Background: Next-generation sequencing (NGS) detects somatic mutations in a high proportion of in... more Background: Next-generation sequencing (NGS) detects somatic mutations in a high proportion of in plasma cell dyscrasias (PCD), but is so far not integrated into diagnostic routine. We correlated NGS data with degree of bone marrow (BM) involvement by cytomorphology (BMC), histopathology (BMH), and multiparameter flow cytometry (MFC) in 90 PCD patients.Methods: Diagnoses in the 90 patients were multiple myeloma (n=77), MGUS (n=7), AL-amyloidosis (n=4), solitary plasmocytoma (n=2). The NGS panel included 8 genes CCND1, DIS3, EGR1, FAM46C (TENT5C), FGFR3, PRDM1, TP53, TRAF3, and 7 hotspots in BRAF, IDH1, IDH2, IRF4, KRAS, NRAS.Results: Mutations were detected in 64/90 (71%) of cases. KRAS (29%), NRAS (16%) and DIS3 (16%) were most frequently mutated. At least one mutation/sample corresponded to a higher degree of BM involvement with a mean of 11% pathologic PC by MFC (range, 0.002 - 62%), and ~50% (3 - 100%) as defined by both CM and HP. Conclusions: The probability to detect a mutati...
Practical guidance on diagnostic and prognostic use of next generation sequencing (NGS) in multip... more Practical guidance on diagnostic and prognostic use of next generation sequencing (NGS) in multiple myeloma (MM) and other plasma cell neoplasms (PCN) has yet to be developed. To this end, we analyzed the correlation of NGS data with the degree of bone marrow (BM) plasma cell (PC) involvement obtained by cytomorphology (CM), histopathology (HP), and multiparameter flow cytometry (MFC) from patients with PCN/MM. To perform this correlation, we analyzed 90 PCN cases, that included MM (n=77), MGUS (n=7), AL-amyloidosis (ALA) (n=4) and solitary plasmocytoma (SP) (n=2). The degree of BM infiltration (percent of PC) was defined by MFC as grade I <1%, grade II 1-3%, grade III >3%; by CM as grade I <10%; grade II, 10-30%; grade III >30% and by HP as grade I <10%, grade II 10-30%, grade III >30%. The newly designed NGS panel consisted of 15 genes including splice sites or hotspots: BRAF (exons 11, 15), CCND1, DIS3, EGR1, TENT5C (FAM46C), FGFR3, IDH1 (exon 4), IDH2 (exon 4),...
Cette revue discute de l'importance de la découverte de nouveaux marqueurs biologiques pour le di... more Cette revue discute de l'importance de la découverte de nouveaux marqueurs biologiques pour le diagnostic et le traitement de la maladie de Waldenström et propose une révision des recommandations thérapeutiques récentes.
BACKGROUND During the last 20 years, treatment for chronic lymphocytic leukaemia (CLL) / small ly... more BACKGROUND During the last 20 years, treatment for chronic lymphocytic leukaemia (CLL) / small lymphocytic lymphoma (SLL) has advanced, with improved clinical outcomes in randomised controlled trials. Currently, no data have been published from Switzerland to assess effectiveness of recent healthcare advances in CLL/SLL on a population-based level. We aimed to estimate trends in incidence, mortality and survival for patients with CLL/SLL in Switzerland. METHODS We retrospectively studied registry data from the National Agency for Cancer Registration (NACR) database in Switzerland from 1997 to 2016. We investigated incidence, mortality and survival in consecutive 5-year periods. Age-specific rates were calculated for three age groups (<65 years, 65–74 years and ≥75 years). RESULTS We obtained 6301 cases with CLL/SLL. Median age at diagnosis was 72 years. From 7.0 per 100,000 person-years in 1997–2002, age-adjusted incidence rates peaked at 7.8 per 100,000 person-years in the second time period, 2002–2006, and declined afterwards to 6.4 per 100,000 person-years in 2012–2016. Mortality declined from 2.4 per 100,000 person-years in 1997–2002 to 2.0 per 100,000 in 2012–2016. Five- and 10-year age-standardised relative survival increased from 77.9% and 55.6%, respectively, in 1997–2001 to 83.6% (p = 0.009) and 64.2% (p = 0.005), respectively, in 2012–2016. Improvement in age-specific relative survival was only significant in the middle age group (65–74 years). Incidence and mortality were significantly higher in males. Females had better relative survival. CONCLUSION We found no clear down- or upward trend in age-adjusted incidence rates. Age-standardised survival improved over time, mainly in the two younger age-groups, but this improvement was statistically significant in those aged 65–74 years only. Males have higher incidence rates, higher mortality and shorter survival than females. Reporting delay and underreporting are major limitations in the interpretation of registry data from patients diagnosed with CLL/SLL.
