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Erik B Erhardt

University of New Mexico, Mathematics and Statistics, Faculty Member

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Papers by Erik B Erhardt

High frequency field measurements of diurnal carbon isotope discrimination and internal conductance in a semi-arid species, Juniperus monosperma

We present field observations of leaf gas exchange, carbon isotope discrimination (Delta) and int... more We present field observations of leaf gas exchange, carbon isotope discrimination (Delta) and internal conductance of CO2 to the sites of carboxylation (gi) collected during summer 2006 using tunable diode laser spectroscopy (TDL). Delta ranged from 27.40/00 to 12.60/00 over diurnal periods with daily means of 16.3 ± 0.20/00 during drought to 19.0 ± 0.50/00 during monsoon conditions. We observed

Parental military service, agent orange exposure, and the risk of rhabdomyosarcoma in offspring

The Journal of pediatrics, 2014

To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) ri... more To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) risk in offspring using data from a large case-control study of childhood RMS. Cases (n = 319) were enrolled from the third trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 319) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate parental military service-related exposures and their associations with childhood RMS by generating aORs and 95% CIs. Statistical significance was defined as P < .05. There were no significant associations between parental military service and childhood RMS. The strongest association was with maternal military service; however, this association was attenuated and did not remain significant after adjusting for covariates (aOR = 2.75, 95% CI 0.71, 10.62). An elevated effect estimate was found when assessing paternal exposure to Agent Orange (AO) and childhood RMS but was no...

A baseline for the multivariate comparison of resting-state networks

by Erik B Erhardt, Eswar Damaraju, and Rogers F Silva

Frontiers in Systems Neuroscience

As the size of functional and structural MRI datasets expands, it becomes increasingly important ... more As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting-state networks (RSNs) of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12-71 years). Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. RSNs were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functiona...

Supplementary Material to: Tracking Whole-Brain Connectivity Dynamics in the Resting State

by Erik B Erhardt, Sergey Plis, and Eswar Damaraju

Conserved patterns of incomplete reporting in pre-vaccine era childhood diseases

Proceedings. Biological sciences / The Royal Society, Jan 7, 2014

Incomplete observation is an important yet often neglected feature of observational ecological ti... more Incomplete observation is an important yet often neglected feature of observational ecological timeseries. In particular, observational case report timeseries of childhood diseases have played an important role in the formulation of mechanistic dynamical models of populations and metapopulations. Yet to our knowledge, no comprehensive study of childhood disease reporting probabilities (commonly referred to as reporting rates) has been conducted to date. Here, we provide a detailed analysis of measles and whooping cough reporting probabilities in pre-vaccine United States cities and states, as well as measles in cities of England and Wales. Overall, we find the variability between locations and diseases greatly exceeds that between methods or time periods. We demonstrate a strong relationship within location between diseases and within disease between geographical areas. In addition, we find that demographic covariates such as ethnic composition and school attendance explain a non-tr...

Family history of cancer and childhood rhabdomyosarcoma: a report from the Children's Oncology Group and the Utah Population Database

Cancer Medicine, 2015

Relatively little is known about the epidemiology and factors underlying susceptibility to childh... more Relatively little is known about the epidemiology and factors underlying susceptibility to childhood rhabdomyosarcoma (RMS). To better characterize genetic susceptibility to childhood RMS, we evaluated the role of family history of cancer using data from the largest case-control study of RMS and the Utah Population Database (UPDB). RMS cases (n = 322) were obtained from the Children's Oncology Group (COG). Population-based controls (n = 322) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate the association between family history of cancer and childhood RMS. The results were validated using the UPDB, from which 130 RMS cases were identified and matched to controls (n = 1300) on sex and year of birth. The results were combined to generate summary odds ratios (OR s ) and 95% confidence intervals (CI). Having a first-degree relative with a cancer history was more common in RMS cases than controls (OR s = 1.39, 95% CI: 0.97-1.98). Notably, this association was stronger among those with embryonal RMS (OR s = 2.44, 95% CI: 1.54-3.86). Moreover, having a first-degree relative who was younger at diagnosis of cancer (<30 years) was associated with a greater risk of RMS (OR s = 2.37, 95% CI: 1.34-4.18). In the largest analysis of its kind, we found that most children diagnosed with RMS did not have a family history of cancer. However, our results indicate an increased risk of RMS (particularly embryonal RMS) in children who have a first-degree relative with cancer, and among those whose relatives were diagnosed with cancer at <30 years of age.

