymphocytes

(Do not confuse these chains with the components of MHC or Ig molecules, although
there is some homology among them; see 15.8.5, HLA/Major Histocompatibility
Complex, and 15.8.6, Immunoglobulins.)
The a and P chains are also referred to as follows:
TCRu and TCRP
Linked u and P chains and linked y and 6 chains result in these terms:
up dimer y6 dimer
ap heterodimer y6 heterodimer
ap receptor .'y6 receptor
ap cell -. y6 cell
ap T cell y6 T cell '

T aP T ~6
CD&p
5
The y, 6, E, 6, and q &ins constitute the CD3 complex. The CD3 chains are also
referred to individually and as dimers:

There are 2 subtypes of the y chain:

The TCR protein has variable 0 and constant (C) regions or domains. The gene for
TCRa is made up of variable 03, joining U), and constant (C) segments, as is the P
chain, which also has a diversity (D) segment. (These are analogbus to the segments
of the immunoglobulin genes; see 15.8.6, Immunoglobulins.) These segments may
also be referred to as follows: .

Subgroups (various nonallelic forms) of the V, D, or J segments are specified nu-

merically, eg:

T-cell expre~sionof a particular segment may be indicated by using a superscript

plus sign:

T-cell Receptor Gene Terminology. Because the V , D, and J gene segments together
encode the variable (V) region of the protein, it is unusual to refer to D or J regions o f
the protein.G3
The V, D, and J gene segments are brought together by DNA re:lrr;lngenlc.n1.
Descriptive terms include the following:
V/J exon, segment, region, gene, for a or y chain gcncs
recombination
 \'/D/J exon, segment, region, gene, for p or 6 chains
recombination
V/(D)/J of a and y or p and 6 chains
VDJ, V/D/J,V-D-J, variable-diversity-joining alternative terms

Official Gene Terminology. Official gene symbols for specific genes of the types
discussed above are presented in 15.6.2, Genetics, Human Gene Nomenclature. The
TCR genes begin with 7Z?and use roman letters that correspond to the Greek letters
of the TCR component chains, and they contain V, C, D, and J corresponding to the ;i
above terms. Like other immune genes, they may contain hyphens:
mc m c ~ V I O - ~3 G C I ~ G Jm c
Alleles. Alleles are indicated with an asterisk and number following the gene name: ,
i
TRBV7-1'0 1 I

REFERENCES
1. IUIS/WHO Subcommittee on Chemokine Nomenclature. Chemokine/chemokine re- '
.,2
ceptor nomenclature./ Interferon Cytokine Res, 2002;22(10):1067-1068.
2. Zlotnik A, Yoshie 0. Chemokines: a new classification system and their role in irn- '
.L
,
munity. Immunity. 22000,12(2):121-127.
3. Murphy PM. Chemokines. In: Paul WE, ed. Fundamental Immunology. 5th ed.
Philadelphia, PA: Lippincott Williams & Willrins; 2003:801-840.
4. Rich RR, Fleisher T, Shearer WT,Kotzin BL, Schroeder HW Jr, eds. Clinical Immu-
nology: Principles and Practice. St Louis, MO: Mosby; 2001.
5. Thomson AW, Lotze hlT. 7be Cytokm Handbook. 4th ed. San Francisco, CA: Aca-
demic Press; 2003.
6. Cytokine Family Database (dbCFC). http://cytokine.medic.kumamoto-u.ac.jp. Up-
dated February 27, 2006. Accessed ~ ~ r i l 3 , 2 0 0 6 .
7. Bernard A, Boumse11 L. The clusters of differentiation (CD) defined by the F i t In-
'
ternational Workshop on Human Leukocyte Differentiation Antigens. Hum Immunol.
1984;l l(1) 1-10.
8. Bernard A. Bemstein I. Bournsell L, et al. Differentiation human leukocyte antigens: a ;
proposed nomenclature. Immunol Today. 1984;5(6):158-159. Q
9 IITTSIWO Subcommittee on CD Nomenclature. Nomenclature for clusters of differ- 1
entiation (CD) of antigens defined on human leukocyte populations. Bull World :ii
..:I
Health Organ. 1984;62(5):809-811. i

10. Singer NG, Todd RF, Fox DA. Structures on the cell surface: update from the Fifth
International Workshop on Human Leukocyte Differentiation Antigens. Arthritis
Rheum. 1994;37(8):1245-1246.
.t
:ih
'
11. zola H. The CD nomenclature: a brief historical summary of the CD nomenclature,
why it exists and how CDs are defined. J Biol Regul Homeost Agents. 1999;13(4):
226-228.
12. Zola H, Swan B. The human leucocyte differentiation antigens (HLDA) workshops:
the evolving role of antibodies in research, diagnosis and therapy. Cell Res.
2005;15(9):G91-694. 4
I 15.8.7 Lymphocytes

13. HCDM: Human Cell Differentiation Molecules. http://www.hlda8.org/. Accessctl ,\1;1y

27, 2006.
14. Liszewski MK,Atkinson JP. The complement system. In: Paul WE, ed. Airrcltrnrc~trrrrl
Immunology. 3rd ed. New York, NY: Raven Press; 193:917-939.
15. Prodinger WM, Wiinner R, ~ r b eA, i ~ i e r i c hM1':Complement. In: I'aul WE, ctl.
Fundamental Immunology. 4th ed. Philadelphia, PA: Lippincott-Raven; 1p)Y:
967-996.
16. Prodinger WM,Wiirzner R, Stoiber H, Dierich MP. Complement. In: Paul \VI:. ctl.
' Fundamental Immunology. 5th ed. Philadelphia, PA: Lippincott Williams & \XJillii~is:
2003:1077-1103.
17. World Health Organization. Nomenclature of complement. Bull World Hecrltl) Orgotr.
1%8;39(6):935-938. : '.
18. Letendre P. Complement: .to be or not to be? Transfusion. 1330;30(5):478-479.
19. playfair JHL, Lydyard PM. Medical Immunology Made Memorable. 2nd ed. New York.
NY: Churchill Livingstone; 2000.
20. Oppenheim JJ,l Feldmann M. Introduction to the role of cytokines in innate host
defense and adapti& immunity. in: -Dumm SK, Hirano T, Vilcek J, Nicola NA. ccls.
Cytokine R e f m e : A Cmpendium of Cytokines and OtherMediators of Hosl Ikj'cJi~.~~'.
J

San Diego, CA: Academic.Press; 2001:3-20.

21. -Leonard WJ. Type I cytokines and interferons and their receptors. In: Paul WE. ed.
Fundamental Immunology. 4th ed. Philadelphia, PA: Lippincott-Raven; 1933:
741-774.
22. Krakauer T, Vilcek J, Oppenheim JJ. Proinflammatory cytokines: TNF and IL-1 families,
chemokines, TGF-p, ahd others. In: Paul 9 ; e d . Fundamental Immunology. 4th ed.
Philadelphia, PA: Lippincott-Raven;.1999:775-$12. . .
23. OShea JJ, Frucht DM, Duckea CS.Cytokines and cytokine receptors. In: Rich KR,
Fleisher TA, Shearer ;WT, Kotzin BL, Schroeder HW Jr, eds. Clinical Immunology:
Principles and Practice. 2nd ed. St Louis, MO: Mosby; 2001:12.1-12.22.
24. Rich RR, Fleisher TA, Shearer WT, Kotzin BL, Schroeder HW Jr, eds. Clitzical Itrrnru-
nology: PrincipIes,and Practice. 2nd ed. St Louis, MO: ~ o s b k2001:A12-A14.
25. Leonard WJ. Type I cytokines and interferons and their receptors. In: Pau! WE.
Fundamental Immunology. 5th ed. Philadelphia, PA: Lippincott Williams 8; Wilkins;
2003:701-474.
26. Fitzgerald KA, O'Neill LAJ, Gearing AJH, Callard RE. 7be Cytokine FactsBook. 2nd ed.
San Diego, CA: Academic Press; 2001.
27. Aarden LA, Uninner TK, Cerottini J-C. et al. Ikvisccl nomenclature for :~ntigen-
nonspecific T cell proliferation and helper factors [letter].J Immunol. 1979;123(6):
2928-2929:
28. Paul WE, Kishirnoto T, Melchers F, et al. Nomenclature for secreted regulatory proteins
of the immune system (interleukins). C 1 i n . w Immunol. 1992;88(2):367.
29. Lagna G, Hata A, Hemmati-Brivanlou A, Massague J. Partnership between DPC4
and SMAD proteins in TGF-beta signalling pathways. Nature. 1996;383(6603):
832-8x1.
30. Ikri~ncrDT.l i b 1771. In: Tsuii K, Aiz;~wahl. Snsnzuki S, eds. HLA 1991: Proceedings
,,/ rh,. El~?utrrhItrternuliotrc~lIiis!ocu~t~~,o~ibilq~
\Vorktbop and Conference Held i n
)oir,l,(i,n',. / a p ~ n6-1.3
. nbcr.nrh.r. 1901 SCX York. NY: Osford University Press:
I<.*)? --I(,
lology

2 M i 7Lrue A~lligt,fu.2005;65(4):30-369. doi:10.1111/~.13~-0039.2005.00379.~.

32. Lkxllnrr KT. .4lbcrt E, Bodmer JG, et al.'Nomenclature for factors of the HLA system,
1987. Hum Immunol. 1989;26(1):3-14.
33. International Histocompatibility Working Group. A brief history of the international
histocompatibility workshops. http://www.ihwg.org/history/history.htrn. Accessed
April 6, 2006.
34. Marsh SGE, Albert ED, Bodmer WF, et al. Nomenclature for factors of the HLA system,
2002. T k u e Antigens. 2002;60(5):407-464. doi:10.1034/j.13~~-003~.2002.600509.x.
35. Bodrner JG. Nomenclature 1991 foreword. Hum Immunol. 1992;34(1):2-3.
36. Marsh SGE, Parham P,Barber LD. The HLA FactsBook. San Diego, CA: Academic Press; ..

2000.
37. Marsh SGE. Nomenclature for factors of the HLA System. http:,!I
.com/HIG/lists/nomenc.html. Updated January 1, 2006. Access
38. Robinson J, Waller MJ, Parham P, et al. IMGT/HLA and IMGT/
databases for the study of the major histocompatibility complex. Nucleic Acids
2003;31(1):311-314. Also available at http://nar.oupjournaIs.org/cgi/content
/full/31/1/3ll?ijkey=W/BIuukIQ8mn&ke~e=ref&iteid=nar. Accessed Ap

for nomenclature usage in HLA reports: ambiguities and conversion to serotyp

Immunogenet. 2002;290):273-274.
40. Klein J, Bontrop RE, Dawkins RL, et al. Nomenclature for the major histoco
ibility complexes of different species:a proposal. Immunogenetics. 1990;31(4):
217-219.

Science; 2001.
42. Haynes BF, Fauci AS. Introduction to the immune system. In: Kasper DL,

43. raze;JK, Capra JD.Immunoglobulins: structure and function. In: Paul

Fundamental Immunology. 4th ed. Philadelphia, PA: Lippincon-Raven; 199.
37-74.
. 44; Naim R,Helbert M. Immunology for Medical Students. St Louis, MO: Mosby; 2002.
45.' Lefranc M-P, Lefranc G. De Jmmunoglobulin FactsBook.San Diego, CA: ~cademic'.''.
Press; 2001.
46. Parslow TG. Immunoglobulins and immunoglobulin ge
Terr AI, Imboden JB, eds. Medical Immunology. 10th ed. New York,
Medical Books/McGraw-Hill; 2001:95-114.
r Capra JD. Immunoglobulins: structure and function. In: Paul WE, ed.
47. ~ o l a GR,
Fundamental Immunology. 5th ed. ~hiladelphia,PA: Lippincott Willi
200347-68.
48. Kao NL. How immunoglob\ilins were named. Ann Intern Med. 192;117(5):445. ,
49. Ceppellini R, Dray S, Edelman G, et al. Nomenclature for human immunoglobulins. i
Bull World ~ e a l t bOrgan. 1964;30:447-449.
50. Ishizaka K, Ishizaka T, Hornbrook MM. Physico-chemical properties
aginic antibody, N: presence of a unique immunoglobulin as a carrier of reaginic
activity. J Immunol. 1966;97(1):75-85.
 15.9.1 Elements

51. Rowe DS, Fahey JL. A new class of human immunoglobulins, I: a unique myeloma
protein. J Med. 1965;121:171-184.
52. Rowe DS, Fahey JL. A new class of human immunoglobulins, 11: normal serum IgD.
J Exp Med. 1%5;121:185-199.
53. Kunkel HG, Fahey JL, Franklin EC, Osserman EF, Terry \VD. Notation for human
immunoglobulin subclasses [letter]. Int Arch Allergy AppI Immunol. 1967;32(2):
247-248.
54. Black CA. A brief history of the discovery of the immunoglobulinsand the origin of the
modem immunoglobulin nomenclature. Immunol Cell Biol. 1937;75(1):65-68.
55. Recommendations far the nomenclature of human immunoglobulins. Biochemistry.
1972;11(18):3311-3312. '
56. Haynes BF, Fauci AS: !ntroduction to the immune system. In: Harrison's Online.
http://hamsons.accessmedicine.com. Accessed September 20, 2004.
57. IUIS Subcommittee on Nomenclature. Nomenclature of the Fc receptors. Bull World
Health Organ. 1989;67(4):449450.
58. IUIS/WHO Subcommittee on IgA Nomenclature. Nomenclature of immunoglobulin A
and other proteirb of the mucosal immune system.J Immunol Methods.
1939;223(2):263-264. Also published in EurJImmunol. 1999,29(3):1057-1058.
59. LeFranc M-P. International ImMunoGeneTics Information System. http://imgt.cines.fr.
Accessed April 6, 2006.
60. Parslow TG. Lymphocytes and lymphoid tissues. In: Parslow TG, Stites DP, Terr AI,
Imboden JB, eds. Medical Immunology. 10th ed. New York, NY: Lange Medical
Books/McGraw-Hill; 2001:40-60.
61. DeFranco AL. Bcell development and the humoral immune response. In: Parslow TG,
Stites DP, Terr AI, Imboden JB,eds. Medical Immunology. 10th ed. New York, NY:
Lange Medical Books/McCraw-Hill; 2001:115-130.
62. ImbodenJB, Seaman WE. T lymphocytes and natural killer cells. In: Parslow TG, Stites
DP, Terr AI, Imboden JB, eds. Medical Immunology. 10th ed. New York, NY: Lange
Medical Books/McGraw-Hi; 2001:131-147.
63. LeFranc M-P, LeFranc G. me T Cell Receptor FactsBook. San Diego, CA: Academic

"
Press; 2001.

Isotopes. Isotopes may be referred to in the medical literature alone or as a com-

ponent of a radiopharmaceutical administered for therapeutic or diagnostic pur-
poses. The nomenclature for the isotopes incorporated in radiopharmaceuticals
follows the international nonproprietary name (INN) drug nomenclature and there-
fore differs from that of isotopes that occur as elements alone.
,
Elements. An isotope referred to as an element r;rther than as part of the name of a
chemical comp&nd may be described at first mention by providing the name of the
element spelled out followed by the isotope number in the same typeface and type
size (no hyphen, subscript, or superscript is used). The element abbreviation may be
listed in parentheses at firsf mention and used thereafter in the article. \\lit11 thc
isotope number preceding the element syrnI~oI;ls :I superscript
t

Of the 13 known isotopes of iodinc. onl! ioclinc 118 i1"l) i, not r : ~ c l l o . ~111.i.
c
1294
! Thc invcsrig:ltc>rs I lo n\.olt! r h Jlfficult\
~ . I ~ cxpcnw
J (,:t l l \ l > #
1.ln.i:(I:
i
r:\(l;o:lrr~vc\va'.rr
15.9 Isotopes

The symbol representing a single clemt.nt should nor be u x d as an al)brt.vution for a

compound (eg, do not abbreviate the compound sodium arsenatc As 74 as ''AS).

Radiopharmaceuticals. The INN designations for radioactive pham~aceuticalsconski

of "the name of the compound serving as the carrier for the radioactivity, the symbol
for the radioactive isotope, and the atomic Since the nonproprietary
'

name comprises all these components, the complete name should be provided at
first mention unless the radiopharmaceuticals being referred to are a general cate-
gory. Subsequently, a shorter term may be used, such as iodinated albumin or
gallium scan.
Although the nonproprietary name for the ridiopharmaceutical may appear to
contain redundant information, maintaining consistent terminology is important for
clarity. For example, technetium Tc 99m is contained in more than 40 nonproprietary
radiophaxmaceuticals, from technetium Tc 99m albumin to technetium Tc 99m te-,!
b o r o ~ i r n e . ' ' ~The
~ ~isotope
~' number appears in the same type (not superscript): j
as the rest of the drug name; and it is not preceded by a hyphen. A few comrnord~ ,

used drugs appear below. For drugs not listed here, consult the most recent edition
of the USP l>ictionaV.'
cyanocobalamin Co 60 . .
fibrinogen 1 125
fludeoxyglucose F 18
gallium citrate Ga 67
indium In 111 altumomab pentetate
indium In 111 satumomab pentedine
iodohippurate sodium I 131
potassium bromide Br 82
sodium iodide I 125
Strontium chloride 89 can be used to treat pain from skeletal metastases.
In an earlier study, 50 patients underwent lung imaging with technetium Tc 1
99m sulfur colloid. .

The patient underwent an exercise stress test with injection of thallous

chloride Tl 201 (thaliiium stress test).
In a discussion that does not refer to administration of a specific drug, the more
general term may be used.
For a patient recuperating from a myocardial infarction who wishes to begin
an exercise program, a treadmill test with or without thallium imaging may
be useful to determine whether the patient is at high risk for recurrent is-
chemia. A

At the beginning of a sentence, the name rather than the element symbol should b
used.
The was treated with sodium iodide I 131 after she was found to'have
hypenhyroidis~n.Iodine 131 levels were then monitored by measuring the .
amount of radioactivity in the patient's urine.

- - - -.: - . -- - . . - a

-. .
 15.9.6 Hydrogen Isotopes

Radiopharmaceutical Compounds Without Approved Names. Compounds may be

combined with radioisotopes for research purposes. Such compounds would not
receive an INN if no commercial use is intended. In lieu of an INN, standard chemical
nomenclature should be followed (see 15.9.1, Elements, or consult the CRC Hand-
book of Chemistry and ~hysic? for more information).
After first mention, the name of the substance can be abbreviated. Use the
superscript form of the isotope number to the left of the element symbol. Enclose
the isotope symbol in brackets and close u p with the compound name if the
nonradioactive isotope of the element is normally part of the compound.
glucose labeled with-radioactive carbon (14c)[or glucose tagged with
carbon 141
[14~lglucose
(not glkose C 14)
Use no brackets and separate the element and compound name with a hyphen if t l ~
compound does not normally contain the isotope element.
amikacin labeled with iodine 125
lZ51-amikacin
If uncertain as to whether the isotope element is normal'ly part of a compound.
consult the USP ~ i c t i o ny1
u for drugs and 'I;beMerck hzdex3for other compouncls.

Radiopharmaceutical Proprietary Names. In proprietary names of r~diopkrrnlaccu-

ticals, isotope numbers may appear in the same position as in the approvetl non-
proprietary names, but they are usually joined to the rest of the name by a hyphcn
and are not necessarily preceded by the element symbol. Follow the USP /lir~itrrrrrr~~~
or the usage of individual manufacturers.
-
Ptl)pP"etaly Nonppnpnefary (Prferred)
Iodotope 1-131 sodium iodide I 131
Glofil-125 iothalamate sodium I 125

Uniform Labeling. The abbreviation ul (for uniformly labeled) may be used \vithout
expansion in parentheses:

Similarly, terms such as carrier-Jree,no carrier added, and carrier added may he
used. In geheral medical publications, these terms should be explained at first
mention, since not all readers will be familiar with them.

Hydrogen Isotopes. Two isotopes of hydrogen have their own specific names. deu-
terium and tritium, which should be used instead of "hydrogen 2" and "hydrogen 3."
In text, the specific names are also preferred to the symbols 'H or D (for deuterium.
which is stable) and 3~ (for tritium, which is radioactive). The 2 forms of h e a y \vater.
D 2 0 and 3 ~ zshould
0 , be referred to by the approved nonproprietary names dell-
terium oxide and tritiated water, respectively.
 I
15.10 Molecular Medicine

Metastable Isotopes. The abbreviation m, as in krypton Kr 81nm or technetium ~i

99m, stands for metastable. The abbreviation should never be deleted, since the term
without the m designates a different radionuclide isomer.

REFERENCES
1. USP Dictiona?y of USAN and International Drug Names. 41st ed. Rockville, MD: US
Pharmacopoeia; 2005.

-
2. Lide DR, ed. CRC Handbook of Chemistry and Physics. 85th ed. Boca Raton, FL: CRC

3. O'Neil MJ, Smith A, Heckelman PE, Budavari S, eds. The Merck Index: An Encyclopedia
of Chemicals, Drugs, &Biologicals. 13th ed. Whitehouse Station, NJ: Merck & Co Inc;
2001.

Naming things is essential

one another, no matter what language orjieki of
ittterest is involved. i%isis as truefor enzymes, genes
and chemicals as it isfor birds,food, flowers, etc.
Keith Tipton and Sinead ~ o ~ c e ' @ ~ ~ )

M olecular Medicine. M
icine. Many c h e s of
some of which are covered in other sections

biochemicals; see
enzyme nomenclature is d
Center for Biotechnology
able information
Thii section provides information on various molecular terms, including

helpful sources include the.MeSH database of the National Library of ~ e d i - '

( h n p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e ~medical texts and
tionaries, and Internet searches. For a review of molecular biology databases, see
2005 Database Issue of Nucleic Acids ~ e s e a r c h . ~

15.11, Neurology. The following sections of chapter 15 substantially deal

lecular terminology: 15.1, Blood Groups, Platelet Antigens, and Granulo
gens; 15.6, Genetics; 15.7, ~emostasis;and 15.8, Immunology.

elsewhere in this chapter:

Entity -

-.
. ._-.-. - ..r

::..; .. .. ...
,
.
 15.10.1 Molecular ~errninolo&: Other Sections of Chapter 15

Entity Section
antitrypsins, antithrombins 15.7.4, Hemostasis, Inhibition of Coagula-
tion and Fibrinolysis
apolipoproteins 15.3.12, Cardiology, Cellular and Molecular
Cardiology
bacterial strains and proteins 15.14.2, Organisms and Pathogens, Bacteria:
Additional Terminology
blood gas terminology 15.16, Pulmonary, Respiratory, and Blood
(eg, Pa021 Gas Terminology
cancer molecules 15.2.5, Cancer, Molecular Cancer
Terminology
15.6.3, Genetics, Oncogenes and Tumor
Suppressor Genes
cellular adhesion molecules 15.7.2, Hemostasis, Endothelial Factors
15.8, Immunology
9
chemokines 15.8, Immunology
chromosomes 15.6.4, Genetics, H u m Chromosomes
cloning'vectors 15.6.1, Genetics, Nucleic Acids and
Amino Acids
clotting factors 15.7.3, Hemostasis, Secondary Hemostasis
clusters of differentiation 15.8, Immunology
(CDs) 15.1.2, Blood Groups, Platelet Antigens, .
and Granulocyte Antigens, Platelet-Specific
Antigens
codons 15.6.1, Genetics, Nucleic Acids and
Amino Acids
colony-stimulating factors 15.8, Immunology
complement 15.8, Immunology
creatine kixiases 15.3.12, Cardiology, Cellular and Molecular
Cardiology
cytokines 15.8, Immunology
D-dimer 15.7.4, Hemostasis, Inhibition of Coagula-
tion and Fibrinolysis
DNA 15.6.1, Genetics, Nucleic Acids and Amino
Acids
genes 15.6.2, Genetics, Human Gene Nomencla-
ture
15.6.3, Genetics, Oncogenes and Tumor
Suppressor Genes
15.6.5, Genetics, Nonhuman Genetic Terms
glycoproteins 15.1.2,Blood Groups, Platelet Antigens, and
Granulocyte Antigens, platelet-Specific
Antigens
15.10 Molecular Medicine

Entity Section
15.7.1, Hemostasis, Primary Hernostasis "

15.7.2, Hemostasis, Endothelial Factors 4

guanine nucleotides 15.3.12, Cardiology, Cellular and Molecular
Cardiology
15.6.1, Genetics, Nucleic Acids and Amino
Acids - 41
hemostatic molecules 15.7.1, Hemostasis, Primary Hemostasis
4
hepatitis antigens and 15.14.3, Virus Nomenclature cq
antibodies !
r'

histones 15.6.1, Genetics, Nucleic Acids and

Amino Acids
HLA antigens 15.8, Immunology d
J;\
immunoglobulins 15.8, Immunology
influenza types and strains 15.14.3, Organisms and Pathogens, Virus
and Prion Nomenclature
integrins 15.7.2, Hemostasis, Endothelial Factors
interferon
interleukins
15.8, Immunology
15.8, Immunology jfi
I
ion channels 15.11.5, Neurology, Molecular ~euroscience
lipoproteins 15.3.12, Cardiology, Cellular and Molecular
.f
Cardiology
muscle cell components 15.3.12, Cardiology, Cellular and Molecular
4
Cardiology I *
mutations 15.6.1, Genetics, Nucleic Acids and
Amino Acids
myosin chains - 15.7.1, Hemostasis, Primary Hemostasis ..I

neurotransmitters and 15.11.5, Neurology, Molecular Neuroscience !

receptors .I
nitric oxide synthase 15.3.12, Cardiology, Cellular and Molecular
Cardiology
15.7.2, Hemostasis, Endothelial Factors J
9
nodal cells 15.3.12, Cardiology, Cellular and Molecular 4
Cardiology $
nucleic acid technology (eg, 15.6.1, Genetics, Nucleic Acids and $
polymerase chain reaction Amino Acids d
[PCRI, single nucleotide
repeats [SNPsl, short tandem
repeats tSTRsl)
nucleosides, nucleotides 15.6.1, Genetics, Nucleic Acids and :*:
8
Amino Acids

- - ., --... .. <.--
 15.10.2 Molecular Terms: Considerations and Examples

Entity Section
phages 15.14.3, Organisms and Pathogens, Virus
Nomenclature
phospholipase 15.7.1, Hemostasis, Primary Hemostasis
plasrninogen activators 15.3.12, Cardiology, Cellular and Molecular
Cardiology
15.7.2, Hemostasis, Endothelial Factors
. platelet-activating factors 15.7.1, Hemostasis, Primary Hemostasis
prions 15.14.4, Organisms and Pathogens, Prions
prostaglandins - 15.7.1, Hemostasis; Primary Hemostasis
restriction enzymes 15.6.1, Genetics, Nucleic Acids and Amino
Acids
retrovirus gene terms 15.6.3, Genetics, Oncogenes and Tumor
Suppressor Genes
9 15.6.5, Genetics, Nonhuman Genetic Terms
RNA 15.6.1, Genetics, Nucleic Acids and Amino
Acids
serotonin 15.11.5, Neurology, Molecular Neuroscience
thromboxanes 15.7.1, Hemostasis, Primary Hemostasis
troponins 15.3.12, Cardiology, Cellular and Molecular
Cardiology
von Wilebrand factor 15.7.3, Hemostasis, Secondary Hemostasis

- m I a m Molecular Terms: Considerations and Examples. Molecular terms often are more
familiar in unexpanded form; their expansions may be obscure. M?lecular terms
often mix numbers, letters, and cases. They may be abbreviations or abbreviations
within abbreviations (for instance, see TAF and subsequent entries in Table 13).
Molecular terms differ from standard abbreviations, which typically are uppercase
initialisms (eg, premadre ventricular contraction, PVC). In contrast, many molecular
terms are (or incorporate) contractions of single words, using all lowercase letters or
muring capital and lowercase letters (eg, apo, apolipoprotein; Hb, hemoglohin ).
Letter prefixes (including Greek letters) and numeric prefixes are linked to thv
main term by hyphens.
al-antitrypsin
0-catenin
y-tubulin
glucose 6-phosphate
However, these terms are not hyphenated:
15 10 Molecular Medicine

t1yphc.n.s are added in adjectival usages, eg:

0-pleated sheet
glucose-6-phosphate dehydrogenase
Hyphens are used as follows in numbers that interrupt a word:
propan-1,2-diol (propanol)
flavan-3-01
For letter or number suffixes, hyphens typically are not used with expanded terms ,
but are handled in various ways with abbreviated terms (see exampl
cited in Table 13):
interleukin .1 (IL-1)
phosphodiesterase 3A (PDE3A)
6-keto prostaglandin F,, (Gketo PGF1d
The chemical prefixes L (levo) and D (dextro) are small capitals:
L-folinicacid
D-glyceraldehyde
Element symbols in chemical names, such as S (sulfur) and N (nitrogen),
cized. Other capital letters are not italicized.
N-acetyl-D-glucosamine
.cytochromeP450
N-terminal, C-terminal
A subscript letter indicates a modifier of the main term.
Pi (inorganic phosphate)
Plus signs and minus signs indicatihg iharges are set superscript. Numeials
quantities of an element within a molecule are set subscript. Numerals
charge are superscript.
HC03-
~e~~ .
Proteins are often expressed as p plus a nuxneral sigmfying the atomic weight in
kilodaltons, eg, p53, a 53-kDa protein. Affixes, such as superscripts, fu
the protein (important because different proteins may have the same we
examples in Table 13. Although the gene symbols for such proteins a
as the same term italicized, eg, the tumor suppressor gene p53, the correct gene
symbols should be used, eg;in humans P53;in mice, Tp53.Use the
at the HUGO Gene Nomenclature Committee Web site (http://www.
/nomenclature/; see also 15.6, Genetics).
The term stem cell has the general meaning of a precursor, pluripotent,'
progenitor cell. Research articles should specify the type(s) of stem cell referre
to, eg, udtclt, embryonic, gemline, hemafopoietic, mesenchymal, neural, periph
blood, sonralic, utnbilicrtl cord-dcri~~ed, unrestricted somatic
~>rcc~<lirig
tern13 :try not all inutually csclusive.)

714

- . -
-. . -
. i
I
15.10.2 Molecular Terms: considerations and Examples

Terms in Table 13 are included as a reference. Some context or exp1;tnation of

such terms is desirable at first mention, but, in contrast to nl,breviations (see 1-1.0.
Abbreviations), first mention need not be a literal expansion ; ~ n dthe tern1 nl:I): I,c
stated as an appositive, rather than in parentheses, eg:
the cyclin-dependent kinase CDK2
When an abbreviation is used in the Suggested Usage at First ~ e n ' t i o ncolumn. it is
assumed that in the article the abbreviated term has already I1ec.n introclucerl ;~nrl
defined or expanded; eg, if INK4 is defined as "inhibitors of CLIK4" at first mcntion, it
is assumed that CDK4 was previously defified or expanded. Providing more infor-
mation is often helpful. For instance, at first mention, p21 may be referred to as ..the
protein p21" or "the CDKI protein p21" or given additional context.

Table 13. Molecular Terms

Suggested Usage at
Term Explanation First Mention

AfJ peptide. Ap42 amyloid-p peptide arnyloid-P peptide (AP), APd2

peptide, or 42-residue form of AD
A$*56 56kDa A$ fragment 56kDa A$ fragment
Ach acetykholine acetylcholine
Acrp30 adipoqteiomplement the protein Acrp30 or adiponectin
(or adiponectin) related 30 kDa-protein
acyl-CoA acyl derivatives of acyl coenzyme A
coenzyme A
acyl-XoA sulfonated acyl-CoA sulfonated acyl-CoA .
ADAMTS [see ~ p t e ~ ] a disintegrinlike and metalloprotease ADAMTS protease
domain (reprolysin-type) with
thrombospondin type 1 motifs
specific ADAMTS, eg, ADAMTS-13; trivial name von Willebrand ADAMTS-13 andlor vWF protease
ADAMTS-13 factor (VWF) protease (see also
15.7, Hemostasis)

adoMet , S-adenosylmethionine
(also SAM)
Akt kinase a serinethreonine kinase, also known Akt protein kinase
as protein kinase 0, related to akr
oncogene (origin: AKT retrovirus isolated
from AKR mouse thymoma)
allo-SCT allogenic stem cell transplantation allogen~cstem cell transplantat~on
--- -
ATCase aspanate tranxarbamoylase- aspartate tranxarbamaylase
- . - ..- -- - -
ATPase adenowne tr~phosphatase adenosine tr~phosphatase
-- .
BNP bra~n(or b-type) natrluret~cpt'QT~de bra~n(or b type) wtr'ureljc
Table 13. Mdecular Terms (CMV

Suggested Usage at
1
Term Explanation First Mention

CAK (=cyclinH/CDK7) CDK-activating enzyme the CDK-~ctivatingenzyme (CAK)

cyclinH/CDK7
CaM calmodulin calmodulin
CDK2, CDK3, CDK7, etc cyclin-dependent kinases the cyclin-dependent kinase
CDK2. etc
- -- --- -- - - -

CDKl CDK inhib~tors(see also INK4 below) CDK inhibitors

CoA coenzyme A coenzvme A
COX-1, COX-2 cyclwxygenases 1 and 2 cyclorlxygenase 1,
wclwxvaenase 2
C-reactive protein protein reactive to pneumococcal cell C-reactive protein (CRP) ,
wall C polysaccharide
cyclin D/CDK4/CDK6, cyclin-CDK complexes the cyclin D/CDK4/CDK6 cpmple:
cyclin E/CDKi! the wclin EICDK2 comdex
C Y P l a CYP2C9. CYP2C19, isoforms of qtochrome PISO enzymes various, eg, cytochrome PTO
i
CYPZD6, CYP3A4 (also cytochrome P450 isozymes) [P: isozyme (CYP1AZ); cytochyome
pigment; 450: 450-nm absorbance] P450 3A4 isozyme (CYP3A4-
P450 3A4 or 3A4)
Dkk-1 Dickko~f-1 the inhibitor ~roteinDkk-1
FO (subscript is zero, not portion of mitochondrialATP synthase context, eg, Fo portion of
capital 0) (F: energy-coupling factor) mitochondria1ATP synthase,

mitochondrialATP synthase,
catalytic portion of ATP synthase,
etc
fructose 1-phosphate, fructose . fructose 1-phosphate,
6-~hosohate fructose 6-ohosohate
FAD flavin adenine dinudeotide - flavin adenine dinudeotide :-a
reduced (hydrogenated) FAD FADH2 or reduced
(or hvdroaenated) FAD
FBPase-1, fructose 1,6-bisphosphatase, fructose fructose 1,6-bisphosphatase,
FBPase-2 2. 6-bisohosohatase fructose 2.6-bisohosohatase
Fd ferredoxin ferredoxin
Fhit fragile histidine triad protein fragile histidine triad protein :
1.
FMN flavin mononucleotide flavin mononucleotide I

\ :1
FMNH2 reduced (hydrogenated) FMN FMNHz or reduced !.Q
 -

Table 13. Molecular Terms (cont)

Suggested Usage at
Term Explanation First Mention

FP flavoprotein flavoprotein (Fp)

Gn auiexent state of cell cvcle Gn ohase
GI arowth or aap 1 phase of cell cvcle GI phase
GZ qrowth or aap 2 phase of cell cvcle G2 phase
G protein guanine.triphosphate (GTP)-binding G protein
protein
.. Ga. 6,
G G prote'in families G, Ge G, protein or family
G1
.2. 6.13 members of G. G1
,2. G1.3 protein
Gw. BY Gg subunit or complex Gpu, $7 subunit or complex
GIP, G6P glucose I-phosphate, glucose glucose 1-phosphate,
$phosphate glucose 6-phosphate
GalN Aalactosamine o-aalactosamine

Gi inhibitory G protein inhibitory G protein

Glc or PClc o-glucose glucose or o-glucose
6., G u l l classes of G protein G
,, Gqlt protein
cis stirnulatory G protein stirnulatow G protein
GlcA o-gluconic acid gluconic acid or ~gluconicacid
GlcNAc (alx, NAG) N-acetylsglucosamine N-acetyl-o-glucosamineGlcNAc
GlcUA wlucuronic acid o-alucuronic acid -
growth factor receptor-bound the protein Grb2
protein 2
H2F(also DHF) dihydrofolate or 7,B-dihydrofolate dihydrofolate (H2F or DHF) or
7.8dihvdrofolate (H7For DHFI
H4F (also THO tetrahydrofolate or tetrahydrofolate or
5.6.7.8-tetrahvdrofolate 5.6.7.8-tetrahvdrofolate
Hb hemoglobin hemoglobin
HbA1,, HbAlb, HbAlc glycated (not glycosylated4~') preferred: glycated hemoglobin
hemoglobin fractions A,,, etc (also: qlycohemoglobin A,,)
HbCO carbon monoxyhemoglobin, carbon monoxyhemoglobin
carboxyhemoglobin
HbOz oxyhemoglobin oxyhemoglobin
HERZ/neu from human epidermal growth ERBB2 (formerly HER2 or
factor receptor 2; preferred term HER2/neu)
is now ERBBZ; see also 15.6.3,
Genetics. Oncogenes and Tumor
Suppressor Genes
Table 13. Molecular Terms (cant)

Suggested Usage at %

Term Explanation First Mention

NMDA N-methyl-paspartate N-methyl-o-aspartate

NMN nicotinamide mononucleotide nicotinamide mononucleotide
NMN+ oxidized NMN NMN+
NMNH reduced (hydrogenated) NMN reduced or hvdroqenated NMN
NMP nucleoside monophosphate nucleoside monophosphate
NOx nitrogen d+des, such as nitrate, nitrogen oxides
nitrite, and nitrosothiols;
nitric oxide (NO) metabolites
NW neuropeptide Y neuropeptide Y
N-terminalfragment of the N-terminal fragment of the
prohgrmone brain natriuretic peptide prohormone brain natriuretic
(see 15.6.1, Genetics, Nucleic Acids peptide
and Amino Acids under ''Amino Acids")
the INK4 p16Ink4,etc

~21 2 1-kDa protein the protein p21

p21Ww'P1.p27K'P1, other CDKI; WAFI: wild type the CDKl p21WAF'~c1P',
etc
~ 5 7 ~ ' ~ ~ p53-activatedprotein 1;
CIPl: CDK-interacting protein 1;
KIP: kinase inhibitor Drotein
- -

P53 53-kDa protein the protein p53 (or simply p53 if a

similarly named protein has already
been introduced) .
057 57-kDa ~rotein the ~rotein1357 (or 135'1)
PE, PPE protein or gene family named for PE and PPE protein families.
amino acid sequence motif (PE: Pro-Glu, PE/PPE gene families, etc
PPE: Pro-Pro-Glu); see 15.6.1, Genetics,
Nucleic Acids and Amino Acids
PQD P-alvco~rotein P-alvco~rotein
Pi inorqanic phosphate inorqanic phosphate
PI phosphatidylinositol phosphatidylinositol
PIP, phosphatidylinositol phosphatidylinositol
4.5-bisphosphate 4.5-bisphosphate
Pol polymerase (eg. DNA. RNA) polymerase
PP. inoraanic ovro~hos~hate inoraanic ovroohos~hate
-

retinoblastoma protein retinoblastomi protein

PW3.36 NPY receptor agonist (P: peptide; peptide YY3-36,the gut
Y: NPY; Y: Y2 receptor; 3-36: hormone PYY3.36
34 amino acid residue numbers)
 15.10.3 Enzyme Nomenclature

Enzyme ~ornenclature.~ Enzyme nomenclature was formalized in the 1950s.' It 1s

formulated by the International Union of aochemistry (IUB)and the International
Union of Pure and Applied Chemistry (IUPAC), more specifically, the Nomencla-
ture Committee of the International Union of Biochelnistry and Molecular Biology
(NC-IUBMB) and the JUPAC-IUB Joint.Cornmission on Biochemical Nomenclature.
There are around 3500 listed enzymes. Officially assigned names and numhers
for enzymes are available at the Enzyme Nomenclature Database: http://www.chem
.
.qmul.ac.uk/iubmb/enzyme/.Rules for enzyme nomenclature are available at http://
www.chem.qmul.ac.uk/iubmb/enzyme/rules.html.
There are 3 types of enzyme name: recommended i?ame (common, working, or
trivial name), systematic name, and Enzyme Commission (EC) number. The recom-
mended name is the nqme by which the enzyme is commonly known. The systematic
name incorporates the reaction the enzyme catalyzes. The EC number is a unique
identifier assigned to each enzyme.
Because systematic names can be unwieldy and recommended names are well
known, recommended names are used in general medical publications. For unam-
biguous identification, the EC number, the systematic narhe, or both may be included
at first mention.
The parts of the EC number are as follows:
class
subclass
sub-subclass
serial number within sub-subclass
The enzyme classes are as follows: .,..'
EC1: oxidoreductases
EC2: transferases
EC3: hydrolases
EC4: lyases
EC5: isomerases
ECG: ligases
Examples are shown below:
EC No. Recommended Name Systematic Name
Ec 1.11.1.7 peroxidase donor:hydrogen-peroxide
oxidoreductase :
EC 2.3.3.10 hydroxyinethylglutaryl-COA acetyl-CoA:acetoacetyl-
(was EC 4.1.3.5) synthase CoA C-acetyltransferase
EC 2.7.1.1 hexokinase ATP:u-hexose
6-phospliotransferasc
acerylcholine
:~cetyll~yclrol:~\c
~-1;1c~.11ii )I.Ix.
11ycIr1
'9Y

EC No. ~ecommendedName
EC 6.5.1.1 DNA ligase (ATPI

XEFERENCES
1. Tipton K, Boyce S. History of the enzyme nomenclature system. Bioinfomatics.
2OO0:16(1):3440.
2. 2005 Database Issue. Nucl Acids Res. http:~nar.oxfordjournds.o&/c~ntent
/vol33/suppl-11. Accessed April 20, 2006.
3. Apte SS. ADAMTS Nomenclature. http://www.lerner.ccf.org/bme/apte/adamt
/nomenclature.php. Published September 30, 2004. Accessed April 20, 2006.
4. Fuentes-Arderiu X "Glycohemoglobin," not "glycated
hemoglobin." Clin Chem. 1330;36(6):1254.
5. Roth M. "Glycated hemoglobin," not "glycosylated or
1983;29(11):1991.
6. S&ron N. Nomenclature of glycoproteins, glycopeptides and peptidoglycans. PU
Appl Cbem. 1988;60(9):1389-1394.
7. Glycated proteins. JCBN/NGIUB Newsletter 1984. http://www.chem.qmul.ac.uk
/iubmb/newsletter/misc/glypro.html.Accessed June 6, 2006.
8. Moss GP; Nomenclature Committee of the International Union of Biochemistry
Molecular Biology (NC-IUBMB) in consultation with
mission on Biochemical Nomenclature UCBN).
tions of the Nomenclature Committee of the International Union of Biochemistry-
Molecular Biology on the Nomenclature and Classification of Enzyme-Catalysed :
Reactions. http://www.chem.qmuI.ac.uk/iubmb/
Accessed April 20, 2006.

Neurology

Nerves. Most nerves have names (eg, ulnar nerve or nervus ulnaris). English
are preferred to Latin.For terminology, consult a medical dictionary, anatomy
Tminologia ~natomica.'

Cranial Nerves. The cranial nerves are as follows:

N m English Name Latin Name
I olfactory olfactorius
I1 optic opticus
I11 oculomotor oculomotorius
IV trochlear . trochlearis
V trigeminal trigerninus
VI abducens abducens
VII facial facialis
VIII vestibulocochlear vestibulocochlearis (acoustic)
IX glossopharyngeal glossopharyngeus
X vagus vagus

-. - . -. . .
 15.11.1 Nerves

Nem Engli~bName Lutin Name

XI accessory accessorius
XI1 hypoglossal hypoglossus
Use roman numerals or English names'when designating cranial nerves:
Cranial nerves 111, IV,and VI are responsible for ocular movement.
The oculomotor, trochlear, and abduiens nerves are responsible for ocular
movement.
Use ordinals when the numeric adjectival form is used:
The third, fourth, and sixth cranial nerves are responsible for ocular
movement.
Vertebrae, Spinal Nerves. Spinal Levels, Derrnatomes, and Somites. These entities
. share a common nomenclature, deriving from spinal anatomic regions: cervical
(neck), thoracic (?nk), lumbar (lower back), sacral (pelvis], and coccygeal (coccyx
or tailbone).
Spinal nerves C1 through C7 are named for the vertebrae above which they
emerge, while T1 through S5 are named for the vertebrae below which they emerge.
Spinal nerve C8 emerges below vertebra C7; there is no C8 vertebra.
Vertebrae and spinal nerves are as follows.
Region Vertebrae Spinal Nemes
cervical C l through C7 C1 through C8
thoracic T1 through T12 T1 through T12
lumbar L1 through L5 L1 through L5
sacrum Sl through S5 S1 through S5
CC'(=cyX 4 fused, not individually coccygeal nerve
designated
The alphanumeric terms need not be expanded and, when clear in contest. ..vcr-
tebra" and "nerve" need not be repeated:
The first cervical vertebra is also known as the atlas, C2 as the axis, ancl C7 ;is
the vertebra prominens.
Portions of a vertebra may be referred to as follows, ie, without the term w~el7rrr:
C5 spinous process
L3 lamina
T12 transverse process
Hyphens are used for intervertebral spaces (including neural foramina) nnd intvr-
vertebral disks, as follows:
Space I)isli
C2-3 (space between C2 and C3) C L -~!~sb
T2-3 (space between T2 and T3) .r2-3 C \ I A
L2-3 (space between L2 and 1.3) J.2.z ~1i.k
15.11 Neurology

C'-1.1 (hpacc tx.t\vccn 0 and T1) C7-T1 disk

Lj-ST (space benveen L5 and S1) L5-S1 disk

L 4 - j diskectomy
(Note: Terrninologia Anatonlica uses disc, not disk. See also 11.0, Correct and Pre
ferred Usage.)
The sacrum, because its vertebrae are fused, does not contain intervertebn
. Its 4 paired foramina are COInmonlj referred to as the first nen
unen), second sacral formnerI (or S2 foramenI>,etc.
Ra~gesof vertebrae are expressed as in the following examples; use letters fori
both the first and last vertebra in the indicated range:
C3 through C7 third through seventh cervical vertebrae (not C3 through 7
T6 through S1 sixth thoracic through Iirst sacral vertebrae
Ranges of vertebrae when used as modifien have one or more hyphens, eg:
C1-C3 arthrodesis
C2-TI spinous processes
C4T3 fusion
L1-L2-L3 motion segments
L1-L4 bone mass density
..
1

L2-S1 canal stenosis

L3-L4L5 fusion
L4-L5 laminectomy
erosion of T9-TI2 vertebrae
The same abbreviations are used for spinal segments or levels, spinal dermatome
and somites. Text should indicate which is W i g referred to, eg, vertebra, spG
nerve (or root, radiculopathy, or distribution), spinal level, dermatome, or somit
Within a clear context, as noted above, the words vertebra, nerve, etc, need not t
repeated. 3
Serious injury of the cervical cord at the level of the C2-C5 vertebrae causes;
respiratory due to injury of spinal nerves C3 through C5. 5

The first patient had herpes zoster in the T9 dermatomal distribution, thej
second patient in the C5 distribution.
L1-S2 radiculopathy
L3-L4-L5 periradicular infiltration

Electroencephalographic ~ e r m s . ~ , ~ ( ~Guidelines
~ ~ ~ " ~ 'for * ~ electroencephalog
.~
:EEG) are available throu the Annerican (Ilinica eurc Soc
erly the American Elecu ncephal[ographic: Soci htt] ns.c
and at the International Federation of Clinical Neurophysiology Web site (IFC
http://www.ifcn.info; formerly the Intemationql Federation of Societies for Electr
encephalography and Clinical ~ e u r o ~ h ~ s i o l o g y ) . ~
 1 5 . 1 1.2 Electroencephalograph~cTerms

Figure 8. Electroencephalographiclead positions, from EEG in Clinical Practice, 2pd ed, by J. R. Hughes,
Boston, MA, Butterworth-Heinemann; 1994:2. Reprinted by permission of Elsevier.

. The International 10-20 System specifies placement of electrodes used in elec-

troencephalography. The 10-20System, which originated in the 1950s,~'~ is so named
because electrodes are spaced 10%or 20% apart along the head (Figure 8).
The terms used in the 10-20 System are widely used and recognized. They are
systematically derived, as follows:
Letters refer to anatomic areas (primarily of the skull, which do not necessarily
coincide with the brain areas from which the electrodes register electrical activ-
ity).
m Odd numbers are for electrodes placed on the left side, even numbers are for
electrodes placed on the right side, and the letter z ("zero") is for midline elec-
trodes.
Electrode Designation Location
A l , A2 earlobe
Cz, C3, C4 central
F7, F8 lateral frontal (anterior temporal)
Neurology

i ~ l c z - f n x,b! A
~ , ~ I ~ I I U I ~ O ILML~IIOII
:
F p 1 . FpL fronul jwlc or prrlronlal
Fz, F3, F4 superior frontal
01, 0 2 occipital
Pz, P3, P4 parietal
T?': T4 midtemporal
T5,T6 posterior temporal
Additional electrodes and other placement systems may be used, for insta
"modified combinatorial nomenclature" also known as the extended 10-20 e
system or the 10% system, which adds electrodes at intermediate 10% positions.
The same electrode may have a diFferent name in the 10-20 and the 10% syste
The added electrodes'result in additional numeric designations for exis
electrodes (eg, C5, F10) and in new letters or letter-number combinati
following examples:
EIectrode ~ e s i ~ k t i o n Location
AFz, AF3, AF4, AF7, AF8 anterior frontal
Cl, C2, C5, C6, centrotemporal
Cpz, CPI-CP6 centroparietal
FCz, FC1-FC10 frontocentral
FP~ midprefrontal
FT7,FT8,FT3,m 1 0 frontotemporal
Iz inion
Nz nasion
Oz midoccipital
PI, P2, P5-PI0 parietal-posterior temporal
POz, P03, P04, P07, PO8 parietwxcipital
S P ~S, P ~ sphenoidal
TI, T2 true anterior temporal
T7-TI0 " centrotemporal -
TP7-PI0 temporal-posterior
Neonatal electrodes may be placed differently (eg, the 12.5% to 25%
Children's Hospital of British Columbia) and may (or may not) have
ignations? eg:
LaF left anterior frontal
LaT left anterior temporal
LFC left frontocentral
LO left occipital
LP left parietal
LST left superior temporal

_ . - .
. i'.
 RaF right anterior frontal
RaT right anterior temporal
RFC right frontocentral
RO right occipital
RP right parietal
RST right superior temporal
-
In figures showing EEGs, electrode symbols usually will be paired. Usually, the
symbols will be beside and to the left of each channel of the tracing but may be above
and below each channel with connecting lines. Authors should include with tracings
a time marker and an indicator of voltage, as in the top tracing (Figure 9).

Figure 9. Sample electroencephalographic tracings (schematic).

Descriptions of EEG potentials include many qualitative terms for waveforms

and frequencies. The following are a few of numerous descriptive terms tnorc tli;~r
Greek letters are spelled out):
alpha rhythm, beta activity, polymorphic delta activity, sleep spindles. spikc-
wave complexes, paroxysms, spikes, sharp waves. delta \,rush. frontal slurp
trahsient, mu rhythm, lambda waves
A comprehensive glossary of EEG terms has been pro\:icled hy the 1I:CN.''
Frequency is given per second (Is). For cycles (c) per second. hcnz (1-iz) is
preferred to c/s (see 18.1, Units of Measure, SI Units):
10-Hz alpha zictivity
a theta frequency of 5 to 7.5 1-12
1;-Hz spindles
(d)-tlz artifact
l ) . ~ ' kKrc,tlncl rhythm of 8 to 1 0 11%
15.1 1 Neurology - ..

Evoked P0tentials..~(p~~~-"),3~14-1~
several wpes of ,-vc1,-~ - ,

elecuical signals) may be recorded: brainstem auditory

somatosensory evoked potentials (ccED- ;--I.-J:-- ----
lowing, which are not mutually e.-----..,. ,.,.
extremity, median nerve, posterior tibia1 nenr-'
including pattern [PVEPI and flash [FVEPI). - --- ---,
- -
recording electrodes and produces tracings.
Electrode terminology resembles that ""'
modified electrodes such as the following, ..,. llldy uc uscu wlrnour expanslo]

BAEP electrodes:
Ac contralateral earlobe
Ai ipsilateral earlobe
EAM external auditory meatus
EAMc contralateral EAM ,;<
EAMi ipsilateral EAM
M1 M2 mastoid process
contralateral M
ipsilateral M

AC anterior cervical
Cl', C2, C3', C4' near EEG C1, C2, C3, C4
C2S, C5S C2, C5 spinous processes
Cc contralateral C3' or C4'

CP midway between C3 or C4 and P3 or p4 ..

. :i
CPc contralateral CP :.j j3
,'?;

CPi insilatenl CP

EP Erb point
EP1, EP2 left and right EP
EPi ipsilateral EP
F P ~ near EEG Fpz
IC iliac aest
L2S. L3S L2, L3 spinous processes
LN lateral neck
LNi ipsilateral LN
PFd, PFp popliteal fossa (distal, proximal)
REF reference
T ~ STlOS,
, T12S T6, T10, T12 spinous processes
 15.11.4 Polysomnography and Sleep Stages

W electrodes:
I inion
LO left occipital
LT left posterior teinporal
MF midfrontal
MO midoccipital
MP midparietal
.RO right occipital
RT * - right posterior temporal
V 'vertex

Waveforms recorded in evoked potential testing are identified with P for positive o r
N for negative plus a number indicating milliseconds between stimulus and response
in normal adults:
t
VEP: N75, N100, N155, P75, P100, PI35
SSEP: N9, N11, N13, N15, N18, N20, N34, N35, P.9, P11, P13, P15,
P27, P37

SSEPs were. . .recorded from the brachial plexus (Erb potential), cervical
spine at C2 (N13), and the contralateral parietal area (N19) with a frontal (Fz)
reference.
SSEPs showed normal Erb point and cervical potentials and significant delay
of scalp components (N20 latency >>3 SDs, N13-N20 central conduction
time >3 SDs, bilaterally).
Persistent delay of the PlOO wave of the pattern-reversal vEP after an epi-
sode of optic neuritis isxonsidered to be compatible with residual demye-
lination within the optic nerve.
An additional SSEP wave is the LP (lumbar potential).
Other waves, eg, in BAEP, are designated with roman numerals:
I through VII vertex-positive waves
I' through VI' vertex-negative waves

BAEPs of the proband showed normal wave I, increased latency of waves 11

and 111 (>3 SDs), and absent IV and V components despite normal hearing
acuity.
1-111 interpeak interval

V/I amplitude ratio

; Polysomnography and Sleep stages.' '* I ' o l ~ - s o ~ r ~ n , , ~Ir\ . rhc:

r ~ ~11,onitorln~
\,~~ of
i various physiologic p;~nrnc*Ier.;~ I I ~ \ U I I . I ~ Itl!lrlrlg
~.I,II~ \lcr-l>.
I V ~ncluclingtlic f o l -
t lowing:
1
k
15.1 1 Neurology
U

r
I

w EEG: standard electrodes are used (see 15.11.2, Electroencephalographic ~ermsj:

1

M Electro-oculogram (EOG): tracings are obtained from the left eye and right eye
~ i l Electrornyogram (EMG): submental (chin) EMG, leg muscle EMG, eg, left anterio;;
tibialis, right anterior tibialis
Respiratory function, eg, oxygen saturation (Sao2), expired C02, and tidal volume
(VT) (see 15.16, Pulmonary, Respiratory, and Blood Gas Terminology) ,..I

ill Electrocardiogram (ECG): see 15.3.1, Cardiology, Electrocardiographic Terms .

Sleep stages are as follows19: ,
rapid-eye movement sleep (REM sleep)
non-rapid eye movenient (non-REM) sleep (NREM sleep)
sleep stage 1
sleep stage 2
sleep stage 3
sleep stage 4

Molecular Neuroscience. The following terms are provided for reference (a rnajo~
source is Nestler et a124 (see also 15.10, Molecular Medicine). Terms with asteriskii
. ,!
. .'
need not be expanded; others should be expanded at first mention. +

Term Expansion or ,lhpkanution

a-adrenergic receptor,
ci receptor' (subtypes:
UlA, ~ I B UID,
, UU, UZBI
ax, I

ci-synuclein
A:, A2* neuropeptide adenosine receptors (also known as 4
purine receptors PI,Pz,see also 15.6.1, Genetics, :
Nucleic Acids and Amino Acids) 3

ACh acetylcholine
.!
AChE acetylcholinesterase
:i
a-amino-3-hydroxy-5-methyl4isoxazole 5
propionic acid class of glutamate receptor
P-adrenergic receptor,
p receptor' (subtypes: I
I

P11 82, 93

BDNF brain-derived neurotrophic factor

CCR3, CCR5, CXCR4 chemokine receptors (see 15.8.1, Immunology, +

Chemokines)
Chl through Ch8 cholinergic nuclei
;:y
CNTF ciliary neurotrophic factor ,-a

COMT - catechol-0-methyltransferase
3
cytokines (see 15.8.4, Immunology, Cytokines)
4
 15.1 1.5 Molecular Neuroscience

Term Expansion or Explanation

opioid 6 receptor
dopamine receptors
DAT - dopamine transporters
excitatory amino acid reuptake transporters

EGF epidermal growth factor

GABA y-aminobutyric acid
GABA receptor classes
GABAergic GABA-mediated
GABA-T GABA transaminase
GABA family transporters

GDNF . ...
GFR
-. glial cell line-derived neurotrophic factor
GDNl-neurturin receptor
G protein-coupled Kir3 channels
histamine receptors
5-hydroxytryptamine, serotonin (preferred
expansion)
5-HTreceptors

serotonin transporter
a polymorphism of the serotonin traqsporter gene
(LPR: length polymorphism region) (see also
15.6.2, Genetics, Human Gene Nomenclature)
interleukins , (see 15.8.4, Immunology, Cytokines)
IP3 inositol triphosphate
K-receptor opioid K receptor
K(ATP) channel potassium channel
K(Ca1 ~ a ~ + - ~ aK+
t e channel
d
Kirl, KSr2, Kir3, Kir4, inwardly rectifying K+ channels
Kir5'
L channels, L-type large-current or long-open-time caZ+channels
channels*
preceptor opioid p receptor
MI through M5' muscarinic receptors
MA0 monoamine oxidnse
MAO.4, MAOa major forms of MAO
N channels* neuron;~lc a 2 + ch;~nnrlz
nAChRs nicotinic ; ~ c e r y l c l ~ ~ ,i tl.i, r(~. p~r t~) r b
15 1 1 Neurology

Tcmt
KET norepinephrine GABA family transporter .ff
neuromedin B'
neuromedin K*
ncuropeptidc Y*
NGF nerve growth factor
NKI NK2 NK3 neuromedin K tachykinin receptors
'2
NMDA N-methyl-D-aspartateclass of glutamate receptor<
nNOS (also NOS1) neuronal nitric oxide synthetase 3A
NSF N-ethylmalearnide sensitive factor
NT-3, NT-4 neurotrophin 3 and neurotrophin 4
NTSl, NTs2 neurotensin receptors
P channels* Purkinje ca2+ channels #
p1, p2* neuropeptide purine receptors (also known as
adenosine receptors Al, A2, see also 15.6.1,
Genetics, Nucleic Acids and Amino Acids)
R-PTK receptor-associated protein tyrosine kinase 'i
<<.
o-receptor opioid o receptor
SERT serotonin GABA family transporter
SNAP-25 synaptosomal associated protein of 25 kDa. ..
SNAPS soluble NSF attachment proteins (note differer
expansion of SNAP than for SNAP-25)
SNARE proteins SNAP receptors
SNAREpins hairpin forms of SNARE proteins
substance P*
T channels* transient ca2+ channels
t-SNARES t: target membranes
VAChT vesicular transporters of ACh
'JAMP vesicle-associated membrane protein, synapto-
brevin
VGAT vesicular transporter for GABA
VGlutTl vesicular transporter for glutamate
W T l vesicular transporter for monoamines
V-SNARE . v: vesicle
YIPYi!, Y4r Y5, Y6 neuropeptide Y receptors
Ge:ne symbols for many of the above terms are found in the list of genes in 15.6
4
Ge:netics, Human Gene Nomeniclature. For reference, gene symbols are given be!$
for terms in the preceding list .R?hose abbreviations do not closely resemble the ga
4<
.
;

SY' nbol:
 15.11.5 Molecular Neuroscience

Term Gene Symbol

AI ADORAl

6 receptor - OPRDI'

H1 HRHl
5-HTu HiTIA
K receptor OPRKl
,u receptor OPRMl

neuromedin K TAC3
NMDA . GRIM
o receptor OPRSl
substance P TAC1
transporters (various) SLC genes (various, eg, SLCGAI)
Y1 NPYZR

REFERENCES
1. Federative Committee on Anatomical Terminology. Teminologia Anatotnicn. Sturr-
gart, Germany: Geog Thieme Verlag; 1998.
2. Victor M, Ropper AH. Adatns and Victor'sPrinciples of Neurology. 7th ed. Ne\v York.
NY: McGraw-Hill; 2001:27-41.
3. Gilmore RL, ed. American ~lectroence~halogra~hic Society Guidelines in Electro-
encephalography, Evoked Potentials, and Polysomnography.] Clin k e u t ~ ~ ~ ~ ~ s i o ~ .
lW4;11(1):1-158. ,

4. Comolly MB, Sharbrough FW,Wong KH. Electrical fields and recording techniques.
In: Ebersole JS, Pedley TA, eds. C u m t Practice of Clinical Electmencephalogr~1pI7~~.
3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:72-99.
5. Reilly EL. EEG recording and operation of the apparatus. In: Niedemeyer E, Lopes da
Silva F, eds. Electmcephalography: Basic Principles, Clinical Applicatio)~~, nt~~l
Related Fields. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 200j:139-1j9.
6. America? Clinical Neurophysiology Society Web site. http:/www.acns.org. Accessed
April 20, 2006.
7. Nuwer MR, Comi G, Einerson R, et al. IFCN st;~nclarclsk)r tligital rccorcling of clinicel
EEG. Electroencepba~ogrClin Neumpbysiol. 1998;106(3):259-261.Also available at
http:/www.ifcn.info. (See IFCN Publications, then IFCN Standards under Useful
Links.) Accessed April 20, 2006.
8. Jasper HH. Report of the Committee on Methods of Clinical Examination in Electro-
encephalography: 1957. Electroencephalogr Clin Neurophysiol. 1958;10:370-375.
9. Rowan AJ, Tolunsky E. Pn'mw of EEG: With a Mini-Atlas. Philadelphia, PA:
Butterworth-Heinemann; 2003.
10. Sharbrough F, Chatrian G-E, Lesser RI', I.uders H, Nuwer M,Picton W Electrocle I'o-
sltion Nomenclature Committee. American ElectroencephalographicSociety guidelines
for standard electrode position nomenclature.] C[in Neurophysiol. 1991;8(2):200-202.
.IC Terms

glossary of terms most common

proposal for the report form for the EEG findings. Electmencepbalogr Clin Neum-
pbysiol Suppl. 1%;52:21-41.
14. American Association of Electro

S123-S138.

ommended standards for electroretinograms and visual evoked potenti

Useful Links.) Accessed April 20, 2006.

, Current Practice of Clinical E l e c t ~ h a l o g

Sleep Medicine; 2001. Also available at http:

Accessed April 20, 2006.

Obstetric ~ e r r n s Two
. colloquial

1G P A . ~ ( The
~ ~ ~ ~G,~P,~a ~ )
letters

specified. In the expansions below, the clinical meaning associated with

G gravida pregnancies
P . Para births of viable offspring
A or Ab aborta abortions
 15.12.3 Apgar Score

For example, G3, P2, A1 would indicate 3 pregnancies, 2 births of viable offspring.
and 1 abortion. In published articles, however, it is preferable to write out the
expression, eg:
gravida 3, para 2, aborts 1
Although some sources, including medical dictionaries, feature roman nurperals with
these expressions, use arabic numerals.
Quantifying prefixes combine with the terms gravida and para (see list below).
Noun forms are gravidity and parity (with prefixes, nulligravidity, multiparity, etc).
Adjective forms are gravid and pamus (with prefixes, muftigravid, nulliparotrs,
primzpamus, etc).
Term 'Meaning
nulligravida gravida 0
primigravida gravida 1
secundigravida gravida 2
multigravida gravida >1
nullipara para 0
primipara para. 1
multipam para > 1
grand multipara para r 5
Even these Latinderived terms are somewhat imprecisea5Therefore, in addition to
use of expansions, further specification (eg, single or multiple births, ectopic preg-
nancy) is required in scientific articles.

- T P A L . ~ (The
~ ~letters
~ ~ in~ this
~ ~expression
) indicate obstetric history as follows:
Lettter
- Expamion
T term deliveries '
P premature deliveries
A abortions
L living children
Often,.4 numbers separated by hyphens are recorded, eg:
TPAL: 3-1-1-4 or 3-1-1-4

which would indicate 3 term deliveries, 1 premature delivery, 1 abortion, and 4 livihg
children. However, the text of a manuscript should define the numerical expressions
and not give the numbers alone:

Apgar ore.^(^^^^.^^^).^.^ 'I'liis sc'on' is :III :IssCssI~icnIof :I I ~ C ' W I ~ O ~ I I ' S I>Iiy~ic;ll

~~'11-
being hascd on the 5 p:lr;imeters of heart rate, I>reathing,m ~ ~ s ctone, l c reflex irrita-
bility, and color, e3ch of which is rated O,1, or 2; the 5 ratings are then summed. The
Apgar score is often rcponed as 2 numbers, from 0 to 10. separated by a virgule or
fonvnrtl Insh, rrflccting ssst.\\rncnt :I[ 1 minute and 5 minutes after hirtli. In general
n~cdic;~ljoi~rri;ils,however. 11 is Ixst ro specify the time inten~als.especially as the
Apg;~rsc.orc may Iw ;i~ses~etl at nthcr intcn;;ils, cg, 10. 15. o r 20 ~iiinutcs.
P
t
I 735
almology Ter

Ambiguous: Apgar of 9/10

Preferred: Apgar score of 9/10 at 1 and 5 minutes
or
Apgar score of 9 at 1 minute and 10 at 5 minutes
The score is named after the late anesthesiologist Virginia Apgar, MD; thus, "Apgar" j
not printed in all capital letters as though for an acronym (although versions of suc
an acronym have been created as a mnemonic device).
i
REFERENCES 1

1. Ely JW.Summarizing the obstetric history [question].J . . 1991;266(23):3344.

2. Pun TC, Ng JC. "Madame is a 30-year-old housewife, gravida X, para Y . . . . " Obstei
Gynecol. 1989;73(2):276-277. J
%

3. Woolley RJ. Parity clarity: proposal for a new obstetric shorthand.J Fam Pract.
1333;36(3):265-266.
4. Cunningham FG, Gant NF,Leveno KJ, Gilstrap LC 111, Hauth JC, Wenstrom KD.
Williams Obstetrics. 21st ed. New York, NY:McGraw-Hill; 2001. i ic
x Summarizing the obstetric history [answed.J M .1991;266(23):3344.
5. ~ u c k JH.
6. Cornminee on Fetus and Newborn, American Academy of Pediatrics, and Committt
on Obstetric Practice,American College of Obstetricians and Gynecologists. Use ar
abuse of the Apgar score. P e d M . 1996;98(1):141-142. 4
7. Apgar V. A proposal for a new method of evaluation of the newborn infant. C u r R
Anesth Analg. 1953;32(4):260-267. h u p : / / ~ . n e o n a t o l o g y . o r g / d a ~ s i ~ ~ / a p g ~
Modified April 27, 2002. Accessed April 20, 2006. 17,

8. Apgar V, Holaday DA, JamesLS,Weisbrot ZM, Bemen C. Evaluation of the newbol

infant: second report. J M .1958;168(15):1985-1988.
Ophthalmology Terms. Some of the terms described in this section are spec$
ophthalmology, and others have special usage requirements in ophthalmology. $
also 11.0, Correct and Preferred Usage.
. 4?
adnexa ocul:iAlthough often used as a synonym for eyelids, the term adnexa gj
(which is .ral) prc~ p e r l des the eyelids, lacrimal and
pendages h e eye and be usec1 with its, inclusiv
diopter-The diopter is a measine of the power of an optical lens and is the recipr
of the focal length in meters. Diopter is abbreviated D when used with a numt
diopter sphere
diopter cylinder
conversion from diopters to rnillieters
correction of 1'0.5 D
The prism diopter is a meaiure of the power of a prism and represents a&
deflection of an image at a distance of 1 m. Its symbol, A, may be used with 1169
after first mention. ., -4
The left eye showed an improvement, with only 25-prism diopter - 3J
hypouopia.
distance exotropia = 35 prism diopters (A); near exotropia = 56
 -.

15.13 Ophthalmology Terms

disc; cup-disc ratio-For the optic disc, spell as disc (not disk). The cup-disc ratio
refers to the ratio of the diameter of the optic cup (a central area of the optic disc) to
the diameter of the optic disc:
cup-disc ratio of 0.6 -
It can be useful to speclfy whether the ratio is vertical, horizontal, or other, eg:
The mean horizontal cup-disc ratio by contour estimated from stereo-
photography was 0.36 f 0.18 (mean f SD).
disc diameters and disc areas-Disc diameters (DD) may be used to indicate location
or dimension of findings oi the ocular fundus with relative distances expressed as
diameters of the optic disc, eg:
2 DD inferior to the fovea
Lesions varied from 0.5 to 4.5 disc diameters (DD; median, 2.0 DD) for the
first group, 0.75 to 7.5 DD (median, 2.5 DD) for the second group, and 1.0 to
9.0 DD (median, 4.0 DD) for the last group.
Disc areas (DA) are also used to indicate relative sizes of findings on the ocular
fundus, as well as in considerations of the size of the disc,.eg:
The scar measured 3 DA.
Significant ischemia was defined as greater than 10 disc areas of retinal
capillary nonperfusion.
reduced disc areas (DA) .. . mean (SD) DA of 2.57 (0.71) rnm2
electroretinogram-Waves of the electroretinogram (ERG) are as follows:

An ERG may be described as normal, subnormal, or negative. Do n u substitute one

of these terms for another. (For visual evoked potentials, see 15.11.3, Neurology.
Evoked Potentials.) Waves of the pattern electroretinograrn (PERG)' are ah follo~~si

Two main components of the PERG are the P50 wave, a positive-deflection wrrvc-
form, and the N95 wave, a negative-deflection waveform. The terms 1'50 ancl N95
may be used without expansion.
fovea and ma$ula--The central retinal fovea is a central portion of the retinal nl;~c~il;~.
The termsfovea and macula should be used specifically and not interchnnge;~\>ly.
Goldmann perimetry-This is a method of assessing the visual field. The tcst diinuli
are described by means of a 3-part term: spot size is designated with roman n i i n l r ~ ~ l s
I through V, and luminance is designated with arabic numerals 1 through -i;111cl
letters a through e. For example:
I-4-e isopter area
I-2-e test object
V-4-e light
 -- .

almology Terms

greatest linear dirnension-'This is,the greatest dimension between 2

boundary of a lesion.
Lesion size was less than or equal to 9 disc areas, and greatest linear di-
mension was less than or equal to 5400 pm.
injection-When used to indicate excess blood, engorgement, or dila
should be changed to hyperemi or vasodilation, eg, conjunctival
conjunctival vasodilation (not conjunctival injection).
intraocular pressure-Measurements of intraocular pressure should
method used, eg, Goldmann applanation tonometry and, if determined,
thickness measurement.
lasers-Lasers used in ophthalmology include the following;
argon laser
erbium:YAG laser
exirner laser
ho1miurn:YAG laser
krypton laser
Nd:YAG laser
photodynamic therapy laser
Q-switched Nd:YAG laser
transpupillary thermal therapy
The term Nd:YAG (ne0dyrnium:yttrium-aluminum-garnet)may be used withou
expansion.
lid&* should be changed to'@i&.
masked-Masked, rather than blinded, should be used in the ophth
erature, when referring to randomization, if there could be confusion.
OD, OS, OU--These abbreviations may be used without expansion
bers, eg, 20125 OU, or descriptive assessmentsof acuity (eg, counting
visual acuity, vision, below):
Abbmkation Derivation Expansion
OD oculus dexter right eye
0s oculus sinister left eye
OU oculus uterque each eye
Note that OU does not mean both eyes, although it is often used incorrectly
vision measurement (eg, visual acuity or visual field) with both eyes at the s
See also visual acuity, visiin, below.
orbit-Orbit refers to the bony cavity that contains the eyeball and its ad
(muscles, vessels, nenres). It should be clear to readers whether authors are refe
tothe orbit, the specific bones that compose it, the structures that fill the orbit, or
combination of these.
visual acuity, vision-Distinguish between uision, a general term, and visual ac
measurable clearness of vision. If a measurement is given, eg, 20/20 (see below),
 -.

15.13 Ophthalmology Terms

"visual acuity." Change "unaided vision" to "acuity without correction." (See :ilso
11.O, Correct and Preferred Usage.)
distance acuity-The Snellen eye chart is a well-known method of assessing
distance visual acuity, resulting in the Snellen fraction, an expression such as 20/LO.
20/15, or 20160. The first number represents the testing distance from chart to pa-
tient; the second number represents the smallest row of letters that the patient c;ln
read. For example, acuity of 20140 indicates that at 20 ft the smallest line read is
readable by a normal eye at 40 ft.
The units for distance acuity are feet (eg, 20 ft) or meters (eg, 6 m). fiy con-
vention, acuity is expressed without these units specified, eg, 20120.JAMA and the
Archives Journals folIqw the author's preference in expressing distance acuity
equivalents as metric, eg, 6/6, or'English, eg, 20120, and do not convert English
fractions to metric or vice versa: Only one type, English or metric, should be used
throughout a manuscript.
Visual acuity is assessed separately for each eye. Other means are also used
to assess visual acuity, eg, counting fingers (CF), hand motions (HM), and light
perception (LP), which is indicated as LP with projection, LP without projection, or
no LP (NLP). Express visual acuity, including numerical.measures and other means,
by using OD or RE (right eye) and OS or LE (left eye). (See also OD, OS, 'OU,
. ,

The visual acuity was 20/40 OD and counting fingers OS. ,

Another method of assessing visual acuity makes use of the Bailey-Lovie acuity
chart and designates acuity using the base 10 logarithm of the minimum angle of
resolution, or logMAR. A logMAR of 0.0 is equivalent to 20/20 Snellen. LogMAR
visual acuities always should be expressed in logMAR.
near visual acuity- ear visual'icuh (reading vision) may be reported by means

visual field-The extent of the visual field is described by means of degrees from a
central point from 0" through 90":

65" nasally
58" up and nasally
REFERENCES
1. Celesia GG, Bodis-Wollner I, Chatrian GE, Harding GFA, Sokol S, Spekreijse H.
Recommended standards for electroretinograms and visual evoked potentials:
report of an IFCN committee. ~ l e c t m ~ e p h a l Clin
o ~ rNezrmphysioI. 1333;87(6):
421-436. Also available at http://www.ifcn.info. (See IFCN Publications, then lFCS
Standards under Useful Links.) Accessed April 20, 2006.
2. Millodot M,Laby DM. Dictionary of Ophthalmology. Woburn, MA: Rutren~cmtr-
Heinernann; 2002.

7 39
15.14 Organ~smrand Pathogen,

6
In fen~pera
re Iu 11guugeshotcld rrof be used i?z atzy
disctusion or uv-iting uhich i ~ z m l mzoological
t~ometlclature,arzd all debares should be conducted
itr u courteous and friendly manner.
Code of Ethics, Inlernational Code
of Zoological ~ o m e n c l a t u r e " ~ ' ~ ~ )
. ,

I kuow the scientific names of beings animalculous.

W . S. Gilbert

Organisms and Pathogens

Biological Nomenclature

Scientific and Vernacular Names. Scientific names are labels used in place of lengthy
descriptions. A scientific name corresponds to a set of formally defined attributes.
The meanings of scientific names are internationally understood.*
Vernacular names or common names are also labels. Vernacular names seen in
medicai publications include fungi, prokaryotes, meningococcus, and StJohn's wort.
Vernacular naines cannot be assumed to correspond to formally defined sets of
attributes and vary by region and language.
. In scientific writing, scientific names should be used when the labeled entity
verifiably corresponds to the set of attributes
least at first mention. Subsequently vernacul
terms, described later in this section) may be used.
Parenthetic mention of the vernacular name
and vice versa, is helpful. For instance:
First ent ti on
Vernacular name St John's wort (Hyper-
icum pt#oratum) who reported taking St John's'
wort tablets"
Scientific name Hrpenrpencum
perforatum
(St John's wort) wort, depending on context;

Biological Nomenclature.. Biological nomenclatu

ganisms and is the source of scientific names.
and practices of classifying organisms2 to reflect their relatedness. Nomenc
"is the assignment of names to the taxonomic groups according to interna
rules. "3@")
Biological nomenclature-the nomencla
paradigm of the 18th-century taxonomist L
replace the long descriptive Latin phrases a

740

- .
L .A-

.
 15.14.1 Biological Nomenclature

Linnaeus' time, international bodies have continued to formalize biological no-

menclature, resulting in the current principal codes:
Code Content
International Code of ' animals, including protozoa and
Zoological ~omenclature' parasites
International Code of fungi and noncultivated plants,
Botanical Nomenclature6 including algae
International Code of bacteria
Nomencluture oJBactwia7
International Code of cultivated plants
Nomenclaturefor
Cultivared ~lunt-8'
Znremational Code of viruses (see 15.14.3, Organisms and
Virus C . $ c a t i o n and Pathogens, Virus Nomenclature)
Nomenclature
I ' 1%
The codes contain principles, .rules, an$ recommendations for name derivations,
priority, validity, and spelling. F?r a name to have international standing, the codes
stipulate valid publication according to specific requirements.
An effort has been made to unify biological nomenclature for all organisms with
a single code, the BioCode, under the auspices of the,Intemational Committee on
Bionomenclature (a joint commitfee of the International Union of Microbiological
Societies and the International union of Biological ~ c i e n c e s ) . ~Another
~ ~ ' proposed
unifying code is the PhyloCode, which meant to reflect phylogeny and to be used
concurrently with-the extant codes, at 1east'initially.lzv1'
"The essence of the,Linnaean revolution was the recognition that the function
of the specific 'name' was merely to label a concept rather than to describe an en-
tity."5'p5) Scientific names change when taxonomy changes, gut not when new
knowledge indicates that the original name is no longer an apt descriptor. (For
instance, it was learned several decades after its discovery that the bacterium Hue-
mopbilus influenzae did not cause influenza,14but the name was not changed.') The
stability of names is crucial, and name changes may cause ham5'P75'~HP"'""1'1e) (see
"perilous name" in the bacteriologic code7).

Resources. A useful source of names of organisms available on the Web, particularly

plant and animal names, is the Index to Organism ~ a r n e s . 'Other ~ resources arc
available at the National Center for 13iotechnology Infornlation Entrcz 'I':~sono~ny
Homepage ( h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u ~ = t : ~ s o ~ ~ o ~ i ~ y ~ . ' ~ '

Style for Scientific Names. This section presents style that applies to scientific. n:lmes.
The nomenclature codes differ in some. style recommendations, I>ut most ~>ul~lic:~-
tions, when possible, will apply style consistently for all scientific names. ex. \ \ r i l l LISC
;~bhreviationsin the same way for animals, plants, and bacteria. Thc.rct'or-'8. st\.lr ,
applied to anirnals, plants, and bacteria is presented together in this section. (5c.c.;~lso
15.1 .I 2. f3ncteria: Additional Terniinology, and 15.14.3, V ~ N SNomcnc~l:~turc.
~lrrnrand Pathogens

Organisms are classifiedin taxonomic groups, also

within different ranks, eg:
Rank Taxon
genus Homo
species Homo sapiens

Major ranks, from most inclusive to most specific, are

phylum (animals, fungi, and bacteria) or division (pla
family, genus, and species.
Stylistic hallmarks of biol
vernacular n a r n e ~ .These
~.~
species: the binomial, also called binary or bino
code, the names of ranks above species usually must be unique; the same sp
designator, however, can be used with multiple
Streptococuspneurnoniae. Across codes, name
the'bacterial genus Bacillus, the stick and leaf
According to the inte
for the second portion of th
zoological code and the spec
Italics are always used for
Diacritical marks (accents)
may be used in the specific epithet, eg, the
c-shaped wing mark.2
AU codes capitalize scientific names.
The bacterial code recommends, ital
journals may wish to style all
Journals, taxa above genus are not italicized. The following examples of
classification~accordingto the 3 codes illustrate style in J A M and th
Journals for capitalization and italihtion (see also 10.5.6; Capitalization,
Nouns, Organisms). The suffixes are typical and specified in each code (eg,
-idae ~animalsl,aceae [plants and bacterial), although
Animal
I~ank! Taxon 1 I~ank
kingdom Animalia kingdom Fungi

phylum Chordata phylum Ascomycota

class Mamrnalia class Ascomycetes class
order Primates order Onygenales
. .

family Horninidae family Onygenacea

genus Homo genus Ajellomyces genus
species- Homo species Ajellomyces
sapiens

.. -
..__.
 15.14.1 Biological Nomenclature

(Another scheme for bacterial taxonomic rank uses domain and phylum, rather than
kingdom and di~ision.~)
Subranks and superranks follow the same style, eg:
Animal Ftrn~i

subphylum Vertebrata
subclass Peronosporomyceticlac
suborder Anthropoidea
superfamily Hominoidea
(See also the section: "Subgenus' and "Subspecific Ranks, Ternary Names." I,c;.lon,.)