The flood events from May 1999 and August 2005 have clearly shown the problems of the hydraulic s... more The flood events from May 1999 and August 2005 have clearly shown the problems of the hydraulic system Thunersee-Aare. Compared to the possible inflow volume, the outflow capacity of the Thunersee is insufficient. A reason for this is the reroute of the Kander into the Thunersee, which was made in the 18th century and increased the catchment area at around 100%. To improve this situation a culvert will be built. With this culvert about 100 m3/s additional water can be derived from the Thunersee. However, the culvert can only bring a significant improvement, if it is used to lower the water level of the lake before an event occurs. For this extensive investigations were carried out to derive indicators for an early flood warning. Thereby we distinguish between indicators, which describe a short to medium term disposition and such, which indicate the beginning of an event.
Background Acquired hemophilia A is a rare autoimmune disease with clinically often significant b... more Background Acquired hemophilia A is a rare autoimmune disease with clinically often significant bleeding diathesis resulting from circulating autoantibodies inhibiting coagulation factor VIII. Half of acquired hemophilia A cases are associated with an underlying disorder, such as autoimmune diseases, cancer, or use of certain drugs, or occur during pregnancy and in the postpartum period. In the other half, no underlying cause is identified. An association of acquired hemophilia A with plasma cell neoplasm seems to be extremely rare. Case presentation We describe a case of a 77-year-old Swiss Caucasian man who was diagnosed with acquired hemophilia A and smoldering multiple myeloma as an underlying cause. Acquired hemophilia A was treated with prednisolone, cyclophosphamide, and immunoadsorption. Extensive workup revealed a plasma cell neoplasm as the only disorder associated with or underlying the acquired hemophilia A. For long-term control of acquired hemophilia A, we considered t...
Hairy cell leukemia (HCL) remains an incurable disease. However, first-line treatment with either... more Hairy cell leukemia (HCL) remains an incurable disease. However, first-line treatment with either intravenous or subcutaneous cladribine generally leads to long-lasting remissions. Although there are excellent long-term data for intravenous application, similar data regarding subcutaneous administration are lacking. We therefore analyzed the long-term outcome of 3 prospective multicenter clinical trials on subcutaneous cladribine performed by the Swiss Group for Clinical Cancer Research (SAKK), which recruited 221 patients with classical HCL between 1993 and 2005. Median overall survival from start of treatment was not reached. Pretreatment anemia, higher Eastern Cooperative Oncology Group score, and higher age were associated with poorer overall survival in multivariable analysis, whereas early progression at 24 and 36 months had no significant impact on overall survival. Second-line treatment was necessary in 53 (23.7%) patients after a median of 5 (range, 0.2-20.4) years, and fir...
Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency... more Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79-7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.
Acquired hemophilia A (AHA) is a rare autoimmune disease caused by circulating autoantibodies inh... more Acquired hemophilia A (AHA) is a rare autoimmune disease caused by circulating autoantibodies inhibiting coagulation factor VIII (FVIII), leading to a clinically significant bleeding diathesis. While in half of AHA cases, no underlying cause is identified, in the other half an association with autoimmune diseases, cancer, the use of certain drugs, pregnancy or the post-partum period is found. We present a case with severe bleeding in which AHA was diagnosed and subsequently a smoldering myeloma was found as underlying disease (case 16, Table 1). We conducted a systematic review of the literature in PubMed looking for the association of AHA and plasma cell neoplasm (PCN) (key words used: hemophilia, inhibitor, factor VIII, myeloma, plasma cell disorder or neoplasms, smoldering myeloma, MGUS, monoclonal gammopathy, paraprotein) and identified 15 additional cases. Description of the cases, sequence of occurrence of both diseases, their treatment, evolution and outcome are here analyzed...