SimTB, a simulation toolbox for fMRI data under a model of spatiotemporal separability

We introduce SimTB, a MATLAB toolbox designed to simulate functional magnetic resonance imaging (... more We introduce SimTB, a MATLAB toolbox designed to simulate functional magnetic resonance imaging (fMRI) datasets under a model of spatiotemporal separability. The toolbox meets the increasing need of the fMRI community to more comprehensively understand the effects of complex processing strategies by providing a ground truth that estimation methods may be compared against. SimTB captures the fundamental structure of real data, but data generation is fully parameterized and fully controlled by the user, allowing for accurate and precise comparisons. The toolbox offers a wealth of options regarding the number and configuration of spatial sources, implementation of experimental paradigms, inclusion of tissue-specific properties, addition of noise and head movement, and much more. A straightforward data generation method and short computation time (3-10 seconds for each dataset) allow a practitioner to simulate and analyze many datasets to potentially understand a problem from many angles. Beginning MATLAB users can use the SimTB graphical user interface (GUI) to design and execute simulations while experienced users can write batch scripts to automate and customize this process. The toolbox is freely available at http://mialab.mrn.org/software together with sample scripts and tutorials.

Nasal immunity is an ancient arm of the mucosal immune system of vertebrates

Nature communications, 2014

The mucosal surfaces of all vertebrates have been exposed to similar evolutionary pressures for m... more The mucosal surfaces of all vertebrates have been exposed to similar evolutionary pressures for millions of years. In terrestrial vertebrates such as birds and mammals, the nasopharynx-associated lymphoid tissue (NALT) represents a first line of immune defence. Here we propose that NALT is an ancient arm of the mucosal immune system not restricted to terrestrial vertebrates. We find that NALT is present in rainbow trout and that it resembles other teleost mucosa-associated lymphoid tissues. Trout NALT consists of diffuse lymphoid cells and lacks tonsils and adenoids. The predominant B-cell subset found in trout NALT are IgT(+) B cells, similar to skin and gut. The trout olfactory organ is colonized by abundant symbiotic bacteria, which are coated by trout secretory immunoglobulin. Trout NALT is capable of mounting strong anti-viral immune responses following nasal delivery of a live attenuated viral vaccine. Our results open up a new tool for the control of aquatic infectious diseas...

Validation of biomarkers in subcortical ischaemic vascular disease of the Binswanger type: approach to targeted treatment trials

Journal of neurology, neurosurgery, and psychiatry, Jan 24, 2015

Vascular cognitive impairment (VCI) is a heterogeneous group of cerebrovascular diseases secondar... more Vascular cognitive impairment (VCI) is a heterogeneous group of cerebrovascular diseases secondary to large and small vessel disease. We hypothesised that biomarkers obtained early in the disease could identify a homogeneous subpopulation with small vessel disease. We obtained disease markers in 62 patients with VCI that included neurological findings, neuropsychological tests, multimodal MR and cerebrospinal fluid measurements of albumin ratio, matrix metalloproteinases (MMPs), amyloid-β1-42 and phosphorylated-τ181. Proton MR spectroscopic imaging showed ischaemic white matter and permeability of the blood-brain barrier (BBB) was measured with dynamic contrast-enhanced MRI. We constructed a 10-point Binswanger disease score (BDS) with subjective and objective disease markers. In addition, an objective set of biomarkers was used for an exploratory factor analysis (EFA) to select patients with BD. Patients were followed for an average of 2 years to obtain clinical consensus diagnoses...

Parental Military Service, Agent Orange Exposure, and the Risk of Rhabdomyosarcoma in Offspring

The Journal of Pediatrics, 2014

To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) ri... more To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) risk in offspring using data from a large case-control study of childhood RMS. Cases (n = 319) were enrolled from the third trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 319) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate parental military service-related exposures and their associations with childhood RMS by generating aORs and 95% CIs. Statistical significance was defined as P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05. There were no significant associations between parental military service and childhood RMS. The strongest association was with maternal military service; however, this association was attenuated and did not remain significant after adjusting for covariates (aOR = 2.75, 95% CI 0.71, 10.62). An elevated effect estimate was found when assessing paternal exposure to Agent Orange (AO) and childhood RMS but was not statistically significant (aOR = 1.72, 95% CI 0.55, 5.41). We found little evidence that parental military service of AO exposure influences the risk of RMS in offspring. These findings are notable in light of the continuing controversies surrounding the intergenerational effects of AO exposure.