Abbreviation of Genus and Other Abbreviations. As described in 14.11. Al,hrc\.ia-

tions, Clinical, Technical, and Other Common Terms, treat each manuscript ponion
(tide, abstract, text, etc) separately. After first mention of the binomial species n;unc.
abbreviate the genus portion of the name. (JMand the Archiues Journals tlo not
use a period.) Do not abbreviate the specific name. Do not begin a sentence \\.it11 : ~ n
abbreviated genus name; either expand or reword.
Staphylococcus aureus is a common cause of hospital-acquired infection.
Nosocornial S aurars infection is also a source of community-acquired in-
fection. -
-- - -
When the genus name is repeated but used with a new specific name. d o nor
abbreviate the genus name until subsequent mention.
~taphylococcusa u m and Staphylococcus epidermidk may be components
of normal flora or pathogens in clinically significant infections, although
S aumts is the more serious pathogen of the two.
Do not abbreviate the specific name, and do not abbreviate the genus name when
used alone.
Not:. . .S au is the more serious pathogen. . .
Not:. ..the more serious pathogen in the genus S
When organisms with genus names that begin with the same letter are mentioned in
the same article, in JAMA and the Archiues Journals, genus is abbreviated after first
mention, for instance:
hospital infections caused by Staphylococct~scaureus and Slreptococczls
faecalis and bacteriuria with S aureus and S faecalis
Style variations in such instances are permissible (eg, if the editor thinks there is any
possibility of confusing genera), nnd'author requests to expancl the genus names
should be honored. J A M and the Archives Journals do not use multilerrcr :~h-
breviations for genus name, eg:
S aurelfi and Sfaecalis (not Sta ar*relrs or Str./clc>ccctlis)
15.14 Organisms and Pathogens

Do not use Zletter abbreviations for the binomial, eg, do not u.w SA for Slap
coccus aureus or SE for Sepidermidis. However, longer expressions that inclyd
scientific name may be abbreviated:
CONS coagulase-negative Staphylococcus species
EHEC enterohemorrhagic Escherichia coli
MRSA methicillin-resistant Staphylococcus a u r m
Abbreviations such as sp nov (species nova, new species) and gen nov (genus
vum, new genus) are used in published proposals of ne
ignations, eg:
Corynebacterium nigricans sp nov
Roseomonas mucosa sp nov and Roseomonas gilardii subsp msea subsp
Wigglesworthiaglminidia sp nov
Wiggksworthia gen novla
New proposals for higher taxa are indicated as in the following e ~ a m f i l e s ' ~ ~
Cycliophora, new phylum
Eucycliophora, new class
Symbiida, new order
Symbiidae, new family
Symbion gen nov
S'bion pandora sp nov
Pmteria piscicida gen et sp nov (Pfiesteriaceae fam nov)
Parachlamydiaceae fam nov and Sjmkaniaceae fam nov
The "nov" abbreviations should be mentioned prominkntly in the article,
. .
title, but need not be included with every mention of the organism name.
Synonyms are expressed as follows:
Fugomyces cyanescm (syn S ' b r r j c cyanescens, Cerinosterus
Mesocestoides vogue (syn M corti)

Subgenus. Subgenus is capitalized, italicized, and placed in parentheses, some

with the abbreviation "subgen," eg:
Mus (Mus) musculus
Moraxella (subgen Branhame&) catarrhalis

Parentheses. For other uses of parentheses within species names, such as.
changes, use quotation &rks or a qualifier such as "formerly," eg:
Bartonella (formerly Rochalimaea) henselae
Helicobacter (formerly Campylobacter)pylori
Issatchenkia orientalis (anamorph Candida h a 3

,.
- =:'C
--
 15.14.1 Biological Nomenclature

Indicate a change in species name with the entire binomial in parentheses ;IS
follows:
Bactemides ureolyticw (formerly Bactemides corndens)
Authorship of the scientific name maybe indicated by personal names, \vhich arc nor
italicized, following the species name. Sometimes parentheses are usecl. \'C'ithin ancl
among codes, conventions for such references vary. Editors should not restyle sucll
terms but rather should verify with authors that the proper form has been used. "L."
alone is the common abbreviation for "Linneaus," eg, Culex pipiens L., but ..Lin-
. -
naeus" should be written in full in publications whose readers are unlikely to know
of this convention. Eximples:

Escherichia coli (Migula) Castellani and Chalmers

Serratia marcescm Bizio
. .

The parentheses indicate that the organism, after initial description, was transferred
into another genus by others, in the case of E coli by Castellani and Chalmers.
Year of published discovery may be included, eg:
Escherichia coli (Migula 1895) Castellani and Chalmers 1919
Saratia marcescm Bizio 1823

Subspecific Ranks, Ternary Names. Subspecific ranks receive ternary or trinomial

names. Subspecific designations are handled diferently for animals, plants, and
bacteria, as in the following examples. (The term var as a synonym for subspecies
was removed from the bacterial nomenclature code in 1990.)
SubspeciJic Rank
Tjpe of Organism (Designator)
- Example
Animal
Higher animal subspecies Mus musculus doinesticus
(no designator)
Protozoon Tmanosoma hrucei gambicnse
Fungus variety (vw) I iislol,lusntu cupsuhrum
var duboisii
Bacteria
Bacterium s~l>spccics sul~sp
(,kttnl?ylohuctcrJL'III.~ Je111.s
(suhsp) Mycohuclerium aviurn suhsp
/~~rci/rrl~erc~rlo.si.s

Plant names may use var, as above, subsp, f (form), and other subspecific epithets,
which are not interchangeable, in ternary names, eg:
Sa frtreja parnassica subsp parnassica
 -. -
15.14 Organisms and Pathogens

Not all 3-word combinations are ternary names:

Ixodes scapularis larvae
Legionella pneumophila pneumonia
Schistosoma mansoni miracidium
Trypanosoma brucei procyclin

lnfrasubspecific Subdivisions. Subdivisions below the subspecies level

subspecific subdivisions) include the serovar (serologically differentiated) a
biovar (biochemically or physiologically differentiated). he suffix. -type
often used in the clinical literature, eg, biotype, serotype. But to avoid confusi
nomenclatural type ("the element of the taxon with which the name is permanen
ass~ciated"~'p'~]),the suffix -var is often preferred in microbiological litera
Infrasubspecific .subdivisions are designated with various numbers, letters, o
terms; follow author usage:
Brucella suis biovar 4
C?@tococcus neofonnans serovar A
Fusarium cucysporhn f sp radicb lycopersici If sp: forma specialis1
Haemophilus injluenzae biotype I
H injluenzae biotype VII
Pseudomonasjluomcm biovar I
Staphylococcus a u m subsp aureus biotype A
S simulans biovar staphylolyticus
UreapIasrna urealyticum parvo biovar
U urealyticum T960 biovar
Yersinia entmcolitica serovar 0 : 8

Anglicized and Vernacular (Trivial, common) Terms. In medical publications,

capitalized anglicized forms are often used for taxa in ranks above genus (see
9.4, Plurals, ~icroorganisms)~~:
Anglicized Tmn Fomzal T m
vertebrates Vertebrata
primates Primates
horninids Hominidae
fungi Fungi.
moniliaceous molds Moniliaceae
prokaryotes Procaryotae
mycobacteria Mycobacteriaceae
chlamydiae Chlamydiales

Collective Genus Terms. Many organisms possess traditional generic pl

nations, which are verifiable in the dictionary. Some also have special adjec

746

. ., --. - .
s5. +.. _.
 15.14.1 Biological Nomenclature

forms. It is also acceptable to add the word organisms or species to the italicized
genus name. See the examples below.
Genus Plural Noun Form Adjectival Form
Cryptococcus ,C?yptococctts species cryptococcal
Eschm'chia Escherichh organisms
I.egionella legionellae
Macaca macaques
Mycobacterium mycobacteria mycobacterial
Pseudomonas . pseudomonads pseudomonal
Salmonella -, salmonellae
Staphylococcus staphylococci staphylococcal
Streptoccus streptococci streptococcal
Treponema treponemes treponemal
T7ypanosoma trypanosomes trypanosomal
a novel Y-nia species
Loxosceles species (brown recluse) spider venom
group A streptococcal infection
viridans streptococcal endocarditis
Genus names often qualify other terms, eg: , ; .
Candida endocarditis
-. Lactobacillus serogroups
b- &ionella pneumonia

Unspecified Species. The name of a genus used alone implies the genus as a whole:
Toxocara infections are frequently acquired from household pets.
The term species is used in cases in which the genus is certain but the species cannot
be determined. For instance, if an author knew that a skin test reaction indic:ltcd
presence of Toxocura organisms I~utwas unsure wl~etlicrthe reaction rcsul~ctlfro111
Toxocara canis infection or Toxocara cali infection, the author might \\.rite:
The source of the patient's infection was Toxocum species.
In thc I:~ttcr cx:ul~l>lc,'li~socsrrzrorg;lnisms woi~lrl:rlso l>c;~cr.cj>~:~l)lc.
1,111 '/i~voc.rrrur
alone would be in~orrect.'"'~

Name Changes. Two recent new nanles have been adopter1 more rc;tclil! 1)). ~ni-
crol>iologiststhan clinicians: Cblamydophifa (see 15.14.2, Bacteria: ~tl;lirion:ll .I'c~-
minology) and P~lnr~rrocystisjiro~eci.~"-*"
'Tile filngal gcnus P1lcJrrnlocystisnow includes 2 authentic species. 'flit- n:tlnc. 01'
the species infec.ti1.t.of mts is P cari~zii.The human pathogen \\.:is t r . ; t ~ ~ . s i r i o ~ ~ : ~ l l \
n;~rijetlI> canlrft f sl> h o ~ t t i ~2nd
l i ~ is now known as P jirvv~ci."'." -'Ilic (I1111ili:rr.
;~l>l~rt*\.i;ttion
I'CI' ni;l) IK. rct;~!nrtlf o r I-'rrcrrn/ocystis pneunioni:~ in Iiirni;u~ant1
nonIlt~m;rnho\rz '"

747

F
1 5 14 Organ~wnrand Pdthoqenr

\'hen .I n;lrne is very new or in dispute, authors are advised to include both
\.cr>rorl,:it first mention:
Chlanaydophila (formerly Chlamydia) pneumoniae
Chlrrmydia pneumoniae (proposed new name Chlamydophilapneumoniae)

Usage. In text dealing with infectious conditions, it is important to distinguish be-.

tween the infectious agent and the condition. Infectious agents, infections, and
diseases are not equivalent.
Incorrect: Legionella pneumophila may be serious or subclinical.
Prefmed: Infection with Legionella pneumophila may be serious
subclinical.
Incorrect: Legionella pneumophilu may be severe.
Prefmed: Legionella pneumophila pneumonia may be severe.

There is no 'bficial" clasn3cation of bacteria. . . .

[Bjacterial classifications are &ed for micro-
biologists, notfor the entities being classified.
Bacteria show little interest in the matter of their
classiJcation.
D. J. Bremer, J. T. Staley, and N. R. ~ r i e $ ( ~ ~ l )

. . . the majority of bacteria in nature have not been

grown or characterized.
R. G,. E. Murray and John G. ~ o l p ~ ' )

Bacteria: Additional Terminology

General. For general guidelines on biological nomenclature that apply to bacteria,

see 15.14.1, Biological Nomenclature. Rules for bacterial nomenclature are found in
the International Code of Nomenclature of ~acteria?Sources of bacterial names
available on the Web are the List of Prokaryotic Names With Standing in Nomen-
clature3' and the German Collection ,of Microorganisms and Cell Cultures bacterial
nomenclature search page.32 General references consulted in preparation of this
section are Murray et a133and Brooks et a1.34

Bacterial Genes, Bacterial gene nomenclature is covered in 15.6.5, Genetics, Non-

human Genetic Terms.

Chlamydia and Chlamydophila. A proposed change in taxonomy has resulted in a ;

number of changes, including name changes of 2 medically important
Chlamydia pneumoniae has become Chlarnydophila pneumoniae
Chlamydia psittaci has become Chlamydophila psittaci. Chlamydia tracho

' -- -
*- .
s'

. ">
 --
- 03 : -
&?.
I

15.14.2 Bacteria: Additional Terminology

remains so named. The proposal has been questioned,3Gand as of this writing t h e

older terminology persists in medical journals and textbooks. The new tenninologs is
used by the Centers for Disease Control and Prevention and major compendia ot'
bacterial names.31"3s37
The TWAR biovar of Chlamydophila'pneumoniaewas named "after the I:II>-
oratory designation of the first 2 isolates-W-183 and ~!3-39."~~'~~"')--'~'

Escherichia coli. The 0:K:H serotype profile of Escherichia coli is based on thC
somatic 0 antigen, capsular K antigen, and flagellar H antigen. The 0 is a c~pital
letter 0 , not a zero. The abbreviations 0 , K, and H within the terms need not I>c.
expanded. Expansion of other components is not necessary but can be helpfill c 351.
nonmotile; NT, not typeable; Orough, 0 antigen, rough). Note the following cs-
amples:
Escherichia coli 06:K13:H1
E coli 0157:H7
0157:NM
0NT:NM
Orough:H9
non-0157
O111:NM (or H-)
Prominent serogroups include 026,0103,0111, and 0128.
Diarrheogenic E coli strains are abbreviated as follows (expand i t first mention in
accordance with 14.11, Abbreviations, Clinical, Technical, and Other Common
Terms):
-
EAggEC enteroaggregative E coli
EIEC enteroinvasive E coli
EPEC enteropathogenic E coli
ETEC enterotoxigenic E coli
STEC Shiga toxin-producing E coli (also called enterohemorrhagic
E coli [EHECI)
WTC verotoxin-producing E coli
Serotype and strain are often mentioned together in various combinations:
015;:~7 STEC
strains of STEC serotypes other than 0157:H7
STEC 0103
Note the following terms representing Shiga toxins:

Gram-Positive, Gram-Negative. I3:l~trnd arc. often g r o i l ~ dn c c o r r l ~ n gto rc:ictlor\ ( 0

the Cram s t ~ i n xorc.
. ~ ~ p l ~ n l ~ z .~l ~~ !i-ol1r1
tn*rllv f o l l o \ \ l n s c.,vt3 ; 1 1 y o 1 0 3. C;II>II.I!II.I-
i [ion. I'ropcr N r > a r l x )

749
i
15 14 Organlrmr and -sthogens

~ r smln
~ m I
.f
'<

Haemophilus. Haenlophilus influenzae strains are defined by capsular antigens,!

designated types a through f, for instance: : 4
Haemophilus inJuenzae type b (Hib)
The name of the vaccine should be expanded at first mention:
Haemophilus inJZuenzaetype b (Hib) vaccine . . . Hib vaccine
H infZuenzae type b (Hib) vaccination
Haemoph aegyptius has een bic
aegypticu '3misspelling.

B Laboratory Media. Microorganism names applied to laboratory media are $iveq

lowercase and roman: 1
bacteroides bile esculi agar
brucella agar
Capitalization indicates a product name: q,.#
:

Haemophilus ID Quad agar v .

Lactobacillus GG. Lactobacillus GG

4+i
refers to a strain of Lactobacillus rhamnosus,
named for the authors who isolated it.41 'I

L Forms. IIph variants, or forms, a1:e fc various b a a eria wit

defective cell walls. Exampk of usage are

,I
IWS:

Helicobacterpylori L-form infection

L-form Bacillus subtilis
*.l,;
L-form bioluminescence
tkt: L form of Mycobacten'um tuberculosis
j
Macrolide Resistance. Macrolide-resistance phknotypes are expressed as follows: ;*
!i$
M phenotype (M:macrolide)
MLSB (L: lincosamide; SB: streptogramin B)
cMLSB (c: constitutive, includes resistance to clindamycin)
iMLSB (i: inducible by macrolides but not by clindamycin)

Mycobacterium avium-intracellulare. This tern indicates that in a particular co

text, the ium and ; intracellukzre are
able.

.'.. .
*,
 - - --
- - 3
t

15.14.2 Bacteria: Additional Terminology

Neisseria meningitidis. Clinically important serogroups of this organism include the

following:
serogroups A, B, C, Y, and W-135
The vernacular name of this organism is meningococcus.

Salmonella. Nomenclature of salmonellae is complex and evolving.4245What had

been considered separate species were shown to be strains. The main stylistic change
. is that the traditional binomial species designation is no longer applied to serotypes,
eg:
Salmonella Typhj, not Salmonella typhi
Editors should query authors if the latter term and its like are used (except, for
instance, in discussions of nomenclature) but otherwise should follow author pref-
erence and apply style as in the following examples:

- Species: Salmonella enfen'ca,S bongori (formerly subspecies V)

, a

-> , . Subspecies, S enterica:

L
grCb
S entaacasubsp enterica subspecies I
t.? S enterica subsp salamae subspecies I1
' La
1.3. S enterica subsp arizonae subspecies IlIa
S enterica subsp diarizonae subspecies IIIb
? .
S enterica subsp houtenae subspecies IV
r-

S enterica subsp indica subspecies VI

- Serotypes (serovars) of subspecies I use italics, roman, and capitals as follows:
Salmonella ser ?hphi (equivalent to S enterica subsp enter& ser Typhi)
After first mention, ser may be omitted:
Salmonella Enteritidis
Salmonella Typhi
Salmonella Typhimurium
When the genus name is repeated, it may be abbreviated:
S Typhi
Serovars of Salmonella are defined by the 0 (somatic), Vi (capsular), and H' (fla-
gellar) antigens. In contrast to E coli strains, when Salmonella serotype is expressed
with those antigens, the letters 0, H, and Vi are not included in the serotype des-
ignation. Colons separate the 0 , Vi, and H designations, which take a variety of forms
(letter, numeric, etc):
Salmonella enterica subsp salamae ser 50:z:e,n,x
Salmonella serotype I1 5O:z:e,n,x
Salmonella serotype IV 45:g,z51:-
Salmonella serotype IIIa @ : ~ z 3 : -
 -
15.14 Organisms and Pathogens

Salmonella subsp arizotue x r o v a r W:qz2,:-

Salmonella Typhimurium 1,4,5,12.1:1,2
Alternatively, geographic or other designations are used:
Salmonella ser Brookfield
Salmonella Typhimurium MR-DT104 +%
Salmonella Typhimurium DT204b ?$. ,

0 antigen groups (0 groups) are A, B, CI, CZ, D, E, and F, eg: 8

$
Salmonella group E ,.&
a group D Salmonella outbreak

/ Strain and Group Designations. Strains and groups are designated in various way!
sometimes alone. sometimes follow in^ the binomial s~eciesname. These additions
u

designations are not italicized. Strains are sometimes designated by the ~ b r e

of a culture collection repository and number. Such abbreviations net not
I ;'
panded-when used in stkin names only, but should be otherwise.24
ATCC 27853 strain of Pseudomonas aerugincsa
CDC EO-2 [EO: eugonic oxidized
CDC group WO-2NO:weak oxidized
Eschenenchia coli ATCC 25922 .."
Staphylococcus aureus NCTC 83
the control strain, NCTC 8325
4
.:
GeobaciIIus stearothmophilus (DSMZ 22; equivalent to ATCC 12980)
cultures obtained from the American 'ljqx Culture Collection, Manassas, V i

I Streptococci. Clinically important groups of streptococci are designated in vario~

ways. Capital letters refer to Lancefield serologic groups, eg:
a-hemolytic streptococci
group A &hemolytic streptococci .
group A Steptococcus pyogenes
group B khemolytic streptococci (S agalactiae)
group C streptococci
. viridans streptococci
Proteins of Streptococcuspyogenes include the following:
a
M protein
.'$
class I M protein 4

class I1 M protein
'!

P substance .:. ';.;

R protein . !

T substance -

752

-. .
I-." "
I).
!$. .-- -
 15.14.2 Bacteria: Additional Terminology
I
i
The cell wall C polysaccharide of Spneumoniae is the basis of the term "C-reactive
protein" (an acute-phase inflammatory protein that reacts with the C poly-
saccharide).
Do not confuse the M protein with the M phenotype of various streptococci a n d
other bacteria (see the "Macfolide Resistance" section above) o r C polysaccharide
with group C streptococci.
The vernacular name of Streptococcuspneumoniae is pneumococcus.

.Vibrio. Vibrio cholerae serogroups are expressed a s in these examples: . .

Vibrio cholerae 01..
V cholerae 0139 -
REFERENCES
1. International Commission on Zoological Nomenclature. International Code (?/Zoolog-
ical Nomenclature. 4th ed. London, England: International Trust for Zoological No-
menclature; 1999. Also available at http://www.iczn.org/iczri/. Accessed April 20.
2006.
2. Jeffrey C. Biological Nomenclatum. 3rd ed. London, England: Edward Arnold; 1989.
3. Bremer DJ, Staley JT,Krieg NR.Classification of procaryotic organis~nsant1 ihr
concept of bacterial speciation. In: Boone DR,Castenholz R\V, eds.Beigeyj. .lltrirrtcrlc~'
SptemaCZc Bacteriology. 2nd ed. Vol 1: 7%eArchaea and the D e e p y Blai~c-hiirgciird
Phototrophfc Bacteria. New York, NY: Springer-Verlag; 2001:27-31.
4. Sneath PHA. Bacterial nomenclature. In: Boone DR, Castenholz RW, eds. H c ~ i ~ c l - : ~
Manual of Systematic Bacteriology. 2nd ed. Vol I: The Archaea and the D L J L ~ ! ~ ~
Branching and Phototmphic Bacteria. New York, NY: Springer-Verlag; 2001:tJJ-KC(.
5. Melville RV. Towards Stability in the Names of Animals: A History of l l ~ bltc~riirrlioir~il
e
Commission on Zoological Nomenclature 1895-1995.London. England: lnternatiotx~l
Trust for Zoologid Nomenclature; 1995.
6 . Greuter W , McNeill J, Bame FR, et al, eds. International Code of Bofuitic~~l ~\'oi~tcrr-
clature (St h u i s Code). Vienna, Austria: International Association for Plant Taxonomy:
Konigstein, Germany: Koeltz Scientific Books; 1999. Also available at http://xv\v\\.
.bgbm.org/IAPT/Nomenclature/Cde/SaintLo/OOO1ICSLContents.htm. Updated
February 12, 2001. Accessed April 20,2006.
7. Lapage SP, Sneath PHA, Lessel EF, Skerman VBD, Seeliger HPR,Clark WA. Irzlei-rlcr-
tional Code of Nomenclature of Bacteria and Statutes of the Itzternational Comivittce
on Spfematic Bacteriology and Statutes of the Bacteriolog~and Applied Microbiolog).
Section of the International Union cfMicmbiological Societies. Washington, DC: In-
ternational Union of Microbiological Societies, American Society for Microbiology;
1992.
8. Trehane P, Brickell CD, Baum BR, et al, eds. Interizuiioi?nl Code of Aroi~zeizclut~ri~~for
Ctrltivated Plants. Wimborne, England: Quarterjack IJublishing; 1995.
9. International Committee on Bionomenclature (ICB). http://wnv.rom.on.ca
/biodiversity/biocode/bioi~b1997.html. Accessed September 13, 2005
10. Ride WDL. Introduction. In: International Commission on Zoological Nomenclnture
international Code of Zoologicaf Nomenclature. 4th ed. London, England: Interna-
t~analTrust for ~oologicalNomenclature; 1999:xix-xis
15.14 Organisms and Pathogens

11. International Union of Biological Sciences Web are. hnp:Mnwwiubb.or& ~ c c r s w d

April 20, 2006.
12. Robinson P, Kornmedahl T. Phylocode: a new system of nomcnclatum. Sci F2ilor.
2002;25(2):52.
13. Phylocode. http://www.ohiou.edu/phylocode. Modified April 20, 2006. Accessed
April 21, 2006.
14. Kolata G. Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for
the Virus That Caused It. New York, NY:Touchstone; 1939.
15. Biosis. Index to organism names. http:/v.organismnames.com. Accessed April 21,
2006.
16. NCBI Entrez Taxonomy Homepage. http:/www.ncbi.nlm.nih.~v/entrez/que&i
?db=taxonomy. Accessed April 21, 2006.
17. Han XY, Pham AS, Tarrand JJ, Rolston KV,He1
acterization of 36 strains of Roseomonas species and proposal of
s p nov and Roseomonas gilardii subsp rosea sub-p nov. Am J Clin Pathol.
2003;120(2):256-264.
18. Aksoy S. W i g g h r t h i a gen. nov. and Wigglesworthiaglom'n
. consisting of the mycetocyte-associated, primary endosymbio
Syst Bacteriol. 1%;45(4):848-851.
19. Funch P, Kristensen RM. Cycliophora is a new phylum with
and Ectoproaa. Nature. 1995;378(6558):711-714.
20. Morris SC. A new phylum from the lobster's lips. Nature. 1995;378(6558)
21. Steidinger KA, BurkholderJM, Glasgow HB, et al. PfiesWpiscicida gen. et sp. n
(Pfiesteriaceae fam. nov.), a new toxic dinoflagellate with a complex life
behavior. JPbycol. 1936;32(1):157-164.
22. Everett KD, Bush RM,Andersen AA. Emended description of the order C
,proposal of Parachlamydiaceae fam. nov. and
raining one monotypic genus, revised taxonomy of the
cluding a new genus and five new sped&, and sta
organisms. Int J Syst Bacteriol. April 19*,49:415-440.
23. Ursing JB.Bacteriologic nomenclature. In: hhisomeuve H, Enckell P
AKS, Thapa R, Vekony M, eds. Scieiue Editors' Handbook. West C1
European Association of Science Editors; 2003;3-4.1:14.
24. AS34 Style Manual for Journals and Book. Washington, DC: Amen
Microbiology: 1991.
25. Style notes: taxonomic names in microbiology and their adjectival
toriall. Ann Intern Med. 1989;110(6):419-420.
26: Stringer JR,Beard CB, Miller FW,Wakefield AE. A new name CPneumocystisjim
for Pneumaystis from humans. Emerg Infict Dis. 2002;8(9):891-896.
27. Cushion MT.Pneumocystis. In: Murray PR, Baron EJ, Jorgensen JH, Pfaller MA, Yo
RH,eds. Manual.of Clinical Micmbio2ogy. 8th ed. Washington, D
2003:i712-1725. .
28. Hughes WT.Pneumocystk carinii vs. Pneumocystis j i m c i : another misnomer
sponse to Stringer et all. Emerg Infect Dis. 2003;9(2):276-277.
29. Stringer JR, Beard CB, Miller RF, Cushion MT.A new name (Pneumocystisjimue
. Pneumocystis from humans (response to Hughes). Emerg Infect
279.
30. Murray RGE. Holt JG. The history of Bergey's Manual. In: Boone DR, Castenho
eds. Bergey's Manual of Systematic Bactm'ofogy. 2nd ed. Vol'l: The Archaea a

754

. ..

- . . - .. /.-----
.i;' :*.:
- . .
. ...
-
.-1- ..
_1-

.'. >: -
..' <..:.. ...!
.. . ,...
2 ,
I A
-- -
is:---
.' .p

15.14.2 ~aheria:Additional Terminology

i
Deeply Branching and Phototmphic Bacteria. New York, NY: Springer-Verlag;
2001:l-13.
31. EuzCby JP. List of prokaryotic names with standing in nomenclature. http://www
.bacterio.cict.fr/ or http://www.bacterio.net. Updated April 19, 2006. Accessed April
21, 2006.
32. DSMZ. Bacterial nomenclature search page. http://www.dsrnz.de/bactnom
Ibactname. Accessed April 24, 2006.
33. Murray PR, Baron EJ, Jorgensen JH, Pfaller MA, Yolken RH, eds. Manual of Clinical
Microbiology. 8th ed. Washington, DC: ASM Press; 2003:991-1004.
34. Brooks GF, Butel JS, Morse SA.Jawetz, Melnick, andAdelbe&s Medical Microbiology.
22nd ed. New York, NY: Lange Medical Books/McGraw-Hill; 2001.
35. Mahony JB, Coombes BK., Chemesky MA. Chlamydia and Chlamydophila. In: Mumy
PR, Baron EJ, Jorgensen Jh,Pfaller MA, Yolken RH, eds. Manual of Clinical Micm-
biology. 8th ed. Washington, DC: ASM Press; 2003:Bl-1004.
36. Schachter J, Stephens RS,Timms P, et al. Radical changes to chlamydia1 taxonomy are
not necessary just yet. Int J Syst Evol Microbiol. 2001;51(pt 1):249.
37. Boone DR, Castenholz RW, eds. Bergey's Manual ofSystetnaticBacteriology. 2nd ed.
Vol I: 7be ~ r d h a e aand the Deeply Branching and Phototmpoic Bacteria. New York,
MI: Springer-Verlag; 2001.
38. Grayston JT, Kuo C-C, WangS-P, Altman J. A new Chlamydia psittaci strain, TWAR,
isolated in acute respiratory tract infections. N Engl J Med. 1986;315(3):161-168.
39. Grayston JT, Kuo C-C, Campbell LA, Wang SP. Chlamydiapneumoniae sp. nov. for
Chlamydia sp: strain TWAR Znt J Syst Bacterial. 1989;39(1):88-90.
40. Saikku P, v a n g SP, Kleemola M, Brander E, Rusanan E, Graystoh JT.An epidemic of
mild pneumonia due to an unusual strain of Chlamydia psittaci. JZnfect Dis.
1985;151(5):832-839.
41. Gorbach SL, Chang TW,Goldin B: Successful treatment of relapsing Clostridium dif-
Jicile colitis with Luctobacillus GG. Luncet. 1987;2(8574):1519.
42. Euz6by JP. Salmonella nomenclature. http://www.bacterio.cict.fr/saImqneIlanom
.html. Updated March 19, 2005. Accessed September 13, 2005.
43. Farmer JJ 111. Enternbacteriawe: introduction and identification. In: Murray PR, Baron
EJ, JorgensenJH, Pfaller MA, Yoken RH,eds. Manual of Clinical Microbiology. 8th ed.
I Washington, DC: ASM Press; 2003:636-653.
44. Bopp CA,Brenner FW,Fields PI, Wells JG, Strockbine NA. E~che~chia, Shigella, and
Salmonella. In: Murray PR, Baron EJ, Jorgensen JH, Pfaller MA, Yolken RH, eds.
Manual of Clinical Microbiology. 8th ed. Washington, DC: ASM Press; 2003:654-671.
45. Brenner FW,Villar RG, Angulo FJ, Tauxe R, Swaminathan B. Guest commentary:
SaImonelIa nomenclature. J Clin Microbiol. 2000;38(7):2465-2467.

Viruses evolve rapidly. . . .[Aldenouincs,for example,

mayprodzzce 250 000 DNA molecules in nn i~fcctcrl
cell. . . .
Leslie Collicr ; ~ n dJohn 0 ~ f o r d " p ' ~ '
15.14 Organisms and Pathogens

(fyou wanted to call one of your children homefor

dinner would~otr go into the street and shout "Homo
sapiens"?
Michael A. Drebot, Eric Henchal,
Brian Hjelle, et a13(p2468) ; ..
.

n;kERsll Virus Nomenclature. Most medical articles describe concrete vi

refore, use the common (vernacular, informal) names of viru
virus, Hantaan virus, orthopoxviruses). To indicate taxonomic
names are used (eg, Human he'pemsvrm.s 5, Hantaan virus,
virus).

Style Rules of ~hurnb.A virus term that ends in -virales, -viridae, or -virinae should
capitalized, eg, change paramyxovirinae to Paramyxovririna
-virus may or may not be formal terms (and may be genuses, species, or subspe
entities); editors should follow author usage. Authors should distinguish formal
c6mmon terms and style them accordingly. It is useful to give the forma( taxon
identity of a virus at first mention in an article; afterward
typically used (unless the article is.discussing taxonomy per
used for spedes and above, so subspecific viral entities (stra
etc) are not capitalized or
Reference sources fo
online databases4'*(more below). See Table 14 (at the end
for formal names, common names, and abbreviations of human (and related)
Background and further style specifics follow.

The Viral Code. International virus taxonomy dates f- 1

report from 1971. V i taxonomy and nomenclature are put forth by the
tional Committee on Taxonomy of V i e s (ICTV) in the International Code of
Classification and Nomenclature &ICI'V.~*~(The ICTV is
Division, International Union of Micrdbiology S
more than 500 virologists worldwide, including 82 A d y groups?.~heeighth
, was issued in 2005.'

Official virus names foi species and higher

updates published in A d i u e s of CTimlogy. Online, official nam ..
be available at the ICTV Web site, htcp://m.danforthcenter.
/ - ~ a i n ~ a ~ e . a sand
~ : at ICTVdb, http://phe
http://w~w.ncbi.nlm.nih.gov/~~~db/).5 The I W d b site also provide
tion about isolates (eg, serotypes,
(It is hoped that this l i i a g e will bring ne
nomenclature and t i 1 entries in gene sequence databases.')
As with bacterial, animal, and plant no
stability and clarity. (See also 15.14.1, Biological Nomenclature.) Names of viral
have standing when approved by the members of the full ICTV? Proposals for
names or changes should be submitted to the ICTV Web site.4
The viral code applies to the ranks of order, family, subfamily, genus,
species (but not lower ranks). A virus may not yet be classified at each rank,
viral species may belong to a family but n

. -- . .. .- --.

i
.

i
----. ..
 15.14.3 Virus Nomenclature

assigned to a family. The rank d species was added to the code in 1 9 9 1 ~and' ~ is
reflected in the approximately 1950 viral species names found in the eighth report.2
(There are around 5500 viruses recognized in the latest report.') International spe-
cialty groups are responsible for viral nomenclature below the rank of species, eg,
types, strains. The code does not govern artificially created and laboratory hybrid
viruses.

Formal vs Vernacular Virus Names. Formal viius names are used for taxonomic
groups (order, family, subfamily, genus, and species) in the abstract state.2""-'2 Use
of the formal name indicates that the group has official standiq according to the
ICTV code. Vernacular ( c o h o n , informal) virus species names are used for actual
entities, eg, laboratory material or outbreak specimens: "concrete viral objects that
cause diseases. .. .1912@2247)

Style of Virus Names. For examples of the typographic conventions described in this.
section, see Table 14, V i s e s of Humans,at the end of the s e ~ t i o n . ~ * ~ * ' ~ . ~ ~
Typical endings for order, family, subfamily, genus, and species are as follows:
Bacteria
Vimes Ending
IEuzmPk ~ r z d i 1n ~
Order Mononegavirales -virales -ales
Family Paramyxoviridae -viridae aceae
Subfamily Paramyxovirinae -virinae -oideae
Genus Respimvim -vinu (varies)
Species Human parainfu&zavim 1 -vim (varies)
I

Latin and English Forms. Formal names of viral genus and above are latinized. Formal
names of species "are English names derived from vernacular common names.""""
English, the scientific lingua franca during the era of viral discovery, is used for
formal virus species names no matter what the language of publication.

Initial Capitals. Formal virus names at each rank have initial capital letters. Other
I capitals are used when a proper noun is part of the name, eg:
I
St Louis encephalitis virus
West Nile virus
Vernacular names do not use initial capitals unless a proper noun is part o f tllc Il;lnl~-.
eg:
La Crosse vints

Italics. Although the viral nomenclature code recommcnd5 ~r:ilic-izing; i l l 3c.ic.1111ftc

virus names (ie, species through order), cotles for o r t , ~ . ~ c,rp;lni\n~s
. differ on u\lng
italics for names of higher taxa. For reasons o f intrrn:iI c.on.;i\tcnc.y..//~.\I/!; ~ n ( l1l1c

,
A r c h i u e ~ ] ~do
~ rnot
~ ~italicize
]~ names of vir;il fax;, ;~tx,\.~- p v n u ,/.4.\1:1 :~ncl111,.
I
Archir,~.~Journals do italicize f~rlnalvir:11 gvnrl, . ~ n c l,pcc-lc,. ~~.II:N.,( I~.IIIc1 1 . 1 1 I , ~ 1 1 'I
(
r5 14 O r g a n i r m ~and Pathogens

qxcics is a change from previous ICTV nomenclature reports that was introduced
1998, to indicate formal approval.I5It is consistent with style in other area
logical nomenclature.) Vernacular names are never italicized.

How to Style a Virus Term. An editor encountering a term ending in -virales,

or -virinae would capitalize the term; for instance, an editor would change parv
viridae to Parvoviridae. An editor encountering a term ending in -virus can
context to determine whether it is a formal or vernacular name (
revise as necessary, querying the author. For instance, an editor mi
poliovirus as is or might change it to the f o h a l species term ~oliouink.
strains, types, serogroups, isolates, etc, are never italicized or capitalized (see
section on those entities below). In legends to figures depicting actual v
eg, electron micrographs, italics and capitals would not be used for the actual
depicted15 Legends to schematic depictions of viruses, however, prob
classes of virus, and formal style should be used.

Formal and Vernacular Names in Articles. Formal names are used for abstract en
verrlacular names for physical entities:
West Nile vim is a member of the genus Fkaviuirus. The presence of
Nile virus was confirmed in mosquitoes and dead crows.. . .
W e used polymerase chain reaction assays io d e t e c t
(family F l a v i v i k , genus Flayivim, speaes .w&~ i l vim)
e .
It is useful, for purposes of identification, to include the formal name initial1
article discussing actual viral entities (with the vernacular name used
after)2,3.10.11.13.

.
s virus . . hepatitis C virus
H q ~ t i t iC
Human herus ..
4 . Epstein-Barr virus
..
Human b m ' m . 3 . varicella-zoster virus
Human immunodeficiency v i m 1 HIV-1 ...
In such articles, the virus and its higher taxonomic classification may be us
included early on, eg:
"Sin Nombre virus (family Bunyauiridue, genus Hantauim,
. Nombre virus) is an etiologic agent of hantavirus pulmonary
potentially fatal illness of humans."Kp2469'
The formal name remains in English, the vernacular name in the la
lication, eg:
Meusla virus ... virus de la rougeole . . . 12.13
Hqatitis B vim . . . el virus de la hepatitis B

Abbreviations. Formal viral species names should not be abbreviated.

names of viral species names may be abbreviated. Recommended a
given in the inte~nationalcode (see Table 14, V i s e s of Humans,
section).* Note that related gene symbols and virus abbreviation
15.6.2, Genetics, Human Gene Nomenclature):

--- - 5-- --.-

. ,. ,
' t i
.; !-.
1;. 15.14.3 V~rurNomenclature

Gene symbol: Gene description with virus abbreviation:

HVBS4 hepatitis B virus (HBV) integration site 4
The viral code recommends that rank always be specified with fomlal n;lmcs :~ndI ~ I ; I I
it precede the virus name: -
the family Paramyxoviridae
the genus Respirovinrs (formerly the genus Paramyxovims)
1.. the species Human parainjluenzavirus 1
V i s names used as adjectives are not italicized,15eg:
human immunodeficiency virus infection
murine leukemia virus polymerase
vaccinia immune globulin
West Nile virus surveillance
Official style calls for temporary'names (recognized taxa whose names are not yet
formally approved) to be presented in roman type within quotation marks:
Sapouirus (formerly "Sapporo-like virus")
"T4-like viruses"
Formal style is unambiguous. Vernacular style can be ambiguous, because the
ending -vimoccurs in comnion names at all taxonomic ranks and in other informal
designations (eg, arboviruses, which includes several families). It is therefore helpful
for authors to specify rank with vernacular terms as well:
the family of retroviruses
-
hantaan virus, a species of the genus Hantauim
the paramyxovirus family
the paramyxovirus subfamily

Plant Virus Alternative. Many plant virologists favor a different style for formal
species names, which uses a binomial term that includes species and genus.6~11~17s18
(Despite the designation "binomial," it may contain more than 2 words.) Plant virus
names in this style consist of an English species name followed by the genus name:
plant alternative: Tobacco mosaic tobamovirus
1d style: Tobacco mosaic vinls (genus Tobarnovirus)

Binomial Proposal. Formal virus species names do not currently follow the binomial
style typical of other organisms (see 15.14.1, Biological Nomenclature), which in-
cludes the genus name and a specific epithet. Confusion exists between terms for
abstract virus species and actual virus entities, which often are distinguished only
I
I
typographically. Virologists have indicated a preference for a binomial style for of-
I ficial virus species Such a style would resemble the plant style described
I
above, giving species and then genus. (For instance, Meades virus would become

I Measles morbilliuirus. The vernacular tern1 measles virus would remain in use for
actual measles-virus entities.) That proposal is under s t ~ d ~ . ' ~ . " ~ ' ~ ~ "

i 759
15.14 Organirmr and Pathogens

Derivations. For derivations of virus nan1t.s. consul[ thc rcporrs of rt~cI C I ~ ' . ' ;i
Sornc virus names are combinations of words; such mrntts are known as sigk
Examples include echovim (enteric q ~ o p a t h i ch u m n orphan virus) and picoma
virus iyico-, BVA , ~ n r s )Variant
. capiraliition--eg, ECHOvirus, picoRNAvirus
not used.

Strains, Types, and Isolates. In clinical and laboratory articles dealing with actui
entities, most terms will refer to strains, serotypes, serogroups, or viral isolates, it
ranks below species. Such terms are not capitalized (unless they include prc
nouns) or italicized. Such terms often contain numbers, letters, or names, eg:
coxsackievirus Al, coxsackievirus A24
Desert Shield virus (a stlain of Nonualk vim) - .1
4
human adenovirus 2 (a strain of Human adenouim C)
human astrovirus 3, Berlin isolate
..
Hantaan virus 76-118 (a serotwe of Hantaun vim)
hepatitis C virus ( H W genotype 1
HCV subtype (or genotype) 3a
hepatitis D virus genotype 1
huqxm poliovirus 1, poliovirus 1, or poliovirus,type 1
'I
'1
..$
human poliovirus 2, poliovirus 2, or poliovirus type 2 .~3
:$
human poliovirus 3, poliovirus 3, or poliovirus type-3 2
human respiratory syncytialvhk A2 . .
.r -

La Crosse virus (a serotype of California encephalitis vim) g

.!j
Norwalk virus (a strain of Norwalk uim) :ic

rotavirus B strain IDIR

tick-borne encephalitis virus European subtype
4
I

2
J
Formal species names may also include numbers or letters (eg, Hutiran h-r~s
I , hepatitis B virus;see Table 14, Viruses of Humans, at the end of this section).'

Hepatitis Terms. Antigens of hepatitis B virus and antibodies to hepatitis B virus are
"S
expressed as follows:
Antigen -
hepatitis B surface antigen
hepatitis B core antigen
Abbreviaticn
HBsAg
Antibody
anti-HBs
anti-HBc
-1 r~

hepatitis B e antigen HBeAg anti-HBe .$

hepatitis B X antigen HBxAg anti-HBx
Do not confuse hepatitis e antigen with hepatitis E virus or anti-HBe with ant$
J:
hepatitis E virus (anti-HE%.
i

Influenza Types and Strains. Strains of influenza A virus are identified by antigenic st
types, defined by the surface proteins hemagglutinin (I-I) and neuraminidase (N), e$
1.;
...
15.14.3 Virus Nomenclature

The H,N suffix is used only for influenza A, but the 3 species of influenza virus may
also contain suffixes with terms for the host of origin (if nonhuman), geographic
origin (or a proper name in older strains), laboratory strain number, and year of
isolation, separated by virgules (forward slashes) and, in the case of influenza A,
followed by the H and N designations in parentheses:
influenza A/New York/55/2004(H3N2)
influenza A/chicken/Hong Kong/317.5/01(H5Nl)
. influenza B/Jiangsu/10/2003
influenza C/California/78

Phages. Phages are virus& that infect bacteria. The t e A phage is shortened from
"bacteriophage." Although the current ICTV nomenclature code prohibits Greek
letters in new virus names, older names with Greek letters have not been changed.
Spelled-out Greek letters are also found; and letters may be uppercase or lowercase;
follow author style. Vernacular terms often include the word phage, eg:
phage 1'4 or T4 phage
Phage groups or genera are sometimes referred to with general terms such as the
following: T e e n phages, actinophages, coliphages, T7 phage group.
Examples of formal phage names include the following:
species Genus
Acholeplasma phage L51 L51 Plecmvim
Entembacteria phage 2 h "1-like viruses"
Entembactetia phage PRDl PRDl
Entembacteria phage QP QP
Entembactetia phage Tl T1
Entmbacteria phage T4 T4
Entembacten'aphage Mu Mu "Mu-like viruses"
Halobactm.um phage 0H 0H "OH-like viruses"
Lactococctls phage c2 c2 "c2-like viruses"
Pseudomonas phage 06 06

All of the above phage viruses have identically named strains, and many more strains
belong to species of similar names. Follow author usage.
Enterobacteria phages QP and MI1 are strains of Entembacteria phage QS.
(For phage cloning vectors, see 15.6.1, Genetics, Nucleic Acids and Amino Acids,
"Cloning Vectors.")

Genes. For genes related to human viruses, see 15.6.2, Genetics, Human Gene So-
rnenclature. For retrovirus gene terms, see 15.6.3, Genetics, Oncogenes and Tllmor
Suppressor Genes, and 15.6.5, Nonhuman Genetic Terms.
 *
Q,
Table 14. Viruses of Humans

Common and
lnfraspecific Names a Formal Species Names Basic Abbreviation Genus Family

adeno-associated virus Adeno-associated virus 1, AAV ~ependovhs Parvoviridae (subfamily:

A d e n w s s ~ i a t e dvirus 2, Parvovirinae)
Adeno-associated virus 3, etc
Alfuy virus : : Murray Valley encephalitis virus ALN Flavivirus Flaviviridae
astrovirus Human astrovi~s HAstV Mamastrovirus Astroviridae
Babanki virus Sindbis virus Alphavirus Togaviridae
BK virus BK po&omavirus BKPyV Polyomavirus Polyomaviridae
Bunyamwera virus . ' Bunyamwera virus BUNV Orthobunyavirus Bunyaviridae . . -. -. .

California encephalitis virus California encephalitis virus CEV . Orthobunyavirus Bunyaviridae

Colorado tick fever virus Colorado tick fever virus Crm ColiL irus Reoviridae .- .

coronavirus: see human coronavirus -- - - .. .

cowackieviruses, eg, Human enterovirusA, CV Enterovirus Picornaviridae
coxsackievirus A10, . Human enterovirus B,
cowackievirus 86, Human enterovirus C
\ cowackievirus A24 --
-I;i
Crimean-Congo Crimean-Congo CCHN Nairovirus Bunyaviridae
I hemorrhagic fever virus hemorrhagic fever virus
.! ::<.$i --
cytomegalovirus Human p
h&
e
~tsvi 5 . HHV-5 Cytomegalovirus Herpesviridae (subfarnib-
. . Betaherpesvirinae)

dengue 'virus Dengue virus DENV Flavivirus Flaviviridae

--. -.
Desert Shield virus Norwalk virus Hu/NV/DSV Norovinrs Calciviridae
-

j . Eastern equine encephalitis virus Eastern equine encephalitis virus EEEV Alphavinrs Togaviridae -...- .. .
.
I
. Ebola viruses, eg, Cote D'lvoire Cote & h i r e ebolavi~s,Reston CIEBOV REBOV Ebolavirus
, Filoviridae
ebolavirus, Reston ebolavirus ebolavirus, Sudan ebolavirvs, SEBOV, ZEBOV *.
1...;7.- Texas, Sudan Ebola virus Maleo, Zaire ebolavic
Zaire Ebola virus Gabon

'I-
., . .. . ..
. ,
. . . .,
.
. .:,. . .
echoviruses, eg, echovirus 1, Human enterovirus B E Enterovirus Picornaviridae
echovirus 2
Picornaviridae
b
enterovirus 68 Human enterovirus D EV Enterovirus
enterovirus 70
Epstein-Barr virus Human herpesvirus,4 HHV-4 Lymphoc~ptovirus . Herpesviridae (subfamily:
Gamrnaherpesvirinae)
tyach virus Eyach virus EYAV Coltivirus Reoviridae
.-

GB virus A GB' virus A, GB virus C GBV-A, GBV-C unassigned Flaviviridae

(10 vlrus C
. .~.
.
.

'.,A r:rur R GB virus B GBV-B Hepacivirus (tentative) Flaviviridae

. . . ...

ddnlndn vLru3 Hantaan virus HTNV Hantavirus Bunyaviridae

...-- -
ee:>ttr~V I ~ U S Hendravirus HeV ' Henipavirus Paramyxoviridae (subfamily:
- - -- --- Paramyxovirinae)
~;V~I!II;S A virur Human hepatitis A virus HHAV Hepatovirus Picornaviridae
. . .. - --
hrpdt~l~ B rvirur Hepatitis B virus HBV . ~rthohe~adnavirus Hepadnaviridae
'Icpa:,l~r B vtrur-A
C ~ ~ . l ! ~ fB. sv1rur.B. elc
. .

p:er~3!;ftrC v~rus Hepatitis C virus HCV Hepacivirus Flaviviridae .

f4CV (lade I
1 t C V r)rnorype l a . rlc

',cr).~:,!~rD vtruc Hepatitis delta virus HDV Deltavirus unassigned

. . -...

'.vr\,i:.l~rE v~ru\ Hepatitis E virus HEV Hepevirus Hepeviridae

: 8 c i ; r ~G
~ .vl:ur
~~: GB virus C HGV unassigned Flaviviridae

.
~ r s vir\rs lype 1,
i ' ~ . f ~ s~mplcx
tierorc rim[)lex virus type 2
.- - - .. .. ..

hef;!rr B v~rur)
->

~:C,(!PIVI~U~ ~irn~de

!#..rnr.~n.tdcnovtruc 2
.
(also simian

? , i n ~ n adenovirurer, cg
. . .-
Human herpesvirus 1,
Human herpesvirus 2
Cercopithecine herpesvirus 1

Human adenovirus A through F, eg,

Human adenovirus C
-
HHV-1, HHV-2

CeHV-1

HAdV
HAdV-2 -... - - - . .
Simplexvirus

Simplexvirus

Mastadenovirus
.-
Herpesviridae (subfamily:
Alphaherpesvirinae)
Herpesviridae (subfamily:
Alphaherpesvirinae)

Adenoviridae
:
d.I I

..X
..I.
 4
-
m
a Table 14. Viruses of Humans (cont)

Common and
lnfraspecific Namesa ' Formal Species Names Basic ~ b b r e v i a t i o n ~ Genus. Family

human coronavirus 229E Human coronavirus 229E, HCoV-229E. Coronavirus Coronaviridae

human coronavirus 0C43 Human coronavirus 0C43 HCoV9C43
human herpesvirus 6. Human herpesvirus 6, HHV-6, HHV-7 Roseolovirus Herpesviridae (subfamily:
herpesvirus 7 Human herpesvirus 7 Betaherpesvirinae)
human immunodeficiency virus Human immunodeficiency virus I , HIV-1, HW-2 Lentivirus Retroviridae (subfamily:
Human immunodeficency virus 2 Orthoretrovirinae)
human papillomavirus . ' Human papillomavirus 5, etc HW-5, etc Betapapillomavirus Papillomaviridae
human papillomavirus Human papillomavirus 4, etc HW-4,
etc Gammapapillomavirus Papillomaviridae
human papillomavirus . Human papillomavirus 1, HPV-1, HW-63 Mupapillomavirus Papillomaviridae
Human papillomavinrs 63
human papillomavirus Human papillomavirus 32, etc HW-32 Alphap?pi//omavirus Papillomaviridae
human papillomavirus 41
Human papillomavi'~~ HW41 Nupapillomavi~s Papillomaviridae
human T-lymphotropic virus 1 Primate T-@mphotmpk virus 1 HTLV-1 Deltaretr~vinrs Retroviridae (subfamily:
I . ;
human T-lymphotropic virus 2 Primate T-lymphotmpic virus 2 HTLV-2 Orthoretrovirinae)
i
I influenza A virus Influenza A virus FLUAV InfluenzavirusA Orthomyxoviridae i
,
. . :J,,.'
influenza A/PR8/34 (HlN1)

!i influenza B virus
influenza B/Lee/40
influenza C virus
influenza C/California/78
Influenza B virus

Influenza C virus
FLUBV

FLUCV
lnfluenzavinrs 8

Influenzavirus C
Orthomyxoviridae

Orthomyxoviridae

1 . . Japanese encephalitis virus Japanese encephalitis virus J N F/JV~V~NS Flaviviridae

I
JC virus JC polyomavirus JCw , Polyomavirw Polyomaviridae
?
I - Kaposi sarcoma-associated Human herpesvirus 8 HHV-B *, ~hadinovirus

, .

, .
 -. ~ .
(aeu!~!~oxAwe~ed E s ~ ! ~ e z u a n / 4 ~ eu~ e dw n ~ [ sn~:nezu~rillu,~':~',.~
:Al!we~qns)aep!J!~oxAweJed S~~J!AOJ!~SJ~ E-AUH ' L-NdH '1 sru!~ezuanl~u!e~ed ueunH '1 snrl~ezu3nl,;,!i',cs~~
..~
5fl~1r.vuo)i~t!t?;
uewnq aar snJineuol~~dPI:

:/(~!~ejqnS)
Jep!J!mOd SnJ!AXodeJed NU0 SnJ!A I~IIA !ID
-
aep!l!n!~elj SnJ!A!Ae/j NHO Sll&l JJAJj ~ ! ~ ~ ~ J J O U7SWO
JL/ S~J!A~ a ~>16eql1ouaq
al TsdrO

.
aep!~!~!>le3 SnJ!AOJON hN SnJA
! y/eIWON S ~ J I AI~~MJON

(aeu!~!~oxAwe~ed
:Al!uejqns) J ~ ~ ! J ! ~ \ o X A W ~ J ~ ~ S~J!A~~IUJH A!N snl!~y e d l ~ SnJ!A q e d l ~
aep!~!y~elj sn~!n!ne/j NAW SNA
! sl!)/eyda3ua Aalle~A ~ J J ~ W s n ~ s!g!leqda>ua
!~ Aalle~A e ~ ~ n m
(aeu!~!~odue~ed
:hl!we~qns)aep!~!~oo(we~ed sn~!~elnqn# AnW S
U
A
I! sdun~, snJ!A sdwnu
1

(~~u!J!AXO~O~JO~~ 9 L-I-96-JJ!eZ SnJ!A xodAayuow

:Al!wejqns) aep!J!nxod . .sru!hwodoyuo IWdW sruy xodAaquow s n ~xodAaquou
!~
(aeu!~!hwodop~oq~
:Al!uejqns) aepyyxod S~J!AXO~IJS~//O~V A3OW snJ!A cun~0!6ejuo~LunJsnlloN S ~ J !wns0!6eiuo~
A un>snllow

MWH sn~!~oUnaudelau
uewn~ - sn~!~ounaudelaw
 SN.MwOJOJ J W W ~ U ~ SnJ!APUOlO> FI
aep!~!neuo~o3 snl,neuoJoD AO3-SUVS X/o)w!dsa~ m e a a a s p a l e ! > o a e - ~JO~s~n ~l ! ~suvs I
i
(,,sasnJ!A ayl-o~odde~,,
aep!~!~ple3 ~ ~ J ~ U JsOn J~)! ~ o d e ~ ASI~H sm!A aroddg snl!A 0~0ddes

-1.
aPp!J!Ae60l . SN!A~~~/V SN.M Jan!# SOU snqn eweK!bes
aep!~!~eSol snJ!qnu A8fltl m.fiellVntl s n ~ ellaqn~
!~
aep!~!~oay SN!A~JO~ 3-AUH '0-AU 3 stzyej0u 'g SVAQO~ Snl!AQOJ
XP!J!A~~O~ SnJ!AeL/d/b. A ~ M SN!A JJA!u SOU SnJ!A JaA!u S O Y I

i.1.
aep!~!~er(ung SWOqalYd NAtl SNM
, JJAJJ Aallen VL
!I . snJ!A JaAa4 k a l l e ~
LJ!~
OOL snJ!Aou!qJ ueunq .
8 SN!AOU!~J uewn~ '8 snJ!Aou!qJ 'LE ~ J ! A O U ! ~uelunq
J
aep!J!AeUJO3!d SnJ!AOUll/g AtlH V S ~ I A O ~U
~ J~ W ~ H 'v SnJ!AOU!ql '6a 'SaSnJ!AOU!qJ
(aeu!~!~ounaud SNM
. sm!~
1eghuA.sholu!dsa~uewnq
:kl!UleJqn~)aep!J!A~XkUeJed StlJ!AOWnJUd /\SUH p&
.i 6uXs ~ O J W ! ~ SuJeJ w t ? ~ snJ!A le!@uk hole~!dsa~
~~P!J!AoP~~~u s~J!A&~ A ~ W SNA
! SJ!qeu SnJ!A Sa!qeJ
E S~J!AO!~O~
Z S~J!AO!~O~
aeplJ!AeUJO>ld SllJ!AOJ3jU;l Ad SN!AO!/W 1 S~J!AO!(O~
(aeU!J!AOAJed nv-6 18 sn~!nohled
:dl~wejqns)aepn!nomed sn~!no~yfi3 A6L0 618 sn~!noruedu e w n ~ gv-6 18 S ~ J ! A O N ~ ~
(aeu!~!~oXhwe~ed P s~!nezu~n/~u!e~ed
uewnH p sn~!~ezuanlju!e~ed
:dl!uejqns) aep!~!~oXhue~ed sn~!~e/nqng P-AUH 'Z-AldH '2 sn~!~ezuanl~u!e~ed
uewn~ '5 sn~!nezuan(ju!e~ed

Al!ue4 snuag ,uope!AaJqqy qsea s a u r e ~sapads leurloj ,salue~>!j!>adseijul

pue u o u r u r o ~

( ~ u o ~suewnH
) 40 sasnJ!A 'VL alqel ,
w
.r
 ;suo!le!Aaqqy ' ~ ' b u!
l suo!iepuawwo>aJ q l ! a~uep~oxe
~ u! suo!le!mqqe asn,
.,la '~dfl0~60~as
'su!e~is'saweu sapads apnpu! hew sa!~luj.sa!~ads~ U ! ~ U O ~aql
~ ~joJslaqwatu
J O J Ile lo s6u!ls!l alaldwo> IOU ale uwnlol s!ql u! sa!Jiu3,

aep!~!~!~elj SnJ!A!Ae/j ' Ad h SnJA

! JJAJJ MO//JA S ~ J !lanai
A ~0llal(
StlJ!A
aep!J!~ebol s~J!A~~@v A33M slj!/eydaJ~~
a~!nbJ UJJJSJM SnJ!A s!l!leqda>ua au!nba UJalSJM

aep!J!A!APl j SnJ!A!AP/ j ANM SnJA

! J/!N JSJM SnJ!A al!N lSaM
sn?,n AJSJJ~MJN q~~!~euro~s
JelnJ!saA 'snq eue!pul
=' ?
yJ!jewoJs Je/nJ!saA WA
JeP!J!AoPqellM SN!AO/nJ!SJA ATNSA 'NSA 'AHA se06ely Sll!JeWOJS Je/nJ!SJA s f l l ! ~s!)!leluols ~eln,!sa~
sru,n s n ~s!g!leqda3ua
!~
aep!~!nebol SN!A~~~/V ,- A33A q~!leqdaJu~au!nba ue/anzaua~ au!nba ue(anzaua~
(aeu!~!~xodop~oq3 ,, . .

:Al!wejqns) aep!J!r\xod S~JIMO~O~JJO AUVA AIJ.I-SI eloye~ s n ~ e! l~o ! ~ e ~

. .. ...
(aeu!J!AsadJaqeqdlv - .. .
:Al!wejqns) a e p ! ~ ! ~ a d ~ a ~ sru,no//a~!~e~ : E ~ A H I '~ E s ~ u ~ ~ a ud e~ wa ny ~ S ~ J !~alsoz-ella>!~e~
A
ua6equado3 s n ~e!u!xeA
!~
(aeu!~!~todop~oq3 e~equys n ~e! !~u ! x e ~
:Al!wejqns) aep!J!nxo,j S~JIMO~O~JJO
' A3VA SNA
! e!u!~~e~ S ~ J !eA! u p m
aep!~!n!~elj sN!n!ne/j A381 .. SNU
, s!J!/~~~~JJuJ
a~uoq-~JU s n ~s!l!leqda>ua
!~ au~oq-q2!1
. .
(J~U!J!AXO~O~JO~(~
:Al!wejqns) aep!J!r\xod s~!~ode~e~ ANVl snl,n xodeuel snJ!A xodeuei
aep!~!~elj . SN!A!A~/~ -N lS snr,n ~!l!/eydJJ~aq1no7 is s n ~s!i!leqda>ua
!~ s!no1 1s
aep!~!~eBol sn~!~ey@y ANIS s q stqpu!~
~ S ~ J s! A~ q p u ! ~
aep!J!Aehung SN!AeJUeH ANs SN!A 3JqWON US
! SnJIA aJqUJON UlS
-
(aeu!J!AoJlaJoqvo
'..
:Al!weiqns) aep!~!no~$ad stu!~w~ae~laa L - A ~ , ,. 1 smp ?!do~~oqdurd-1
a)ew!~d s n y >!do~loqdw!+l uptwlr
15 14 Organ isms and Pathogens

KQma Prions. l ' l ~ ctollo\ving A r c ~!~x-A.w n~mr-s2nd at~l~reviations

of transmissi
dorm c n c . ~ ~ ~ h ~ l l o ":~ ~ ~ I ~ i c s ~ ~ ~ ~
Dis~use Abbreviation
tmvine spongifom encephalopathy BSE
("mad cow disease")
Creutzfeldt-Jakob disease CJD
familial CJD fCJD
iatrogenic CJD iCJD
sporadic CJD sCJD
variant CJD (formerly new variant CJD [nvCJD]) vCJD
chronic wasting disease of mule deer and elk CWD
exotic ungulate encephalopathy (nyala, greater EUE
kudu, oryx)
fatal familial insomnia FFI
feline spongiform encephalopathy FSE
Gerstmann-SMussler-Scheinker syndrome GSS
kuru
scrapie
transmissible mink encephalopathy TME
transmissible spongiform encephalopathy TSE
(Do not confuse "kudu" and "kuru.")
The infectious agents of TSEs are known as 7SEagents orpriom. Th
(from "proteinaceous infectious particle") reflects the agents' proposed
or identity with spongiform encephalopathy-related pathologic p
author preference for the terms ZSE agent andption.
Proteins related to spongiform en~ephalopathiesin humans
. .
follows:
PrP . prion protein
PrP27-30 PrP of 27-30 kD
prpc cellular PrP
P~P* .scrapie-type PrP
PrP-res protease-resistant PrP
PrP-sen protease-sensitive PrP
rPrP recombinant PrP
BOVP~P'~ (bovine)
F~P~P* (feline)
HUP~P"~ (human)
HUP~P~ (human)
MD~P~P'~ (mule deer and elk)

--- - - ..
 15.14.4 Prionr

MkPrpSC (mink )
MoPrP (mouse)
N~~P~P* (nyala and greater kudu)
C OvprpSC (ovine Iscrapiel)
Tg(HuPrP1 (transgenic)
Tg(M0PrP-PlOlL)
The last term refers t o a transgenic mouse line with a proline to leucine mutation at
residue 101 (see also 15.6.1, Genetics, Nucleic Acids and Amino Acids).
For prion-related genes, see 15.6.2, Genetics, Human Gene Nomenclature.

REFERENCES
1. Collier L, Oxford J. Human Virology:A Textfor Students of Medicine, Dentistry, and
Micmbiology. New York, NY: Oxford University Press; 1993.
2. Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA. Virus Taxonomy: Clas-
siJication and Nomenclature of Viruses:EEighth Report of the International Committee
on Taronomy of Vinises. San Diego, CA: Elsevier Academic Press; 2005.
3. Drebot MA, Henchal E, Hjelle B, et al. Improved clarity of meaning from the use of
both formal species names and common (vernacular) virus names in virological lit-
erature. Arch Vimi. 2002;147(12):2465-2471.
4. Donald Danforth Plant Science Center. ICTVNet. http://www.danforthcenter.org
/itab/imet/asp/-MainPage.asp. Accessed April 21,2006.
5. Biichen-Osmond C. ICTVdb: The Universal Virus Database of the International
Committee on Taxonomy of Viruses. http://phene.cpmc.colurnbia.edu and http://
www.ncbi.nlm.nih.gov/ICTVdb/. Updated February 18,2005. Accessed April 21,2006.
6. Van Regenrnortel MHV, Fauquet CM, Bishop DHL, et al, eds. Vim Taxonomy Clas-
sijcation and Nomenclature of Viruses:S m t h Report of the International Committee
*
on Taronomy of Viruses. San Diego, CA:Academic Press; 2000.
7. Fauquet CM, Fargette D. Intemational Committee on Taxonomy of Viruses and the
3,142 unassigned species. Vim1J. 2005;2:64. doi:10.1186/1743-422~-2-64.
8. Mayo MA, Fauquet CM, ManiloffJ. Taxonomic proposals on the Web: new ICIV
consultative procedures. Arch Virol. 2003;148(3):603-611.
9. Van Regenmortel MHV. Virus nomenclature. In: Maisonneuve H, Enckell PH,
Polderman AKS, Thapa R, Vekony M, eds. Science EditorsJHandbook.West Clandon,
England: European Association of Science Editors; 2003;§3-4.2:1-4.
10. Van Regenmortel MHV, Mahy BWJ. Emerging issues in virus taxonomy. Emerg Infect
DS. 2004;?10(1):8-13.
11. Van Regenmortel MHV. V i s e s are real, virus species are man-made, taxonomic '
constructions. Arch Viml. 2003;148(12):2481-2488.
12. Van Regenmortel MW, Fauquet CM. Only italicised species names of viruses have a
taxonomic meaning. Arch V i d . 2002;147(11):2247-2250.
13 Van Regenmortel M W . On the relative merits of italics, Latin and binomial nomen-
clature In virus taxonomy. Arch Vim[. 2000;145(2):433-441.
14. Van Repenmonel MHV, Mayo MA, Fauquet CM, Maniloff J. Virus nomenclature:
conzcn\u\ \cr\us chaos Anb Viml. 2000;145(10):2227-2232.
15 V.ln R~.~cnrnc,nrl hltlV How 10 write the names of vin~sspecies. Arch Virol.
iY)').l 1011-1942
&+<?I)
 t
15.15 Rychia tric Terminology

16. Gllsher CH. Mahy BL7. Taxonomy: get it nght o r Icave tt alone. Am J T W Med
2003;68(5):505-506.
17. Van Regenmonel MHV. Perspectives on binomial names of virus species. Arch Vi
2001;146(8):1637-1640.
18. Brunt A, Crabtree K, Dallwitz M, Gibbs A, Watso
Online: Descriptions and Lists From the VIDE D
/vide/refs.htm#names. Accessed December 4, 2006.
19. Asher DM. Transmissible spongiform encephalo
Jorgensen JH, Pfaller hiA, Yolken RH, eds. Man
Washington, DC: ASM Press; 2003:1592-1604.
20. Prusiner SB. Novel proreinaceous infectious particles cause scrapie. Science.
1982;216(4542):13&144.
21. Prusiner SB. Prion diseases and the BSE crisis. Science. 1997;278(5336):245-251. i

Psychiatric Terminology

Diagnostic and Statistical Manual of

chiatkc Association has published 5 editions o
mental disorders. Each edition has been titled Diagnastic and tati is tical Manual
Mental Disorders and has used .the abbreviation DSM
DSM-I (1952)
DsM-n (1968)
DSM-IlZ (1980)
DSM-LGR (1987)
DSM-N (1994)
Using DM-Was an example, these books
American Psychiatric Association. Diagnastic and Statistical Manual of
MentalDisorders.4th ed. W a s h i i o n , DC: American Psychiatric Association; ...
1994.
A text revision of DSM-Nwas publish
ofMentalDisorders, Fourth Edition, TextReukiion,
is a revision of the text describing the diagn
course, and differential diagnosis of the d
categories. However, the diagnostic classification and criteria in DSM-N-7R
changed from those in the 1994 D W
diagnostic criteria, it gives
those of DSM-Wand date
diagnostic criteria should
criteria per se. If a reference citation pertains to the updated descriptive material
W-ZR, that should be cited If a citation
updated descriptive material in D M - T R , it would be best to clarify that in the t
Beginning with DSM-ZD, the diagnostic system involves an assessment on seve
axes as follows:
Axis I . Clinical Disorders
'
Other Conditions That May Be a Focus of Clinical Attention

-- -
 15.16.1 Symbols

Axis I1 Personality Disorders

Mental Retardation
Axis 111 General Medical Conditions
Axis IV Psychosocial and Environmental Problems.
Axis V Global Assessment of Functioning
For proper expressions of editions of DSM, ,see 14.11, Abbreviations, Clinical,
Technical, and Other Common Terms. For proper capitalization of designators of
axes in DSM, eg, Axis 1, see 10.4, Capitalization, Designators.
..
Other Psychiatric Terminology. For appropriate use of.terms such as manic and
schizophrenic, see 11.1, Cdrrect and Preferred Usage, Correct and Preferred Usage of
Common Words and Phrases.
For molecular terms, see 15.11.5, Neurology, Molecular Neuroscience.

B p ulmonary, Respiratory, and Blood Gas Terminology. Standardization of sym-

bols in respiratory physiology dates from at least 1950.'
Despite the familiarity of abbreviations in pulmonary and respiratory medicine,
authors and editors are encouraged to expand all terms at first mention, except as
noted.
Symbols and abbreviations are both used. Symbols consist of separate elements
in various combinations whose letters may differ from the initial letters of the ex-
pansion, eg, Q (perfusion). Abbreviations are usually initialisms.

Symbols. Symbols and their subgrouping into main symbols and modifiers are con-
sistent with approved nomenclature formulated circa 1980 by the Commission of
Respiratory Physiology (International Union of Physiological Sciences) and the Pub-
lications C~mmitteeof the American Physiological ~ o c i e t ~ .The' ' ~ fojlowing group-
ings of pulmonary-respiratory symbols are adapted from ~ i s h r n a n . ~
Main symbols are typically Capital letters set on the line and are the first elements
of an expression. The same letter may stand for one entity in respiratory 111ec1x1nic.s
and another in gas exchange (eg, P stands for pressure in respiratory mechanics anrl
partial pressure in gas exchange). The following are examples (note clots al,ove
some letters to indicate flow):
compliance, concentration
diffusing capacity
fractional concentration in a dry gas
pressure, partial pressure
volume of blood
perfusion (volume of blood per unit time or hlood no\\.)
resistance, gas (respiratory) exch;lngc r:irio
saturation
specific conductance
volume of g:ts
ventilation (vol~rnlcpc.r \:r\,! r,ll\,.t
ionary, xespiratory, and Blood Gas Terminology

Modifiers are set as small capitals (not subscript):

A alveolar
B barometric
DS dead space
E expired, expiratory
FT end-tidal
I inspired, inspiratory
L lung
T tidal
. Lowercase-letter modifiers (which are not subscript)
both appear; note bar in last term:
a arterial
aw airway
b blood
c ap$av
d pulmonary end-capillary
i ideal
I1ISLX maximum
P pulse oximeq
v venous .
-v mixed venous
Gas abbreviations are usually the last element of
co carbon monoxide
carbon dioxide -
N2 nitrogen
02 oxygen
(Note: At other times, when gas abbreviations a
are used, eg, carbon monoxide tC01.)
The mah-symbols and m d i e r s are comb
common examples are the following:
Tenn Expansfon
Pco2 partial pressure of carbon dioxide
Pacol partial pressure of carbon
dioxide, artkrial
Po2 partial pressure of oxygen rnm Hg or kPa
Pao, partial pressure of oxygen, arterial rnm Hg or kPa
'

(Note: The above 4 terms may be given without expansion at first mention; see
14.11, Abbreviations, Clinical, Technical, and Other Common Terms, and 18.0,
of Measure.)

. !.
- - . - . -- . ...-
9 &-.
. .
 1
I

15.16.1 Symbols
-
Expansion Typical UniB of eastw we^'-'
PA02 partial pressure of oxygen, mm Hg or kPa
alveolar
Pm2 partial pressure of oxygen,
mixed venous
PB barometric pressure
P A O- ~Pao2 alveolar-arterial difference
(or gradient) in partial
pressure of oxygen
(preferred to AaDoz)
Cao2 . oxygGn concentration
(or content), arterial
Cdo2 oxygen concentration
(or content), pulmonary
end-capillary'
CL lung compliance

DLCO diffusing capacity of lung for

carbon monoxide
FEN^ fractional concentration of fraction
nitrogen expired gas
FIO~ fraction of inspired oxygen fraction
P~max maximum expiratory pressure cm H20 or mm Hg
P~max maximum inspiratory pressure cm H20or mm Hg
Raw airway resistance -
cm H20 L-' :s-' or
kPa L-' s-'
Saoz arterial oxygen saturation Yo
sGaw specific airway conductance L .s-' .cm H20-' or
L .s-' .k ~ a - '
SPOZ oxygen saturation as
measured by pulse oximetry
VDS volume of dead space mL or L
VE L expired volume per unit time L/min
vo2 oxygen consumption mL/min or L/min or :
mmol/min
~o,max maximum oxygen consumption mL/min or L/.min or
mmol/min
V/Q ventilation perfusion ratio ratio
(also VA/Q)
VT tidal volume mL or L
'Note: Sometimes quantities are given per unit body weight, eg, \'T In I ~ r c . r \ pc.:
kilogram.
15.16 Pulmonary, Respiratory, and Blood Gas Terminology -

IAbbreviations. The following are some common abbreviations from pulmo&

Function testing; they should always be expanded at first mention: fl
CC closing capacity L
CV closing volume L
ERV expiratory reserve volume L
FEF forced expiratory flow L/min
FEFZ5,,, FEF, midexpiratory phase L/min or L/s
FEFzoo-lzoo FEF between 200 and 1200 rnL L/min or L/S
of forced vital capacity (FVC)
FEV
FEvl
forced expiratory volume
FEV in the first second of expiration
I.
L .
l

.
1 .>

FNC forced inspiratory vital capacity L .* .:

FRC functional residual capacity mL or L
FVC forced vital capacity L .i
.3
-S
RV inspiratory reserve volume L <$
:$
NC inspiratory vital capacity L 9
MVV maximum voluntary ventilation L/min
,
-3
:'j
3
PEF, PEFR peak expiratory flow rat& L/min 3
RV residual volume L j
. r(
-2
TLC total lung capacity L 3
i
VC vital capacity L
.rd SP

?
Mechanical Ventilation. The following-should be expanded at first mention: 1
.i
APRV airway pressure release ventilation i2
BiPAP bievel positive airway pressure (cm H20) 4
CPAP continuous positive airway pressure (cm H20) d
ECMO extracorporeal membrane oxygenation
ET tube endotracheal tube
'!
HFV high-frequency ventilation
NIPPV noninvasive positive pressure ventilation
NN noninvasive ventilation
PAV proportional assist ventilation
PEEP positive end-expiratory pressure (cm HzO)

REFERENCES
1. Pappenheimer JR, Comroe JH, Cournand A, et al. Standardization of definitions2
symbols in respiratory physiology. Fed P m . 1950;9:602-605.
2. Fihman AP, ed. Handbook of Physiology: A Critical, Comprehensive Presentatic
Physiological Knowledge and Concepts.Vol2, section 3, pt 1. Bethesda, MD: A&%
Physiological Society; 1986:endpapers. f
*$
 ...

15.17.2 Terms

3. Macklem PT. Symbols and abbreviations. In: Fishman AP, ed. Handbook of Physiology:
A Critical Comprehensive Pmentation of Physiological Knowledge and Concepts. Vol
2, section 3, pt 1. Bethesda, MD: American Physiological Society; 1986:ix.
4. West JB. Pulmonary Pathophysiology: 7be Essentials. 6th ed. Philadelphia, PA: Lip-
pincott Williams & Wilkins; 2003.
5. West JB. Respiratory Physiology: Zhe Essentials. 7th ed. Philadelphia, PA:,Lippincott
Williams &: Wilkins; 2005.
6. Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Hanison's
Princz@lesof Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005:A-14.
'

7. Albert RK,Spiro SG, Jett JR Clinical Respiratoy Medicine. 2nd ed. Philadelphia, PA:
Mosby; 2004.
8. McMillan JA, DeAngelis b,Feigin R, Warshaw JB. Oski's Pediatrics. 3rd ed. Phila-
delphia, PA: Lippincott Williams & Wilkins; 1999.

Radiology Terms

Resources. Available radiologic glo&aries include the following!:

Thoracic radiology: "Glossary of Terms for Thoracic Radiology"*
Computed tomography of the lung: "Glossary of Terms for of the ~ u n ~ s " ~
Breast imaging: BI-RADS ~ t l a s ~
Magnetic resonance: ACR Glossary of URT fm,' Glossary of Magnetic Re-
sonance ~ e r r n s ~
H Ulmonography: Recommended Ultrasound ~erminology'
General, for laypersons and nonspecialists: Radiology1nfo8
In addition to the terminology explained in this section, see .11.0, Corfect and Pre-
ferred Usage, for terms such as radiography, mtgm, and x-ray; 14.14, Abbrevia-
tions, Radioactive-Isotopes,and 159, isotopes; 2nd 18.0, Units of Measure, for units
such as H (Hounsfield) and keV (kiloelectron volt).

Terms. The following terms are commonly used in radiology?

b value-The b factor or b value is associated with diffusion-weighted magnetic
resonance imaging (diffusion-weighted MRI or DWI). It measures "strength (intensity
and timing) of the diffusion gradient"9; units are seconds per square millimeter.
maximum b value of 1221 s/mm2
Four gradient strengths were applied, resulting in b values of 0 ant1
1000 s/mm2 applied sequentially in the X, Y, and Z gradient directions.
Doppler-See 15.3.6, Cardiology, Echocardiography.
echo train-A sequence of echoes. "Echo twin is not a unit of n~easure""I,ut is
cxprc3sc.d as in these examples:
(.: h o train length 5
t., 1)s tr;llrl Icngth 18
15.17 Radiology Terms

echo train length 16

echo tiain length 20
l
a long echo-train-length Idimensional fast-spin echo sequence
k-space-This term refers to mathematical space with frequency and phase as co-
1
ordinates, rather than spatial ~oordinates.~
Our pulse sequences collected data spirally in k-space.
k-space filtering
k-space sampling
number of excitations/signals-Change "number of excitations" to "number of signals
acquired" (applies to MRI).
TI, TI p, T2, TZ*-These are types of relaxation time in magnetic resonance imaging,516
. I
.. .

They need not ,be expanded.

T1 spin-lattice or longitudinal relaxation time
. Tlp spin-lattice relaxation time in the rotating frame
C

T2 spin-spin or transverse relaxation time '

i %
n* time constant for loss of phase coherence among spins
TE, TR-Expand echo time (TE)and repetition time (TR)as in this example:
cardiac-gated repetition time (TR) greater than 2400 milliseconds; echo times
(TEs), 20 and 80 milliseconds

REFERENCES ,.;I-
1. Skryd PJ. Radiologic nomenclature and abbreviations. Radiology. 2201;218(1):10-ll.'
Also available at http://radiology.rsnajnls.org/cgi/
September 22, 2005.

Nomenclature Committee of the-~leischnerSociety. AJR Am J Roentgenol.

1984;1430>509-517. '

0 1 0 0 . 119%;200(2):327-331.
4. American College of Radiology. BI-RADS Atlas. http:&vw.a
?CID=97&DID=142,Accessed September 22, 2005.
5. Hendrick RE, Bradley WG Jr, H a m SE, et al. ACR Revised Glossary 2
Glossay of MRI Terms. 5th ed.) Chicago, IL: American College of Rad
http://~.acr.org/s-acr/sec.asp?CID=3611D=22815. Accessed
6. European Magnetic Resonance Forum. Glossary of magnetic resona
http://www.emrf.org/E~cation%2Oand%2~raining/Glossa~h2OPage%2OE.h~.
Accessed April 21, 2006.

Ultrasound in Medicine; 1997.

8. RadiologyInfo. http://www.radiologyinfo.com/glossary/gloaryl.cfm. Accessed A
21, 2006.
9. Lang D. Usage and nomenclature. In: Radiological Society of North America
In-HouseSfy& Ma~zlral.Oak Brook Ternce, IL: RSNA; 2001.

776
 16.1 16.2
Eponymous vs NoneponymousTerms Nonpossessive Form

Eponyms are names or phrases derived from or including the name of a person or
.place. These terms are used in a descriptive or adjectival sense1 in medical and sci-
entific writing to describe entities such as diseases, syndromes, signs, tests, methods.
and procedures. These eponymous terms should be distinguished from true posses-
sives (eg, Homer's Iliad). Medical eponyms are numerous (a Web site2 devoted to
medical eponymslists more than 70001, are frequently used in medical publications,
and are treated in dictionaries of eponyms covering general medicine3 and some
specialties, eg, neurology?
Eponyms historically have indicated the name of the describer or presumptive
discoverer of the disease (eg, Alzheimer disease) or sign (eg, Murphy sign), the nanle of
a person or kindred found to have the disease described (eg, Christmas disease), or.
when based on the name of a place (technically, toponyms),the geographic location
in which the disease was found to occur (eg, Lyme disease). Traditionally, epnynls
named after the describer or discoverer took the possessive form (-3 and those named
for other persons or for places took the nonpossessive form. As the use of the pos-
sessive form for all eponyms has become progressively less common (see 16.2, Non-
possessive Form), this formal distinction has faded.
Correct use of eponyms should be considered with a view toward clarity and con-
sistency, the awareness that meanings can change over time and across cultures, and a
A-
desire to minimize misunderstanding in an increasingly global medical community.

Eponymous vs Noneponyrnous Terms. Use of eponyms in the biomedical liter-

ature should be considered with regard to their usefulness in transmitting medical
information. Although some eponyms are evanescent, many are permanently inte-
grated into the body of medical knowledge. Eponyms have a degree of historical and
cultural value and sometimes become well known. In the converse of historical
value, it has been argued that certain eponyms should not be used because the
named individual was involved in war crimes.' In any case, many eponyms can be
replaced with a noneponymous term consisting of a descriptive word or phrase that
applies to the same disease, condition, or procedure. For example:
osteitis deformans, instead of Paget disease of bone
hemolytic uremic syndrome, instead of Gasser synclrome
Thc 1 1 s of ~ the noneponynlous term may provide information about location or
funcr~;!n:tnd m;iy serve the goal of clarity in international bionledical communica-
t l o n '17iv noneponyrnous term may l w prefcrrcd in such contexts. This will also
;~\.oltii - t ,nfu%lngtllstincrly diffcrrnt di.xr.~.wibnritivswith sirnilar eponylilous names
cii.;r.:~.;eof lnmc. I';lgcl tiisc:~%c.
( c . ~ . iJ;~gc-r of lhc. ~nlpple).
16 2 Nonpo$lcrrlve Form

In .wrlle c a x s readers ~ r u tx
y more fmn111;rr\vith the e
on the use of either the noneponymous or the ejmnymous term would be contrary
a major purpose of scienrific writing, which is to disseminate ~nformationthat can
quickly understood by all. Placing the descriptive term(s) in parentheses after fi
mention of che eponymous term is another option that may be helpful, for examp
Stein-Levcnthal (polycystic ovary) syndrome
Stevens-Johnson syndrome (bullous erythema multiforme)
The eponym, but not the noun or article that accompanies it, should be capitalize
Babinski sign
Osler nodes
the Fisher exact test
Derivative adjectival forms of prcger names are not capitalized, eg:
parkinsonian gait (from Parkinson disease)

Form. There is some continuing debate over the use of

~on~dssessive
sessive form for eponyms, but a transition toward the nonpossessive form has
place. A major step toward preference for the nonpossessive form occurred wh
National Down Syndrome Society advocated the use of Down syndrome, rather
Down's syndmme, arguing that the syndrome does not actually belong to anyon
The previous (ninth) edition of this manual? the seventh edition of the Council
Science Editors style manual: the Dictionary of Medical ~ponyrns,~ and
edition of Stedman's Medical ~ictiona$ recommend a
form for eponymous terms. However, the 30th edition of Dorland's
Medical Dctionary takes an intermediate position, stating, ''The use of
sive form ending in 's for eponyms is becoming progre
entries for eponymic terms in this Dictionary reflect this ongoing
The Dictionary therefore presents an inconsistent mixture of forms."1°
. . 'One reason for preferring the nonpbssessive form is that, although epo
. possessive nouns using proper names, they are structurally adje
not convey a m e possessive sense.' For example, the nahe A&ison, as used
scribing "Addison's disease,"is used as a noun modifier, with the s e k e of the
fier being clearly nonpossessive. %me possessive eponyms have ev
of derived adjectives, as exempfied in the term addismian
onyms are used in an attributive sense, they-haveco
over time (eg, Nobel Prize, Petri dish). Thus, the w i t i o n o
possessive form is consistentwith a linguistic perspective and a1
usage.'
Use of the nonpo&essive form of eponyms has beco
genetics, and such usage, recommended by McKusick in Mendelian Inheri
Man: A Catalog ofHuman Genes and Genetic iso or den," is appropriate
areas of medicine. MgKusick's reasons for avoiding the possessive form of ep
included the comment that "the eponym is merely a 'handle'; often the person
name is used was not the first to describe the co
full syndrome as it has subsequently become kno
scription may not belong to the named individual, providing an additional reas
avoid the posxssive form.
 16.2 Nonpossessive Form

The following examples illustrate the advantages of the nonpossessive form in

particular categories of eponymous terms with regard to spelling and pronunciation.
r When the word following begins with a sibilant c, s, or z (eg, syndrome, sign,

Bitot spots Looser zones

Cullen sign Reye syndrome
Korsakoff psychosis Schwann cell

Colles fracture Meigs syndrome

Fordyce disease Posadas mycosis
~ r a v e kdisease Wilms tumor
Grawitz tumor Yates correction

R When a hyphenated name is involved:

Brown-Sequard syndrome
9 When 2 or more names are involved:
Charcot-Marie-Tooth disease
Dejerine-Sottas dystrophy
a When an article (a,an, the) precedes the term:
an Opie paradox
a Schatzki ring
Occasionally, the nonpossessive eponymous term may appear awkward. This can
often be addressed by using the before the term:
.;be ~vogadronumber the starling law
the Pascal principle the Tukey test

Alternative stylings for eponymous terms m y include the use of ($

angle of Virchow
circle of Willis
The possessive form is used when it is part of an established nonmedical eponymous

Russell's viper
St John's wort
The possessive form is retained if it is part of the name of an organization or WAS used
in the original of a quotation or citation:
The Alzheimer's 'Associ;~tion
Thc possessive form is :~lsoret:~inctll i ~ noneponyj1loLl\
r tcernl\ tlc\t~rlI~lllg
tl~u)rtlcrx
ch;lr;ccteristic of certain occupations or ;rctivi[ies:

7 79
Uonpc ,sessive Form

coal worken' pneumoconiosis

woolsorrer's d k ~ x
gamekeeper's thumb
In view of the adjectival and descriptive, rather than possessive, sense of epon
the advantages of the nonpossessive form in particular instances, the recomme
dations of authorities, and in keeping with the desire to promote clarity and co
sistency in scientific writing, we reconunend (with the exceptions noted above)
the nonpossessive form be used for eponymous terms.