Treatment of multiple myeloma has changed considerably over the last two decades with remarkable ... more Treatment of multiple myeloma has changed considerably over the last two decades with remarkable reduction in mortality rates in clinical trials and in population-based studies. Since health care systems and patient management differ between countries, population-based data from cancer registries with high coverage may provide further insight into real-life achievements and unmet needs. We report on the first population-based nation-wide study of incidence, mortality and survival of multiple myeloma in Switzerland covering the era of autologous stem cell transplantation and the first proteasome inhibitors and immunomodulatory drugs. We performed a retrospective registry study with data from the National Institute for Cancer Epidemiology and Registration (NICER) database in Switzerland from 1994 to 2013. We identified 5770 patients with multiple myeloma. Incidence has increased from 419 new cases per year in 1994-1998 to 557 new cases per year in 2009-2013 while the age-adjusted inci...
Although major steps have been recently made in understanding the role of the distinct subsets of... more Although major steps have been recently made in understanding the role of the distinct subsets of dendritic cells (DC)/antigen-presenting cells (APC), further studies are required to unravel their precise role, including in-depth immunophenotypic characterisation of these cells. Here, we used eight-colour flow cytometry to investigate the reactivity of a panel of 72 monoclonal antibodies (including those clustered in seven new Cluster of Differentiation, CD) on different subsets of APC in peripheral blood (PB) samples from five healthy adults. These experiments were performed in the context of the Tenth International Workshop on Human Leukocyte Differentiation Antigens (HLDA10). Plasmacytoid DC was the only cell population that expressed CD85g and CD195, whereas they lacked all of the other molecules investigated. In contrast, myeloid DC mostly expressed inhibitory C-type lectin receptors (CLRs) and other inhibitory-associated molecules, whereas monocytes expressed both inhibitory and activating CLRs, together with other phagocytosis-associated receptors. Within monocytes, progressively lower levels of expression were generally observed from classical monocytes (cMo) to SLAN − and SLAN + non-classical monocytes (ncMo) for most of the molecules expressed, except for the CD368 endocytic receptor. This molecule was found to be positive only in cMo, and the CD369 and CD371 modulating/signalling receptors. In addition, the CD101 inhibitory molecule was found to be expressed at higher levels in SLAN + vs SLAN − ncMo. In summary, the pattern of expression of the different signalling molecules and receptors analysed in this work varies among the distinct subsets of PB APCs, with similar profiles for molecules within each functional group. These findings suggest unique pattern-recognition and signalling capabilities for distinct subpopulations of APCs, and therefore, diverse functional roles.
The unconditional Barnard&amp;#x27;s test for the comparison of two independent proportions i... more The unconditional Barnard&amp;#x27;s test for the comparison of two independent proportions is difficult to apply even with moderately large samples. The alternative is to use a χ2 type, arc sine or mid-p asymptotic test. In the paper, the authors evaluate some 60 of these tests, some new and others that are already familiar. For the ordinary significances, the optimal tests
The asymptotic inferences about the difference (d=p 2 −p 1) or ratio (R= p 2 /p 1) of two proport... more The asymptotic inferences about the difference (d=p 2 −p 1) or ratio (R= p 2 /p 1) of two proportions (p 1 and p 2) are very common in medicine and in applied statistics, in general. Both the cases may be included within the general case of inferences about the parameter L=p 2 −α−βp 1 (recently interest has been shown about this parameter from the perspective of clinical trials). In the article the authors review the 12 principal statistics proposed in the relevant literature, propose 15 new ones, group them into families, correct existing errors in the definitions of some and, finally, define and analyze the most desirable properties they should have. In addition, they offer a simple formula that allows all the cases to be analyzed in a similar fashion, together with a computer program (http://www.ugr.es/local/bioest/Z_LINEAR.EXE) which permits asymptotic tests related to L to be carried out. KEY WORDS: confidence intervals; difference of proportions; risk ratio; z-test; chisquared test. 2000MSC codes: 62F03 and 62F05.
A great amount has been written over the years in many different publications about a suitable te... more A great amount has been written over the years in many different publications about a suitable test for independence in 2×2 tables: the conditional test (Fisher’s exact test) or the unconditional test (Barnard’s test). In this paper the authors carry out a review of what has been written and refute two of the principal arguments in favour of conditioning (in fact they are the only two that have not been refuted): Fisher’s example of the flowers and the argument of causal models (which gives rise to Greenland’s paradox). In agreement with I. S. Helland [Ann. Stat. 49, 351–356 (1995)] they show the importance of deciding which is the (real or conceptual) target population, and this, together with the existence or not of an ancillary statistic, is what allows a decision to be taken on the appropriateness or not of conditioning.