Evaluation of dual nasal delivery of infectious hematopoietic necrosis virus and enteric red mouth vaccines in rainbow trout (Oncorhynchus mykiss)

Vaccine, 2015

Please cite this article in press as: LaPatra S, et al. Evaluation of dual nasal delivery of infe... more Please cite this article in press as: LaPatra S, et al. Evaluation of dual nasal delivery of infectious hematopoietic necrosis virus and enteric red mouth vaccines in rainbow trout (Oncorhynchus mykiss). Vaccine (2015), http://dx.a b s t r a c t Farmed fish are susceptible to different infectious disease agents including viruses and bacteria. Thus, multivalent vaccines or vaccination programs against two or more pathogens are valuable tools in aquaculture. Recently, nasal vaccines have been shown to be very effective in rainbow trout. The current study investigates, for the first time, the use of the nasal route in dual vaccination trials against two important aquatic diseases, infectious hematopoietic necrosis virus (IHN) and enteric red mouth (ERM) disease. Rainbow trout received live attenuated IHN virus (IHNV) vaccine and the ERM bacterin using four different vaccine delivery methods and were challenged with virulent IHNV or Yersinia ruckeri 7 (100 deg day) and 28 (400 deg day) days post-vaccination. The highest survival rates against IHNV at day 7 were obtained by nasal vaccination either when IHNV and ERM were delivered separately into each nare or when they were premixed and delivered to both nasal rosettes (group D). Protection at 28 days against IHNV was similar in all four vaccinated groups. Early protection against ERM was highest in fish that received each vaccine in separate nares (group B), whereas protection at 28 days was highest in the i.p. vaccinated group (group E), followed by the nasally vaccinated group (group B). Survival results were supported by histological observations of the left and right olfactory organ which showed strong immune responses one day (14 deg days) after vaccination in group B vaccinated fish. These data indicate that dual vaccination against two different pathogens via the nasal route is a very effective vaccination strategy for use in aquaculture, particularly when each nare is used separately during delivery. Further long-term studies should evaluate the contribution of adaptive immunity to the protection levels observed.

On Network Derivation, Classification, and Visualization: A Response to Habeck and Moeller

by Erik B Erhardt and Eswar Damaraju

In the decade and a half since Biswal's fortuitous discovery of spontaneous correlations in funct... more In the decade and a half since Biswal's fortuitous discovery of spontaneous correlations in functional imaging data, the field of functional connectivity (FC) has seen exponential growth resulting in the identification of widely-replicated intrinsic networks and the innovation of novel analytic methods with the promise of diagnostic application. As such a young field undergoing rapid change, we have yet to converge upon a desired and needed set of standards. In this issue, Habeck and Moeller begin a dialogue for developing best practices by providing four criticisms with respect to FC estimation methods, interpretation of FC networks, assessment of FC network features in classifying sub-populations, and network visualization. Here, we respond to Habeck and Moeller and provide our own perspective on the concerns raised in the hope that the neuroimaging field will benefit from this discussion.

Data Visualization in the Neurosciences: Overcoming the Curse of Dimensionality

In publications, presentations, and popular media, scientific results are predominantly communica... more In publications, presentations, and popular media, scientific results are predominantly communicated through graphs. But are these figures clear and honest or misleading? We examine current practices in data visualization and discuss improvements, advocating design choices which reveal data rather than hide it.

Assessing dynamic brain graphs of time-varying connectivity in fMRI data: Application to healthy controls and patients with schizophrenia

by Jing Sui, Yuhui Du, Qingbao Yu, Hao He, Erik B Erhardt, and Robyn Miller

NeuroImage, Jan 15, 2015

Graph theory-based analysis has been widely employed in brain imaging studies, and altered topolo... more Graph theory-based analysis has been widely employed in brain imaging studies, and altered topological properties of brain connectivity have emerged as important features of mental diseases such as schizophrenia. However, most previous studies have focused on graph metrics of stationary brain graphs, ignoring that brain connectivity exhibits fluctuations over time. Here we develop a new framework for accessing dynamic graph properties of time-varying functional brain connectivity in resting-state fMRI data and apply it to healthy controls (HCs) and patients with schizophrenia (SZs). Specifically, nodes of brain graphs are defined by intrinsic connectivity networks (ICNs) identified by group independent component analysis (ICA). Dynamic graph metrics of the time-varying brain connectivity estimated by the correlation of sliding time-windowed ICA time courses of ICNs are calculated. First- and second-level connectivity states are detected based on the correlation of nodal connectivity...

Correspondence between structure and function in the human brain at rest

Frontiers in Neuroinformatics, 2012

Correspondence between structure and function in the human brain at rest. Front. Neuroinform. 6:10.