ACKNOWLEDGMENTS
Principal author: Richard M. Glass,MD
This chapter is.a revision of the chapter on eponyms in the previous edition
this manual. Jeanette M. Smith, MD, JM,was the principal author of that chapt

REFERENCES
1.h d e r s o n n . The language of eponyms.jR Coll Physkianshrzd. 1996;30(2)rl
2. Who named it? http://www.whonarnedit.com. Accessed December 8,2006.
3. Firkin BG,Whitworth JA. Dictionary $Medical Eponyms. 2nd ed. Pearl ~i(er,
Parthenon Publishing Group Inc; 1936.
4. Koehler PJ, Bruyn GW, Pearce JMS, eds. Neutological Eponyms. New York, NY:
ford University Press; 2000.
5. Jeffcoate WJ.Should eponyms be actively detached from diseases?Lancet.
2006;%7(9519):1296-1297.
6. Thumbs-up on Down syndrome? Copy Editor. Ap,d/May 1994:1,7.
7.Iverson C, Flanagin A, Fontanarosa PB, et al. American Medical Association
Style: A Guidefor Autbors and Editors. 9th ed. Baltimore, MD:V i &
lW8.
8. Style Manual Committee,Council of Science Editors. Scientifi Style and Formak
CSE Manual for Authors, Editors, and Publisbm. 7th ed. New York, NY:
University Press, in cooperation with the Council of Science Editors, Res
2006:83.
9. Stedman's Medical Dictionury. 27th ed. Baltimore, MD: Lippincott Wiiams & W
2 0 0 0 ~ .
10. Donland's Illt(stm&d Medical Dictionary. 30th ed. Philadelphia, PA: Sau
2003~~~.
11. McKusick VA. ~ e n d e l k Znbenentance
n in Man: A Catalog of Human Genes arui
netic Disorders. 11th ed. Baltimore, MD: Johns Hopkins University Press; 1994:xl,

.-.--.,- ...
.
.. -- ... .- . ..

a,:.., L .-
 17.1 17.3
Greekletter vs Word Greek Alphabet

17.2 17.4
Capitalization After a Greek Letter Page Composition and Electronic Formats

Greek letters are frequently used in statistical formulas and notations, in mathema-
tical composition, in certain chemical names for drugs, and in clinical and technical
terms (see 14.11,Abbreviations, Clinical, Technical, and Other CommonTerrns; 14.12,
Abbreviations, Units of Measure; 15.0, Nomenclature; 20.0, Study Design and Sta-
tistics; and 21.0, Mathematical Composition).
Badrenergic
K light chain
IFN-X
''?-$-cIT
nuclear factor KP

err Greek Letter vs Word. The editors ofJAM4 and the AuchivesJournals prefer the use
of Greek letters rather than spelled-out words, unless usage dictates otherwise. Consult
. - Dorland's and Stedman's medical dictionaries for geneml terms. These sources mily
diier in the representation of terms, ie, a-fetoprotein (symbol) (Stedmarz 5) ancl alpha
fetoprotein (Dorlanci's). If the Greek letter, rather than the word, is found in either
of these sources for the item in question, use the letter in preference to the word.
a For chemical terms, the use of Greek letters is almost always preferred.

i .
P-P'mene
o For electroencephalographic terms, use the word (see 15.11.2, Nonicncl;~turc..
Neurology, Electroencephalographic Terms).
lambda waves

I
i
6 For drug names that contain Greek letters, consult the sources listecl in 15..r.
Nomenclature, Drugs, for preferred usage. In some cases, when the Greek letter is
part of the word, as in betamethusone, the Greek letter is spelled out ;lncl set
closed up. For some names, the approved nonproprietary n;uiie t:~kesthe \vol.tl
and not the letter, as in beta carotene, with an intervening space. (However. the
chemical name for beta carotene is p-carotene.)

Capitalization After a Greek Letter. In titles, subtitles (except in references).

headings, table column heads, line art, and at the beginning of sentences. the firs
non-Greek letter after a lowercase Greek letter should be capitalized.

I
17.3 Greek Alphabet

i!
P-Blocker use during pregnancy increases the risk that an infant will be small
for gestational age.
:q
Do not capitalize the Greek letter itself, unless the word itself normally includes,
Greek capital letter. In this case, the first non-Greek letter after the capital le
should be lowercased. . , ..
P-Hemolytic streptococci were identified.
A'-3,4-trans-tetrahydrocannabinolis 1 of 2 psychoactive isometric principles
in cannabis.
For hyphenation in words that contain Greek letters, consult Special Combinations i
8.3.1, Punctuation, Hyphens and Dashes, Hyphen.
. i

Greek Alphabet. Capital and lowercase Greek letters are listed below. .<,-
6

Name of Letter Greek Lowercase Greek Capital

Alpha a A
0
Beta P B
Gamma Y r
Delta 6 A i
Epsilon E E
Zeta 6 z I'

Eta 'l
Theta 8
Iota
Kappa
Lambda
Mu
Nu
Xi
Omicron
Pi
Rho P P
Sigma (3 C
Tau r T
Upsilon - u Y
Phi - + , 0
Chi X X
Psi $ S
Omega a R
 t i0

17.4 Page Composition and Elertronic Formats

-. ' Page Compo.sition and Electronic Formats. If Greek letters need to l u rn:lrkcrl or
modified on page proofs, this can be done by writing the letters "Gk" in the margin.
followed by a description of the character (eg, "Gli lowercase mu").
jI Greek letters can pose problems for some Internet browsers. The ])?st solution
I for editors is to make sure their text outputs Greek letters in a universal, platforn~-
independent, nonproprietary standard for character encoding, such as Unicode.
. . Most word processing and typesetting programs can generate Greek letters chat
already are Unicode encoded. Greek letters in running text should never be saveti 1s
graphics; these files are much' larger than text and take much longer to download.
. . Also, Web graphics are not s.ca1able and tend not to print well.

ACKNOWLEDGMENT
Principal author: Brenda Gregoline, ELS
 Units of Measure

18.1 18.4
51 Units Use of Numerals With U n i g
18.1.1 Base Units 18.4.1 Expressing Quantities
18.1.2 Derived Units 18.4.2 Decimal Format
18.1.3 Prefixes 18.4.3 Number Spacing
18.4.4 Multiplicationof Numbers
18.2 18.4.5 Indexes
Expressing Unit Names and Symbols
18.2.1 Capitalization 18.5
18.2.2 Products and Quotients of Conventional Units and SI Units in JAMA
Unit Symbols and the Archives Journals
18.5.1 Length, Area, Volume, Mass
18.3 18.5.2 Temperature '
Format, Style, and Punctuation 18.5.3 Time
18.3.1 Exponents 18.5.4 Visual Acuity
18.3.2 Plurals 18.5.5 Pressure '
18.3.3 Subject-Verb Agreement 18.5.6 pH
18.3.4 Beginning of Sentence, 18.5.7 Solutions and Concentration
Title, Subtitle 18.5.8 Energy
18.3.5 Abbreviations 18.5.9 Drug Doses
18.3.6 Punctuation 18.5.10 Laboratory Values
18.3.7 Hyphens 18.5.1 1 Radiation
18.3.8 Spacing 18.5.12 Currency

I
The presentation of quantitative scientificinformation is an integral component of bio-
medical publication. Accurate communication of scientific knowledge and presen-
tation of numerical data require a scientificallyinformative system for reporting units
of measure.
-
Sl Units. The International System of Units (Le ~ ~ s t 2 m International
e &Unites o r SI)
represents a modified version of the metric system that has been established by
intemational agreement and currently is the official measurement system of most
nations of the world.' The SI promotes uniformity of quantities and units, minimizes
the number of units and multiples used in other measurement systems, and can
express virtually any measurement in science, medicine, industry, and commerce.
In 1977, the World Health Organization recommended the adoption of the SI by
the intemational scientific community. Since then, many biomedical publications
throughout the world have adopted SI units as their preferred and primarj method
for reporting scientific measurements. However, in the United States, most physi-
cians and other health care professionals use conventional units for many common
clinical measurements (eg, blood pressure), and many clinical laboratories report
most lal~oratoryvalues by means of conventional units. ~ccordingly,some bio-
mrtlical put>lications,including JAMA and the Archives Journals, have adopted an
; ~ p p r o : ~f o~r hreporting units of measure that includes a combination of SI units and
c.r)nvr.r\ti<,n:~Iiinits. (See 18.5, Conventional Units and S1 Units in .JAMA and the
:tn.h:~ur Io~lr~;ils.) Authors. scientists, clinicians, editors, and others involved in
18 1 51 U n ~ t s

prepdring and prcxrc~\ingrrun

with appropriare use of units of masure and shoul
reporting of scientific information is clear and a
conversion from conventional units to S1 units, or vice versa.

Base Units. The SI is based on 7 fundamental units (base units) that refer to 7 b
quantities of measurement (see the tabulation below). These units form the structu
from mhich other measurement quantities are composed.
Quantity
Length meter m
Mass
Time second s
Electric current ampere A
Thermodynamic kelvin K
.temperature
Luminous intensity candela cd
Amount of substance mole mol
Although not included among the 7 base units, the liter is
fundamental measure of capacity or volume. The liter is
measurement of volume for liqui
of volume for solids. Although the kelvin is the SI unit
ature, the degree Celsius is used with the SI for tempeiature measurement in
medical settings.

Derived Units. Other SI measurement quantities are

are expressed as products or qu
have special names and symbols and may be used
press other derived units. See the following tabulation.

Quantity Name
Area
Volume cubic meter
Speed, velocity meter per second m/s m/s
Density, mass kilogram per kg/m3 kg/m3
density
Specific volume cubic meter
' per kilogram
Concentration mole per mol/m3 rnol/m3
cubic meter
Frequency
Force newton
Pressure, stress
Work, energy

-- -.
- ., -
7
-
-- ..
2
I 18.1.3 Prefixes

Derivation From
Quantity Name Buse Unit
Luminous flux lumen
Power, Watt
radiant flux
Electric potential volt
Electric charge coulomb
Electric resistance ohm
Capacitance farad
Magnetic flux -. weber
Magnetic flux density tesla
Inductance henry

Prefixes. Prefixes are combined with base units and derived units to form multiples
of SI units. The factors designated by prefixes are powers of 10,and most prefixes
involve exponents that are simple multiples of 3, thereby facilitating conversion
procedures using successive multiplications by lo3 or
Factor &fix Symbol
10" YOtta Y
lo2' zetta z
10l8 exa E
1015 pets P
10l2 tera T
lo9 gigs G
lo6 mega . M
lo3 kilo k
lo2 hecto h
deka (deca)
deci
centi
milli
micro
nano

femto

( : ~ I I ~ ~ M ~I )LI C It'oniicd
I I~ ~ S( L -\ of 2
I)). fllc. c.onll)~n.rt~c,rl l~ioreSI prefixes gener;tll! ;ire
nor u.wxl It IS prcfec~ble[(I u.Y.;ln expression \vrrIi ;i single prefix.
18.2 Expressing U n ~ tNamm and Symbols 1
il

Pn.jrn~I:nm (nanornctrr)
Atuid: mpm (millimicromc~er)
The kilogram is the only SI base unit with a prefix as part of iu name and symbol
However, because compound prefixes are not recommended, prefixes relatin
mass are combined with gram (g) rather than kilogram (kg).
Preferred: mg (milligram)
Avoid: pkg (microkilogram)

,Expressing Unit Names and Symbols. The S I includes conventions for expressln
d
unit names and abbreviations (often referred to as symbols) and for displaying thea
in text.

L1:klCCapitalization. The SI unit names are written lowercase (eg, kilogram) when spc
out, except for Celsius (as in "degrees Celsius"), which is capitalized. ~bbreviatip
or symbols for SI units also are written lowercase, with the following exceptions:
.u
w Abbreviations derived from a proper name should be capitalized (eg, N for nea
K for kelvin, A for ampere), although nonabbreviated SI unit names derivecl j
a proper name are not capitalized (eg, newtons, amperes).
i
w An uppercase letter L is used as the abbreviation for liter to avoid confusionG
the lowercase letter 1 and the number 1. 4
w Certain SI prefixes are capitalized to distinguish them from similar lowei
abbreviations:
M denotes the prefix mega (105, whereas m denotes the prefix milli (10-
mg denotes milligram g), whereas MHz denotes megahertz (lo6 %
P denotes the prefix peta (10'3, whereas p denotes the prefix pico (lo-??
€2
IProducts and Quotients of Unit Symbols. The product of 2 or more SI units sh
be indics~tedby a space befween themo i b y a raised multiplicatic dot#, The
plication dot must be positioned Pro1~erlyto distinguish it from dec
which is set on the baseline. (See 21.6, Mathennatical Composition Zxpr, w i n
tiplication and Division.) When the unit of measure is the product of 2 or more-,
either abbreviations (symbols) or nonabbreviated units should be used. ~ b b r e a
and nonabbreviated forms should not be combined in products.
Preferred: newton meter is expressed as newton meter
0rNmorN.m
Avoid: .
newton. m or N meter
When numerals are used to denote a quantity of measurement, it is preferable t~
the abbreviated form of the SI unit.
Peferred: 50 N m
Avoid: 50 newton meter
The quotient of SI unit symbols may be expressed by the forward slash or virgul
or by the use of negative exponents. If the derived unit is formed by 2 abbrev
 18.3.4 Beginning of Sentence. Title, Subt~tle

units of measure (eg, pg/L), the quotient also may be expressed by means of the
forward slash or negative exponents.
Preferred: pg/L or pg L-' or pg - L-'
Avoid: pg per L -
When the unit names are spelled out in a quotient or in text, the word per should be

Preferred: The power output was measured in joules per second.

Avoid: T h e power output was measured in joules/second [or J/s].
Expressions with 2 or more units of measure may require use of the forward slash.
dot products, negative &ponents, or parentheses. (See 21.6, Mathematical Compo-
sition, Expressing Multiplication and Division.)
mL .kg-' .min-' or mL/kg/rnin'
m2.kg. s-2 - A - ~or (mZ.kg)/(s2. A?

Format, Style, and Punctuation. The format, style, and punctuation gui~lelin~s
generally apply for SI reporting but also are used for reporting most values in con-
ventional u'nits.

reporting style uses exponents rather than certain abbrwiations, such

Prefemd: m2
sq m
P~ferred: m3
Avoid: cu m

Plurals. The same symbol is used for single and multiple quantities. Unit syml~olsarc.
not expressed in the plural form.
Pr.f~md: 1 L 70 L
Avoid: 1Ls 70Ls
Prefcm-ed: 1g 1500 g
Avoid: 1 g s l S 0 0 gs

Subject-Verb Agreement. Units of measure are treated as collective singular (not

plural) n a n s and require a singular verb.
To control the patient's fever, 500 mg of acetaminophen was [not zuerd atl-
ministered at the time of admission and 1 0 O lrlg n.;is recprcd 4 hours later.

Beginning of Sentence, Title, Subtitle. A unlr of mc.15lrt-cth;~rtolIo\~sa ni~nll~er ;~r

the heginning of a sentence, title, or .sul)ti~lc. c\c.n t l ~ o c ~ ~ l ~
t l 1~ .~l,t,rc.v~;~rc.tl.
\ l l o ~ ~ l ,lc,r
the same unit ofmeasr~rt.is nt>brcviatcui~f ~r .rplw.ir\ c.Iv\\-llcrcI r i rhr \ : I I ~ I C .;cnrc.n(.t.

79 1
 -. -
18.4 Use of Numerals With Units 1
(See 19.2.1,Numbers and Percentages,spelling Out Numbers, Beginning a 9
Title, Subtitle, or Heading; and 19.2.2,Numbers and Percentages, Spelling 0uf'
bers, Common Fractions.) d
Abbreviations. Most units of measure are abbreviated when used with numer4
4
a virgule construction. Certain units of measure should be spell
tion, with the abbreviated form in parentheses. Thereafter, the abbrevia
should be used in text. (See 14.12, Abbreviations, Units of Measure.) - Ii
!
1Punctuation. Symbols or abbreviations of units of measure are not followec
4
period, unless the symbol occurs at the end of a sentence.
,j
The patient's weight was 80 kg [not 80 kg.] and had increased by 10%. *

Hyphens. A hyphen is used to join 2 spelled-out units of measure.

C.
pascal-second
A hyphen is used to join a unit of measure and the number,associated
the combination is used as an adjective. (See Temporary Compoun
Punctuation, Hyphens and Dashes, Hyphen.)
an 8-L container a 10-mm strip

Spacing. W1th the exception of the percent sign, the degree sign (for tempe
angles), and n o d and molar solutions (see 18.5.7, Conventional Units and
inJ A M and the Archives Journals, Solutions and Concentdon), a full space 1
appear between the arabic numeral indicating the quantity and the unit of m;
140 nmol/L (not 140nmol/L) 1
135-150 nmol/L . .,

120 mm Hg
u
40% adherence rate 3
400/6-50%
45" angle
temperature of 37.5"C (not 37.5" C or 37.5 "C)

Use of Numerals With Units .

Expressing Quantities. Arabic numerals are used for quantitieswith units of,n
(see 19.1, Numbers and Percentages, Use of ~urn6ral.s).By SI convention, i?
erable to use onlv numbers between 0.1 and 1000 and to use the a ~ ~ r o ~ r i a t e : ?
for expressing quantities. For example, 0.003 mL is expressedas 3 p.L; 15
expressed as 15 kg.
Some clinical measurements are expressed in quantities and units that may
numbers outside this preferred range. For such values, the use of scientificnoti
acceptable.
20 000 000 A may be expressed as 20 million amperes or as 2 x 10' A *;av

. -.-
 18.4.3 Number Spacing

Reported SI values should follow recommendations for preserving the propcr

number of significant digits. (See 20.8.2, Study Design and Statistics, Significant Ilipits
and Rounding Numbers, Rounding.) The use of these increments is intenclecl to
eliminate reporting results beyond the appropriate level of precision.
;
Decimal Format. The decimal format is recommended for numbers i~sedwith units of
measure. Numerical values less than 1 require placement of 0 befoie the decim:~l
marker.
Preferred: 0.123
Avoid: .123-'

However, certain statistical values, such as a levels and P values, should be reported
without the use of 0 before the decimal marker. (See 19.7.1, Numbers and Percentages,

Statistical significance was defined as P< .01.

Fractions should not be used with SI units.
Preferred: 2.5 kg
Avoid: 2% kg
Mixed fractions occasionally are used in text to indicate less precise measurements
and most commonly involve units of measure representing time;
After more than 7%years of investigation, the effort to develop a new vac-
cine was abandoned.
The decimal format also could be used:
After more than 7.5 years of investigation, the effort to develop a new vac-
cine was abandoned.

Number Spacing. By SI convention, the decimal point is the only punctuation mark
permitted in numerals, and it is used to separate the integer and decimal parts of the
number. The SI does not use commas in numbers, in particular because the comma is
used in some countries as the decimal sign. Integers (whole numbers) with more
than 4 digits are separated into groups of 3 (using a thin space) with respect to the
decimal point. Four-digit integers are closed up (without a space). Decimal digits also
are grouped in sets of 3 digits beginning at the decimal sign, with the same closed-up
spacing for 4-digit groups. (See also 19.1.1, Numbers and Percentages, Use of Nu-
merals, Numbers of 4 or More Digits to Either Side of the Decimal Point).
Preferred Amid
1234 1,234
123 456 123,456
12 345.678 901 12,345.678901
1234.567 89 1,234.56789
1 234 567.8901 1,234,567.8901
793
 k --- ....
18.5 Conventional Units and 51 Units in JAMA and the Archives Journals

combined with letters, including trial registration identifiers.

Chicago, IL 60610
This study was supported by grant MCH-110624.
Trial Registration: clinicaltrials.gov Identifier: NCT00381954

(x3O OOO), or scientific notation (eg, 3.6 x 10~1~).

represent an SI convention.

body mass index (BMI), calculated as the weight in kilograms divi

height in meters squared

for reporting units of measure that includes a combination of SI units and

tional units.

Length, Area, Volume, Mass. Measurements of length, area, volume, and

tiomaire, the original measure should be retained.

The patients were asked, "Do you have difficulty walking 15 feet?"

7 94
 18.5.2 Temperature

Table 1. Conversions t o Metric Measures

Known Metric
Symbol Quantity - Mu1tiply.b~ To Find Symbol

Length
in inches 2.54 , centimeters cm
ft . feet 30 centimeters cm
ft feet 0.3 meters m
vd vards 0.9 meters m
miles 1.6 kilometers km
Area
sa in sauare inches 6.5 sauare centimeters cm2
square feet 0.09 sauare meters
bquare yards 0.8 square meters m2
square miles 2.6 square kilometers km2
Mass
oz ounces 28 grams 9
Ib pounds 0.45 kilograms kg
Volume
8P teaspoons 5 milliliters mL
tbs~ tablesmns 15 milliliters mL
- fl oz fluid ounces 30 milliliters mL
c cups 0.24 liters L

Pt US pints 0.47 liters L

-- -
at US auarts 0.95 liters . L

aal US oallons 3.8 liters L

cu ft cubic feet 0.03 cubic meters

--- --... . ..
m3
.

cu yd cubic yards 0.76 cubic meters m3

Temperature. The Celsius scale ("C) is used for temperature measurelncnt r:~rli~r
than the base SI unit for temperature, the kelvin (K), which has little applic;~tionin
medicine. Although both kelvin and Celsius scales have the sxme intcn.;tl \.;~luc.li)r
temperature differences, they differ in their absolute values. For zxample. tculpcr-
ature of 273.15"K is equal to 0°C. Temperature values generally arc reportccl in
degrees Celsius, and values given in degrees Fahrenheit ( O F ) are convenccl t o rlr-
grees Celsius ("C).
(OF - 32)(0.556) = "C
 I/IO~" 6'E-8'0 SS' 1 1w/6d S-Z-S'O ewseld .'olrug auo~epo!~~ . I

11lo'JJ" 0'8-1'1 E9L0.0 lP/6d €2-5 L lun~a~ p ~ >!u!ln~ajou!cuy-g

e

l/louJd SE-8 L6'96 lP/6~ 9E'O-80'0 ewseld ppe q~knqO~!uJyZ'

~IIo'JJ~~
ZS-PE 80L' L 1~/6d OE-OZ ewsqd 'wnJas upe?!wV

l/loVJ 291-ZE PZ'E 1w/6u OSQL ewseld 'wnJaS ~eloze~dlv

llle~d o'z-5.0 ~9~0'0 i/n OZL-OE , wnJg aseleqdsoqd au!le?lv

111ou~d OSZ-ss PL'LZ IPPU 6-2 ewseld 'wruas auoJalsoppj

--
illeqd E 1.0-20.0 ~910'0 iln S'L-O' 1 urnas ~S~IOPIV
l/le?u LP > L99'9 L l/n 8'2 > wn~as aseua6o~pAqaploqo3lv

116 0s-SE 0L 1~16 US-S'E wn~a~ u!wnqlv

. ..-
111eqd 89.0-L 1.0 L910'0 i/n 0p-01 wn~a~ b l v ) aseJa)sueJpu!ole au!uely

-
I/IO'JJ~ 92 > ZZ'O iw/6d OZL > ewseld , ( ~ 1 2 auouJoq
~) ~!do~lo3!~o3oua~p~
--
l/le?u 0S t 0 6 1 L99.9 L l/n O'SZ-S' L 1 wn~a~ aseu!ureap au!souapv
s OVSZ 0'1 S O+SZ . Poolq alollM W V ) awl
u!iseldoqwo~qi[e!ued pale;l!vv

l/~e~u 06' ~99.9L i/n S'S > wn~as aseleqdsoqd p!3v

.-
1/1owur
.. . LL'O> , ZLL'O 1~/6w 0-1 > ewseld 'wn~as auoia>v
~/IOUJ~ OOL> ' ~6.~6 lP/6~ > ewseld 'wn~as alelaJeola>y
 Ceruloplasm~n Serum 20-40 mg/dL ' 10 200-400 mg/L
C t:loramphen~col Serum 10-25 ~9/mL 3.095 31-77 um01/L
Ihlord~azepoxide
; Serum, plasma 0.4-3.0 ~9/mL 3.336 1.3-10.0 umol/L
Chlor~de Serum, plasma 96-106 mEq/L 1.O 96-106 mmol/L
--
r t,lorpromazrne Plasma 50-300 ng/mL 3.126 157-942 nmol/L
:~lorpropam~de Plasma 75-250 mg/L 3.61 270-900 umol/L
Cholecalciferol (see Vitamin D)
Cholesterol (total)
Desirable Serum, plasma C 200 mq/dL 0.0259 c 5.18 mmol/L
ilorderline high Serum, plasma 200-239 mg/dL . 0.0259 5.18-6.18 mmol/L
High Serum, plasma 2240 mg/dL 0.0259 a r6.21 mmol/L
-.-
'I.licil?:terol, high-density (HDL)
(low level) Serum, plasma c 40 mg/dL 0.0259
- --
c 1.03 mmol/L
::i~oii!sterol,
..-..,..-..
low-density (LDL) (high level) Serum, plasma > 160 mg/dL 0.0259 4.144 mmol/L
C holinesterase Serum 5-12 mg/L 2.793 14-39 nmol/L
Chorionic gonadotropin (p-hCG)
~
(rionpregnant) Serum 5.0 mlU/mL 1.O 5.0 IU/L
i:hromium Whole blood 0.7-28.0 ua/L - 19.232 13.4-538.6 nmol/L
Serum
Citrulline Plasma 0.2-1 .O mg/dL 57.081, 12-55 umol/L
Clonazepam Serum 10-50 ng/mL 0.317 0.4-15.8 nmol/L
. --
Clonidine Serum. ~lasma 1.O-2.0 no/mL 4.35 4.4-8.7 nmol/L
Clozapine Serum 200-350 ng/mL 0.003 . C.5-1.0 pmol/L
Coagulation factor I Plasma " 615-0.35 g/dL 29.41 4.4-10.3 pmol/L
. . -
i ; ~brinogen) Plasma 150-350 mg/dL 0.01 1.5-3.5 g/L
,. . .. - -- .. -. -.

Cnoqulalion factor II (prothrombin) Plasma 70-130 % 0.01 0.70-1.30 Proportion of 1.0

-. . -
OD
0
N
Table 2. Selected Laboratory Tests, With Reference Ranges and Conversion Factorsa fcont)

Reference Range, Conventional Conversion Factor Reference

Analyte Speclmen Conventional Unit Unit (Multiply by) Range, SI Unit SI Unit
Coaoulation factor V Plasma 70-130 % 0.01 0.70-1.30 Proportion of 1.0
Coaoulation factor VII Plasma 0.01 0.60-1.40 Proportion of 1.0
Coaaulation factor Vlll Plasma 0.01 0.50-2.00 Proportion of 1.0
Coaaulation factor IX Plasma 70-130 % 0.01 0.70-1.30 Proportion of 1.0
Coagulation factor X Plasma 70-130 . % 0.0 0.70-1.30 Proportion of 1.0
Coagulation factor XI Plasma 70-130 % 0.01 0.70-1.30 Proportion of 1.O
Coagulation factor-Xll . ' Plasma 70-130 % 0.01 0.70-1.30 Propcntbnof 1.0
Cobalt Serum 4.0-10.0 MIL 16.968 67.9-1 69.7 nd/L
Cocaine (toxic) Serum > 1000 na/mL 3.297 > 3300 nmdA
Codeine Serum ' 10-100 ng/mL 3.34 33-334 d / L
Coenzyme Q10 (ubiquinone) Plasma 0.5-1.5 ~g/mL 1.O 0.5-1.5 w/L
Copper Serum 70-140 pg/dL 0.157 11-22 (undfi
COD~ODO~D~V~~~ Urine < 200 ua124 h 1.527 < 300 rtd/d
Corticotropin Plasma < 120 pg/mL 0.22 < 26 pmd/L
Cortisol Serum, plasma 5-25 119/dL 27.588 140-690 nd/L
Cotinine Plasma 0-8 MIL 5.675 0-45 nd/L
C-peptide Serum 0.5-2.5 ng/mL 0.331 0.17-0.83 nd/L
C-reactive orotein Serum 0.08-3.1 ms/L 9.524 0.76-28.5 n&/L
Creatine Serum 0.1-0.4 mg/dL 76.25 8-31 P ~ A
Creatine kinase (CK) Serum 40-1 50 u/L 0.01 67 0.67-2.5 rkaA
Creatine kinase-MB fraction Serum 0-7 ng/mL 1.O 0-7 rtg/L
. .
Creatinine I.:.: .:. - .. .. . . . --.,. . .. 5ehm. plasma. . ,..,. .!.0.6-1.2 .....
;
, . .mg/dL .. .. 88.4 53-106 d / L
Creatlnlne clearance Serum. ~lasma 75-125 mL/min/1.73 m2 0.01 67 1.24-2.08 m~/s/m'
Cvan~de(10x1~) Whole blood > 1.0 ~g/mL 23.24 > 23 pmol/L
Cycllc--
adenoslne monophosphate (CAMP) Plasma 4.6-8.6 ng/mL 3.04 14-26 nmol/L
Cyc lorportne Serum 100-400 ng/mL 0.832 83-333 nmol/L
- --
Cystlne Plasma 0.40-1.40 mg/dL 41.61 5 16-60 pmol/L
D-dimer
.- .--. -
.
Plasma < 0.5 ~g/mC 5.476 < 3.0 nrnol/L
Dehvdroea~androsterone(DHEA) Serum 1.8-12.5 na/mL 3.47 6.2-43.3 nmol/L
Dchvdroep~androsterone
sulfate (DHEA-S) Serum 50-450 uddL
~eoxycort~co~~erone Serum 2-19 ng/dL 30.5 61-576 nmol/L
Deslprarnlne
. --. . Serum, plasma 50-200 ng/mL 3.754 .' 170-700 nrnol/L
D~azeoam Serum. ~lasma 100-1000 na/mL 0.0035 0.35-3.51 umol/L
Plasma 0.5-2.0 nq/ml
D~ll~azem
-- - Serum < 200 mg/L 2.412 < 480 pmol/L
D~sopyram~de Serum, plasma 2.8-7.0 pg/mL 2.946 8.3-22.0 pmol/L
-
Dooam~ne Plasma
--
c 87 oa/mL 6.528 < 475 ~mol/L
Serum, ~ l a m a 30-1SO
Electrophoresis (protein)
Proportion of total protein
Albumin Serum
-- - - -- -- -

~~-Globul~n
-- - -- -- - Serum 2.5-5.0 % . 0.01 0.025-0.05 Proport~onof 1.0
2,-Globulin Serum 7.0-13.0 % 0.01 0.07-0.1 3 Prooortion of 1.0
Serum '8.0-14.0 % 0.01 0.08-0.14 Proportion of 1.0
Y-Globulin Serum 12.0-22.0 % 0.01 0.12-0.22 ' ' Proportion of 1.0
 ' Table 2. Selected Laboratory Tests, With Reference Ranges and Conversion Factorsa (contl

Reference Range, Conventional Conversion Factor Reference

Specimen Conventional Unit Unit (Multiply by) Range, 51 Unit SI Unit

Concentration
Albumin Serum 3.2-5.6 g/dL 10.0 32-56 g/L
a,-Globulin Serum 0.1-0.4 g/dL 10.0 1-10 9/L
a,-Globulin Serum 0.4-1.2 a/dL 10.0 4-12 g/L
Serum 0.5-1.1 g/dL 10.0 5-11 g/L
y-Globulin Serum 0.5-1.6 g/dL 10.0 5-16 g/L
Eosinophils (see White blood cell count)
Eohedrine (toxic) Serum >2 ~9/mL 6.052 > 12.1 prnol/L
Eoine~hrine Plasma <60 IJ~/~L 5.459 < 330 pmol/L
Erythrocyte count (see Red blood

Erythrocyte sedimentation rate Whole blood 0-20 mm/h 1.O 0-20 mm/h
Elythropoietin Serum 5-36 IU/L 1.O 5-36 IU/L
Estradiol (E2) Serum 30-400 pg/mL 3.671 110-1470 pmol/L
Estriol (Ed Serum 540 na/mL 3.467 17.4-138.8 nmol/L
Estrogens (total) Serum 60400 ~'g/mL 1.O 60-400 ng/L
Estrone (El) Serum, plasma 1.5-25.0 pg/mL 3.698 5.5-92.5 prnol/L
Ethanol (ethyl alcohol) Serum, whole . <20 mg/d~ 0.2171 <4.3 . mmol/L
blood
> 20 > 138
1 . Ethchlorvynol (toxic) Serum, plasma ~g/mL 6.915 pmol/L

I Ethosuximide Serum 40-100 . mg/L 7.084 280-700 pmol/L

* '
Ethylene glycol (toxic) Serum, plasma > 30 mg/dL 0.1611 >5 mmol/L

. .
 ienfluram~ne Serum 0.04-0.30 UC~
/IL 4.324 0.18-1.30 umol/L
fentanyl
-- .. . .- . ..-. -
Serum 0.01-0.10 W/mL 2.972 0.02-0.30 pmol/L
ierr11.n Serum 15-200 .ng/mL 2.247 33-450 pmol/L
1,-Feroprote~n
- .-
Serum < 10 ng/mL 1.O < 10.
[legr,>dat~onproducts
F~or~n
- - Plasma < 10 N/mL 1.0 < 10 mg/L
i ibrmcnjen Plasma 200-400 mg/dL 0.0294 5.8-1 1.8 pmol/L
- - - -- --- -
Flecdrr~de
- - - - -
- Serum, plasma 0.2-1 .O ~g/mL 2.413 0.5-2.4 pmol/L
Flucr~de
-. - - - Whole blood < 0.05 mg/dL 0.5263 < 0.027 mmol/L
il~axrt~ne Serum 200-1100 ng/mL 0.00323 0.65-3.56 pmol/L
Flura?epam (tox~c)
- Serum, plasma > 0.2 )~g/mL 2.5 > 0.5 pmol/L
Folare (follc ac~d)
.- - . - --- -- - -- -.
Serum 3-16 ng/mL 2.266 . 7-36 nmol/L
hormone (FSH)
F o l l ~ ~~r~rnulatlnq
e Serum, plasma 1-100 mlU/mL 1.0 1-100 IU/L
-- -- -
F r u ~ l o ~ a rrre
n Serum 36-50 mg/L 5.581 200-280 mmol/L
- - - --. - -
Frucrwe Serum 1-6 mg/dL 55.506 55-335 pmol/L
-- - - .-
. .

Galaclose
-- Serum, plasma < 20 mg/dL 0.0555 < 1.10 mmol/L
Gasrr n Serum 25-90 pg/mL 0.481 12-45 pmol/L
- - .-
G e n i , > ~(In
i Serum 6-10 ~g/mL 2.090 12-21 pmol/L
--
Gluc .ic;o.i
-. - -- Plasma 20-100 ~g/mL 1.o 20-100 ng/L
Glucoq,e Serum 70-1 10 mg/dL 0.0555 3.9-6.1 mmol/L
Glut o:e 6 ~tiosph,~re Whole blood 10-14 u/g 0.01 67 0.17-0.24 nkat/g
dctiydrorjrna:e hemoglobin hemoglobin
- . - ..------ -.
c dc ~d
C>ILJ:~V~I Plasma 0.2-2.8 mg/dL 67.967 15-190 pmol/L
- ..
C~lu!J-~me
. --.- ---. .-. -- .-- --Plasma---
. ,
6.1-10.2 mg/dL 68.423 420-700 pmol/L
(GGT)
-~~Gi~r:~rnylrranslerase
- -. .
Serum 2-30 u/L 0.01 667 0.03-0.51 . pkat/L
Glureih~mtde Serum 2-6 M/mL 4.603 9-28 prnol/L
. . . -.-
. ---- -- -...
-Glyccrol
- - . . (free)
. .... . ... - -.- .--- .... - -
Serum
-- -- .--- - .- - 0.3-1.72 mg/dL 0.1086 0.32-0.187 mmol/L
0)
0
Table 2. Selected Laboratory Tests. With Reference Ranaes and Conversion FactorsaIcont)

Reference Range, Conventional Conversion Factor Reference

Analyte Specimen Conventional Unit Unit (Multiply by) Range, SI Unit 51 Unit

Glycine Plasma 0.9-4.2 mg/dL 133.2 120-560 lrmd 'I

Gold Serum < 10 ua/JL 50.770

-
< 500 nmol/l
Growth hormone (GH) Serum 0-18 ng/mL 1.O 0-18 ~g/l
--
Haloperidol Serum, plasma 6-24 ng/mL 2.66 16-65 nmd/L
Haptoglobin Serum 26-185 mg/dL 10 260- 1850 m9/L
~ematocrit Whole blood 41-50 % 0.01 0.41-0.50 Proporton of 1 0
Hemoglobin Whole blood 14.0-17.5 g/dL 10.0 140-175 g/L --. _
Mean corpuscular hemoglobin (MCH) Whole blood 26-34 ~9/cell 1.o 26-34 ~91cell --
Mean corpuscular hemoglobin
concentration (MCHC) whole blood 33-37 g/dL 10 330-370 g/L
Mean corpuscular volume (MCV) Whole blood 80-100 pm3 1.O 80-100 fL
Hemoglobin A,, (glycated hemoglobin) Whole blood 4-7 % of total 0.01 0.04-0.07 Proportion of
hemoglobin total hemoglobin
Hemoglobin A2 Whole blood 2.0-3.0 % 0.01 0.02-0.03 Proportion of 1.0
Histamine Plasma 0.5-1 .O P~/L 8.997 4.5-9.0 nmol/L
- - - - - -

Histidine Plasma 0.5-1.7 mg/dL 64.45 32-110 prnol/L

Homocysteine Plasma 0.68-2.02 mg/L 7.397 5-15 pmol/L
Homovanillic add Urine 1.4-8.8 mg/24 h 5.&9 8-48 prnol/d
Hydrocodone Serum < 0.02 N/II-IL 3.34 < 0.06 prnol/L
Hydromorphone Serum 0.008-0.032 ua/mL 3504 28-1 12 nrnol/L
&Hydroxybutyric acid Plasma
5-Hydroxyindoleacetic acid (5-HIW Urine 2-6 11-19/24
h 5.23 10.4-31.2 pmol/d
Ibuprofen Serum 10-50 . pg/mL 4.848 50-243 pmol/L
lmipramine Plasma 150-250 ng/mL 3.566 536-893 nmol/L
immunoglobulin A (IgA) Serum 40-350 mg/dL 10 400-3500 mg/L
lrnmunoglobulln D (IgD) Serum 0-8 mg/dL 10 0-80 mq/L
lmrnunoglobulin E (IgE) Serum 0-1500 0.001 0-1.5 mg/L
lrnmunoalobulin G (laGI Serum 650-1600 ma1dL 0.01 6.5-1 6.0 OIL
lrnrnunoglobulin M (IgM) Serum 54-300 m~/dL
Insulin Serum 2.0-20 plU/mL ' 6.945 . 14-140 pmol/L
lnsulinlike arowth factor Serum 130450 na/mL 0.131 18-60 nmol/L
Iodine Serum
Iron Serum 60-150 )1g/dL 0.179 * 10.7-26.9 pmol/L
Iron-bindinocaoacitv Serum 250450 ua1dL 0.179 44.8-80.6 umol/L
Plasma
lsoniazid Plasma 1-7 pg/mL .7.291 7-51 pmol/L
lsooro~anol(toxic) Serum. olasma
- - - -
> 400 ma/L 0.01'66 > 6.64 mmolIL
Kanarnycin Serum, plasma 25-35
Ketamine Serum 0.2-6.3 . ~lg/mL 4.206 0.8-26 pmol/L
17-Ketosteroids Urine 3-12 ma124 h 3.33 i0-42 umolld
Lactate Plasma 5.0-15 mg/dL 0.111 0.6-1.7 mmol/L
Lactate dehydroaenase (LDH) Serum 100-200 u/L 0.0167 1.7-3.4 ukat/L
LDH isoenzymes
LDi Serum 17-27 % 0.01 0.1 7-0.27 Proportion of 1.0
LD, Serum . 27-37 % 0.01 0.27-0.37 Proportion of 1.0
LD3 Serum 18-25 Yo 0.01 0.1 8-0.25 Proport~onof 1.0
1D4 Serum 3-8 % 0.01 0.03-0.08 Proportion of 1.0
 .- --
Table 2. Selected Laboratory Tests, With Reference Ranges and Conversion Factorsa.(cont)

Reference Range, Conventional Conversion Factor Reference

Analyte Specimen Conventional Unit Unit (Multiply by) Range, SI Unit 51 Unit

IDS Serum 0-5 % 0.01 0-0.05 - 1 .o

Proport~onof
Lead Serum < 10-20 pg/dL 0.0483 < 0.5-1.O pmol/L
Leucine Plasma 1 .O-2.3 mg/dL 76.237 75-175 pmol/L
Leukocytes (see White blood cell count)
Lidocaine Serum, plasma 1.5-6.0 ~g/mL 4.267 6.4-25.6 pmol/L
Lipase Serum 31-186 u/L 0.01667 0.5-3.2 pkat/L
--
Lipoprotein(a) [Lp(a)] Serum 10-30 mg/dL 0.0357 0.35-1.0 prnol/L
--
Lithium Serum 0.6-1.2 mEa/L 1 .O 0.6-1.2 mmol/L
Lorazepam Serum
- -

Luteinizing hormone (LH) Serum, plasma 1-104 mlU/mL 1 .O 1-104 IU/L - ---
Lycopene Serum 0.15-0.25 mg/L 1.863 0.28-0.46 , pmol/L
- ..
Lymphocytes (see White blood cell count)
Lysergic acid diethylamide Serum < 0.004 W/mL 3726 < 15 nrnol/L
Lysine Plasma 1.2-3.5 rna/dL 68.404 80-240 umol/L
~ysozyme Serum, plasma 0.4-1.3 mq/dL 10 4-13 mg/L
Magnesium Serum 1.3-2.1 mEq/L 0.50 0.65-1.05 mmol/L -
Manganese Whole blood 10-12 pg/L . 18.202 182-218 nrnol/L .

Maprotiline Plasma 200-600 no/mL 1 .O 200-600 ua/L

Melatonin Serum
Meperidine Serum, plasma 400-700 ng/mL 4.043 1620-2830 nrnol/L
Mercury Serum <5 4.985 c 25 nmol/L
I
 Methadone Serum, plasma 100400 ng/mL 0.00323 0.32-1.29 pmol/L
Methamphetamine Serum 0.01-0.05 ~g/mL 6.7 0.07-0.34 pmol/L
Methanol Plasma < 200 ~g/mL 0.0312 < 6.2 mmol/L
Methaqualone Serum, plasma 2-3 ig/m~ 4.0 8-12. pmol/L
Methemoolobin
- - -
whole blood < 0.24 a/dL 155 < 37.2 pmol/L
Methemoglobln whole blood < 1.0 % of total 0.01 < 0.01 Proportion of
hemoglobin total hemoglobin
Methlclllln Serum 8-25 mg/L 2.636 22-66 pmol/L
Meth~on~ne Plasma 0.1-0.6 mg/dL 67.02 6-40 pmol/L
Methotrexate Serum, plasma 0.04-0.36 mg/L 2200 90-790 nmol/L
Methyldopa Plasma 1-5 pg/mL 4.735 . ' 5.0-25 pmol/L
Metoorolol Serum. ~lasma 75-200 na/mL 3.74 281-748 nmol/L
P2-Microglobulin Serum 1.2-2.8 mg/L 1.O 1.2-2.8 mg/L
Morohine Serum. ~lasma 10-80 na/mL 3.504 35-280 nmol/L
Serum
Naproxen Serum 26-70 pg/mL 4.343 115-300 pmol/L
Niacin (nicotinic acid) Urine 2.4-6.4 mg/24 h 7.30 17.5-4617, pmol/d
Nickel Whole blood 1.O-28.0 udL 17.033 17-476 nmol/L
--

Nicotine Plasma 0.01-0.05 mg/L 6.164 0.062-0.308 pmol/L

Nitrogen (nonprotein) Serum 20-35 mg/dL 0.714 14.3-25.0 mmol/L
Nitroprusside (as thiocyanate) 6-29 pg/mL 17.2 103-500 pmol/L

Norepinephrine Plasma 110-410 pg/mt 5.91 1 650-2423 pmol/L

Nortriptyline Serum, plasma 50-150 ng/mL 3.797 190-570 nrnol/L
Ornithine Plasma 0.4-1.4 mg/dL 75.666 30-106 pmol/L
Osmolality Serum 275-295 mOsm/kg . 1.O 275-295 mmol/kg

Osteocalc~n Serum 3.0-13.0 ng/mL 1.O 3.0-13.0 pg/L

- . . . . . . . --
Q)
0
w
 2
0 Table 2. Selected Laboratory Tests, With Reference Ranges and Conversion Factorsa(cont)

Reference Range, Conventional Conversiar?Factor Reference

Analyte Specimen Conventional Unit Unit (Multiply by). Range, SI Unit 51 Unit

Oxalate Serum 1 .O-2.4 mg/mL 11.107 1 1-27 pmol/L

Oxazepam Serum, plasma 0.2-1.4 pg/mL 3.487 0.7-4.9 pmol/L
Oxycodone Serum 10-100 ng/mL 3.171 32-317 nrnol/L
Oxygen, partialpressure (Po2) Arterial blood 80-100 mm Hg 0.133 11-13 kPa
Paraauat Whole blood 0.1-1.6 ua/mL 5.369 ' 0.5-8.5 umol/L
Parathyroid hormone Serum
Pentobarbital Serum, plasma 1-5 ~g/mL 4.439 4.0-22 pmol/L
Pepsinogen Serum 28-100 ng/mL 1 .O 28-100 pg/L
pH (see Blood gases)
Phencvclidine (toxic) Serum. ~lasma . 90-800 na/mL 4.109 370-3288 nmol/L
Phenobarbital Serum, plasma 15-40 ~9/mL 4.31 65-172 pmol/L
Phenylalanine Plasma 0.6-1.5 mg/dL 60.544 35-90 pmol/L --
Phenylpropanolamine Serum 0.05-0.10 ~g/mL 6613 330-660 nrnol/L .-
.

Phenvtoin Serum, ~lasma 10-20 ma/L 3.968 40-79 ~mol/L

Phos~horus(inorsanic) Serum 2.3-4.7 ms/dL 0.323 0.74-1.52 mmol/L
Placental lactogen Serum 0.5-1.1. WmL 46.296 23-509 nmol/L -. ..

Plasminogen (antigenic) ' ' Plasma 10-20 W/dL 0.1 13 1.1-2.2 prnol/L ---
Plasminogen activator inhibitor Plasma 4-40 ng/mL 19.231 75-750 prnol/L
Platelet count (thrombocvtes) Whole blood 150-350 xl O ~ / U L 1 .O 150-350 XI O~/L

Porphyrins (total) Urine 20-120 bg/L 1.203 25-144 nrnol/L

Potassium Serum 3.5-5.0 ' mEa/L 1 .O 3.5-5.0 rnmol/~
I Prealhumin Serum 19.5-35.8 ma/dL . 10 195-358 mo/L
 Urine < 2.5 mg/24 h 2.972 < 7.5 pmol/d

.
Serum. plasma .. 5-12 ~g/mL 4.582 23-55 pmol/L
Serum, plasma 4-10 ~g/mL 4 25 17-42 pmol/L

- Serum 0.1 5-25 ng/mL 3.18 0.5-79.5 nmol/L

Serum 3.8-23.2 p9/L 43.478 90-140 pmol/L
-.

--
Plasma . 1.2-3.9 mg/dL 86.858 104-340 pmol/L
Propoxyphene
... -... - .. Plasma 0.1-0.4 ~9/mL 2.946 0.3-1.2 pmol/L
Propranolol Serum 50-100 ng/mL 3.856 193-386 nmol/L
. -.
Prostate-spcc~f~c
- ant~gen Serum < 4.0 ng/mL 1.O 1 <4.0 P~/L
Prote~n(rotal)
...................
Serum 6.0-8.0 g/dL 10.0 60-80 g/L
Prothrombtn tlme (PT) Plasma 10-13 5 1 .o 10-13 s
-.. ---
Proloporphyr~n
..................
Red blood cells 15-50 W/dL 0.0178 0.27-0.89 pmol/L
Prot:~pryl~ne Serum. ~lasma 70-250 ua/dL 3.787 266-950 nmol/L

Pyr,dsr~nc(see V~tamlnB6)
- .

Pyrw.are Plasma 0.5-1.5 mg/dL 113.56 60-170 pmol/L

-
Qulnldlne Serum 2.0-5.0 ~g/mL 3.082 6.2-15.4 pmol/L
- - --
Red blood cell count Whole blood 3.9-5.5 xl 0 6 / u ~ 1 .O 3.9-5.5 x~o'~/L
Ren~n Plasma 30-40 pg/mL 0.0237 0.7-1 O
. pmol/L
.- .- ---
Ret~culocytecount Whole blood 25-75 xl 0 3 / p ~ 1.O 25-75 x 1O ~ / L

Ret~culocytecount Whole blood 0.5-1.5 % of red 0.01 0.005-0.015 Proportton of

blood cells red blood cells

Retlnol (see V~taminA)

R~boflavin(see Vitamin 0,)
Rifampin Serum 4-40 mg/L 1.215 i 5-49 - . - pmol/L -. .
I
Salicylates Serum, plasma 150-300 ![g/mL 0.0724 1086-2
2- -- - - 1 72 ~trnol/L
...
Selenium
--- ---. Serum, plasma 58-234 WL -.-- 0.0127
.................... 0.74-2.97 pmol/L
5
-.
 1/1owd L'V-L'Z 669'2 1~16d S'L-O'L ewseld ' w n ~ a ~ au!zep!~o!ql
1/10wd L'OZ-L'P WL'P 1~16d s- 1 ewseld ' t u n ~ a ~ ~quado!ql
(18 u!wel!A aas) au!we!u

1/10uJd L 11-95 SS'S ~ 1 6 d 0Z-OL ewseld 'wrua~ au!llAlldo~lll

l/lowu 9' LP-P'OL LPEO'O 1 ~ 1 6 ~ 00Z 1-00E urnas auo~apopal

l/loUJ' 89 L-PZ L6'6L 1~/6w L 'Z-E'O ewseld au!~nel
u!qol6owaq lelol u!qol6owaq
40 uo!uodo~d 010'0 > LO'O PO1 40 % 0.1 > Pmlq alollM u!qo16owaqaaw~1n~
l/louJd 066-0 LE 88L'LE 116~ ZE-OL wnJag alellnS
-

l/loUJd 081 > ZPL '0 1~/6d OPZ > eluseld d a3uasqns

1110u~u 09-8 L LEL'O 1 ~ 1 6 ~ OSP-OEL

l/lowu LL-EL 968'8 1~/6d O'Z-5' L wn~a~ u!lnqol6 6u!pu!q-auow~oqxas

l/lowd PL'L-8Z'O 89500'0 1~16u 002-05 Poolq ~ l o W (au!weadhfio~pAq-S)u!uolo~a~
l/lowd €61-59 95 1.56 lP/6~ O'Z-L'O ewseld au!~a~

(JUO~) p h o w o q e i papalas .Z a l q e l
o u e j uotsJaAuo3 pue sabue~a>uaJaJag4 1 ! 's~sal
~ ,
 I

Thyroglobulin Serum 3-42 ng/mL 1.O 3-42

Thvroid-stimulatina hormone TTSH) Serum . 0.4-4.2 mlU/L 1.O 0.4-4.2 mlU/L
Thyroxine, free (ma) Serum 0.9-2.3 ng/dL 12.871 12-30 pmol/L
Thyrox~ne,total (TJ Serum 5.5-12.5 W/dL 12.871 71-160 nmol/L
- .-
Thyroxtne-bindlng globulin Serum 16.0-24.0 ~g/mL 17.094 206-309 nmol/L
- . --
Tlrsue plasrnlnogen activator
.. .
-
Plasma < 0.04 IU/mL 1000 < 40 IU/L
Tobramyc~n Serum, plasma 5-10 ~g/mL 2.139 10-21 pmol/L
icca~n~de Serum 4-10 pg/mL , 5.201 21-52 pmol/L
1-Tocopherol
.- .-- (we
-
..
V~taminE)
Toiburaw!de Serum 80-240 ~g/mL 3.70 296-888 pmol/L
-- -- - -- -
iranrfprrt~
- . -- -- Serum 200-400 wl/dL 0.0123 . 2.5-5.0 pmol/L
Trtqb,certdcr Serum c 160 mg/dL 0.01 13 1.8 mmol/L
Trmdothyronlne, free (FT,) Serum ' 1.4-4.4 pg/mL . 0.0154 0.22-6.78 pmol/L
--- --
Trl~odothyron~ne,
total (T3) Serum 60-180 ng/dL 0.0154 0.92-2.76 nmol/L
-- -
Trooon~nI Serum 0-0.4 na/mL 1.0 3-0.4 ua/L
-- -

'ro~onlnT
- -
Serum 0-0.1 ng/mL 1.o 0-0.1 P~/L
'-,plophan Plasma 0.5-1.5 mg/dL 48.967 25-73 pmol/L
-- -
1, os~ne Plasma 0.4-1.6 mg/dL 55.19 20-90 pmol/L
I ro.l n~troqen Serum 8-23 mg/dL 0.357 2.9-8 2 mmol/L
- -
I r .lcsd Serum 4.0-8.0 mg/dL 59.485 240-480 pmol/L
L I fmq(sn
, >I>
--
Ur~ne 1-3.5 mg/24 h . 1.7 1 7-5.9 pmol/d
'I
. I I ( ' Plasma 1.7-3.7 mg/dL 85.361 145-315 pmol/L
-
.,I ! ,otc ,)I ,d Serum, plasma ' 50-100 M/mL 6.934 346-693 pmol/L 34
,O I , ~n Serum, plasma 20-40 ~g/mL 0.690 14-28 pmol/L I
--
. 1 .'.r ~ , l d r(l . ~ (VMA)
d Urlne 2.1-7.6 mg/24 h 5.046 11-38 pmol/d
. I 3c.1.c ~rrl~rtinal
polypept~de Plasma < 50 pg/mL 0.2960 < 15 pmol/L
w
A
W
 Table 2. Selected Laboratory Tests, With Reference Ranges and Conversion Factorsa(cont)

Reference Range, Conventional Conversion Factor Reference

Analyte Specimen Conventional Unit Unit (Multiply by) Range, SI Unit SI Unit

Vasopressin Plasma 1.5-2.0 pg/mL 0.923 ' 1.O-2.0 pmol/L

-- -- - - - -

Verapamil Serum, plasma 100-500 ng/mL 2.20 220-1100 nmol/L

Vitamin A (retinal) Serum 30-80 pg/dL 0.0349 , 1.05-2.80 pmol/L
Vitamin 6, (thiamine) . Serum 0-2 ~g/dL 29.6 0-75 nmol/L
Vitamin B2 (riboflavin) Serum 4-24 ~g/dL 26.6 106-638 nrnol/L
Vitamin B3 Whole blood 0.2-1.8 ~g/mL 4.56 0.9-8.2 pmol/L
Vitamin B6 (pyridoxine) Plasma 5-30 ng/mL 4.04.i 20-121 nmol/L
\
Vitamin BI2 Serum 160-950 pg/mL 0.7378 118-701 pmol/L
'$1
. . Serum 0.4-1.5 mg/dL 56.78 23-85 pmo~/~
I Vitamin C (ascorbic acid)
:
c +# Vitamin D (1.25 dihydroxyvitamin D) Serum 25-45 Pg/mL 2.6 60-108 pmol/L

j1 . Vitamin D (25-hydroxyvitamin D) Plasma 14-60 ng/mL 2.496 35-150 nmol/L

Vitamin E (a-tocopherol) Serum 5-18 ~g/mL 23.22 12-42 pmol/L

. :i
Vitamin K Serum 0.13-1.19 ng/mL 2.22 0.29-2.64 nmol/L

I . Warfarin Serum, plasma 1.0-10 ~g/mL 3.247 3.2-32.4 pmol/L

I White blood cell count Whole blood 4500-1 1000 /pL 0.001 4.5-1 1 .0 XI O~/L
 Lvmohocvtes Whole blood 10004800 /PL 0.001 1.O-4.8 XIO~/L

Monocytes Whole blood 0-800 IP

'L 0.001 0-0.80 XI O~/L

Eosinophils Whole blood 0-450 /PL 0.001 0-0.45 XI O~/L

Basophils Whole blood 0-200 /PL 0.001 0-0.20 xlo9/~

Differential count (number fraction)

Neutrophils-segmented Whole blood 56 . % 0.01 0.56 Proportion of 1.0

Neutrophils-bands Whole blood 3 YO 0.01 0.03 Proportion of 1.0

Lvrnohocvtes Whole blood 34 % 0.01 0.34 Proportion of 1.0

Monocytes Whde blood 4 % 0.01 0.04 Proportion of 1.0

Eosinophils Whole blood 2.7 YO 0.01 0.027 Proportion of 1.0
Basoohils Whole blood 0.3 % 0.01 . 0.003 Proportion of 1.0
Zidovudine Serum, plasma 0.15-0.27 Pg/mL 3.7 0.56-1.01 pmol/L
Zinc Serum 75-120 Pg/dL 0.153 11.5-18.5 pmol/L

'The laboratory values and reference ranges are provided for illustrationonly and are not intended to becomprehensiveor definitive. Each laboratory determines its own values, and reference ranges
are highly method dependent. Reference values given are for adults. For some entries for which specific molecular masses are not known (eg, proteins), reference values in 51 are given as mass
amounts per liter.
The information in this table is adapted from and based on the following sources: (1) ~ r a A. k Ferraro M, Sluss PM, Lewandrowski KB. Laboratory reference values. N Engl J Med.
2004;351(15): 1548-1563; (2) Young DS, Huth EJ. 51Units for ClinicalMeasu~ment.Philadelphia, PA: American College of Physicians; 1998; (3) Henry JB, ed. Clinical Diagnosisand Management by
LaboratoryMethods. 20th ed. Philadelphia, PA: WB Saunders; 2001; (4) Kasper DL, Braunwald E, Fauci AS, et al, eds. Harrison's Principlesof InternalMedicine, 16th ed. New York, NY: McGraw Hill;
2004: and (5) Goldman L, Ausiello 0.Cecil Textbook of Medicine. 22nd ed. Philadelphia, PA: WE Saunders; 2004.
18.5 Convent~onalUntts and 51 unl:, In J A M A and the Xrchrves Journals
, 4
f'or I.~l~)r;~ior?
\.I~UL-\ rr-lx~ncJ ~r~./.+\l.-l
;ind in the ArchiuesJournals, factors
ion\-cn~ng convr.rl11on;llunllh ro SI unlts ~ h ~ iLX:
~ provided
ld in the article. In text,
converhlon lactor should tx: given once, at first mention of the laboratory value, .in .
parentheses follo\ving the conventional unit.
- '

The blood glucose concentration of 126 mg/dL (to convert to millirnoles

per liter, multiply by 0.055) was used as a criterion for diagnosing dia-
betes.
X II

For articles in which several laboratory values are reported in text, the conversio>
factors may be listed in a paragraph at the end of the "Methods" section. For
or tables, the conversion factors should be included in legends or in foo
respectively, but not in the abstract of the article. (See Footnotes in 4.1.3,
Presentation of Data, Tables, Table Components.)
Hematologic values should be reported by means of conventional units. '4.;
The complete blood cell count showed a hemoglobin level of 13.4 g/d~,,j.!
'f'-'

hematocrit of 41%, platelet count of 180 000/$, and white blood sell count 1 I,,.
of 6500/p.L. 1- :
For enzymatic activity, the international unit (IU) is used; 1IU equals the amoundof
enzyme generating 1pmol of product per minute. I..
I

The peak follicle-stimulatinghormone level was 48 mIU/mL.

Radiation. Measurements of ionizing radiation and radioactivity should be reported

by means of SI units. The SI units for radiation are established by international
agreement.' The unit for activity of a radionuclide is the becquerel; the absorbed
dose of radiation (absorbed per unit weight of tissue) is the gray (Gy); and the dose
equivalent used to indicate the detrimental effects of an absorbed radiation dose on
biological tissue is the sievert (Sv).
A 1-Gy dose is equivalent to 1 joule (J) of radiation energy absorbed per kilo-
s older, non-SI term and is still in use as a unit
gram of organ or tissue weight. ~ a d - ithe
of absorbed dose (100 rad = 1 Gy). However, equal doses of all types of ionizing
radiation are not equally harmful. Alpha particles produce greater harm than beta
particles, y rays, and x-rays for a given absorbed dose. To account for this difference;
radiation dose is expressed as equivalent dose in sieverts (sv)?
SI units fpr radiation and factors to convert values from SI units to conventional
units are shown below.
Non-SI
Quantity SI Unit (Symbol) Conversion Factors Unit
Radioactivity becquerel (Bq) 1 Bq = 2.7 x lo-" curie
Ci (approx)
1 Ci = 3.7 x 10'' Bq '

1 Bq = 27 picocurie (pCi)
Absorbed dose gray (Gy) 1 Gy = 100 rad rad i,
1 rad = 0.01 Gy" .:\
1
 18.5.12 Currency

12'01 1 -S1
Qzcantity SZ Unit (Symbol) Conuersiolz Factors lhrit
"Dose" equivalent sievert (Sv) 1 Sv = 100 rem rem
. 1 rem = 0.01 Sv
aAlthough 1rad = 1cGy, the centi- prefix is generally not preferred in SI. Therefore. despite
the appeal of one-to-one conversion, rad should be convened to gray, not'centigrdy.

Although SI units are peferred, authors of some articles, such as those reporting
studies involving nuclear medicine or radiation oncology, may prefer to report re-
sults in both SI units and.non-SI units. As with units for laboratory results, conversion
factors to convert racjhtion units from SI units to conventional units should be
provided in the artic1e;either in the text, in footnotes to tables or figures, or in the
"Methods" section.

Currency. Amounts of money in US, Canadian, and British currency are expressed as
a decimal number or whole number preceded by the symbol for the unit of measure
. for the currency.

The cost-effectiveness analysis suggested a $7000 difference between the

2 treatment strategies.
--- - - - -

Table 3. Selected InternationalCurrencies and Symbols

Country Currency . Symbol or Abbreviation

Argentina Argentine peso $

Australia Australian dollar A$

Austria Austrian shillinas AT5
---

Bahamas Bahamian dollar

~ -

Belaium Euro (replaces Belgian franc) €

Bermuda Bermuda dollar BdB

Bolivia boliviano $

Brazil Brazilian real R$

Canada Canadian dollar Can$
chile Chilean ~ e s o Ch$
China ' yuan renminbi Y
Colombia Colombian peso ColB i
Cuba Cuban peso $

Czech Reoublic Czech koruna Kt

- -

Denmark Danish krone . kr

Dominican Republic Dominican peso ROB

Egypt Egyptian pound f

European Union Euro E
Finland Euro (replaces markka) E
France €
-- Euro--(replaces
----franc) --- - ..-...
....--.- - ... .. -- --
 '7
Table 3. Selected Internatonal Currencies and Symbols (conr) !q

Country Currency Symbol or ~bbrevlatib;

I
Germany Euro (replaces deutsche mark) E

Hungary forint ft ...

India ru~ee Rs
1:
F

rial IRR ,:i-#$g

new Iraqi dinar
Irelacd Euro (replaces pound) €
-
Israel Israeli new sheqel
Italy Euro (replaces lira) €
Jaoan ven u4
Jordan Jordanian dinars

Lebanon Lebanese pound

The Netherlands Euro (re~lacesauilder)

New Zealand New Zealand dollar NZP
,$f
Norway Norwegian krone kr :.d

Peru neuvos soles S/

Poland zlotv
Portugal Euro (replaces escudo) €
Russia ruble
Saudi riyal

South Africa rand R

Spain Euro (replaces pesata) €
-- --

Sweden Swedish krona

Switzerland Swiss franc
Taiwan Taiwanese new dollar
Thailand baht B I
Turkey Turkish new lira Tf
United Kingdom pound sterling f
United States of America US dollar P
Vietnam dong d
 18.5.12 Currency

In J A M and the Archiues Journals, for amounts reported in non-US currency, the
.current exchange rate should b e used to calculate the amount in US dollars, and that
amount should be shown in parentheses, A list of some international currencies a n d
their symbols is provided in Table 3. Online currency converter programs also are
available.lo'"
The baseline amount for the cost-benefit analysis was estimated from the
procedure cost of CaD $3000 (US $2800).
The projected cost of the llew research laboratory was €25 million (US $47.7
million).

ACKNOWLEDGMENTS ',
Principal authors: Phil B. Fontanarosa, MD, MBA, a n d Stacy Christiansen, MA
I thank Lupe Morales, J A M , for her assistance with preparation of the tables in
this chapter.

REFERENCES '

1. Bureau International des Poids et Mesures. 7be International Sjstenz of Units (SI). 8th
ed. h~p://wwwl.bipm.org/utils/common/pdf/si~brochure~8.pdf. Accessed August 7, .
2006.
2. Dorland's IlIustratedMedical Dictionay. 30th ed. Philadelphia, PA: WB Saunders Co;
2000.
3. Kriska AM, Caspersen CJ. Introduction to a collection of physical activity question-
naires. Med Sci Sports Exwc. 1997;29(6):S5-S9.
4. I h t z A, Ferraro M, Sluss PM, Lewandrowski KB. Laboratory reference values. N Engl
J Med. 2004;351(15):1548-1563.
5. Young DS, Huth EJ. SI Unitsfor Clinical Measurement. ~hi'ladei~hia, PA: American
College of Physicians; 1998.
6. Henry JB, ed. Clinical Diagnosis and Management by Luboratoty Methods. 20th ed.
Philadelphia, PA: W B Saucders Co; 2001.
7. Goldman L, Ausiello D. Cecil Tdbook of Medicine. 22nd ecl. I'hiladelphia, PA: WI3
Saunders Co; 2004.
8. Kasper DL, Braunwald E, Fauci AS, et al, eds. Hanison's Principles of Intet71alAlc~cf-
icine. 16th ed. New York, NY: McGraw-Hill; 2004.
9. Canadian Centre for Occupational Health and Safety. What is ionizing racliation?
www.ccohs,ca/oshanswers/phys~agents/ionizing.html. Accessed August 7, 2006.
10. Codes for representation of currencies and funds. Geneva, Switzerland: Intern:~tion;ll
Organization for Standardic~tion;2004. littp://www.xc.co1ii/iso4217.li~1ii.Accc.asc*tl
August 7, 2006.
11. 0anda.com Quick Converter. ~.oanda.com/converter/classic.Accessetl Augu>t -.
2006.
 19.1 19.3.1 Rounded Large Numbers
Use of Numerals 19.3.2 Consecutive Numerical Expressions
19.1.1 Numbers of 4 or More Digits to
Either Side of the Decimal Point 19.4
19.1.2 Mixed Fractions Use of Digit Spans and Hyphens
19.1.3 Measures of Time .
19.1.4 Measures of Temperature 19.5
19.1.5 Measures of Currency Enumerations

19.2 19.6
Spelling Out Numbers Abbreviating Number
19.2.1 Beginning a Sentence, Title, Subtitle,
or Heading 19.7
19.2.2 Common Fractions Forms of Numbers
19.2.3 One Used as a Pronoun 19.7.1 Decimals
19.2.4 Accepted Usage 19.7.2 Percentages
19.2.5 Ordinals 19.7.3 Reporting Proportions and Percentages
19.7A Reporting Rates and Ratios
193 19.7.5 Roman Numerals
Combining Numeals and Words

Any policy on the use of numbers in text must take into account the reader's im-
pression that numbers written as numerals (symbols) appear to emphasize quantity
more stronglythan numbers spelled out as words. Because numerals convey quantity
-
more efficiently than spelled-out numbers, they are generally preferable in technical
writing. In literary writing, by contrast, spelled-out numbers may be more compatible
with style. Despite these general principles, usage may appear inconsistent when a
publication chooses to use numerals in some instances and words in otheis. The
guidelines outlined in this section attempt to reduce these inconsistencies and avoid
use of numerals that may be jamng to the reader. In situationsthat are not governed
by these guidelines, common sense and editorial judgment should prevail.

Use.of Numerals. In scientific writing; numerals are used to express numbers in

most circumstances. Exceptions are the following:
m Numbers that begin a sentence, title, subtitle, or heading
n Common fractions
a Accepted usage such as idiomatic expressions and numbers used as pronouns
Other uses of "one" in running text
Ordinalsfin! through ninth
Numbers spelled out in quotes or pr~l>li,ll~d
tirlc5 (Scc 1'1.2. Spcll~ngOut
Numbers.)
Note the followin): ~.xamplesof nurl~cr.rl\111 1 ~ x 1
 - - ..

19.1 Use of Numerals

The relative risk of exposed individuals was nearly 3 times that of the
trols.
In the second phase of the study, 3 of the investigators administered
tests to the 7 remaining subjects. The test scores showed a 2- to 2.4-fol
improvement over those of the first phase.
In 2 of the 17 patients in whom both ears were tested, we were una
obtain responses from either ear. While testing patient 3, we experienced
technical problems consisting of unmanageable electrical artifacts.
Groups 1 and 2 were similar 'in terms of demographic and clinical
acteristics (Table 1). Table 2 lists the 4 tests that were performed.
A 3-member committee from the Food and Drug Administration visited the
researchers.

lkaglNumbers of 4 or Mqre Digits to Either Side .of the Decimal Point. commas ar
used in 1arge.numbers. In 4-digit numbers, the digits are set closed up. For
of 10000 or greater, a half-space or thin space is used to separate every 3
starting from the right-most integer (or, in numbers with decimals, from the left
decimal point). For numbers with 5 or more digits to the right of the d e
half-space is used between every 3 digits starting from the right of the
(see also 18.4, Units of Measure, Use of Numerals With Units).
The exact weight of the salt was 8.45398 g, but its reported value was
rounded to 8.4540 g.
Our analytical sample included all 2455 communitydwelling individuals 65,
years or older, representing 32 294 810 elderly persons in the United .States.:

Mixed Fractions. For less precise measurements, mixed fractions

stead of'decirnals. These expressions usually involve time. C
typically spelled out (see 19.2.2, Spelling Out Numbers, Common Fractions). - .!.,
The surgery lasted 3% hours.
The patient was hospitalized for 5% days.
Of the patients returning for a second visit, half received the interventio

Measures of Time. Measures of time usually are expressed as n

Abbreviations, Days of the Week, Months, Eras). When dates
should be used for day and year; the month should be spelled out unless liste
table. Conventional form for time and dates (11:30 PM on February 25, 19
preferred to European o i military form (2330 on 25 February
military time may clarify the time course in figures that depict a 24-hour expe
times of drug dosing, and the like. For time, if the hour of
used and set in small capitals (see also 22.0, Typography).
the hour, the minutes may be omitted (eg, 3 PM). With 12 o'clock, simply use n
midnight, whichever is intended.
 19.2.1 Beginning a Sentence, Title, Subtitle, or Heading

At 5:45 AM, October 15, 1994, the researchers completed the final experi-
ment.
The 21st century officially began just after midnight on January 1, 2001.
When referring to a position as\t would appear on a clock face, express the position
by means of numerals followed by "o'clock."
The needle was inserted at the Po'clock position.
But: The procedure was scheduled to begin at 9 AM.
See 8.2.3 (Punctuation, Comma, Semicolon, Colon, Colon) for punctuation in ex-
pressions of time.

Measures of Temperature. Use the degree symbol with Celsius or Fahrenheit mea-
-
sures of temperature. The degree symbol should be closed up (see 18.3.8, Units of
Measure, Format, Style, and Punctuation, Spacing).
The plates were cultured at 17OC, 3°C lower than usual. -
Measures of Currency. For sums of money, use the appropriate symbol to indicate
the type of currency (eg, $, e, &; see also 18.5.12, Units of Measure, Conventional
Units and SI Units in J A M and the ~rchives ~ournals,*~urrenc~).
Hi charge for the medication was $55.60 plus $0.95 for shipping.
The equivalent sum in euros was €30.

Spelling Out Numbers. Use words to express numbers that occur at the beginning
- of a sentence, title, subtitle, or heading; for common fractions; for accepted usage
and numbers used as pronouns; for ordinalsfitst through ninth; and when part of a
published quote or title in which the number is spelled out. When spelling out
numerals, hyphenate twenty-one through ninety-nine when these numbers occur
. alone or as part of a larger number. When numbers greater than 100 are spelled out,
d o not use commas or and (eg, one hundred thirty-two).

Beginning a Sentence, Title, Subtitle, or Heading. Ilse worcls for any number that
begins a sentence, title, subtitle, or heading. However, it n~dybe better to reword the
I sentence so that it does not begin with a numher.
Three,huncirecl twenty-eight men and 126 women were inclucletl in the . .
study.
Better: The study population comprised 328 men and 126 women.
Participants: Seventy-two thousand three hundred thirty-seven post-
menopausal women aged 34 to 77 years.
Bettec Participants: A total of 72 337 pbstmenopausal women aged 34 t o 77
years.
Three patients were identified; 2 had hypertension and 1 had cli:~l>etcs.
Numerals may be used in sentences that begin with a specific year, I I L I ~ :~\.oidIx-
ginning'sentencrs with years if possible.
19.2 Spelling Out Numben

1(?)5 rrurkr4 the iuth Itnnlversrr) of the bombing of Hiroshima.

k v r t ~ n1c
: yclr 1W5 marked the 50th anniversary of the bo
Hirosh~~ru.
2005 was the medical school's centennial year.
Befter:The medical school's centennial year was 2005.
When a unit of measure follows a number that begins a sentence, it too must
written out, even if the same unit is abbreviated elsewhere in the sa
Because this construction can be cumbersome, rewording the
preferable (see 18.3, Units of Measure, Format, Style, and Punctuation).
Two milligrams of haloperidol was administered at 9 PM, followe
3:30 AM.
Beftm At ~ P M2, mg of haloperidol was administered, followed at 3:30 AM
1mg.

Common Fractions. Common fractions are expressed with hyphen

w h d e r the fraction is used as an adjective or a noun. Mixed fractions
e@ressed in nurnerali(see 19.1.2, Use of Numerals, Mixed Fractions).
Of those attending, nearly three-fourths were members of the
There was a half-second delay before the concert hall was illuminated, .
We require a two-thirds ,mjority for consensus.
. In ?me cases, fractions can be expressed with an indefinite article preceding
denoniinator. Sudh consuuctions do not use the hyphen.
The test concluded after half an hour.
A quarter may be used in place of one-fourth.
A quarter of the consensus panel dissented.

One Used as a Pronoun. The word one should be spelled out when used as.
pronoun or noun.
The investigatorscompared a new laboratory method with the
These differences may be concealed if one looks only at the
William James uses the idea of the one and the many as th
of the philosophical mind.

Accepted Usage. Spell out numbers for generally accepted usage, such as idioma
expressions. One frequently appears in running text without refe
per se and may appear a w h a r d if expressed as a numeral.
replaced by a or a single without changing the meaning, the wo
the numeral is usually appropriate. Other numbers, most often zero, two) and la
rounded numbers, also may be written as words in circumstances in which use
the numeral woi~ldplace an unintended emphasis on a precise quantity or would
confusing.

,. ...-- - ... ? . -- .
: +
:. 19.2.5 Ordinals

Any one of the 12 individuals might have been holding the winning ticket.
[In this example, one may be superfluous. Depending on the intent, the fol-
lowing may be an equivalent sentence: Any of the 12 individuals might have
been holding the winning ticket.] ,
The study was plagued by one problem after another.
In the article, one researcher estimated that firearms are used for protective
purposes in the United States several hundred thousand times annually.
Models were developed to allow for the inclusion of one-time variables.
We appear to be moving from one extreme to another.
On the one hand, &e blood glucose concentrations were substantially ini-
proved; on the other hand, the patient felt worse.
Medical futility has become one of the dominant topics in medical ethics in
recent ygars.
In one recent case, the bonus amounted to $1 billion.
We ought to bring together in one place all that we have learned on a given
subject.
- The outcome wa$ a zero-sum gain.

A zero should not be placed to the left of the decimal point of a Pvalue, both
because it could be confused with ,the'letter 0,and because a P value is
always less than 1.0.
Conventional wisdom has it that there are at least two sides to every issue.
Please include an example or two of the following scales.
I would like to ask the patient a question or two about her perception of her
illness.
He quoted the Ten Commandments. [See also 10.0, Capitalization.1.
Many of the mass-vaccination campaigns have been large, with tens of
thousands of persons immunized, and expensive, costing as much as a half-
million dollars.
Duriqg one of the laboratory ~ n sit,was observed that samples from cases 1,
3, and 9 had faint electrophoretic bands due to suboptimal DNA quality.
But: During 1 of the 17 laboratory runs, it was observed.. . . [See 19.3.2,
Combining Numerals and Words, Consecutive Numerical Expressions.]

Ordinals. Ordinal numbers generally express order or rank, rather than a precise
quantity. Because they usually address ndntechnical aspects of the objects they
modify, ordinals are often found in literary writing. The numerical expression of
commonly used ordinals (lst, 2nd, 3rd, 4th, etc) may appear jarring and intempt the
flow of the text. For this reason the ordinalsfirst through ninth 2re spelled out.
l'he third patient was not availal>lefor reevaluation.
I r 113sbecome second nature.
19 3 Comblnlng Numerals and Words

Thc nurneric form oi ordlmls grrarcr t t i ~ r l11rt1rh13 uell c~rat,llslirdin literary t

lurh. 1 lth, and so on) excctpc ar t t l r twpnnlng of 3 xntrncr, title, subtitle
heading. Use the following su15xt.s:-SI, -trd, -rd, -1h. These suffixes should not
superscripted.
Eleventh-hour negotiations settled the strike.
The pandemic will continue well into the 21st century.
He celebrated his 80th birthday.
But: Some forms are spelled out by convention, eg, Twenty-fifth Amend-
ment.
If a sentence contains 2 or more ordinals, at least 1of which is greater than ninth,
should be expressed in numeric form.
Children in the 5th and 10th grades were included in the survey.
The first and third patients treated experienced complete remissions.

cdmbining Numerals and Words. Use a combination of numerals and words

express rounded large numbers and consecutive numerical expressions.

Rounded Large Numbers. Rounded large numbersc such as those starting

million, should be expressed with numerals and words.
The disease affects 5 million to 6 million people. [Note that the
is repeated to avoid ambiguity.]'
The word million signifies the quantity lo6, prhile billion signdies the
Although billion has traditionally signified 10" (1 million million) in
British medical journals1 now use billion to indicate the quantity lo9
be expressed in million rather than billion ifthe latter term could create ambigui
that case, the decimal should be moved 3 places to the right. Trillion should be
to denote the quantity 10".
The projected budget is U.5 billion. .
Or: The projected budget is a 5 0 0 million.
The budget deficit is expected to expand to $1 trillion by 2020.

Consecutive Numerical ~xpressions.When 2 numbers appear cons

sentence, either reword the sentence or spell out 1 of the numbers
Study participants were providedtwenty 5-mL syringes.
Avoid: In the cohort of 1500,690 were men.
Bettec In the cohort of fifteen hundred, 690 were men.
O r In the cohort, 690 of the 1500 individuals were men.
The envelope contained 3 copies of the manuscript and one 3
However, numerals may be listed consecutively if they refer to items in an array:
always, clarity and common sense should guide usage. .