Background: Next-generation sequencing (NGS) detects somatic mutations in a high proportion of in... more Background: Next-generation sequencing (NGS) detects somatic mutations in a high proportion of in plasma cell dyscrasias (PCD), but is so far not integrated into diagnostic routine. We correlated NGS data with degree of bone marrow (BM) involvement by cytomorphology (BMC), histopathology (BMH), and multiparameter flow cytometry (MFC) in 90 PCD patients.Methods: Diagnoses in the 90 patients were multiple myeloma (n=77), MGUS (n=7), AL-amyloidosis (n=4), solitary plasmocytoma (n=2). The NGS panel included 8 genes CCND1, DIS3, EGR1, FAM46C (TENT5C), FGFR3, PRDM1, TP53, TRAF3, and 7 hotspots in BRAF, IDH1, IDH2, IRF4, KRAS, NRAS.Results: Mutations were detected in 64/90 (71%) of cases. KRAS (29%), NRAS (16%) and DIS3 (16%) were most frequently mutated. At least one mutation/sample corresponded to a higher degree of BM involvement with a mean of 11% pathologic PC by MFC (range, 0.002 - 62%), and ~50% (3 - 100%) as defined by both CM and HP. Conclusions: The probability to detect a mutati...
Practical guidance on diagnostic and prognostic use of next generation sequencing (NGS) in multip... more Practical guidance on diagnostic and prognostic use of next generation sequencing (NGS) in multiple myeloma (MM) and other plasma cell neoplasms (PCN) has yet to be developed. To this end, we analyzed the correlation of NGS data with the degree of bone marrow (BM) plasma cell (PC) involvement obtained by cytomorphology (CM), histopathology (HP), and multiparameter flow cytometry (MFC) from patients with PCN/MM. To perform this correlation, we analyzed 90 PCN cases, that included MM (n=77), MGUS (n=7), AL-amyloidosis (ALA) (n=4) and solitary plasmocytoma (SP) (n=2). The degree of BM infiltration (percent of PC) was defined by MFC as grade I <1%, grade II 1-3%, grade III >3%; by CM as grade I <10%; grade II, 10-30%; grade III >30% and by HP as grade I <10%, grade II 10-30%, grade III >30%. The newly designed NGS panel consisted of 15 genes including splice sites or hotspots: BRAF (exons 11, 15), CCND1, DIS3, EGR1, TENT5C (FAM46C), FGFR3, IDH1 (exon 4), IDH2 (exon 4),...
Cette revue discute de l'importance de la découverte de nouveaux marqueurs biologiques pour le di... more Cette revue discute de l'importance de la découverte de nouveaux marqueurs biologiques pour le diagnostic et le traitement de la maladie de Waldenström et propose une révision des recommandations thérapeutiques récentes.
BACKGROUND During the last 20 years, treatment for chronic lymphocytic leukaemia (CLL) / small ly... more BACKGROUND During the last 20 years, treatment for chronic lymphocytic leukaemia (CLL) / small lymphocytic lymphoma (SLL) has advanced, with improved clinical outcomes in randomised controlled trials. Currently, no data have been published from Switzerland to assess effectiveness of recent healthcare advances in CLL/SLL on a population-based level. We aimed to estimate trends in incidence, mortality and survival for patients with CLL/SLL in Switzerland. METHODS We retrospectively studied registry data from the National Agency for Cancer Registration (NACR) database in Switzerland from 1997 to 2016. We investigated incidence, mortality and survival in consecutive 5-year periods. Age-specific rates were calculated for three age groups (<65 years, 65–74 years and ≥75 years). RESULTS We obtained 6301 cases with CLL/SLL. Median age at diagnosis was 72 years. From 7.0 per 100,000 person-years in 1997–2002, age-adjusted incidence rates peaked at 7.8 per 100,000 person-years in the second time period, 2002–2006, and declined afterwards to 6.4 per 100,000 person-years in 2012–2016. Mortality declined from 2.4 per 100,000 person-years in 1997–2002 to 2.0 per 100,000 in 2012–2016. Five- and 10-year age-standardised relative survival increased from 77.9% and 55.6%, respectively, in 1997–2001 to 83.6% (p = 0.009) and 64.2% (p = 0.005), respectively, in 2012–2016. Improvement in age-specific relative survival was only significant in the middle age group (65–74 years). Incidence and mortality were significantly higher in males. Females had better relative survival. CONCLUSION We found no clear down- or upward trend in age-adjusted incidence rates. Age-standardised survival improved over time, mainly in the two younger age-groups, but this improvement was statistically significant in those aged 65–74 years only. Males have higher incidence rates, higher mortality and shorter survival than females. Reporting delay and underreporting are major limitations in the interpretation of registry data from patients diagnosed with CLL/SLL.