Bayesian Simultaneous Intervals for Small Areas: An Application to Variation in Maps

International Journal of Statistics and Probability, 2012

The 5.1 ka aridization event, expansion of pinon-juniper woodlands, and the introduction of maize (Zea mays) in the American Southwest

The Holocene, 2012

Pollen analysis is frequently used to build climate and environmental histories. A distinct Holoc... more Pollen analysis is frequently used to build climate and environmental histories. A distinct Holocene pollen series exists for Chaco Canyon, New Mexico. This study reports linear modeling and hypothesis testing of long distance dispersal pollen from radiocarbon-dated packrat middens which reveal strong relationships between piñon pine (Pinus edulis) and ponderosa pine (Pinus ponderosa). Ponderosa pollen dominates midden pollen assemblages during the early Holocene, while a rapid shift to a much higher proportion of piñon to ponderosa pine pollen between c. 5440 and 5102 cal. yr BP points to an aridization episode. This shift is associated with higher 18

High-frequency field measurements of diurnal carbon isotope discrimination and internal conductance in a semi-arid species, Juniperus monosperma

Plant, Cell & Environment, 2009

We present field observations of carbon isotope discrimination (D) and internal conductance of CO... more We present field observations of carbon isotope discrimination (D) and internal conductance of CO2 (gi) collected using tunable diode laser spectroscopy (TDL). D ranged from 12.0 to 27.4‰ over diurnal periods with daily means from 16.3 Ϯ 0.2‰ during drought to 19.0 Ϯ 0.5‰ during monsoon conditions. We observed a large range in gi, with most estimates between 0.04 and 4.0 mmol m -2 s -1 Pa -1 . We tested the comprehensive Farquhar, O'Leary and Berry model of D (Dcomp), a simplified form of Dcomp (Dsimple) and a recently suggested amendment (Drevised). Sensitivity analyses demonstrated that varying gi had a substantial effect on Dcomp, resulting in mean differences between observed D (Dobs) and Dcomp ranging from 0.04 to 9.6‰. First-order regressions adequately described the relationship between D and the ratio of substomatal to atmospheric CO2 partial pressure (pi/pa) on all 3 d, but second-order models better described the relationship in July and August. The three tested models each best predicted Dobs on different days. In June, Dsimple outperformed Dcomp and Drevised, but incorporating gi and all non-photosynthetic fractionations improved model predictions in July and August.

Carbon stable isotopic composition of soluble sugars in Tillandsia epiphytes varies in response to shifts in habitat

by Erik B Erhardt and Louis Santiago

Oecologia, 2010

We studied C stable isotopic composition (d 13 C) of bulk leaf tissue and extracted sugars of fou... more We studied C stable isotopic composition (d 13 C) of bulk leaf tissue and extracted sugars of four epiphytic Tillandsia species to investigate flexibility in the use of crassulacean acid metabolism (CAM) and C 3 photosynthetic pathways. Plants growing in two seasonally dry tropical forest reserves in Mexico that differ in annual precipitation were measured during wet and dry seasons, and among secondary, mature, and wetland forest types within each site. Dry season sugars were more enriched in 13 C than wet season sugars, but there was no seasonal difference in bulk tissues. Bulk tissue d 13 C differed by species and by forest type, with values from open-canopied wetlands more enriched in 13 C than mature or secondary forest types. The shifts within forest habitat were related to temporal and spatial changes in vapor pressure deficits (VPD). Modeling results estimate a possible 4% increase in the proportional contribution of the C 3 pathway during the wet season, emphasizing that any seasonal or habitat-mediated variation in photosynthetic pathway appears to be quite moderate and within the range of isotopic effects caused by variation in stomatal conductance during assimilation through the C 3 pathway and environmental variation in VPD. C isotopic analysis of sugars together with bulk leaf tissue offers a useful approach for incorporating short-and long-term measurements of C isotope discrimination during photosynthesis.

Capturing inter-subject variability with group independent component analysis of fMRI data: A simulation study

NeuroImage, 2012

A key challenge in functional neuroimaging is the meaningful combination of results across subjec... more A key challenge in functional neuroimaging is the meaningful combination of results across subjects. Even in a sample of healthy participants, brain morphology and functional organization exhibit considerable variability, such that no two individuals have the same neural activation at the same location in response to the same stimulus. This inter-subject variability limits inferences at the group-level as average activation patterns may fail to represent the patterns seen in individuals. A promising approach to multi-subject analysis is group independent component analysis (GICA), which identifies group components and reconstructs activations at the individual level. GICA has gained considerable popularity, particularly in studies where temporal response models cannot be specified. However, a comprehensive understanding of the performance of GICA under realistic conditions of inter-subject variability is lacking. In this study we use simulated functional magnetic resonance imaging (fMRI) data to determine the capabilities and limitations of GICA under conditions of spatial, temporal, and amplitude variability. Simulations, generated with the SimTB toolbox, address questions that commonly arise in GICA studies, such as: (1) How well can individual subject activations be estimated and when will spatial variability preclude estimation? (2) Why does component splitting occur and how is it affected by model order? (3) How should we analyze component features to maximize sensitivity to intersubject differences? Overall, our results indicate an excellent capability of GICA to capture between-subject differences and we make a number of recommendations regarding analytic choices for application to functional imaging data.