826

- >
, --.. _.-. . .
 19.4 Use of Digit Spans and Hyphens

The life expectancy of groups 1, 2, and 3 was 69, 83, and 75 yt.;lrs, respec-
tively.
Abbreviations or symbols may follow numbers. In this case, if there is potential for
misunderstanding, it is preferable to reword the sentence.
There are 2 D2dopamine receptor isoforms.
Better: The D2dopamine recebtor has 2 isoforms.
The investigators were able to identify 3 y-aminobutyric acid-mediated sites.
Better: The investigators were able to identify 3 sites mediated by
y-aminobutyric acid
Superscripts that indicate references may be mistaken for exponents if they im-
mediately follow a numeral.
Increased morbidity has been associated with a BMI less than 1 8 and~ greater
than 273. [This can be reworded: Smith and ones^ found that a BMI of less
than 18 was associated with increased morbidity. They also found that
with a BMI greater than 27 had increased m ~ r b j d i t ~ . ~ l

Use of Digit Spans and Hyphens. Digits should not be omitted when indicating a
span of years or page numbers in the text. Hyphens may be used in text when a year
span is used as the identifying characteristic of a study (eg, the 1982-1984 NHANES
survey), but only when the actual dates of the study have been defined previously in
the text, if the dates are not defined in the text, the hyphen is ambiguous and may or
may not mean that the dates indicated are inclusive. In certain circumstances, such as
fiscal year or academic year, the actual span may be understood and no definition is
required; in these cases the hyphen is acceptable at first mention and throughout the
- text.
The students participated in the study during the 1994-1595 academic year.
Substantial profits were anticipated for fiscal years 1996-1998.
Sir William Osler (1849-1919)
Use of to also may inuoduce ambiguity. To should be used rather than through only
when the final digit is not included in the span and through instead of to when the final
digit is included in the span. However, in some circumstances, such as life span, his-
torical periods, fiscal oracademic yedr, page numl>ersin text, or age ranges, the meaning
is clear withaut making a distinction between to and through, and to may be used.
The participants ranged in age from 23 to 56 years.
The second enrollment period spanned January 30, 1991. to September 1 ,
1993. [In this example, the enrollment period ended on August 31.I
Or The second enrollment period sp;~nnedJ;~nnary31, 1971, tl~ro~lghAu-
KIlSt .3 I , 199.4

Tirnc spans m.iy In.icfcrrtvf 10 by 1nc;ln o f tl!.p}lcn 1,ytn.cc.rl \-c.lr> ) r l t c. :iiv.in-

inx t\.~sI,t*c.n m;l<lcclear a1 thc first nlvntion.

19.5 Enumerations

The mortality rate ratio of 2.01 (95% CI, 1.80-2.24) indicates that ~ h ~llort;lllr)-.
c
rate during 1968-1978 was about twice that during 1979-1992.
A hyphen may be used within parentheses or in tables to indicate spans, incl
confidence intervals, without further definition, provided the meaning is clear.
However, if one of the values in the span includes a minus sign (most co
found in confidence intervals), the word to should be used to
word to should then be used in place of the hyphenthroughou
consistency. (See also 8.3, Punctuation, Hyphens and Dashes, and 20.8, Study Desi
and Statistics, Significant Digits and Rounding Numbers.)
The mean number of years of life gained was 1.7 (95% confidence interval,
1.3-2.1).
The mean number of years of disease-free l i e gained was 0.4 (95
fidence interval,-0.1 to 0.9).
After the drug was injected, the seizures continued for a brief perio
seconds), then ceased.
The fourth edition contains a discussion of recommended preve
sures (pp 1243-1296).
The median age of the individuals in the sample was 56 years
yead.
If the unit of measure for the quantity is set closed up with the number, the u
should be repeated for each number.
The temperature remained normal throughout' the day.Cl6.5"
The differences between groups were relatively small (5%8%).
But: The pressure gradient varied widely (10-60 mm Hg)throu
If the unit of measure changes within the parentheses, to is used.
Because of the wide range of measurements (2 mg to 3 . 7 1~
played our results on a logarithmic scale.

Enumerations. Indicate a short series of enumerated items by numerals run in

enclosed within parentheses in the text (see also 8.5, Punctuation
Brackets).
The testing format focused on 6 aspects: (1) alertness and co
language, (3) naming, (4) calculations, (5) construction, an
For long or complex enumerations, indented numbers followed b
parentheses, may be used. - .

In response to other issues:

1.The study was conducted under 2 protocols that prespecified that the
would be pooled for the analyses.
2. A particular regression procedure (model selection stepdown) was
plied individually for clinical outcomes.

-- -- . --.
 19.6 Abbreviating Number

3. The relative risk of all serious adverse events was comparable to the
relative risk at 6 months.
If enumerated items contain further enumerations of their own, it is best to provide
this information in a box or table.
Bullets without enumeration may'be used for emphasis and clarity when the
specific order of the items is not important. If the items are complete sentences, begin
each item with a capital letter and end.it with a period.

I The current labeling provides the following instructions:

Use should be hpited to physicians experienced in emergency treatment
of anaphylaxis.
Initial dosage should be based on skin testing.
The patient should be observed for at least 20 minutes after injection.
Immunotherapy should.be withheld when a P-blocker is used.
If the bulleted items are not complete sentences, no end punctuation is needed
and the use of a capital or lowercase letter on the first word of each item is a
matter of judgment, often determined by length (capital letters on initial letter of
longer items, lowercase on initial letters of shorter items), with consistency within a
single list.

I Anorexia nervosa includes the following:

Low body weight with refusal to maintain a healthy weight
Fear of being overweight despite having an extremely low body weight
Disturbed body image or denial of the degree of underweight
Absence of a menstrual period

I Signs and symptoms of cardiogenic shock may include

hypotension
cold, clammy skin
low urine output
confusion

Abbreviating Number. The word number may be abbreviated No. in the hocly
of tables and line art or in the text when used as a specific designator. Do nor
use the number sign (#) in place of the abbreviation. The word nunzber shoi~ltl
always be spelled out when it is used as a proper noun (eg, "Social Securiry
number").

NO. of participants

I A NO. 10 catheter was placed in the femoral a r t c n

\%en referring to numbers of individuals in a stutl!.--in r;rt,lr.\. fig~rrtrb.:~ntl\\ 1t11,n
parentheses-the abbreviation N is used ~ v h c nrckrrlrlKt ( , r!lv rntirv \.ir~\j\lc 11 rc.:vr-.
to a subsample. (See also 20.9. Stucly I k . \ c ~ n:rc?tl s ~ . ~ ~ , q( ; lI O(, \.. I ~ 01 ~ I . I ~.I\
I\II~
Terms.)
 -.

19.7 Forms of Nurnhers

Patients were enrolled at each study site (N= 2758) and ran
intervention (n = 1378) or placebo (n = 1380).

Forms o f Numbers

m,
Decimals. The decimal form should be used when a fraction is given with an ab
'viated unit of measure (eg, 0.5 g, 2.7 rnrn) to reflect the precision of the
(eg, 38.0 kg should not be rounded to 38 kg if the scale was accurate
kilogram). (See also 18.4.2, Units of Measure, Use of Numerals With
Format.)
The patient was receiving gentamicin sulfate, 3.5
serum gentamicin level reached a peak of 5.8
mL after the third dose.
Place a zero before the decimal point in numbers less than 1, except
the 3 values related to probability: P, a,and P. These values cannot equal 1
when rounding (see 20.9, Study Design and Statis
~ e & u s ethey appear frequently, eliminating the zero can save su
tables and text. (Although other statisticalvalues also may never e
less frequent, and to simplify usage, the zero before the decimal point is inclu
P = .16
1- p = .80
Our predetermined a level was .05.
But: K = 0.87
Note, however, that a and p may sometimes be used to indicate
some of these cases their values may be 1 or greater.
Cronbach a = 0.78
standardized p coefficient = 2.34
By convention, a zero is not used in front of the decimal point of the measure of
bore of a firearm.
.22-caliber rifle

Percentages. The term percent derives from the Latin per centurn, meanin
hundred, or in, to, or for every hundred. The te
be used with specific numbers. Percentage is a
amount that can be stated as a percent. Percentile is defined a
100 that indicates the percentage of the distribution that is
Ten percent of the work remained to be done.
Heart disease was present in a small percentage of
Five percent of the participants had heart disease.)
Her body mass index placed her in the 95th percentile of the study group. :

Unless otherwise indicated, data in the table are expressed as number'

(percentage).

830
 19.7.3 Reporting Proportions and Percentages

Use arabic numerals and the symbol % for specific percentages. The symbol is set
closed up to the numeral and is repeated with each number in a series or r;ingc 01'
percentages. ~ncludethe symbol % with a percentage of zero.
A 5% incidence (95% confidence interval, 1%9%) was reported.
The prevalence in the populations studied varied from 0% to 20°/0.
At the beginning of a sentence, spell out both the number and the word per-cent. even
if the percentage is part of a series or range. Often it is preferable to reword the
sentence so that a comparison between percentages is more readily apparent.
Twenty percent to 30% of patients reported gastrointestinal symptoms.
Bettec The percentaie of patients who reported gastrointestinal symptoms
ranged from 20% to 30%.
Oc Between 20%and 300h of the patients reported gastrointestinal symptoms.
When referring to a percentage derived from a study sample, include with the per-
centage the numbers from which the percentage is derived. Th'is is particularly im-
portant when the sample size is less than 100 (see also 20.8, Study Design and
Statistics, Significant Digits and Rounding Numbers). To give'primacy to the original
data, it is preferable to place the percentage in parentheses.
Of the 26 adverse events, 19 (73%) occurred in infants.
Any discrepancy in the sum of percentages in a tabulation (eg, due to rounding
numbers, missing values, or multiple procedures) should be explained in the text,
table footnote, or figure legend.
The t e m p e r c e n t change,percent increase, and percent decrease are often used
- in place of p e n t a g e of change. Although these less formal terms are acceptable,
their usage must be precise. They generally are computed as the difference between
an index value and either an earlier or later value, divided by the index value. Al-
though a percent increase may exceed 100°h, a percent decrease generally cannot.
A percent decrease can also be expressed as a negative percent increase.
These terms must be differentiated from percentage point change, increase, or
decrease, which are obtained by subtracting one percentage value from another. For
example, a change in rate from 20% to 300/0 can be referred to either as an increase of
10 percentage points, as in "the intervention group improved 10 percentage points,"
or as ;I 501M,incrc:~sc(pcrccnl cllangc), ;IS in "'l'llc. intcrvcnlion group sliowcd ;I 501W1
improvement': ([30%/6-20%?20%).The 2 terms are not interchangeable. Since the
percent change does not indicate the actual beginning or ending values or the
magnitude of the change, the actual values should he provided whenever possil;le.

Reporting Proportions and Percentages. Whenever possilAc, proportions and per-

ccnt;lgcs sl~oi~ltl
Ilc ;lcco~np:~nictl
I)y llic ;1clu:11~ L I I ~ C I .( 1; 1I) I;O~ nI t.clcnoniin;~tor
l (ti)
from which they were derived. The numerator and denominator should be
expressed as "n of d," not by the virgule construction "~z/d,"which could imply
that the numbers were computed in an arithmetic operation.
Death occurred in 6 of 200 patients.
Not: Death occurrecl in (;/200 p:rtients.
19 7 Forms of Numbers
.
3.
:43
For cl;lr~ty.when a numerator and denominator are accompanied by a resultin3
proportion or percentage, the proportion or percentage should not intervene be
tween the numerator and denominator. +
3
Death occurred in 6 of 200 patients (3%).
Death occurred in 3%(6 of 200) of patients. . +'
Of the 200 patients, death occurred in 6 (3%). + I

.jJ
Of the 200 patients, 6 (3%) died. r

Not: Death occurred in 6 (3%) of 200 patients.

.d
The denominator may be omitted if it is clear from the context. aJ

Death occurred in 3 patients (1%).

3
In expressing 3 series of proportions or percentages drawn from the same samplej
the denominator need be provided only once.
Of the 200 patients. 6 (3%)died. 18 (9%) experienced an adverse event. and'l
22 (11%) were lost

Reporting Rates and Ratios. Use the virgule

- construction for rates when placed
parentheses (eg, 1/21 but never in running text. A colon is used for ratios .O
Rates should use the decima1format when the denominator is understood to
otherwise, the denominator should be specified. %+

3:
!
Of all individuals exposed, children were affected at a rate of 0.05. '
'

-1
'
.5
The infant mortality rate was 3 per 10 000 live births. 1
Not: The infant mortality rate was 3/10 000 live births.
'4
1
Roman Numerals. Use roman numerals with proper names (eg, Henry Ford 111). Note
that no comma is used before the numeral. However, arabic numerals should $
used as designators in all other cases (eg, round 2, Table 4, year 5; see also 10.4;
Capitalization, Designators) unless roman numerals are part of formally establish4
!!
nomenclature (see 15.0, Nomenclature).
Step I diet schedule I1 drug
level I trauma center
3
Axis I diagnosis
But: type 2 diabetes mellitus, phase 3 study I

Use roman numerals for cancer stages and arabic numerals for cancer grades (5'
also 15.2, Nomenclature, Cancer). In pedigree charts, use roman numerals to indicr
generations and arabic numerals to indicate families or individual family membiz
(see also Pedigrees in 4.2.2, Visual Presentation of Data, Figures, Diagrams). ~ o n d
numerals also may be used in outline format (see 4.1, Visual Presentation of Da ,!
Tables). 9
<
In bibliographic material (eg, references or book reviews), do not use roman
numerals to indicate volume number, even though roman numerals may have bee;
used in the original. However, if roman numerals were used in the original title or @
an outline, refer to the title or outline as it was published, with roman numerals:
Retain lowercase roman numerals that refer to pages in a foreword, preface, 01
introduction. Roman numerals may alsb be used to number supplements to journals
i . .
19.7.5 Roman Numerals

so that roman numerals appear adjacent to page numbers in references to the work.
In this case, the roman numerals should be retained.
For the use of roman numerals in biblical and classical references, follow the
most recent edition of the Chicago Manual of Style (see also 3.0, References).
The following list indicates h e roman equivalents for arabic numerals. In gen-
eral, roman numerals to the right of the greatest numeral are added to that numeral,
and numerals to the left are subtracted. A horizontal bar over a roman numeral
multiplies its value by 1000.
I XX
I1 XXX
111 XL
'n L
v Lx
VI LXX
w Lxxx
VIII xc
M C
X CC
XI CCC
XI1 CD
XI11 D
XIV DC
XV DCC
XVI DCCC
XVII. CM
XVIII M
XIX V

ACKNOWLEDGMENT
Principal authors: Stephen J. Lurie, MD, PhD, and Margaret A. Winker, MD

REFERENCE.
1. Billion bites the dust [opinion]. Nature. 1992;358(6381):2.

ADDITIONAL READINGS AND GENERAL REFERENCES

American Psychological Association. Publication Manual of the American P.y~c~~olr~,qicul
Association. 5th ed. Washington, DC: American Psychological Association; 2001.
7hr. Cl~icngo,%fanualof S@e. 15th ed. Chicago, IL: University of Chic;igo Press: 2006.
Style 51:inunl Committee, Council of Science Editors. Scie~zlijicSt~~le
a d I"or.111rrl: 'I!](,C,:S/l.
. ~ l t i ~ : : r n l /~rtrhors.
r)r Publishers. 7th ed. New York, N Y : Rockekller I;ni\.c.rsi[!.
FAitors, and
I'rt.\\ li! I tx)lxr;al~onnirh the Council of Science Editors, Reston, VA; 2006.
 20.1 20.5
The Manuscript: Presenting Study Design, Cost-effectivenessAnalysis, Cost-Benefit
Rationale, and Statistical Analysis Analysis
20.1.1 Abstract and Introduction
20.1.2 Methods 20.6
20.1.3 Results Studies of ~ i a ~ n o s tTests
ic
20.1.4 Discussion (Comment)
20.7
20.2 Survey Studies
Randomized Controlled Trials
20.2.1 Parallel-Design Double-blind Trials 20.8
20.2.2 Crossover Trials Significant Digits and Rounding Numbers
20.2.3 Equivalence and Noninferiority Trials 20.8.1 Significant Digits
20.8.2 Rounding
20.3
Observational Studies : 20.9
. 20.3.1 Cohort Studies Glossary of Statistical Terms
20.3.2 Case-Control Studies
203.3 Case Series 20.10
Statistical Symbols and Abbreviations
20.4
Meta-analysis

' The essence of life h statistical improbability on a

grand scale.
Richard ~awkins'

There are three kinds of lies: lies, damn lies, and

statistics. . ,

Attributed to Disraeli by Mark wain'

Statistical concepts, such as the margin of error in a public opinion poll or the
probability of rain or snow, appear in everyday conversation. But, just as one may
understand'how the heart functions and how blood circulates but not be able to
perform a cardiac catheterization, an understanding of statistical concepts does not
enable one to perform the work of a statistician. Although the concepts may be
familiar, the tools of statistics may be misapplied and the results misinterpreted
without a statistician's help.
In medical research, the quality of the statistical :in;~lysisand clarity of pre-
sentation of statistical results are critic;tl to ;I study's v:~lid~ry1)ecisions about statis-
tical analysis are best made at the tirne thnt the study is designed and generi~llyshould
not be deferred until after the d;ata have txbcn collt.cred I-l\,cnthe most sophisric;lrrd
statistical analysis cannot salv:~gca funtl.~rncn~;illy .study. Rt.g:irdless of lilt:
fl:~n.~=d
statistician's role. authom (\vho ni.iy ~nc-luclcm \t:lri.;r~c~;inh)
:lrc resl>on>~ldc t o r the
:lppropri;itv d c \ i g ~ :ln:l\~hi~,
~, kind prcwm~:itjor\of lhr .,I\IC\\., rr,1~\t.,.
20.1 The Manuscript: Presenting Study Design. Rattonale. a n d ~tat~rtical
Analyrlr

Many excellent statistical [exLi arc .ivailal)lc.and a con~prchcnsivcapp

far beyond the scope of this chapter. iiowever, authors, editors
editors should have a general understanding of study designs, s
concepts, and the use of statistical tests and presentation. Although few rules e
guide how statistics should be presented, presenting statistics briefly but comp
and consistently should improve the reader's understanding of the analysis. .;,

The Manuscript: Presenting Study Design, Rationale, and

sis. Each portion of the manuscript should contribute to the reader's understan
of why and how the study was done and should help pers
hypothesis or study question is clearly stated, carefully conside
(2) the methods are designed to answer the question and the analysis is app
(3) the results are credible, and (4) the implications are placed in context
limitations do not preclude interpretation of the results.
Words used herein that are defined in the glossary (see 20.9, Glossary of S
tistical Terms) are given in a different font.

t.llkAbstmd and Introduction. The structuredabstract should enable the reader to

the study hypothesis and methods quickly and easily.2 The context for the s
question and the h.ypothesis (objective) should be cle
..
whether enalapril reduces left ventricular mass ."),.thestudy d
and setting from which the sample was drawn described, an
measures explained. The results should include some explan
appropriate,with point estimates and confidence interv
The conclusions should follow from the results without ove
Abstract format is too brief to permit detailed explanation of statisti
basic descriptionmay be appropriate(eg, "The screeningtest was v
of a btstrap procedure .and performance tested with a re
teristic curve.").
The introduction should include a concise review of the relevant literature t
provide a context for the study question and a rationale for the choice of a particul
method. The study-hypothesis or purpose should be clea
tence(s) before the "Methods" section. Results or conclusions do not belong in the
introduction.

Methods. The "Methods" section should include enough information to enable a

knowledgeable reader to replicate the study and, given the original data, verfy the
reported results. Components should include as many of the following as are a p
plicable to the study design:
Study design (see sections 20.2-20.7).
Yeads) (and exact dates if appropriate) when the study was conducted.
Disease or condition to be studied-how was it defined7
Setting in which - participants were studied (eg, comm
ulation, primary care clinic), as well as geogmphic 1
name of institution.
I '.. 20.1.2 Methodr

8 Individuals or other data studied-who or what was eligible; inclusion and exclusion
criteria; if all participants were not included in each analysis, reason for exclu-
sions; informed consent and approval by institutional review board or ethics
committee when appropriate (see 5.8.1,Ethical and Legal Considerations, Pro-
! tecting Research Participants' and Patients' Rights in Scientific Publication, Ethical
Review of Studies and Informed Consent). If results for any of the participants
have been previously described, provide citations for all reports or ensure that
different reports of the same study can be easily identified (eg, by using a unique
study name).
I
I
Any remuneration or other compensation for participants.
rn Intervention(s), including their length. In general, authors should provide suffi-
cient detail to allow readers to replicate the interventions. This would also permit
comparison with other studies. Treatment of any control or comparison groups
should also be described in detail.
Outcomes and how they were .measured, including reliability of measures and
whether investigators determining outcomes were blinded 'to which group re-
ceived the intervention or underwent the exposure.
Other variables and how they were measured-for, example, demographic vari-
ables and risk factors for the disease. Such variables are often used to assess or
adjust for confounding of the relationship between the dependent and independent
variables.
Preliminary analyses: if the study is a preliminary analysis of an ongoing study, the
reason for publishing data before the end of the study should be clearly stated,
along with information regarding whether and when the study is to be completed.
-
Authors should indicate whether such analyses were preplanned at the time the
study began.
Source to obtain original or additional data if other than from t$e authors. For
example, data tapes are often obtained from the US government; the source -
should be stated. The Web can be used to store or display data or information that
could not be included in the manuscript. For information essential to the study,
the information should be included in the manuscript, if at all possible. If this is
not possible, the editors should request and consider retaining a copy, as Web
sites and uniform resource locators (URLs) may change and become inaccessible.
The source also may be listed in the acknowledgment.
Statistical methods, including procedures used for each analysis, what a level was
considered acceptable, power of the study (which should have been calculated
before the study was conducted to determine sample size), assumptions made,
any data transformations or multiple comparisons procedures performed, steps
used for developing a model in multivariate analysis, and pertinent references fr,r
statistical tests and type of software used. Authors should provide evidence [ ~ ; I I
the data meet the assumptions of the statistical tests used. Test sr;~tistics~ I 1 o t 1 I c I
include degrees of freedom whenever applic~lllc.11 is al\v;~ysprefcr~l~lc. for r o u l t ,
to be presented in terms of point estimates 2nd confidence intervals. \ \ . l l ~ c hi o l l \ c.\
more information than do P values.
20.2 Randomized Controlled Trials

If the study has been registered in a central trial registry, thr name of the reg
and the trial number should be provided. (See 20.2, Randornucd Controlled Tri

Results. The "Results"section should include the number of individuals or other

units initially eligible for study, the number at its inception, and the number w
were excluded, dropped out, or were lost to
example,JAMA requires a figure showing th
trials (see 20.2, Randomized Co
statistics about the sample and, if approp
outcome measures should be discussed
followed by secondary outcome measure

thus such analyses should be u

type I error). If one statistical
should be clearly stated in the "Methods" section. If more than one statistical test
been used, the statisticaltests performed should be disc
specific test used reported along with the correspon
results (eg, relative risk, odds ratio) may overstate the
between groups, particu
senting relative results, authors should
tendency of the groups (ie, mean or median). .

~iscu'ssion(Comment). Whether the hypothesis was supported or refuted by

results should be addressed The study result should
lished literature. The limitations of the study should be
sources of bias and how these problems might affect con
Ev:dence to support or refute the problems introduced
provided. The implications for clinical practice, if -
future research
should be based on the
ented by the study sample.
. .

-1Randomized Controlled Trials. The

leads to the strongest inferences about the effect of
controlled trials assess efficacy of the
ized, and highly monitored settings, and usually
patients. Thus,their results might not reflect the e
settings, or in other groups of individuals who were not enrolled in the trial.

20.3, Observational Stu

quality of the study,.replicate the study inte

mation for comparison with other studies.
checklist (Table 1) to help ensure c
chivesJournals require that authors
mittee of Medical Journal Editors (ICMJE) (www.icmje.org) recommends foil
this reporting procedure. While completing the checklist does not guarantee
study has been performed well, it can help ensure that the information criti
interpretation of the study is provided and

838

. . pt-.
i 20.2 Randomized Controlled Trials

published, readers. Journal editors may nonetheless also ask authors to provide a
more detailed description of the study protocol. Although such information may not
necessarily appear in the published article, it may help reviewers and editors to,more
thoroughly evaluate the manuscript.
A flow diagram is also important to outline the flow of participants in the study,
including when and why participanp dropped out or were lost to follow-up and how
many participants were evaluated for the study end points. Authors should include a
flow diagram (Figure 11, and, if the manuscript'is accepted for publication, the flow
diagram generally should be published with the study. The number of groups after
randomization shown in the diagram should correspond to the number of inter-
vention and control groups in the study. CONSORT continues to be adapted to specific
types of RCTS.~Current ,information is available from the CONSORT Web site
(www.consort-statement.org).
The report should include a comparison of characteristics of the participants in
the different groups in the trial, usuallyas a table. However, performing significance
testing on the baseline differences between groups is controversial. (Even \vith
perfect random assignment, anaverage of 1 in evely 20 comp;lrisons will I,c ;Ippe:ir
to be "significant" at the .05 level by chance alone; such random findings illustrr~tethe
dangers of post hoc analyses.) Furthermore, in small studies, large differences may
nonetheless be statistically nonsignificant due to limited statistical power. None-
theless, it is usually helpful for authors to report statistical comparisons 1,etwem
groups. Such information should be interpreted not as a test of a null hypothesis of
baseline differences between groups, but rather as a general estimate of the ni;lg-
nitude of any baseline differences that may have been confounded with the inter-
vention. These results should be reported either in. a table or 'in running test.
This information would help the reader decide whether the authors shoitld Ii;iv~~
- accounted for these baseline differences in their statistical analysis of the presperifirtl
. ..
outcomes.
In analyzing the data from a randomized trial, it is usually b s t to report the
results of an intention-to-treat (ITTI analysis. That is, the final results are based on
. .. analysis of data from all of the who were originally randomized, whether
or not they actually completed the trial. Such participants may have varying degrees
of missing dam, however, and thus ITT analyses usually involve some method for
imputation of these missing results. For noninferiority and equivalence trials, how-
ever, ITT analysis may overstate the equivalence of experimental conditions. In these
trial designs, results should also be reported only for those participants who com-
pleted the trial (as-treated analysis, completers' analysis, etc). (See 20.2.3, Random-
ized Control'led Trials, Equivalence :inti Noninferiority Trials.)
There is ongoing debate about the circumstances in which it may be unethiql to
perform an RCT.~"There is general agreement, however, that RCTs are unethical if
the intervention is already known to be superior to the control. in the population
under investigation, or if participants could be unclilly harmed by any condition in
the experiment.
The decision to perform specific interim analyses is usually made before the
study begins6(pp130.258) (Data and safety monitoring boards, however, may monitor
adverse events continually throughout the course of the study.) Investigators also
usually define prospective stopping rules for such analyses; if the stopping rule is met,
this generally means that collection of additional data woilld not change the inter-
pretation of the study. If the criteria for the stopping rules have not been met, the
 ---._ ...

Table 1. Checklist o f Items t o Include When Reporting a Randomized Triala

Section and
Topic Item No. Descriptor on Page No.,

T~tleand abstract 1 How participants were allocated to interventions

(eg, "random allocation," "randomized," or
"randomly assigned").
Introduction 2 Scientific background and explanation of rationale.
Backaround
Methods 3 Eligibility criteria for participants and the settings and
Partici~ants locations where the data were collected.
Interventions 4 Precise details of the intewentions intended for each
qrou~ and how and when thev were actualh administered.
Objectives 5 Specific objectives and hypotheses.
Outcomes

blinded to group assignment. If done, how the success

of blindina was evaluated.
 . .
,
;I.** . . . . '

. .

20.2.1 Parallel-Design Double-blind Trials

Table 1: Checklist o f Items t o Include W h e n Reporting a Randomized Triala (cont)

Section and Reported

Item No. Descriptor on Page No.

Outcomes and 17 For each primary and secondary outcome, a summary

estimation of results for i c h group, and the estimated effect
!
size and its precision (eg, 95% confidence interval).
Ancillary 18 Address multiplicity by reporting any other analyses
analyses performed: including subgroup analyses and adjusted
analyses, indicating those prespecified and
those exploratory.
Adverse events 19 AH important adverse events or side effects in each
intervention group.
Comment 20 Interpretation of the results, taking into account
I! interpretation study hypotheses, sources of potential bias or imprecision,
I
and the dangers associated with multiplicity of analyses
and outcomes.
E!
E Generalizability
Overall evidence
21
22
Generalizability (external validity) of the trial findings.
General interpretation of the results in the context of .
current evidence.

'From Moher et aL4

results of interim analyses should not be reported unless the treatment has important
adverse effects and reporting is necessary for patient safety. If a report is an interim
analysis, this should be clearly stated in the manuscript with the reason for reporting
the interim results. The plans for interim analyses and reports contained in the
original study protocol should be described and, if the interim analysis deviates from
those plans, the reasons for the change should be justified. If a manuscript reports the
final results of a study for which an interim analysis was previously published, the
reason for publishing both reports should be stated and the interim analysis refer-
enced.
Publication bias is the tendency of authors to submit and journals to preferentially
publish studies with statistically significant results (see also 20.4, Meta-analysis). To
address the problem of publication bias, the ICMJE now requires, as a condition of
publication, that a clinical trial be registered in a public trials registry.9 The ICMJE
policy applies to any clinical trial starting enrollment after July 1, 2005. For trials that
began entollment prior to this date, the ICMJE member journals required registra-
tion by September 13,2005.The policy defines a clinical trial as "any research project
that prospectively assigns human subjects to intervention or comparison groups to
study the cause-and-effect relationship between a medical intervention and a health
outcome."

Parallel-Design Double-blind Trials. In this study design, participants are assigned to

only 1 treatment group of the study. These trials are generally designed to assess
n~hethcr1 o r r n o r c rreatrnents are superior to the others. Participants and those
admin~stennprl~e1nrrn.ention should all be unaware of which intervention indi-
t ldt1.11 pnrc~c~p.inrs :ire rccc~vlng('.double-blinding"). Ideally, those rating the out-
to trc;~trnentassignn~ent("triple-blinding"). Blinded
~ o r n c ,shor~lcl.rl.o l w l~,l~ntlc.tl
20 2 Random~zedControlled Trials

-
No. excluded
No. not meeting Inclusion criteria
No, refused to partldpate
No. other reasons

No. assigned to receive intervention No. assigned to r&bm intecvenh

No. receivedintecvention as assigned No. receivedInterventionas assigned
No. did not receive as- Intmtlon No. dld not receive asslgned intervention
1-=er
(give ( g i i reasons)
I
No. lost to foNowup No. lost to fdlow-up
( g h -1. csive 5
No. dsantinoedmtenwxh No. dsconbnuedhtenrentii
(give reasons) (eive-1
I
No.!ncMedin~~naty& No.lnckdedhanalysls
No.exaded fromarrafysfs N o . ~ ~ d u dfmanalysis
d
(give- (give reaxas)

Figure 1. CONSORT flow diagram showing the progress of patients throughout the trial. Fro
str!:ctions for Authors. JAMA 2006;296(1):107-115.

parallel-design trials are often the optimal

or other therapy, since known and unknown potentially c
be randomly distributed between intervention and
diagram should clearly indicate how many partid
ment group, how many were lost at various stag
individuals did not complete the tri
cealment, and assessment of the success o
significant diierence between groups, authors
equivalenk such a conclusion would require an equivalent
(see 20.2.3, Randomized Controlled Trials, Equivalence and

Crossover Trials. In a crossover trial, p

ments under investigation, usually in a
prespecified amount of time (a "washout peri
The participants and the investigators
ment (double-blinded). This experimental d
treatments. Each participant serves as'his o
variability when comparing treatment
detect a significant effect. Most considerati
apply. Rather than indicating which partic
the CONSORT flow diagram should indicate how many were assigned to e
quence of conditions. Other information important to this study design inc
possible carryover effects (ie, effect
intervention)-andlength of washout
completely before crossover to the other t

842

:. ~ , A ~ - c , -
. i
, :. -.
 20.2.3 ~~uivalence
and Noninferiority Trials

differs from the original study protocol, how and why decisions wert made to cross
over to the alternate treatment and when the crossover occurred should be stated.
The treatment sequence should be randomized to ensure that investigators remain .
blinded and that no systematic diierences arise because of treatment order. Other-
wise, unblinding is likely, treatment order may confound the analysis, and carryover
effects will be more difficult to assess. The amount of time between each intervention
(the washout period) should also be-prespecified. If carryover effects are significant,
or if a washout period with no treatment is undesirable or unethical, a parallel-group
design (possibly with a larger sample size) may be necessary.

Equivalence and Noninferiority ~rials.It is sometimes desirable to compare a less

expensive treatment or intervention against a treatment or intervention that is already
known to be effective. In thkse cases, it would be unethical to expose participants to
an inactive placebo. Thus, these trial designs assess whether the treatment or inter-
vention under study (the "new intervention") is no worse than an existing alternative
(the "active control").
In equivalence and noninferiority trials, authors must prespecLFy a margin of
noninferiority (A), within which the new intervention can be assumed to be no worse
than the active control. There are a number of methods for arriving at the value A.
Because diierent methods of estimating A may be more defensible in some situa-
tions than others, authors should provide clear explanations of their method and
rationale for arriving at their value for A. Noninferiority trials test the 1-sided hy-
pothesis that the effect of the new intervention is no more than A units less than the
active control. Equivalence trials, which are'less common than noninferiority trials,
test h e Zsided hypothesis &t ihe effect of the new treatment lies within the range of
A to -A.
Although use of intention-to-treat"(1~~) analysis is optimal in trials that test
-
whether one treatment is superior to another, use of such analysis can bias the results
of equivalence and noninferiority trials. Thus, in addition to I'IT an?lysis, autllors
should report results for only participants who completed the trial.
Interpretation of the results depends on the confidence interval for the difference
between the new intervention and the active placebo, and whether this confidcncc
interval crosses A, -A, and 0. See Table 2.
Authors should refer to specific CONSORT guidelines for reporting the design
and results of equivalence and noninferiority trials."

obsekational Studies. In an ol,scrv;t\ional slucly, 1I1crcsc.;ucllcr itlvllrilivs ;I (.on

dition or outcome of interest and then measures factors that may be rclarcrl to r l l : ~ ~
outcome. Although observational studies cannot lead to strong causal infrcnc.c.5.
they may nonetheless suggest certain causal hypotheses. To infer c;lus:~tionin 01,-
servational studies, investigators attempt to estal,lish n scclucnce o f events-il'c.\.cnl
A generally precedes event D in time, then it is possil,lc th:~tA m:ty I,c rcsponsil)lc.Ii)r
causing 13. Such studies may I,c cither retrospective (rlw invc.5lig;1tor1ric.s 10 nx.c , l i -
struct what happened in the past) or prospective (the inve>~ig;~lor iclcm~ilic\;I g1.1I ! I ~ ) 11 (

individuals and then observes them for a spc.cifietl I)C'TI(KI o f t i 1 1 1 ~ ) . I'roy)cx I I \ c

studies generally yield more reliable ~onclusionstti;~n'lo rctrospcc.rl\c >rucllc.\
Cross-sectional studies observe i11cliviclu:lls21 ;I hlnglc po~nrIn 11111c. ~ L I C11 \ILICIIC.\
may l ~ ehelpful for suggesting relationslllp, ; I ~ , ~ l , r:.lll.tl,it..
nx I t t ~ rC . I I : ~ O ( . I ~ I C I I L , -

whether one condition may precede or follo\v nnotllCr -1-11k1, c-rc , \ \ - - c c . r l o ~ l ; ~, rIt ~ c l ~ c \
 Paper Section
and Topic Item No. Noninferiority or Equivalence Trials

Title and abstract lb How participants were allocated to interventions (eg, "random
allocation," "randomized," or "randomly assigned"), specifying
that the trial is a noninferiority or equivalence trial.
Introduction
Background
Methods 3b Eligibility criteria for participants (details whether participants in the
Participants

efficacy, and how and when they were actually administered.

Objectives Specific objective and hypotheses, including the hypothesis
concerning noninferiority or equivalence.
Outcomes

trial are identical (or very similar) to those in any trial(s) that
established efficacy of the reference treatment and, when
applicable, any methods used to enhance the quality of measurements
(eg, multiple observations, training of assessors).

Randomization
Sequence generation
Allocation concealment

Implementation ' 10 Who generated the allocation sequence, who enrolled participants, .'
and who assigned participants to their groups.
Blinding (masking)

was evaluated.
Statistical methods

-- . .- . .
 I
20.2.3 Equivalence and Noninferiority Trials I, .

-
Table 2. Checklist of Items for Reporting Noninferiority or Equivalence Trials (Additions o r Modifications t o
the CONSORT Checklist Are Indicated i n Footnotes)= (cont)

paper Section
and Topic Item No. Noninferiority or EquivalenceTrials .

Results 13 Flow of participants through each stage (a diagram is strongly

Participant flow recommended). Specifically, for each group report the numbers of
participants randomly assigned, receiving intended treatment,
completing the trial protocol, and analyzed for the primary outcome.
Describe protocol deviations from trial as planned, together
- with reasons.
. Recruitment 14 Dates defining the periods of recruitment and follow-up.
--
Baseline data 15 Baseline demographic and clinical characteristics of each group.
Numbers analyzed 16a Number of participants (denominator) in each group included in
each analysis and whether "intention-to-treat" and/or alternative
analyses were conducted. State the results in absolute numbers
when feasible (eg, 10 of 20, not 50%).
Outcomes and estimation 17= . For each primary and secondary outcome, a summary of results for
each group and the estimated effect size and its precision (eg, 95%
confidence interval). For the outcome(s) for which noninferiority
or equivalence is hypothesized, a figure showing confidence
intervals and margins of equivalence may be useful.
Ancillary analyses 18 Address multiplicity byreporting any other analyses performed.
. including subgroup analyses and adjusted analyses, indicating
. those prespecified and those exploratory.
Adverse events
: - - 19 All important advene events or side effects in each
intervention group.

Comment 20a . . , Interpretation of the results, taking into account the n~ninferiorit~
Interpretation . . or equivalence hypothesis and any other trial hypotheses, sources
of potential bias or imprecision, and the dangers associated with
multiplicity of analyses and outcomes.
Generalizability 21 ~eneralizability(external validity) of t h i trial findings.
overail evidence 22 General interpretation of the results in the context of current evidence.

'From Piaggio et al."

bExpansionof corresponding item on CONSORT checklist.""

cannot establish causation, but they may nonetheless be helpful for suggesting hy-
potheses to guide more rigorous studies.
Because individuals .in observational studies are not randomly assigned to con-
ditions, there are often large baseline differences between groups in such stildies. For
instance, individuals with Ixtter cxercise habits often differ in a nunll~crof impon;~nt
ways (eg, education, income, diet, smoking) from those who do not exercise refii~I;~rly.
Because exercise is confounded with these varial,les, it is clificult to know ~llvtllcr
exercise itself is responsil3le for any differences in health outcomes. Rese:~rchcrsmay'
use several different statistical techniques to minimize the effects of confounding. In-
cluding matching, stratification, multivariate analysis, and propensity analysis.
Even with the most extensive attempts to minimize confoundir~g.11 I > ; ~ l \ \ . r > \
possible that results cf observationzl studies m:.?- :: ! ~ . ~ : t dcir :n nth6.r v:rri.~lrlc.\ r ti.41
20.3 Observational Studies

the authors did not measure. k - ~ u s co f this un

confounding in obxrvarional studles. the results are
of RCTs. Sometimes the results of obxn.ationa1 stu
those of RCTS.'~On the other hand, because observational studies are
based on the outcomes of a large range of people in realistic situations, th
useful insights to disease processes as they occur beyond the limited c
RCTs. Furthermore, observational studies may be the only way to investigate certain
problems (eg, automobile crashes, exposure to toxic chemicals) for which it would
be unethical to perform RCTs.
There are currently no standardized guidelin
of observational studies. Although the CONSORT group is currently de
guidelines for case-control and cohort studies, it is unclear at this tim
will become as widely accepted as the CONSORTguidelines for RCTs. Current
formation q n be found on the CONSORT Web site (www.consort-s

C.7,lkk Cohort Studies. A prospective cohort study follows a group or coho

who are initially free of the outcome of interest. Individuals in a cohort gene
shate some underlying characteristic, such as age, sex, or exposu
Some studies may comprise several different coh
for a predetermined period, long
the outcome of interest. Individuals w
those who did not. The report of the'
- and the length of follow-up, what independent variables were measured

for follow-up and whether they differed from those with c

also be included. All adverse events should be reported.
Any previous published reports of closely related studies from the same co
should be cited in the' text or should be clear from the
rningham Study). All previous reports on the same or s
cited.
Retrospective cohort studies may be
study outcomes when formulating the hypothesisand de
independent variables, but many of the strengths of prospective cohort studies
with retrospective studies, such as identifying the population to study and de
the variables and outcomes before the events occur.

c a L ~ o n t r oStudies.
l Case-controlstudies, which are aiways retrospective, comp

should never be selected on the basis

investigation.Cases and controls generally are matched according to specific c
teristics (eg, age, sex, or duration o
However, if the matched vahables are.
terest (not necessarily with the disease or outcome
. found the analysis (see also overmatching). The independent variable is
an item of interest (eg, a drug or disease). Informatio
and controls must be included, and inclusion and exclusion criteria must be liste
each. Cases and controls should be drawn from th
avoid selection bias. Pairs (1:l match) or groups (e

846

. -. - - . -
 20.3.3 Case Series

controls may be matched on 1 or more variables. The analysis generally is unpaired,

however, because of the difficulty in matching every important characteristic. Non-
etheless, paired analysis reduces the necessary sample size to detect a difference and
may be justified if individuals are well matched. Recall bias is common in all retros-
pective studies and is especially a concern when participants believe that a factor
related to the independent variable may be associated with the outcome. If recall bias
may have occurred, the authors should discuss how they addressed this possibility.
In a nested case-control study, the cases and controls are drawn from some
larger population or cohort that may have been convened for some other purpose. In
these instances, authors 5hould clearly indicate how the original sample was defined,
the size of the original sample, and how the cases and controls were selected from -it.

Case Series. A case series describes characteristics of a group of patients with a par-
ticular disease or patients who have undergone a particular procedure. A case series
may also involve observation of larger units such as groups of hospitals or munici-
palities, as well as smaller units such as laboratory samples. Case series may be used
to formulate a case definition of a disease or describe the experience of an individual
or institution in treating a disease or performing a type of procedure. Case series
should comprise consehtive patients or observations seen by the individual or
institution to minimize selection bias. A case series is not used to test a hypothesis
because there is no comparison group. (Occasionally comparisons are made with
historical controls or published studies, but these comparisons are informal and
should not include formal statisticalanalysis.) A report of a case series should include
the rationale for publishing the population description and inclusion and exclusion
criteria. Case series are subject to several types of biases, and therefore authors should
be particularly careful about the kinds of conclusions that can b e drawn from them.
- . .

Meta-analysis. eta-analysis is a systematic pooling of the results of 2 or more

studies to address a question of interest or hypothesis. ~ c c o r d i to
i ~Moher and
01kin,13
[Meta-analyses] provide a systematic and explicit method for synthesizing
evidence, a quantitative overall estimate (and confidence intervals) derived
from the individual studies, and early evidence as to the effectiveness of
treatments, thus reducing the need for continued study. They also can ad-
dress questions in specific subgroups that individual studies may not have
examined.
A rned-analysis quantitatively summarizes the evidence regarding a treatment,
procedure, or association. It is a more statistically powerful test of the null hypothesis
than is provided by the separate studies themselves because the sample size is
substantially larger than those in the individual studies. However, a number of issues
make rneta-analysis a muchdebated forir.of analysis.'4-'9 TO help standardize the
presentation of rneta-analysis, JAMA recommends use of the QUOROM flow dia-
gram and checklist (http://www.consort-statement.org/QUOROM.pdf for reporting
mtlr:t-analyses of RCTs, and the MOOSE checklist (http://www.consort-~atement
~~rs~'~n~tinrives/~0OSE/moose.pdf) for reporting meta-analyses of observational
\111(11t'\

1.0 rnsurc th;tt the meta-analysis accurately reflects the available eviclencc, the
r ~ ~ c . r l ~ c x i h idcntil).ing
possible s t ~ ~ d ifor
e s inclusion sllould I>eexplicitly statctl (ex.
 ---.....
7alysii

literature search, reference se

published work). Authors sh
search terms used. A search strategy that includes several approaches to identify

positive results, is a potentia

Unpublished studies may b
inclusion criteria. One appr
the result is to define the nu
the results of a meta-analy

ICMJE policy applies to a

trials that began enrollm
registration by Septemb
project' that prospectively assigns human subjects to intervention or coriQaris
groups to study the cause-and-effect relationship between a medical interventi
and a health outcome."
Other controversi
clusion, ,whether and how studies should be rated for quality:' and
how to combine resul

in a trial.
Gerbarg and ~ 0 1 w i t . have
z ~ ~ suggestedthat criteria for combining studies

concern is the influence a small number of large trials may have on the results;

random-effects model is generally preferred.

analyses on a variety of
 20.6 Studies of Diagnostic Tests

Cost-effectiveness Analysis, Cost-Benefit Analysis. Although a treatment or

screening technique may be shown to be effective in an RCT, recommending it in
general practice would not necessarily be rational. Such interventions may be prohi-
bitively expensive, or they may benefit only a small number of people at the expense
of a large number of people, or they may lead to significant "downstream" costs that
would eventually negate any immediate savings or benefit. Thus, it is possible that
interventions that appear less effective may actually lead to the greatest societal
benefits over the long term.
Cost-effectiveness and cost-benefit analyses comprise a set of mathematical
techniques to model these complex consequences of medical interventions. Cost-
effectiveness analysis "compares thenet monetary costs of a health care intervention
with some measure of.clinical outcome or effectivenesssuch as mortality rates or life-
years saved."26 cost-genefit analysis is similar but converts clinical measures of
outcomes ints monetary units, allowing both costs and benefits to be expressed on a
single scale. This use of a cornmon.metric thus enables comparisons between dif-
ferent treatment or screening smtegies.
The results of a cost-effectiveness analysis are usually expressed in ternls of a
cost-effectiveness ratio, for example, the cost per year of life gained. The use of
quality-adjusted life-years (QALYs) or disability-adjusted life-years (DALYs) pennits di-
rect comparison of different types of interventions using the same measure for
outcomes. The use of such composite measures allo.ws researchers to weigh the
relative benefits of length and quality of life.
The complexity of these analyses and the many decisions required when
selecting data and choosing assumptions may be of particular concern when the .
analysis is perforrned'by an investigator or company with financial interest in the
treatment being e~aluated.~'Suchanalyses may have biases that are difficult to tlctect
.. even with the most rigorous peer review process.28
- One approach frequently used by cost-effectiveness analysts is to define :\ I,ase
case that represents the choices to be considered, perform an aqalysis for tlie Ixtse
case, and then perform sensitivity analyses to determine how varying the tklta usvcl
and assumptions made for the base case affects the reeults. Sometinles anthors tcst
their conclusions by performing bootstrap or jackknife analyses. This involves t;tking
a very large number of repeated random samples from the datn ant1 tllcn ol>scsvi~ig
whether this procedure generally replicates the previous analytic conclusions. A
number of journals have published guidelines and approaches to cost-efkctivt.ness
analysis, hut consensus has yet to emerge on their or intcrprct;~tion.-'.'
nethel he less, mlthors sl~oulclclcarly intlic.;~tc.;111 sousccs oI' cl;~t;t li,r ! ) o t I ~1rr;llliiclll
effects and costs. Graphical approaches may help readers better understand the I~asic
conclusions of the analysis.%JAMA requires authors of cost-effectiveness analysts
and decision analyses to suhmit :I copy of the rlccision tree comprising tlicir motlrl.
Although this need not necesxtrily I)e inclucled in the I,orly of tlic pul~lisl~ccl :~r~iclc-.
such information is necessary for reviewers and editors to assess the details of thc
model and its analysis.
i Studies of Diagnostic Tests. Correct treatmen1 clepentis o n ;iccilr;ilc tli;~gnosis. !
I
I Di;~pnostictests ma)' tncludc. sirnpks procc.dorc5 .iilc-h :I. php~c';ll or- IIII!.S~<.;II I
I es;rniinntic,n. 3s well :IS t > l O t ~ fc\ts
l :~nc!r;lc\~olo,ci<~,ll;lgin,g1'rt\ t\~.txno~tic. Ic\l\.
i I
20.7 Survey Studies

however, can be relied on to yield accurate diag

important to study the performance of diagnostic tests. Bossuyt et a135s
Exaggerated and biased results from poorly designed and repo
nostic studies can trigger their premature dissemination and lead
into making incorrect treatment decisions. A rigorous evaluation
diagnostic tests before introduction into clinical practice could n
duce the number of unwanted clinical consequences related to
estimates of test accuracy, but also limit he
necessary testing.
Studies to determine the diagnostic accuracy of a test are a vital part in
process. JMrecommends that authors use the Standards for Rep
nostic Accuracy (STARD) checklist in reporting such analyses
-statement.org/Initiatives/newstand.htm).
Studies of diagnostic tests generally yield estimates of likelihood ratios, sen
specificity, positive predictive values, and negative predictive values. Authors
repoft confidence intervals associated with these statistics. It is also common for
studies to report receiver operating characteristic curves.

Survey Studies. In a survey study, a rep

to describe their opinions, attitudes, or be
exercise, smoking>,.authors should provide
correlateswith the actual, observed behaviors of a similar samp
is, the survey instrument should have been shown to have validity. If the
instrument is different in any way from that given to the previous validation
(eg, wording, order, or omission of questions), then it may no longer be a
measure of those behaviors.'
For surveys, as for other studies, it is critical to .describe
exclusion criteria, as well as how and when individuals left
initially identified. Flow diagrams can be a useful way of
There is currently no standard reporting format for su
authors have usually reported no more than a single r
To address this situation, the American Ass
(AAPOR) has published a set of expanded definitio
defines response rate as "the number of complete in
divided by the number of eligible reporting units in the sample." The do
points out that this general definition allows for at le
computing this statistic, dependiig on how the numbers of "complete
and the "number of eligible reporting units" are defined. The document
define 4 possible equations for cooperation rates
viewed of all eligible units ever contacted), 3 equations for refusal rates (the.
portion of all cases in which a housing unit or resp
and 3 equations for contact rates (the proporti
sponsible member of the housing unit was reached by the survey). Thus,
should be clear about how they assigned individuals to categories and whi
gories they used to compute these statistics.
The AAPOR document defines specific
mon survey designs: random-digit-dial tel
mail surveys. Future updates of the AAPOR document will discuss Internet-

850

-:..a,
-. -.... .. - .
 20.8.2 Rounding

surveys. As with observational studies, meta-analyses, and cost-benefit sturlies, thcrc

are currently no universally agreed-upon reporting criteria for survey studics.
Survey studies may be either longitudinal (the same respondents are sun~cyccl;it
several time points) or cross-sectional. Causality may be cautiously inferrer1 from
longitudinal surveys, but never from cross-sectional surveys. Case-control studics
(see 20.3.2) and cohort studies (see 20.3.1) may exclusively use survey n~ethodology
to obtain their dependent variables, and thus in practice the distinction between
observational studies and survey studies may be nuanced.

Significant Digits and Rounding Numbers. When numbers are expressed in

scientific and biomedical articles, they should reflect the degree of accuracy of the
original measurement.-Numbersobtained from mathematical calculations should be
rounded to reflect the original degree of precision.

Significant Digits. The use of a numeral in a numbers column (eg, the ones column)
implies that the method of measurement is accurate to that level of precision. For
example, when a reporter attempts to estimate the size of a crowd, the estimate might
be to the nearest tens of number of people, but would not be expressed as an exact
number, such as 86, unless each individual was counted. Similarly, when an author
provides a number with numerals to the right of the decimal point, the numerals
imply that the measurement used to obtain the number is accurate to the last place a
numeral is shown. Therefore, numbers should be rounded to reflect the precision of
the instrument or measurement; for example, for a scale accurate to 0.1 kg, a weight
should be expressed as 75.2 kg, not 75.23 kg. S.imilarly, the instrument used to
measure a concentration is accurate only to a given fraction of the concentration, for
example, 15.6 mg/L, not 15.638 mg/L (see Table 2 in 18.5.10, Units of Measure,
Conventional Units and SI Units in Jm and ,the Archives Journals, Laboratory
Values, for the appropriate number of significant digits). Numbers that result from
calculations, such as means and SDs, should be expressed to nq more than 1 sig-
nificant digit beyond the accuracy of the instrument. Thus, the mean (SD) of weights
of individuals weighed on a scale accurate to 0.1 kg should be expressed as 62.45
(4.13) kg. Adult age is reported rounded to 1-year increments, so the mean could be
expressed as, for example, 47.7 years.

Rounding. The digits to the right of the last significant digit are rounded up or down.
If the digit to the right of the last significant digit is less than 5, the last significant digit
is not changed. If the digit is greater than 5, the last significant digit is rounded up to
the next higher digit. (For example, 47.746 years is rounded to 47.7 years and 47.763
years is rounded to 47.8 years.) If the digit immediately to the right of the last
significant digit is 5, with either no cligits or :1l1 zeros ;~licrthe 5, lhc I:~stsignif rant
digit is rounded up if it is odd and not changed if it is even. (For example, 47.7500
would become 47.8; 47.65 would become 47.6.) If the digit to the right of the last
significant digit is 5 followed by any number other than 0, the last significant digit is
rounded up (47.6501 would become 47.7).
P values and other statistical expressions raise particular issues about rounding
For more information about how and why to round P values and other statistlc;~l
terms, see P value in 20.9, Glossary of Statistical Terms. Briefly, P values shoultl Iw
expressed to 2 digits to the right of the decimal point (regardless of nhethcr ~ t l r .I'
value is significant),unless P < .01, in which case the Pvalue should he e x p n \ ~ .I~O !
20.9 Glo,ury of Stat~st~cal
Term,

Table 3. S e l e a ~ o no f Commonly U u d Stat~rticalTechniquesa

k a l e of Measurement
1 intervalb . Ordinal

2 Treatment groups Unpaired t test Mann-Whitney X2 Analysis-of- i\

rank sum test contingency table;
Fisher exact test :.I
if 56 in any cell ' $
1
2 3 Treatment groups Analysis of variance Kruskal-Wallis X2 Analysis-of- . ' $
statistic contingency table;*
Fisher exact test :j
if 56 in any cell 3
Before and after 1 Paired t test Wilcoxon signed
treatment in same rank test
individual
Multiole treatments in Reoeated-measures Friedman statistic Cochran O

Asmiation between Linear regression and Spearman rank

2 variables Pearson product correlation coefficients
moment correlation
<,:!

aAdaptedwith permission from Glantz, Primer of 8iostatisticsmO The McGraw-Hill Companies, Inc. . :!
b~ssumesnormally distributed data. If data are not normally diibuted, then rank the obsenrations and use $
methods for data measured on an ordinal scale.
. -7-4
'For a nominal dependent variable that is time dependent (such as mortality over time), use life-table analysis fct?
nominal independent variables and Cox regression for continuous andlor nominal independent variables. . a
. .&
.
;-,7
.3

3 digits to the right of the decimal point. (One exception to this rule is when rounding
pfr6n-i 3 digits to 2 digits would result in P appearing nonsignificant,such as P= .
In this case, expressing the P value to 3 places may be preferred by the author.

expressed is P <.001, since additional zeros do not convey useful information.?',~t~

- P values should never be rounded up to 1.0 or down to 0. While, such a p '

ference is based on the assum~tionthat events occur in a ~robabilistic.rather d&

was either absolutely predestined (P= 1.0) or absolutely impossible (P= 0) to occur;
Thus, very large and very small P values should always be expressed as P >.99 an.d
.$
P < .001, respectively. * 3+

\3d
Glossary of Statistical Tenns. In the glossary that follows, terms defined else-:
where in the glossary are printed in this font. An arrowhead (+)indicates points tq
consider in addition to the definition. For detailed discussion of these terms, *e
referenced texts and the resource list at the end of the chapter are useful sources.
Eponymous names for statistical procedures often differ from one text to another
(eg, the Newman-Keuls and Student-Newman-Keuls test). The names provided $
this glossary follbw the Dictionary of Stafi3tical T& published for the Interj

852

.--. .
 ..
.. 2%.. -.

20.9 Glossary of Statistical Terms

national Statistical 1 d t u t e .Although statistical texts use the possessive form for most
eponyms, the possessive form for eponyms is not used in JAMA and the Archives
Journals (see 16.0, Eponyms).
Most statistical tests are applicable only under specific circumstances, which are
generally dictated by the scale properties of both the independent variable and the
dependent variable. Table 3 presents a guide to selection of commonly used statis-
tical techniques. This table is not meant to be' exhaustive but rather to indicate the
appropriate applications of commonly used statistical techniques.

I abscissa: horizontal or x-axi; of a graph.

absolute risk: probabiliti..of an event occurring during a specified period. The ab-
solute risk equals the relative risk times the average probability of the event during
the same time, if the risk factor is a b ~ e n t . ~ See
~ ~ absolute
~ ~ ' ) risk reduction.
absolute risk reduction: proportion in the control group experiencing an event minus
the proportion in the intervention group experiencing an event. The inverse of the
absolute risk reduction is the number needed to treat. See absolute risk.
accuracy: ability of a test to produce results that are close to the true measure of the
phenomenon40<P3mGenerally, assessing accuracy of a test requires that there be a
criterion standard with which to compare the test results. Accuracy encompasses a
number of measures including reliability, validity, and lack of bias.
1. actuarial life-table method: s e i life table. Cutler-Ederer method.
1 , .
adjustment: statistical techniques :used after the collection of data to adjust for the
effect of known or potential confounding A typical example is ad-
- justing a result for the independent effect of age of the participants (age is the in-
dependent variable).
I aggregate data: data accumulated from disparate sources.

I
agreement: statistical test performed to determine the equivalence of the results
obtained by 2 tests when one test is compared with another (one of which is usually
but not always a criterion standard).
+Agreement should not be confused with correlation. Correlation is used t o test
the degree to which changes in a variable are related to changes in another, \vhcrcas
agreement tests whether 2 variables are equivalent. For example, an investig;~tor
compares results obtained by 2 methods of measuring hematocrit. Method A gives a
result that is always h c t l y twice that of method B. The correlation between A :~ndI3
is perfect since A is always twice B, but the agreement is very poor; method A is not
equivalent to method B (written communication, George W. Brown, MD. Septem1,cl-
1993). One appropriate way to assess agreement has been described by 131nnd ;~rlcl
~ltrnan.~'
algorithm: systematic process carried out in an ordered, c)lpically branching scclilcncc.
of steps; each step depends on the outcome of the previous An ;~Igoritl,~n
may be used.clinically to guide treatment decisions for an indiviclual paricnt 0 1 1 rlw
basis of the patient's clinical outcome or result.
20.9 Glossary of 5la11st1calTerms

3 (alpha). (I level: size of the I i k e l i h d i~cceptahleto the invt-stigarors

lationstli;)ot>scntedbetween 2 variables o Juc to cti~ricc([tic prot~dt>ilrty of a type I
error); usually a = .05. If a = .05, P < .05 ~ ~ 1 lx
1 1 corlsidcrcd !+~gn~fic--nt.

analysis: process of mathematically summarizing and comparing data to confirm or

refute a hypothesis. Analysis serves 3 functions: (1) to test hypotheses regarding
differences in large populations based on samples of the populations, (2) to control
. .
for confounding variables, and (3) to measure the size of differences between groups
or the strength of the relationship between variables in the study.4Mp2s)
analysis of covariance (ANCOVA): statisticaltest used to examine data that include both
continuous and nominal independent variables and a continu
is basically a hybrid of multiple regression (used for continuous independent va+
ables) and analysis of variance (used for nominal independent variable^).^^(^*^^' :

analysis of residuals: see linear regression.

analysis of variance (ANOVA): statistical method used to compare a cont
pendeqt variable and more than 1 nominal independent variable. The null
in ANOVA is tested by means of the F test.
In l-way ANOVA there is a single nominal independent variable with 2 or m
levels (eg, age categorized into strata of 20 to 39 years, 40 to
and older).When there are only 2 mutually exclusive catego
independent variable (eg, male or female), the l-way ANOVA is equ
t test.
A 2-way ANOVA is used if there are 2 independent variables (eg, age
and sex), a 3-way ANOVA if there are 3 independent variables, etc. If more
nonexclusive independent variable is analyzed, the proce
ANOVA, which assesses the main effects of the independent variables
interactions. An analysis of mahieffects in the 2-way ANOVA above
independent effects of age group or sex; an association between female sex4
systolic blood pressure that exists in one age group but not another
an interaction between age and sex exists. In a factorial 3-way ANOVA wi
dependent variables A, B, and C,there is one 3-way interaction term 01 x B x
different 2-way interaction terms 01 x B, A x C,and B x 0, and 3
(A, B, and 0.A separate F test must be computed for each different main effect'
interaction term.
If repeated measures are made on an individual (such as
pressure over time) so that a matched form of analysis is appropriate, but
confounding factors (such as age) are to be controlled for simultaneously,
measures ANOVA is used. Randomized-block ANOVA is
signed by means of block r a n d o m i z a t i ~ n . ~ ~ ( ~ ~ * ~." ~ ~ ~ )
-) An ANOVA can establish only whether a significant difference exists
groups, not which groups are significantly different from each other. To det
which groups differ significantly, a pairwise analysis of a
variable and more than 1 nominal variable is performed by a pro
Newman-Keuls test or Tukey test, as well as many others. These
procedures avoid the potential of a type I error that might occ
applied at this stage. Such comparisons may also be compuied through the us
orthogonal contrasts.

- .- .
- .- . . --
<-*-*- .s -. *
 1 20.9 Glossary of Statistical Terms

power. A value of .20 for P is equal to .80 or 80% power. A f3 of..l or .2 is most
i
I
frequently used in power calculations. The f3 error is synonymous with type II error.43
bias: a systematic situation or condition that causes a result to depart from the true
i value in a consistent direction.-Bias refers ,to defects in study design (often selection
bias) or measurement.4Mp3m)One method to reduce measurement bias is to ensure
that the investigator measuring outcomes for a participant is unaware of the group to
which the participant belongs (ie, blinded assessment).
bimodal distribution: nonnormal distribution with 2 peaks, or modes. The mean and
median may be equivalent, but neither will describe the data accurately. A population
composed entirely of schoolchildren and their grandparents might have a mean age
of 35 years, although eGeryone in the population would in fact be either much
younger or much older.
binary variable: variable that has 2 mutually exclusive subgroups, such as male/
female or pregnanthot pregnant; synonym for dichotomous variab~e.~~'~'~)
binomial distribution: probability with 2 possible mutually exjusive outcomes; used
for modeling cumulative incidence and prevalence (for example, the
probability of a person having a stroke in a given population over a given period; the
outcome must stroke or no stroke). In a binomial sample with a probabilityp of
the event and n number of participants, the predicted mean ispx n and the predicted
variance i s p ( p -1).

1
biological plausibiliv. evidence that an independent variable can be expected to exert
a biological effect on a dependent variable with which it is associated. For example,
studies in animals were used to establish the biological plausibility of adverse effects
of passive smoking.
-
II bivariable analysis: see bivariate analysis.
bivariate analysis: used when 1 dependent arid 1 independent variable are to be
assessed.4Mp263'Common examples iaclude the t test for 1continuous variable and 1
binaryvariable and the XZtestfor 2 binary variables. Bivariate analyses can be used for
hypothesis testing in which only 1 independent variable is taken into account, to
compare baseline characteristics ~ f . groups,
2 or to develop a model for multivariate
regression. See also univariate and multivariate analysis.
+ Bivariate analysis is the simplest form of hypothesis testing but is often used
incorrectly, either because it is used too frequently, resulting in an increased like-
lihood of 'a type I error, or because tests that assume a normal distribution (eg, the
t test) are applied to nonnormally distributed data.

Bland-Altman plot: a method to assess agreement (eg, between 2 tests) developed by

Bland and ~ l t m a n . ~ '
blinded (masked)assessment: evaluation or categorization of an outcome in which the
person assessing the oiltcome is unaware of the treatment assignment. Masked as-
sessment is the tern preferred by sonir investigntors and journals, particul;lrly those
in nphthnlmology.
20.9 Glossary of Statistical Terms

-3 Blinded assessment is important to prevent bias on thtr part o f the ~nvestigar

performing the assessment, who may be influenced by t l ~ rstudy qucsrion an
consciously or unconsciously expect a certain test result.
blinded (masked) assignment: assignment of individuals participating in a prospective
study (usually random) to a study group and a control group without the investigator '

or the participants being aware of the group to which they are assigned. Studies m
be single-blind, in which either the participant or the person administering the
tervention does not know the treatment assignment, or double-blind, in which .
neither knows the treatment assignment. The term triple-blinded is sometimes u
to indicate that the persons who analyze or interpret the data are similarly unaware of '!
treatment assignment. Authors should indicate who exactly was blinded. The term
masked assignment is preferred by some investigators and journals, particularly those
in ophthalmology.
block randomization: type of randomization in which the clnit of randomization is not
the individual but a larger group, sometimes stratified on particular variables such as
age or severity of illness to ensure even distribution of the variable between ran-
domized groups. -
Bonferroniadjustment: one of several statistical adjustments to
applied when multiple comparisons are made. The a level (usually .05) is divided by ..
the number of comparisons to determine the .a level that will be considered statis-, .
tically significant. Thus, if 10 comparisons are made, an a of .05 would become:
a = -005for the study. Alternatively,the P value may be multiplied by the number
comparisons, while retaining the a of .05.44pp31"2)Alternatively, the Pvalue may'
multiplied by the number of comparisons, while retaining the a of .05. For example, a
P value of .02 obtained for 1of 10 comparisonswould be multiplied by 10 to get the,]
final result of P = .20, a nonsignificant result.
* The Bonferroni test is a conservative adjustment for large numbers of com-
parisons (ie, less likely than other methods to give a significant result) but is simple
and used frequently.
 . .. 20.9 Glossary of Statistical Terms

Brown-Mood procedure: test used with a regression model that does not assume a
normal distribution or common variance of the It is an extension of the
median test.
C statistic: a measure of the area under a receiver operating characteristic curve.
case: in a study, an individual with the outcome or disease of interest.
case-control study: retrospective study in which individuals with the disease (cases) are
compared with those who do not have the disease (controls). Cases and controls are
identified without knowledge of exposure to the iisk factors under study. Cases and
controls are matched on certain important variables, such as age, sex, and year in
which the individual was. treated or identified. A case-control study on individuals
already enrolled in a cohort study is referred to as a nested case-control s t ~ d ~ ~ " ~ " "
Thistype of case-control study may be an especially strong study design if char-
acteristics of the cohort have been carefully ascertained. 9ee also 20.3.2, Ohsenla-
tional Studies, Case-Control Studies.
+ Cases and controls should be selected from the same population to n~inimizc
confounding by factors other than those under study. Matching cases and controls on
too many characteristicsmay obscure the association of interest, because if cases ancl
controls are too similar, their exposures may be too similar to detect a difference (scc
cvermatching).
case-fatality rate: probability of death among people diagnosed as having a disc;~sc..
The rate is calculated as the number of deaths during a specific period divided 1)). tlic
number of persons with the disease at the beginning of the period?4'p3H'
case series: retrospective descriptive study in which clinical expsrience with a
number of patients is described. See 20.3.3, Observational Studies,
. a '
Case Series.
I
categorical data: counts of members of a category or class; for the analysis each
member or itemshould fit into only 1category orclassMpZ9)(eg, sex or race/ethnicity).
The categories have no numerical significance. Categorical data are summarizetl I>y
proportions, percentages, fractions, or simple counts. Categorical data is synony~i~oi~s
with nominal data.
cause, causation: something that brings about an effect or result; to be distinguishecl
from association, especially in cohort studies. To establish something as a cause it
must be known to precede the effect. The concept of causation includes the con-
tributory cquse, the direct cause, and the indirect cause.
censored data: censoring has 2 different statistical connotations: (1) data in yhich
extreme values are reassigned to some predefined, more, moderate value; (2) data in
which values have been assigned to individuals for whom the actual value is not
known, such as in survival analyses for individuals who have not experienced the
outcome (usually death) at the time the data collection was tern1in:lted.
The term I@-censored dara means that data lvere censorcd from thc lo\\. cnrl o r
left of the distribution; right-ce~uoreddara come from tile high cncl or r~ghtof thc
d i s t r i b ~ t i o n ~ ~dig,
' ~ ~ irt
" survival analyses). For cx;lnlple. if dat:~l o r f:~llsa r c c.;lte-
gorized as individuals who have 0, 1, or 2 or marc f:lllr;.f;~llsc.xcccdinp 2 h:~vet)cen
right-censored.
20.9 Glossary of Stat~rt~cal
Term,

central limit theorem: t h r ~ c ~ r rhat

~ r n >[arcs[flat the mean o!a I ) L I I I I ~ K .o!
~ .UIII~IC\\.ith
S
variances that arc not largr. rclativc to tlw entire arnplc \vi11 ~nc.r~:r>~ngl>. Jl~j~roxlrndre
a normal distribution as the sample size increases. This is thr. I ) J S I f o r 111c l n l p ~ n a n c e
of the normal distribution in statistical testing.UKPw'
central tendency: property of the distribution of data, usually measured by mean,
median, or r n ~ d e . ~ ~ ' ~ ~ ' )
X2test (chi-square test): a test of significance based on the x2 statistic, usually used for
categorical data. The observed values are compared with the expected values under
the assumption of no association. The goodness-of-fit test compares the observed
with expected frequencies. The X2 test can $so compare an observed variance with
hypothetical variance in normally distributed samples.sP33) In the case of a con-
tinuous independent variable and a nominal dependent variable, the x2
can be used to determine whether a linear relationship exists (for example,
lelationship between systolic blood pressure and stroke)?0(pp284-*5)
+ The Pvalue is determined from X2 tables with the use of the'specified a level
and-the df calculated from the number of cells in the x2 table. The x2st
be reported to no more than 1 decimal place; if the Yates correction was used,
should be specified. See also contingency table.
E&nple: The exercise intervention group was least likely to have expe
enced a fall in the previous month (X: = 17.7; P = .02).

Note that the #for x$ is specified using a subscript 3; it is derived from the
ber of cells in the x2 table (for this example, 4 cells in a 2 x 2 table). The value
the x2 value. The P value is determined from the x2 value and dJ
Results of the X2 test may be biased if there are too few observations &en
or fewer) per cell. In this case, the Fisher exact test is preferred.
choropleth map: map of a region or country that uses shading to display qua
&ta.42(P28' See also 4.2.3, Visual Presentation of Data, Figures, Maps.
chunk sample: subset of a population selected for convenience without
whether the sample is random or representative of the population.38(P3uA
is convenience sample.
Cochran Q test: method used to compare percentage results in matche
matching), often used to test whether the observations made by 2 obs
systematic manner. The analysisresults ih a Q statistic, which, with th
the P value; if significant, the variation between the 2 observers cannot be
by chance a l ~ n e . ~See ~ ' also
~ ~ interobserver
~) bias.
coefficient of determination: square of the correlation coefficient,
multiple regression analysis. This statistic indicates the proportion
the dependent variable that &n be predicted from the independen
the analysis is bivariate, the correlation coefficient is indicated as rand the
of determination i s r2. If the correlation coefficient is derived from
analysis, the correlation coefficient is indicated as R and the coefficient of dete
nation is 2.See also correlation coefficient.

860

. -
z i-
.3.: ' ~ m . n ~ l t r r r c ..* If
 20.9 Glossary of Statistical Terms

Example: The sum of the'R values for age and body mass index was 0.23.
[Twenty-three percent of the variance could be explained by those 2 vari-
ables.]
+ When values of the same dependent variable total more than 1.0 or loo%,
then the independent variables have an interactive effect on the dependent variable.

coefficient of variation: ratio of the standard deviation (SD) to the mean. The coeffi-
cient of variation is expressed as a percentage and is used to compare dispersions of
different samples. The smaller the coefficient of variation, the greater the precision.43
The coefficient of variation-isalso used when the SD is dependent on the mean (eg,
the inaease in height with age is accompanied by an increasing SD of height in the
population).
cohort a group of individuals who share a common exposure, experience, or
characteristic, or a group of individuals followed up or traced over time in a cohort
study.38<p31)
cohort effect change in rates that can be explained by the common experience or !
characteristic of a group or cohort of individuals. A cohort effect implies that a current
pattern of variables may not be generalizable to a different ~ o h o r t . ~ ~ ~ ~ ~ )
Example: The decline in socioeconomic status with age was a cohort effect
explained by fewer years of education among the older individuals.
! /

cohort study: study of a group of individuals, some of whom are exposed to a

variable of interest (eg, a drug treaunent or environmental exposure), in which
participants are followed up over time to determine who develops the outcome of
interest and whether the outcome is associated with the exposure. Cohort studies
may be concurrent (prospective) or nonconcurrent ( r e t r o ~ ~ e c t i v e ) !See
~~~~~~~~)
also 20.3.1, Observational Studies, Cohort Studies.
+Whenever possible, a participant's outcome should be assessed by individuals
who do not know whether the participant was exposed (see blinded assessment).

concordant pair. pair in which both individuals have the same trait or outcome (as
opposed to discordant pair). Used frequently in twin ~tudies!~@~~'
.conditional probability: probability that an event E will occur given the occurrence of
F, called the conditional probability of E given F. The reciprocal is not necessarily
true: the probability of E given F may not be equal to the probability of F given
E.44(~55)

confidence interval (CI): range of numerical expressions within which one can be
confident (usually 95% confident, to correspond to an a level of .05) that the popu-
lation value the study is intended to estimate lies.40(p329)
The CI is an indication of the
precision of an estimated population value.
+Confidence intervals used to estimate a population value usually are symmetric
or nearly symmetric around a value, but CISused for relative risks and odds ratios may
not be. Confidence intervals are preferable to p values because they convey in-
formation about precision as well as statistical significance of point estimates
!0.9 Gloss y of Statistical Terms

+ Confidence intervals are expresxd with a Iiypt~cnsepamtlnp [he 2 values. T

avoid confusion, the word to replaces hyphens if one o f thc \.slues
number. Units that are closed up with the nun~enla
closed up are repeated only with the last numeral
and Rounding Numbers, and 19.4,Numbers and Percentages, Use of
Hyphens.
Example: The odds ratio was 3.1 (95% CI, 2.2-4.8). The prevale
in the population was 1.2% (95% CI, 0.8Ywl.6%).

confidence limits (CLs): upper and lower boundaries of the confidence interval, ex'
pressed with a comma separating the 2 v a l ~ e s . ~ ~ ' ~ ~ ~ '
Example: The mean (95% confidence limits) was 30% (28%, 32%).
confounding: (1) situation in which the apparent effect of an ex
caused by an association with other factors that
situation in which the effects of 2 or more causal
cannot be separated to identify the unique effects of any of them;
which the measure of the effect of an exposure on risk is distorted because of 4

association of exposure with another factor(s) that influences the outcome un

study.42(P3s See also confounding variable.
confounding variable: variable that
not an intermediate variable, and
Unless it is possible to adjust for confou
distinguished from those of the factors being studied. Bi can
ment is made for any factor that is caused in part by the exposure and
correlated with the outcome.2xP35' Multivariate analysis is used to control the.
of confounding variables that have been measured.
contingency coefficient: the coefficient CWote: not to be confus
used to measure the strengh of association between 2

contingency table: table created when categorical variables are used to calculat
pected frequencies in an analysis and to present data, especially for a xZ test'
dimensional data) or log-linear models (data with at least 3 dimensions).
contingency table has 2 rows and 3 columns. The df are calculated as (nu
rows - lXnumber of columns -1). Thus-,.a 2 x 3 co
2 dJ
continuous data: data with an unlimited
There are 2 kinds of continuous data: ratio data and interval data. Ratio-level
have a true 0, and thus numbers can meaningfully
weight, systolic blood pressurg, cholesterol level).
as 150 kg. Interval data may be measured with a
point. Thus, 32°C is not half as warm as 64"C, although temperature may be
sured on a precise continuous scale. Continuous data include more information
categorical, nominal, or dichotomous data. Use of parametric statistics requires
continuous data have a normal distribution, or that the data can be transformed
normal distribution (eg, by computing logarithms of the data).
 20.9 Glossary of Statistical Terms

contributory cause: independent variable (cause) that is thought to contribute to the

occurrence of the dependent variable (effect). That a cause is contributory should not
be assumed unless all of the following have been established: (1) an association exists
between the putative cause and effect,(2) the cause precedes the effect in time, and
(3) altering the cause alters the probability of occurrence of the effect."p327' Other
factors that may contribute to establishing a contributory cause include the concept
of biological plausibility, the existence of a dose-response relationship, and consistenq
of the relationship when evaluated in different settings.
control: in a case-control study, the designation for an individual without the disease
or outcome of interest; in.a cohort study, the individuals not exposed to the in-
dependent variable of interest; in a randomized controlled trial, the group receiving a
placebo or standard tre&ent rather than the intervention under study.
controlled clinical trial: study in which a group receiving an experimental treatment is
compared with a control group receiving a placebo or an active treatment. See also
20.2.1, Randomized Controlled Trials, Parallel-Design Double-blind Trials.
convenience sample: sample of participants selected because they were available for
the researchers to study, not because they are necessarily representative of a partic-
ular population.
+ Use df a convenience sample limits generalizability and can confound the
. analysis depending on the source of the sample. For instance, in a study comparing
cardiac auscultation, echocardiography, and cardiac catheterization, the patients
studied, simply by virtue of their having undergone cardiac catheterization and
I
echocardiography, likely are not comparable to an unselected population. ;-

correlation: description of the strength of an association among 2 or more variables,

-
each of which has been sampled by means of a representative o r naturalistic method
from a population of The strength of the association is described by
the correlation coefficient. See also agreement. There are many reasons why 2 vari-
ables may be correlated, and thus correlation alone does not prove causation.
+ The Kendall r rank correlation test is used wnen testing 2 ordinal variables, the
Peanon product moment correlation is used when testing 2 normally distributed
continuous variables, and the Spearman rank correlation is used when testing 2 non-
normally distributed continuous variable^?^
+ Correlation is often depicted graphically by ineans of a scatterplot of the cl:~ta
(see Example F4 in 4.2.1, Visual Presentation of Data, Figures, Statistical Graphs). The
more circular a scatterplot, the smaller the correlation; the more linear a scatterplot,
the greater the correlation.

correlation coefficient: measure of the association between 2 vari;~l~les. The coeffi-

cient falls between -1 and 1; the sign inclimtes the direction of the relationship ;tntl
the numl~erthe lnagnitude of the relationship. A positivc sign inclit.;ttcs r l i ; ~tllca
~ 1.i
2 variables increase or decrease together; a negative sign inclicates thitl incrc;tscs !
in one are associated with decreases in the other. A v;~lueof 1 or - I intlic;ttcs i11:11
the sample values fall in a straight line, while a value of 0 indicates no rel:~tionsliip.
The correlation coefficient should be followed by a measure of the signific;~nc~ o f rl~c
correlation, and the statistical test used t6 measure correlation shoulcl I>eslxc.ific.cl.

863
20.9 Glossary of Statistical Terms

Example: Body mass index increased with age (Pearson r = 0.61; P < .001); '
years of education decreased with age (Pearson r = -0.48; P = .01).
-) When 2 variables are compared, the correlation coefficient is expressed by
when more than 2 variables are compared by multivariate analysis, the correlati
coefficient is expressed by R. The symbol ? or R' is termed the coefficient
termination and indicates the amount of variation in the dependent variable that
be explained by knowledge of the independent variable.

cost-benefit analysis: economic analysis that compares the costs accruing to a

dividual for some treatment, process, or procedure and the ensuing medical con- :

sequences, with the benefits of reduced loss of earnings resulting from prevention of :
death or premature disability. The cost-benefit ratio is the ratio of marginal b
(financial benefit of preventing 1 case) to marginal cost (cost of preven
~ a s e ) . ~ See
~ ' ~also
~ ~20.5,
' Cost-effectiveness Analysis, Cost-Benefit Analysis.
cost-effectiveness analysis: comparison of strategies to determine which provides thf:
mmt clinical value for the cost?3 A preferred intervention is the one that bill coa
least for a given result or be the most effective for a given cost.30(pp383P3OutcomeS
are expressed by the cost-effectiveness ratio, such q cost per year of life saved. Se
also 20.5, Cost-effectiveness Analysis, Cost-Benefit Analysis. .
..
cost-utility analysis: form of economic evaluation in which the outcomes of
native procedures are expressed in terms of a single utility-basedmeasuremelit, a
often the quality-adjusted life-year ( Q A L Y ) . ~ ~ ' ~ ~ ~ )
covariates: variables that may mediate or confound the relationshi
dependent and dependentvariables.Because patterns of covariatesmay
cally between groups in a trial or observational study, their effect should be
for during the analysis. This can be accomplished.in a number
analysis of covariance, multiple regression, stratification, or propensity
Cox-Mantel test method for corn aring 2 survival curves that d&s not assums
B'
particular distribution of &tarM similar to the log-rank test.45@113) ..
'

Cox proportional hazards regression model (Cox proportional hazards model): in

vival analysis, a procedure to determine relationships between survival
treatment and prognostic independent variables such as age?xp290)
function is modeled on the set of independent variables and assumes that the
function is independent of time. Estimates depend only on the order in which
occur,not on the times they OCCLU.~*T~US,authors should generally
they have tested the proportionality assumption of the Cox model, which
that the ratio of the hazards between groups is similar at all points in
proportionality assumption w o ~ l dnot be met, for instance, if one group experien
an early.surgein mortality while the other group did not. In this case, the ratio of
hazards would be different early vs late during ,the time of follow-up.
criterion standard: test considered to be the dignostic stand& for a particu
ease or condition, used as a basis of comparison for other (usually noninvasiv
Ideally, the sensitivity and specificity of the criterion standard for the disease
be 1000h.'(A commonly used synonym, gold standard, is considered jar
~orne.~~'P'~') See also diagnostic discrimination.
 20.9 Glossary of Statistical Terms

Cronbach a: index of the internal consistency of a test,44'p65' which assesses the

correlation between the total score across a series of items and the comparable score
that would have been obtained had a different series of items been ~ s e d . ~ The"~~~'
Cronbach a is often used for psychological tests.
crossdesign synthesis: method for evaluating outcomes of medical interventions,
developed by the US General Accounting Office, which pools results from databases
of randomized controlled trials and other study designs. It is a f o m ~of meta-analysis
(see 20.4, ~ e t a - a n a l ~ s i s ) . ~ ~ ( ~ ~ ~ )
crossover design: method of comparing 2 or more treatments or interventions. In-
dividuals initially are randomized to one treatment or the other; after completing the
first treatment they are crqssed over to 1 or more other randomization groups and
undergo other courses of treatment being tested in the experiment. Advantages arc
that a smaller sample size is needed to detect a difference between treatments, since :I
paired analysis is used to compare the treatments in each individual, but the rlis-
advantage is that an adequate washout period is needed after the initial course o f
treatment to avoid carryover effect from the first to the second treatment. Oider of
treatments should be randomized to avoid potential b i a ~ . ~ See ~ 20.2.2,
' ~ ~ Ran-
~ '
domized Controlled Trials, Crossover Trials.
cross-sectionalstudy: study that identifies participants with and without the condition
or disease under study and the characteristic or exposure of interest at the sanle point
in time.40(p329)

+ Causality is difFicult to establish in a cross-sectional study because the out-

come of interest and associated factors are assessed simultaneously.
crude death rate: total deaths during a year divided by the midyear popul:~tion.
Deaths are usually expressed per 100000 persons?4'pa'
cumulative incidence: number of people who experience onset of a disease or outcomc
of interest during a specified period; may also be expressed as a rate or ratio.""1""'
Cutler-Ederer method: form of life-table analysis that uses actuarial techniques. The
method assumes that the times at which follow-up ended (because of death or tlic
outcome of interest) are uniformly distrilxltetl during the time period, :IS opposctl 10
the Kaplan-Meier method; which assumes that termination of follow-up occurs at the
end of the time block. Therefore, Cutler-Ederer estimates of risk tend to be slightly
higher than Kaplan-Meier Often an intervention and control group
are depicted pn 1 graph and the curves are compared by means of a log-rank test.
This is also known as the actuarial life-table method.
cut point: in testing, the arbitrary level at which "normal" values are separated from
"abnormal" values, often selected at the point 2 SDs from the mean. See also receiver
operating characteristic ~ u r v e . ~ ~ ' ~ ~ ~ '
DALY: see disability-adjustedlife-years.
data: ~c>llection
of items of i n f ~ r m a t i o n . ~(Datum,
~ ' ~ ~ ' the singular form of this word,
i . ~rn:cl!. ~ ~ s c )c l
Gloss Y of Statistical Terms
:$
data dredging (aka "fishing expedition"): jargon meaning post hoc analysis, with n 0 ."32
a~
d
priori hypothesis, of several variables collected in a study to identify that have a.!
1
statistically significant association for purposes of publication. .I
;a
+ Although post hoc analyses occasionally can be useful to generate hy-{
potheses, data dredging increases the likelihood of a type I error and should be I
avoided. If post hoc analyses are performed, they should be declared as such and the i
number of post hoc comparisons performed specified. i
Yi
i
decision analysis: process of identifying all possible choices and outcomes for aI
particular set of decisions to be made regarding patient care. Decision analysis 4
generally uses preexisting data to estimate the likelihood of occurrence of e a c h
outcome. The process is displayed as a decision tree, with each
branch point representing a decision in treatment or intervention
represented by a square at the branch point), or possible
(usually represented by a circle at the branch point).
outcome may be expressed as a utility, such as the quality-adjusted
Figye 2. c

vascular surgery

Death
I
I I Mvccardialinfarction

I I
Oprabie coronary attery disease

coronary artery dlsease

Figure 2. Decision tree showing decision nodes (squares) and chance outcomes (circles),J
branches are labeledwith outcome states. The subtrees to which the decision tree refers are depict9
a separate figure for simplicity. Adapted from Mason JJ; Owens DK, Harris RA, Cooke JP, HlatkyJ
The role of coronary angiography and coronary revascularization before noncardiac vascular su
JAMA. 1995;273(24):1919-1925. -.
'jl

degrees o f freedom (df): see df.

dependent variable: outcome variable of interest in any study; the outcome &l
intends to explain or e ~ t i r n a t e (eg,
~ ~ death,
~~~~ myocardial
' infarction, or red2
in blood pressure). Multivariate analysis controls for independent variables'"
variates that might modify the occurrence of the dependent variable (eg, age, s+
,.8
other medical diseases or risk factors). .$k
 20.9 Glossary of Statistical Terms

descriptive statistics: method used to summarize or describe data with the use of the
mean, median, SD, SE, or range, or to convey in graphic form (eg, tiy using a histo-
gram, shown in Example F5 in 4.2.1, Visual Presentation of Data, ~igures.Statistical
Graphs) for purposes of data presentation'and analysis.44'p73)
df (degrees of freedom) (df is not expanded at first mention): the numl~ero f ar-
ithmetically independent comparisons that can be made among members o f a
sample. In a contingency table, df is calculated as (number of rows - l)(number o f
columns - 1).
+ The df should be reported as a subscript after the related statistic, such as the t
test, analysis of variance, ana test (eg, ~ 2 =
X2 3 17.7, P = .02; in this example, thc
subscript 3 is the number.?f df ).
diagnostic discrimination: statistical assessment of how the performance of a clinical
diagnostic test compares with the criterion standard. To assess a test's al~ilityto
distinguish an individual with a particular condition from one without the condition,
the researcher must (1) determine the variability of the test, ( 2 ) define a population
free of the disease or condition and determine the normal range of values for that
population for the test (usually the central 95% of values, but in tests that are
quantitative rather than qualitative, a receiver operating characteristic curve may be
created to determine the optimal cut point for defining normal and abnormal), and
0determine the criterion standard for a disease (by definition, the criterion standard
should have 1000h sensitivity and specificity for the disease) with which to compare
the test. Diagnostic discrimination is reported with the performance measures sen-
sitivity, specificity, positive predictive value, and negative predictive value; false-positive
rate; and the likelihood ratio.40<pp151-'63'See Table 4.

