84 research outputs found

    The Partition Function of Multicomponent Log-Gases

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    We give an expression for the partition function of a one-dimensional log-gas comprised of particles of (possibly) different integer charge at inverse temperature {\beta} = 1 (restricted to the line in the presence of a neutralizing field) in terms of the Berezin integral of an associated non- homogeneous alternating tensor. This is the analog of the de Bruijn integral identities [3] (for {\beta} = 1 and {\beta} = 4) ensembles extended to multicomponent ensembles.Comment: 14 page

    Genome-wide imputation identifies novel associations and localises signals in idiopathic inflammatory myopathies.

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    OBJECTIVES The idiopathic inflammatory myopathies (IIM) are heterogeneous diseases, thought to be initiated by immune activation in genetically predisposed individuals. In this study we imputed variants from the Immunochip array using a large reference panel to fine-map associations and identify novel associations in IIM. METHODS We analysed 2,565 Caucasian IIM samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically-matched controls. We imputed 1,648,116 variants from the Immunochip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM, and clinical and serological subgroups. RESULTS The human leukocyte antigen (HLA) locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, three in the whole IIM cohort (SDK2 and LINC00924 - both novel, and STAT4), with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM, for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells. CONCLUSIONS We report novel and strong associations in IIM and PM, and localise signals to single genes and immune cell types. This article is protected by copyright. All rights reserved

    Identification of Novel Associations and Localization of Signals in Idiopathic Inflammatory Myopathies Using Genome-Wide Imputation

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    OBJECTIVES: The idiopathic inflammatory myopathies (IIM) are heterogeneous diseases, thought to be initiated by immune activation in genetically predisposed individuals. In this study we imputed variants from the Immunochip array using a large reference panel to fine-map associations and identify novel associations in IIM. METHODS: We analysed 2,565 Caucasian IIM samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically-matched controls. We imputed 1,648,116 variants from the Immunochip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM, and clinical and serological subgroups. RESULTS: The human leukocyte antigen (HLA) locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, three in the whole IIM cohort (SDK2 and LINC00924 - both novel, and STAT4), with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM, for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells. CONCLUSIONS: We report novel and strong associations in IIM and PM, and localise signals to single genes and immune cell types

    2016 ACR-EULAR adult dermatomyositis and polymyositis and juvenile dermatomyositis response criteria-methodological aspects

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    Objective. The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods. Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results. Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion. Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis

    Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

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    Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≄ II, EF ≀35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

    The Spatial Scope of Competition and the Geographical Distribution of Entrepreneurship: Magazine Foundings and the U.S. Post Office

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    We propose that the geographic distribution of entrepreneurship evolves as developing communication systems alter the spatial scope of competition Our arguments imply that as spatial barriers to communication diminish founding events will be less sensitive to local context and more sensitive to distant competition. We test this argument with data on the first modern communication system, the US post office, and foundings of organizations that depended on it for distribution: magazine-publishing ventures. We find that as the postal system expanded, the spatial scope of competition among magazines increased: magazines in distant locations exerted more negative effects on local founding rates, whereas magazines in the focal location exerted less positive effects on local founding rates These findings reveal how spatial barriers to competition shape the geography of entrepreneurial activity

    Close, but not the same: Locally headquartered organizations and agglomeration economies in a declining industry

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    Departing from research on expanding, high-technology industries, we study the impact of agglomeration in a declining, low-technology industry. The setting is U.S. footwear manufacturing between 1975 and 1991, when import competition rendered local support critical for survival. We examine how agglomeration-related survival benefits depended upon the presence of locally headquartered manufacturing plants and whether such benefits came at the expense of other local industries. Consistent with ecological arguments, plant failure rates were higher in agglomerations but this effect was attenuated and, in some cases, reversed in agglomerations with more locally headquartered plants. Moreover, only locally headquartered plants experienced such benefits; remotely headquartered plants failed at higher rates in agglomerations. Although more footwear manufacturing jobs were retained in agglomerations with many locally headquartered plants, such locales also exhibited lower manufacturing job growth in other industries. These findings lend greater generalizability to agglomeration theories and also imply trade-offs at the community level.Agglomeration Industrial cluster Location advantage Organizations Manufacturing

    Racial Disparity in Leadership: Evidence of Valuative Bias in the Promotions of National Football League Coaches

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    The authors propose that racial disparity in organizational leadership representation will persist until valuative bias favoring white men ceases to influence advancement from the lower-level positions where most careers begin. They consider how racial disparity results from the organizational matching of individuals to positions with different advancement prospects (i.e., allocative bias) and by the provision of differential rewards within those positions (i.e., valuative bias). Analyzing career history data for over 1,300 National Football League coaches from 1985 to 2015, the authors find that white assistant coaches were promoted at higher rates than Black coaches—holding constant many factors including unit and individual performance—both before and after a league-wide intervention explicitly implemented to close the racial gap in leadership representation. They further demonstrate that this white promotion advantage is specific to the position typically occupied before promotion to head coach. Simulations demonstrate how racial disparity persists even absent bias in positional allocations; eliminating valuative bias at early career stages is, thus, necessary to achieve racial parity in leadership representation.This accepted article is published as Rider, C., Wade, J., Swaminathan, A. & Schwab, A., Racial Disparity in Leadership: Evidence of Valuative Bias in the Promotions of National Football League Coaches. American Journal of Sociology, July 2023, 129(1), 227-275. DOI: 10.1086/725389. Posted with permission
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