High frequency field measurements of diurnal carbon isotope discrimination and internal conductance in a semi-arid species, Juniperus monosperma

We present field observations of leaf gas exchange, carbon isotope discrimination (Delta) and int... more We present field observations of leaf gas exchange, carbon isotope discrimination (Delta) and internal conductance of CO2 to the sites of carboxylation (gi) collected during summer 2006 using tunable diode laser spectroscopy (TDL). Delta ranged from 27.40/00 to 12.60/00 over diurnal periods with daily means of 16.3 ± 0.20/00 during drought to 19.0 ± 0.50/00 during monsoon conditions. We observed

Parental military service, agent orange exposure, and the risk of rhabdomyosarcoma in offspring

The Journal of pediatrics, 2014

To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) ri... more To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) risk in offspring using data from a large case-control study of childhood RMS. Cases (n = 319) were enrolled from the third trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 319) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate parental military service-related exposures and their associations with childhood RMS by generating aORs and 95% CIs. Statistical significance was defined as P < .05. There were no significant associations between parental military service and childhood RMS. The strongest association was with maternal military service; however, this association was attenuated and did not remain significant after adjusting for covariates (aOR = 2.75, 95% CI 0.71, 10.62). An elevated effect estimate was found when assessing paternal exposure to Agent Orange (AO) and childhood RMS but was no...

A baseline for the multivariate comparison of resting-state networks

by Erik B Erhardt, Eswar Damaraju, and Rogers F Silva

Frontiers in Systems Neuroscience

As the size of functional and structural MRI datasets expands, it becomes increasingly important ... more As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting-state networks (RSNs) of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12-71 years). Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. RSNs were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functiona...

Supplementary Material to: Tracking Whole-Brain Connectivity Dynamics in the Resting State

by Erik B Erhardt, Sergey Plis, and Eswar Damaraju

Conserved patterns of incomplete reporting in pre-vaccine era childhood diseases

Proceedings. Biological sciences / The Royal Society, Jan 7, 2014

Incomplete observation is an important yet often neglected feature of observational ecological ti... more Incomplete observation is an important yet often neglected feature of observational ecological timeseries. In particular, observational case report timeseries of childhood diseases have played an important role in the formulation of mechanistic dynamical models of populations and metapopulations. Yet to our knowledge, no comprehensive study of childhood disease reporting probabilities (commonly referred to as reporting rates) has been conducted to date. Here, we provide a detailed analysis of measles and whooping cough reporting probabilities in pre-vaccine United States cities and states, as well as measles in cities of England and Wales. Overall, we find the variability between locations and diseases greatly exceeds that between methods or time periods. We demonstrate a strong relationship within location between diseases and within disease between geographical areas. In addition, we find that demographic covariates such as ethnic composition and school attendance explain a non-tr...

Family history of cancer and childhood rhabdomyosarcoma: a report from the Children's Oncology Group and the Utah Population Database

Cancer Medicine, 2015

Relatively little is known about the epidemiology and factors underlying susceptibility to childh... more Relatively little is known about the epidemiology and factors underlying susceptibility to childhood rhabdomyosarcoma (RMS). To better characterize genetic susceptibility to childhood RMS, we evaluated the role of family history of cancer using data from the largest case-control study of RMS and the Utah Population Database (UPDB). RMS cases (n = 322) were obtained from the Children's Oncology Group (COG). Population-based controls (n = 322) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate the association between family history of cancer and childhood RMS. The results were validated using the UPDB, from which 130 RMS cases were identified and matched to controls (n = 1300) on sex and year of birth. The results were combined to generate summary odds ratios (OR s ) and 95% confidence intervals (CI). Having a first-degree relative with a cancer history was more common in RMS cases than controls (OR s = 1.39, 95% CI: 0.97-1.98). Notably, this association was stronger among those with embryonal RMS (OR s = 2.44, 95% CI: 1.54-3.86). Moreover, having a first-degree relative who was younger at diagnosis of cancer (<30 years) was associated with a greater risk of RMS (OR s = 2.37, 95% CI: 1.34-4.18). In the largest analysis of its kind, we found that most children diagnosed with RMS did not have a family history of cancer. However, our results indicate an increased risk of RMS (particularly embryonal RMS) in children who have a first-degree relative with cancer, and among those whose relatives were diagnosed with cancer at <30 years of age.