The flood events from May 1999 and August 2005 have clearly shown the problems of the hydraulic s... more The flood events from May 1999 and August 2005 have clearly shown the problems of the hydraulic system Thunersee-Aare. Compared to the possible inflow volume, the outflow capacity of the Thunersee is insufficient. A reason for this is the reroute of the Kander into the Thunersee, which was made in the 18th century and increased the catchment area at around 100%. To improve this situation a culvert will be built. With this culvert about 100 m3/s additional water can be derived from the Thunersee. However, the culvert can only bring a significant improvement, if it is used to lower the water level of the lake before an event occurs. For this extensive investigations were carried out to derive indicators for an early flood warning. Thereby we distinguish between indicators, which describe a short to medium term disposition and such, which indicate the beginning of an event.
Background Acquired hemophilia A is a rare autoimmune disease with clinically often significant b... more Background Acquired hemophilia A is a rare autoimmune disease with clinically often significant bleeding diathesis resulting from circulating autoantibodies inhibiting coagulation factor VIII. Half of acquired hemophilia A cases are associated with an underlying disorder, such as autoimmune diseases, cancer, or use of certain drugs, or occur during pregnancy and in the postpartum period. In the other half, no underlying cause is identified. An association of acquired hemophilia A with plasma cell neoplasm seems to be extremely rare. Case presentation We describe a case of a 77-year-old Swiss Caucasian man who was diagnosed with acquired hemophilia A and smoldering multiple myeloma as an underlying cause. Acquired hemophilia A was treated with prednisolone, cyclophosphamide, and immunoadsorption. Extensive workup revealed a plasma cell neoplasm as the only disorder associated with or underlying the acquired hemophilia A. For long-term control of acquired hemophilia A, we considered t...
Hairy cell leukemia (HCL) remains an incurable disease. However, first-line treatment with either... more Hairy cell leukemia (HCL) remains an incurable disease. However, first-line treatment with either intravenous or subcutaneous cladribine generally leads to long-lasting remissions. Although there are excellent long-term data for intravenous application, similar data regarding subcutaneous administration are lacking. We therefore analyzed the long-term outcome of 3 prospective multicenter clinical trials on subcutaneous cladribine performed by the Swiss Group for Clinical Cancer Research (SAKK), which recruited 221 patients with classical HCL between 1993 and 2005. Median overall survival from start of treatment was not reached. Pretreatment anemia, higher Eastern Cooperative Oncology Group score, and higher age were associated with poorer overall survival in multivariable analysis, whereas early progression at 24 and 36 months had no significant impact on overall survival. Second-line treatment was necessary in 53 (23.7%) patients after a median of 5 (range, 0.2-20.4) years, and fir...
Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency... more Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79-7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.
Acquired hemophilia A (AHA) is a rare autoimmune disease caused by circulating autoantibodies inh... more Acquired hemophilia A (AHA) is a rare autoimmune disease caused by circulating autoantibodies inhibiting coagulation factor VIII (FVIII), leading to a clinically significant bleeding diathesis. While in half of AHA cases, no underlying cause is identified, in the other half an association with autoimmune diseases, cancer, the use of certain drugs, pregnancy or the post-partum period is found. We present a case with severe bleeding in which AHA was diagnosed and subsequently a smoldering myeloma was found as underlying disease (case 16, Table 1). We conducted a systematic review of the literature in PubMed looking for the association of AHA and plasma cell neoplasm (PCN) (key words used: hemophilia, inhibitor, factor VIII, myeloma, plasma cell disorder or neoplasms, smoldering myeloma, MGUS, monoclonal gammopathy, paraprotein) and identified 15 additional cases. Description of the cases, sequence of occurrence of both diseases, their treatment, evolution and outcome are here analyzed...