-
+ Because the values used to report diagnostic discrimination are ratios, they
can be expressed either as the ratio, using the decimal form, or as the percentage, by
multiplying the ratio by 100.
Example: The test had a sensitivity of 0.80 and a specificity of 0.95; the false-
.=
positive rate was 0.05.
01:The test had a sensitivity of 80% and a specificity of 95%; the falsc-
positive rate was 5%.

Table 4. Diag?ostic Discrimination

Disease by Disease Free by
Test Result Criterion Standard Criterion Standard

Positive a (true positives) b (false positives)

Negative c (false negatives) d (true negatives)
- -
a + c = total number of permnr b d = total number of persons

pos!tlve precjlct~vevalue = 2-
at; +
~ e c ; ve
~ !pred~cliveva!ue - -.
C-d
L'
, of S t ~ t i , t ~ c aTerms
J

+ W'l1c.n rhc. dircgnosric dl.~.rir~linalron

ot .I tcsr ,.t ddzfincd. thc. tnclrvrduals tested
~ ~ O I I I C rcprrx-nt
I rhc full s p a r u r n of [hr d i w ~ w3 r d rcllc-ct rtw popullttion on whom .
Ijc asscssed in the general population.

made dichotomous for purposes of analysis (eg, age <65 yeadage > 65 years). This

disability-adjustedlife-years (DALY): A quantitative indicator of burden of disease

Antonym .isconcordant pair.

discrete variable: variable that is counted as an integer; no fractions are po
Examples are counts of pregnancies or surgical procedures, or respons
to a Likert scale.

distribution: group of ordered values; the frequencies or relative frequencies of all

possible values of a character is ti^.^^^^^^) Distributions may have a normal distribution :

(bell-shaped curve) or a nonnormal distribution (eg, binomial or.Poissondistribution).

dose-response relationship: relationship in which changes in levels of exposure are
associated with changes i n ~ h efrequency of an outcome in a consistent direction.
This supports the idea that the agent of exposure (most often a drug) is responsible
for the effect seen.4Mp330)
May be tested statistically by using a X2 test for trend.
 20.9 Glossary of Statistical Terms

Duncan multiple range test: modified form of the Newman-Keuls test for multiple
~om~arisons.~~(~~~)
Dunnett test: multiple comparisons procedure intended for comparing each of a
number of treatments with a single ~ o n t r o l ? ~ ( ~ "
Dunn test: multiple comparisons procedure based on the Bonferroni a d j u ~ t m e n t . ~ ~ ' ~ ~ ~ '
Durbin-Watson test: test to determine whether the residuals from linear regression or
multiple regression are independent or, alternatively, are serially ~ o r r e l a t e d . ~ ~ ' ~ ~ '
ecological fallacy: error that occurs when the existence of a group association is used
to imply, incorrectly, the wistence of a relationship at the individual
effectiveness: extent to which an intervention is beneficial when implemented under
the usual conditions of clinical care for .a group of patients,4NP330)as distinguished
from efficacy (the degree of beneficial effect seen in a clinical trial) and efficiency
(the intervention effect achieved relative to the effort expended in time, money, and
resources).
effect of observation: bias that results when the process of observation alters the
outcome of the &dy.4Mp330'See also Hawthorne effect.
effect size: observed or expected change in outcome as a result of an intervention.
Expected effect size is used during the process of estimating the sample size nec-
essary to achieve a given power. Given a similar amount of variability between
individuals, a large effect size will require a smaller sample size to detect a difference
than will a sx'naller effect size.
efficacy: degree to which an intervention produces a beneficial result under the ideal
conditions of an i n ~ e s t i ~ a t i o n ,usually
4 ~ ~ ~ in
~ ~a)randomized controlled trial; it is
usually greater than the intervention's effectiveness.
efficiency: effects achieved in relation to the effort expended in money. time, and
resources. Statistically, the precision with which a study design will estimate a
parameter of i n t e r e ~ t . * " ~ ~ ~ ~ - ~ ~ )
effort-to-yield measures: amount of resources needed to produce a unit change in
outcome, such as number needed to treat43; used in cost-effectiveness and cost-
benefit analyses. See 20.5, Cost-effectivenessAnalysis, Cost-Benefit Analysis.
error: diifereqce between a measured or estimated value and the true value. Three
types are seen in scientific research: a false or mistaken result obtained in a stu,dy;
measurement error, a random forin of error; and systematic error that skews resulii in
a particular direction.42Cpp56-57)
estimate: value or values calculated from sample observations that are used to ap-
proximate the corresponding value for the popu~ation.4MP330'
event: end point or outcome of a study; usually the dependent variable. Thc event
should be defined before the study is conducted anti :~ssesseciby a n indiviclual
blinded to the intervention or exposure categon; of rhc srudy p a n i c ~ p ~ n t .
exclusion criteria: characteristics of potential study par~l~lp.ln~% o r c,rllcr ~ . I I ; I tI1.1t v. 111
exclude them from the study salnple (such as Imng yc,\lngcr rtl;~n65 yc:lr>.hi>tory(if
cardiovascular disease, expected to move \ v ~ t h ~onI,), , n r l l , 0 1 rtlr In*:;~r~nlrip o f rllr
20.9 Glossary of Stat~rtlcalTerrnl

study). Like inclusion criteria. csClusior. cr~rcriashould tx dcfincd txforc any in-
dividuals are cnrollcd.
explanatory variable: synonymous with independent variable. but prrlcnrd by some
because "independent" in this context does not refer to statistical independtln~e.~@)
extrapolation: conclusions drawn about the meaning of a study for a target population
that includes types of individuals or data not represented in the study ~ a r n ~ l e . ~ ~ ~ ~ ~ )

scoring systems for rating scales and questionnaires.

crimination.

synonymous with variance ratio d i s t r i b u t i ~ n . ~ ~ ( ~ ~ ' )

treatment effect in each study all estimate the same true difference. This is not o
the case, but the model assumes that it is close enough to the truth that the results
not be m i s l e a d i r ~ ~ . ~Antonym
~ ~ " ~ ' is random-effects model.
Friedrnan test: a nonparametric test for a design with 2 factors that uses the
rather than the values of the observation^.^^^^^) Nonparametric analog to anal
variance.
F test (score): alternative name for the variance ratio test (or F rati0),4~(~'~) whi
results in the F score: Often encountered in analysis of v a r i a n ~ e . ~ ~ ~ ' ~ ' )

870
 20.9 Glossary of Statistical Terms

Example: There were differences by academic status in perceptions of the

quality of both primary care training (FInGclz
= 6.71, P = .01) and specialty
training (F1.682 = 6.71, P = .01). [The numbers set as subscripts for the F test
are the df for the numerator and denominator, r,espectively.l

funnel plot in meta-analysis, a graph of the sample size or standard error of each
study plotted against its effect size. Estimates of effect size from small &dies should
have more variability than estimates from larger studies, thus producing a funnel-
'shaped plot. Departures from a funnel pattern suggest publication bias.
gaussian distribution: see normal distribution.
gold standard: see criteridn standard.
goodness of f i t agreement between an observed set of values and a second set that is
derived wholly or partly on a hypothetical The Kolmogorov-Smirnov test
is one example.
group association: situation in which a characteristic and a disease both occur more
frequently one group of individuals than another. The association does not mean
that all individuals with the characterjstic necessarily have the disease.4MP331)
group matching:-processof matching during assignment in a study to ensure that the
groups have a nearly equal distribution of particular variables; also known as frc-
:quency ~natchin~.*p~~l)
Hartley test test for the equality of varkances of a number of populations t k ~ :ire
t
normally distributed, based on the ratio between the largest and snlallest sample
variations.~~~)
I 6 .
liawthorne effect: effect produced in a study because of the participants' awarc.ncss
- that they are participating in a study. The term usually refers to an effect on the
control group that changes the group in the direction of the outcome, resulting in a
smaller effect ,.t)rllLm
A related concept is effect of observation. Tlic 1 In\vt'.-
effect is different than the placebo effect, which relates to participants' espectatio11.s
that an intervention will have specific effects.
hazard rate, hazard function: theoretical measure of the likelihood that an indiviclu:~l
will experience an event within a given period?2'p73' A number of hazard rates for
specific intervals of time can be combined to create a hazard function.
hazard ratio: the ratio of the hazard rate in one group to the hazard rate in another. It
is calculated from the Cox proportional hazards model. The interpretation of the
hazard ratio is similar to that of the relative risk.
heterogeneity: inequality of a quantity of interest (such as variance) in a number of
groups or populations. Antonym is homogeneity.
histogram: graphical representation of data in which the frequency (quantity) within
each class or category is represented by the area of a rectangle centered on the class
interval. The heights of the rectangles are proportional to the observed frequencies,
See also Example F5 in 4.2.1, Visual Presentation of Data, Figures, Statistical Graphs.
Hoeffding independence test: bivariate test of nonnormally distri'wted continuous data
to deterlnine whether the ekments of the 2 groups are independent of each ot~ler."'~""
 -..
20.9 Glossary of Statistical Terms

Hollander parallelism test: determines whether 2 regression lines for 2 independent'

variables plotted against a dependent variable are parallel. The test does not require a
normal distribution, but there must be an equal and even number of observations
corresponding to each line. If the lines are parallel, then both independent variables

homogeneity: equality of a quantity of interest (such as variance) specifically in a ,

number of groups or populations.~P94) Antonym is heterogeneity.

homoscedasticity: statistical determination that the variance of the different variables :

under study is eq~a1.42'p7R' See also heterogeneity.

between groups or relationships among variables and that'any such difference

relationship, if found, would occur strictly by chance. Hypothesis testing includes

reject the null hypothesis.

is expected to improve on its own, but may be overly optimistic in conditionsthat

uncertainty with which they can be predicted.

individuals affected during an interval (eg, year) or as a rate calculated as

number of individuals who develop the disease during-a period divided by

year.

inclusion criteria: characteristics a study participant must possess to be included in

study population (such as age 65 years or older at the time. of study enrollment
w'lling and able to provide informed consent). Like exclusion criteria, inclusion
teria should be defined before any participants are enrolled.

872
 I
20.9 Glossary of Statistical Terms I

independence, assumption of: assumption that the occurrence of one event is in n o

way linked to another event. Many statistical tests depend on the assutnption t l u r
each outcome is independent.42'p83'This may not be a valid assumption if repeatecl
tests are performed on the same individuals (eg, blood pressure is me;~suredsc-
quentially over time), if morethan 1 outcome is measured for a given individu:ll (eg.
myocardial infarction and death or all hospital admissions), or if more than 1 inter-
vention is made on the same individual (eg, blood pressure is measured during 3
different drug treatments). Tests for repeated measures may be used in those cir-
. cumstances.

independent variable: variable postulated to influence the dependent variable within

the defined area of relationships under s t ~ d ~ . ~The ~ ' term
~ " ~does not refer to
statistical independence: so some use the term explanatory variable
Example: Age, sex, systolic blood pressure, and cholesterol level were the
I
independent variables entered into the multiple logistic regression. I

indirect cause: contributory cause that a* through the biological mechanism that is
the direct & u ~ e . ~ p ~ ~ "
Example Overcrowding in the cities facilitated trarismission of the tubercle
bacillus and precipitated the tuberculosis epidemic. .[Overcrowding is an
indirect cause; the tubercle bacillus is the direct cause.]

inference: process of passing from observations to generalizations, usually with

calculated degrees of un~ertainty.~~(98~'
Example: Intake of a high-fat diet was significantly associated with cardio-
vascular mortality; therefore, we infer that eating a high-fat diet increases the
risk of cardiovascular death.

instrument erroc error introduced in a study when the testing instrument is not
appropriate for the conditions of the study or is not accurate enough to measure the
study (may be due to deficiencies in such factors as calibration,
accuracy, and precision).
intention-to-treat analysis, intent-to-treat analysis: analysis of outcomes for in-
dividuals based on the treatment group to which they were randomized, rather than
on' which treatment they actually received and whether they completed the study.
The intention-to-treat analysis generally avoids biases associated with the reasons
that participants may not complete the study and should be the main analysts of a
randomized t r i a ~ . ~ ~ ' See
~ ' ~ 20.2;
" Randomized Controlled Trials.
+ Although other analyses, such as evaluable patient analysis or per-protocol
analyses, are often performed to evaluate outcomes based on treatment actually
received, the intention-to-treat analysis should be presented regardless of other
analyses because the intervention may influence whether treatment was changed
and whether participants dropped out. Intention-to-treat analyses may bias the re-
sults of equivalence and noninferiority trials; for those trials, additional analyses
should be ~resented.See 20.2.3, Randomized Controlled Trials, Equivalence and .
Noninferiority Trials.
20.9 Glossary of Statistical Terms

interaction: see interactive effect.

interaction term: variable used in analysis of variance or analysis o
2 independent variables interact with each other (eg, when a
energy expenditure on cardiac output, the increase in cardia
crease in energy expenditure might differ between men and
term would enable the analysis to take this difference into a
interactive effect effect
which the effect of an independent variable is influen
~ t h e r . ~ ~ ' ~The
' ~ ' 'interactive effect may be additive (ie
effects present separately), synergistic (ie, the 2 effects
than the sum of the effects present separately), or
together have a smaller effect than,the sum of the e
interim analysis: data analysis carried out during a
effects. Interim analysis should be determined as part of the study protocol prior
. patient enrollment and specify the stopping rules if a particular treatment effect
reached?(p130)
interobserver bias: like
response than another observer because of factors unique to
strument. For example,
particular set of signs and symptoms as
basis of his or her beliefs, or a physician
diagnose alcoholism in a patient b e a u
Cochran Q test is used to assess inte
interobserver reliability: test used
particular'measure or o
+ Although the proportion of times that 2 observers agree can be rep0
does not take into account the nu
alone. For example, if 2 observers
they should agree 50% of the
agreement while taking cha
[(observed agreement) - (a
pected by chance). The value of K may range from 0 (poor agreement) to 1
agreement) and may be classified by various descriptive terms, such as s
0.201, fair (0.22-0.40), moderate (0.41-0.60), substantial (0.61-0.80), and near
. (0.81-0.99).-~'-*~'

3 In cases in which disagreement may have especially grave consequ

such as one pathologist rating a slide "negative"' and another rating a slide "
carcinoma," a weighte
severity of the consequence
interobserver variation: see interobserver reliability.
interquartile range: the dista
to describe the dispersion
a range more accurately
The ir ierquartile range d

-
 20.9 Glossary of Statistical Terms

describes the inner 60% of values; the interdecile range describes the inner 80% of
values.38(~~102-103)
interrater reliability: reproducibility among raters or observers; synonymous with
interobserver reliability.

interval estimate: see confidence interval.4Mp331)

intraobserver reliability (or variation): reliability (or, conversely, variation) in mea-
surements by the same person at different times!Mp33" Similar to interobserver reli-
ability, intraobserver reliabjlity is the agreement between measurements by one
individual beyond that expected by chance and can,be measured by means of the K
statistic or the Pearson product moment correlation.

intraraterreliability: synonym for intraobsewer reliability.

jackknife dispersion test technique for estimating the variance and bias of an estimator,
applied to a predictive model derived from a study sample to determine whether the
model fits subsamples from the model equally well. The estimator or model is applied
to subsamples of the whole, and the differences in the results obtained from the
subsample comparedwith the whole are analyzed as a jackknife estimate of variance.
.This method uses a single data set to derive and validate the m ~ d e l . ~ * ' ~ ' ~ ~ '
+Although validating a model in a new sample is preferable, investigators often
use techniques such as jackknife dispersion or the bootstrap method to validate a
model to save the time and expense of obtaining an entirely new sample for 'pur-
poses of validation.
Kaplan-Meier method: nonparametric method of compiling life tables. Unlike the
Cutler-Ederer method, the Kaplan-Meier method assumes that termination of follow-
- up occurs at the end of the time block. Therefore, Kaplan-Meier estimates of risk tend
to be slightly lower than Cutler-Ederer estimates!MP308' Often an intervention and
control group are depicted on one graph and the groups are comp&ed by a log-rank
test. Because tlie method is nonparametric, there is no attempt to fit the dat:~to a
theoretical curve. Thus, Kaplan-Meier plots have a jagged appearance, with discrete
drops at the end of each time interval in which an event occurs. This method is also
known as the product-limit method.
K (kappa) statistic: statistic used to measure nonrandom agreement between ol,-
servers or m e a ~ u r e m e n t s . ~See
~ ' ~interobserver
~~) and intraobserver reliability.
Kendall r (tau) rank correlation: rank correlation coefficient for ordinal data."N'''"'
Kolmogorov-Srnirnov test: comparison of 2 independent samples of continuous data
without requiring that the data be normally distrib~ted"'~'~"; may I,e used ro rcst
goodness of fit.43
Kruskal-Wallistest: comparison of 3 or more groups of nonnormally distributed data 10
determine \vllelher they cliffer signific;~ntly.'"'1~'7' tcasl is :I non-
I'lic. Kn~sk:~l-\~';~lIis
parametric an;ilog o f analysis of variance ;lntl gcncr;llizc\ thc I-\;~lllldcWilcoxon rank
sum test to [he multiple-sanlplc c a x YYp""
kurtosis: the \y:lv In which ;I unimcxl;~lz\~n.c- clc*\.l:llc. frorli ;I normal dlrtribution:
( I e p t l A ~ ~ nor~ ~n .l o) r r f1.11 (~>I,I[I.~LI~IIC
n u y 1%- ~ l l o i>t*:~kc.cl
r~ ! il1.111
.I I>~)II!).II
(II\- ,

( '-
l r ~ l > u)!Ir ~"'1"
20.9 Glossary of Statrstrcal Terms

Latin square: for111 of c-ornplctc trrrtnlent crossover design use

~n;ilsthar cl~rnlnstcathe effcct of treatment
but each drug is fol1out.d by another drug on
following 4 x 4 array, letters A through D co
corresponds to a patient, and each column corresponds to th
drugs are gi~en.~P'*"
Fitsr Drug Second Drug nird Drug Fourth Drug
Patient 1 C D
Patient 2 A C
Patient 3 D B
Patient 4 B A

See also 20.2.2, Randomized Controlled Trials, Crossover Trials.

lead-time bias: artifactual increase in survival time that results from earlier det
of a disease, usually cancer, during a time when the disease is asymptomati~
time bi2s produces longer survival from the time of diagnosis but not longe
from the time of onset of the di~ease.~~''"See also length-time bias. ,
3Lead-time bias may give the appearance of a survival benefit from s
when in fact the inaeased survival is only artifactual. Lead-time bias is u
generally to indicate a systematic error arising when
begin at comparablk stages in the natural course of the condition.

least significant difference test: test for comparing mean values arising in
variance. An extension of the t test.40@115)
least squares method: method of estimation, partial
minimizes the sum of the differences between the observed responses and
predicted by the r n ~ d e l . ~ ' ~
The
' ~ resession
~) line is created so that the sum of
squares of the residuals is as small as possible.
left-censored data: see censored data.
length-time bias: bias that arises when a sampling s
because patients with more frequent clinic visits
those with less frequent visits. In a screening stu
patients with frequent visits is more likely to detect slow-growing tumors than w
sampling patients who visit a physician only when symptoms a r i ~ e . ~ ~See @'~)
lead-time bias.
life table: method of organizing data that allows examination of the experi
or more groups of individuals over time with v
increment of the follow-up peridd, the number
numtzr dying of disease or developing disease can be calculated. An as
the life-table method is that an individual not
half the incremental follow-up period.44(p'43)(The Kaplan-Meier met
Cutler-Ederer method are also forms of life-table analysis but make
sumptions about the length of exposure.) See Figure 3.

... .... ..
 20.9 Glossary of Statistical Terms

Irradiation Treatment No. Dead/Tolal

Pekic only 851167
Pekic plus para-aortic 671170

No. at risk
167 141 117 101 86 77 66 56 45 33 25
170 154 132 117 106 97 84 74 59 43 24
0 I 1 I I I I I I I I 1
0 1 2 3 4 5 6 7. . 8 9 10

Years in Study
Figure 3. Survival curve showing outcomes for 2 treatments groups with number at risk at each time '
point. While numbers at risk are not essential to include in a survival analysis figure, this presentation
conveys more informationpanthe curve alone would. Adapted from~otmanM, Pajak TF, Choi K. et
.al. Prophylactic extended-field irradiation of para-aortic lymph nodes in stages llB and bulky IB and IIA
c e ~ c acarcindmas:
l ten-year treatment results of RTOG 79-20. JAMA. 1995;274(5):387-393.

+ The clinical life table describes the outcomes of a cohort of individuals

- classified according to their exposure or treatment history. The cohort life table is
used for a cohort of individuals born at approximately the same time and followed
up until death. The current life table is a summary of mortality of the population over
a brief (1- to 3-year) period, classified by age, often used to estimate life expectancy
for the population at a given age.42@9n
likelihood ratio: probability of getting a certain test result if the patient has the con-
dition relative to the probability of getting the result if the patient h e s not have the
condition. For dichotomous variables, this is calculated as sensitivity/(l - specificity).
The greater the likelihood ratio, the more likely that a positive test result will occur in
a patient who has the disease. A ratio of 2 means a person with the disease is twice as
likely to have a positive test result as a person without the disease.43The likelihood
ratio test is based on the ratio of 2 likelihood function^.^"^"^' See also diagn;ostic
discrimination.

Likert scale: scale often used to assess opinion or attitude, ranked by attaching a
number to each response such as 1, strongly agree; 2, agree; 3, undecided or neutral;
4, disagree; 5 , strongly disagree. Thc score is ;I s ~ m
of t i l e numerical responses to
each question.44(p144)
Lilliefors test: test of normality (ils~ngthC Kolmogorov-Smirnov test s1;ltistic) in .rvhicli
mean and variance ;Ire cstin~:ltctlf r o r ~I ~~I CC~.II;IC w l ' ' ' " '
20.9 Glo y of S t a t ~ n ~ cTerms
al

linear regression: sutistic-.ll mr-rhod ux-d r o r.orlll-nrr continuous dependent and in:

frequenr!~performed using least squares regression.

variation in yexplained by thexvariables (correlation),and the variances of the fitted

coefficients a and b (and their S D ~ ) . ~ ~ ( ~ ~ ~ ~ )

determination 2 demonstrates that 67% of the variance in weight is explained by

height.)43

logistic regression: type of regression model used to analyze the relationship betwe
a binary dependent variable (expressed as a natural log after a logit transform
and 1or more independent variables. Often used to determine the independent

ponents, they are substantially more complicated than linear regression eq

the Web.)
 20.9 Glossary of Statistical Terms

log-rank test: method of using the relative death rates in subgroups to compare
overall differences between survival curves for different treatments; same as the
Mantel-Haenszel test.3gpp122v124)
main effect: estimate of the independent effect of an explanatory (independent)
variable on a dependent variable in analysis of variance or analysis of ~ o v a r i a n c e . ~ ~ ' ~ " ~ )
Mann-Whitney test: nonparametric equivalent of the t test, used to compare ordinal
dependent variables with either nominal independent variables or continuous indepen-
dent variables converted to an ordinal ~ c a l e . ~ ~ ( ~
Sirnil
' * ' ar to the Wilcoxon ranksum test.
MANOVA: multivariate analysis of variance. This involves examining the overall sig-
nificance of all dependent variables considered simultaneously and thus has less risk
of type I error than would a series of univariate analysis of variance procedures on
several dependent variables.
Mantel-Haenszel test: another name for the log-rank test.
Markov process: process of modeling possible events or conditions over time that
assumes that the probability that a given state or condition wiil be present depends I
only on the state or condition immediately preceding it and that no additional in-
formation about previous states or conditions would create a more accurate esti-
mate.44@155'
masked assesiment synonymous with blinded assessment, preferred by some in-
vestigators'and joumals to the term blinded, especially in ophthalmology.
masked assignment: synb~ymouswith binded assignment, preferred by some in-
vestigators and journals to the term blinded, especially in ophthalmology.
I , >, t .
matching: process of making study and control groups comparable with respect to
factors other than the factors under study, generally as part of a case-control study.
Matching can be done in several ways, including frequency matching (matching on
frequency distributions of the matched variable[sl), category (matching in broad
groups such as young and old), individual (matching on individual rather than group
characteristics), and pair matching (matching each study individual with a control
individ~al).~~'~'~')
McNernar test form of the x2 test for binary responses in comparisons of matched
pairs.42!p'03) The ratio of discordant to concordant pairs is determined; the greater the
number of discordant pairs with the better outcome being associated with the
-.
treatment int:rvention, the greater the effect of the i n t e r ~ e n t i o n . ~ ~ ' ~ ' ~ ~ ' - .

mean: sum of values measured for a given variable divided by the number of val~es;
a measure of central tendency appropriate for normally distiibuted data.49(~29)
+ If the data are not normally distributed, the median is preferred. See also
average.
measurement error: estimate of the variability of a measurement. Variability of a
given parameter (eg, weight) is the sum of the true variability of what is measured
(eg, day-to-day weight fluctuations) plus the variability of the instrument or observer
measurement, or variability caused by measurement error (error variability, eg, the ?. :
scale used for weighing). The intraclass correlation coefficient R measures the re-
lationship of these 2 types of variability: as the error variability tleclines nlith respecr
Gloss y of Statistical Terms

to true variability, R increases, up to 1 when error variance is 0.If all v3ri3bility is a

result of error variability, then R = 0.46(p30)
median: midpoint of a distribution chosen so that half the values for a given variable '
appear above and half occur be lo^.^^^^'^) For data that do not have a normal
distribution, the median provides a better measure of central tendency than does the
mean, since it is less influenced by o u t ~ i e r s . ~ ' ' ~ ~ ~ )
median test: nonparametric rank-order test for 2 gro~ps.38@128'
meta-analysis: See 20.4, Meta-analysis.
missing data: incomplete information on individuals resulting fr
of causes, including loss to follow-up, refusal to participaterand
the study. Although the simplest approach would be to remove such participants
from the analysis, this'would violate the intention-to-treat principle. ~urthermore,
certain health conditions may be systematically associated w
missing data, and thus removal of these individuals could
generally better to attempt imputation of these missing valu
cluded hthe analysis.
mode: in a series of values of a.givenvariable, the number that oc
used most often when a distribution has 2 peaks (bimodal distri
also appropriate as a measure of central tendency for categori
Monte Carlo simulation: a family of techniques for modeling complex systems
which it would otherwise be difficult to obtain sufficient data. In general, Mo
Carlo simulations use a computer algorithm to generate a large number of rand
"observations." The patterns of these numbers are then assessed for underly
regularities.
mortality rate: death rate described by the following equation: [(number of
during period) x (period of observation)l/(number of
values such as the crude mortality rate, the denominator is the number of individ
observed at the midpoint of observation. See also crude death rate.
+~ortalityrate is often expressed in terms of a standard ratio, such as dea
100000 persons per year.
Moses ranklike dispersion test
populations, applicable whe
multiple analyses problem:
performed on one group of
The problem is particularly an issue when the analyses
outcome measures. Multiple analyses can be appropriately adjusted for by me
Bonferroni adjustment or 'any of peveral multiple comparisons procedures.
multiple comparisonsprocedures: any of several tests us
differ significantly after another more general test
difference exists but not between which groups. The
problem of a type I error caused by sequentially applying tests, such as the
intended for repeated use. Authors should specG
a priori, or whether the decision to perform them was post hoc.
 20.9 Glossary of Stat~rt~cal
Term,

-) Some tests result in more conservative estimates (less likely to be significant)

than others. More conservative tests include the Tukey test and the Bonferroni ad-
- justment; the Duncan multiple range test is less conservative. Other tests include the
Scheff6 test, the Newman-Keuls test, and the Gabriel as well as many
others. There is ongoing debate among statisticians about when it is appropriate to
use these tests.
multiple regression: general term for analysis procedures used to estimate values of
the dependent variable for all measured independent variables that are found to be
- associated. The procedure used depends on whether the variables are continuous or

nominal. When all variables are continuous variables, multiple linear regression is
used and the mean of the dependent variable is expressed using the equation
+ +
Y = a Blxl PZx2f' ' -- + Pkxk,where Y is the dependent variable and k is the
total number of independent variables. When independent variables may be either
no&al or continuous and the dependent variable is continuous, analysis of co-
variance is used. (Analysis of covariance often requires an interaction term to account
for Werences in the relationship between the independent and dependent vari-
ables.) When all variables are nominal and the dependent variable .is time-
dependent, life-table methods are used. When the independent variables may be
either continuo& or nominal and the dependent variable is nominal and time-
dependent (such as-incidenceof death), the Cox proportional hazards model may be
used. Nominal dependent variables that are not time-dependent are analyzed by
means of logistic regression or discriminant a n a ~ ~ s i s . ~ ' @ ~ ~ ~ ~ ~ )
multivariable analysis: another name for multivariate analysis.
multivariate analysis any statistical test that deals with 1 dependent variable and at
least 2 independent variables. It may include nominal or continuous variables, hut
ordinal data must be converted to a *;minal scale for analysis. The multivariate
approach has 3 advantages over bivariate analysis: (1) it allows for investigation of
the relationship between the dependent and independent variables 'while controlling
for the effects of other independent variables; (2) it allows several comp;~risonst o I>c
made statistically without increasing the likelihood of a type I error; and (3) it can I>c
used to compare how well several independent variables individually can estimate
values of the dependent ~ a r i a b l e ? ~Examples
( ~ ~ ~ ~include
~ - ~ analysis
~ of variance.
multiple (logistic or linear) regression, analysis of covariance, Kruskal-Wallis test.
Friedman test, life table, and Cox proportional hazards model.
N: total number of units (eg, patients, households) in the sample under study.
~xajnple:We assessed the diagnoses of admission all patients admittetl from
the emergency department during a 1-month period (N = 127).
n: number of units in a subgroup of the sample under study.
Example: Of the patients admitted from the emergency department (N =
127), the most frequent admission diagnosis was unstable angina (n = 38).

natural experiment: investigation in which a change in a risk factor or exposure

occurs in one group of individuals but not in another. The distribution of individuals
into a particular group is nonrandom and, as opposed to controlled clinical trials, the 2'
change is not brought about by the i n ~ e s t i g a t o r . ~ The
~ ~ pnatural
~ ~ ~ ' experiment is
 -
20.9 Glossa ry of Statistical Terms

often used to study effects that cannot be studied in a controlled trial, such ;u th
incidence of medical illness immediately after an earthquake. This is also referred t
as a "found experiment.
naturalistic sample: set of obse
such a way that the distribut
sentative of the distribution in the population.40(p3322)

the disease or outcome under

cause.
negative predictive value: the probability that an individual does not have the dis
(as determined by the criterion standard) if the test result is
measure takes into account
general term is posttest probability. See ~iagnosticdiscrimination.
nested casecontrol study: case-control study in which cases and controls are

codtrol study are that the

occurrence of each case
of time in the analysis,
same population.40@111
20.3.2, Observational Studies, Case-Control Studies.

n-of-1 trial: randomized controlled trial that uses a single patient and an
measure agreed on by the patient and physician. The n-of-1 trial may be
clinicians to assess which of 2 or more possible treatment options is bette
individual patient.50

t-emely rare, eg, a genetic mutation).

nomogram: a visual means of representing a mathematical equation.
nonconcurrentcohort study: cohort study in which an individual's group a

nonnormal disfribution: data that do not have a normal (bell-shaped curve) di

tion; includes binomial, Poisson, and exponential distributions,as well as many o

.e& c
 20.9 Glossary of Statistical Terms

3 Nonnormally distributed continuous data must he either transformerl t o ;I

normal distribution to use parametric methods or, more commonly, analyzcrl 11). non-
parametric methods.

nonparametric statistics: staiistical procedures that do not assume that the clat;~con-
form to any theoretical dktribution. Nonparametric tests are most often ~~sccl fix
ordinal or nominal data, or for nomormally distributed continuous data convencrl t o
an ordinal scale40<p332)(for exampre, weight classified by tertile).
normal distribution: continuous data distributed in a syrnmet-ical, bell-shaped cunrc
with the mean value corresponding to the highest point of the curve. This dis-
tribution of data is assumed in many statistical procedures.wP330' This is also called a
gaussian distribution. ' 1
+ Descriptive statistics such as mean and SD can be used to accurately describe I
I
data only if the values are normally distributed or can be transformed into a normal
distribution.
I
normal range: measure of the range of values on a test among those
without the disease. Cut points for abnormal tests are arbitrary and are often defined
as the central 95% of values, or the mean of values f 2 SDs.
null hypothesis: the assertion that no true association or difference in the study
outcome or comparison of interest between comparison groups exists in the larger i,
population from which the study samples are ~btained.~'(~~!"In general, statistical I
tests cannot be used to prove the null hypothesis. Rather, the results of statistical
testing can reject the null hypothesis at the stated a likelihood of a ,type I error.
1,
I

number needed to harm: computed similarly topumber needed to treat, but number of
patients who, after being treated for a specific period of time, would be expected to
experience 1bad outcome or not experience 1good outcome. .
number needed to treat (NNT): number of patients who must be treated with an
intervention for a specific period to prevent 1 bad outcome or result in 1 good
O U ~ C O ~ The . ~ is ~the~ reciprocal
~ NNT ~ ~ ~ of ~the~ absolute ~ )reduction, 'the
~ ~ risk
difference between event rates in the intervention and placebo groups in a clinical
trial. See also number needed t o harm.
+ The study patients from whom the NNT is calculated should be representative
of the population to whom the numbers will be applied. The NNT does not take into
account adverse effects of the intervention.
odds ratio (OR): ratio of 2 odds. Odds ratio may have different definitions depknding
on the study and therefore should be defined. For example, it may be the odds of
having the disease if a particular risk factor is present to the odds of not having the
disease if the risk factor is not present, or the odds of having a risk factor present if the
person has the disease to the odds of the risk factor being absent if the person does
not hrt1.e the disease.
+ 'The odds ratio typically used for a case-control or cohort study. For a study
of ~ncldentcases w ~ t han ~nfrequentd~sease(for example, <Ph incidence), the odds, --
-:
rnr~oapproulmates the relative risk 42'p"n' When the incidence is relatively frequent,

883
20 9 Glmwry of Sla?ist~calTerms --_

rhc odds r ~ t i omay be arithmetically corrected to better approximate the relativ

r~sk.~'

+ The odds ratio is usually expressed by a point estimate and 95% confide
interval (CI). An odds ratio for which the CI includes 1 indicates no statistics

than 1, there is a statistically significant increase in risk.

1-tailed test: test of statistical significance in which deviations from the null hypothe;'
'
in only 1 direction are c o n ~ i d e r e d . ~Most~ ( ~commonly
~ ~ ~ ) used for the t test.
+ One-tailed tests are more likely to produce a statistically significant result tha
are 2-tailed tests. Since the use of a 1-tailed test implies that the intervention coul

ordinal data: tvDe of data with a limited number of categories with an inheregti

cance; stage and grade. Ordinal data can be s&unarized by means of the mediin ,
quantiles or range.
+ Because increments between the numbers for ordinal data generally are nOJ
fixed (eg, the difference between a grade 1 and a grade 2 heart murmur is n? !I
quantitatively the same as the difference between a grade 3 and a grade 4 hea
murmur), ordinal data should be analyzed by nonparametric statistics. 7
ordinate: vertical or y-axis of a graph. ,:~fl

begun; in prospective studies such as cohort studies and controlled trials, the
comes occur during the time of the study.4"(~333'

describe the central tendency of data that have extreme outliers. .$ j

1
+ If outliers are excluded from an analysis, the rationale for their exclyf
should be explained in the text. A number of tests are available to determine whel
an outlier is so extreme that it should bk excluded from the analvsis.

variables because the variable used for matching is strongly related to the mech
by which the independent variable exerts its
matching cases and controls on residence within a certain area could obs
For exampl

an environmental cause of a disease. Overmatching may also be used to refer,

3
matching on variables that have no effect on the dependent variable, and there
are unnecessary, or the use of so many variables for matching that no suit;
controls can be f o ~ n d . ~ ~ ' ~ ' ~ ~ )
 20.9 Glossary of Statistical Terms

oversampling: in survey research, a technique that selectively increases the likelihood

of including certain groups or units that would otherwise produce too few responses
to provide reliable estimates.
paired samples: form of matching that can include self-pairing, where each partici-
pant serves as hi or her own control, or artificial pairing, where 2 participants are
matched on prognostic ~ariables?~(~'*) Twins may be studied as pairs to atteinpt to
separate the effects of environment and genetics. Paired analyses provide greater
power to detect a Werence for a given sample size than d o nonpaired analyses,
since interindividual differences are minimized or eliminated. Pairing may also be
used to match in case-control or cohort studies. See Table 3.
paired t test t test far, paired data.
parameter: measurable characteristic of a population. One purpose of statistical
analysis is to estimate population parameters from sample observation^.^^(^'^^) The
statistic is the numerical chamcteristic of the sample; the parameter is the numerical
characteristic of the population. Parameter is also used to refer to aspects of a model
(eg, a regression model).
parametric statistics: tests used for continuous data and that require the assumption
that the data Wig tested are normally distributed, either as collected initially or after
transformation to the In or log of the value or other mathematical
The t test is a parametric statistic. See Table 3.
Pearson product moment correlation: test of correlation between 2 groups of normally
distributed data. See diagnostic discrimination.
percentile: see quantile.
: ...._

placebo: a biologically inactive substance administered to some participants in a clin-

ical trial: A placebo should ideally appear similar in every other way to the experi-
mental treatment under investigation. Assignment, allocation, an; assessment should
be blinded.
placebo effect: refers to specific expectations that participants may have of the in-
tervention. These can make the intervention appear more effective than it actually is.
Comparison of a group receiving placebo vs those receiving the active intervention
allows researchers to identify effects of the intervention itself, as the placeho effect
should affect both groups equally.
point esfimate: single value calculated from sample ohsewations that is usecl as the
estimate of the population v:~lue,or pararnetei"xP333'., in most cir~irrnst:~nc.cs
;IC-
companied by an interval estimate (eg, 95% confidence interval).
Poisson distribution: distribution that occurs when a nominal event (often clisc:lsc or
death) occurs rare^^.^^(^'*^' The Poisson distribution is used instead of a binomial
distribution when sample size is calcirl;~redfor :I study of events th;~tc x c u r r;lrc*l!..
population: any finite o r infinite collection of ~ncli\~lcli~alr from \vliicl~;I s;rr\iplc is '
dr.\vn for n study to obtain estim:~tcsto ;~pprosini:rrc [hc v:~lucsth~rt\ ~ o l r l t lI)c
i f ttlc-cntin. yw)prrl:~tionwere s;trnplcrl.' "l'"J-'!\ l~op~11:1fr~
r,l>t;~inrtl ) I ) 111:ry 1% clrli~ic~l

r~.lrr~,\vIy
( c ~:!I1 , in<llviil~~:ll\
c'~lx)w<l l o :I \l)c.c.ilic I V ; I , I I I ~I. .\ . I( . 1I1I1 ~
--L
) ov \\.i(lc.ly1t.s. : i l l

incI~vrtltr;~ls;it ri3k k,r coron;lry ~~~~~y rli.\c:~sc).

20 9 Glossary ~t 51611\t~aITerm$

acc{)unt thc trryucncy wirh which a particular event occurs and the frequency with
which a given risk factor occurs in the population. Population attributable risk dde;

positive predictive value: proportion of those participants or individuals with a pos-

itive test result who have the condition or disease as measured by the criterion
standard. This measure takes into account the prevalence of &e condition or the

of interest alone.

posttest probability: the probability that an individual has the disease if the test
is positive (positive predictivevalue) or that the individual does not have the d
the test result is negative (negative predictive v a ~ u e ) . ~ ~ ~ ~ ~ )

study is begun. If the sample is too small to have a reasonable chance (usu
90%)of rejecting the null hypothesis if a true difference exists, then a negative r
may indicate a type II error rather than a true failure to reject the null hypoth

they should be described in theU'Comment"section and their post hoc nature

stated.
. ,

Example: We determined that a sample size of 800 patients would have 8

power to detect the clinically important difference of 10031at a = .05.

886

.,... .A
-.
%
. v .-
;
-
.k' i
 20.9 Glossary of Statistical Terms
I

precision: inverse of the variance in measurement (see measurement the

degree of reproducibility that an instrument produces when measuring the same
event. Note that precision and accuracy are independent concepts; if a blood pres-
sure cuff is poorly calibrated against a standard, it may produce measurelnents that
are precise but inaccurate. -
pretest probability: see prevalence.
prevalence: proportion of persons with a particular disease at a given point in timt-.
Prevalence can also be interpreted to mean the likelihood that a person selecrccl
at random from the population will have the disease (synonym: pretest probabil-
ity).4Mp33' See also incidence.
principal components analysis: procedure used to group related varial~lesto Iiclp
aescribe data. The variables are grouped s o that the original set of correlatetl v a r i ; ~ l > l ~ ~
is transformed into a smaller set of uncorrelated variables called the princip:~lc.om- +

ponents.42@'3') Variables are not grouped according to dependent and independent

variables, unlike many forms of statistical analysis. Principal conlponents ;~naly>ihih
similar to factor analysis. j
t
prior probability: in Bayesian analysis, the probability of an event based on previous i
information before the study of interest is considered. The prior probability nlay be
informative, based on previous studies or clinical information, or not, in which case
the analysis uses a uniform prior (no information is known before the study of
interest). A reference prior is one with-minirnal information, a clinical prior is hasecl
o n expert opinion, and a skeptical prior is used when large treatment differences are
I
not e ~ ~ e c t e d . ~ When
~@~~ Bayesian
') analysis is used to determine the posterior !-
probability of a disease after a patient has undergone a diagnostic test, the prior !L

probability may be estimated as the prevalence of the disease in the population from
I
- which the patient is drawn (usually the clinic or hospital population).
probability: in clinical studies, the number of times an event occurs in a study group
divided by the number of individuals being
product-limit method: see Kaplan-Meier method.
propensity analysis: in observational studies, a way of minimizing bias by selecting
controls who have similar statisticallikelihoods of having the outcome or intervention
under investigation. In general, this involves examining a potentially large number of
variables for their multivariate relationship with the outcome. The res~lltingnioclel is
then used to predict cases' individual propensities to the oLltcome or intervention.
Each case can then be matched to a control participant with a similar propensity.
Propensity analysis is thus a way of correcting for underlying sources o f hias when
computing relative risk.
proportionate mortality ratio: number of individuals who die of a particular disease
during a span of time, divided by the number of individuals who die o f all clisc;~sc%
during the same period.4NP334) This ratio may also be expressed as a mte. te, a r;lilo
per unit of time (eg, cardiovascular deaths per total deaths per yeiir)
prospective study: study in which participants with ancl R ' I ~ ~ O L I I :In C - S ~ I,\,IT,, .,I(.
identified and then followed up over time; the outcomes of inicre\t 1 1 . 1 ~(. T i ( ,i ,, I I I ,
44CpZOj)
1 -.-
at the time the study commences. Antonym is retrospectwe s t u d y
 . t
.. :

y of Statistical Terms

pseudorandomization: assigning of ~ndividualsto groups in a no

eg, selecting every other individual for an intervention or asigninp panicipa
Social Security number or birth date.
publication bias: tendency of articles reporting positive and/or "
submitted and published, and studies with negative or confirmatory results not
submitted or published; especially important in meta-analysis, but also in
systematic reviews. Substantial publication bias has been demonstrated fro
"file-drawer" problem.52See funnel plot.
purposive sample: set of observations obtained from a population in such a way
the sample distribution of independent variable values is determined by the
searcher and is not necessarily representative of distribution of the
population.aP33'
P value: probability of obtaining the observed data (or data that are more extrem
the null hypothesis were exactly true.44(p206)
+ While hypothesis testing often results in the P value, P values
only information about whether the null hypothesis is reje
intervals (CIS) are much more informative since they provide a plausible
values for an unknown parameter, as well as some indication of the power o
study 2s indicated by the width of the C I , " ( ~(For ~ ~ ~ ~an odds
~ example,
0.5 with a 95%.CI of 0.05, to 4.5 indicates to the reader the [imlprecision
estimate, whereas P= .63 does not provide such information.) Confidence
are preferred whenever possible. Including both the CI and the P va
more information than either a l ~ n e . ~ ' ' 'This
~ is especially true if the
provide an interval estimate and the P value to provide the resu
testing.
+ When any P value is expressed, it should be clear to the reader what'
rameters and groups were compared, what statistical test was performed, and
degrees of freedom ( d f ) and whether the test was 1-tailed or 2-tailed (if these
tinctions are relevant for the statistical k t ) .
3 For expressing P values in manuscripts and articles, the actual valu
should be expressed to 2 digits for P1.01, whether or not P is significant.
rounding a Pvalue expressed to 3digits would make the Pvalue no
as P= .049 rounded to .05, the Pvalue can be left as 3 digits.) If P< .01,it shod
expressed to 3 digits. The actal P value should be expressed (P= . a ) , rather
expressing a statement of inequality (P < .05), unless P< .001.Expressing P to
than 3 significant digits does not add useful information to.P< .
values with extreme results are sensitive to biases or departures
model.37(~198)

P values should not 'be listed simply as not significant or NS,since

analysis the actual values are important and not providing exact Pvalues is
incomplete reporting,37(p'95)~ecause'thePvalue represents the
test and not the strength of the association or the clinical importance of the re
values should be referred to simply as statistically significant or not significant;
such as highly signiJicant and very highly significant should be avoided.

. - +.-
. _..--*^..... T
 20.9 Glossary of Statistical Terms

-B JA.\IA and the ~ t i h ~ lJournals

rs do not use a zero to the left of the decimal
point, since statistically it is not possible to prove or disprove the null hypothesis
completely when only a s;lmple of the population is tested ( P cannot equal 0 or 1,
except by rounding). If P< .00001, Pshould be expressed as P < .001 as discussed. If
P > .999, P should be expressed as P> .99.
qualitative data: data that fit into discrete categories according to their attributes, such
as nominal or ordinal data, as opposed to quantitative data.42(p136)
qualitative study: form of study based on observation and interview with individuals
that uses inductive reasoning and a theoretical sampling model, with emphasis on
validity rather than reliability of results. Qualitative research is used traditionally in
sociology, psychology, and group theory but also occasionally in clinical medicine to
explore beliefs and motivations of patients and physicians.53
quality-adjusted life-year (QALY): method used in economic analyses to reflect the
existence of chronic conditions that cause impairment, disability, and loss of in-
dependence. Numerical weights representing severity of residual disability are based
on assessments of disability by study participants, parents, physicians, or other re-
searchers made as part of utility analysis?2(p136)
quantile: method used for grouping and describing dispersion of data. Commonly $
used quantiles are the teaile (3 equal divisions of data into lower, middle, and upper
ranges), quartile (4 equal divisions of data), quintile (5 divisions), and decile (10
divisions). Quantiles are also referred to as percentiles.3Xp165)
+ Dammay be expressed as median (quantile range), eg, length of stay was 7.5
days (interquartile range, 4.3-9.7 days). See also interquartile range.

quantitative data: data in numerical quantities such as continuous data or

~ o ~ n t s(as~ opposed
~ ( ~ ~to ~qualitative
~ ) data). Nominal and ordinal data may be
- treated either qualitatively or quantitatively.
. .
quasi-experiment: experimental design in which variables are specified and partici-
pants assigned to groups, but interventions cannot be controlled by the experi-.-
menter. One type of quasi-experiment is the natural e~~eriment.~~'p'~')
r: correlation coefficient for bivariate analysis.
R: correlation coefficient for multivariate analysis.
r2: coeficient of determination for bivariate analysis. See also correlation coefficient.
R': coefficientof determination for multivariate analysis. See also correlation coefficient.
random-effects model: model used in meta-analysis that assumes that there is a uni-
verse of conditions and that the effects observed in the studies are only a sample,
ideally a random sample, of the possible e f f e ~ t s . ~ ~
Antonym
' ~ ~ ~ "is fixed-effects model.
randomization: method of assignment in which all individuals have the same ch:~nc.cs
of being assigned to the conditions in a study. Individuals may be randomly assigncrl
at a 2:l or 3:l frequency, in addition to the usual 1:1 frequency. 1':lrticip;tnts III;I!.
or may not be representative of larger population.37'"'3') Simplc ~llctllotl~ I ,I-
20.9 Glossary o f Statistical Terms

randomization include coin flip or use of a random numlx.

randomization.
randomizedcontrolled trial: see 20.2.1, Randomized Controlled Trials, Parallel-D
Double-blind Trials.
random sample: method of obtaining a sample that ensures
the population has a known (but not necessarily equal, for example, in wei
sampling techniques) chance of being selected for the
range: the highest and lowest values of a variable measured in a sample.
Example: The mean age of the participants was 45.6 years (range, 2
years).
rank sum test see Mann-Whitney test or Wilcoxon rank sum test.
rate: measure of the occuzence of a disease or outcome per unit of time
expressed as a decimal if the denominator is 100 (eg, the su
0.02). See also 19.7.3, Numbers and Percentages, Forms
Proportions and Percentages.
ratio: fraction in which the numerator is not necessarily a subset of the de
unlike a proprtion40@33n (eg, the assignment ratio was 1:2:1 for each
[twice as many individuals were assigned to the second gro
groupsl).
recall bias: systematic m o r resulting from individuals in one group beiig mo
than individuals in the other group to remember past event^.^^(^^*^)
+ Recall b i is especially common in case-control studies that assess risk
for serious illness in which individuals are aske
such as environmental exposure in an individual who
-
receiver operatin,g characteristic curve .(ROC curve): graphic
extent to which a test can be used to discriminatebetween p
disease,4*@lm and to select an appropriate cut .p
normal results. The ROC curve is created by plotting sensitivity vs (1 -
The area under the curve provides some measure of how well the test pe
larger the area, the better the test. See Figure 4. The
,.. under the ROC curve.
+.The appropriate cut is a functio
requue high sensitivity, whereas a diagnostic or co
specificity. See Table 2 and diagnostic discrimination.

reference group: group of presumably disease-free individuals from which

of individuals is dr& and tested to establish a range of normalval .. .
teSt.40(~335)
. .

' regression analysis:'statisticaltechniques used to

function of 1or more independent variables; ofte
See also linear regression, logistic regression.

. "4- .
. . .. .

-.
- .. .. sv2.,. i,*"
 20.9 Glossary of Statistical Terms

False-Positive Rate (1Specificity)

Figure 4. Receiver operating-characteristiccurve. The 45" line represents the point at which the test is
no better than chance. The area under the curve measures the performance of the test; the larger the
area under the curve, the better the test performance. Adapted from Grover SA, Coupal L, Hu X-P.
Identifying adults at increased risk of coronary disease: how well do the current cholesterol guidelines
work? JAMA. 1995;27410):801-806.
X

relative risk (RR): probability of developing a n outcome within a s ~ e c i f i e dperiod if a

risk factor is present, divided by the probability of developing the outcome in that
same period if the risk factor is absent. The relative risk is applicable to ranrlomizcd
clinical trials a n d cohort ~ t u d i e s * ~ Ffor
~ ~case-control
~); studies tlle.odds ratio can I,c
used to approximate the relative risk if the outcome is infrequent.
3 The -relative risk should b e accompanied by confidence intervals.

Example: The individuals with untreated mild hypertension had a rel;~ti\.c.

risk of 2.4 (95% confidence interval, 1.9-3.0)for stroke or transient isclicmir
attack [In this example, individuals with untreated mild hypenension:\\.crc
2.4 times more likely than were individuals in the comparison group t o Ii;~\.e
a stroke or transient ischemic attack.]
relative risk reduction (RRR): proportion of the control group experiencing a gi\.cn
outcome minus the propoltion ol' the trcdtment group experiencing thc o u ~ c o ~ i l c .
divided by the proportion of the control group expeiiencing the outcome.
reliability: ability of a test to replicate a r e s ~ ~given
lt the same measurement concli-
tions, ;I.; tIistingllishetl from validity, which is the al,ility o f a test to me:~surcwh;~tit R- 2:
intcndcd t o nleasure.. l ( p l 4 5 )
20.9 Glossary of Statrstrcal Terms

repeated measurer: ~ 1 1 ~ l y sJcb~gned

i3 to cake into account the lack of indep
ot cvc~lt\when meahures are repeated in each participant
prcssurc. \vc~ght.or test scores). This type of analysis emphasizes
sured for a participant over time, rather than the differences between pa
over time.
repeated-measures ANOVA: see analysis of variance.
reporting bias: a bias in assessment that can occur when individuals in one group are
nlore likely than individuals in another group to report past events. Reporting bias is
especially likely to occur when different groups have differe
not report For example, when examinin
lescent girls may be less likely than adolescent boys to report being sexua
See also recall bias.
reproducibility: ability of a test to produce consistent results when repeated under
same conditions and interpreted without knowledge of the prior results
with the same test40(p336>;
same as reliability.
residual. measure of the discrepancy between observed and predicted valves.
residual SD is a measure of the goodness of fit of the regression line to th
gives the uncertainty of estimating a pointy from a point x . ~ * ' "
residual confounding: in observational studies, the. possibility that differenc
outcome miy be caused by unmeasured or unmeasurable factors.
response rate: number of complete herviews with reporting units
number of eligible units in the sample.36 See 20.7, S w e y Studies.
retrospective study: study performed after the outcomes of interest ha& alrea
ci~rrecl~~@ mpst
' ~ ~commonly
); a case-control study, but also may be a retrospe
cohort study or case series. Antonym is prospective study.
.. right-censored data: see censored data.
risk: probabilitythat an event will occurduring a specified peri0d:Ris
number of individuals who develop the disease during the
number of disease-free persons at the beginning of the period. . .

risk f a c t o ~characteristic or factor that is associated with an increased prob

developing a condition or disease. Also called a risk marker, a risk factor
necessarily imply a causal relationship. A modiiable risk factor is
modiied through an i n t e r v e n t i ~ n ~ ~ @ (eg,
' ~stopping
) smoking or treating
vated cholesterol level, as opposed to a genetically linked characteristic fo
there is no effective treatment).
risk ratio: the ratio of 2 iisks. See also relative risk.
robustness: term used to indicate that a statistical procedure's assumptions
commonly, normal distribution of data) can be violated without a substantial
on its c o n c l ~ s i o n s . ~ ~ ~ * ' ~ ~ )
root-mean-square: see standard deviation.
rule of 3: method used to estimate the number of observations r
chance of observing at least 1 episode of a serious adverse e

892

.. . . -. . 7.
f i
 20.9 Glossary o' Statist~calTerms

observe at least 1case of penicillin anaphylaxis that occurs in about 1in 10 000 c:\sch
treated, 30 000 treated cases must be observed. If an adverse event occurs 1 in 15 000
times, 45 000 cases need to be treated and o b ~ e r v e d . ~ ~ ' ~ " ~ '
run-in period: a period at thk start of a trial when no treatment is aclministcrccl
(although a placebo may be administered). This can help to ensure that patients : I I . ~
stable and will adhere to treatment. This period may also be used to allow patic-nts
to discontinue any previous treatments, and so is sometimes also called a washout
period.
-
I sample: subset of a larger population, selected for investigation to draw conclusions
or make estimates about the larger population.s2(p336~ -
sampling error: error introduced by chance differences between the estimate ob-
tained from the sample and the true value in the population from which the sample
was drawn. Sampling error is inherent in the use of sampling methods and is mea-
sured by the standard error.ap336)

I Scheffk test: see multiple comparisons procedures.

I SD: see standard deviation.

I SE: see standard error.

I SEE: see standard error of the estimate.

selection bias: bias in assignment that occurs when the way the study and control
groups are chosen causes them to differ from each other by at least 1 factor that
affects the outcome of the
+ A common type of selection bias occurs when individuals from the study
group are drawfl from one population (eg, patients seen in an emergency department
- or admitted to a hospital) and the control participants are drawn from another (eg,
clinic patients). Regardless of the disease under study, the clinic patients will be
healthier overall than the patients seen in the emergency department or hospital and
will not be comparable cantrols. A similar example is the "healthy worker effect":
people who hold jobs are likely to have fewer health problems than those who d o
not, and thus comparisons between these groups may be biased.

I SEM: see standard error of the mean.

sensitivity: proportion of individuals with the disease or condition as measured by
the criterion standard who have a positive test result (true positives divided by all
those with the d ~ ~ e a s e ) . ~See ~ ~ ~4)and diagnostic discrimination.
" ( ~Table i

sensitivity analysis: method to determine the robustness of an assessment by ex-

amining the extent to which results are changed by differences in methods, values of
variables, or a ~ w i m ~ t i o n s ~ applied
~ ( ~ ' ~ ~in' decision
; analysis to test the robustness of
the concli~sionto changes in the assunlptions.
signed rank test: see Wilcoxon signed rank test.
significance: \t:~tis~ically, the testin): of thr null hypothesis of no difference between __:
grou 1)s.A 51gnitic;lntresr~ltrcjccts ttir null hypothesis. Statistical significance is highly .
tlcpcnclent o n s;~lnpicsize and provides no information about the clinical sig-
nific-:~ricc.
o f r l l ~ ,rc?;,l]t (:Iinic;ll signifir.:lncc, on the. other h;lntl, involves a judgment :.
of S t a t ~ s t ~ c aTerms
l

trary.
sign test: a nonparametric test of significance that depends on the signs (positive
negative) of variables and not on their magnitude; used when combining the resu
of several studies, as in m e t a - a n a ~ ~ s i s . ~See
~ ' ~also
' ~ ) Cox-Stuart trend test.
skewness: the degree to which the data are asymmetric on either side of the centr

skewed.44(~~2*239'
snowball sampling: a sampling method in which survey respondents are asked
recommend other respondents who might be eligible to participate in the surv

cultural patterns in the population under investigation.

determination.
specificity: proportion of those without the disease or condition as measured b
criterion standard who have negative results by the test being

crimination.
standard deviation (SD; does not need to be expanded at first mention): comm
used descriptive measure of the spread or dispersion of data,the positive square
of the The meanf 2 SDs represents the middle 95% of values
tained. .
+ Describing data by means of SD implies that the data are .normallydistribute
if they are not, then the interquartile range or a similar measure involving quantiles

the f construction. --
standard error (SE; does not need to be expanded at first mention): positive
root of the variance of the sampling distribution of the stat is ti^.^^'^'^^) Thus,

tistical Graphs).
 20.9Glossary of Statistical Terms

standard error of the difference: measure of the dispersion o f the differences txt\vccn
samples of 2 populations, usually the differences between the means of 2 samples;
used in the t test.
standard error of the estimate: SO of the observed values allout the regression
line.38(p195)

standard error of the mean (SEM): An inferential statistic, which describes the certainty
with which the mean computed from a random sample estimates the true mean of the
population from which the sample was d r a ~ n . ~ ?If~multiple
~" samples of a pop-
ulation were taken, then.95% of the samples would have means would fall within
f2 SEMs of the mean of all the sample means. Larger sample sizes will be accom-
panied by smaller S E M because
~ larger samples provide a more precise estimate of
the population mean than d o smaller samples.
-) The SEM is not interchangeable with SD. The SD generally describes the
observed dispersion of data around the mean of a sample. By contrast, the SEM
provides an estimate of the precision with which the true population mean can be
inferred from the sample mean. The mean itself can thus be understood as either a
descriptive or an inferential statistic; it is this intended interpretation that governs
whether it should be accompanied by the SD or SEM.In the former case the mean
simply describes the average value in the sample and should be accompanied by the
SD, while in the latter it provides an estimate of the population mean and should
be accompanied by the SEM. The interpretation of the mean is often clear from the
text, but authors may need to be queried to discern their intent in presenting this
statistic.
standard error of the proportion: SD of the population of all possible values of the
proportion computed from samples of a given
standardization (of a rate): adjustment of a rate to account for factors such as age or
sex.40<pp3M350)

standardized mortality ratio: ratio in which the numerator contains the observed
number of deaths and the denominator contains the number of deaths that would be
expected in a comparison population. This ratio implies that confounding factors
have been controlled for by means of indirect standardization. It is distinguished from
proportionate mortality ratio, which is the mortality rate for a specific d i ~ e a s e . ~ ~ ' ~ ~ ~ "
standard normal distribution: a normal distribution in which the raw scores have been
recomputed to have a mean of 0 and an SD of 1.44'p245'Such recomputed values arc
referred to as r'scores or standard scores. The mean, median, and mode are all equal to
zero.
standard score: see z score.38<p136)
statistic: value calculatecl from sample clat:~th:~tis 11s~cl t o cstirn:~!~ ;I v:~lt~c. 01.pa-
,I* , > $ $ - I

rameter in the larger population from which the sample \v:ls ol~t;tinccl. :I4

distinguished from data, which refers to thc ;1~tu;1lV ; I I L I C . ~ c ,lvainccl \ . I ; I C I I I cc I ,I ( )-

servation (eg, measurement, chart review, p;iric.nr intcl~.~c.\\ )

stochastic: type of measure that implie.; tlw I>rr\r.n< (,! . I I . i r . ~lt

~ ,111 \ . \ I 1 . 1 1 ~ 1 ~ .
<.,,,,,,-, -.
20.9 Gloss y of Statistical Terms
ii
stopping rule: rule, based on a test statistic or other funaion, specified as part of the "
design of the trial and established before patient enrollment, llut specifics a limit for
4 I
the observed treatment difference for the primary outcome rneasurc, which, if ex- *
ceeded, will lead to the termination of the trial or one of the study gro~ps.7'p2~' The
stopping rules aie designed to ensure that a study does not continue to enroll 4
patients afier a significant treatment difference has been demonstrated that would.,!
still exist regardless of the treatment results of subsequently enrolled patients. .aA
..
.I

stratification: division into groups. Stratification may be used to compare groups:

separated according to similar confounding characteristics. Stratifiedsampling may$
be used to increase the number of individuals sampled in rare categories of inrzj
dependent variables, or to obtain an adequate sample size to examine differences?
. among individuals with certain characteristics of intere~t.~~~'")
'1
Student-Newman-Keuls test see Newman-Keuls test.
.a

Student t test see t test. W. S. Gossett, who originated the test, wroie under the nam4
Student because his employment precluded individual publication.42(p166> SimP!
using the term t test is preferred.
study group: in a controlled clinical trial, the group of individuals who undergo a
intervention; in a cohort study, the group 'of individuals with the exposure or chat
acteristic of interest; and in a cas&control study, the group of cases.mp33n ;4
L 4

sufficient cause: characteristic that will bring about or cause the diease.40<P33n 2p
supportive criteria: substantiation of the existence of a contributory cause. potent$
supportive criteria include the strength and consistency of the relationship, t&. t l
presence of a dose-response relationship, and biological plausibility!0<P33n
surrogate end points: in a clinical trial, outcomes that are not of direct clinical $
portance but that ark'believedto be related to those that are. Such variables are oh$
physiological .measurements (eg, blood pressure) or biochemical (eg, cholesteq
level). Such end points can usually be collected more quickly and economically &
clinical end points, such as myocardial infaiction or death, but their clinical relevanc
may be less certain. 'q
'4
survival analysis: statistical ~roceduresfor estimating the survival function and fc
w

mak;ing inferences about LOW affected by treatment and

tors!Xp163) See life table.
target population: group of individuals to whomlbne wishes to apply or exuapolal
- . .
the results of an investimtion. not necessarilv the ~ooulation
target population is differe frorn the populatic>nstudied, whether the study
If t.6

can be extrapolated to the lrget POP'ulation sh~ouldbe discussed.

?4
r (tau): see Kendall r rank correlation. ...*
i

trend, test for: see X2 test.