SimTB, a simulation toolbox for fMRI data under a model of spatiotemporal separability

We introduce SimTB, a MATLAB toolbox designed to simulate functional magnetic resonance imaging (... more We introduce SimTB, a MATLAB toolbox designed to simulate functional magnetic resonance imaging (fMRI) datasets under a model of spatiotemporal separability. The toolbox meets the increasing need of the fMRI community to more comprehensively understand the effects of complex processing strategies by providing a ground truth that estimation methods may be compared against. SimTB captures the fundamental structure of real data, but data generation is fully parameterized and fully controlled by the user, allowing for accurate and precise comparisons. The toolbox offers a wealth of options regarding the number and configuration of spatial sources, implementation of experimental paradigms, inclusion of tissue-specific properties, addition of noise and head movement, and much more. A straightforward data generation method and short computation time (3-10 seconds for each dataset) allow a practitioner to simulate and analyze many datasets to potentially understand a problem from many angles. Beginning MATLAB users can use the SimTB graphical user interface (GUI) to design and execute simulations while experienced users can write batch scripts to automate and customize this process. The toolbox is freely available at http://mialab.mrn.org/software together with sample scripts and tutorials.

Nasal immunity is an ancient arm of the mucosal immune system of vertebrates

Nature communications, 2014

The mucosal surfaces of all vertebrates have been exposed to similar evolutionary pressures for m... more The mucosal surfaces of all vertebrates have been exposed to similar evolutionary pressures for millions of years. In terrestrial vertebrates such as birds and mammals, the nasopharynx-associated lymphoid tissue (NALT) represents a first line of immune defence. Here we propose that NALT is an ancient arm of the mucosal immune system not restricted to terrestrial vertebrates. We find that NALT is present in rainbow trout and that it resembles other teleost mucosa-associated lymphoid tissues. Trout NALT consists of diffuse lymphoid cells and lacks tonsils and adenoids. The predominant B-cell subset found in trout NALT are IgT(+) B cells, similar to skin and gut. The trout olfactory organ is colonized by abundant symbiotic bacteria, which are coated by trout secretory immunoglobulin. Trout NALT is capable of mounting strong anti-viral immune responses following nasal delivery of a live attenuated viral vaccine. Our results open up a new tool for the control of aquatic infectious diseas...

Validation of biomarkers in subcortical ischaemic vascular disease of the Binswanger type: approach to targeted treatment trials

Journal of neurology, neurosurgery, and psychiatry, Jan 24, 2015

Vascular cognitive impairment (VCI) is a heterogeneous group of cerebrovascular diseases secondar... more Vascular cognitive impairment (VCI) is a heterogeneous group of cerebrovascular diseases secondary to large and small vessel disease. We hypothesised that biomarkers obtained early in the disease could identify a homogeneous subpopulation with small vessel disease. We obtained disease markers in 62 patients with VCI that included neurological findings, neuropsychological tests, multimodal MR and cerebrospinal fluid measurements of albumin ratio, matrix metalloproteinases (MMPs), amyloid-β1-42 and phosphorylated-τ181. Proton MR spectroscopic imaging showed ischaemic white matter and permeability of the blood-brain barrier (BBB) was measured with dynamic contrast-enhanced MRI. We constructed a 10-point Binswanger disease score (BDS) with subjective and objective disease markers. In addition, an objective set of biomarkers was used for an exploratory factor analysis (EFA) to select patients with BD. Patients were followed for an average of 2 years to obtain clinical consensus diagnoses...

Parental Military Service, Agent Orange Exposure, and the Risk of Rhabdomyosarcoma in Offspring

The Journal of Pediatrics, 2014

To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) ri... more To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) risk in offspring using data from a large case-control study of childhood RMS. Cases (n = 319) were enrolled from the third trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 319) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate parental military service-related exposures and their associations with childhood RMS by generating aORs and 95% CIs. Statistical significance was defined as P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05. There were no significant associations between parental military service and childhood RMS. The strongest association was with maternal military service; however, this association was attenuated and did not remain significant after adjusting for covariates (aOR = 2.75, 95% CI 0.71, 10.62). An elevated effect estimate was found when assessing paternal exposure to Agent Orange (AO) and childhood RMS but was not statistically significant (aOR = 1.72, 95% CI 0.55, 5.41). We found little evidence that parental military service of AO exposure influences the risk of RMS in offspring. These findings are notable in light of the continuing controversies surrounding the intergenerational effects of AO exposure.