Treatment of multiple myeloma has changed considerably over the last two decades with remarkable ... more Treatment of multiple myeloma has changed considerably over the last two decades with remarkable reduction in mortality rates in clinical trials and in population-based studies. Since health care systems and patient management differ between countries, population-based data from cancer registries with high coverage may provide further insight into real-life achievements and unmet needs. We report on the first population-based nation-wide study of incidence, mortality and survival of multiple myeloma in Switzerland covering the era of autologous stem cell transplantation and the first proteasome inhibitors and immunomodulatory drugs. We performed a retrospective registry study with data from the National Institute for Cancer Epidemiology and Registration (NICER) database in Switzerland from 1994 to 2013. We identified 5770 patients with multiple myeloma. Incidence has increased from 419 new cases per year in 1994-1998 to 557 new cases per year in 2009-2013 while the age-adjusted inci...
Although major steps have been recently made in understanding the role of the distinct subsets of... more Although major steps have been recently made in understanding the role of the distinct subsets of dendritic cells (DC)/antigen-presenting cells (APC), further studies are required to unravel their precise role, including in-depth immunophenotypic characterisation of these cells. Here, we used eight-colour flow cytometry to investigate the reactivity of a panel of 72 monoclonal antibodies (including those clustered in seven new Cluster of Differentiation, CD) on different subsets of APC in peripheral blood (PB) samples from five healthy adults. These experiments were performed in the context of the Tenth International Workshop on Human Leukocyte Differentiation Antigens (HLDA10). Plasmacytoid DC was the only cell population that expressed CD85g and CD195, whereas they lacked all of the other molecules investigated. In contrast, myeloid DC mostly expressed inhibitory C-type lectin receptors (CLRs) and other inhibitory-associated molecules, whereas monocytes expressed both inhibitory and activating CLRs, together with other phagocytosis-associated receptors. Within monocytes, progressively lower levels of expression were generally observed from classical monocytes (cMo) to SLAN − and SLAN + non-classical monocytes (ncMo) for most of the molecules expressed, except for the CD368 endocytic receptor. This molecule was found to be positive only in cMo, and the CD369 and CD371 modulating/signalling receptors. In addition, the CD101 inhibitory molecule was found to be expressed at higher levels in SLAN + vs SLAN − ncMo. In summary, the pattern of expression of the different signalling molecules and receptors analysed in this work varies among the distinct subsets of PB APCs, with similar profiles for molecules within each functional group. These findings suggest unique pattern-recognition and signalling capabilities for distinct subpopulations of APCs, and therefore, diverse functional roles.
The unconditional Barnard&amp;#x27;s test for the comparison of two independent proportions i... more The unconditional Barnard&amp;#x27;s test for the comparison of two independent proportions is difficult to apply even with moderately large samples. The alternative is to use a χ2 type, arc sine or mid-p asymptotic test. In the paper, the authors evaluate some 60 of these tests, some new and others that are already familiar. For the ordinary significances, the optimal tests
The asymptotic inferences about the difference (d=p 2 −p 1) or ratio (R= p 2 /p 1) of two proport... more The asymptotic inferences about the difference (d=p 2 −p 1) or ratio (R= p 2 /p 1) of two proportions (p 1 and p 2) are very common in medicine and in applied statistics, in general. Both the cases may be included within the general case of inferences about the parameter L=p 2 −α−βp 1 (recently interest has been shown about this parameter from the perspective of clinical trials). In the article the authors review the 12 principal statistics proposed in the relevant literature, propose 15 new ones, group them into families, correct existing errors in the definitions of some and, finally, define and analyze the most desirable properties they should have. In addition, they offer a simple formula that allows all the cases to be analyzed in a similar fashion, together with a computer program (http://www.ugr.es/local/bioest/Z_LINEAR.EXE) which permits asymptotic tests related to L to be carried out. KEY WORDS: confidence intervals; difference of proportions; risk ratio; z-test; chisquared test. 2000MSC codes: 62F03 and 62F05.
A great amount has been written over the years in many different publications about a suitable te... more A great amount has been written over the years in many different publications about a suitable test for independence in 2×2 tables: the conditional test (Fisher’s exact test) or the unconditional test (Barnard’s test). In this paper the authors carry out a review of what has been written and refute two of the principal arguments in favour of conditioning (in fact they are the only two that have not been refuted): Fisher’s example of the flowers and the argument of causal models (which gives rise to Greenland’s paradox). In agreement with I. S. Helland [Ann. Stat. 49, 351–356 (1995)] they show the importance of deciding which is the (real or conceptual) target population, and this, together with the existence or not of an ancillary statistic, is what allows a decision to be taken on the appropriateness or not of conditioning.
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Papers by Martin Andres