,*.?I
trial: co~:xolled experiment with an uncertain o ~ t c o r n e ~used
~ ~most
~~~ common
);
to refer to a randomized studv.
 f .-
. t*.
20.9 Glossary of Statistical Terms

triangulation: in quali[ative research, tht. sirnulraneous use of several different

techniques to study the same phenomenon, thus revealing and avoiding biases that
may occur if only a single method were used.
true negative: negative test result in an individual who does not have the disease or
condition as determined by the criterion standard.4wp338) See also Table 4.
true-negative rate: number of individuals who have a negative test result and rlo not
have the disease by the criterion standard d'ivided by the total number of inclivicluals
who do not have the disease as determined by the criterion standard; usually ex-
pressed as a decimal (eg, the true-negative rate was 0.85). See also able 4.
true positive: positive test result in an individual who has the disease or conclition :ts
determined by the crite'rion See also Table 4.
true-positive rate: number of individuals who have a positive test result and li:~\.cthc
disease as determined by the criterion standard divided by the total numher o f in-
dividuals who have the disease as measured by the criterion standard; usually cs-
pressed as a decimal (eg, the true-positive rate was 0.92). See also Talde 4.
t test: statistical test used when the independent variable is binary and the dependent
variable is continuous. Use of the t test assumes that the dependent vari;~l~lc II;I!; ;I
normal distribution; if not, nonparametric statistics must be used!ap260'
-) Usually the t test is unpaired, unless the data have been measured in the s:~nic
individual over time. A paired t test isappropriate to assess the clxungc oI' rl~c
parameter in the individual from baseline to final measurement; in this cnsc. thc
dependent variable is the change-fromone measurement to the next. These changes
are usually compared against 0,o n the null hypothesis that there is no change from
time 1to time 2.
3 Presentation of the t statistic should include the degrees of freedom (df ).
whether the t test was paired or unpaired, and whether a I-tailed or 2-tailed test was
used. Since a 1-tailed test assumes that the study effect can have only 1 possible
direction (ie, only beneficial or only harmful), justification for use of the 1-tailed test
must be provided. (The 1-tailed test at a = .05 is similar to testing at a = .10 for a 2-
tailed test and therefore is more likely to give a significant result.)
The difference w:~ssignificant by a 2-tailed test for paired san~ples
(tls = 2.78, P = .05).
+ The t test can also be used to compare different coefficients of variation
Tukey test: a type of multiple comparisons procedure.
2-tailed test: test of statistical significance in which deviations from the null hypothesis
in either direction are c ~ n s i d e r e d . ~For~ ' ~most
~ ~ ~outcomes,
' the 2-tailed test is ap-
propriate unless there is a plausible reason why only 1 direction of effect is con-
sidered and a 1-tailed test is appropriate. Commonly used for the t test. I x ~ cnn t ;rlso
be used in other statistical tests.
2-way analysis of variance: see analysis of variance.
 . .
- -.
,ary of Statistical Terms

type I error: a result in which the sample data lead to

despite the fact that the null hypothesis is actually
is the size of a type I error that will be permitted, usually .05.
-3 A frequent cause of a type I e
increase the likelihood that a signifi
type I error, one of several multiple comparisons procedures can be used.
type I1 error: the situation where the sample data lead to a failure to reject the
hypothesis despite the fact that the null hypothesis is actually false in
+ A frequent cause of a type I1 error is in
power calculation should be performed when a study is planned
sample size needed -toavoid a type I1 error.
uncensored data: continuous data reported as collected, without adjustment, as '
posed to censored data.
uniform prior: assumption that no useful information regarding the outcome o
terest is available prior to the study, and thus that all individuals
probabilky of the outcome. See Bayesian analysis.
s the number 1;a relative risk of 1 a
unity: ~ o n y m o uwith
a regression line with a slope of 1 is said to have a slope of unity.
univariable analysis: another name for univariate analysis.
univariate analysis statistid tests
of central tendency (mean or med
apply to an analysis in which the
purpose of the analysis is to describe the
pares with the population, and determine
distribution of 1 or more of the variables in the study. If the characteristics
sample do not reflect those of the
results may not be genemhble to that p
unpaired analysis: method that compares 2 treatment
are not given to the same individual. Most case-control studies also use u
analysis.
unpaired t test: see t test.
.--
U test: see Wilcoxon rank sum test.
utility: in decision theory and clinical decision arm
preference of achieving a particul
an outcome vs the discomfort of the
experienced by the patient with a disea~e.~*(~"~) C
time trade-off and the standard gamble. The result
along a continuum from death (0) to full health or absence of disease (1.0).
quality number can' then be multiplied by the nu
health state produced by a particular treatment to obtain the quality-adjusted life-ye
See also 20.5,'~ost-effectiveness Analysis, Cost-Benefit Analysis.

.L -,_.\.. .
. . ,.>..,::,.;.,
.i.,
.
\ t
20.9 Glossary of Statistical Terms

validity (of a measurement): degree to which a measurement is appropriate for the

question being addressed or measures what it is intended to measure. For example, a
test may be highly consistent and reproducible over time, but unless it is compared
with a criterion standard or other validation method, the test cannot-be considered
valid (see also diagnostic discrimination). Construct ualidity refers to the extent to
which the measurement corresponds to theoretical concepts. Because there are no
criterion standards for constructs, construct validity is generally established by
comparing the results of one method of measurement with those of other methods.
Content validity is the extent to which the measurement samples the entire domain
under study (eg, a measurement to assess delirium must evaluate cognition). Cri-
terion validity is the extent to which the measurement is correlated with some
quantifiable external critsrion (eg, a test that predicts reaction time). Validity can be
concurrent (assessed simultaneously) or predictive (eg, ability of a standardized test
to predict school performance).42(p171)
+ Validity of a test is sometimes mistakenly used as a synonym of reliability; the
two are distinct statistical concepts and should not be used interchangeably. Validity
is related to the idea of accuracy, while reliability is related to the idea of precision.
validity (of a study): internal validity means that the observed differences between
the control and comparison groups may, apart from sampling error, be attributed to
the effect under study; external validity or generalizability means that a study can
1
produce unbiased inferences regarding the target population, beyond the partici-
pants in the s t ~ d ~ ? ~ ' ~ " ~ '
Van der Waerden test nonparametric test that is sensitive to differences in location for
I
i
2 samples from otherwise identical populations.38<p216) II
variable: characteristic measured as part of a study. Variables may be dependent
(usually the outcome of interest) or independent (characteristics of individuals that
- may affect the dependent variable).
variance: variation measured in a set of data for one variable, defined asthe sum of the
squared deviations of each data poht from the mean of the variable, divided by the
df (number of observations in the sample - 1).44(p266' The SD is the square root of
the variance.
variance components analysis: process of isolating the sources of variability in the
outcome variable for the purpose of analysis.
variance ratio distribution: synonym for F distribution.42(p61)
visual analog scak scale used to quantify subjective factors such as pain, satisfaction,
or values that individuals attach to possible outcomes. Participants are asked to in-
dicate where their current feelings fall by marking a straight line with 1extreme, such
1
as "worst p i n ever e~~eriencecl," at one encl of the scale and the other extreme,
\ ~ I C . I I ;IS "lx~i~l-l'rc~c~,"
;I[ 111~.OIII<T < * ~ i t'1'11~-
l. l i - ~ - I i 1 1 ~ ( I < . ~ Vof
( t a x 3 < ~p;~in)
C * i \ (l\~;t~~\ifit-(l iI
I>y nleasuring the distance from the mark on the scale to the end of the scale. 'L'l'L"H'

I
washout period: see 20.2.2, Randomized Controlled Trials, Crossover Trials.
Wilcoxon rank sum test: a nonparametric test tll:~r I-anks and sums ol')servations
from coml>inccIs;lmpIes and compares the result wit11 the sum of ranks from 1
- :

899
20 10Statistical Symbols and Abbreviations
e

sample.~P220'
U is the statistic that results
Mann-Whitney test.
Wilcoxon signed rank test: nonpararnetric test in which 2 treatments that hav
evaluated by means of matched samples are compared. Each observation is
according to size and given the sign of the
treatment effect was positive and vice vers
Wilks A (lambda): a tes
the effect size for all the dependent vari
adjusts significance levels for multiple comparisons.
x-axis: horizontal axis of a graph. By convention, the independent variable is plo
on the x-axis. Synonym is abscissa.
Yates correction: .continuity correction us
continuous frequencies closer to the co
are deri~ed.~*@"~'
y-axis: vertical axis of a graph. By conve
y-axis. Synonym is ordinate.
axis of a 3dimensional graph, generally placed so that it ap
z-axis: third
project out toward the reader. The z-axis and x-axis are both used to
dependent variables and are often used to demonitrate that the 2 indep
ables each contribute independently to the dependent variable. See x-ax
z score: score used to analyze co
value from the mean value, expressed
score is frequently use
well as behavioral score^.^^(^'

statistical Symbols
expansion except where note
the abbreviation may be pl
abbreviation used thereafter (see also 14.11, Abbreviations, Clinical, Techni
Other Common Terms). Most terms other than mathematical symbols can
found in 20.9, Glossary of Statistical Terms.
symbol 'or
Abbreviation Description
1x1 absolute value
C sum
>
2 greater ,than or equal to
< less than
-
< - less than or equal to
A hat, used above a parameter to denote an estimate
ANOVA ,, analysis of variance'
N O V A analysis of covariance*

900

+ ..
 20.10 Statistical ~ ~ r n b and
o ~ sAbbreviations

Symbol or
Abbrmiation Description
alpha, probability of type I error
confidence coefficient
beta, probability of type I1 error; or population
regression coefficient
power of a statistical test
sample regression coefficient
co&dence interval*
coefficient of variation (~1%)
x 100'
difference
degrees of freedom (v is the international symbol55
and also may be used if familiar to readers)
Mahalanobis distance, distance between the means
of 2 groups
delta, change
delta, uue sampling error
epsilon, true experimental error
exponential
expected value of the variable x
frequency; o r a function of;'usually followed by an
expression in parentheses, eg, f(x)
F test, ratio of 2 variances, with df = v1,v2 for
numerator and denominator, respectively, and
(I - a) = confidence coefficient
.-
likelihood ratio X2
null hypothesis
alternate hypothesis; speclfy whether 1- or 2-sided
kappa statistic
lambda, hazard function for interval i; eigenvalue;
or estimate of parameter for iog-linear models
Wilks lambda
natural logarithm
logarithm to base 10
multivariate analysis of variance*
~x)pill:itionmean
size of a subsa~nple
rt ) r . ~ l s~mplesize
t ~ o Symbols
l and Abbrw~at~onr A
:1
$b.n1001or
Abbnzwfron Descnptlon
4 .I

OK odds ratio'
P statistical ~robabilitv
X: test or statistic, with 3 df shown as an example
r bivariate correlation coefficient
-v 11

R multivariate correlation coefficient .p

si
r2 bivariate coefficient of determination
R~ multivariate coefficient of determination ,+
RR relative risk* S-
I
P rho, population correlation coefficient
!
SD standard deviation of a difference D
sample variance
sigma squared, population variance
G sigma, population SD
SD standard deviation of a sample
,r--
SE standard error
3!
SEM standard error of the mean
<I
t Student fi s~ecifva level. df: 1-tailed vs 2-tailed
T Kendall tau
T2 Hotelling statistic .:r.pi
--9
U Mann-Whitney U Wdcoxon) statistic ,r-
-4
jZ arithmetic mean
z z score .

ACKNOWLEDGMENTS Y

Principal authors: Margaret A. Winker, MD; updated by Stephen J. Lurie, MD,

Dedicated to George W. Brown, MD, whose patient but persistent teal
ied to this chapter.

Theodore Colton, ScD; Peter Cummings, MD, PhD; Robert M. Golub, MD; and E;
Vaisrub, PhD, for reviewing prior versions .of this chapter.

1. Partington A, ed. l%e Oxford Dictionary of Quotations. 4th ed. Oxford, ~ngland?
Oxford University Press; 1992. %
2. Haynes RBI Mulrow CD, Huth EJ, Altman DG, Gardner MJ. More informative abstr
revisited. Ann Intenz Med. 1330;113(1):69-76. *'3
3. Guyan G, Rennie D, eds. Users'Guides to the Medical Literature:A Manual for Eoide
Based Clinical practice. Chicago. IL: AMA Press: 2002:7.
 20.10 Statistical Symbols and Abbreviations

4. Moher D, Schulz KF, Altman D; for the CONSORT Group. The COSSORT statement:
revised recommendations for improving the quality of reports of parallel-group ran-
domized trials. JAMA. 2001;285(15):1987-1991.
5. Campbell MJ. Extending CONSORT to include cluster trials. BMJ. 22004;326(7441):654-
655.
6. Weijer C, Shapiro SH, Cranley Glass K. For and against: clinical equipoise and not the
uncertainty principle is the moral underpinning of the randomised controlled trial.
BMJ 2000;321(72263):756-758.
7. Hellman D. ~vidence,-belief,and action: the failure of equipoise to resolve the ethical
.tension in the randomized clinical trial. J Law Med Ethics. 2002;30(3):375-380.
8. Meinert CL. Clinical'Trials Dictionary: Terminology and Usage Recomme~zdatiorzs.
~altimore,MD: Harbor Duvall Graphics; 1996.
9. DeAngelis CD, Drazen JM, Frizelle FA, et al. Clinical trial registration: a statement from
the International Committee of Medical journal Editors. J A M . 2004;292(11):1363-
1364.
10. Piaggio G, Elboume DR, Altman DG, Pocock SJ, Evans SJW; for the CONSORT Group.
Reporting of noninferiority and equivalence randomized trials: an extension of the
CONSORT statement. JAMA. 2006;295(10):1152-1160.
11. D. Moher D,Schulz KF,Altrnan DG, for the CONSORT Group. The CONSORT st:ltC-
ment: revised recommendations for improving the quality of reports of pa~tllcl-
group randomized trials. Ann Intern Med. 2001;134(8):657-662.
12. Rossouw JE,Anderson GL, Prentice RL, et al; Writing Group for the WWmcn'?; Hc:tlrh
Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy
postmenopausal women: principal results from the Women's Health Initkttivti ran-
domited controlled trial. JAMA. 2002;288(3):321-333;
13. Moher D, O l k i I. Meta-analysis of randomized controlled clinical trials: a concern ti)r
standards. ]M.1395;274(24):1962-1964.
14. Bailar JC 111. The practice of meta-analysis. J Clin Epidemiol. 1995;48(1):149-157.
15. Shapiro S. Meta-analysis/shmeta-analysis.Am J Epidemiol. 1994;140(9):771-778.
16. Pettiti DB. Of babies and bathwater. Am JEpidemiol. 1994;140(9):779-782.
17. Greenland S. Can meta-analysis be salvaged? Am J Epidemiol. 1994;140(9):783-787.
18. Chalrners TC, Lau J. Meta-analytic stimulus for changes in clinical trials. Stat ~Metbvrls
Med Res. 1993;2(2):161-172.
19. Jadad AR, McQuay HJ. Meta-analyses to evaluate analgesic interventions: a systematic
qualitative review of their methodology. J Clin Epideiniol. 1996;49(2):235-243.
20. Sampson M, Barrowman NJ, Moher D, et al. Should meta-analysts search EMBASE in
addition to MEDLINE?J Clin Epidemiol, 2003;56(10):943-955.
21. Eastcrhrook I'J, Berlin J, GoPll;~n R, Matthews Dl<.I'i~l~lic;~tionI ~ i i in
~ sclinic;~lrcsc~lrch.
Luncet. 1991;337(8746):867-872.
22. Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews.
BMJ. 1994;309(6964):1286-1291.
23. Gerbarg ZB, Honvitz RI. Resolving conflicting clinic;~lrri;~ls:g~~idelincs for nlCt;c-
analysis. J Cli11!$ide~tliol. 19XX;*lI ( 5 ) 502-509.
24. Thompson SG. K'hy sources of hctero~rnciry111 n~c~t.~-nn:~lv.ii.< >hr>ul<I Irt- invr.sr~y;~!c.tl
BMJ. 199.1;30()(61(~5):1351-l?ii.
25. Bero I-, Rcnnie r) T - 1 1 ~C<.KIIKI~CC ~ l l . i f ~ ) r : ~ r~~ oI rVl ~ . ~, ~~~ ,; iI ~~r l~~ ..~ ~n i cr l~ ~ r i ~ .
s<~i>in;rtir~p
\ptc.ln.l(lc rc,vlr:w\ l)fthe r-ftc-c.t\ of I\c;iIrIl c-:lrc, ,/..I.\I/I I(?)i.2-.4(2.1~l c ) A i .
19.W
Statistic:al Symbols and Abbrev~at~onr

26. Udvahelyi IS. Coldltz C A , Rm A. Epsrrln Ail. Cosrcffm~

analyses in the medical 11rer-ture:are the methods being u.xd cmrrectly? .4rlrr I
Med. 1992;116(3):238-244.
27. Kassirer JP, Angell M. The Journal's policy on cost-effective
1994;331(10):669-670.
28. Hill SR, Mitchell AS, Henry DA. Problems with the interpretation of pharmacoe
nornic analyses: a review of submissions to the Australian Pharmaceutical Bene
Scheme. J M . 2000;283(16):2116-2121.
29. Russell LB,Gold MR,Siege1JE, Daniels N, Weinstein MC. The role of cost-effective
analysis in health and medicine. J M . 1996;276(14):1172-1177.

1996;276(16):1339-1341.
31. Drummond MP,Jefferson TO. Guidela ,esfor authors and peer reviewers of econ
submissions to the BM/. BMJ. 1%;313(7052):275-283.
32. Drurnmbnd MF, Richardson WS, OBrien BJ, Levine M, ~ e ~ l ' a D;nd
Based Medicine Working Group. Users' guides to the medical literature: how ro
aiticle o n economic analyses of clinical practice, A: are

cost effectiveness into evid

vices. Am J Ptw Med. mi;2m)(~~ppl):36-43.

accurate reporting
2003;58(8):57.5-580.
36. American Assodation for Public Opinion Research. Standard
positions of case d e s and outcome rates for surveys. http:
/pdfs/standarddefs_4.pdf. Accessed August 1,2006.

1992.

Scientific & Technical; 1990. .

39. Glantz SA. P r i m of Biastatistics. 2nd ed. New York, NY: McGraw-Hill Book Co
1981:
40. Reigelman-RK, Hirsch @. Studying a Study and Testing a Test. 2nd ed. ~ o s t o n ,
. Little Brown & Co Inc; 1989.
41. Bland JM, Altman DG. Statistical methods for assessing agreement between two
methods of .clinicalmeasurement. Lancet. 1986;1(8476):307-310.
42. Last JM.A Dictionary oJEpidemiology. 3rd ed. New York, NY:Oxford University P
1995. .. .

1997.
44. Everitt BS. Z3e Cambn'dgeDictionury ofStatistics in the Medical Sciences. Cambrid
England: Cambridge University Press; 1995.
 20.10 Statlstrcal Symbols and Abbrevlat~onr

45. Homedes N. The dix~l>ility-;~dji~srccl life yc:lr (1)hl.S) ilt-finit~on.mc;l.\urclllc.nt .tncl

potential use. h t t p : / / ~ ~ . w o r l d b a n k . o r g / l ~ t m l / e ~ o r k p
/wp-00068.html. Accessed April 30, 2005.
46. Ingelfinger JA, Mosteller F, Thibodeau LA, Ware JH. BiosIuIislics it? Clit~icolAft.clicitic,.
3rd ed. New York, NY: ~c~raw- ill Book Co Inc; 1994.
47. Hosmer DW, Lemeshow S. Applied Logistic Regressiott. New York, hV: John Wile! &
Sons Inc; 1989.
48. Everitt BS. tati is tical Mefhodsfor ~edicai'1nuesti~ations. 2nd ed. New York, NI':john
Wiley & Sons Inc; 1994.
49. Colton T. Statistics in Medicine. Boston, MA: Little Brown & Co Inc; 1974.
50. Guyatt G, Sicken D, Taylor DW, et al. Determining'optimal therapy: randomized trial
in individual patients. N Engi J Med. 1986;314(14):889-892.
51. Zhang J, Yu KF. What's the relative risk? a method of correcting the odds ratio in
cohort studies of common outcomes. JAMA. 1998;280(19): 1690-1691.
52. Scherer RW, Dickersin K, Langenberg P. Full publication of results initially presented
as abstracts: a meta-analysis. JrlMA. 1994;272(2): 158-162.
53. Pope C, Mays N. Reaching the. parts other methods cannot reach: an introduction to
qualitative methods in health and health services research. BMJ. 1995;311(6996):42-45.
54. Brown GW. Standard deviation, standard error: which "standard" should we use?
AJDC. 1982;136(10):937-941.
55. Geng D. Conventions in statistical symbols and abbreviations. CBE Views. 1992;
15(5):95-96.

ADDITIONAL READINGS AND GENERAL REFERENCES

Friedman LM,Furberg CD, DeMets'DL. Fundamentals of Clinical Triak. 3rd ed. St Louis,
MO: Mosby-Year Book Inc; 1996.
!
Norman GR, Streiner DL. PDQ Statistics. 3rd ed. Philadelphia, PA: BC Decker Inc; 2003. !
Sackett DL, Haynes RB, Guyatt GH, Tugwell P. Clinical Epidemiology: A Basic Science for
Clinical Medicine. 2nd ed. Boston, MA: Little Brown & Co Inc; 1991.
Streiner DL, Norman GR. PDQ Epidemiology. 2nd ed. St Louis, MO: Mosby-Year Book Inc;
1996.
Mathematical Composition

Copy Marking Expressing Multiplication and Division

21.7
Displayed vs Run-In Commonly Used Symbols

Typography and Capitalization

21.4 21.9
Exponents Punctuation
21.4.1 Fractional Exponents vs Radicals
21.4.2 Negative Exponents . . 21.10
21.4.3 Logarithmic Expressions Spacing With Mathematical Symbols

Long Formulas

Mathematical formulas and other expressions involving special symbols, character

and adherence to typographic conventions and capitalization rules in equations

require special note (see also 8.5, Punctuation, Parentheses and Brackets, and 22.0,

elements of equations:

&& x2
Inferior ~2 x2

Inferior to superior PI

Superior to superior
Inferior to inferior
Superior to inferior
Inferior with superior and subinferior

In expressions that involve both superscripts and subscripts, the subscript is usually
aligned directly under the superscript. In online publication, this alignment can gen-
erally be created only by using an image.

907
21.3 Stacked vs Unstacked

Displayed vs Run-In. Si~nplcfor~ilulasmayremain within the texr of the manuscript

if they can be set on the line:
The pulnlonary vascular resistance index
PVRI = (MPAP - PCWP)/CI, where MP
pressure; PCWP, pulmonary capillary
Long or complicated formulas sh
symbols and signs should be ma
as copy or as prepared art, depending on th
of software for equation preparation. For online publications, formulas that require
more than 1 line must either be shown as an image or depicted by means of spe-
cialized mathematical software.
Whether run into the text or centered, an equation is an element of the sentence !
that contains it. Punctuation and grammatical rules thus apply to it, just as they do to
all other sentence elements. For example, if the equation is the last element in a
sentence, it must be followed by a period. If there are 3 equations in a list, they must
be separated by commas and the final equation must be preceded by "an&"
If there are numerous equations in a
each other or are referred to after initial presentation, they should be nu
consecutively. Numbered equations should each be set on a separate line, centered,
with the parenthetical numbers set flush left.
(1) x = rcos8
(2) y = rsin8
(3) z = (x+y)
Standard abbreviations should
Abbreviations, Units of Measure). For sho
express an equation as words in the ru
formula:
Attributable risk is calculated by subtracting the incidence among the .
nonexposed from the incidence among the exposed.

Stacked vs Unstacked. Stacking of

inator by a horizontal line) should
slash in place of the horizontal lin
ation, Forward Slash [Virgule, Solidus], In Equations).

y = (XI+ x~)/(xI- x2) instead of y = *

Xl - x2

Whenever a fraction is unstacke

called "fences" in mathematical notation) should be used as appropriate
ambiguity. For instance, the expression
b+ c
a+-+e,
d
if written as a + b + c l d + e, is
such as

C
 21.4.3 Logarithmic Expressions

The expression's meaning is unambiguous if set off as follows:

. . a+[(b+c)/dl+e.
Parentheses should be use$ to set off simple expressions. If additional fences are
needed for clarity, parenthetical expressions should be set off in brackets, and
. bracketed expressions should be set off with braces. Note that parentheses are thus
always the innermost fences (see In Formulas in 8.5.2, Punctuation, Parentheses and
Brackets, Brackets). All fences should be present in matched pairs.
{[(a+ b)/cl+ [(d + e)/fl)+g

Exponents

Fractional Exponents vs Radicals. Use of radicals may sometimes be avoided by

substituting a fractional exponent:
(a2- @)*I2 instead of d m .
As with unstacking fractions, if clarity is sacrificed by making the equation fit within
the text, it is preferable to set it off. For example, E = 1.96 {[P(1 - ~ ) l / r n I ' / ~fits
within the text, but the centered

might be more easily understood.

Negative Exponents. A negative exponent denotes the reciprocal of the expression.

as illustrated in these examples:

A negative exponent may simplify some expressions within running text:

A .
may :~lsoI,e written as A(.X+.)J)-' o r A / ( ; Y + . ] ' ) ' .
(x +.Y)~

Logarithmic Expressions. The term log is an abbreviation of logarithm. A system o f

logarithms may be based on any number, although logarithmic systems based on the
numl~ers10, 2, and the irr:~tionnlnumber e are most common. The base should be
su1)scripted ;111dfolio\\. tllc \\.orcl log. In the following examples, note that logarithms
. ~ r c:~l\va!.s c.onlpurc.tl Irt ,rn ~.xpolientsof the number that forms their basis.
 __ _.

,lng M u l t i p l i c a t i o n a n d Division

Logarithms based on e (which is approximately 2.71) are called natu

and are often represented as In.
In 2.71 = 1
The terms "8"and "exp 2'are identical in meaning and are interchangeable
The latter is preferable for constructions involving additional subscripts or super
scripts. For instance, "exp(2 - 1)" is identical to " 8 - I ,"but the former is preferrq
because it is easier to set and to read. I<
i8
I Long Formulas. Long formulas may be given in 2 or more lines by breaking them a
operation signs outside brackets or parentheses and keeping the indention the s q
whenever possible (some formulas may be too long to permit indention). If line
begin with-an operation sign, they should be lined up
with the first character to
right of the relation sign in the line above.

However, if a formula loses comprehensibility by being unstacked and broke

and/or if it fits the width of the column, it is preferable to leave it stacked.
-
Percent Excess Weight Loss = (Baseline Weiht - Ideal Weight)
..*-- ...
Baseline Weight - Ideal Weight
..-. 4
.t.*

Expressing Multiplication and Division. The produa of 2 or more terms?'$

cluding units of measure, is conventionally indicated by a raised multiplication dot
(eg, 7 kg m 3 or by 2 or more characters closed up (eg, y = mz+ b). ~ o w e v ' s i i
scientific notation the times sign O<) is used (eg, 3 x lo-'' cm) (see 18.4.4, Unit:
Measure, Use of Numerals With Units, Multiplication of Numbers). An asterisk s
not be used to represent multip
rams. Note: However, there may be
provide the reader with the exact e
A forward slash, a horizontal line, a negative exponent, or the wordper may.
used to express rates, which are generally obtained by dividing one unit by anothi
For example, velocity (meters per second) may be expressed as T V ~

m .
m/s or -
s
or m-s-'

Complex rates involve division of a rate by another unit. Complex rates that
frequently are conventionally indicated by. 2 slashes in the same expression, eg
...L.,7

The dose was 25 -mg/kg/d. ;lt3

23
Plasma renin activity was 1.3 ng/mL/h.
i'
..L

~cceleratioia t the surface of the earth is 9.8 m/s/s (or 9.8 rn/s2). :)
'?A

Most complex rates, however, are developed for particular applications. For ql
these less commonly used rates should be expressed as "alb per c." For instance
The infusion was 2 mL/kg per minute. I
 21.7 Commonly Used Symbols

Negative exponents may also be used to express such a rate when appropriarc:
2 m~.kg-'.min-' (see 18.2.2, Units of Measure, Expressing Unit Names and Syrnln,ls.
Products and Quotients of Unit Symbols). Common sense and clariry should guitlc
this decision.

Commonly Used Symbols. Some commonly used symbols are as fo1lon.s:

Symbol Description
> greater than
.? greater than or equal to
>> much greater than
< less than '

I less than or equal to

<< much less than
f plus or minus (This symbol should not be used to
indicate variability around a central tendency (eg,
"The control group had a mean [SDI value of 12 [7l," not
"The control group had a mean of 12 f 7.")
L' integral from value of a to value of b

5
a=l
summation from U = 1 to a = 30

a=l
i? product of a = 1 to a = 30

A delta (change, difference between values)

f function
# . not equal to
x approximately equal to
- similar to (reserve for use in geometry and calculus;
use words in other cases where "approximately" is meant)
=
- congruent to
-
- defined as
co infinity
! factorial, eg, n! = rz(n - 1) ( n - 2 ) . .. I
he following symbols are usually reserved for specific values
IT pi (approximately 3.1416). Do not confilsc with ilppercasc n.
e base of the system of natural logarirhins (npproximarcly 2.7183). Sec
21.4.3, Exponents, Logarithmic E~pressrons In sr;~ti.;rlc;~l cclir;~tions.
however, "e" may ;~lsorepresent the v r r o r tcrnl irl .I rcgrc53lon
equation.
i the square root ot' - 1
For a list o f ;rddition;~lsymln>l\ rt1.11 .lrr. rl\c.tl In ,r.ir~\r~c b. \cc.70 10. 4tl1(]!. I ) t , y ~; g
~ n~r ~
l
Statistics, Statistic;~lSynlln,I. .ir~,l; I ~ J ~ ~ . C~ . 1\ .,I . I I ~ (
2 1 9 Punctuat~on

The tollon.~nl:drc cs;rmplc. oI'rhcw c t ~rlilllonlyuwcl rrl~~t~~.lnarical

13
> 10' CFUs/rnL J13 2.x dx
24.5 f 0.5 F-J?
L z 2 x 10" m r ! (n - r)!
f(x>=x+hX (8 + e-")/I2
y = &/dr Y=p,+P2+e
P < .001
n
.
kg m s-2
C aixi
i=O

x + $7 + 2 + $ + . . . + 5 (note that in this case the operation sig

on both sides of the ellipses)
Online journals shc-ald ensure that any symbols rendered in HTML a
across most commonly used browser platforms. An image should be
incompatibility is possible. The World Wide Web consortium (http://www.
provides updated information about browser compatibility issues. *

Typography and Capitalization. 'In general, variables, unknow

constants (eg, x, y,z,A, B, C ) are set in italics, while units of measure
m), symbols Cincludiing Greek characters [see 17.0, Greek Letters]), and
set roman. Also, subscripts or superscripts used as modifiers are set
Ci, = clearance of inulin.
Arrays (A) and vectors 0 should be set boldface. Mathematical functions, su
sin, cos, In, and log, are set roman.
V =oai+bj+ck

A=
[
a11 a12 a13
a21 a22 az3
a31 a32 a33 I .
,For equations that are set off from the text, the words and letters sh
and the equation should be capitalized by the same rules that apply t
Capitalization, Titles and Headings):
...
Efficacy Money Saved by Its Use
U=
- X
Toxicity Risk Cost of Contrast Medium

Age-Specific Attributable Risk = (RR( - l)/RRI

Punctuation. Punctuation after a set-off equation is helpful and often cla&

meaning. Display equationsaare often preceded by punctuation.
In the linear quadratic equation model, the survival probability for ce
receiving a j increment of radiation, D,,is as follows:

S = exp( - - ID,),
where a and /? are the parameters of the linear quadratic equation mode

-
, ..-'
-.
-. ...
+
4 ' '-.
I Do not use periods after a set-off equation if the equation is preceded by a period.
I
!I Spacing With Mathematical Symbols. Thin spaces should be used before and
after the following mathematical symbols: f,
n, C ,and I.
-
=, <, >, 5 ,2,+, -, + ,X, ., z , , n, I,
a f b a=b a+b a-b a s b ax6 a.b a>b b<a
Symbols are set close to numbers, superscripts and subscripts, and parentheses,
brackets, and braces.

ACKNOWLEDGMENT
Principal author: Stephen J. Lurie, MD, PhD

ADDITIONAL READINGS AND GENERAL REFERENCES

Style Manual Committee, Council of Science Editors. Scientijc Style and Format: 7be CSE
Manual forAuthors, Editors, and Publishers. 7th ed. New York, NY:Rockefeller University
Press, in cooperation with the Council of Science Editors, Reston, VA; 2006.
Swanson E, O'Sean A, Schleyer A. Mathematics Into Type. Updated ed. Providence, RI:
American Mathematical Society; 1999.
 22.1 22.4
Basic Elements of Design Layout

22.2 22.5
Typefaces. ~onts,and Sizes Specific Uses of Fonts

-
22.5.1 Lowercase
22.3 22.5.2 Capital (Uppercase)
Spacing 22.5.3 Boldface
22.3.1 Letterspacing 22.5.4 Italics
22.3.2- Word Spacing 22.5.5 Small Caps
22.3.3 Line Spacing

Typography is the efJicient means to an essentially,

and only accidentally esthetic, end,for the enjoy-
ment of patterns is rarely the reader's chief aim.
. . . any disposition ofprinting material which,
whatever the intention, has the effect of coming
between author and reader is wrong.
Stanley Morison
(inventor of Times New Roman font)'

- Good design is a blend of function and form, and

the greater of these isfunction. nisis as true of
typographyas it is of an opera house or space shuttle.
- Typographyfails if it allows the reader's interest to
decline. It fails absolutely fi it contributes to the de-
struction of the reader's interest.
I Colin ~ h e i l d o n '

Typography is broadly defined as the composed arrangement and appearance of text

and other elements on a surface that involves elements of design. The editor and
graphic designer oftenlcooperate in the process of creating the typography and design
for a book, monograph, or journal (in print or online), with the goal of achieving a
balance of form and readability.
According to typographer Edmund Arnold, good design and typography for
English-language publications follow the linear flow of the Latin alphabet and sup-
port the act of reading.' The English language is read from left to right and from top
to bottom. According to Arnold, when a reader of such language begins to read a
printed page, the eyes first fall naturally to the top left corner and then move across
and down the page, first from left to right and then in a right-to-left sweep to the next ex.+

line, until reaching the bottom right corner. Any design or typographic element that
forces the reader to work against this natural flow (reading gr:iviiy) interrupts the

917
22.1 Basic Elclrnents of Design

reading rhythm and should be avoided.' Wheildo

which half of the participants read an article wi
"reading gravity" principles and half read the same article but with a design
not follow these principles. Rates of comprehension for those reading th
designed to comply with the principles of reading gravity were better (67%
19% fair, and 14% poor) than those reading the same article that disregard
principles of reading gravity (32% good, 30% fair, and 38% poor).'
Typography for reading on a computer or other digital medium should follo
the basic principles of reading as described above. There. are a number of shared
design considerations (eg, consistency and size
phasis, subheadings, or calling out citations
about overly long or wide mbles o
'ditional attributes and concerns that are not s
that address a different set of reading, browsing, and searching habits. For exam
Web page must work across different computer platforms, browsers, and screen
and the publisher cannot control how the typographic elements (such as type
font, size, and color) appear on different users' screens; the Web is desig~edfor
tera'ctivity and scrolling, solinks and navigati
and brightly lit screens may lead to eye strain
different format than the same text designed for print. This chapter focuse
on typography for the printed page and for Latin character sets. Resources
and typography for the Web are listed amo
References at the end of the chapter. Ma
design, typography, and composition m
Glossary of publishing Terms.

1 Basic Elements of Design. Good des

invites and leads the reader through
legibility and ~om~rehension."~ The basic elements of.design that affect typograp
include the following:
Contrast: This refers to the contra
small units'of information (such as title and -byline,side heads and
text). In addition, the evenness of darkness or blackness of letters
affects legibility; this evenness de
spacing between letters, words, a
n.Rhythm: The rhythm of the design refers to repetition of similar units, in
opposition and juxtaposition, eg, spacing and proportion of type to the pag
other design elements, and repetition of graphic contrasts or similarities.
Size: The size of type and other elements affects legibility and the overall
pearance of a composed page. The size relationships within the design refer to
optical images of the type ahd gra
manners in which they appear o
Color: In this context, color has
type (letters and characters) and
nonblack colors, which attracts
publishing; however, the use of color for these purposes is limited.
 22.1 Basic Elements of Design

Movement and Focal Points: The elements of a page should guide the reader's eye
along the lines of composition unconsciously, from large to small, from top to
bottom, from left to right, from dark to light, and should follow the gravity of
reading.
In scholarly publishing, a number of typographic and design elements, such as pre-
scribed text format, titles and headings, bylines, abstracts, tables, figures, lists, equa-
tions, block quotations, and reference citations and lists, must be considered and
incorporated. Consistent use of typographic style within a specific work (eg, journal,
book) enhances readability and is recommended for scholarly publications.
This often requires style sheets based on standards for a specific
publication.
The examples of journal pages shown in Figures 1 and 2 include some of these
typographic elements of design as they are used in the print versions ofJAMA and the
Archives Journals.

T&-+ Prevalence of Overweight and Obesity

in the United States, 1999-2004
C p I " I. we,,fl,n
Mm m D . G d .WPH
L*ZR h i i n , FWl ~ ~ ~ w l d r a n s l t ~ o l ~ ~ d ~ d ~ t
~ r & - ~ l m p m * ~ e ~ a ~ m R D h-d-nd-hdum
J. l'ahlr. M4 MP11
bhrrine P.tl* PhD

- -)nu-
c m m

livter&2 tc
related,
M &

Figure 1. Layout o f page 1 o f a JAMA article.

2 2 2 Typefaces. Fonts. and Slzer

Title- An Obsc~vationi~l
Study of Cognitive Impairment
in Amyotrophic Lateral Sclerosis

Figure 2. Layout of page 1 of Archives journal article.

limes New Roman Italic

Times New Roman Bold
limes New Roman Bold Italic
Figure 3. A family of type.
 22.2 Typefaces. Fonts, and Sizes

The typeface for the body text of this book is ITC Garamond Light, and Frutiger is
used for the chapter titles, heads, and subheads.
There are 2 common forms of typeface: serif and sans serif (Figure 4). Serif
typefaces (eg, Times Roman) have a short, light line (serif) projecting from a letter's
main strokes. Sans serif typefaces (eg, Arial) are unadorned letters without the short
line projections. Serif type is generally believed to be more readable than sans serif
type for large amounts of print text because serifs on the letters guide the eyes along
a line of copy and the modulated thick and thin strokes of serif types help distinguish
individual letters and words to'be Thus, for print publications, serif type is
generally used for body text because of its readability; sans serif type is used for
contrasting and complementaryelements and to attract attention (eg, titles, heads).'"

Figure 4. Serif and sans serif letters.

The font for a publication typically includes 7 styles: roman lowercase letters.
roman capitals (uppercase letters), boldface capitals, boldface lowercase letters, italic
capitals, italic lowercase letters, and small capitals. Each of these styles may also
include different weights or heaviness of stroke (eg, light, regular, heavy, black, extra
bold, condensed). Each font also includes numerals, punctuation marks, commonly
used symbols and diacritical marks (eg, accents, tildes, umlauts), and ligatures and
diphthongs (2 or more letters joined together); ligatures (eg, w andfl may be vowels
and consonants, whereas diphthongs (eg, e)are vowels only. It is important to note
that not all serif and sans serif typefaces share similar characteristics and not all
typefaces include all font characteristics. For more discussion on typeface char-
acteristics, see Binghurst's 'licleElements of Typographic style.*
The size of type is conventionally referred to as its point size. The height of
characters in a specific font is measured in points; each point is approximately g,
inch, 12 points equals 1 pica, and 6 picas equals 1 inch. The height of a letter in a
specific font is measured by its x-height (so named because it is derived from the
height of a lowercaseXI.The x-height is the distance between the baseline of a line of
1 type and the top of the main part of the lowercase letter, not including ascenders and
descenders. An ascender is the part of a letter that rises above the x-height of the font
I
as seen in the letters b, d,J; h, k, and t. A descender refers to the pan of the letter that
dips below the baseline (eg, p, q, y, and Q) (see Figure 5). The width of a specific
character is measured by pitch, which refers to how many characters can fit in an inch.
Ascender
.... ............................. X-height
Baseline

Figure 5. The x-height, ascenders, and descenders of letters i

I
Typefaces are commonly ;lt.:iil;ltdc :ind uscd in (,-point to 7'-pc,int sizes. 'fylx.
-.. - i9
sizes below 14 points:Ir~.pc.n~r;lIly t~wtlf o r IMKI). ~ c s .~ncI
f . xi/- of 1 . 1 ~ ) ( ' I l j [ , ; ~ n c;l~ t x ) t L .
are g c n e ~ ~ lt~svtl
l y f o r tlly,1;1~ Ol,(irjl;rlI,c,cl!.-tcst[yl)c
r!.p-x ( C S , tirlc.5 ;~nclI~c.;~cllinc..~).
sizes range I)clwr.cn 0 . ~ r l c l12 ~>c)ir>th' The ~ n ~ i sizc
n t of t l ~ c .1 ~ xtesf
1 ~for filisl,tx,k 11.
975, 1n Figttrc. I , !!I(* {h I I ~ V, I / ~ , (,t f I > t -I n d y tc*xf 15 10. :111d111~. \17<' of I I I ~tIflr.i x 2 0
 1 lxa1 JOJ 'J~A~MO .8u!8ueq=un
H pue paxy aq ~ e Su!~eds
w p l o '(paypsn!un)
~
pa88a~]as 1xal JOJ .Bqxdssanal aqj JO ssau~qB!~ JO ssauuado aql pue ' a ~ e j
a q JO htsuap JO ssauylap a q 'alhsadh E JO q p ! pue
~ az!s lu!od a q Lq palel
s! l e q SPJOM uaamaq 8qseds paquualapa~daAeq sa3ejadL.L - 6 u p e d ~p l o ~

aqsadXt aql ~erga)oN -8moedsrauq

Gu!oeduanal ON

-8upedsraual a q 8 q 8 u e p Lq srwm ~w.pa d h JO auq

a m m s d d e a q q sa8uerp 30 sa~durexa303 9 asn8!~aas s-,'hg!q@al 8upnpas il
8 w a x -aurosaq 1
I

I
wsn! sasn I- ul 'a!) I:
3y 03 xk.uaue ue q w d e Jaquy so satpa801 Jasop =anal
aamaq 8 u p d s ~ U01 pasn
I uayo q (sraueJerp uaafi
.uo!suarla~duro~ Supgas ~ a L m p pue &!sap !
!
p a aqs ad& lnq '8qsedsraual ~ e q d so3 o
e a s a u .paxm@qaq plnoqs ssauaI uaawaq sa~edsayl ' A p a p ~
srauaI uaawaq a x d s atp 01 srajaJ % q x d s r a u q-6upedua))a')

z essaqo a q JO ~uapuadapqs! asaq JO auou fsaql

'SPJOM 'sraual uaawaq 8 q ~ d asw uo spuadap ad& 30 h9qepeal.l .6upad~
I
- a ~ a l d wL~sea
o ~ 01 aka a q JOJ 8uol o o awl ~ t? .
sllnsas ap!M dpl s! l e y avo aI!qM 's8qpua aqI 1~uopeuaqdAq aA!ssaDxa u! s l ~ n s a ~
ossw 001 q leyl q p ! uwnlw ~ e 'asm q3ea UI 'aug sad a ~ q a d aw h JO ( S J ~ I D W E ~ D
L l ~ 1 t ? ~ o ~ daaqiqdla
de) y , a~l e p o i m o plnoys
~ ~ q p ! uwnlo~ ~ a q 1eq JO leap!
aug sad ssa~x.~erp 05 01 op l a p l s a s n s s u o ! ~ u a ~ u'slewno!
o~ Ll~eloqxu! pasn
~ n ~ BsU U O Juu1n~o3-ald~1nus JOA -sus!sap uurn1o~-a1Bu!s01 paqns lsaq aJe
l ~ w e JOq ~s'aqwnu saqB!~;uurnloD a q 30 au!l I uo ly (saeds pue uo!~cnmund
pnpq) s ~ a l ~ a r SL e q01~ 59. uaqM lsaq s! h!l!qepea~ 3eql asaBns uopua~uosa u o
SA leuno!) uopeylqnd.pue ' ( u w n ~ o sl o ~ '-z '-I 'Ba) ~euuojuwnloD 'aqs ad&
h a q BU!~JODDEsa!JeA Jaqwnu leuqdo a q l ,.,'(sJaA!J 'srappel 'Ba) s p ~ o , ~
amaq s a ~ e d saqqfi Bqpw]s!p pue ~ ! ~ w q a! pa~lods
~ aSed e JO uo!~euaqdAq
saDxa p!oAe 01 pue syooq pue sap!lre leu~no!jo 8u!pea~jo uo!suaqa~druo~
paads JOJ auq lad sJalDeJaqDJosaqmnu leru!ldo ur: sa%ns suo!luaAuoD a l d ! ~ l n ~
.au!od 21 s! ura a q 'adh lu!od-z~101 !nu!od 6 s! ma aql 'adh lU!0d-6 u! 'aldwexa
, ,;w,, aseDJaMol e JO az!s aql Allesy>ads'az!s yi!.~
J sa!JeA a n p asoqilb a d h jo az!s
aa JOJ alnscaw r: s! rp1q.N .nu.>u! PaJnsrnul s! ad.(] JO Hu!xdr; [nuoz!Joq a i u
.eaJc .d.Q 1\11 1 0 qldap .at[] pur .au!l r: JO qi3ua1 2111 ~ J ~ P C I L 01
U p.xn PI r.mi
q ~ .(8u!pr1\)
, .xl.il jo P.>UII i1>.3\u.x\ a~rcf.;.a111 > J ~ < ~ . I U01I pxn (SIC . ~ J Cn u q
 22.3.3Line Spacing

set flush left and flush right (justified), the spacing may need to be more flexit~lc.For
justified text, an average word space of a fourth of an em is ideal, with a minimuln
and maximum range of a fifth of an em to half an em.2

Line Spacing. Line spacing refers to the vertical distance between the base of 1 line of
text and the base of the next line of text. Line spacing is traditionally known as
leading for the strips of lead once used between lines of printer type. The space
between lines of type is measured in points. ~ e n e r a l lleading
~, is 20% larger than the
copy size.3 For example, 10-point copy would be set o n 12 points of leading or line
r
spacing (10/12), as is shown for the body copy in Figure 1. Optimal line spacing
requires consideration of the type size, layout density, and line length. Generally,
longer lines call for increa~edline spacing for optimal readability. See Figure 7 for
different examples of changes in line spacing that change the appearance of the text.
More open line spacing also calls for wider margins; tighter line spacing can be
done within narrower margins.

No line spacing
Line spacing (or leading). Note that
the type size and style are identical in
each line; only the space between the
lines changes.

I-Point line spacing

Line spacing (or leading). NO& that
the type size and style are identical in
each line; only the space between the
lines changes.

2-Point line spacing

Line spacing (or leading). Note that
the type size and style are identical in
'
each line; only the space between the
lines changes.
~igure7. Line spacing.

The conventions for letterspacing and word spacing vary depending on the
amount of spacing between lines, column width and depth, and whether the text is
justified (set as a squared-off block) or unjustified (set with a ragged right margin).
For example, a smaller type size may be used o n a wider column if the line spacink is
1
adequate for readability. The nature of the composed material will suggest whether
,
I variations in typography may be effectively used.
I
I
Layout. Layout is the arrmgement of all the elements of design and typography on
the page for optin1;il readability, taking into account the contest and aesthetic re-
quirc.rncnts of the test. To create emphasis, complernentar) typefaces and various
fonts \vithin s typcfnce may t~ Howcver, only n fc\v compatible typefaces
should he used st once. Xlultiple typcf3ces on a single p;lgc can compete for atte- ". - 4
ntion. :lrc d~>tr;lct~ng,
nnd irnpc.de readal>i~ity.'.~
T\vo ty,>cf;lr.c.>
1;) :;crif for body test
22.5 Specific Uses of Fonts

and a sans serif for titles and subheads) with appropriate use of styles, such a bol
and italics, will most often suffice for a scholarly publication.3 The typesize an
weight create emphasis or continuity, as needed. Headings and subheadings create
the outline within the text to frame the article. In page layout for a scholarly journal,
all of the elements of design and typography come together. See Figures 1 and 2 for
examples. For more details on overall design elements, see resources at the end of
this chapter.
Examples of some specific uses of lowercase and capital letters, italic and bold-
face fonts, and small capital letters are provided in 22.5, Speciftc Uses of Fonts, with
cross-references to other chapters and sections.

Specific Uses of Fonts

Lowercase. Lowercase letters are smaller than capital (or uppercase) letters and are
differently configured (eg, a, A). The term lowercaseoriginates from the earlier use of
manually set wooden or metal characters that were kept by compositors in 2 cases;
the lower case contained the smaller letters and the upper case contained the larger
capital letters.' Sentences are typically set with the initial letter of the first word of a
sentence as a capital letter and all other letters lowercase. In titles, the initial letter of
each major word is set as a capital letter and all other letters are lowercase. Some

and Headings).
Heterogeneity in Incidence Rates of Schizophrenia and Other Psychotic
Syndromes
Depressive Symptoms, Vascular Disease, and Mild Cognitive Impairment:
Findings From the Cardiovascular Health Study

I
lowercase for article titles and mixed capitals and lowercase for book titles (see also
3.9.1, References, Titles, English-Language Titles).

initial letters in the first word of sentences and for proper names. They are als
used as the initial letter of major words in titles, heads, and subheads. (Caput

that begins a paragraph and drops through several lines of text. It may be us
complicated page to draw the reader's attention to the beginning of an
chapter, or important section (see Figure 1for an example). An initial cap may
be a raised cap when the capital letter is raised above the main line of text. ,
Boldface. A general scheme of heads and side heads may call for the use of bol
type for first- and second-level heads and for first-level side heads in the t

924
 22.5.4 Italics

although heading styles and formals vary among journals (see also 2.8, Manuscript
Preparation, Pans of a hlanuscript, Headings, Subheadings, and Side Headings). For
example:
METHODS (level 1 head, flush left, bold caps)
Statistical Analysis (level 2 head, bold caps and lowercase)
Clustering Data.--(level 3 head or first-level side head, paragraph indent, run
into the text, bold caps and lowercase). '

Boldface may also be used in text to call out references to figures or tables.
Demographic data for'the participants in the study are shown in Table 1.

Italics. Iialics is a form of roman type style that slants to the right. Italics have multiple
uses. However, setting large blocks of body text in italics should he avoided because
legibility is reduced. Use italics as follows:
a For level 4 heads (second-level side heads)
When terms are described as terms, and letters as letters (see also 8.6.7, Punctu-
ation, Quotation Marks, Coined Words, Slang, and 8.7.5, Punctuation, Apostro-
phe, Using Apostrophes to Form Plurals):
The page number is called the folio.
In his handwriting the n's look like u's.
For titles of books and journals, proceedings, symposia, plays, paintings, long
poems, musical compositions, space vehicles, planes, and ships (see also 10.2,
Capitalization, Titles and Headings):
Archives of General Psychiatty
USS Constitution
Verdi's Requiem
a For epigraphs set at the beginning of a work (see the beginning of this chapter).
For some non-English words and phrases (see also 12.2, Non-English Words,
Phrases, and Accent Marks, Accent Marks [Diacritics]) that are not shown among
English terms in the current edition of Merriam- Webster's Collegiate Dictiona y or
in accepted medical dictionaries. Italics are not used if words or phrases are
considered to have become part of the English language, eg, cafe au lait, in vivo,
in vitro, en bloc.
For lowercase letters used in alphabetic enumerations of items or topics (the
parentheses are set roman): (a), (b), (c), etc.
For genus and species names of some microorganisms, plants, and animals when
used in the singular and the names of a variety or subspecies. Plurals, adiccti\.:~l
forms, taxa above genus (eg, class, order, filmily) are not it:llicizccl (sets also 15.1.1.
I
I Notnenclaturc, 0rg:lnisms :~nclI'nthogcns):
22.5 Specific Uses of Fonts

staphylococcal
Streptococcus (But: organisms, streptococcal, streptococci)
a For portions of restriction enzyme terms (see also 15.6.1, Nomenclature, Genetics,
Nucleic Acids and Amino Acids)
m For gene symbols but not gene names (see also 15.6.2, Nomenclature, Ge
Human Gene Nomenclature; 15.6.3, Nomenclature, Genetics, Oncogen
Tumor Suppressor Genes; and 15.6.5, Nomenclature, Genetics, Nonhuman Ge-
netic Terms)
er For chemical prefixes (N-, cis-, trans-, p-, etc) (see also 15.4.4, Nomen
Drugs, Chemical Names, and 15.10, Nomenclature, Molecular Medicine)
m For mathematical expressions such as lines, variables, unknown quantities, and
constants (see also' 21.0, Mathematical Composition). Numerals or abbreviations
for trigonometric functions and differentials are not italicized:
sin x = a / b
rr For sbme statistical t e w (see also 20.10, Study Design and Statistics, S
Symbols and Abbreviations):
P df z
I u
'a For the abbreviation for acceleration due to gravity, g,'to distinguish it
gram (see also 14.11, Abbreviations, Clinical, Technical, and Other Common
Terms)
n For legal cases (see also 3.16, References, US Legal References), eg, Roe v Wade
For the term sic (see also Insertions in Quotations in 8.5.2,
entheses and Brackets, Brackets)
.
a In fonnal resolutions, for Resolved
m Sparingly,.for emphasis

maSmall Caps. In this typeface style, all the letters take the shape of a capital letter,
However, in the place of lowercase letters, smaller capital letters are used. The small
caps generally, but not always, align with the same x-height as the regular r o q
face, in the same typeface. Use small capital letters as follows:
.AMand PM in time (see also 18.5.3, Units of Measure, Conventional
Unit3 in JAUA and the Archives Journals, Time)
6 BC, BCE, CE, and AD (see also 14.3, Abbreviations, Days of the Week, Months, E
Some prefixes in chemical forinulas (L for levo-, D for dextro-) (se
Nomenclature, Drugs, Chemical Names, and 15.10, Nomenclature, Mole
Medicine)

.- .- .-
- c " e,'.
-.
.!
 22.5.5 Small Caps

ACKNOWLEDGMENTS
!
Principal author: Annette Flanagin, RN, MA
I
I thank Karen Adams-Taylor and Mary Ellen Johnston,JAMA and Archives Jour-
nals, for reviewing the manuscript and providing important suggestions for im-
provement; and Chris Meyer, JAM4 and Archives Journals, for creating the figures.

REFERENCES
1. Wheildon C. T m & Layout: How Typography and Design Can Get Your Message
AcroscOr Get in the Way. Berkeley, CA: Strathmore Press; 1995.
2. Binghurst R. The Elements of ~$gra~hicStyle. Version 3.1. Vancouver, BC: Hartley &
Marks; 2005. .
3. Keane KA. Ten things editors need to know about magazine design. Editorial Eye.
2006;29(5):10-11.
4. Goldberg R. Digital Typography: Practical Advice for Getting the Tjpe You Want When
You Want It. San Diego, CA: Windsor Professional Information, LLC; 2000.

ADDITIONAL RESOURCES AND GENERAL REFERENCES

Ambrose G, Hams P. 73e Fundamentals of Typography. Lausame, Switzerland: AVA
Publishing; 2006.
Appendix A: design and production--basic procedures and key terms. In: l%e Chicago
Manwl of Style. 15th ed. Chicago, IL: University of Chicago Press; 2003:803-856.
Craig J. Designing With Type. 5th ed. New York, NY: Watson-Guptill Publishers; 19%.
Felici J. me Complete Manual of Typography. Berkley, CA: I'eachpit I'ress; 2005.
Heller S, Meggs PB. Tats on Typ: Critical Writings on Typography. New York, NY: All-
worth Press; 2001.
Lynch PJ, Horton S. Web Styk Guide: Basic Design Principlesfor Creating Web Sites. 2nd
ed. New Haven, CT:Yale University; 2001. http://www.webstyleguide.com. Accessed June
14, 2006.
Nielsen J, Loranger H. Prioritizing Web Usability. Berkeley, CA: New Riders Press; 2006.
Pocket Pal: A Handy Little Book for Graphic Ark Production. 19th ed. Memphis, TN:
~nternationalPaper Co; 2003.
. Typography. In: Kasdorf WE. l%e Columbia Guide to Digital Publication. New York. S Y :
Columbia University Press; 2003:227-246.
Web Page Design for Designers. http://www.wpdfd.com. Accessed May 27, 2006.
 23.1 23.3, '
Editing and Proofreading Marks Electronic Text Editing

23.2
Proofreading Sample

Editing and ProofreadingMarks. Corrections often need to be marked on printed

manuscripts and typeset copy. hi following marks are common in publishing and
used by manuscript editors, proofreaders, and others involved in marking copy to ix
corrected. Instructions, queries, and clarifications not to be typeset should be circled.

I Insertion and Deletion

Caret (insert)

Close up space

Correct typographical error

Delete

Delete and close up

Delete underline Word 9

Spell out

Stet text (let stand as set)

Positioning

Align

I3reak line

Center

Flush left

Hanging indent
2 3 . 1 E d ~ t ~ nand
g Proofread~ngMark,

lu\rlt!.

.\lo\c Icl1

hlove right

Lower

Raise

Transpose

Punctuation

Period

Comma

Colon

Semicolon

Apostrophe

Single quotation marks

Double quotation marks

Prime sign

Hyphen

Equals sign

Minus sign

Plus sign

Plus/minus sign

Em dash

En dash

Parentheses

Brackets
 23.1 Editing and Proofread~ngMark,

Braces

Slash

Backslash

Bullet

. Query to author

Set when known

Insert space

Insert thin space

Equalize space

Indent 1 em space

Begin a new paragraph

Run in text (no paragraph)

Style of Type

Wrong font

Lowercase

Lowercase with initial capitals @ an example

Capitalize

Set roman or regular type (lightface;

@ -
word

not bold or italic) @ or @

Set in italic type a word
Set in boldface typr @ word
-A
23.3 Electronic Text Ed~ting

Set In boldface italic type

Small caps @ word

Small caps with inlt~alfull cap~tals

a_n
-- example
- -
Subscript letter or number 2'
Superscript letter or number
5
Proofreading Sample. The following example shows how a proof was marked for
corrections and how the corrected text appears in the revised proof.

-, Unfortunate15the goal of inducing actual regression of atherosclerosis has

x e m a i n e d dusive. Most atherosclerosis tiiials have demonstrated that active
==^-modulating therapy, primarily using statin drugs, can reduce the rate of
disease p r o g r e s s i o n . w T w o small, single-cenMtrials have suggested
.= @
that statins might induce regression, but methodological issues including
small sample sue have limited the interpretation and generalization of re-
su1tsW

Unfortunately, the goal of inducing actual regression of atherosclerosis has

remained elusive. Most atherosclerosis trials have demonstrated that active
lipid-modulating therapy, primarily using statin drugs, can reduce the rate of
disease progression.12-!4~19Two small, single-center trials have suggested
that statins might induce regression, but methodological issues including
small sample size have limited the interpretation and generalition of re-
su1ts.16.17

Electronic Text Editing. Many word processing programs have text editing fu
tionality that allows users to view edits and track changes. It is common for insertio
to be underlined and deletions to be struck through. Each program offers tools
show or hide the editing marks, notes about formatting, and embedded comments
How reviewers respond to the editing depends not only on the word proc
program but also on the technologies and workflow involved. For example,
uscript editors atJAMA send authors edited manuscripts as PDF files showing t
insertions and deletions as well as embedded comments and questions. Authors
respond by using advanced editing tools directly on the PDF, by printing out
marking up the copy and returning via fax, or by outlining corrections and qu
answers in an e-mail message.
When manuscript editing is performed electronically, often the editor ins
codes into the electronic file that allow the file to be automatically typeset for ini
placement of elements (eg, title, abstract, text, tables, figures, reference list).
coding also allows the content to undergo conversion to another language
HTML or SGML) for publication online. These codes may or may not appear on
edited typescript. The examples below illustrate the same passage of text with
codes hidden and then revealed after the file is run through a process to conv
the text to XML code:

-- -
 23.3 Electron~cText Edtttng

In a large collort of consrcutivc p;~ticntsundergoing tirug-eluting stcnr im-

plantation, we noted a 9-month cumulative stent thromlmsis incidence of
1.3%,substantially higher than rates reported in major clinical trials (0.4%at 1
year for sirolimus and 0.6%at 9 months for paclitaxel).3.5With widespread
availability of drug-eluting stents, the scope of percutaneous coronary
intervention has been expanded to'more complex lesions and patients. In
our study, 26% of the population had diabetes and 78% of the lesions were
complex. The clinical consequences of stent thrombosis were severe, with a
case-fatality rate of 45%.
<para>In a l a r g e .cohort of consecutive p a t i e n t s undergoing
drug-eluting s t e n t implantation, we noted a 9-month
cumulative s t e n t thrombosis incidence of 1,3%, substan-
t i a l l y higher than r a t e s reported i n major c l i n i c a l t r i a l s
(0.4% a t 1 year f o r sirolimus and 0.6% a t 9 months f o r
.
p a c l i t a x e l ) <reflink i d r e f = " r e f - jbr50003-3 r e f -jbr50003-
5 " / > With widespread a v a i l a b i l i t y of drug-eluting s t e n t s ,
the scope of percutaneous coronary i n t e r v e n t i o n has been
expanded t o more complex . l e s i o n s and patients.. I n our
study, 26% of the population had d i a b e t e s and 78% of the
l e s i o n s were complex. The c l i n i c a l consequences of s t e n t
thrombosis were severe, with a c a s e - f a t a l i t y r a t e of
45%.</para>
The examples below illustrate the coding/tagging behind an edited, linked JU
reference. The first paragraph is what the author would see; the second illustrates all
the codes behind the tagging.
<jm>l. Iakovou I, Schmidt T, Bonizzoni E, et a1.-Incidence,predictors, and
outcome of thrombosis after successful implantation of drug-eluting stents.
J A M . 2005;293(17):2126-2130. Medline:15870416</jrn>
<refitem id="ref-jle50384-1"><author><first~I</first~~last~Iakovou
.
<Aast></author><author><first>T</first><last>Schmidt<Aast>
</author><author><first>E</first><last>Bonizzoni<Aast>
</author><etal></etal><title>Incidence, predictors, and outcome
of thrombosis after successful implantation of drug-eluting stents.
</title><jmlname>JAMA</jmlname><refcitation><year>2005 .
</year><volume>293</volume> <issueno> 17</issueno> <fpage>2126
</fpage> <Ipage>2130</lpage></refcitation><pmid> 15870416
</pmid> </ie fitem>

ACKNOWLEDGMENT
Principal author: Stacy Christiansen, MA
This glossary is intended to define terms commonly encountered during editing and
publishing as well as those industry terms that also have a more common vernacular
meaning. The glossary is not all-inclusive. New terms and new usage of existing
terms will emerge with time and advances in technology. Definitions for the terms
herein were compiled from the ninth edition of this manual and the sources listed at
the end of the chapter. Terms used in .definitions that are defined elsewhere in this
glossary are shown in a different font.

AA: Author's alteration; a change or correction made by an author; used in correcting,

proofs (compare EA and PE).
access: The ability to locate specific inforination in a body of stored data. Data stored on
magnetic tape are accessed sequentially; data stored on disc may be randomly accessed.
acid-free paper: Paper made by alkaline sizing, a treatment that improves the paper's
resistance to liquid and vapor and improves the paper's permanence.
advertorial: Promotional or advertising content that has the appearance of editorial
content (see 5.12.3, Ethical and Legal Considerations, Advertisements, Advertorials,
Supplements, Reprints, and E-prints).
against the grain: See grain direction.

Al: Native file format of Illustrator (Adobe).

align: To place text and/or graphics to line up horizontally or vertically kith related
elements.
alphanumeric: Letters, numbers, and symbols used as a code, eg, for a computer
command.
ANSI: Acronym for American National Standards Institute, Inc.

API: Abbreviation for application program (or programming) interface, a set of

routines, protocols, and tools for building software applications. A good API makes it
easier to develop a Program by providing all the building blocks. A programmer puts
the blocks together.
application: A computer program that enables the user to perform a specific task, eg,
word processor, Web browsers, graphic tools.
archive: To copy files from a long-term storage unit for backup purposes.
art repair. art rebuilding: Replacing text, symbols, arrows, and lines on line art to
jx(xlucc i1lustr;ltions that are consistent in format, type, and size. e
4 .
.:
artwork: Illu.~rr.ir~~~ematerial, such as photographs, drawings, and graphs, intended
f o r rc.prcxlr~ction(sty! 4.0, Visual I'resentation of Data).
ascender: Thepart of lowercase letters, such as d, f, h, and k, that extends above the
rnidponion or x-height of the letter (compare descender).
ASCII:Acronym for American Standard Code for Information Interchange (prd
nounced [ask-eel); a code representing an alphanumeric group of characters that is
recognized by most computers and computer programs.
ASCII file: A computer file containing only ASCII-coded text.
ASTM: Abbreviation for American Society for Testing and Materials.
author's editor: An editor who substantially edits an author's manuscript and prepares -
it to meet the requirements for publication in a particular journal.
backstrip: A strip of paper affixed to the bound edges of paper that form a journal's
spine.
back up (v), backup (n): Saving copies of digital files on disk, tape, or other medium; a :
duplicate file or disk.

or 2 words at the too of a DaQeor column (see widow) or the first line of a ~ a r a ~ r a ~ h

I.
bandwidth: The capacity of a communication system in transferring data. i:

banner: The rectangular graphic at the top of a Web page. Also, in advertising, a

advertiser's own Web site. Vertical ads are also called towers or skyscrapers.
baseline: The imaginary line on which the letters in a line of type appear to rest.

25x38 in, of 80-lb coated paper will weigh 80 lb.

baud rate: In telecommunications and electronics, the signaling rate; a baud is the
number of changes to the transmission media per second in a modulated signal.
BBS: Abbreviation for bulletin board system.
binary system: A system of numbers using only the digits 1and 0 for all values; it is the
basis for digital computers.

or gluing (see also loose-leaf bjnding, perfect binding, saddle-stitch binding, and se- !
1ective.binding). (2) The cover and spine of a book or journal.
BinHex: Coding format that converts binary data into ASCII characters.
i
bit: A binary digit, either 0 or 1; the smallest unit of digital information.
 Glossary of Publishing Terms

bitmap (bmp): Also called raster graphic image or digital image, a data file or structure
representing a generally rectangular grid of pixels, or points of color, on a computer
monitor, paper, or other display device (see also tag, tagged, and nFF);also, the file
format built into Windows and native to Microsoft Paint; supports 1-to 24-bit depth
and index color.
bitmap fonts: Low-resolution fonts designed for computer screens, whose characters
are represented by bitmaps or by a pattern of dots.
black: One of the 4 process printing colors (see CMYK).
blanket: A fabric coated with.&bber or other material that is clamped around a print-
ing cylinder to transfer ink from the press plate to the paper (see also offset printing).
bleed: A printed image that runs off the edge of a printed page. A partial bleed extends
above, below, or to the side of the established print area but dbes not continue off the
page (see also live area).
blind folio: ~ ' ~number
a ~ counted
e but not printed on the page (see folio).
blind image: An image that fails to print because of ink receptivity error.
blog: Abbreviation for weblog. A weblog is a journal-style Web site that is frequently
updated and intended for general public consumption. Blogs generally represent the
personality of the author.
blueline(s): The proof sheet(s) of a book or magazine printed in blue ink that shows
exactly how the pages will look when they are printed.
blueprint blackprint: A photoprint made from film that is used to check position and
relative arrangement of text and image elements.
body type: The type characteristics used for the main body text of a work.
boilerplate: A section of text that can be reused without changes.
boldface (bf): A typeface that is heavier and darker than the text face used (see 22.0,
Typography).
bot: A computer program that automates tasks. See also spiderling].
bouncing reject: A rejected manuscript that is returned to the editorial office with re-
quest for reconsideration (see 5.11.5, Ethical and Legal considerations, Editorial Re-
sponsibilities, Roles, Procedures, and Policies, Editorial Responsibility for Rejection).
bps: Abbreviation foq bits per second. A measurement of the speed with which data
travel from one place to another (compare baud rate).
broadside: Printed text or illustrations positioned on the length rather than the width
of the page, requiring the reader to turn the publication on its side to read ir; LISLI:~~~!.
used for tables and figures that are wider than the normal width of a publication.
browser: See Web browser.
bug: Something that causes an error in computer software or hardn-are (see ;ilso
virus).
- L
I .
-
Gio\wr) of Publa$tr!ng :ernY

bullet: .An J I I ~ I C L ~Jot of .I h e a ~ yweight (-)used to highlight individual elements ina

11x1 I wc. centered d o t )

byline: A Irne oi text at the beginning of an article listing the authors' names (compare
signature 121) (see 2.2, hlanuscript Preparation, Bylines and End-of-Text Signatures,
and 5.1.1, Ethical and Legal Considerations, Authorship Responsibility, Authorship:
Definition, Criteria, Contributions, and Requirements).
byte: A unit of digital information that can code for a single alphanumeric symbol; 1
byte equals 8 to 64 bits.
CAD: Abbreviation for computer-aided design or computer-assisted design.
I'I
calibrate: To adjust a device such as a scanner or a monitor, image setter, or printing
press to more precisely reproduce color.
5I
caliper:Thickness of paper or film measured in terms of thousandths of an inch (mils
or points); also the tool used to measure the thickness of paper.
Y
call-outs: Quotes of reprinted text, usually bolder and larger than that of the original
text, used to place emphasis, improve design, or fill white space. Also ciilled pullout
quotes.
I
:

camera-ready: Copy, including artwork and text, that is ready to be photographed for
reproduction without further composition or alteration.
CAP: (1) Abbreviation for computer-aided publishing or computer-assisted publish-,:;
ing. (2) As a proofreading or editing mark, short for capital letter.
caption: The text accompanying an illustration or photograph. See also legend and
4.0, Visual Presentation of Data.
CAR: Abbreviation for computer-assisted reading. .
I -
case: The cover of a hardbound book (see also lowercase and uppercase).
CD: Abbreviation for compact (or computer) disc
4
containing data or used for storing 4
data.
CDI: Abbreviation for interactive compact disc containing data.
CD-ROM: Acronym for compact (or computer) disc, read-only memory; a compact disc
containing data that can be read by a computer. Many CD-ROMs are interactive and,
have sound, graphics, and video.
cell: In tables or spreadsheets, a unit in an array formed by the intersection of a column
and a row; in computer terminology, a basic subdivision of a memory that can hold 1
unit of a computer's basic operating data (see also 4.0, Visual Presentation of Data).
centered dot: A heavy dot (.) used to highlight individual elements in a list (see
bullet). Also, a lighter centered dot (.) is used in mathematical composition to signify
multiplication and in chemical formulas to indicate hydration.
central processing unit (CPU): The component in a digital computer that interprets
instructions and processes data contained in software.
CEPS: Acronym for color electronic prepress systems; electronic color equipment
used to perform electronic retouching, cloning, and pagination.

938

. .
 Glossary of Publishing Terms

bitmap (bmp): Also called raster graphic image or digital image, a data file or structure
representing a generally rectangular grid of pixels, or points of color, on a computer
monitor, paper, or other display device (see also tag, tagged, and TIFF); also, the file
format built into Windows and native to Microsoft Paint; supports 1- to 24-bit depth
and index color.
bitmap fonts: Low-resolution fonts designed for computer screens, whose characters
are represented by bitmaps or by a pattern of dots.
black: One of the 4 process printing colon (see CMYK).

blanket: A fabric coated withrbbber or other material that is clamped around a print-
ing cylinder to transfer ink from the press plate to the paper (see also offset printing).
bleed: A printed image that runs off the edge of a printed page. A partial bleed extends
above, below, or to the side of the established print area but does not continue off the
page (see also live area).
blind folio: A page number counted but not printed on the page (see folio).
blind image: An image that fails to print because of ink receptivity error.
blog: Abbreviation for weblog. A weblog is a journal-style Web site that is frequently
updated and intended for general public consumption. Blogs generally represent the
personality of the author.
blueline(s): The proof sheet(s1 of a book or magazine printed in blue ink that shows
exactly how the pages will look when they are printed.
blueprint blackprint: A photoprint made from film that is used to check position and
relative arrangement of text and image elements.
body type: The type characteristics used for the main body text of a work.
boilerplate: A section of text that can be reused without changes.
boldface (bf): A typeface that is heavier and darker than the text face used (see 22.0,
TYpography).
bot: A computer program that automates tasks. See also spiderfingl.
bouncing reject: A rejected manuscript that is returned to the editorial office with re-
quest for reconsideration (see 5.11.5, Ethical and Legal Considerations, Editorial Re-
sponsibilities, Roles, Procedures, and Policies, Editorial Responsibility for Rejection).
bps: Abbreviation for bits per second. A measurement of the speed with which clat:!
travel from one place to another (compare baud rate).
broadside: Printed text or illustrations positioned on the length rather than the width
of the page, requiring the reader to turn the publication on its side to read it: usu:11Iy
used for tables and figures that are wider than the normal width of a public:ltion.
browser: See Web browser.
bug: Something that causes an error in computer software or hardware (sec :IISO
virus).
-.
G l o r w r y of Publ*\tlnng Tern15

bullet: ..\I, J I I ~ I ~ LdIo t o i ;it~t.;ivy weight (-) used to highlight individual elements ina
II\I 1 wc centered dot).

II
byline: A lint: of text at the beginning of an article listing the authors' names (compare
signature 121) (see 2.2, Manuscript Preparation, Bylines and End-of-Text Signatures,
and 5.1 .l, Ethical and Legal Considerations, Authorship Responsibility, Authorship:
Definition, Criteria, Contributions, and Requirements).
byte: A unit of digital information that can code for a single alphanumeric symbol; 1
byte equals 8 to 64 bits.
CAD: Abbreviation for computer-aided design or computer-assisted design.
calibrate: To adjust a device such as a scanner or a monitor, image setter, or printing
I
press to more precisely reproduce color.
caliper: Thickness of paper or film measured in terms of thousandths of an inch (mils
or points); also the tool used to measure the thickness of paper.
call-outs: Quotes of reprinted text, usually bolder and larger than that of the original
tqxt, used to place emphasis, improve design, or fill white space. Also d l e d pullout
quotes.
camera-ready: Copy, including artwork and text, that is ready to be photographed for
reproduction without further composition or alteration.
CAP: (1) Abbreviation for computer-aided publishing or computer-assisted publish-.
ing. (2) A s a proofreading or editing mark, short for capital letter.
caption: The teqaccompanying an illustration or photograph. See also legend and
4.0, Visual Presentation of Data.
CAR: Abbreviation for computer-assisted reading. .
case: The cover of a hardbound book (see also lowercase and uppercase).

CD: Abbreviation for compact (or computer) disc containing data or used for storing
data.
CDI: Abbreviation for interactive compact disc containing data.

CD-ROM: Acronym for compact (or computer) disc, read-only memory; a compact disc
containing data that can be read by a computer. Many CD-ROMs are interactive and
have sound, graphics, and video.
cell: In tables or spreadsheets, a unit in an array formed by the intersection of a column
and a row; in computer terminology, a basic subdivision of a memory that can hold 1
unit of a computer's basic operating data (see also 4.0, Visual Presentation of Data).
centered dot: A heavy dot ( 0 ) used to highlight individual elements in a list (see
bullet). Also, a lighter centered dot (.) is used in mathematical composition to signify
multiplication and in chemical formulas to indicate hydration.
central processing unit (CPU): The component in a digital computer that interprets
instructions and processes data contained in software.
CEPS: Acronym for color electronic prepress systems; electronic color equipment
used to perform electronic retouching, cloning, and pagination.
 G l o s ~ r yof Publishing Terms

CPU: Abbreviation for central processing unit.

crawl, Web crawler : See spiderling].

crop: To trim a photograph or illustration to fit a design or to cut off unwanted

portions.
crop marks: Lines placed on the sides, top, and bottom of a photograph or illustration
indicating the size or area 'of the image to be reproduced.
CTP: Abbreviation for computer-to-plate; a printing process that transmits a digital
image directly from a computer file to a plate used on a press, eliminating the need
for film or negatives.
cursor: An on-screen indicator, such as a blinking line, arrow, hollow square, or other
image (usually mouse or keystroke driven), that marks a designated place on the
. screen and indicates current point of data entry or modification, menu selection, or
program function.
cyan: One of the 4 process printing colors (cyan, magenta, yellow, and black); a shacle
of blue (see CMYK).
data: Factual information (eg, measurements) used in calculation, analysis, and
discussion; information in digital form that can be organized, manipulated, stored.
and transmitted.
data bank: A corrlpilation of information stored in a computer for retrieval and use.
database: A collection of stored data from which information can be extracted and
organized in various forms and formats, usually for .rapid search and retrieval.
debug: To trace and correct errors in a computer program.

demand printing: A part of the publishing industry that creates short-run, customized
print publications quickly and on individual request.
demographic versions: Different versions of an issue of a publication'containing
specific inserts targeted for specific readers; the inserts are usually advertisements.
descender: The part of such letters as p, q, and y that extends below the main body of
the letter or baseline (compare ascender and see x-height).
desktop color separation: A computer file format that separates an EPS (encapsulated
PostScript) color file into the 4 color elements: cyan, magenta, yellow, and black.
desktop publishing (DTP): A microcomputer-based publishing system consisting of a
computer, paginat& software, ~ a n n e r and
, output device.
digital asset management (DAM): A centralized system for archiving, searching, and
retrieving tligitnl files :~ndassociatetl metadata. Also known as enterprise digital asset
I ~ ~ : I I ~ : I ~ C I I I~Ci Ii c~ c[ l, i ;:ISSCI
~ I I I : I I I : I ~ C oI rI Icligi[;~l
C I ~ ~;ISSCI
, \v;II.L~~Io~Is~I~~.

digitize: To tr;~nsform:I printed character or irnage into hits o r binary digits, so that it
c:in tw cntcrctl into ancl rn;lni[>ill:ltcclin ;I c.onlpil[cr.
disc. disk: A t.~rci~l;~r
.inti rc.~r~c.~.~l
pl;~rcc.o;ltr.cl \ v i r l ~:I 1n;lgnc-ric.\ L I I > \ I ; I I ~ ( ~ ;rncI t15ccl ior tlie s[or;igc
8 1 cl.11.1
( ( ht.c. I 1 0 , (:orrebe I : I I K I I ' I ~ ~ I ~ cI .. I: II, < ~ ~~
I. ~ I
--..
.
Glossary of Publishing Terms

diskette: Another term for a disc used I'or,sromgc (,I ~nft,rlll.irlon.u~u;rllyIn p r ~ o n s l .

computers.
display type: Type that differs from the body type of the text of ;1 prlntcd work. Dibplay
faces are used in titles, headings, and subheadings and are usually larger than the
body type.
doc: Microsoft Word file format and extension (.doc).
document: Organized coherent information in written, printed, or digital format.
document delivery: A service that allows users to search online databases of indexes
and tables of contents to identify articles and request copies of those articles to be
delivered by mail, by fax, or online.
DOI: Abbreviation for digital object identifier, a means of identifying a WWW .
fileor Internet document. A DO1 provides a means of persistently idenufylng a piece
of intellectual property on a digital network and associating it with related current
data in a structured extensible way.
domain: An lnternet location, and the last part of an e-mail address indicating the type
of business, eg, .corn, .net, .edu, .org, .mil, .gov, or letters that indicate a country, eg,
.ca, .uk, .fr.
domain name: The name that identifies an Internet site. Domain na
more pahs (foilowing www.), separated by dots. The part on the left is more
and the part on the right is more general, eg, Oxford University Press' d
is www.oup.co.uk.
DOS: Abbreviation for disk operating system (pronounced [dossl); operating system
used by most PC-compatible computers and workstations.
dot: In a halftone, an individual printing element or spot (see also dot gain and do
per inch).
dot gain: A printing defect that causes dots to print larger than they should, resultin
in darker tone and color than intended.
dot matrix printer: A printer that produces hard copy from a series of wires (p
strike against an ink source. The dots created forni characters. Quality varies;
uscripts printed on dot matrix'printers may not be easily read by some o
scanners for typesetting because the spaces between the dots create an une
structure (see also ink-jet printer, laser printer, and line printer).
dots per inch (DPI): A measure of the resolution of a printed image (als
per inch).
double spread: Printed material (text, tables, illustrations) that extends across 2 pag
(left- and right-hand pages); also cal1ed.a spread or a 2-page spread.
download: The process of transferring digital files from a remote computer to a 1
computer.
DPI: Abbreviation for dots per inch.
drive: The computer hardware, consisting of the motor, read/wri
electronics, that is used with a disc.

342

.-.-- - - . -
*..:-. .. . -*?
.i@
;,: 2
 Glossary of Publishing Terms

DRM: Abbreviation for digital tights management, a system used to protect the copy-
rights of data distributed or accessed via the lnternet or other digital media. A DRM
system protects intellectual property by encrypting the data or marking the content
with a digital watermark so that the content cannot be distributed.
drop cap, dropped cap: The initial letter of a word (usually beginning a paragraph) set
in boldface, larger than the body text (see also initial).
drop folio: A page number printed at the bottom of the page (see folio).
DSL: Digital subscriber line that provides an extremely high-speed lnternet connec-
tion with the same wires as a regular telephone line.
DSSSL: Abbreviation for document style semantics and specification language; an
output specification standard used with SGML-coded documents and a DTD to drive a
typesetter or printer.

DTD: Abbreviation for document type definition, which defines the structure of
content (ie, journals or books) with a list of elements (ie, title, author, abstract,
paragraphs). The DTD is the blueprint for SGML and XML documents.
dummy: A layout of a page or an entire journal, to represent the size'and appearance
after printing.
duotone: A 2-color halftone reproduction from a black-and-white photograph;
i
usually reproduced in black and 1 other color.
DVD: Abbreviation for digital versatile disc or digital video disc. An optical disc
storage media format that can be used for data storage, including movies with high
video and sound quality. DVDs resemble compact discs, as their physical dimensions
are the same, but they are encoded in a different format and at a much higher density.
EA: Abbreviation for editor's alteration or correction (compare AA and PE).

e-commerce: Electronic commerce; business that is conducted over the internet using
any of the applications that rely on the Internet. e-Commerce .can be a transaction
between 2 businesses, or between a business and a customer.
editor: (1) Someone who directs a publication or heads an editorial staff and/or
decides on the acceptability of a document for publication (eg, editor, editor in
chief); manages a publication (eg, managing editor); prepares a document for pub-
lication by altering, adapting, and refining it (eg, manuscript editor, copy editor,
author's editor). (2) In computer terminology, a program used to create text files or
make changes to a n existing file. Text or full-screen editors allow users to move
through a document with direction keys, keystrokes, and a mouse- or command-
driven cursor. Line editors allow the user to view the document as a series of num-
bered lines (see also context-sensitive editor and SGML editor).
editorial: (1) Of or relating to an editor or editing. (2) A written expression of opinion
that may or may not reflect the official position of the publication. (3) Published
rnater~:ilthat 15 not promot~on,il(eg. not an advertisement).
editorial assistant: Onc ~ v l i ons.;~..;ts~n the cdirorial procedures and processes of -. . >
,
.,
editing :~ricip ~ ~ l ~ l i ~ l ~ ~ n ~

943
P,bl,rh.njl Terms

1, , t ~ r r l . ~ i.I: journal published in digital format (eg, on the World

e-journal: I.'lr.\-tron~~
W ~ d eWeb o r CD-ROM) th;~l13 accessed via a computer.

elite type: l'ypc\vriter type that equals 12 characters to the inch (see also pica type).
ellipsis: A series of 3 periods ( . . .) used to indicate an omission or that data are not
, :~~~ilalAe.
em: A measurement used to specib to the typesetter the amount of space desired for
indention, usually equal to the square body of the type size (eg, a 6-point em is 6
points wide).
e-mail: Electronic mail; an online system that allows people to send messages to each
other through their computers.
em dash: A punctuation mark (-1 used to indicate an interruption or break in thought
in a sentence; also used after introductory clauses and before closing clauses or
designations (compare en dash and see 8.3, Punctuation, Hyphens and Dashes).
EMF: Abbreviation for Enhanced MetaFile, the 32-bit file format created by Microsoft
Windows. O

emulsification: A condition in offset printing that results from a mixing of the water-
based fountain solution and oil-based ink on the press (see also fountain).
emulsion side: The side of a photographic film to which a c h d c a l coating is app1ie.d
and on which the image is developed.
en: Half an em (see also em).
enamel: The surface of shiny, coated paper.
en dash: A punctuation mark (-) (longer than a hyphen and half the length of an em
dash) used in hyphenated or compound modiliers (compare em dash and see 8.3;
Punctuation, Hyphens and Dashes).
end mark: Asymbol, such as a dash (-1 or an open square (01, to indicate the end of
an article; often used in news stories.
EPS (encapsulated PostScript): A graphics file format. An EPS lile is a PostScript file that
satisfies additional restrictions for high-resolution graphics. These restrictions are
intended to make it easier for software to embed an EPS file within another PostScript
document.
e-publication: Electronic publication; a work published in digital format (eg, online,
'
CD-ROM)that is accessed via a computer.
ethernet: A method of networking computers in a local area network (LAN).
expanded type: Type in which the characters are wider than normal (see 22.0, Ty-
pography).
export: To convert and transfer data from one application into another applicati
(compare import).
extensible markup language: See XML.
face: Typeface; style of type (see also font).
 Glossary of Publishing Terms