Evaluation of dual nasal delivery of infectious hematopoietic necrosis virus and enteric red mouth vaccines in rainbow trout (Oncorhynchus mykiss)

Vaccine, 2015

Please cite this article in press as: LaPatra S, et al. Evaluation of dual nasal delivery of infe... more Please cite this article in press as: LaPatra S, et al. Evaluation of dual nasal delivery of infectious hematopoietic necrosis virus and enteric red mouth vaccines in rainbow trout (Oncorhynchus mykiss). Vaccine (2015), http://dx.a b s t r a c t Farmed fish are susceptible to different infectious disease agents including viruses and bacteria. Thus, multivalent vaccines or vaccination programs against two or more pathogens are valuable tools in aquaculture. Recently, nasal vaccines have been shown to be very effective in rainbow trout. The current study investigates, for the first time, the use of the nasal route in dual vaccination trials against two important aquatic diseases, infectious hematopoietic necrosis virus (IHN) and enteric red mouth (ERM) disease. Rainbow trout received live attenuated IHN virus (IHNV) vaccine and the ERM bacterin using four different vaccine delivery methods and were challenged with virulent IHNV or Yersinia ruckeri 7 (100 deg day) and 28 (400 deg day) days post-vaccination. The highest survival rates against IHNV at day 7 were obtained by nasal vaccination either when IHNV and ERM were delivered separately into each nare or when they were premixed and delivered to both nasal rosettes (group D). Protection at 28 days against IHNV was similar in all four vaccinated groups. Early protection against ERM was highest in fish that received each vaccine in separate nares (group B), whereas protection at 28 days was highest in the i.p. vaccinated group (group E), followed by the nasally vaccinated group (group B). Survival results were supported by histological observations of the left and right olfactory organ which showed strong immune responses one day (14 deg days) after vaccination in group B vaccinated fish. These data indicate that dual vaccination against two different pathogens via the nasal route is a very effective vaccination strategy for use in aquaculture, particularly when each nare is used separately during delivery. Further long-term studies should evaluate the contribution of adaptive immunity to the protection levels observed.

On Network Derivation, Classification, and Visualization: A Response to Habeck and Moeller

by Erik B Erhardt and Eswar Damaraju

In the decade and a half since Biswal's fortuitous discovery of spontaneous correlations in funct... more In the decade and a half since Biswal's fortuitous discovery of spontaneous correlations in functional imaging data, the field of functional connectivity (FC) has seen exponential growth resulting in the identification of widely-replicated intrinsic networks and the innovation of novel analytic methods with the promise of diagnostic application. As such a young field undergoing rapid change, we have yet to converge upon a desired and needed set of standards. In this issue, Habeck and Moeller begin a dialogue for developing best practices by providing four criticisms with respect to FC estimation methods, interpretation of FC networks, assessment of FC network features in classifying sub-populations, and network visualization. Here, we respond to Habeck and Moeller and provide our own perspective on the concerns raised in the hope that the neuroimaging field will benefit from this discussion.

Data Visualization in the Neurosciences: Overcoming the Curse of Dimensionality

In publications, presentations, and popular media, scientific results are predominantly communica... more In publications, presentations, and popular media, scientific results are predominantly communicated through graphs. But are these figures clear and honest or misleading? We examine current practices in data visualization and discuss improvements, advocating design choices which reveal data rather than hide it.

Assessing dynamic brain graphs of time-varying connectivity in fMRI data: Application to healthy controls and patients with schizophrenia

by Jing Sui, Yuhui Du, Qingbao Yu, Hao He, Erik B Erhardt, and Robyn Miller

NeuroImage, Jan 15, 2015

Graph theory-based analysis has been widely employed in brain imaging studies, and altered topolo... more Graph theory-based analysis has been widely employed in brain imaging studies, and altered topological properties of brain connectivity have emerged as important features of mental diseases such as schizophrenia. However, most previous studies have focused on graph metrics of stationary brain graphs, ignoring that brain connectivity exhibits fluctuations over time. Here we develop a new framework for accessing dynamic graph properties of time-varying functional brain connectivity in resting-state fMRI data and apply it to healthy controls (HCs) and patients with schizophrenia (SZs). Specifically, nodes of brain graphs are defined by intrinsic connectivity networks (ICNs) identified by group independent component analysis (ICA). Dynamic graph metrics of the time-varying brain connectivity estimated by the correlation of sliding time-windowed ICA time courses of ICNs are calculated. First- and second-level connectivity states are detected based on the correlation of nodal connectivity...

Correspondence between structure and function in the human brain at rest

Frontiers in Neuroinformatics, 2012

Correspondence between structure and function in the human brain at rest. Front. Neuroinform. 6:10.