F&G: Abbreviation for folded and gathered signatures of a publication for final review
before publication.
FAQs: Acronym for frequently asked questions; often used by Web site and home
page designers to help users access and search for information and resolve common
problems.
fax: Short for facsimile; transmission of printed or digitized material through tele-
phone lines.
figure: An illustration, eg, photograph, drawing, graph (see 4.0, Visual Presentation
of Data).
tile: A collection of related, digitilly stored information that is recognized as a unit b y
a computer.
, filler: (1) Editorial content used to fill whitespace created by articles or advertisements
not filling an entire page. (2) Chemicals used to fill the spaces between fibers in
'
paper to improve the paper's opacity.
finish: The surface of paper.
tirewall: In computer terminology, a security software program or device that blocks
or restricts entry into a local area network from the Internet.
floppy disk: A flexible disc coated with magnetically sensitive material used for
temporary storage of information, usually used with personal computers (see also
diskette).
flush: Lines of type aligned vertically along the left margin (flush left) or the right
margin (flush right).
flush and hang: To set the first line flush left on the margin and indent the rell~aining
lines.
.
flyleaf: Any blank page at the front or back of a book.
folio: A page number placed at the bottom or top of a printed page (see also drop
folio and blind folio).
. font: The complete assortment of qualities (eg, size, pitch, and'spacing) and styles
(eg, boldface, italic, etc) of a particular typeface (see 22.0, Typography).
foot The bottom of a page (compare head).
footer: Sec running foot:
form, press form: A group of assembled pages (usually 8, 12, 16, or 32 pages), printed
at the same time, then folded into consecutively numbered pages (see also signa-
ture).
format: The shape, size, style, margins, type, and design of a publication.
FOSI: Acronym for formatted output specification instance (pronounced [foss-eel).
FOSI is a style sheet language for SGML and XML (see also specifications and DTD).
'ubl~sh~ng
Terms

fountain: I;] ottw-t (111tlofir~pI11~.

1 pr~rltirlg.ttlC p n of ttlc press that contains the damp-.,
ening device and w,lut~c,n I u > u ~ l l y\v:rt~-r. 1,uffercd acid, gum, and alcohol); in'
nonoffsrt printing, Lhe part of the press that contains the ink.
four-color process: See CMYK.
FPO: Abbreviation meaning for position only; refers to low-resolution graphics used
in place of high-resolution graphics to show placement of artwork and photog
before printing.
FPS: Abbreviation for frames per second.
FTP: Abbreviation for file transfer protocol. A method for exchanging files be
computers on the Internet.
function key: A key on a computer keyboard that gives an instruction to the m
or computer, as opposed to the keys for letters, numbers, and punctuation marks;
often labeled F (eg, F1, F2).
galley proof: A proof of typeset text copy run 1column wide before being made into a
page.
gatefold: A foldout page.
GB: Abbreviation for gigabyte; a unit of computer storage, equal to approximately 1
billion bytes.
Gbps: Abbreviation for billions of bits per second; when spelled GBps, it
gigabytes per second.
ghost author: An author who meets all criteria for authorship but is not named in the
byline of a publication (see 5.1.2, Ethical and Legal Considerations, Authorship Re-
sponsibility, Guest and Ghost Authors).
ghosting: Shadows produced by uneven ink coverage (variations are caused by wide
contrasts in the colors or tones being printed).
GIF(.gif ):Acronym for graphicsinterchangeformat.Acompressedg
used for images (eg, logos, cartoons) that do not require many colors
gigabyte: See GB.
glossy: A photograph or line art printed on smooth, shiny paper that traditi
been required by some publishers for print reproduction.
gopher: An online Web browser that allows a user to locate online addresses and
topics in text-only format (no graphics).
gradation: A transition of shades between black and white, between one color and
another, or between one color and white.
grain direction: The direction of the fibers in a sheet of paper created when the paper
is made.
granularity The level of specificity with which parts of a digital document are iden
tified by a context-sensitive editor.
 Glossary of Publishing Terms

graphical user interface (GUI): Pronounced [goo-eel; a computer display format th:it
allows the user to select commands, run programs, and view lists of files and other
options by pointing, a cursor to icons or menus (text lists) of items on the screen.
I

I .
gray scale: A range of grays with gradations from white to black. A gray-scale image
contains various shades of gray.

iI greeking: (1) A simulation of .a reduced-size page used by word-processing appli-

cations during the print preview function because it is usually not possible to shrink
text size in proportion to the pagesize. The graphic symbols used to represent text
I resemble Greek letters; hence the term greeking. Also called Lorem ipsurn, or lipsum.
(2) Refers to nonsense text or gray bars inserted in a page to check the layout.
gutter: The 2 inner margins of facing pages of a publication, .from printed area to
binding.
hairline: The thinnest stroke of a character.
hairline rule: A thin rule, usually measuring one-half point.
halftone: A black-and-white continuous-tone artwork, such as a photograph, that has
shades of gray (see also duotone and 4.0, Visual Presentation of Data).
halftone screen: A grid used in the halftone process to break the image into dots. The
fineness of the screen is denoted in terns of lines per inch (eg, 120, 133, 150).
H&J: Abbreviation for hyphenation and justification; the determination of line breaks
and the division of words intb lines of prescribed measurement (see justify).
handwork: Extra work the printer does by hand, such as stripping in type or making
part of a page opaque.
hard copy: Printed copy, in contrast to copy scored in digital format.
hardware: Machinery, circuitry, and other'physical entities (compare softwire).
head: The top of a page (compare foot).
header: See running head.
head margin: Top margin of a page.
home page: The first screen a user views when connecting to a specific site on the
Web.
'
WTML: Abbreviation for hypertext markup language; codes (tags) used to prepare a
file containing both text and graphics for placement on the Internet via the Web.
http: Abbreviation for hypertext transfer protocol; a computer connection used at the
beginning of a Web address to connect with a Web site and transfer information and
graphics across the Web.
https: Abbreviation for hypertext transfer protocol, secure. This protocol is used for
performing financial and other types of transactions that require secure transmission
-I

of information.
hyperlink: (v) The nonlinear relating of information, images, and sounds that allows a
computer user to jump quickly from one topic, item, or representation to another b y
 . . . .... . .
I
.J>
. . ,

Glossary of Publishing Terms

clicking a mouse-driven cursor on a high1ighrc.d \vor{i ( ) r icon. ( n J rt~ch~gtrl~~titt-d

word or icon.
icon: A small graphic image, usually ;I visual mnemonic, d~~ipl;~).r-cl
on 3 computer
screen, easily manipulated hy the user, that represents common computer com-
mands (eg, a trash can may represent a command for deleting unwanted text or files).
image setter: A device that plots an array of dots or pixels onto photosensitive material
(f1111)line I,y line, until ;In enlire page is created (including text, graphics, and color). .
l'lle film can I,e outpilt as a ncpativc o r positive with resolutions from 300 to 3000
dots per inch.

sions printed per hour.

imprint The name of the publishing house or entity that issues a book; the imprint is"
typically found at the bottom of the title page. It may or may not be the same as the
name of the publishing company, and a publishing company may have,various,
imprints.
indent To set a line of type or in from the'margin or margins (see 22.0,
Typography).
inferior: See subscript.

white space above (see also dropped cap).

ink fountain: Device on the press that supplies the ink to the inking rollers.
ink-jet printer: A device by which ink is forced through a series of nozzles onto paper,
commonly used with personal computers. This method of printing is usually used to,
produce the mailing address or a short message to the subscriber (see also laser
printer, line printer, and dot matrix printer).

948
 Gtor~ryof Publishing Terms
!

jI in register: See register.

insert: Printed material (a piece of paper or multiple pages) that is positioned be-
I
!
I
tween the normal pages of a publication during the binding process. The insert is
i usually printed on different paper than that used in the publication; it is often an
i advertisement.
instant messaging: Text-based messaging similar to e-mail except it allows the user to
communicate with others in real time through the Internet.
interface: The ability of individual computers to interact; also, the actual hardware
' that performs the function.
international paper sizes: The iange of standard metric paper sizes as determined by
the International Standards Organization (150).
Internet: A global network connecting millions of computers for communications
purposes, developed in 1969 for the US military, that grew to include educational and
research institutions. The Internet facilitates data transfer and communication ser-
vices, such as remote login, file transfer (FTP), electronic mail (e-mail), newsgroups,
and the World Wide Web.
Internet service provider (ISP): A commercial entity that provides access to she Internet.
intranet: A private network with restricted access to specific users (eg, employees of
a company or members of an organization).
ISBN: The International ~ k n d a r dBook Number, a 13digit number that uniquely
identifies books and booklike products published internationally (eg, the ISBN for
this manual is 97&0-19-517633-9).
ISO: Abbreviation for International Standards Organization.
. ISSN: The International Standard Serial Number, an &digit number that identifies
periodical publications as such, including electronic serials (eg, the ISSN foi-JAMA is
0098-7484).
IT: Abbreviation for information technology.
italic A typestyle with characters slantkg upward and to the right (italic) as opposed
to roman type (see 22.0, Typography).
JPG or JPEG: Abbreviation for Joint Photographic Experts Group. JPEG is a com-
pressed graphic file (usually with the extension .jpg or .jpeg) normally used for im-
ages that require many colors (eg, photographs).
justify: To add or delete space between words or letters to make copy align at the left
and right margins (see also unjustified and 22.0, Typography).
kerning: Modification of spacing between ch;~r:~cters,
uslr:~llvt o hring letters closer
together, to improve overall appearance.
keyboard: Input device of ;I computer o r typcsettcr. with k c v s rcprcscr~tin~
lvtterh. i
numbers, punctuation marks, and functions t h ~ pt ~ v cin5tn,crlc,n5 rhc cc,rnl>ilrcSr. - j
See also function key.
'ublishing Terms

keyline: Tissue or acetate overlay separating or defining elements and color for line
art or halftone artwork.
ladder: Four or more hyphens appearing at the end of consecutive lines; a typo- :'
graphic pattern to be avoided.
LAN: Acronym for local area network, a computer network restricted to an loca
(eg, a home, office,. or small group of buildings such as a college) (compare
laser printer: A highquality printer that uses a laser beam to produce an image on a
drum (see also dot matrix printer, ink-jet printer, and line printer).
layout: A drawing showing a conception of the finished product; includes siz
positioning of the elements.
leaders: A row of dots or dashes designed to guide the reader's eye across sp
page.
leading: Pronounced [led-dig); the spacing between lines of type (also ca
spacing); a +over term from hot metal composition. For example, 9-point type on
11 points of line space allows 2 points of leading below the type (see 22.0, Tfiog-
raphy).
legend: Descriptive text accompanyinga figure, photograph, or illustration;
(key) that explains symbols on a map or chart (see also caption and 4
Presentation of Data).
ligature: Two or more connected letters, such as a?,'set as connected (see
pography).
line a r t Illustration composed of lines and/or lettering, eg, charts, graph
Visual Presentation of Data).
line printer: A machine, driven by a computer, that prints out stored data
a time (see also dot matrix printer, ink-jet printer, and laser printer).
line spachg: See leading.
lines per inch (LPI):A unit of measurement for halftone screens.
listserve: A digital mailing list progmn that manages e-mail addresses
discussion group. The listserve program duplicates the messages sent
users and automatically sends them to every user in the group. Listserv
trademark.
lithographic printing: Formal term for offset printing.
live area: The area of a page withii the margins.
login: The name used to gain access to a computer system or network.
logo: One or more words or other combinations of letters or designs
easy recognition and promotion of company names, trademarks, etc.
long page: In makeup, a page that runs longer than the live area or marg
(compare short page).

-- -
. ...
_._. . , ..
 Glossary of Publishing Terms
I
loose-leaf binding: Binding that pennits pages to be readily removed and inserted
(compare perfect binding, saddle-stitch binding, and spiral binding).
lossy: Image compression method that removes minor tonal and/or color variations,
causing loss of inforrmation (detail) at high compression ratios.
lowercase: Letters that are not capitalized.
U W compression: Lempel-Ziv-Welch (not a file .format): nonlossy compression al-
gorithm that allows for compression of image data without loss of quality.
macro: A series of automatically executed computer commands activated by a few
programmed keystrokes; useful for repetitive tasks.
magenta: One of the 4 process printing colors (cyan, magenta, yellow, and black); a
shade of red (see CMYK).
mainframe: A large, powerful central processing computer.
makeready: The part of the printing process that immediately precedes the actual
press run, in which colors, ink coverage, and register are adjusted to produce the de-
sired quality; may also apply to the binding process.
makeup: The arrangement of type lines and illustrations into pages or press forms for
review or printing (see also imposition; compare live area).
manuscript: A typed (or occasionally handwritten) composition before it is published.
manuscript editor: See copy editor. .
margin: The section of white space surrounding typed,'composed, or printed copy
(see also white space).
mark up: The process of marking manuscript copy with directions for style and
composition (see also imposition).
master proof: The set of galley proofs or page proofs that cames all corrections and
alterations.
masthead: A listing of editorial, production, and publishing staff; editorial boards;
contact information; subscription and advertising information; important disclaimers
(see also boilerplate and colophon).
matte finish: The surface of dull-coated paper.
MB: Abbreviation for megabyte; a unit of con~puterstorage, equal to approximately 1
million bytes.
measure: The length of the line (width of the column) in which type is com~~oscrl
or
set, usually measured in picas and points.
megabyte: See MB.
memory: The pan of ;I conlpurcr in \\,llic.h tligit:tl inform;ttion is pc.rnl;lnc.ntI\-. \ r ( , l . ~ c l
(see also RAM).
menu: A serics of optlons ~n;I soti\v;trc progranl. 115uallypr-esc~ntrtl
o n 1 1 ) ~ .I O I , I ~ L I [ C . I
screcn ;I.; ;I 11st of I ~ S ~I p ~ , , , , l ,
 ..
Terms
Publ~rh~ng

metadata: Data about data. For example, a library catalog contains information
( mctadata) about publications (data). Metadata is used in markup languages, such as . '
HTML, SGML, and XML.
MHz: Abbreviation for megahertz, a unit that measures a computer system's cycle
speed; 1 MHz equals 1 million cycles per second.
MIME: Abbreviation for multipurpose internal mail extensions, the standard for at-
taching nontext files to standard Internet mail messages.
modem: Modulator-demodulator; an electronic telecommunication device that con-
verts computer-generated data (digital signals) into analog signals that can be carried
over telephone liqes.
rnoirk pattern: An undesirable wavy pattern caused by incorrect screen angles,
overprinting halftones,.or superimposing 2 geometric patterns.
monitor: A video output device for the display of computer-generated text and
graphics.
mouse: A.hand-operated device that controls the movement of'a cursor on a corn-
puter screen.
MOV: QuickTime video file format.
MPEG: Abbreviation for Motion Picture Experts Group. MPEG-1 fil
short animated files on the Web. MPEG-2 files are a much higher resolutio
being developed for digital television and movies.
MSL: Abbreviation -formust start left, indicating an article must start on a left-hand
page. Compare MSR.
MSR: Abbreviation for must start right, indicating an article must start on a ri
page. Compare MSL. -
multimedia: Interactive electronic products created from digitized data refo
include text, images, and sound that allow the user to interact with the .informati
on a computer screen.
multitasking: Performing simultaneous functions or manipulations on one compu
or workstation, or performing simultaneous dam manipulations in one
program.
network: Two or more computers connected to share resources (see also Intern
intranet, LAN, and WAN).
newsgroup: The common nomenclature for Usenet News, a tool for group discuss
on the Internet. Newsgroups function as group e-mail by providing a posting site
discussion on a particular topic. One can participate by posting a query or by rea
answers to queries that have already been posted.
nonlossy: Image compression without loss of quality.
nonproportional spacing: Spacing that does not allow for the adjustment of sp
between characters to eliminate extra white space; all letters have the same spa
which creates more space around narrow letters and decreases readabil

. -
 Glossary of Publishing Terms

object An itcm or computer represenmion of something (icon or text) that a user can
select and/or manipulate to perform a task.
oblique: Type that is slightly slanted but not italic.

OCR: Abbreviation for optical character reader (or recognition); in digital composi-
tion and typesetting, an OCR input device is capable of scanning a typescript and
replicating the typed characters. An OCR device creates a digital document that can
be edited and searched, as opposed to a scanner, which simply transfers images from
paper to a digital file.
offset, offset printing: Commonly usedterm for offset lithographic printing; a printing
method in which an image is transferred from an inked plate cylinder to a blanket
made of rubber or other synthdtic material and then onto a sheet of paper.
on-demand printing: See demand printing.
opacity: (1) A quality of paper that prevents type or images printed on one side from
showing through on the other side. (2) The covering power of ink in printing. -
opaque: To block out (on the film negative) those areas that are not to be printed. I
i
operating system (0s): A program that controls the overall operations of a computer
system, intermediating between the application software programs and the hardware,
such as MS-DOS, UNE, Windows, or OS/2.
!
!

optical character readerlrecognition: See OCR.

orphan: One or 2 short words at the end of a paragraph that fall on a separate line at
the bottom of a page or column, or a single line of type that starts at the bottom of a
page or column (compare widow; see also bad break).
outline halftone: A portion taken from a halftone that is the shape or modified shape
of a subject.
out of register: See register.

overlay: A hinged flap of paper or transparent plastic covering for a piece nf artwork.
It may protect the work and/or allow for instructions or corrections to be marked for
the printer or camera operator.
overprinting: Printing over an area or page that has already been printed.

overrun: Production of more copies than the number ordered (see also press run ancl
print order; compare underrun).
page proof: A proof that is set or printed in the form of the finished page (see also
proof).
paginate:To number, mark, or arrange the pages of a document, rn;~nuscript.:~rticle.
or book.
Pantone Matching System colors: See PMS.
paragraph: A unit of text set off by indention, horizontal space, bullets, or other
typogr~phicaldevice.
parse:?'() ;rn:~lyzefile..; hy checking tags (coclcs) to cnsurc t l i : ~ t thcy :Ire. L ~ s c c.or.rc.c.lly.
tl
'"blb,?>,ngTetcn

password: 4 I)rlt I *-I<. ~IX.LJ x;~inaccess to a locked system.

~ c )

pasteup: A 111~r\k 01'

; t ~ . ~ ~ . ~ i i t ) I ! .I ~ L . elements of type and artwork as a guide to the
1)rlrlrc.r I'c)r makeup.

PC: :\l>l>rcviarionfor personal computer, usually self-contained (keyboard, monitor,

[~rinter,central processing unit, and memory devices), as opposed to a terminal or
networked computer; ofren used to refer to IBM-compatible computers.
PCT (or PICT): hlacintosll graphics file format most coinmonly used for bitmap images. *

PDA: Al>breviation for personal digital assistant, a handheld device, that combines
con~pi~~ing,
telephone/hx, Internet, and networking features.
PDF: Abbreviation for portable document format, a proprietary file format that cap-
tures the elements of a printed document as an electronic image that can be viewed,
navigated, or prinied.
PDL: Abbreviation for page description language. The code generated by a typeset-
ting or page-layour system that tells the output device, such as a laserprinter or image
setter, where to place elements on a page.
PE: Abbreviation for printer's error or publisher's error; used in correcting proofs to
indicate an error attributable to the printer or publisher (compare AA and EA).
peer review: The process by which editor; ask experts to read, criticize, and comment
on the suitability of a manuscript for publication (see 6.0, Editorial Assessment and
Processing, and 5.11.4, Ethical and Legal Considerations, Editorial Responsibilities,
Roles, Procedures, and Policies, Editorial Responsibility for Peer Review).
peer-reviewed journal: A journal containing editorial content that is peer reviewed.
penalty copy. Copy that is dimcult to typeset (heavily corrected, difficult to read,
heavy with tabular material, etc), for which the typesetter charges more than the
regular rate.
perfect binding: Process in which signatures ate collated, the gutter edge is cut and :

loose-leaf binding, saddle-stitch binding, and spiral binding).

perforate: To punch lines of small holespr slits in a sheet so that it can be tom off with
ease.

point).

pitch: In fixed-pitch fonts, pitch refers to the number of characters per inch. Common

assigned independent color and intensity.

 Glossary of Publishing Terms

plate: (1) A sheet of metal, plastic, rubber, paperboard, or other material used as a
printing surface; the means by which an image area is separated from a nonimage
area. (2) A full-page, color book illustration, often printed on paper different from
that used for the text.
PMID: Abbreviation for PubMed identification number, the unique identifying
number assigned to a record when it is entered into PubMed.
PMS (Pantone Matching System) colors: A color identification system matching specific
shades of approximately 500 colors with numbers and formulas for the corre-
sponding inks, developed by Pantone Inc.
PNG: Portable (public) network graphic file format.

pockets: Sections on a binder in which individual signatures are placed and then
selected as required for each copy t o be bound.
point: The printer's basic unit of measurement, often used to determine type size: 1
point equals approximately %2 inch; 12 points equal 1pica.
Postscript:A page description language and programming language used primarily in
the electronic and desktop publishing areas (see also PDL and EPS). .
PowerPoint: Microsoft software, used to make slide show presentations. File format
extensions are the default .ppt (presentation), .pot (template), and .pps (PowerPoint
Show).
ppi: Abbreviation for pixels per inch, unit of measurement for digital images.

preprint: An article or part of a book printed and distributed or transmitted digitally

before publication and/or review.
press form: See form.

press plates: The plates used to print multiple copies on the press (see also plate).

press run: The total number of copies of journals, books, or other materials printed.

primary colors: Cyan (C), magenta (MI,and yellow (Y). These 3 colors, when mixed
with black (K), will closely reproduce all other colors. See CMYK.
print order: The number of copies of printed n~aterialordered.

printout: Paper output of a printer or other device that produces normal-reading

copy from computer-stored data.
print run: See press run:

process printing colors: Cyan, magenta, yellow, and black (CMYK); used to produce
color illustrations in print publications.
program: A set of instructions for a computer. To program is to create such a set of
instructions.
programmable key: A key on a computer's keyboard that, when pressed alone or in
combination with other keys, produces a computer command (see also macro and
function key).
-- _
' ?
Glossary of Publishing Terms

proofreader. One ~ v h orcatls or rcvie\vs proofs for errors.

based on character width and increases readability.

protocol: A system for transmitting data between 2 devices that establishes the type of
error checking to be used; data compression structures; how the sending device will.
indicate that it has finished sending a message; and how the receiving device will
indicate that it has received a message; also a detailed plan for a scientific study.
PSD: Photoshop (Adobe) file format.

selected information.
PubMed: A searchable database of scientific and biomedical literature compiled by
the US National Library of Medicine.
pullout quotes, pull quote: See call-outs.

RAM: Acronym for random access memory; temporary computer memory used by a

computer is shut down.

raster: A digitized image that is mapped into a grid of pixels; therefore, the image is '

resolution-dependent.The color of each pixel is defined by a specific number of bits.

raster image processor (RIP): A device that produces a digital bitmap to show an
image's position on a page before printing.
RC (resin-coated) paper: Paper used in composition to produce a type proof of the
quality needed for photographic reproduction.
RDF: Abbreviation for resources description framework, a general framework for
describing a Web site's metadata.
'
ream: Five hundred sheets of paper (see also basis weight).
recto: A right-hand page (compare verso).

register: To print an impression on a sheet in correct relationship to other impressions

already printed on the same sheet, eg, to superimpose exactly the various color

not exactly aligned, they are out of register.

remake: To alter the makeup of a page or series of pages.
reprint: A reproduction of an original printing in paper or digital format.

956
 Glossary of Publishtng Terms

reproduction proof: A high-quality proof for use in photoengraving or offset litl~og-

raphy.
resolution: A measurement of the visual quality of an image according to discrimi-
nation between distinct elements; the fineness of detail that can be distinguishctl in
an image (see also dots per inch).
reverse-out, reverse t e x t or reverse image: Text or image that appears in white sur-
rounded by a solid block of color or black.
RGB: Abbreviation for red, green, blue, the primary additive colors used in color
computer monitors.
right-reading: Produced to read as original copy from right to left, as in right-reading
film (compare wrong-reading):
RIP: Abbreviation for raster image processor.
river: A streak of white space running down through lines of type, breaking up the
even appearance of the page; to be avoided.
ROB: Abbreviation for run-of-book; advertising term meaning a regular page, as
opposed to an ad insert (ie, appears in all versions of the publication).. Can also refer
to placement anywhere space is available in the publication.
roman: A typestyle with upright characters, as opposed to italic (see 22.0, Typography).

RSS: Abbreviation for Really Simple Syndication, Rich Site Summary, or RDF Site
Summary, an XML format for syndicating Web content.
RTF: Abbreviation for rich text fonnat; a generic word-processing format that uses
ASCII codes to preserve the formatting of a file.

runaround: Type composed or set to fit around an illustration, box, or other design
element.
run in: To merge a paragraph with the preceding paragraph.

running foot: A line of copy, usually giving publication name, subject, title, date,
volume number, and/or authors' names, app,earing at the bottom of consecutive
pages. Also called footer.
running head: A line of copy, usually giving publication name, subject, title, date,
volume number, and/or authors' names, appearing at the top of consecutive pages.
Also called header. .
runover: Material not fitting in she space allowed (see also live area and long page). :

saddle-stitch binding: Process by which signatures, or pages, and coven are assembled
by inserting staples into the centerfold (see also loose-leaf binding, perfect binding,
and spiral binding).
sans serif: An unadorned typeface; a letter without a short line projecting from thc rop
or bottom of the main stroke of the letter (compare serif and see 22.0. Typogr:tpll)).
scaling: Determining the appropriate size of an image and the nmotlnr of rctt\~ctiono r
enlargement needed for the image to fit in a specific arc;\.
- .\
Glo JublishingTerms

scanner: A device that uses an electronic reudcr tcyc) tu tr~nsiurnltype. characten,

and images from a printed page into a digital ion]]; or 3 dc\-~cr
that produces color-
separated film or images (see also OCR).
score: To indent or mark paper or cards slightly so they can be folded exactly at
certain points.
SCORM: Acronym for sharable content object reference model. A st
based education, it defines how the instruction elements are comb
scribe: Thin strips of nonprinting areas, such as those between figure parts.
scripting language: Programming language used to add additional features to a Web
page, such as graphic displays.
search engine: A program that enables users to search for documents
selective binding: A method of binding in which specific contents
produced are determined by instructions transmitted electronically from a computer.
Signatures, or specific groups of pages, are selected to produce a copy for a specific
recipieht or recipient group.
self-cover: A cover for a publication that is made of the same paper used for the text
and .printed as part of a larger press form.
separation: Converting images to CMYK for printing; also used to refer to the
negatives created for each of the 4 colors (see also color separation).
serif: An adorned typeface; a short, light line projecting from the top or botto
main stroke'of a letter (compare sans serif and see 22.0, Typography).
server. A computer software package or hardware that provides specific services to
other computers.
SGML: Abbreviation for standard generalized markup language; m
are used to capture, or encode, the logical structure of an electronic d
distinct from its visual presentation. SGML formed the basis for HTML and XML (see
also ASCII and DTD).
SGML editor. A context-sensitive editor based on SGML.

short page: In makeup, a page that runs shorter than the establis
(compare long page). ..

show-through: Inking that can be seen on the opposite side of the paper, because~
the heaviness of the ixik or the thinness of the paper.
sidebar: Text or graphics placed in a box and printed on the right o
page.
signature: (1) A printed sheet comprising several pages that have been folded, so
the pages are in consecutive order according to pagination. (2) A line of text
pearing at the bottom of an article that lists the author(s).
signature block: A block of text that automatically appears at the bottom of an e-ma
message, discussion group, and/or forum post that contains the writer's name and
also ~:icludethe writer's title, company name, location, e-mail address, and pers

-
 Glorwry of Publtrh~ngTerm,

message; also sometimes used after letters, book revie~vs,and other small Irerns of
COPY.
sink: Starting type below the top line of the live area, which leaves an area of white
space.
site license: (1) A licensing agreement that permits access and use of digital infor-
mation at a specific site. (2) A fee paid to a software company to allow multiple users
'

at a site to access or copy a piece of software.

sizing: Adding material to a paper to make it more resistant to moisture.
slug: A line or lines of copy inserted to draw the attention of the reader, often set
between ides in enlarged, b?ld type.
small caps: Capital letters that are smaller than the typical capital letters of a specific
typeface, usually the site of the i-height of the font (see also 22.0, Typography).
software: Programs and procedures required to enable a computer to perform a
specific task, as opposed to the physical components of the system (compare
hardware).
solid: Style of type set with no space between lines.
solidus: A forward slanted line (/) used to separate numbers, letters, or other char-
acters (also called forward slash; see also virgule and 8.4, Punctuation, Forward Slash
[Virgule, Solidus]).
spacing: Lateral spaces between words, sentences, or columns; also paragraph in-
dentions (see leading).
spam: Electronic junk mail or newsgroup postings.
specifications(specs): Instructions given to the printer that include numbers of copies
(press run or print order); paper stock, .coating,and size; and color, typography, and
design.
spider[ingl: Software that regularly checks the lnternet for Web pages to feed a s~grch
engine. Also called a bot, crawler, or Web crawler.
spine: The backbone of a perfect-bound journal or book. The width of the spine
depends on the number and thickness of pages in the publication (see also perfect
binding).
spiral binding: A process of binding a publication with wires or plastic in a'spiral form
inserted through holes along the binding side (see also loose-leaf binding, perfect
binding, saddle-stitch binding, and selective binding).
spot color: One or more extra colors on a page.
spread: Two pages, facing each other; see also double spread.

sRGB: A color profile with a very limited amount of color v;tluc\. pr~ni:~r~lyclc.s~gr~t.cl
for vivid images displayed over the Internet Kot suirnhlt, t o r prlnt rcprocl~~cilon
standard generalized markup language: Src SGML
Publishing Terms

r;
stet: Instruction that marked or crossed-out copy or type is to be retained as it,
originally appeared.
STM: Abbreviation for scientific, technical, and medical field of publishing.
stock: Type of paper for printing.
storage: The capability of a device to hold and keep data.
storing data: Placing data in computer storage by recording the data in digital form on
magnetic, optical, or other medium, such as discs and tapes, either inside or outside
<
the computer.
straight copy: Material that can be set in type with no handwork or special prol
gramming (copy that contains no mathematical equations, tables, etc).
strapline: The "subtitle" portion of a logo or slogan.
. strikethrou some te : for deletic - - superimposing
- -
through the main body of the character(s).
0

strip:To join film in a unit according to a press imposition before platemaking.

style: A set of uniform rules to guide the application of grammar, spelling, typogra-
phy, composition, and design.
.
1
subhead: A subordinate heading (see 22.0, Typography). g
subscript: A number or symbol that prints partly below the baseline, eg, A2 (also called
inferior).
subscription: The price for a publication; usually set in annual terms. 3
superior: See.supencript.
superscript: A number or symbol that prints partly above the baseline, eg, (ah
called superior). 4.

SWK: Abbreviation for "set when known." Used to indicate information (such as page::'
numbers) that will be inserted later in the production process. 1
a 4

SWOP: Abbreviation for specifications for Web offset publications; a color proofing
system used to check color consistency.
3
..$
syntax: The spelling and grammar of a programming language that communicates to
the computer exactly what the user wants. The computer comprehends what is typed
only if it is typed in the computer's language.
tag: (v) To insert a style or composition code in a computer file or document; (n) the 3
code inserted in a computer file or document.
tagged: Coded, ie, a document'or file with the codes inserted in the text.
TCPIIP: Abbreviation for transmission control protocol/Internet protocol; the
guage governing comn~unicationbetween computers on the Internet.
tear sheet: A page cut or tom from a book or periodical.
text: The main body of type in a page, manuscript, article, or book. Also used fo~
electronic files that contain only characters, no formatting or illustrations.
 Glossary of Publishing Terms

text editor. An application used to create, view, and edit text files.

text wrap: A feature of word processors that makes it possible to wrap text around an
illustration. Also called text flow.
thumbnail: A miniature display of a page or graphic.

TIFF (or TIF): Acronym for tagged image file format; a file format that allows bitmapped
images to be exchanged between different computer applications; the preferred
format for images, including photographs and line art.
tints: Various even tone areas 0f.a solid color, usually expressed in percentages.

tip, tip-in, tip-on: A sheet of paper or a signature glued to another signature before
binding.
TOC: Abbreviation for table of contents.
toner: Imaging material or ink used in photocopiers, computer printers, and some
off-press proofing systems.
trademark: A legally registered word, name, symbol, slogan, or any combination of
these, used to iden@ and distinguish products and services and. to indicate the
source and marketer of those products and services (see 5.6.16, Ethical and Legal
Considerations, Intellectual Property: Ownership, Access, Rights, and Management,
Trademark).
transparency: (1) A transparent object such as a photographic slide that is viewed by
shining light through it; color positive film (traditional/conventional). (2) Effect
- created by pixels turned "off" or by a mask ([alpha channel] digital/electronic).
transpose (tr): A proofreading and editing term meaning to switch the positions of
2 elements (eg, characters, words, sentences, or paragraphs).
trap, trapping: The process of printing one ink on top of another to produce a third
color, or to avoid thii white spaces between colors.
trim: The edges that are cut off 3 sides-the top (head), bottom (foot), and right
(face)--of a publication after binding.
trim line, trim marks: The line or marks indicated on copy to show where the pi~gc
ends or needs to be cut.
trim size: The final size of the publication.

TTP: Abbreviation for t ~ xtransfer

t protocol; a method for moving text from one place
to another on the Internet (see also FTP).
turnaround time: The period of time between any 2 events in,publishing(eg, between
manuscript submission and acceptance, between manuscript scanning and
telecommunication to the printer).
type: (n) Printed characters; a small metal block with a raised character on one sicle.
used to produce characters on paper; (v? the act of typing text or entering cornnrands
into a cornputcf on ;I keylw).irrl.
-
typeface: h n;inlc.tl t y p ~clv\lgn. sirch ;is 13:iskemille. Helvetica, or Times Komiln.
prod~rc.ccl:13 :I c-oniplc.tc.f ~ t (4c.v
l ~ 22 0. 'I'vpogr;l[>hy).
'ublishing Terms

type gauge: A type-measurement tool calibrated in picas and points.

typescript: A manuscript output by a computer printer or in typewritten form (see
also hard copy).
typesetter: h person, firm, or machine that sets type.
typestyle: The general characteristics of a typeface (eg, roman, boldface,
condensed type) (see also 22.0, Typography).
typo: A typographical error in a published work, such as a misspelling or missing
letter.
udlc: Abbreviation for uppercase/lowercase (letters); as an editing mark, it would
indicate using capital and small letters, eg, New York, New York, rather than NEW
YORK, NEW YORK.
underrun: Production of fewer printed copies than was ordered (see also press run
and print order; compare overrun).
UNlX (or Unix): A computer operating system designed to be portable, multitasking,
and multiuser in a time-sharing configuration. UNM is characterized by vario
concepts: plain text files, command line interpreter, hierarchical file system, treatin
devices- and certain types of interprocess communication as files, etc. UNM is
trademark for a powerful operating system, a suite of programs that ma
puter work.
unjustified: A ragged or uneven margin (compare justify and see 22.0, Typography).
upload: To transfer a digital file or data from a local computer to a remote co
uppercase: A capital letter.
URL: Abbreviation for uniform resource locator; an address for a document or info
mation available via the Internet or Web (eg, http://www.jama-archives.org).
vector graphics: The use of geometric primitives such as points, lines, curves,
polygons to represent images in computer graphics; resolution-independent grap
images that can be defined by mathematical .equations and scaled with no loss
quality.
verso: A left-hand page (compare recto).
virgule: A forward slanted line (n used to separate numbers, letters, or other
acters (also called forward slash; see also solidus and 8.4, Punctuation, Fo
[Vir'gule, Solidus]).
virus: A computer program,, usually hidden in another program, that replicates
inserts itself into other programs without the user's knowledge and tha
causes harm to the or destroys data.
VR: Abbreviation for virtual reality.
WAIS: Abbreviation for wide-area information server (see server).
WAN: Acronym for wide-area network. A WAN is typically made up of 2 or more 1
area networks (LANs); the best-known WAN is the Internet.
 Glossary of Publishing Terms

watermark: (1) An image or set of characters produced by thinning a specific area of

paper that is visible when the paper is held up to light; often used to show a company
logo. (2) Faint characters imposed over type or images on a page to prevent unau-
thorized copying or distribution.
web: (1) An offset lithographic printing press. (2) A continuous roll of paper used in
printing.
Web: See World Wide Web.

Web browser: A program for quickly searching and accessing ilnformation on the
. Web.
Web crawler: See spideriing].
- ,
web press:.A lithographic press that prints on a continuous roll (web) of paper.
webRGB: A color profile with a very limited number of color values, primarily designed
for vivid images displayed over the Internet. Not suitable for print reproduction.
Web server: A computer that has Web server software installed and is able to connect
to the Internet.
weight: The weight of 500 sheets (a ream) of.paper. See basis weight.
well: A part of a journal, usually the midd!e pages, in which advertising is not al-
lowed; usually reserved for important scientific and clinical articles in biomedical
journals. Regular features,such as news articles, essays, letters, and book reviews, are
typically run outside the editorial well, where ad interspersion may be.allowed. .
vJf: Abbreviation for wrong font; incorrect or inconsistent type size or typeface.
white space: The area of a page that is free of any text or graphics (compare live area).
widow: A short line ending a paragraph and positioned at the top of a page or
column, to be avoided (compare orphan; see also bad break).
Wi-Fi: The underlying technology of wireless local area networks (LANs), first de-
veloped for mobile computing devices and now used for increasingly diverse ap-
plications.
WMF: Windows MetaFile, a file format created by Microsoft.
word processor: A general term for a computer program with which text consisting of
words and figures can be input, edited, recorded, stored, and printed.
workstation: Computer used for engineering applications, desktop publishing, soft-
ware development, and other types of applications that require a reasonable amount
of computing power and high-quality graphics capabilities.
World Wide Web (WWW): The world's biggest network, used to access infomation via
the Internet with a Web browser (also called the Web).
WORM: Acronym for write once, read many, a technology used to write data per-
n1.1nently onto n t l ~ c kontt rime and allow it to be read many times.
worm: See virus

WPD: 5ficrohoft \['( )rcll'c.rfcc( file for,jl:lt.

lo,,dry of P ~ b l t s h ~ nTerms
g

wrong-reading: I'ILK~LILCL!
10 rc.iJ .I. .I 1111rr(l r IIII.ISC ! I ~ ) I I II C ~ I 10 r1gt1101 [ I I C original
(,I>!.. ~I~LI:III!. rcfcrh lo fill11 (conll>.rrctright-readrng 1
WWW: Scc U : ~ r l dWide Web.

WYSIWYG: Acronym for "what you see is what you get" (pronounced [wizzy-wig]),
meaning that which is displayed o n the colnputcr screen is essentially how the final
product will appear after printing.
x-height: A vertical measurement of a letter, usually equal to the height of a lowercase
letter without ascenders or descenders (eg, x).
XLS: Microsoft Excel file format.

XML: Abbreviation for extensible markup language. Like HTML and SGML, XML is a
markup language designed to describe content by means of user-defined tags and a
DTD to describe the content.

yellow: One of the 4 process printing colors (cyan, magenta, yellow, and black) (see
CM YK).
zip: (n) A compressed file archive that appears as a single file. (v) To compress files
by means of a data compression format that allows files to take u p less space on a disc
or hard drive.

ACKNOWLEDGMENT
Principal author: Jennifer Reiling,JAMA
The following reviewed this section and offered suggestions for revision: Monica
Mungle and J. D. Neff, JAMA and Archives Journals; and Nina Sandlin, Americun
Medical News.
SOURCES

African American Literature Book Club. http://aalbc.corn/writers/publishing_glo~

.htrn. Accessed February 2005.
Angelfire glossary. http://www.angelfire.com/ny3/diGi8tech/PGlossary.h. Accessed
February 2005.

2005.
Brown University computer science glossary. http://www.cascv.brown.edu/compute
/cxxmanual/~ossary/o.htm. Accessed February 2005.
Carbon Colour. Glossary of printers' terms. http://www.carbon.co.uk/glossary.html.
Accessed February 2005.
The Digital Object Identifier System. hnp://www.doi.org. Accessed February 2005.

,February 2005.
ELearning guru. http://e-learningguru.com/gloss.htm~S.
Accessed February 2005.

. -.
 Glossary o f Publishing Terms

Frequently asked questions about the ISBN. http://www.isbn.org/standards/home/isbn

/us/isbnqa.asp#Ql. Accessed June 2006.
A Glossaty of Printing and Paper Terms. Dayton, OH: Mead Corp; 1995.
Hale C, ed. Wired Style: Principles of Englkb Usage in the Digital Age. San Francisco, CA:
Hardwired; 1996.
Hewlett-Packard Upstream CIO. Glossary. http://www.upstreamcio.com/glossary.asp.
Accessed February 2005.
Information & Education Technologli, University of California. http://iet.ucdavis.edu
/glossary.cfm/. Accessed February 2005.

i Intemetnews.com. hnp://inews.w&bopedia.com.Accessed September 2006.

ISSN International Centre. http://www.issn.org/en/node. Accessed ~ u n e2006.
I John Wiley & Sons Inc. Glossary. http://www.wiley.com/college/busin/icmis/~akman
1 /outline/glossary/glossary.htm.Accessed July 2005..
Kasdod WE. Be Columbia Guide to Digital Publishing. New York, IVY: Columbia
University Press; 2003.
Merriarn-Webster's CollegiateDictionary. 11th ed. Springfield, MA: Memarn-Webster; 2003.
NetLingo: the Internet dictionary. http://www.netlingo.com. Accessed ~ e b m a r y2005.
Nau England Journal of Medicine. Author center: how to prepare your figures. http://
authors.nejrn.org/Mis Jtech.asp. Accessed March 2005.
Noe C. A book collector's glossary. http://www.the-bookman.com/main/Glossary.htm.
I Accessed February 2005.
'FWketpul,19th ed. Memphis, TN: International Paper Co; 2003.
Prepressure Page Web site. http://www.prepressure.com. Accessed April 2006.
PubMed tutorial. h t t p : / / w w w . n l m . n i h . g o v / b s d / p u b m e d ~ t u t oAc-
~.
cessed February 2005.
Xainwater Press Web site. http://www.rainwater.com.Accessed May 2006.
Red Hat glossary. http://www.redhat.com/docs/glossary/. Accessed.February 2005.
Scholarly journals at the crossroads: a subversive proposal for electronic publishing.
http://www.arl.org/scomm/subversive/glossary.html. Accessed February 2005.
& a l l ~ ~ ~ o n l i n~el .o s s a 4of Internet terms. http://www.smallbizonline.co.uk
/glossary-of-internet-terms.php. Accessed June 2006.
Steven Black Consulting. Glossaly of terms. http://www.stevenblack.com
/int1%20glossary.html#b. Accessed May 2006.
University of Chicago. http://ccs.uchicago.edu/technotes/n1isc/Glossar~/~loss4.htn1l.
Accessed February 2005.
University of Waterloo. http://www.graphics.u~ater~~~.~a/content/sidebar/glossa~.l~tn~l.
Accessed February 2005.
UNIX tutorial for beginners. http:~www.ee.sur~~y.~.~k/Tc.aching/~nis/.
Accessecl
February 2005.
ssary of Publishing Terms

1111p , ;\\ \\ \\ \ I I I I .
Vihiss Tecl~nc>Iogieb. 1 1 1~ I I I I . I ~ ~ - ~ I CI L I~I ~ ~.\<!L L~- X~W -O~ t ~t-I>ni~ry
1 ~ ~J~
2005.

materials in large print. l~ttp://n~vw.ga.wa.go\~/ada/lgprin~.htn.

Accessed February 2005.
WEbopedia. http://www.webopcdia.con~.
Accessed February 2005.

February 2005.
Wiktionary: a multilingual free encyclopedia. http:fien.wiktionary.org/wiki/Main-Page.
Accessed July 2005.
WordNet: a lexical database for the English language. http://wordnet.princeton.edu.
Accessed February 2005.

phrases commonly found in licensing agreements. http://www.library.yale.edu/-llicense

/definiti.shtml.'~ccessed ~ u2005.
l ~

6
 25.1 25.7
General Dictionaries Peer Review

25.2 25.8
Medical and Scientific Dictionaries Illustrations/Displaying Data

25.3 25.9
. . General Style and Usage Databases

25.4 25.10
Medical/Scientific Style and Usage Guidelines

25.5 25.11
Writing Professional Scientific Writing, Editing,
and Communications Organizations

I-
25.6 and Groups
Ethical and Legal Concerns

- The resources listed in this chapter are provided for information only and do not
'
imply an endorsement by the A M Manual of Style.

General Dictionaries
. <I<*

. ;
.'ih
"-Acronym Finder. http://www.acronymfinder.com
*"
7be.AmericanHeritage Dictionary of the English Language. 4th ed. Boston, MA:
-.Iioughton Mifflin Co; 2000.

Memiam-Webster's CollegiateDictionary. 11th ed. Springfield, MA: Merriam-Webster

I
'

Inc; 2003. http://www.m-w.com/dictionary.htm

Oxford Dictionaiies Online. http://www.askoxFord.com

yourDictionary.com. http://www.yourdictionary.com

t Medical and Scientific Dictionaries

BioTech Life Science Dictionary. http://biotech.icmb.utexas.edu/search/dict
I -search.html

I Dorland's Illustrated Medical Dictionary. 30th ed. Philadelphia, PA: Saunders: 1003
Jablonski S. Dictiona~yof Medical Acronyms 6 Abbreviations. 5th ed. Philndclpl~l.~.
I PA: Hanley & Belfus Inc; 2004.
25.4 Medical/Scientific Style and Usage

Stedman's Medical Dictionary. 28th ed. Baltimore, MD: Lippincott Williams &
Wilkins; 2005.

General Style and Usage

Acronym Finder. http:f/www.acronymfinder.com
Bernstein T. The Cirrejiul \Vriloc A Modern Guide to English Usage. New York, NY:
Free Press; 1998.
Brooks BS, Pinson JL. Working With Words:A Concise Handbook fo
and Editors. 4th ed. New York, NY: BedfordISt Martins Press; 1999.
The Chicago Manual of Style: n e Essential Guidefor Writers, Editors, and Pub-
lishers. 15th ed. Chicago, IL: University of Chicago Press; 2003.
Follett W, Wensberg E, ed. Modern American Usage:A Guide. New York, NY: Hill &.
Wang; 1998.
Fowler H W ,Burchfield RW, ed. m e New Fowler's Modem English
New York, NY: Oxford University Press; 2000.
Gamer BA, ed. A Dictionary of Modern English Usage. 2nd ed. New York, NY:
Oxford University Press; 1998.
'
Gamer BA. Gamer's Modern American Usage. 2nd ed. New York, NY: Oxford
University Press; 2003.
Kasdorf WE. The Columbia Guide to Digital Publishing. New York, NY: Col
University Press; 2003.
Lederer R, Dowis R. Sleeping Dogs Don ?.hay:PracticalAdvicefor the Gram
Challenged, and That's No Lie. New York, NY: St Martins Press; 2001.
McGovem G, Norton R, O'Dowd C. The Web Content Style Guide: An
Refemzcefor Online Writers,Editors and Managers. London, England:
2001.
Pavlicin K, Lyon C. Online Sole Guide: Terms, Usage, and Tips. St Paul, MN: Elva Resa
Publishing; 1998.
Walker JR, Taylor T. The Columbia Guide to Online Style. New York, NY: Columbia
University Press;.1998.
Webster'sDictionary of English Usage. Reprint ed. Springfield, MA: Merriam-Webster
Iric; 2002.
Wissner-Gross E. Unbiased:Editing in a Diuerse Society. Ames: Iowa S
Press; 1999.

Medical/Scientific Style and Usage

American Psychological Association. Publication Manual of the Am
logical Association. 5th ed. Washington, DC: American Psychologic
2001.

968

.
. +..
 i5.5 Writing

ASM Style Manual forJoumak and Book. Washington, DC: American Society of
Microbiology; 1992.
Cohn V, Cope L. News & Numbm: A Guide to Reporting Statistical Cfairnsand
Controversies in Health and Other Fields. 2nd ed. Ames: Iowa State University
Press; 2001.
Coghill AM, Garson LR, eds. The ACS Style Guide; Eflective Cotnmunicariotz of
Scientific Information. 3rd ed. New York, NY: Oxford University Press; 2006.
Davis NM. Medical Abbreviations: 28,000 Conveniences at the Expense of
Communications and Safety. 13th ed. Huntingdon Valley, PA: Neil M Davis
Associates; 2006.
Rubens P, ed. Science and Tecbn<calWriting:A Manual of Style. 2nd ed. New York.
NY: Routledge; 2001.
Style Manual Committee, Council of Science Editors. Scientific Style and Formal: 7I1e
CSE Manual forAuthors, Editors, and Publishers. 7th ed. New York, NY: Rockefeller
University Press, in cooperation with the Council of Science Editors, Reston, VA: 2006.
Sutcliffe AJ, ed. The New York Public Library Writer'sGuide to Style and Usage. Nen-
York, N Y : HarperCollins Publishers; 1994.

Writing
Albert T. A-Z of Medical Writing. London, England: BMJ Books; 2000.
Day RA. How to Write and PubliYb a Scientijic Paper. 6th ed. Phoenix, AZ: Oryx
Press; 1998.
Day RA. Scientijic EngliYb: A Guidefor Scientists and Other Professionals. 2nd ed.
Phoenix, AZ: Oryx Press; 1995.
Gordon KE. The Deluxe Trartsitive Vampire: The UltimateHandbook of Grainmarfor
the Innocent, the &gw, and the Doomed. New York, NY: Pantheon Books; 1993.
Gordon KE. The New Well-Tempered Sentence: A Punctuation Handbook for the
Innocent, the Eagel; and the Doomed. Rev ed. New Haven, CT: Ticknor & Fields;
1993.
Huth EJ. Writing and Publishing in Medicine. 3rd ed. Baltimore, MD: Lippincott
Williams 8r ilki ins; 1999.
Iles RL. Guidebook to'~etter
~ e d i c a Writing.
l Olathe, KS: Island Press; 1997.
Longman Language Activator He@ You Write and Speak Natuml English.
2nd ed. White Plains, NY: Addison Wesley; 2000.
Lunsforcl AA. I h . s y \Vri/cr A I'ockc~t Glri(fc~.
2nd ccl. I\( sto on, hlh: ~~ctlIi)rtl/Sl
h1;lrr ins
l'ress; 2002.
Miller C, Swift K. 771cil(~nri/x)ob
of .Yo~z.~c.~-~cl ~ trd L~ncoln.SE I'm-
\ V t ~ f t r ?2nd
verse; 2001 -
25.7 Peer Review

O'Conner 1'. Woe Is I: The Gmmmaphobe's Guide to Better English in Plain English.
Expanded ed. New York, NY: Riverhead Books; 2003.
Penrose AM, Katz SB. Writing in the Sciences: Exploring Conventions of Scient@c
Discourse. New York, NY: Longman; 2004.
Strunk WJr, White EB. TheElementsofStyle.4th ed. New York, NY: Allyn & Bacon; 2000.
I1 '

Truss L. Eats, Shoots and Leaves: The Zero ToleranceApproach to Punctuation.

New York, NY: Gotham Books; 2004.
Wallraff B. Word Court: Wherein Verbal virtue IS ~ezuarded,CrimesAgainst t h e k n -
guage Are Punished, and Poetic justice Is Done. New York, MT: Narcourt.Inc; 2000.
Wallraff B. Your Own Words. Boulder, CO: Counterpoint Press; 2004.
Walsh B. Lapsing Into a Comma: A Curmudgeon's Guide to the Many Things That
Can Go Wrong in Prinhand How to Avord Them. Lincolnwood, IL: Contempo-
rary Books; 2000.
Warriner JE. English Grammarand Composz'tion: Complete Course. Franklin ed. ~ e w
York, NY: Harcourt Brace Jovanovich Publishers; 1988.'
Williams J. Style: T m Lessons in Clarity and Grace. 6th ed. New York, NY:
2000.

Ethical and Legal Concerns

Fischer MA, Perle EG, Williams JT. Perle and Williams on Publishing Law. 3rd ed.
Englewood Cliffs, NJ: Aspen Law & Business; 2006.
Garner BA. ElementsofLqalStyle. 2nd ed. NewYork, NY:OxFordUniversityPress; 2002.1
Goldstein N, ed. Associated Pms Stylebook and Briefing on Media Law. Rev and
.. 1
updated ed. Cambridge, MA: Perseus Publishing; 2007.
Goldstein P. Copyright's Highway-Fmm Gutenbetg to the CelestialJukebox. Rev ed.
Stanford, CA: Stanford University Press; 2003.
Hart JD. Law of the Web:A Field Guide to Internet Publhhing. Denver, CO: Bradford
Publishing Co; 2003.
Hydson Jones A, McLellan F, eds. Ethical Imrer in Biomedical Publication. Balti-
more, MD: Johns Hopkins University Press; 2000.
I
f

International Trademark Association. http://www.inta.org/ 4

Maggio R. Talking About People: A Guide to Fair and Accurate Language. Phoenix,.,
AZ: Oryx Press; 1997.
Schwartz M; Task Force on Bias-Free Language of the Association of American
University Presses. Guidelinesfor Bias-Free Writing.Bloomington: Indiana Univer
3
sity Press; 1995.

Peer Review I

Fifth International Congress on Peer Review and Biomedical Publication.

http://ww.jama-peer.org

970

4
 m

25.9 Databases

Godlee F, Jefferson T, eds. PeerRm'ew in Health Sciences. 2nd ed. London, England:
BMJ Books; 2003.
Weller A. Editorial Peer Review: Its Strengths and Weaknesses.Medford, NJ: Infor-
mation Todav Inc: 2001.

mm lllustrations/Displaying Data
, Briscoe MH. Preparing Scient@cIllustrations: A Guide to Better Posters, Presenta-
1 tions, and Publications. 2nd ed. New York, NY: Springer-Verlag; 1996.
Cleveland WS. m e Elements of Graphing Data. Summit, NJ: Hobart Press; 1994.
Cleveland WS. Visualizin~
D a t ~Summit,
. NJ: Hobart Press; 1993.
Frankel F. Envisioning Science:-l%e Design and Crafr of the Science Image. Cam-
bridge, MA: MIT Press; 2002.
Harris RL. Information Graphics: A ComprehensiveIllustrated Reference. New York,
NY: Oxford University Press; 2000.
Tufte ER. l%e Cognitive Style of PowerPoint. Cheshire, CT: Graphics Press; 2003.
Tufte ER. Envisioning Information. Cheshire, CT: Graphics Press; 1990.
Tufte ER.'me Visual Display of Quantitative Information. Cheshire, CT: Graphics
Press; 1983.
Tufte ER. Visual Explanations: ma& and Quantities, Euidence and Narrative.
Cheshire, '3':Graphics Press; 1997.

Databases
Biosis
http://www .biosis.org
Biological/biochemical information

I CAB1 Publishing
http://www.cabi-publishing.org/
Abstracts/databases
CAS
http://www.cas.org
Chemistry, toxicology, chemical engineering information
Centers for Disease Control and Prevention
http://www.cdc.gov
CINAHL
http://www.cinahl.corn
Nursing and allied ht;llrh information
C o c h ~ ~ nLci b ~ ~ n
http.,i/\\.\\.\\. ~lpt!.~rc.-
.;(,,fr\\.;lrr. c:c,m/cochr~nc.
-
 L\tl%ASE.conl
// \\.m.\\.
t111p C.IIII>.,W. < , , l l )
Hionlrdical and ~~h.~rtn;l~vlugical information
Gale Director). of Online. Portable, and Internet Databases
http://library.dialog.con~/bluesheets/html/b10230.html
GDB Human Genome Database
http://www.gdb.org
Human Genome Organization (HUGO)
http://www.gene.ucl.ac.uk/hugo
Human Genome Variation Society
http://www. hgvs.org
Institute of Medicine
http://www.nas.edu/iom
MEDNDX
http:/]www.medicalndx.com/
Medical search engine
Medstract.org
http://www.medstract.org
Acronyms and initialisms specific to biology and medicine
. The Merck Manual
http://www.merck.com/mrkshared/mmanual/home.jsp
National Academy of Sciences
http://www.nas.edu

Physician's Guide to the Internet

http://physiciansguide.com
ProMED-mail
http://www.promedmaiI.org
Global electronic reporting system for outbreaks of emerging infectious disea
toxins, a program of the International Society for Infectious Diseases
PsycINFO
http://www.apa.org/psycinfo
Psychiatry/psychology information (abstracts only)
Thomson Scientific
http://www.isinet.com .

US National Library of Medicine Databases

http://www.nlrn.nih.gov
Includes MEDLINE, National Center for Biotechnology Information (NCBI),
Gateway, and PubMed
25.1 1 Professional Scientific Writing. Editing, and Communications Organizations and Groups

World Health Organization

http://www.who.int/en

Guidelines
CONSORT
http://www.consort-statement.org
A research tool that takes an evidence-based approach to improve the quality of
reports of randomized trials
The COPE Report
http://www.publicationethics.org.uk
Committee on Publication Ethics ,
Declaration of Helsinki
http://www.wma.net/e/policy/b3.ht&
Ethical principles for medical research involving human subjects
EMWA Guidelines
http://www.emwa.org/Mum/EM\XTAguidelines.pdf
European Medical Writers Association
GPP Guidelines
http://www.gpp-guidelines.org
The Good Publication Practice (GPP) guidelines encourage responsible and ethical
publication of the results of clinical trials sponsored by pharmaceutical companies.
ICMJEUniform Requirements
http://www.ICMJE.org
International Committee of Medical Journal Editors
PhRMA Principles
http://www.phrma.org/clinicalIuials/
Principles on conduct of clinical trials and communication of clinical trial results'
WAME Policy Statements
http://www.wame.org/resources/policies
World Association of Medical Editors

Professional scientific Writing. Editing. and ~ommunic~tions

Organizations and. Groups
American Copy Editors Society (ACES)
38309 Genesee Lake Rd
Oconomowoc, WI 53066
Newsletter: Newsletter of American Copy Editors Sociey
Web site: http://www.copydesk.org
American Medical Writers Association (AMWA)
40 W Gude Dr, Suite 101
Rockville, MD 20850-1192
Telephone: (301) 294-5303
I';Ix:(301 ) 29.1-7006
E-mail: amwa@an1w;1.org
2 5 1 1 Pfofe\slonal S c ~ e n t ~ fW
~ rc~ t ~ n g
E .d ~ t ~ r i g
and
. Comr-u!:~tat~or~r
Org~nlz~t~o
and
n , GrouPl

Aswiation uf b;lnh Scicrlcc Ecl~~on

(Ahl)
Newsletter: Blllrlir~e
Web site: I~ttp://\\ww.~t.sc.urg
Association o f karnctl ;und l'rofessional Society Publishers (ALPSP)
South House, The Street
Clapham, Worthing B N l j 31111
West Sussex, UK
Telephone: +44 (011903 871 686
Fax: +44 (011903 871 457
E-mail: [email protected]
Journal: kurnerl IJublishing
Newsletter: ALPSP Almi
Web site: http://www.alpsp.~rg/journal.l~t~~~
Board of Editors in the Life Sciences (BELS)
Web site: http://www.hels.org
Committee on Publication Ethics (COPE)
BMJ Publishing Group Ltd
BMA House
Tavistock Square
London WClH 9JR, England
Telephone: +44 (0)20 7383 6602
Fax: +44 (0)20 7383 6668
E-mail: [email protected]
Web site: http://www.publicationethics.org;uk
Copy Editor (Newsletter)
McMurry Inc
McMurry Campus Center
1010 E Missouri Ave
Phoenix, AZ 85014
Telephone: (888) 626-8779
Web site: iittp://www.copyeditor~com
Council of Science Editors (CSE)
c/o Drohan Management Group
12100 Sunset Hills Rd, Suite 130
Reston, VA 20190-5202
Telephone: (703) 437-4377
Fax: (703) 435-4390
E-mail: [email protected]
Journal: Science Editor
Web site: http://www.councilscienceeditors.org
The Editorial Eye (Newsletter)
EEI Communications
66 Canal Center Plaza, Suite 200
 25.1 1 Professional Scientific Writing, Editing, and Communications Organizations and Groups

Alexandria, VA 22314-5507
Telephone: (703) 683-0683
Fax: (703) 6834915
E-mail: [email protected]
. Web site: http://www.eeicornmunications.com/eye/index.html

European Association of Science Editors (FASE)

E-mail: [email protected]
Journal: European Science Editing
Web site: http://www.ease.org.uk .

Europeari Medical Writers Association (EMWA)

Industriestrasse 31
CH-6300 Zug, Switzerland
'Telephone: +41 41 720 3306
Fax: +4141720 3308
E-mail: [email protected]
Web site: http://www.emwa.org
Grammar Hotline Directory
Writing Center
Tidewater Community College
1700 College Cres
Virginia Beach, VA 23456
Telephone: (757) 822-7170
Fax: (757) 427-0327
E-mail: [email protected]/
- Web site: h t t p : / / w w w . t c c . e d u / s t u d e n t s / r e s o u r c e s / ~
International Committee of Medical Journal Editors (ICMJE)
Christine Laine, MD,MPH
ICMJE Secretariat Office
American College of Physicians
190 N Independence Mall W
Philadelphia, PA 19106-1572
Telephone: 215-351-2660
' Fax: (215) 351-2644
E-mail: [email protected]
Web site: http://www.icmje.org
L
MedLinguistics
Medical Linguistics Consulting
28221 Center Ridge Rd, Suite D-20
Westlake, OH 44145
Telephone: (440) 808-5840
E-mail: [email protected]
Newsletter: MedicaLinguistics Update
Web site: http://www.medlinguistics.com
Society for Scholarly Publishing (SSP)
10200 W 44th Ave, Suite 304
Wheat Ridge, CO 80033-2840
25.1 1 Professional Scientific Writing, Editing, and Communications Organ~zar~onr
and Group

Telephone: (303) 422-3914

Fax: (303) 422-8894
E-mail: [email protected]
Journal: Journal of Scholarly Publishing
Web site: http://www.sspnet.org
Society for Technical Communication (STC)
901 N Stuart St, Suite 904
Arlington, VA 22203-1822
Telephone: (703) 522-41 14
Fax: (703) 522-2075
E-mail: [email protected]
Journals: Intercom, Technical Communication
Web site: http://www.stc.org
World Association of Medical Editors (WAME)
Web site: http://www.wame.org

ACKNOWLEDGMENT
Principal author.Jennifer Reiling,JAMA.
 AAPOR (American Association of Public Opinion isotopes, 527-528
Research), survey studies, 850 journal individual word, 479-500
abbreviations journal names, 48, 472-479
academic .degrees, 442- 446 legal material citation format, 7677
addresses, 449- 450 mathematical composition, 908
..address format, 449- 456 MEDLINE, 479-500
agency names, 458-472 military services and ranks, 446-448
amino acids, 604-605 molecular neuroscience terminology,
amino acids sequence variations, 607 730-733
article titles and subtitles, 12 molecular terms, 713-720
Bethesda System for Reporting Cervical mouse strains, 656
Cytology, 549-551 names of persons, 456- 458
biological nomenclature, 741,743744 No. (number), 829
book edition numbers, 55 nonhuman histocompatibility
business firms, 458 terminology, 694
chemical compounds, 526-527 nucleotide sequence variations, 593
chemokine terminology, 677-679 ophthalmology ternlinoloby, 736-738
chromosome terminology, 640-644, orgahization names, 454-455,45& 472
654-655 parentheses, 357
clinical and technical terms, 501-519 pluralization, 369
clot degradation terminology, 675 professional societies, 458- 472
clotting factor terminology, 670-672 publisher reference citation format, 56
collaborative groups, 472 pulmonary and respiratory terminology.
',"
cross-references, 432 771-774
-+y + .. cytokine terminology, 684-685,687 punctuation, 334-335456 457
days of the week, months, eras, 448-449 radioactive isotopes, 527-528
definition, 441 references, 41
.. . DNA, 586-587 RNA terminology, 598
drug names, 574 running foot, 19
echocardiographic terminology, 559-561 Sa~monelfunomenclature, 751-752
elements, 526-527 in situ hybridization, 646647
elements in isotope terminology, 707-710 S1 units, 790, 792
endothelial factors terminology, social titles, 456-458
668-669 spongiform encephalopachies terminology.
' enzymes, 602-603 768-769
figures, 119 state and province names, 451- 454
gene symbols, 609632 ' statistical, 900-902
genus, 743-744 tables, 92-96
gravity, 926 'time, 796
group authorship, 472 titles of persons, 446- 448
guidelines for, 442 unit5 of measure, 519-525
heaclings, 26 L I S : I ~ rulc.~.
~ 501-5112
I~r~lloslasis,067-008 V L ' I ' ~ ! ~ ~ ~i IcCr ~ ~ ) i ~ ~ o lo~y,
-2.\.7?.1
indexing, 429- 430, 501 V ~ M I tertninology, 750.- i s -51,
inhibition of coagulation terminology, 674 al)norm;ll vs normal. nl.x.,ll\ c., ., ),,:

institutes, 458- 472 11Xlgr, .%ql-$x2

interleukin tern~inology,686-(*7 :tIn)n xs lcrlltttuf~,L,,,lc.,.,$.<,:
I S 0 (International Organization for A / ~ r i ~ l # I~~v I ~ <.\f,,,ll<,.v I,, ,- <
Standarclization),456 ; ~ l ) . w i ~\ ~u ..I ! I \ I. II I ~~ l , . : : , , , : ,,,,, q:~.
Index

absolute risk, statistical definition, 853 statistical analysis, 32-33,35

absolute risk reduction, statistical table derivation, 95
definition, 853 written communications, 146
abstracts acronyms
acknowledgments, 146 capitalization, 379-380
fair use, 199 definition, 441
indexing, 435-436 manuscript preparation, 10
manuscript preparation, 11, 20-24,836 tables, 96
online-only articles, 37 actuarial life-table method. See Cutler-Ederer
reference citation format, 49-50 method; life table .
scientific presentations, 292-293 acute vs chronic, usage, 383
structured, 4,20-23,325 adapt vs adopt, usage, 383
tables totals and percentages, 89-90 addenda, original article, 27
unstructured, 23-24 addresses, 12-13,28-29,449-456
academic degrees, capitalization, 378 adherence vs compliance, usage, 384
accent marks in non-English words, 422-423 adjectives, 322, 363
acceptance date, 27 adjustment, statistical definition, 853
acceptance of manuscript, 27-28 adopt vs adapt, usage, 383
access to data statement adverbs, 322-323
acknowledgments, 183 adverse drug reactions, 566-567,569
disclosure, 173-174 adverse effect vs side effect, adverse event,
International Committee of Medical Journal adverse reaction, usage, 384
Editors, 142,144-145,183 advertising
peer reviewers, 183 advertising-to-editorial page ratio, 281
accident vs injury, usage, 382-383 advertorials, 282-283
accuracy, statistical'definition, 853 content, 27&280,282
acknowledgments criteria for in health care, 278-280
access to dam statement, 142,144145,182-183 editorial responsibilities, 276
additional contributions, 35-36 e-prints; 287-288
author contributions, 142-144 reprints, 287-288
authorship, 14 scheduling, 282
authorship criteria, 130,132 separation from editorial content, 310
citation fonnat, 36 sponsored supplements, 283-284
conflict of interest, 170-173 Web sites, 285
contributions recognized. 140-141 advertorials, 282-283
degrees, 35 afFect vs effect, usage, 384
disclaimer, 33-34 affiliation footnotes
'editing assistance for manuscripts, 132 conflict of interest, 172
editorial assessment, 35 format, 17-19
editorial assistance. 141 group authorship, 137
equipment in research, 584 punctuation, 340
financial disclosure, 30-31,142 title page of manuscript, 28
funding or grant support, 31, 140-141, African American, usage, 415-416
145-146.173 age, inclusive language, 416
group authorship, 30, 136,141-142 age, referents, 410
institutional affiliation, 35-36 agency names, abbreviations, 458-472
manuscript preparation, 27-36 age vs aged, school-age, school-aged, teen:
nonspecific groups, 141 teenaged, usage, 384-385
online journals, 35,37 aggravate vs irritate, usage, 385 .
online sponsorship, 287 aggregate data, statistical definition, 853
order of elements, 143-144,146 agreement, statistical definition, 853
patient and subject anonymity, 230 . airplane names, 372,925
permission of those acknowledged, 146 algorithm, statistical definition, 85.3
previous presentations, 34 algorithms, visual illustrations, 107,110
references in manuscripts. 837 alleles .
reproi:~ctionof tables and figures, 34-35 bacterial gene terminology, 658
reviewer credits, 222 blood group terminology, 541
sponsorship. 32. 145-146.173 tI1A terminology. 630-694
 Index

immunoglobulin rerminolosy, 700-701 appendixes to articles, 36

mouse gene terminology. 650-652.654 appositives, punctuation with comma, 337
symbols, 628-632 apt vs liable, likely, usage, 385-386
T-cell receptor gene terminology, 704. area, dual reporting conventional and
yeast gene terminology, 657 SI units, 794
allelic variant, nomenclature, 594 area under the curve (AUC), statistical
u (alpha), statistical definition, 854 definition, 855
alphabetizing, 92, 425-429, 432 articles (a, an! the)
ALPSP (Association of Learned and Professional eponyms, 779
Scholarly Publishers), 185, 193, 974 reference titles, 44, 46
although vs though, usage, 385 usage, 412
American Association of Public Opinion Research article titles
(AAPOR), 850 abbreviations, 12
American Clinical Neurophysiology Society, 724 capitalization, 12
American Medical Writers Association (-A), city, state, and country names, 12-13
141, 973 drug names, 11
American Society of Magazine Editors genus and species names, 11-12
advertising policies, 276 numbers, 11
advertorials, 282-283 reference citation format, 46
sponsored supplements, 283 short title, 20
amino acid terminology, 604607 title page of manuscript, 8-13
among vs between, usage, 385 article types, 3-5 '

analog and analogue, usage, 385 article vs manuscript, paper, typesctipt,

analysis, statistical definition, 854 usage, 386
analysis of covariance (ANCOVA), statistical artifact, statistical definition, 855
definition, 854 ;lswssment. skltisticnl tlefinition. 855
analysis of residuals. See linear regression assignment, statistical definition. 855
analysis of variance (ANOVA), statistical assignment of copyright, 193-196
definition, 854-855 association, statistical definition, 855-856
anatomy, terminology, 410 Association of Learned, and Professional Scholarly
ANCOVA (analysis of covariance), statistical Publishers (ALPSP), 185, 193,974
definition, 854 association vs relationship, usage, 386
anonymity assure vs ensure, insure, usage, 386-387
acknowledgments, 141 as vs because, since, usage, 386
authorship, 132-133 attenuate vs attenuation, usage, 387
peer review, 221-222 attributable risk, statistical definition, 856 ,
photographs, 121 attributable risk percentage, statistical
anonymous authorship, 189 definition, 856
ANOVA (analysis of variance), statistical attributable risk reduction, statistical
definition, 854-855 definition, 856
Ansari-Bradley dispersion test, statistical AUC (area under the curve), statistical
definition, 855 definition, 855
Anthony Nolan Research Institute, 688 audiotapes, reference citation format, 62
antibodies, 538, 694-696 (see also monoclonal audit of editorial process, 272-274
antibodies) author information, 16-19
Anticybersquatting Consumer Protection Act, author pays, definition, 184-185
214 authorship
antigens, nomenclature, 538-539 acknowledgments, 129. 132
Apgar score, 735-736 anonymous authorship, 132-133
apologetic quotation marks, 360 author contributions, 29-30, 142-144
apostrophe changes in, 134-135
compound terms, 362 ' conflict of inrerest. 12')- 130
eponyms, 778 confllcr of inrere.kr d~\i-lc,\i~rc..1'0-173
joint possession. 362-363 c o n t r ~ t x ~ r o 128r,
plural format~ons,363 ~ < ~ p v r l ~191 l l- ~l o, \
possessive, 362 c < > r r c - y w n d ~ n;a;~tl~~,;,
g ;:1
prime sign, 363 < rIler1.1 12S- 13i1
time ancl money, 363 c l c ~ r t l ; l n (;ip.li tt.lrlon O! .I,III,OI 1 4 1
. , ! l ~VI.~.I;>
t ~ s I , <,II:IIIII,,~/ I binomial species names, 742-744
,lchn~:~, nn. 12-. I :ti binomial style for virus species, 759
I ~ r n J ~ r ol gr ~ m n rsuppon, 31 BioCode, 741
gl1031~i1111orh.131-132 biological plausibility, statistical definition, 857
RrOUp and collalwr~tivc..14. 51, 135-137, 472 biopsy, usage, 387-388
gucst nurliorship. 131 bivariatelbivariable analysis, statistical
nurnkr of aurhors, 133-134 definition, 857
online-only articles. 37 Bland-Altman plot, statistical definition, 857 :

order of. 134 blinded (masked) assignment, statistical

[>scudonymousauthorship, 132-133 definition, 858
scienrilic nlisconduct, 166 blinded peer review, 220-221, 264-265, 306-307
rirlc page of rnanuscripr, 13 blinding vs masking, usage, 388, 738
:~urIiors'names, reference citation format, block quotations, 361-362
44- 45, 54 block randomization, statistical definition, 858
average. statistic~ldefinition, 856
awards, capitali~?tion,372, 376
axis labels in figures, capitalization, 119
blood gas terminology, 771-774
blood group terminology, 536-542, 615-616
blotting terminology, 601
%
axis tern~sin electrocardiop;raphy 556 Blwn~hocvteterminolom. 701
boldface m e -
2

back-formations of words, 407- 408 indexing, 431

bacterial nomenclature table stubs, 87
gene terminology, 658 totals in tables, 89
principles of, 531-532 usage, 924-925
strains, 752 Bonfemni adjustment, statistical definition, 858
terminology, 748-753 book reviews
bar graphs, 101-104, 114 authorship criteria, 129
base moieties in drug names, 570-572 conflict of interest disclosure, 171
base units in SI. 788 format, 5
Bayesian analysis, statistical definition, 856 libel, 239
&ell terminology, 701 reference format, 51
because of vs caused by, due to, owing to, books
usage. 387 chapter title reference Citation, 53-54
because vs as, since, usage, 386 online books. references. 42
Belmont Report, 227-228 page number citation format, 56
Beme Convention, 188, 207-208 print references, 42
(beta) level, statistical definition, 856-857 punctuation in references, 56
Bethesda System for Reporting Cervical reference citation format, 46, 67-68
Cytology, 549-551 titles in italics, 925
bemeen vs among, usage, 385 bootstrap analysis, 849
bias bootstrap method, statistical definition, 858
conflict of interest, 171 box and whisker plot, 106, 114
indusuy-sponsored studies, 173-174 boxes, 123
meta-analysis, 848 brackets
peer reviewers, 174175 case change in quotations, 359
selection in casecontrol study, 846-847 '
ellipses and capitalization change, 365
selection in case series, 847 formulas, 358,910
in study design, 838 mathematical composition, 908-909 .'!
bias, statistical definition, 857
biblical material, in references, 62, 343
bibliognihic databases
within parentheses, 358
quotations, 357-358
breastfeed vs nurse, usage, 388
< 14
duplicate submission, 151-152 brief reports, 3
group authorship identification, 136-13 British Approved Names (BAN), 565
libelous material, 241 Brown-Mood procedure, statistical definition,
retractions, 161-162 business 'firms, abbreviations, 458
bibliographic elements in references, 41 bylines
bimodal distribution, sratistical difinirion, 857 acknowledgments, 146 it

binary variable, staristical definition. 857 author affiliations, 18-19 . P..

binomial distriburion. statistical definiriun. 857 corresponding author. 28-29 I
 Index

death of an author. 17 legislation, 376

disclaimer, 33-34 mathematical composition, 912
group authorship, 15-16, 135-136 monuments, 372
number of authors, 133-134 mouse and rat gene nomenclature, 649650
pseudonymous authorship, 133 mouse gene terminology, 633
punctuation, 15-16 mouse strains, 655
reference citation format, 51, 67 musical compositions, 372
title page of manuscript, 13-14 non-English words, 46, 422
nucleotides, 593
cadaver vs donor, usage, 388 numbers, 372
Caenorhabditis elegans, gene terminology, 657 organisms, 47,377, 742-743
cancer terminology, 546-551, 833 organization names, 377-378
can vs may, usage, 388 paintings, 372
capitalization planes (airplanes), 372
academic degrees, 378 plays, 372
atronyms, 379-380 pluralization, 363
airplanes, 372 prefixes. 372
article titles, 12, 371 proprietary drug names, 568-569
awards, 372, 376 proprietary names, 376,584
axis labels in figures, 119 pulmonary and respiratory terminology.
bacterial gene terminology, 658 771-774
book chapter references, 53 quoktion marks, 360,371
broadcasts, 372 reference titles. 372
chromosome terminology, 654 restriction enzyme terminology, 601
compass directions, 375 seasons, 377
complement terminology, 681-682 sentences, 371
composite figures, 117 ship names, 372
computer terms, 380 SI units, 790
conferences, 377-378 small caps, 772-774,926
conjunctions, 372, 377-378 . sociocultural designations. 375-376
coordinating conjunctions, 372 software, 372
..corporations, 372 space vehicle names, 372
deities, 377 suffixes, 372
designators, 378-379 tables, 378-379
DNA sequences, 592 table stubs, 87, 371
' drug names, 376 taxa, 742-743
..'electrocardiographyterminology, 555-556 test names, 377
electronic systems, 372 titles, 371-372
enumerations in tables, 829 titles of persons, 378
eponyms, 376,778 trademarks, 372, 376
' equipment, 376 .trade names, 380
Escherichia coli, 749 uppercase usage, 924
events, 376 use of ellipses, 365
figures, 119, 378-379 viral terminology, 756-758
gene symbols, 609 wheri not to use, 379
genus and species names, 372; 377 words derived from proper nouns, 376
geographic names, 374 yeast gene terminology, 657
governmental agencies, 377-378 cardiology
Gram stain, 749-750 cardiac muscle terminology, 562
Greek letters, 372, 781-782 cellular and molecular terminology,
headings. 372 562-563
holid;~)-s,377 coronary artery angiographic classifications
hyphenated cornpuuntLs. 373-374 terminology, 561
hyphcnnr~on.3.17 echocardiographic terminology, 553-554
indexing, 429 ejection fraction, 558
inqtirution n:lrnes 577-3% eleflrocardiography terrninoIogy, j53-563
intcrc:l[qx.il conlpountl~.?.?(I gcnc ~erminology.617-618
inrc.rlc~~k~nI t ~ r l n ~ n o l o(kY()-(hi;-
~y, hc:ln t l t . ~ ~l:lssific:l~i~~,
: ~ ~ 5(,1-562
 . .,,<l,,3l<>;b
-
ljt.~rl
I. r * , , : . , l . . , . . I

> O I ~ J1 8
1111p1.1nk~l
r ! l # i f l a 4.

~ ~ \ tlcf~l~r~ll.~~or~.
L . I ~ ~ I Icflrr\
,si
ClIJtlon
duplicate publication, 148
<<o
figures. 120
559-%~ group authorship, 137-138
jugular venous pulsc ter~ninologv.557 legal material, 72-73
nlurnlur terminology. 557 open-access publishing, 185
pacen1;lkt.r codes, 561-562 public domain, 139
case, ststistical definirion, 859 punmation, 42-44
case-control study, 846-847,851 references, 42-44
case-control study, statistical definition, 859 retractions, 161
case-fatality rate, statistical definition, 859 citation format, 14,36
case repom. 4. 229-231 classical material, reference citation format, 62
. cases, case-control study, 846-847 classic vs classical, usage, 389-330
case series, statistical definition, 859 clichh, 325
case series, study design, 847 client vs consumer, patient, case, subject,
case vs patient, subject, client, consumer, usage, 388389
usage, 388389 clinical imaging, 112
catatonic, usage, 389 clinical practice guidelines, 4
categorical data, statistical definition, 859 cliical terms, abbreviations, 501-519
categorical variable. See nominal variable clinical trial registration, 183
cause/causation, statistical definition, 859 clinical trials, online-only articles, 37
caused by vs because of, due to, owing to, cliician vs praaitioner, provider,
usage, 387 usage, 390,400-401
CC chemokine subfamily, 677-678 clock referents, 411
CD (cluster of differentiation) cell terminology, cloning vector terminology, 601
679480,701-703 clot degradation terminology, 675
CD-ROMs,62,6768,% clotting factor terminology, 669-674
cellular adhesion molecules. 619,668 coagulation test terminology, 675676
cellular and molecular cardiology terminology, Codvan Q test, statistical definition, 860
' 562-563 codingltagging, proofreading, 932-933
censored data, statistical definition, 859 codons, DNA, 589,591-592,595,604
central limit theorem, statistical definition, 860 codom, RNA, 597-598
central tendency, statistical definition, 860 d o n s , and amino acids, 604,607
cesarean delivery vs cesarean section, usage, 389 coefficient of determination, statistical
chapter numbers in book references, 56 definition, 860861
charge, 714 coeff~cientof variation, statistical definition,
chemical compounds, hyphenation, 351 861
chemical formulas, 358,526-527 cohort, statistical dehition. 861
chemical names of drugs, 569 cohort effect, statistical definition, 861
chemical prefixes cohort study, 846,851
capitalition, 374 cohort study, stadstical definition, 861
Greek letters, 781 Collaborating Centre for International Drug
indexing, 426 Monitoring, 567
italics, 926 collaborative authorship, references, 44- 45
small caps, 926 collaborative groups, 51,135-138,472
chemokine terminology, 677-679 collective nouns, 319,329
x2 test (chi-square test), statistical definition, 860 collective works, copyright, 191-192
Chicago Manual of Style, citation format, 14 colloquialisms, 324325,409
chief corr;plaint vs chief concern, usage, 389 colon
Chlamydia and Chlamydopbila, taxonomy, biblical material, 343
74s-749 definition, 342
Chlamydophila,747-748 enumerations, 343
choropleth map, statistical definition, 860 numbers, 343
chromosome terminology, 637-648,652-655 quotations, 343
chronic vs acute, usage, 383 ratios, 343,832
chunk sample, statistical definition, 860 references, 41.343
circumlocution, 406-407 time, 343
cis, 374 when not to use, 342-343
 Index

colony-stimulatingfactor terminology, 577-578, confidence intervals, 843, 850

685-686 confidence limits (CLs), statistical definition.862
colors (graphs), 114 confidentiality
column headings, 86-87 case reports, 229-231
combination drug names, 572-573 conflict of interest, 17j
comma definition, 218
addresses, 340 editorial board members selection, 224
chromosome terminology, 646 editors selection, 224
conjunctions, 337-338 errors requiring correction, 180
dates, 340 financial disclosure, in
degrees and titles, 340 HIl'AA (Health Insurance I'ortability and
dialogue, 341 Accountability Act), 230
genotype terminology, 630 journalistic privilege, 223-224
.HLA terminology, 693 legal proceedings, 223-224
indicating omission, 341. peer review, 158, 199, 218-223, 261-262,
numbers, 340-341 264-265,36307
organization names, 337 - peer reviewers, 221
parenthetical expressions, 338-339 scientific misconduct, 158, 161, 166, 222
placement, 341 conflict of interest
quotations, 360 acknowledgments, 142, 170-173
references, 41 author requirements, 170-173
separating groups of words, 336-337. authorship dteria, 129-130
series, 337-338 defamation, 240-241
setting off phrases, 337-338 definition, 168
.-.
units of measure, 341 disclosure, 30-31
usage, 336 editorial assessment, 301
Comment (Discussion), manuscript preparation, editorial board members, 175, 177, 271-272
26,838 editors, 1.75..177
Committee of the Interriational Union of financialdixlosure, 168-170, 177
Biochemistry and Molecular Biology industry-sponsored studies, ,173-174
(Nc-TUBMB), 721 journal editors, 261-262
Committee on National Statistics, 1 8 1 ~ 1 8 ~ peer review, 169-170,220
Committee on Publication Ethics (COPE) peer reviewers, 174175,.177,306
editorial freedom, policies for, 253-257 relevant, 169
informed consent, 227 unpublished material, 176
peer review and confidentiality, 218-219 confounding, case-control sudy, 846-847
scientific misconduct and retraction, 160 confounding, statistical definition, 862
common fractions, 824 confounding variable, stitistical definition, 862
.. . compare to vs compare with, usage, 390 Congressional hearings in reference citations, 76
compass directions, capitalization, 375 conjunctions . .
compilations, copyright, 192 capitalization, 372, 377-378
complement terminology, 680-683 HL4 termindogy, 693
compliance vs adherence, usage, 384 punctuation with comma, 337
compose vs comprise, usage, 390 conjunctive adverbs, punctuation with
composite figures and legends, 116-li7 semicolon, 341-342
composition, manuscript preparation, 309 consensus statement, 4
compound official titles, hyphenation, 351-352
compound subject, definition, 329-330
CONSORT (Consolidated Standards of or tin^
Trials)
compound words, hyphenation, 344-348 equivalence and noninferioricy'trials, 843-846
comprise vs compose, usage, 390 flow diagrams, 107, 842
computer t e r n , capitalization, 380 format for randomized controlled trial, 838-841
conclusions, 22-23 observational studies, 846
concordant p:tir, st:ttistical definition, 861 constitnt gene .segment, 699
l'ontlitional prol~ability, statistical definition, 861 consumer vs client, case, patient, subject, usage,
conference repons, 5 388-389
tvnfrrcnccs. 200-201, 377-378
(Onfidrncc inren;ll (CI), st;ttistical clefinition,
contingency coefficient, statistical definition,862 --
,

I
contingency table, statistical definition, 862 \

Wb1 - t i o Z
continual vs continuol~s,ils;tge. 390-391
Index

continuous data, sr;ltistical d c f ~ n ~ r ~NLo~>.

contractions, 317,322
contrast VS. COntCISt agent, conlrJsr III.IICII.I~. ,,rr, lnJn Ancry snjilujirs[)h~~ L I J * \ ~ I I L allt>rls

contrdst medium, usage. 391 tcnlunology. 563

contributory cause, sratistical definition, 863 corporations, apitaliulion, 372