Bayesian Simultaneous Intervals for Small Areas: An Application to Variation in Maps

International Journal of Statistics and Probability, 2012

The 5.1 ka aridization event, expansion of pinon-juniper woodlands, and the introduction of maize (Zea mays) in the American Southwest

The Holocene, 2012

Pollen analysis is frequently used to build climate and environmental histories. A distinct Holoc... more Pollen analysis is frequently used to build climate and environmental histories. A distinct Holocene pollen series exists for Chaco Canyon, New Mexico. This study reports linear modeling and hypothesis testing of long distance dispersal pollen from radiocarbon-dated packrat middens which reveal strong relationships between piñon pine (Pinus edulis) and ponderosa pine (Pinus ponderosa). Ponderosa pollen dominates midden pollen assemblages during the early Holocene, while a rapid shift to a much higher proportion of piñon to ponderosa pine pollen between c. 5440 and 5102 cal. yr BP points to an aridization episode. This shift is associated with higher 18

High-frequency field measurements of diurnal carbon isotope discrimination and internal conductance in a semi-arid species, Juniperus monosperma

Plant, Cell & Environment, 2009

We present field observations of carbon isotope discrimination (D) and internal conductance of CO... more We present field observations of carbon isotope discrimination (D) and internal conductance of CO2 (gi) collected using tunable diode laser spectroscopy (TDL). D ranged from 12.0 to 27.4‰ over diurnal periods with daily means from 16.3 Ϯ 0.2‰ during drought to 19.0 Ϯ 0.5‰ during monsoon conditions. We observed a large range in gi, with most estimates between 0.04 and 4.0 mmol m -2 s -1 Pa -1 . We tested the comprehensive Farquhar, O'Leary and Berry model of D (Dcomp), a simplified form of Dcomp (Dsimple) and a recently suggested amendment (Drevised). Sensitivity analyses demonstrated that varying gi had a substantial effect on Dcomp, resulting in mean differences between observed D (Dobs) and Dcomp ranging from 0.04 to 9.6‰. First-order regressions adequately described the relationship between D and the ratio of substomatal to atmospheric CO2 partial pressure (pi/pa) on all 3 d, but second-order models better described the relationship in July and August. The three tested models each best predicted Dobs on different days. In June, Dsimple outperformed Dcomp and Drevised, but incorporating gi and all non-photosynthetic fractionations improved model predictions in July and August.

Carbon stable isotopic composition of soluble sugars in Tillandsia epiphytes varies in response to shifts in habitat

by Erik B Erhardt and Louis Santiago

Oecologia, 2010

We studied C stable isotopic composition (d 13 C) of bulk leaf tissue and extracted sugars of fou... more We studied C stable isotopic composition (d 13 C) of bulk leaf tissue and extracted sugars of four epiphytic Tillandsia species to investigate flexibility in the use of crassulacean acid metabolism (CAM) and C 3 photosynthetic pathways. Plants growing in two seasonally dry tropical forest reserves in Mexico that differ in annual precipitation were measured during wet and dry seasons, and among secondary, mature, and wetland forest types within each site. Dry season sugars were more enriched in 13 C than wet season sugars, but there was no seasonal difference in bulk tissues. Bulk tissue d 13 C differed by species and by forest type, with values from open-canopied wetlands more enriched in 13 C than mature or secondary forest types. The shifts within forest habitat were related to temporal and spatial changes in vapor pressure deficits (VPD). Modeling results estimate a possible 4% increase in the proportional contribution of the C 3 pathway during the wet season, emphasizing that any seasonal or habitat-mediated variation in photosynthetic pathway appears to be quite moderate and within the range of isotopic effects caused by variation in stomatal conductance during assimilation through the C 3 pathway and environmental variation in VPD. C isotopic analysis of sugars together with bulk leaf tissue offers a useful approach for incorporating short-and long-term measurements of C isotope discrimination during photosynthesis.

Capturing inter-subject variability with group independent component analysis of fMRI data: A simulation study

NeuroImage, 2012

A key challenge in functional neuroimaging is the meaningful combination of results across subjec... more A key challenge in functional neuroimaging is the meaningful combination of results across subjects. Even in a sample of healthy participants, brain morphology and functional organization exhibit considerable variability, such that no two individuals have the same neural activation at the same location in response to the same stimulus. This inter-subject variability limits inferences at the group-level as average activation patterns may fail to represent the patterns seen in individuals. A promising approach to multi-subject analysis is group independent component analysis (GICA), which identifies group components and reconstructs activations at the individual level. GICA has gained considerable popularity, particularly in studies where temporal response models cannot be specified. However, a comprehensive understanding of the performance of GICA under realistic conditions of inter-subject variability is lacking. In this study we use simulated functional magnetic resonance imaging (fMRI) data to determine the capabilities and limitations of GICA under conditions of spatial, temporal, and amplitude variability. Simulations, generated with the SimTB toolbox, address questions that commonly arise in GICA studies, such as: (1) How well can individual subject activations be estimated and when will spatial variability preclude estimation? (2) Why does component splitting occur and how is it affected by model order? (3) How should we analyze component features to maximize sensitivity to intersubject differences? Overall, our results indicate an excellent capability of GICA to capture between-subject differences and we make a number of recommendations regarding analytic choices for application to functional imaging data.