control, statistical definition, 863 corrections
controlled clinical tri:rl, srari.srical cit;~rionsin listed references. 52
MI.+
(lcli~~itio~~, error i l l ~ ~ ~ ~ l ~111:1lcri;1l.
l i s l ~ c310 ~l
conlrollerl clinic;rl lri;rl, sludy clcsixn. X.W-X4 I ~~oticcs, duplicate pul)licrtion. 5.2
controlled vocabulary, indexing, 24, .ijj- 430 reference citation format, 52
controls, 388-389,846-847 scientific errors, 162
convenience salnple, st:rtistiorl rlcfinition. 863 correlation, sratisticdl definition. 863
copyediting, 308-309 Sw ULSU III;IIIII.W~~~>~S correlation coefficient, statistic-a1 definition,
copyediting marks, 929-932 863-864
copy marking, mathematical compositiol~,907 correlative conjunctions, 325-326
copyright correspondence, 5, 177, 198-199.See ako letters
al,slclc~s,IF) lo the editor
adaptation and reproduction, 197-200 correspondiig author
anonymous authorship, 133,189 access to data statement, 173
assignment or license, 193-196 acknowledgments, financial contributions, 141
Association of Lamed and Professional authorship criteria, 129, 131
e
Scholarly Publishers (ALI'SP), 185 contact information, 28-29
authorship criteria, 129-130 duplicate publication, 151
collective works, 191-192 group authorship. 135.137
conferences, 200-201 scientific misconduct, 160, 166
correspondence. 198-199 cost-benefit analysis, statistical definition, 864
definition, 179,186 cost-benefit analysis, study design, 849
discussants, 200-201 cost-effectiveness analysis, statistical
DMCA (Digital Millennium Copyright ACT), 188 definition, 864
domain names, 213234 cost-effectivenessanalysis, study design, 849
duplicate publication, 151-152 . cost-utility analysis, statistical definition, 864
duration of protection, 188-193 Council of Science Editors (CSE)
electronic media, 188,200-201 authorship criteria, 129
fair use exdusions. 200 conflict of interest, 169
federal employees. 195-196 editorial freedom, policies for, 253-257
history, 186 peer review and confidentiality, 218-219
institutional owners, 1% scientific misconduct and retraction, 160
international, 207-208 covariates, statistical definition, 864
international treaties, 188 covert duplication. See duplicate publication
Internet, 188 Cox-Mantel test, statistical definition, 864
liability concerns, 241-242 Cox proportional hazards [regression] model,
linkiig and framing, 200 statistical definition, 864
misappropriation of data, 158 cranial nerve terminology, 722-723
moral rights of artk~~ and writers and credit lines, admowledgments, 146
copyright, 208 criterion standard, statistical definition, 864
notice and registration, 196-197 Cronbach a, statistical definition, 865
ordl communications, 199 crossdesign synthesis, statistical definition, 865
ownership, 179-184 crossover design, statistical definition, 865
permission of those acknowledged, 146 crossover trial, study design, 842-843
pseudonymous authorship, 189 cross-references
reprint permissions, 202-207 abbreviations, 430,432
reproduction or adaption permission, 202 alphabetizing, 432
resources, 208-209 corrections to published material, 310
trademarks, 210-214 double posting, 428,432-433
trade names, 213 indexing, 426,428
transfer, 195,200-201 vocabulary control, 435
US Copyright Law of 1976,187-188 cross-sectional study, 843-844,. 851
written communicdtions, 199 cross-sectional study, statistical.definition,865
 Index

crude death rate, statistical definition, 865 defamation laws, definition, 226
C statistic, statistical definition, 859 defibrillator code terms, 560
cumulative incidence, statistical definition, 865 deflection terms in elecuocardiography, 553-j56
currency (money), 817418,823 degrees
Cutler-Ederer method, statistical definition, 865 academic, 13, 442- 446
cut point, statistical definition, 865 acknowledgments, 35
CXC chemokine subfamily, 677-678 manuscript preparation, 14-15
CXC3 chemokine subfamily, 677-678 personal communications citations, 61
cybersquatting, 214 -punctuation of honorifics, 334-335
cytokine terminology, 684-685 punctuation with comma, 340
degrees of freedom (df), statistical definition, 867
dagger to indicate death of an author, 17 dehumanizing language
DALYs (disability-adjusted life-years), 849 disciplines or specialties, 408-410
DALYs (disability-adjusted life-years), statistical inclusive language, 412-416
definition, 868 patients vs cases, 388-389
dangling participles, 323 survivor vs victim, 402
dashes, 344, 352-353 deidentification, patient and subject anonymity,
data, statistical definition, 865 , 232
databases deities, capitalization, 377
bacterial gene terminology, 658 delayed open access, definition, 185
embedded indexing, 436 Department of Health and Human Services, 156
Enzyme Nomenclature Database, 721 Department of Health and Human Services
genomic sequence information, 596-597 Regulations foi the Protection of H u n ~ ~ n
HGVS, 593-594 Subjects, 228
IMGT/HLA Sequence Database, 688 dependent clauses; punctuation with ro1nm;l. 337
Mouse Genome Database, 650 dependent varialjle; st;ttistic~ldefinition. 866
nucleotides, 597 derivative chromosomes, 647-648
Online Mendelian hiheritance in Animals derivative works, 192, 199
( O W , 657 derived units, 788-789
Online Mendelian Inheritance in Man (OMLM), dermatome terminology, 723-724
610,631 - ? I -- describe vs report, usage, 391
'

proteins, 597 t,. I

descriptive articles, 4
Rat Genome Database, 650 " descriptive statistics, statistical definition. 866
reference citation formac70-71 design, typography, 91&920
SearchGene5 (Human Gene Nomenclature designators, capitalition, 378-379
Database), 610 device terminology, 583-584
viral nomenclature, 756 df (degrees of freedom), statistical definition. ~ 6 7
data dredging, statistical definition, 866 diabetes mellir~sterminology, 391
data extraction in review or meta-analysis diacritics in non-English words, 422- 423
abstract, 23 , diagnose vs evaluate, examine, identify, usilgr.
data sharing, 181-183 391
data sources in review or meta-analysis, 22 diagnostic discrimination, statistical definition.
data synthesis in review or meta-analysis 867468
abstract, 23 diagnostic tests, study design, 849-850
dates diagrams, 106-110,120
comma, 340 , dialogue, 341, 359
question mark, 335 dichotomous variable, statistical definition: 868
references, 48, 56 diction, definition, 324-325
virgule, 354 die from vs die of, usage, 391
days of the week, months, eras, abbreviations, digital files, figures submission, 120
447- 450 digital images, 158-159, 199-200
death/incapacitation of author, 131 Digital Image Submission Criteria (DISC), 12 1
death of an author, in byline, 17 Digital Millennium Copyright Act (DMCA), 188
decimal forms of numbers, 773, 830 digital object identifier (DOI), 27-28, 63-67
decimals, 334 diphthongs, definition, 921
decision analysis, statistical definition, 866 direct cause, statistical definition, 868
decision trees, 107, 109 disability, inclusive lang~l:ige,416- 4 17
clehln:~tion,clefinition, 235-238 lifc.-yc:~rs(I)Al,Yz), 8.10
tlis:ll)iliry-:~tlj~~~tccl
dex

disability-adjusred life-years (DALYs), st;~tistical INN (intern3tic)n:il r~)npr\

,prl<-ur)I ~ J ~ ~ C I .

definition, 868 565-566

disclaimer, acknowledgments. 33-34 moieties, 570-572
disclosure multipledrug regimens, 573-574
access to data staremenr, 173-174 names that include a percenrage, 573
conflict of interesr, 169 nonproprietary Generic) names, 567-569
etlitori:~lpolicy, 272 mdiopharmaceuticals, 579
onlinc pccr rcviewers, 174 stereokomers, 572
~xcrreview and confidentiality, 219-220 study design, 838-847
discordant pair, statisricxl definition, 868 terminology, 565-572
discrete variable, statistic~lldefinition. 868 trivial names, 570
cliscrilninzint analysis, statisrical definition, 868 dual reporting conventional and SI units,
discussants, 51-52.200-201 794-797
I>iscussion(Comment), manuscript preparation. due to vs owing to, caused by, because of,
26,838 usage, 387
d1 . - vs. disk, usage, 392,724,737
..
u Dukes cancer stage system, 549
disease names, :.)rphenation, 350-351 Duncan multiple range test, statistical
disinterested vs uninterested, usage, - 392 definition, 869
disks, intervertebral, terminology, 723-724 Dumen test, statistical definition, 869
dispersion, sta!istical definition, 868 Durn test, statistical definition, 869
dissertations, reference citation format, 58-59 duplicate publication
distribution, statistical definition, 868 acceptable forms, 149-150
diversity (Dl gene segment, 699-700,703-704 definition, 148
division in mathematical composition, 910-911 editorial policies for, 151-152
DMCA (Digital Millennium Copyright Act), 188 notification, 152-153
DNA peer review and confidentiality, 219
families terminology, 603-604 ' reference citation format, 52
general terminology, 585-593 release of scientific data. 292
sequence terminology, 583-593 duplicate submission, notification, 152-153
sequence variations, 593-597 Durbin-Watson test, statistical definition, 869
doctor vs physician, usage, 392 DVDs, reference citation format, 62
DOI, 27-28,63-67
domain names, trademark protection, 213-214 EASE (European Association of Science Edit01
donor vs cadaver. usage, 388. 260.466.975
dosage vs dose, usage, 392 echocardiographic terminology, 557-558
dose-response relationship, statistical ecological fallacy, statistical definition, 869
definition. 868 editing, authorship criteria, 132
dot (point) graph, 105-106 edition number, book reference citation
double-blind vs single-blind peer review, 307 format, 55
double negaiives. 322 editorial, definition, 4
double posting, 426428,432-433,435 editorial assessment
dropped cap, 924 acknowledgments, 35
- . Dmwpbih mhnogaster, gene terminology, conflict of interest, 169
656-657 criteria for evaluation, 303304
drug names onliie-only articles, 38
article titles and subtitles, 11 peer review, 301-302
capitalization, 376 policies and procedures for, 263-264
Greek leners, 781 revisions, 307-308
proprietary trade names, 357 editorial assistance, acknowledgments, 141
unswctured abstracts, 24 editorial audit, 272-274
drug names that include a percentage, 573 ' editorial board members
drugs confidentiality in selection, 224
chemical names of drugs, 569 conflict of interest, 175, 177
code designations. 570 role of, 270-272
combination names, 572-573 editorial freedom and integrity, 243-257
development and approval process, 566567 editorial policy, scientific misconduct, 159-16
dosages, 797 editorial priority for publication, W)4
hormone terminology, 574-576 editorial processing, 308-3439
cul~torinlresponsibili~ies government orgnniwtion reports, 69-70
acceptance of manuscript, 267-268 1..Is1.uxvc.s.
. 71
advertising, 276 online conference proceedings. 7 1
audit of editorial process, 272-274 online journals. 6467
board members selection, ,271 online newspapers, 69
manuscript editing, 929-933 software. 70
news releases, 296-298 videotapes, 62
peer review, 264-265 Web sites, 68-69
quality review afrer publication, 274 reprints, 201
reprints and e-prints, 287-288 tal~les,84, 96
revision, 266 titles and quotation marks. 361
roles, procedures, and policies, 260-270 electronic systems, capitalization, 372
editorials electroretinogram terminology, 737
authorship criteria, 129 elements, abbreviations, 526-j27
conflict of interest disclohre, 171 elements in isotope terminology. 707-708
defamation, 238-239 ellipses
unsigned, 132-133 change in capitalization, 365
editors definition, 364
board members selection, 271 incomplete expressions, 364
confidentiality in selection, 224 omissions from text, 364-366
conflict of interest, 175, 177 quotations, 359
effectiveness, randomized controlled uial, 838 in tables, 88
effectiveness, statistical definition, 869 tables, 366
effective vs effectiveness, efficacious, efficacy, elliptical comparisons, 326
usage, 392 e-mail
effect of observation, statistical definition, 869 corresponding author, 29
effect size, meta-analysis, 848 . figures, preparing to submit, 120
effect size, statistical definition, 869 online advertising, 286
&ect vs affect, usage, 384 personal communications citations, 61
efficacy, randomized controlled trial, 838 reference citation format, 71
efficacy, statistical definition, 869 embargo, news, 292-294
efficacy vs effectiveness, usage;392 embedded indexing, definition, 436
efficiency, statistical definition, 869 em dash, usage, 352-353
effort-to-yield measures, statistical definition. 869 en dash, use with hyphenated phrase, 352-353
eg vs ie, usage, 393 endemic vs epidemic, hyperendemic,
eISSNs, 479 pandemic, usage, 393
ejection fraction, 558 endothelial factors terminology, 668-669
elec'tmrdiography terminology, 553-556 enerhy vs c-alorie, kilocxlorie, usage, 796797
electrodes, 724-730 ensure vs assure, insure, usage, 386-387
electroencephalognphic terminology, 724-727 Entrez Genome, 658
electrcxncephalography, Greek letters, 781 enumerations, punctuation
electrogram terminology, 556 colon, 343 .
electronic markup, 308-309, 932 parentheses, 356, 828
electronic media. See ako online journals period, 334
controlled vocabulary indexing, 435- 436 semicolon, 342
copyright, 188 , enumerations, rounding numbers, 826827
discussants, permission to cite, 200-201 enzymes, 601-603,720-722, 925
editorial priority for publication, 303 epidemic vs endemic, hyperendemic,
editorial processing, 308-309 pandemic, usage, 393
Greek letters typesetting, 783 epigraphs, 24-25
linking and framing, 200 eponyms
~ V C ~ ; I K I I ~ Os,I I,500
III:II>LIS(.~~I>! , l ' : ~ ~ ~ i ~ : ~ l i x570.
. : ~ 77s~io~i,
jOO-.3 10, 9.52-933
prooI.rc:~di~~g, c'orrcct L I S : I ~ C 777-7x0
.
reference citation For~lvat,62-64 indexing, 434- 435
audiotapes. 62 nonpossessivc forn~,7-r;
CI)-KOMS, 67-(>8 ~I:llis~ic.;~l rcrtll., ~ 5 1
~l~tl:ll)~lsc.s,
70-7 1 c-l)ril~ls,Lol, rc,-rlN,, 2 s -
e-m:~il,71 ~ ~ ~ l ~ l l i35u b,n s( M,I - - O I I I
$ 1 1 <
equipment fewer vs less, usage, 394
capitalization, 376 fibrinolysis terminology, 675
conflict of interest, 173 fiction, defamation, 239
terminoloby, 583-584 fictional characters, trademarks, 211
trade names, 357 fields (tables), 87-88
equivalence trials, 839, 843-845 FIG0 cancer staging system, 549
erectile dysfunction vs impotence, usage, 393 figures. See also legends and illustrations
error, statistical definition, 869 abbreviations, 119
error bars, 115 algorithms, 107, 110
errors requiring correction, 180, 270, 310 appendixes, 36
erythropoietin terminology, 578, 686 arrows and indicators, 117-119
Escherichia coli, 749 axis labels, 114
ester designations in drug names, 570-572 bar graphs, 101-104
estimate, statistical definition, 869 capitalization, 119,378-379
etc, usage, 393 citation, 120
euphemisms, 325 clinical imaging, 112
European Association of Science Editors (EASE), components, 11%114
260, 466,975 decision trees, 107, 103
European Medical Writers ~ssockdtion definition, 98
CEMWA), 141.975 diagrams, 106-110
evaluate vs diagnose, examine, identify, usage, 391 digital image manipulation, 158-159
event, statisticardefinition, 869 dot (p~int)graph, 105-106
events, capitalization. 376 flowcharts, 106-107
evidence in structured abstracts for review, 23 frequency polygons, 100, 102
evoked potentials, 728729 headings, 26
examine vs evaluate, diagnose, identify, histograms, 100, 102
usage, 391 horizontal bar graphs, 103
exclamation point, 336.355-356 illustrations, 112
exclusion criteria, case-control study, 846-847 individual-value graphs, 106
exclusion criteria, statistical definition, 869-870 legends, 114
expendable words, 406- 407 line graphs, 98-99
explanatory variable, statistical definition, 870 logarithmic scales, 114
exponents, 791,909 manuscript preparation, 309
expressions of concem, scientific misconduct, maps, 111-112
161-166 100% bar graphs, 104
extrapolation, statistical definition, 810 online-only articles, 36-38
pedigrees, 110-111
Fab C i u n o g l o b u l i n fragment), 695-696 pedigree studies, 232
fabrication of data, scientific misconduct, 156-157 permission to reproduce or adapt, 34-35,
factor analysis, statistical definition, 870 119-120
factorial, 336 photographs, 112, 121
factors, dotting (coagulation), 670-673 photomiuographs, 119
fair use exclusions in copyright, 197-200 pie charts, 105
false negative, statistical definition, 870 placement in text, 119
false-negative rate, statistical definition, 870 preparation for submission, 120-121
false positive, statistical definition, 870 references, 42
false-positive rate, statistical definition, 870 reproduction quality, 120
false singulars, pluralization, 369-370 scatterplots, 99-101
false singulars and plurals, 328 statistical analysis, 117
falsification of data, scientific misconduct, 156158 survival plots and survival curves, 99-100
Far Western blotting, 601 3-dimensional figures, 115
fasted vs fasting, usage, 394 titles, 115-116, 120
Fc C i u n o g l o b u l i n fragment), 695-6%, 698 UXS,81-82
F distribution, statistical definition, 870 film, usage, 394
federal employees, 191196 fin~ncialdisclosure
1:etleral Trade Dilution Act, 213 acknowledgments,30-31, 140-141, 142
fences (nnthematical composition), 908-9O9 conflict of interest, 168-173
fever vs temperature, usage, 394 unpublished material, 176
 Index

Fl.\t)cr c x a d S~~ILUK;II dehnttmn. 870 nomenclature system, 531-532

fixcd-mffm%ITIodrl. ma-amlysis, 848 symbol conventions, 609-632
fixed-effectsmodel, statistical definition, 870 T-cell receptor gene terminology, 703-704
flowcham, 106-107 viral terminology, 761
flow diagrams gene symbols, names in italics, 926
QUOROM, 847 genetic pedigree studics, 6660-666
study design, 839, 842 genetic pedigree studies and patient anonymin.
survey studies, 850 121, 232
FlyBase, 656 genomic sequence information, 596597
FlyNome, 656 genotypes, 540-541, 595,629-631,688-691
follow vs follow up, observe, usage, 394-395 genus and species names
fonts abbreviations, 743744
definition, 920 article titles and subtitles, 11-12
sans serif type, 920-922 capitalization, 374, 377
serif type, 920-922 herbals and dietary supplements, 581-582
usage, 924-926 italics, 925
Food and Drug Administration approval, 566-567 plant virus terminology, 759
footnotes pluralization, 746-747
abbreviations in tables, 96 reference citation format, 47
affiliation, 17-19 viral terminology, 756-758
bottom-of-page, 43 geographic names, capitalization, 374
column headings, 87 German Collection of Microorganisms and Cell
figures and tables, 34-35 Cultures, 748 ,
order of authorship, 134 gen~nds,323-324
parentheses in text, 357 ghost authors, authorship criteria, 131-132
running foot/head, 19 global vs international, usage, 395
tal>lrs, 88, 90-95 glyr-dted hemoglobin vs glycosylated
title page of manuscript, 16-19 hemoglobin, usage, 395
formulas, 358,910 glycoprotein complexes terminology, 667.669
forward slash. See virgule (solidus) glycoproteins, 543,619,719
fractions, 793, 824,908909 Goldmann perimetry terminology, 737-738
fragments in immunoglobulin terminology, gold standard. See criterion standard
695636,698 goodness of fit, statistical definition, 871
fraud. See scientific misconduct governmental agencies, capitalization, 377-378
frequency polygons, 100,102 government bulletins, reference citation
Friedman test, statistical definition, 870 format, 46, 57-58
fruitfly gene terminology, 656-657 government reports, reference titation
F test (score), statistical definition, 870-871 format, 69-70
funding or grant support GPA (obstetricterminology), 734-735
acknowledgments, 140-141, 145-146 Gram stain, 749-750
authorship criteria, 128-129 Grand Rounds, 4
conflict of interest, 173 granulocyte antigens, 544,615-616
online-only articles, 37 graphs, 120, 198
peer review, 307 Greek letters
scientific misconduct, 160 alphabet, 782
Funnel plot, statistical definition, 871 capitalization, 371, 373, 781-782
fusion oncogenes, terminology, 635-636 chernokine terminology, 677-679
co~nplenientterminology, 681-682
gaussian distribution. See normal distribution. cytokine terminology, 687
gender/sex, inclusive language, 319, 412-413 decimal forms of numbers, 830
gender vs sex, usage, 395 etythropoietin terminology, 578
eeneric drug names, 567-568 he~nost;~sis, 671
gcncs HlA rcrrninology. 689. 692
amino acids. 604-607 ~mrnt~noglolx~lin chain rrrminology. 696697
general tcnninology. 5K.>-t;i>' indexing. 'IT- ,428
inlmuno~lol>uIcn(t=rm~nolo~y, 6+)-70i) ~ n l ~ l t \ ~of
! ~, (~~, .n~ ~ ~ i l . ~
terrninolop).
!jon 6-4
n?olccul.rr r;lnccr r c m ~ ~ n o l o 5il-552
~v. lnlc.rfcrl ,n rc.rrrl~nol,,py.5-65?' -.
r 1 l o ~ ~ ~ l l l nc!lrowtcncc
.lr !tml1nt,loxy. 3 3 - 3 3 ~ ~ ~ ~ I C - { II V~ 7I : I? I? 1 n t ~ 1 ~ >(,.%).(~9-
~~,
 heterogeneity, statistical definition, 871
HGNC (HUGO Gene Nomenclature
~ l ~ ~ ~ l c cncurwience
ular terminology, 730-733 Committee), 609
~nulecularterms. 713-720 HGVS (Human Genome Variation Society),
nucleotide sequence variations, 596 nomenclature, 593-594
streptococci, non~mclature,752 HIPAA (Health Insurance Portability and
rable stubs, 87 Accountability Act), 230
T-cell terminology, 702-703 histocompatibility antigen terminology, 688-691
thron~bolysistcmlinology. 672 Ilbtogram, statistical definition, 871
typesetting, 783 hiaograms, 100,102
viral terminology, 761 histologic grade terminology, 546
\,s word, 781 histone terminology, 587-589
Greek words historic vs historical, usage, 395
letters vs words, 781 HLA, general terminology, 531-532,688-691
plurals, 368 Hoeffding independence test, statistical
group association, statistical definition, 871 definition, 871
group authorship holidays, capitalization, 377
~l~breviations, 472 Hollanderpadelism test, statistical definition,87
acknowledgments, 30, 141-142 homogeneity, statistical definition, 872
bibliographic databases, 136138 homonyms, definition, 324
bylines. 15-16 homoscedastiaty, statistical definition, 872
corresponding author, 137 . honorary authors, criteria, 132-133
criteria, 135-137 horizontal bar graphs, 103
group names, 472 hormone tenninology, 574576,614,686
journal articles, 137-138 Hosmer-Lemeshow goodness-of-fit test,
nwnuscript preparation, 10, 15 sacistical definition, 872
group matching, statistical definition, 871 Hotelliig Tstatistic, statistical definition, 872
guarantors HUGO Mutation Database Initiative, 593-594
access to data statement, 173 Human Cell Differentiation Molecules
author contributions, 29-30 workshops, 679
authorship criteria, 129 human chromosome terminology, 637-648
group authorship. 135 human genes, 608632.650-652
guest authors, authorship criteria, 131 Human Genome Variation Society (HGVS),
nomenclature, 593594
Huemopbilus nomenclature, 750 human s u b j j research, 226-228
Iraplotype in HW terminology, 690-694 human viral terminology, 762-767
haplotype in pedigree, 665 hydrogen isotope terminology, 709
Hanley test, statistical definition, 871 hyp&demic & pandemic;usage, 393
Hawthorne effect, statistical definition, 871 hyperintense vs hypointense, usage, 3%
hazard function, statistical definition, 871 hyphen
hazard rate, statistical definition, 871 bacterial gene terminology, 658
hazard ratio, statistical definition. 871 chemical compounds, 351
headings, 26,924-925 darity, 348-349
health care, usage, 395 complemt%t terminology, 682
Health Insurance Portability and Accountability definition, 344
Act (HIPAA), 230 digit spans, 827-828 .
heart disease classification terminology, 560-562 disease names, 350-351
hean sound terminology, 556 DNA sequences, 592
heavy chain immunoglobulin terminology, electnxardiography terminology, 554-555
6%-697 en dash in the same phrase, 352-353
helper T-cell terminology, 702-703 eponyms, 779
hemophilia terminology. 672-673 geographic entities, 351
hemostasis, 618-620,667-676 HLA terminology, 690,692
hepatitis virus terminology, 760 molecular terms, 713720
herbals and dietary supplements terminology, mouse and rat gene nomenclature. 649-650
580-582 nematode gene terminology, 657
HER2/neu,634-635 non-English expressions, 351
heterogeneity, meu-analysis. 848 numbers, 346-347
 Index

obstetrics terminology, 735 incomplete expressions, punctuation with

peptide sequence, 606 ellipses, 364
prefixes, 347, 349-350 IND (investigational new drug), 566567
ranges and dimensions, 349 indefinite pronouns, 319
ratios, 345 independence, assumption of, statistical
Si units, 792 definition, 873
special combinations, 352 independent variable, statistical definition, 873
suffixes, 350 independent variables, 846-847
temporary compounds, 344-348 indexes, as units of measure, 794
vertebrae terminology, 723-724 indexes, to published material
when not to use, 350-352 . copyright, 189
hypothalamic hormone terminology, 574-575 letters to the editor, 270
hypothesis, 836, 846 to published works, 311
. hypothesis, statistical definition, 872 indexing. See also cross-references
abbreviations;429-430, H)1
-ic, -ical, usage, 396 abstracts, 435- 436
ICANN (Internet Corporation for Assigned alphabetizing, 425- 429
Names and Numbers), 215214 cypitalization, 429
ICTV (International Committee on Taxonomy chemical prefixes, 426
of Viruses), 756 consistency, 428 .
i d e n t . vs examine, evaluate, diagnose, controlled voc&ulary, 435-436
usage, 391 corrections to published material, 311
idioms, 324 embedded, 436
ie vs eg, usage, 393 Greek letters, 427; 428
iUusuations. (See also figures) inversions, 433
abbreviations, 119 journals, 435- 436
fair use exclusions iir copyright, 198 locators,, 430- 431
permission of those acknowledged, 146 main headings, 429-431.433-434
return of after rejection, 265 -. MESH (Medical Subject Headings), 24,435-436
usage, 112-113 nomenclature, ,428,.430
visual identifiers, 117-118 ,numbers, 426- 427
IMGT/HL4 Sequence Database, 688 online journals, 14, 436 ,

immunize vs inoculate, vaccinate, usage, 396 periodicals, 435-436 .

immunoglobuli punctuation, 425-426.431
fragment terminology, 695696,698 ' software, 311 :
general terminology, 695-699 styles, 425; 431
gerie terminology, 6 9 - 7 0 subentry leveiz, 433-434
structure, 695-696 types of, 431 ' '

immunology, 620-624, 677-704 typography, 431

impaired vs intoxicated, usage, 396 vocabulary control, 434-436
imperative mood, 320 indicative mood, 320
implanted cardioverters/defibrillators, indirect cause, statistical definition, 873
terminology, 561-562 individual-value graphs, 106
imply vs infer, usage, 397 infectious conditions, usage, 748
impotence vs erectile dysfunction, usage, 393 inference,statistical definition. 873
imputation, statistical definition, 872 infer vs imply, usage, 397
IMRAD (Introduction, Methods, Results, and influenza virus terminology, 760-761
Discussion) informed consent
letters to the editor, 5 Belmont Report, 227-228
manuscript preparation, 26 deidentification, 232
original articles. 3 drug development, 566
.\rutly design. 836-838 genetic pedigree studies. 232
In.lcrlve c o l n p o n e n l s in rlruK r,.ttlica\. 5-0-i72 human subjects rese:~rch,intern:~tion:~l
organization puidelines. 228
institution;lI review I,ojrcl, 226-27
news slorics. 232
"nline-only anicles, 37
P:lllenl itntl sul~ject
:tnonyrnity. 2.%)-Z.3I
Index

inl'r;~.sul,spccih~ Ixtctcr~.llnanes. 7.10 news llledla wlittlorls, ?!.?-LY-I

Injir-lfinjier rule. 291 p~tientand subject anonymiry, 230
inl~il,itic)nof coagulation terl~linology.67-1 peer review and confidentiality, 218
initi:llisms. 379-380. 4 i Z permission of those acknowledged.
irii~i:~lsol' a Ixrrson. 450- 457 references, 40
initials of a person. footnc)rcs, 17 scientific mixondud and retraction,
injrcring vs injection. intmvrnous drug sponsored supplements, 283-284
user. usage, 397 International Committee on
injury vs accitlent. usdge, 382-383 Bionomenclature. 741
INN (internatiorx~lnonpropricr:~ryI X I I ~ ~ 565-567
), International Committee on Coagulation and .
inoculate vs immunize, vaccin:lte, ilslge, 3% Thrombosis, 673
in order to, usage, 397 International Committee on Standardized Genetic
in press reference citation format, 60 Nomenclature for Mice, 649,652 I
in situ hybridization. abbreviations and
symbols, 646-647
International Committee on Taxonomy of V i s e s
( I n v ) , 7%
.;
institutes, 458-472 International Congresses on Peer Review in
institutional owners, copyright, 196 Biomedical Medicine, 304
institutional'reviewboard (IRB), 226-229,232 international copyright, 207-208
institution names, capitalization, 377-378 International Digital Enterprise Alliance, 121
instructions for authors international editions, 203206
authorship criteria, 130 international editions, stmdards for licensing,
conflict of interest, 169-170 201, 206-207
journals, 273 International Federation of Clinical , ..
manuscript preparation', 7-8 Neurophysiology, 724 1
"
peer review, 307 International Registration of Trademark, 213
reprints. 310 International Society of Blood Transfusion QSBT) . 1
instrument error, statistical definition. 87.3 terminology, nomenclature, 542-544
insulin terminology, 575-576 International Standard Serial Numbers (pISSNs
insure vs ensure, assure, usage, 386-387 and eISSNs), 479 2
integrins, 619,669 ' International System for Human Cytogenetic
intellectual property, 179-184,209-210,219 Nomenclature 0 , 6 3 7 - 6 4 8
intention/intent-to-treatanalysis, 839,843 International System for Human Gene
intention/intent-to-kt analysis, statistical Nomenclature (ISGN), 608
definition, 873 International System d Units (SI units),
interaction. See interactive effect. abbreviations, 519-525
interaction term, statistical definition, 874 international mdemarks, 2U
interactive effect, statistical definition, 874 internationalvs global, usage, 395
intercapped compounds, capitalization, 380 Internet. See also online journals; Web sites
interference, scientific misconduct, 156 copyright, 188
interfern%&general terminology, 576577,687 manuscript submission, s 3 0 6
interim analysis, randomized controlled plagiarism, 158
trial, 839,841 reference citation format, 63-64
interim analysis, statistical definition, 874 Internet Corporation for Assigned Names and
interleukin tkninology, 577,684-687 Numbers QCANN),213214
International Committee of Medical Journal interobserver.bias,statistical definition, 874 '1
Editors (ICMJE) interobserver reliabilitylvariation, statistical ;i
access to data statement, 142,144145, 183 definition, 874
advertising in publications, 310 . interquartile range, statistical definition,
advertising policies, 276-277 874875 <.
advertising-to-editorial page latio, 281 intemter reliability, statistical definition, 875 :
authorship criteria, 128-130 interval estimate. See confidence interval I
conflict of interest, 169 intoxicated vs impaired, usage, 376
corrections publication, 270 inmobserver reliabilitvlvariation.
,, statistical
correspondence column, 5 definition, 875 ?
duplicate publication, 148-149 intramter reliability, statistical definition, 875 .:
 Index

intravenous vs injection, injecting drug user, plane (airplane) names, 925

usage, 397 plays, 925
introduction, manusaipt preparation, 836 pluralization, 369
Introduction, Methods, Results, and Discussion ship names, 925
(IMRAD). See IMRAD (Introduction, space vehicle names, 925
Methods, Results, and Discussion) statistical terms, 926
invasion of privacy, definition, 226 subgenus in bacterial nomenclature, 744
inversions, indexing, 433 S~mPosiaproceedings, 925
invertebrate gene terminology, 656457 taxonomic rank, 742-743
investigational new drugs m), 56567 viral terminology, 757-758
ionizing radiation, units of measure, 816-817 word emphasis, 360
IRB (institutional review board), 226229, 232 (intentionlintent-tetreat) analysis, 839,
irregardless vs regardless, usage, 397 843,873
inifate vs aggravate, usage, 385 IUPAC-IUB~ o i nCommission
t on Biochemical
ISBT, 542-544 Nomenclature, 721
ISCN (International System for Human
cytogenetic Nomenclatuie), 637 jackknife analysis, cost-benefitlcost-effective
ISGN (International System for Human Gene analysis, 849
Nomenclature), 608 jackknife dispersion test, statistical
IS0 (International Organization for . definition, 875
Standardization), 456,479 jargon, 325,408-410
isolate terminology, 760 joining (Dgene segment, 699-700, 703-704
isotopes joint possession, a p o h p h e , 362-363
abbreviations, 527-528 joint works, copyright, 195
radiopharrnaceuticals, 579 journal articles
terminology, 707-710 capitalization, 372-373
issue numbers, references, 48 duplicate publication, i51-152
italics group adorship, 137-138
. abbreviations of gravity, 926- order of .elements, 146
airplane names, 925 public domain information, 293-234
allele terminology, 628-629 reference citation format, 46, 472-500
books, reference citation f6rmat, 46 journalistic privilege, confidentiality, 223-224
book titles, 925 'journal names
cardiology terminology, 557 abbreviations, 48,472- 479
chemical prefixes, 926 capitalization, 372
element symbols in chemical names, 714 individual word abbreviations, 479-j~
e-mail addresses, 29 hternational Standard Serial Numbers (plssxs
emphasis, 926 and eISSNs), 479
enzyme names, 602,925 PubMed, 473-500
epigraphs, 2425 references, 48
foots, 925 journal oversight committee, 248, 240, 2 j 1 - 2 ~ 3
gene symbols, 610,613-615,926 journals. See also online joumals
genus and species names, 925 authorship criteria, 128-130
HLA terminology, 691 conflict of interest disclosure, 169-175
human' oncogenes, 633 data sharing, 181-183
indexing, 431 , defense against libel, 240-241
journal names, 48 digital image manipulation, 158-159
journal titles, 925 digital image submission guidelines. 1 9 9 - 2 1 ~
legal case names, 226 duplicate submission policy, 152
legal material citation format, 73 editorial freedom and integrity, 243-246
lowercase letters, 925 eclitorial responsil,ilitics. 260-270
1ll:l~~l~lll:lti~':l~
Co~liposi[iol). 012, 020 ~ I I C ~ ~ S4:35-.1.50
~ I I ~ ,
Illollsc grne ler~ninology,050-052 indexing tyl~cs,4;51
rnusical compositions, 925 institutional owners of copyrights, I96
non-English words, 421, 925 IKR approval, 227
nonhllm;ln genetic terllls, 649 iol1m:llistic ~,ri\,ilegc,223-224
nllclcOtitlt! Sccluence v;lri:ltiol>s,595 ()lWn-:lcccssnlovvrncnt, IWI-185
paintings. 925 Patient and sul)iecr anonymity, 230-231
journals (continued) ~ ~ t ~ ~ ~ t u n i ~ ~ ~ rI c1;~ g r d p t ~ > ,
peer review and confidcnrialiry. 219-L'ch p u r i ~ < u ~ l~~1 1<1~1pdrenthcscs,
n 5%)
photographs and patient anonpity. 232 slirll~n$ctur~acrisaiain figures. I I +
placement of corrections, 270 utleb. 1 3
record retention policies, 183-184 Iegislarion. 75-78.376
references, 42,47-48 length, dual reporting conventional and SI
retractions, 161-165 unib, 794
review articles, 5 length-time bias, statistical definition. 876
scientific misconduct, 159-161 less vs fewer, usage, 394
sections of articles, capitalization, 379 lcitrr of retraction, scientific misconduct, 160
jugular venous pulse terminology, 557 letters, pluralization, 369
letterspacing. 922
Kaplan-Meier method, statistical definition, 875 letters to the editor
K (kappa) light chain, 697 advertising comment, 277
K (kappa) statistic, statistical definition, 875 authorship criteria, 130
karyotype te&ology, 639-640 conflict of interest disclosure. 171
Kendall r (tau) rank correlation, statistical correspondence, 5
definition, 875 defamation, 23&239
kerning, definition, 922 policies and procedures for, 268-270
keywords, 24 postpublication review, 308
keywords, embedded indexing, 436 usage, 4
kilocalorie, calorie vs energy, usage, 796-797 L forms, 750
Kolmogorov-Smirnov test, statistical liable vs apt, likely, usage, 385-386
delinition. 875 libel
K~skal-Wallistest, statistical definition. 875 defense against, 240-241
kurtosis, statistical definition, 875 definition, 235237
legal resources, 241-242
labels in figures, 115,119 letters to the.editor, 269
laboratory codes, 655 opinion vs fact, 238
laboratory media terminology, 750 licensing international editions, 201,206-207
laboratory values, reference ranges and life table, statistical defmition, 876-877
conversion factors, 797-8'16 ligature, definition, 921
labomtory values, terminb~ogy,jargon, 411-412 light chain immunoglobulin
Lactobacillus GG nomenclature.. 750 - terminology, 697
k (lambda) light chain. 697 likelihood ratio, diagnostic tests, 850
lasers in ophthalmology terminology, 738 likelihood ratio, statistical definition, 877
Latin square, statistical definition, 876 likely vs liable, apt, usage, 385-386
Latin words, 368,757 Likert scale, statistical definition, 877
law journals, reference citation format, 78 Lilliefors test,staWcal definition, 877
layout, 923-924 linear regression, statistical definition, 878
leader gene segment, 700 line graphs, 98-99
leading, definition, 923 lime spacing, 923
lead terms, 553,725-729 linking and framing, 200,286
lead'he bias, statistical definition, 876 lipoproteins, 562-563
least significant difference test, statistical List of Prokaryotic Names With Standing in
definition, 876 Nomenclature, 748
least squares method, statistical definition, 876 location, statistical definition, 878
left-censored data. See censored data locators, indexing, 430-431
legal case names in italics, 926 logarithmic expressions, 909-910
legal material, reference citation format, 72-75 logistic regression, statistical definition, 878
legal proceedings, 219,223-224,230 log-linear model, statistical definition, 878
legends. See also figures logos, online advertising, 286-287
box and whisker plot, 106 logos and trademarks, 211
composite figures, 116-117 log-rank test, statistical definition, 879
digital image manipulation, 158159 lowercase letters
error bars. 115 clotting factor terminology, 671
fiiures, 115-116 DNA sequences, 592
permission of those acknowledged, 146 enzyme names, 602
 Index

iLalia, 925 r n ~ r k ~ nr.opy.

g 9-9-95?
supersaipt nuclrotida. 590 bfarkov process. sta~~s~rcal drfin~r~on. 8-9
usage, 924 masked assessment, statistic;tl definition. 879
lucency vs opacity, usage, 398 masking vs blinding. u.wRe. UIR
mass, dual reporting conventional anti SI
macrolide-resistance nomenclature, 750 units, 794
Madrid System, trademarks, 213 matching, statistical definition, 879
magnification of photomicrographs. 117 ~nathematicalcomposition
main effect, statistical definition, 879 brackers in formulas. 358
main headings, indexing, 429- 431, 433- 434 copy marking, 307
major histocompatibililty complex (MHC; Mhc). displayed vs run-in formulas. 908
682694 exponents, 909
makeup of a joumal issue, 310 italics, 926
malignancy, malignant neoplasm, malignant logarithmic expressions, 909-910
tumor, usage, 398 multiplication, 910-911
management vs treatment, usage, 398 parentheses, 358
manic, usage, 389 spacing with symbols, 913
Mann-Whitney test, statistical definition, 879 stacked vs unstacked fractions. 908
MANOVA (multivariate analysis of variance), symbols, 911-912
statistical definition, 879 matrix vs table, 84-85 -
Mantel-Haenszel test, statistical definition, 879 may vs can, usage, 388
manufacturers of equipment, 583-584 McNemar test, statistical definirion, 879
manuscripts
acceptance, 267-268
mean, statistical definition, 879
measurement error, statistial definirion.
k ..

acknowledgment of receipt, 262-263 879-880

breaches of confidentiality, 158 mechanical ventilation terminology, 774
conflict of interest, 169-170 median, statistical definition, 880
duplicate submission, 152-153 median test, statistical definition, 880
duplicate submissions on same data, 183 media relations, 290-298
electronic media, 309 Medical Subject Headings (MeSH), 435- 436
Internet submission, 304-Mb MEDLINE
plagiarism, 158 anonymous authorship, 133
preparation controlled vocabulary indexing, 24, 436
abstracts, 20-24, 836 corrections to published material, 310
acknowledgments, 27-36 journal abbreviations, 19, 479-500
authorship, 14-16, 128-130 number of cited authors, 134 . .

Comment, 26,838 references for authors' dames, 44- 45

isc cuss ion, 838 MEDWATCH, 566
editing, 309 MeSH (Medical Subjea Headings), 24, 435- 436
figures,309 meta-analysis
footnotes, 16-19 duplicate publication, 148
foreign names, 13-14 figures, 107
introduction, 25,836 review articles, 4.
makeup of a journal issue, 310 structured abstract format, 22-23
Methods, 25, 836837 study design, 847-848 . .

online journals, 8, 36-38 meta-analysis, statistical definition, 880

proofreading, 309-310 metastable isotopes terminology, 710 ;
Results, 2526,838 methods II .
tables, 309 figures and statistical analysis, 117
titles and subtitles, 8-13 IRB approval, 227-228
rejection of, 166, 220, 223, 261, 265-266, 308 manuscript preparation. 836-837 i
scientific misconduct, 156, 166 original article, 25
scicnlific. I>l.cscn[;~tions,203 1%1Iirt11 ;III(I SIII)~CC.I
; I I I ~ I I ~ I I I 250
~ I ~ ,
s1atistic:ll ;ln;rlysis, 142, 144-145 r~cc/ethnicitycl:lssification, 415
manuscript vs article, paper, typescript, .. .
sponsorship, acknowledgments, 145-146, 173
usage, 386 II\etl'ic conversions, 795
In:lps, 111-112, 114 M).i(; (n~:~jor I~isrocomp:rtil~ility conlplcx),
marker chromosomes, 647-648 688-693
Mhc (major histocompatibility complcs. multiplication
animals), 694 mathematical composition, 910-911
microorganisn~s,368-369,657 punctuation, 334
military services and ranks, abbreviarions. SI units, 790-791,794
446-448 multivariate analysis, statistical definition, 881
militate vs mitigate, usage, 398 murmur terminology, 556557
misappropriation of data, scientific misconduct, musical compositions, 372,925
156,158 mutations. See sequence variations
misplaced modifiers, 322 Mycobactm.um auium-intracellulare
misrepresentation, scientific misconduct. nomenclature, 750
156-157
missing data, statistical definition, WO names of persons
mitigate vs militate, usage. 398 abbreviations, 456-458
nlixed Fractions, 793,822 foreign, 13-14
mode, statistical definition, 880 initials, 456-457
n~odifiers(noun strings) in references, 13-14,45
d.:finition. 316,322 prefixes and particles, 45-46
hyphenation, 350-351 naming drugs, 567-568
nlisplaced modifiers, 322 National Center for Biotechnology
modifying enzyme terminology, 603 Information. 658
moieties, 530-591,682 National Center for Biotechnology Informationt
moiery designations of drugs. 570-572 Enuez Taxonomy, 741
molar concenuations. units of measure. 795 National Institutes of Health (NIH), 155,
molecular cancer terminology, 551-552 180,226-227
molecular formulas in immunoglobulin National Library of Medicine
terminology, 698 corrections (errata), 270
n~olecularmedicine, terminology. 624-626. duplicate submission, 152
710-720 electronic references, 63
molrcuhr neuroscience terminology, 7N733 expressions of concern, 161-165 -
money (currency), 363.817-818.823 journal names. 472
nlonoclonal antibodiks,578579,670 MEDLINE abbreviations, 479
lnonoclonal antibody terminology, 578579 number of authors, 134
monographs, reference atation format. 53. references. 40
58,68 retractions, 161-162
Monte Carlo simulation, statistical National Science and Techhology Council.
definition, 880 scientific misconduct, 156-157
monuments, capitalintion. 372 natural -5 statistical definition, 881-882
mood of verbs, 320 naturalistic sample, statistical definition, 882
MOOSE (Meta-analysis of Observational Studies necessary cause, statistical definition, 882
in Epidemiology), 107,847 negative predictive value, diagnostic tests,850
moral rights of artisrs and writers and negative predictive value, statistical
copyright, 208 definition, 082
mortality rate, statistical definition, 880 negative vs positive, normal, abnormal, usage,
Moses ranklike dispersion.test, statistid 381-382
definition, 880 Neiseriu menfngitfdisnomenclature, 751
mouse, strain terminology, 65.5-656 nematode, gene terminology, 657
mouse chromosome terminology, 652-655 nerve terminology, 722-733
mouse gene terminology, 531,649-655,769 nested casecontrol study, statistical definition,
Mouse Genome Database. 650 882
Mouse Genome InFormatics, 655 nested case-coniol study, study design, 847
movies, capitalization, 372 neurology, gene terminology, 626-628
multiple analyses problem, statistical new drug applications, 565
definition, 880 Newrnan-Keuls test, statistical definition, 882
multiple comparisons procedures, statistical news embargo, 292-294
definition, 880-881 news media, 290-291,294-296
multiple-drug regimens, 573-574 newspaper articles, reference citation format, 57
multiple endocrine neoplasia terminoloby, 551 news releases, 61,296-298
multiple re&?-ession,statistical definition, 881 news releases, reference citation format. 72
 Index

news rrpnlnx. drf3mation. 239

news stories, photographs and patlent rnod~ficn(noun strings), 316
anonymiry, 232 modifying gerunds, 316
NIH (National Institutes of Healrh). 155, predicate, 330
180, 226227 subjectcomplement agreement, 3 16-317
No. (number), abbreviated, 829 subject-verb agreement, 327-328
n-of-1 trial, statistical definition, 882 nucleic acid, general terminology, 584-607
nomenclature nucleoside and nucleotide terminology. 58i-i')J.
biological organisms, 740-753 599-600
complement terminology, 680-681 nucleotide databases, 597 *
definition, 530-532 nucleotides, sequence variations, 593-597
drug names, titles and subtitles, 11 null hypothesis, randomized controlled trial. 839
enzymes, 720-722 null hypothesis, statistical definition, W3
FlyBase, 656 number, abbreviated as No.. 829
HLA system, 688-691 ilumbering and citation of references. -t2- -1.4
hormone terminology, 574-576 number needed to harm, statistical definition. ,W.J,
indexing, 428, 430 number needed to treat (NNT), st;itisric~l
interleukin, 686-687 definition, 883
mouse and rat gene, 649-655 numbers
pulmonary and respiratory terminology, article titles and subtitles, 11
771-774 capitalization, 371, 373, 376
viral terminology, 756-761 chromosome terminology, 654
nominal variable, statistical definition, 882 decimal forms of, 830
nomogram, statistical definition, 882 digit spans and hyphens, 827-828
nonconcurrent cohort study, statistical DNA sequences, 591-592
definition, 882 electrodes, 725
non-English words forms of expression, 821-822
capitalization, 373 4 digits or more, 793-794, 822
italics, 925 hyphenation, 346347
and phrases, 421-423 indexing, 426 427
quotation marks, 361 nucleotide sequence variations, 593, 596
reference citation format, 46-47 oncogene terminology, 635
nonhuman genetic terms, 649-659 ordinal, 825-826
nonhuman histocompatibility terminology, 694 percentages, 830-832
noninferiority trials, 839, 843-845 pluralization, 369
nornormal distribution, statistical definition, punctuation with comma, 340-341
882-883 punctuation with parentheses, 356
nonparametric statistics, statistical definition, 883 reference citation format, 48, 56
nonphysician provider, usage, 401 rounding, 851-852
nonproprietary names, 567-568, 583-584 in tables, 82, 84;87-88, 96
nonrestrictive clauses, punctuation, 318-319 used as pronouns, 824-825
nontabular material, 84, 121-123 use of colon, 343
normal distribution, statistical definition, 883 words in large numbers, 826
normal range, statistical definition, 883 nurse vs breastfeed, usage, 388
normal vs abnormal, negative, positive,
usage, 381-382 obituaries, 5
Northern blotting, 601 objective, 22
notices observational studies, study design, 843-846
copyright registration, 196197 observe vs follow, follow up, usage, 394-395
corrections (errata), 270 obstetrics terminology, 734-736
duplicate publication, 52, 152-153 odds ratio (OR), st;~risticaldefinition. 883-884
expressions of concern, 161-165 -0logy. us;cgC.. 399
retractions, 52 OMlA (Online 3lc.ntl(.l1:cn Inhcr~!:~ncv In
nouns AI\III~:II\ I (I<-

collective, 329 O!.fIZ3l I ( )!,I,:,<, \!<.:,,<4,,.l,! 1;. l!>!,?Y2:.,!.., .. 1r: \.l,,r1 ,,

collective, pluralization, 367-368 OI'\ 1 4 :

definition, 315 l , r n t \ w , n *,! ,!,,,, ~ :..- !:*: ::.:... ,. '.. .. . .

'

gerunds, 323 , ,!',, ,

3>.,.::,-\ :. : . :. '. . . .
.
.-
. . .
oncoprolein iem~inology,635-636 reference citation format, 61
l-kiilcd rest, staristical definition. 884 reference list, 41
IoO%r Ix~rgr~phs.10.4 order of elements, acknowledgments,
online I>ooks,rcfcrcnces. 42 143144, 146
online confcrcncc prcrctdings/prcscnt3~ions, ordinal dlra, statistical definition, 884
reference ciulion fomxii. 71-72 ordinal numbers, use of words, 825-826
online journals ordinate, statistical definition, 884
lccephlnce date. 27-2A organisms
;icknowlrclg~l~cnu, 34-35 capitalization, 377,742-743
:itldcncl:t, 27 indexing, 428,430
advertisin&and sponsorship, 285-287 names in italics, 925 .
advertising content, 277-278 pluralization, 368-369
advertising-tc-editorial page ratio. 281 reference citation format, 47
appendixes, 36 terminology, 740-753
articles (supplementary material), 36-38 viruses. 75767
codict of interest disclosure. 170 organization names
corrections publication, 270 ' abbreviations, 454455,458472
figures, permission to reproduce, 113-120 capitalization, 377-378
group authorship. 137,141-142 punctuation with comma, 337
headings format, 26 organization reports, reference citation
indexing,74,436 format, 69-70
leuers to the editor, 269-270 original articles
libelous material, 241 definition, 3
manuscript acknowledgment, 263 editorial assessment,303
number of cited authors, 134 rnanwcript preparation, 2526
open-access movement, 184-185 online-only articles, 37
order of elements, 1% orphan h g s , 568
patient and subject anonymity, 121 outcome, statistical definition, 884
peer review, 219220,304 outlien (outlying values), statistical
peer reviewers, 174 definition, 884
postpublication review,308 overmatching, casecontrol study, 846
publication of rables, 84 overmatching, statistical a t i o n , 884
record retention policies, 184 ovasampling, statistical definition, 865
reference citation format, 6467 over vs under, usage, 399
references, 42 owing to vs due to,caused by, becaw o
release of urgent public need information, usage, 387
293 ownership and control of data, 179-184
~tractions,161-162
scientific presencltions. 293 pacemaker code terminology, 5591561
search engines, 301 package inserts,reference atation format,
submission requirements, 8 page makeup and composition, 309
symbols in mathematical composition, 912 page numbers, 48,56,430-431
tables, % paintings, 372,925
trademark protection, 213-214 paired samples, statistical definition, 885
WPOPP~Y, 918 paired t test, statistical definition, 885
Online Mendelian Inheritance in M i l s pamphlets, reference citation format, 46
( O W ) , 657 pandemic vs epidemic, endemic, hyperel
Online Mendelian Inheritance in Man usage, 393
(OMIM), 610 paper vs manuscript, article, typescript,
online newspapers. reference citation format, 69 usage, 386
opacity vs lucency, usage, 398 paragraphs, definition, 331
open-access movement, 184-185,193, 264-265 parallel construction
operation vs surgical procedure, usage, 399 correlative conjunctions, 325-326 .
ophthalmology terminolqy. 7 5 7 3 9 elliptical comparisons, 326
opinion v:,fact, libel, 238 lists, 327
oral communicaiions series or comparisons, 326-327
permission of those acknowledged. 146 parallel-design double-blind trials, study
permission to cite. 61. 1% design, 841-842
 Index

parallel publication, 149

breaches of confidentialiry, 158
Parameter, statistical definition, 885
confidentiality, 218-223, 261-262, 300-307
Parametric statistics, statistical definition, 885 conflict of interest, 169-170
parentheses definition, 304
abbreviations, 357
duplicate submissions on same ti:~r:~. 1x3
biological nomenclature, 740 editorial assessment, 301-303
with brackets, 358 ,
editorial responsibilities, 264-26j
chromosome terminology, 646 letters to the editor, 269
clotting factor terminology, 670 online journals, 304
digit spans and hyphens, 828 open-access publishing, 184-18j
DNA sequences, 593 outcome, 307
enumerations, 356, 828829 postpublication review, 308
exclamation point, 355-356 . reviewer selection, 306
explanatory footnotes, 357 signed, 221-222
legal material citations, 73 statistical review, 306
legends, 356 submission requirements, 8
long formulas, 910 unsigned editorials, 133
mathematical composition, 908-909 peer reviewers
nematode gene terminology, 657 access to data statement, 183
numbers, 356 confidentiality, 221
organisms terminology, 744-745 conflict of interest, 174175, 17
parenthetical expressions, 357 fair use exclusions in copyright, 198-199
parenthetical plurals, 357 PEN (pharmacy equivalent name), ,573
period, 355-356
peptide sequence, amino acid terminology,
question mark, 355-356 605-606
references in text, 41-42,356 percentages, 830-832
SI units, 792
percentile. See quantile
i supphnentary expressions, 355 period
t trade names, 357 , abbreviations, 456
parenthetical e r ~ r e s s i ~ nPuncution,
~~' 338-339 chr?monme t e ~ o l o g y 655
,
parenthetical ~lur* subject-veh agreement, i
definition, 333
328,357 . .. ellipses and omission of text, 365
participants, 21, 388-389 e-mail addresses, 29
participle, 323 enumerations, 828829
past tense, 321 placement, 334-335 I
patents i
PUnCtuation with parentheses, 355-356
definition, 179, 209-210 references, 41
liability concerns, 241-242 periodicals, indexing, 435- 436
reference citation format, 59 permissions
pathogens, 428, 747-748 e-prints, 203-206
pahi and anonYmitY, 121.219-220.226 figure and table reproducti&, 95, l l ~ l 2 0
patient vs care, subject, COnsumer, client, usage, identifiable subjects, 230-231
388-389 oral communications, 199
product moment correlation, statistical photographs, 121
definition, 885 reprints, 203-206
pedigrees reproduction or adaption, 202
format recomm~ndations,660-666 transcripts of discussions, symposia, and
patient and subject anonymity, 121 conferences, 200-201
studies, patient anonymity, 232
written communications, 199
visual illustrations, 110-111 Personal communic;~tions
I'edigree St;~ntl:~rdiz;~tion '~.;lsk 1:orc.c. (,r 111~. ; ~ ~ ~ k n c ~ w l c t1/16
l~t~~~n~.~, .
N:~tion:~lSociety of ~ ; ~ n ~ l i ~ c . i ~~c , I
~ C ~ I I I111~ I,S1 ~ 01
Counsclors, 600 l ~ ~ l ~ ~c cll.ll,l>!~
. l l < li,rlll:tl,
~~ 01
peer rcvicw ,.
l ~ . l ~ . t c . l l , ll\l ,1
; ~ ~ k t l o \ r ~ l r 222
c l ~ ~ ~ ~ ~ ~ ~ ~ ,
I*.'\~)ll.lIj l I , , l l . . # , 11.. < I - , 11 5 I I I
;~tltlencl:~,
17 /)I 1 111.~1, . . I :. , ,,.. ; : L - , -I!,
"ppendises, 30
l~lintletl,220.22 1, z t l ~4:, ;-
ill~.i>:,-,( , ! , I (,,,i - 1 ! -
I,!,.:.:: , , .>~. I' , :\ .I.<.:;: l:.l::.,(. , PI:.\ ', -'
l ) t . ~ - r l u lpc3,
) 1)Iwd ~ r i u i I) C ~ ~ I I,G, .
I I H4 , ~'~v < ic\1rth J ~ J~Pg r ~ p nhx~~ c$ 556
,
. II.,[,IS I-..
~ ) I I C I ~ L H > l x ~111-4 ~~~~~ \ ~ r u M xgnunts
r (immunoglobulin genes),
p ~ ~ c n ~ y [~wI UsI I,U I >gc-ix-.\, 02~)-041 byy. 703
phcnotypcs. rlwcrol~rirrcAs~\rrncr.. 3u l f r r u r n v i p l l r j l m w i , 747-748
phenotypes, nonliumn gencuc ~cnlx,,~ 5 3 . 1-V
656.658 article rypes, 5
Pliiladelphia chromosonie, h7-648 punctuation with ellipses, 364-365
phonetics, punctuation with virgule, 354 punctuation with virgule, 354-355
phosphate nucleotide terminology, 599-600 quotation marks, 361
photographs titles in italics, 925
electronic submission, 120 point estimate, statistical definition, 885
Cdir use exclusions in copyright. 108 point size, 921-922
informed consent, 121 Poisson distribution, statistihl definition, 885
journal submission, 5 polymorphism. See allelic variant
patient confidentiality. 226. 230-232 polysomnography terminology, 729-730
permission of those acknowledged, 146 population, statistical definition, 885
return of after rejection. 265
titles, 116 definition, 886
unethical alteration of, 112 pob~rivepredictive value, diagnostic tests, 850
visual indicators, 117-118, 121 positive predictive value, statistical
photomicrographs, 117, 120, 356 definition, 886
PhyloCode. 741 positive vs negative, nonnal, abnormal, usage,
physician vs doctor, usage, 392 381-382
pie charts, 105 possessive pronouns, 317,362,413-414
pISSNs, 479 possessives with eponyms, 777-780
pituitary hormone terminology, 575 posterior probability, statistical delinition, 886
placebo, statistical definition, 885 post hoc analyses, randomized controlled
placebo effect, statistical definition, 885 trial, 839
place on vs put on, usage, 400 . post hoc analysis, statistical definition, 886
plagiarism, 156,158
plant virus terminology, 759 posttest probabiity, statistical definition, 886
platelet antigens, gene terminology, 615-616 power, statistical definition, 886
platelet factor terminology, 6674% practice parameters, 4
platelet-spdc antigens, terminology, 543-544 practitioner vs clinician,provider, usage, 390
plays, 372, 925 precision, statistical defmition, 887
pluralization preferred atation format, 36
abbreviations, 369 prefixes .
apostrophe, 363 . capitalization, 373
cardiology terminology, 556 hyphenation, 347,349-3M
collective nouns, 367-368 immunoglobulin terminology, 697
false singulars, 369-370 molecular t e r n . 713-720
formation, 367 oncogene terminology, 635
genus and species names, 746-747 restriction enzyme terminology,603
Greek words, 368 SI units, 789
Latin words, 368 prefixes and particles, references, 45-46
letters, 369 preprints, definition, 288
numbers, 369 presentations at meetings
organisms, 368-369, 746-747 acknowledgments, 34
SI units, 791 reference citation format, 59-60
symbols, 369 present perfect tense, 321
when not to use, 369 present tense, 320-321
years, 369 press conferences, prepublication, 292
plus and minus signs, 645, 714 press releases
alleles, 593, 653. 658 author guidelines, 296
blood group phenotype, 539-540, 543 duplicate publication, 149
CD markers, 702 embargoes, 294
charge, 714 reference citation format, 61-62
chromoson~es.645 release of scientific data, 290
 Index

Pressure, units of measure, 796 "negative" studies, 304

pretest probability, statistical definition, 887 peer review, 304
prevalence, statistical definition, 887 publication bias, statistical definition. ~8
primary hemostasis terminology, 667468 publications, capitalization, 372
prime sign, 363 public domain, 189-191, 1%
principal components analysis, statistical publisher, book reference citation foml:lt, j j-jb
definition, 887 PubMed, 184,. 473-500
----
print references, 42 PubMed identification number (PMID), reference
prion nomenclature, 768-769 citation format, 63-64
prior probability, statistical definition, 887 pulmonary and respiratory terminology, 771-774
privacy rights, 229-231, 285-287 punctuation. See also individual symbols
probability, statistical definition, 887 abbreviations, 334-335, 456- 457
product-limit method. See ~ a d l a n - ~ e i metho e r ld affiliation footnotes, 340
professional societies, abbreviations, 458- 472 alignment of data in tables, 89-90
pronouns allele terminology, 628 .
definition, 317 book reference citation format, 55-56
inclusive language, 413414 bylines, 15-16, 136
indefinite, 319 citations, 42-44
modifying gerunds, 316 clotting factor terminology, 670
numeials, 824-825 complement terminology, 682
personal pronouns, 317 contractions, 322
possessive pronouns, 362 dialogue, 341
pronoun-pronoun agreement, 319 . DNA sequences, 592-593
pronoun-verb agreement, 319
electrocardiography terminology, 554-555
relative pronouns, 317-318 e-mail addresses, 29
proofreading, 309-310, 929-932 enumerations, 334,828-829
Propensicy analysis, statistical definition, 887 eponyms, 779-780
proper nouns, 374.376 . -
HLA terminology, 690-694
proportionate mortality ratio, statistical
indexing, 425-426, 431
definition, 887 journal titles, 479
pro~ortionsand percentages, forms of mathematical composition, 908-910,912-913
expression, 831-832 modifiers (noun strings), 316
proprietary names multiplication, 910
capitalization, 376-377 non-English words, 422
drugs, 568-569 nonrestrictive clauses, 3 1 ~ 3 1 9
equipment, 583-584 nucleotide sequence variations, 593
herbals and dietary supplements, 582 numerals, 793-794
radiopharmaceuticals, 709 quotation marks, titles and subtitles, 11
Prospective studjr, statistical definition, 887 ratios, 832
prostitute vs sex worker, usage, 400 references, 41, 44-45
protein databases, 597 roman numerals, 457
proteins, molecular terms, 552, 715-720 SI units, 791
proteins, Streptococci, 752 tables, 95-36
protein S and S protein, 674, 683 purposive sample, statistical definition, 888
protein terminology, 714-715 (See ako amino P value, rounding numbers, 851-852
acids, glycoproteins, lipoproteins, P value, statistical definition, 888-889
oncoprotein terminology)
provider vs clinician, practitioner, usage, 330, QMY (quality-adjusted life-year), cost-
400- 401 benefitlcost-effective analysis, 849
provisional acceptance of a manuscript, 268 QALY (quality-adjusted life-year), statistical
~ s e l ~ c ~ o n y n 3lltIlorship,
~ous 132-133, 189 clefinition,H89
pscllclonynls, rr:ldeln;lrks, 2 1 1 QI{S conll'lex, 554-557
~ ~ ~ ~ ~ ~ ~ ~ ~ ) st;~[ih[i~.:~j
r ~ ~ n ~(lcfinirion,~ ~ l l l ~ ~ i ~ qu;llit:ltive
t i o n , data, sr;~tisricaldefinition, 889
~ ) ~ ~ ~ 'f ~e lr ~ ~. l~~i rn7 :lo, )~l. -~- ] ~ ~ , (iLl;llit:ltivestlldy, st;lristical definition, 889
\ , l fK rl , <,3S<)
~ ~ ~ ~ ~ I lt l O ,
(tu:lIiry-atljustcd lik-ye;~r(QALY), cost-
[ ~ I I I I I I .!ll<>,,
~ I,!.!,
L I C ~ I E I I I , ln. s:, 1
T!,r'!.l .!!>.I!.>
,,!,
I)crlefit/cosr-eft'rctive ;~nalysis,849
(lu.tlit!.-:lt!jus[ed life-year (QALY), statistical
,.
..
- -
.. 1
.*.I
clcfinition,tUjg
 ~ . ~ L !~ I I~ ~ I J ~ ~ VUO,
I I A , A. I~.~T:II:>,BI<
.K\
, -G-.-lu
l.,;w<i ,Jl>. 92.4
qi1JntllJl1\cL ~ I - .>IJII<ILJI ~Iriln~l~t>n.
h*\ IJI~~~SJIII-C~~CLI\ I I U ~ C I , mcu-analy~~\,
C I U ~ > I - C X ~ C\r;r~lsrlc;ll
~ I I I I Cdctin~uon.
~I. ti* r~nclumcffcctsn d c l . sclcu~st~ral
dchnit~on,889
qucslion !nark, jjj-jj(, r~ndon~ization, statis~icaldefinition. 889-890
QUOKOM (Quality of Hcponing oi .\lct:~- r~ndornizedcontrolled trial, statistical
~nalyses),flow di3granis. 107. R 4 7 definition. 890
quot:~tionmarks randomized controlled trials
spologctic fonn. 360 cost-benefit/cost-effectiveanalysis, 849
article titles and subtitles, 11 drug development, 5 6 5 6 7
I h c k quotations, 361-362 flowchans, 107
capirali7;ltion. 360 manuscript preparation, 9-10
coined words, 360 QUOKOM flow diagrams, 847
colnllla placement. 341 study design, 838-841
common words used in 3 technical vs observational studies, 845-846
.sense, 361 random sample, statistical definition, 830
definitions of non-English words, 361 range, statistical definition, 890
diacritics in non-English words. 422 rank sum test, statistical definition, 890
dialogue, 359 rank, taxonomic, 742-743
electronic files, 361 rate, statistical definition; 890
indirect discourse, 361 rates and ratios, 832
non-English words, 360 Rat Genome and Nomenclature Cornmitree, 64;
omission, 360 Rat Genome Database, 650
organisms terminology, 744-745 ratio, statistical definition, 890
placement, 359-360 ratios, 343,345,354
poems, 361 reagent terminology, 583%
quotations, 359 recall bias, ow-control study, €?46-847
radio broadcasts, 361 recall bias, statistical definition, 890
single quotation marks, 359 receiver operating characteristic curve (ROC
slang, 360 curve), diagnostic tests, 850
so-called, 361 receiver operating characteristic curve (ROC
songs, 361 curve), statistical delinition, 890
television broadcasts, 361 receptors in immunoglobulin terminology,
titles, 359 698-699
usage, 358 redundant publication. See duplicate publication
viral terminology, 759 . redundant words and phrases, 405-406
quotations referees, peer review, 303
capitalization, 371 reference group, statistical definition, 890
epigraphs, 24-25 references
insertions in brackets, 357-358 abbreviations, 41
punctuation with colon, authors' names, 44-45,s
quotation marks, 359 biblical material, 62, 343
reference citation format, 61-62 bibliographic elements, 41
use of ellipses, 365-3156 books
use of [sic], 358, 359 chapter numbers, 56
complete bibliographic data, 41, 52-53
r, statistical de'inition, 889 edition number, 55
R,statistical definition, 889 editors, 54
R ~statistical
, definition, 889 page numbers, 56
rZ,statistical definition. 889 place of publication, 55-56
race/ethnicity, inclusive language, 414- 4 publisher, 56
radiation, units of measure, 816817 translators, 54
radioactive isotopes, 24. 527-528 v ~ l u m enumbers, 54-55
radio broadcasts, 62,361,372 year of publication, 56
radiographs, electronic submission, 120 capitalization, 372-373
radiography, usage, 401 CD-ROMs, 62,6768
radiology, usage, 401 citation lists and number of authors, 134
radiology rerminology, 775-776 classical material, 62
 corrections, 52
databases, 70-71 government bulletins. 57-58
duplicate publication, 148 newspapers, 57
electronic media, 62-64 package inserts, 59
e-mail, 71 patents, 59
general style, 40-41 radio broadcasts, 62
government reports, 69-70 serial publications, 58
headings, 26 special collections, 59
illustrations, 119 supplements, 49
journal articles, 4749 television broadcasts, 62
complete bibliographic data, 41 theses, 58-59
corrections, 52 videotapes, 62
dates, 48 subtitles, 47
discontinuous pagination, 48 tables, 95
discussants, 51-52 television broadcasts, 62
duplicate publication, 52 textual citations, 42
issue numbers, 48 titles, 45-46
names of journals, 48, 472-500 Uniform Requirements, 4041
no named author, 51 unpublished data, 6041
page numbers, 48 unpublished mate.ria1, 59-61
parts of an issue, 49 visual media, 41
retractions, 52 Web sites, 68-69
secondary citation, 49-50 regardless vs irregardless, usage, 397
special departments, 50-51 regime vs regimen, usage, 401
special issues, 49 regression analysis, statistical definition. H ~ N
supplements, 49 regression line, statistical definition. Wl
theme issues,49 regression to the mean, statistical
journal names abbreviations, 472-500 definition, 891
law journals, 78 rejection, letters to the editor, 269
legal material rejection of a minuscript
case atation, 73-75 appeal of decision, 261, 307-308
commerikd services citation, 77-78 court case, 223
congressional hearings citation, 76 duplicate submission. 152-153
federal administrative regulation editorial responsibilities, 255-260
citation, 76 ' news embargo, 293
method of citation, 72-73 peer review and confidentiality, 220
qatute citation; 75-78 scientific misconduct, 166
legislation, 75-78 relationship vs association, usage.
lit format, 41 relative pronouns, 317-318
monographs, 53 relative risk (RR), statistical definition. 891
news releases, 72 relative risk reduction (RRR), statistid
non-English language, 46-47 definition, 891
numbering and citatioh, 42-44 reliability, statistical definition, 831
online conference proceedings/presentations, repeated measures, statistical
71-72 , definition, 892
online journals, 64-67 repeated-measures ANOVA. See analysis of
online newpapers, 69 variance (ANOVA)
organization reports, 69-70 repeat vs repeated, usage, 401
personal communications, 61 reporting bias, statistical definition, 892
press releases, 61-62 repon vs describe, usage, 391
p~lnctuation,41. 343, 356 reprints
cluol.lIions. 61-62 :lclvertising, 2#
r:t<Ito!)ro.{d<.:i,[s,62 corrections public;ltion, 270
-c-( 0tic1.1y ( I ! . I ! I ~
61) -62
~. journal anicles, 310
.d:!:-.\.I:,. -:; permissions, 201, 203-206
s:llrs, 276
s ~ ' l ) ~ ( ) ( ~ t ~ csl:~[is~i(.:~I
i l ~ i l i ~ y(,l c : l i ~ l i l i ( ~ fX92
~,
~ ( ' I ) ~ ~ ~ 01'J ~[(.XI.~ ~ e. :l I( I. l~: ~~ J~I2.30. ~I ~ :2.1
~ I~ i ~ ~ ~ ~ ,
Index

research misconduct. See scientific miscontluct scdtterplots, figures, 9-101

research reports, 3 Scheffk test. See multiple conipanxms
research subject, usage, 388-389 procedures
rcsidu;~l,st:~tisticaldefinition, 892 schizophrenic, usage. 389
residual confountling, 01)sewationnl studies, 845 school-age vs school-aged, age, aged, teenage.
residual confounding, statistical definition, 892 teenaged, usage, 384-385
respective vs respectively, usage, 401-402 scientific misconduct
response me, statistical definition, 892 authorship, 166
restriction enzyme terminology. 601-(fi3 breaches of confidentiality, 158,161
restrictive clauses, 318 confidentiality, 222
Results, 21-22,25,838 corrections publication, 270
retractions, 52,160-165,241 definitions, 155-157
retrospective study, statistical definition, 892 digital image manipulation, 158-159
retroviral gene terminology, 658-659 editorial policy, 159-161
review articles expressions of concern, 161-166
conflict of interest disclosure, 171 fabrication of data, 157
defamation, 238-239 falsification of data, 157
journals, 5 omission of data, 157
types of articles, 3 4 peer review and confidentiality, 219
revised editions, copyright, 192-193 plagiarism, 158
revision, editorial responsibilities, 266 rejection of a manuscript, 166 . C
rhetorical questions, question miirk, 335-336 retractions, 160-165
p (Spearman rank correlation), statistical scientific presentations, media relations, 291-292
definition, 894 SD (standard deviation), statistical definition, 8%
right-censored data. See censored data. SE (standard error), statistical definition, 894
RIPE Network Coordinating Centre, 456 search engines, 287,301,436
risk, statistical definition, 892 SearchGene5(Human Gene Nomenclature
risk factor, statistical definition, 892 Database). 610
risk ratio, statistical definition, 892 seasons, capitalition, 377
RNA terminology, 597-599 secondary citation. reference citation
ROC curve (receiver operating characteristic format, 61-62
curve), statistie definition, 890 secondary hemostasis terminology, 669-674
Roman numerals secondary publication, 149, 151
cancer staging terminology, 546 section vs slice, usage, 402
clotting factor terminology, 670-672 SEE. See standard error of the estimate
correct usage, 832-833 selection b i i , 846-847
human chromosome terminology, 637 . selection bias, statistical defmition, 893
nematode gene terminology, 657 self-archiving, defmition, 184
nerve tenn@iology, 722-723 SEM (standard error of the mean), statistical
punctuation, 457 defmition, 895
restriction enzyme terminology, 602 semicolon
table, 833 chromosome terminology, 646,654
root-mean-square. See standard deviation (SD) conjunctive adverbs, 341-342
rounding numbers, 826827,851-852 definition, 341
RR (relatiw: risk), statistical definition, 891 enumerations, 342
RRR (relative risk reduction), statistical genotype terminology, 630
definition, 891 references, 41
rule of 3,statistical definition, 892-893 separating independent clauses, 341-342
rules in tables, 90 sensitivity, statistical definition, 893
run-in period, statistical definition, 893 sensitivity analysis, 848-850
running foot, title page of manuscript, 19 sensitivity analysis, statistical definition, 893
running head, title page of manuscript, 19 sentence fragments, 325
sequence variations
Salmonella nomenckdmre, 751-752 allele terminology, 628
salt designations in drug names, 570-572 amino acids, 607
sample, statistical definition, 893 clotting factor terminology, 672-674
sampling error, statistical definition, 893 gene terminology, 615-616
sans serif type, 920-922,923 nematode gene terminology, 657
 Index

nucleotides, 593-597 slander, definition, 235-237

RNA terminology, 598 slang, 325. 360
von Willebrand factor terminology, 674 slash. See virgule (solidus)
yeast gene terminology, 657 , sleep stages terminology. 729-730
serial publications, reference citation format, 58 slice vs section, usage, 402
series or comparisons, 326-327 small caps, 714, 772-774. 926. See also
serif type, 920-922, 923 capitalization
settings in structured abwracts, 21 snowball sampling, statistical definition. 894
sex, referents, 410 social titles, abbreviations, 456458
sex/gender, inclusive language, 412-413 sociocultural designations, 375-376, 415-416
sexual orientation, inclusive language, 417 software
sex vs gender, usage, 395 antiplagiarism, 158
sex worker vs prostitute, usage, 400 capitalization, 372
shading digital image manipulation, 158-159
' figures,114 figures, 120
genetic pedigree studies, 661-662 indexing, 31 1
rules in tables, 90 reference citation format, 70
table stubs, 87 scientific misconduct and, 156
vertical bar graphs, 103 spell-check, 324
ship names, 372, 925 table preparation, 97
SI (Systkme International &Unit&) units 3dimensional figures, 11j
abbreviations, 519-525,790, 792 solidus (see virgule)
base units in SI, 788 solution concentrations, units of me;lsure. 795
capitalization, 790 somite terminology, 723-724
conversions from conventional units, 795 song names in quotation marks, 361
definition, 787-788 Southern blotting, 601
derived uniu;, 788789 Southwestern bloning, 601
dual reporting conventional and SI units, space vehicle names, 372. 925
794797 spacing
exponents, 791 4 digits or more, 822
expressing quantities, 792-793 line. 923
hyphenation, 792 mathematical composition, 913
laboratory values, reference ranges and SI units, 792
conversion factors, 797-816 typogtaphy, 922
multiplication of. 790-791, 794 word, 922
parentheses, 792 Spearman rank comelation (p), statistic11
pluralization, 791 definition, 894
prefixes, 789 special collecrions, reference citation form:^^. 55)
punctuation, 791 species in virus nomenclature, 757-758
radiation, 816-817 specificity, statistical definition, 894
spacing, 792 spinal nerve terminology, 723-724
subject-verb agreement, 791 split infinitives, 322
time, 796 spongiform encephalopathies terminology,
sic, in quotations, 358, 359 7G8-769
sidebars, 84, 122-123 sponsorship
side effea vs adverse effect, event, reaction, acknowledgmmts, 32, 145-146, 173
usage, 384 authorship criteria, 130
side heads in boldface type, 725 online-only articles, 37
signature blocks, comespondlng author, 28-29 S protein and protein S, 674, 683
signed rank test. See Wilcoxon signed rank test staging, tumor terminology, 546-549
significance, randomized controlled trial, 837 standard deviation (SD), statistical definition, 894
significance, statistical definition, 893-894 standard error (SE), statistical definition, 894
significant d~gits,rounding numbers, 826, 851 standard error of the clifference,st;~tistical
sign test, stat~sticaldefinition, 894 definition, 895
since vs because, as, usage, 386 st;~ndartlerror of [he estimate, st;~tistic;~l
single-blind vs double-bl~ndpeer review, 307 clefinition, 895
single quot:ltion marks, 359 srandard error of t l ~ enlt.:ln (SEMI, st;~Iistical
skewness, statistical definition, 894 clefinition, 895
Index

i
standard error of the proportion, statistical study group, statistical definition, 896
definition, 895 subentry levels, indexing, 433-434 1
standardization (of a rate), statistical subgenus in bacterial nomenclature, 744
definition, 895 subheads. 924-925
standardized mortality ratio, statistical subject and patient anonymity, 121
definition, 895 subject-verb agreement
standard normal distribution, statistical collective nouns, 329
definition, 895 compound subject, 329-330
standard score. See z score definition, 327
STARD (Standards for Reporting of Diagnostic every and m n y a, 330
Accuracy), 107, 850 false singulars and plurals, 328
state and province names, abbreviations, intervening phrase, 327-328
451-454 one of tbose and plural verb, 330
statistic, statistical definition, 895 parenthetical plurals, 328,357
statistical analysis shift in number and disagreement, 330
access to data statement, 174
acknowledgrn-nu, 32-33, 35, 142, 1.44145
subject and predicate differ, 330
the number and a number, 330-331
[
figures, 117 with SI units of masure, 791 I
peer review, 306 . subject vs patient, case, consumer, client,
4
1 .I

:4
tables, 96 usage, 388-389
statistical symbols and abbreviations, 300-902 subjunctive verbs, 320 c I ;

statistical techniques, 852-853 submission requirements

statistics, terminology in italics, 926 editorial assessment, 301 . .
Statute of Anne, 187 figures, 120-121 .a: ". '.
stem cell terminology, 714
stereoisomen, 572
Internet, 304-306
print and online, 743
/
, . ..
!

. .,
..<i
i. ,+:.Q
stochastic, statistical definition, 895 Web sites, 263 : :g
stopping rule, statistical definition, 896
suains
bacterial nomenclature, 752
influenza nomendature, 760-761
subspecific ranks in bacterial nomendature,

subtitles
7457%
substantial contribution, authorship criteria, 128 '<
14
viral terminology, 758, 760 articles, 8-13 .*
stratification, statistical definition, 896 first word capitalization, 371 3
streptococci nomenclature, 752-753 hyphenated compounds, capitalization,
suuaured abstract format 375374
copyright, 199 numbers, 11
original artide, 20-22 reference citation format, 47
review articles, 22-23 sufficient cause, statistical definition, 896
types of articles, 4 suffixes
stubs in tables, 87-88,92 capitalization, 373 .
Studen:-Newman-Keulstest.-See Newman- colony-stimulatingfactor terminology, 577-578 8
Keuls test hyphenation, 350
Student t test See t test - . 395
-ic,. - i d ,. usage,
study design molecular terms. 714
case-control study, 846847 monoclonal antibody terminology, 578-579
case series. 847 nonproprietary drug names, 567-568
cohon study, 846 -ology, usage, 399
cost-benefit analysis, 849 taxonomic rank,742-743
cost-effectiveness analysis; 849 suggestive vs suspicious, usage, 402
crossover trial, 842-843 supplements, 49, 283-284
diagnostic tests, 849-850 supportive criteria, statistical delinition, 8%
equivalence and noninferiority trials, 843-845 surgical procedure vs operation, usage, 399
meta-analysis, 847-848 surnames, prefixes and particles, 45- 46
observational studies, 843-846 surrogate end points, statistical definition, 8% 4
parallel-design double-blind trials. 841-842 survey studies, study design, 850-851
nndoinized controlled trial, 566-567, 838-841 survival analysis, statistical definition, 896
rexarch and statistical analysis, 835-836 survival plots and survival curves, 99-100
{
u w c y ztudics. HSO-851 survivor vs victim. usage. 402
3
 Index

suspicious vs suggestive, usage, 402 totals, 89-90

symbols unirs of measure, 95-96
capitalization, 371, 374 uses, 81-82
chromosome terminology, 6 4 0 4 4 vs text, 81
figures, 114 tabulations, 82-83
fruitfly gene terminology, 656-657 target population, statistical definition. 896
gene T-cell terminology, 704 T (tau). See Kendall T (mu) rank correl;~tion
genetic pedigree studies, 660-666 taxonomy of organisms, 436, 740-743. 756-7j H
mathematical composition, 911-912 T-cell receptor gene terminology, 702-703
molecular neuroscience gene terminology, Tcell terminology, 701-703
732-733 technical terms, abbreviations, 501-519
mouse gene terminology, 650-653 teenage vs teenaged, age, aged, schtml-age.
nematode gene terminology, 657 school-aged, usage, 384-385
ophthalmology terminolo&, 736-737 television broadcasts, 62, 361, 372
: pluralization, 369 temperature, units of measure, 795. 823
pulmonary and respiratory terminology, temperature vs fever, usage. 394
771-774 tenses of verbs, 320-321
sequence variations, 595 terminate vs abort, usage. 382
in siru hybridization, 646-647 ternary names in bacterial nomenclarurr. 745-7-46
SI units, 788-790 test names, capitalization. 377
spacing, 913 text, 81, 119, 197-198
statistical, 900-902 textual citations of references, 42 .
table footnotes, 91 that vs which, usage, 318
trademark, 212, 584 theses, reference citation format, 58-59
yeast gene terminology, 657 though vs although, usage. 385
symposium discussions, copyright, 200-201 3-djrnensional figures, 115
synonyms, cross-references, 432 . thrombolysis terminology. 672-674
Systkme International &Unit& (see SI) thrombophilias terminology. 672-673
thyroid hormone terminology, 575
tables time
abbreviations, 92-96 designators in small caps. 926
alignment of data, 89-90, 92 punctuation with apostrophe, 363
appendixes, 36 punctuation with colon. 343
boldface type, 89, 925 units of measure, 7%. 822-823
capitalization, 371, 373-374, 378-379 title page of manuscript
column headings, 86-87 acknowledgments, 1%
components, 84, 86-90 affiliation footnotes, 28
ellipses, 88, 366 article title and subtitle, 8-13
enumerations, 829 bylines, 13-14
fields, 87-88 conflict of interest, 172
footnotes, 90-95 corresponding author, 28-29
headings, 26 death of an author, 17
manuscript preparation, 309 disclaimer, 33-34
matrix form, 84 financial discjosure, 30-31
No. (numbek), abbreviated, 829 footnotes, 16-19
numbers, 87-88, 96 group authorship, 15-16, 135-137
online-only articles, 36-38 numerals, 821, 823-824
organization of information, 84 online-only articles, 37
permission to reproduce, 34-35, 95 nlnning foot, 1')
prepa~ltion,97 nlnning he:ltl, 19
prlnrtu:~tion,95-90 sllorl lillc. LO
rcl'erenccs, 42. 44 SI ur1il.s. 70 1-792
row he;~dings,87 Wcl) silch, OH-(19
rules and shading, 90 titles
SoFtware, 97 articles, 8-13, 372-373
statistical analysis, 96 capit:tiization. 372
stubs in, 87 COmpOuncl c,f'fici;rl [i[\c-.I l ~ p ~ l v r l . ~ '.:: ~i ~
5:'

t;~bul;~tions,8j
 biological nomenclature, 746
drugs, 570
troponins, 562, 618
h!.phrn;ltcJ colnpounds. capitalizarion, true negative, statistical definition, 897
373-374 true-negative rate, statistical definition, 897
legends. 120 true positive, statistical definition, 897
nulnlxrs, 11 we-positive rate, statistical definition, 897
punctu:rtion wit11 comma, 340 t test, statistical definition, 897
quotation marks, 11, 359, 361 Tukey test, statistical definition, 897
ind do mi zed controlled trials, 9-10 tumor staging terminology, 548552
references. 45- 46 tumor suppressor gene terminology, 616-617,
in r ~ l ~ l r84-86
s, 636
tradc~narks.21 1 2-tailed test, statistical definition, 897
titlcs and culk. fcx)cnoces. 17-!9 2-way analysis of variance. See analysis of
titles of persons. 378. 446448 variance (ANOVA)
titr~tevs titration, usage, 403 typefaces, 920, 922
T-lymphocyte tcrnlinol?gy, 701-702 type I error, statistical definition, 898
TNM staging system tcrn~inology,546-549 type I1 error, statistical definition, 898
toxic vs toxicity, uuge, 403 typesaipt vs paper, manuscript, article,
TI'AL (obstetric terminology), 735 usage, 386
tr:~dedress, traden~arks.211 typesetting Greek letters, 783 e
trademarks typography
abandonment or dilution. 212-213 blood groups and platelet antigens, 536-542
application for protection, 211-212 cancer terminology, 546-552
capitalization, 372, 376 cardiology, 553-563
definition, 179, 210 definition, 917-918
drug names, 568-569 design elements, 918-920
infringement, 214 DNA sequences, 589-593
liability concerns, 241-242 fonts, 920-922
in references, 584 human gene nomenclature, 608632
symbols. equipment. 584 indexing, 431
use in publication, 213 layout, 923-924
trade names letterspacing, 922
capitaliiation, 380 mathematical composition. 912
copyright, 213 nonhuman genetic terms, 649-659
proprietary drug names, 568-569 plant virus terminology, 759
punctuation, 357 platelet factor terminology, 667-668
Trade-Related Aspeas of Intellectual Property restriction enzyme terminology, 601603
Rights (TRIPS), 188, 208, 211 RNA terminology, 598
trans, 374 viral terminology, 757
transitions, and paragraphs. 331
translated articles, 149
translation of non-English words, 421 ultrasonographyvs ultrasound, usage, 403-404
translators in book references, 54 UMLS (Unified Medical Language System),
transmissible spongiform encephalopathy nomenclature, 532
terminology, 768-769 uncensored data, statistical definition, 898
transplant vs transplantation, usage, 403-404 underlining in chromosome terminology, 646
treatment vs management, usage. 398 under vs over, usage, 399
trend, test for. See x2 test (chi-square test) unethical-studies,228-229, 839, 843
trial, statistical definition, 896 Unified Medical Language System (UMLS), .
triangulation, statistical definition, 897 nomenclature, 532
trinomial names% bacterial nomenclature, uniform labeling terminology, 709
745-746 uniform prior, statistical definition, 898
TRIPS (Trade-Related Aspects of Intellectual Uniform Requirements for Manuscripts
I'ropeny Kighu). 188. 208. 21 1 Submitted to Biomedical Journals, 8,
trivial names 40, 128
allele terminologv. 629 uninterested vs disinterested, usage, 392
amino acid terminology. 60-1-607 unique identifiers, 532, 596, 721
 Index

units of measure partic~ple,323

abbreviations, 519-525 plural, 330
indexes, 794 spl~tinfinitives. 322
manuscript preparation, titles and subtitles, 11 subject-verb agreement, 327-328, ji7. 791
metric to English unit conversions, 795 subject-verb disagreement. 330
pressure, 796 tense, 320-321
punctuation with comma, 341 verb phrases, 322
SI units, 787-792 voice, 320
tables, 92, 95-96 vernacular names, 740, 756
.temperature, 823 vertebrae terminology, 723-724
time, 796,822-823 vertebrate genetic terminology. 649-6ih
title page of manuscript, 823-824 Vibrio cholerae nomenclature. 7 i 3
visual acuity, 796 victim vs survivor, usage, 402
unity, statistical definition, 898 ' video files, digital image manipulat~on.158- 1 i c )
, univariable analysis, statistical definition, 898 videos, reference citation format, 66
univariate analysis, statistical definition, 898 videotapes, reference citation fornxit. 62
unpaired analysis, statistical definition, 898 viral nomenclature, 756-767
unpaired t test. See t test viral terminology, 756-759
unpublished material virgule (solidus)
copyright, duration of, 190-191 CD (cluster of differentiation) cell
fair use exclusions in copyright, 198 terminology, 679
financial disclosure, 176 dates, 354
peer review and confidentiality, 219-220, equations, 354
265-266 expressions of equivalence or duality, 353
unpublished material, reference citation genotype terminology, 629-632
format, 59-61 HLA terminology, 690, 693
unsigned editorials, authorship, 132-133 karyotype terminology, 640
uppercase letters, usage, 924 mouse strains, 655-656
USAN (US Adopted Names Council), 565-566 phonetics, 354
US Copyright Law of 1976, 187-188 poetry, 354-355
US Department of Health and Human Services rates and ratios, 832
Regulations for the Protection of Human ratios, 354
Subjects, 228 SI unit quotients, 790-791
use vs usage, utility, utilize, usage, 404
U test. See Wilcoxon rank sum test
used to mean per, 354 .
virus terminology, derivarions, 760
utility, statistical definition, 898 vision vs visual acuity, usage, 404
utility vs utilize, use, usage, 404. visual acuity, units of measure, 796
visual acuity vs vision, usage, 404
vaccinate vs inoculate, immunize, usage, 396 vitamin terminology, 579-580
validity (of a measurement), statisticaldefinition. vocabulary control, indexing, 434- 436
898-899 voice of verbs, 320
validity (of a study), statistical definition, 899 volume, du;d reporting conventional and
validity.(of a study), survey studies, 850 SI units, 794
Van der Waerden test, statistical definition, 899 volume numbers in references, 48, 54-55
variable, sutistichl definition, 899 von Willebrand factor terminology, 673-674
variable (V) gene segments, 699-700, 703-704
variables in cohort study, 846 washout period, crossover trial, 842
variance components analysis, statistical washout period, sra~isric:ildefinition. 899
definition, 899 Web sircs
variance ratio distribution, st;itisric:il tlefinirion. :itlvcnis~n~. ?St ? S i
899 ~ l n l I l 0 1 1\r)l.~fi
~ i { r y . ~ r ~l r.il\ ~l ~ r t ~ l rO. W
V, D,anti J gene seRtncnl\. (,'PI 7 ~ 1 ~ 1- ,I ] < - I ) - + . I ~ \ I K l l l l l ~ ' l i lr i: ( 11<111
,;i\ 10.1
verb pllr;~.ses.$12 t ( I;;'., ,I<; -4,

verbs , ..rr,., r:, ,:I, !, . . . .!.,,..',,,.<:!:!.,zr!:,,; ;:i,

.> ,-
 N : UL. )I a n . L r r u.w exclusions in copyright,
108
U,,,rlJ .kiwiation of Medical Editors (WAME)
conflict of interest, 169
editorial freedom, policies for, 253-257
infom~edconsent, 227
news media relations, 292
peer review and confidentiality, 218-219
inanuscript submissions. 263 scientific misconduct and retraction,
blouse Genome Informatics, 6jj 160-161
organisms terminology, 741 World Intellectual Property Organization
reference citation format, 63-64,68-69 (WIPO), 188,207-208,213
references, 42 writing group, authorship, 136137
references in manuscripts, 837 written assignment of copyright, licensing,
retractions; 161-162 194-195
typography, 918 written communications, 61,146, 139
UMLS Metathesaurus, 532
Wellcome Trust, data sharing, 181 x-axis, graphic display, 113-114
Western blotting, 601 x-axis, statistical definition, 900
who vs whom, upge, 317-318 XC chemokine subfamily, 677-678
Wilcoxon rank sum test, statistical
definition, 899 Yates correction, statistical definition, 900
Wilcoxon signed rank test, statistical y-axis, graphic display, 113114
definition, 900 y-axis, statistical definition, 900
Wilks 5 (lambda), statistical definition, 900 years, pluralization, 369
WIPO (World Intellectual Property yeasts, gene termjnology, 657
Organization), 188,207-2OJ3,213
word spacing, 922 z-axis,statistical definition, 900 .
works for hue, 189,196,198-199 2.score, statistical d'efinition. 900