Courant-like brackets and loop spaces

We study the algebra of local functionals equipped with a Poisson bracket. We discuss the underlying algebraic structures related to a version of the Courant-Dorfman algebra. As a main illustration, we consider the functionals over the cotangent bundle of the superloop space over a smooth manifold. We present a number of examples of the Courant-like brackets arising from this analysis.Comment: 20 pages, the version published in JHE

ATTRIBUTABLE RISK ESTIMATE OF SEVERE PSORIASIS ON MAJOR CARDIOVASCULAR EVENTS

Le principal défi du CTA est de faire face à la rapide mutation du milieu dans lequel nous travaillons : nous adapter à l’évolution fulgurante des technologies de l’information et de la communication (TIC) et, en réponse à certains des paradigmes du développement qui ont mal vieilli, identifier de nouveaux modèles et des mécanismes novateurs répondant aux besoins actuels de développement. En 2006, nous nous sommes démarqués de l’approche “business as usual”. Nous avons introduit quelques changements dans notre gestion et notre culture organisationnelle et, par là même, dans notre état d’esprit. Dr. Hansjörg Neun Directeur, CTALe principal défi du CTA est de faire face à la rapide mutation du milieu dans lequel nous travaillons : nous adapter à l’évolution fulgurante des technologies de l’information et de la communication (TIC)... Dr. Hansjörg NeunDirecteur, CT

Effect of psoriasis severity on hypertension control: a population-based study in the United Kingdom.

IMPORTANCE: Hypertension is prevalent among patients with psoriasis. The effect of psoriasis and its severity on hypertension control is unknown. OBJECTIVE: To determine the association between uncontrolled blood pressure and psoriasis, both overall and according to objectively measured psoriasis severity, among patients with diagnosed hypertension. DESIGN, SETTING, AND PARTICIPANTS: Population-based cross-sectional study nested in a prospective cohort drawn from The Health Improvement Network (THIN), an electronic medical records database broadly representative of the general population in the United Kingdom. The study population included a random sample of patients with psoriasis (n = 1322) between the ages of 25 and 64 years in THIN who were included in the Incident Health Outcomes and Psoriasis Events prospective cohort and their age- and practice-matched controls without psoriasis (n = 11,977). All included patients had a diagnosis of hypertension; their psoriasis diagnosis was confirmed and disease severity was classified by their general practitioners. MAIN OUTCOMES AND MEASURES: Uncontrolled hypertension was defined as a systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher based on the blood pressure recorded closest in time to the assessment of psoriasis severity. RESULTS: There was a significant positive dose-response relationship between uncontrolled hypertension and psoriasis severity as objectively determined by the affected body surface area in both unadjusted and adjusted analyses that controlled for age, sex, body mass index, smoking and alcohol use status, presence of comorbid conditions, and current use of antihypertensive medications and nonsteroidal anti-inflammatory drugs (adjusted odds ratio [aOR], 0.97; 95% CI, 0.82-1.14 for mild psoriasis; aOR, 1.20; 95% CI, 0.99-1.45 for moderate psoriasis; and aOR, 1.48; 95% CI, 1.08-2.04 for severe psoriasis; P = .01 for trend). The likelihood of uncontrolled hypertension among psoriasis overall was also increased, although not statistically significantly so (aOR, 1.10; 95% CI, 0.98-1.24). CONCLUSIONS AND RELEVANCE: Among patients with hypertension, psoriasis was associated with a greater likelihood of uncontrolled hypertension in a dose-dependent manner, with the greatest likelihood observed among those with moderate to severe psoriasis defined by 3% or more of the body surface area affected. Our data suggest a need for more effective blood pressure management, particularly among patients with more severe psoriasis

Factors Influencing Sleep Difficulty and Sleep Quantity in the Citizen Pscientist Psoriatic Cohort.

IntroductionSleep is essential for overall health and well-being, yet more than one-third of adults report inadequate sleep. The prevalence is higher among people with psoriasis, with up to 85.4% of the psoriatic population reporting sleep disruption. Poor sleep among psoriasis patients is particularly concerning because psoriasis is independently associated with many of the same comorbidities as sleep dysfunction, including cardiovascular disease, obesity, and depression. Given the high prevalence and serious consequences of disordered sleep in psoriasis, it is vital to understand the nature of sleep disturbance in this population. This study was designed to help meet this need by using survey data from Citizen Pscientist, an online patient portal developed by the National Psoriasis Foundation.MethodsOur analysis included 3118 participants who identified as having a diagnosis by a physician of psoriasis alone or psoriasis with psoriatic arthritis. Demographic information, psoriasis severity and duration, sleep apnea status, smoking and alcohol consumption, itch timing, and sleep characteristics were included. Two separate multivariate logistic regression models in STATA were used to determine whether the presence of psoriatic arthritis, age, gender, body mass index, comorbid sleep apnea, psoriasis severity, timing of worst itch, smoking status, or high-risk alcohol consumption were associated with sleep difficulty or low sleep quantity, defined by the American Academy of Sleep Medicine as less than 7 h of sleep per night on average.ResultsResults from the multivariate logistic regressions found that sleep difficulty was associated with psoriatic arthritis (OR 2.15, 95% CI [1.79-2.58]), female gender (2.03 [1.67-2.46]), obese body mass index (BMI ≥ 30) (1.25 [1.00-1.56]), sleep apnea (1.41 [1.07-1.86]), psoriasis severity of moderate (1.59 [1.30-1.94]) or severe (2.40 [1.87-3.08]), and smoking (1.60 [1.26-2.02]). Low sleep quantity was associated with obese BMI (1.62 [1.29-2.03]), sleep apnea (1.30 [1.01-1.68]), psoriasis severity of moderate (1.41 [1.16-1.72]) or severe (1.40 [1.11-1.76]), and smoking (1.62 [1.31-2.00]). Sleep difficulty and low sleep quantity were not associated with age, alcohol consumption, or timing of worst itch.ConclusionThese results are potentially meaningful in several aspects. We identify an important distinction between sleep difficulty and sleep quantity in psoriatic disease, whereby having psoriatic arthritis and being female are each associated with sleep difficulty despite no association with low sleep quantity. Furthermore, there is conflicting evidence from prior studies as to whether psoriasis severity is associated with sleep difficulty, but this well-powered, large study revealed a strong, graded relationship between psoriasis severity and both sleep difficulty and low sleep quantity. Overall, our results show that both sleep difficulty and low sleep quantity were associated with multiple factors in this analysis of a large psoriatic cohort. These findings suggest that dermatologists may gather clinically useful information by screening psoriatic patients for trouble sleeping and low sleep quantity to identify potential comorbidities and to more effectively guide disease management

Auto-validation of fluorescent primer extension genotyping assay using signal clustering and neural networks

BACKGROUND: SNP genotyping typically incorporates a review step to ensure that the genotype calls for a particular SNP are correct. For high-throughput genotyping, such as that provided by the GenomeLab SNPstream(® )instrument from Beckman Coulter, Inc., the manual review used for low-volume genotyping becomes a major bottleneck. The work reported here describes the application of a neural network to automate the review of results. RESULTS: We describe an approach to reviewing the quality of primer extension 2-color fluorescent reactions by clustering optical signals obtained from multiple samples and a single reaction set-up. The method evaluates the quality of the signal clusters from the genotyping results. We developed 64 scores to measure the geometry and position of the signal clusters. The expected signal distribution was represented by a distribution of a 64-component parametric vector obtained by training the two-layer neural network onto a set of 10,968 manually reviewed 2D plots containing the signal clusters. CONCLUSION: The neural network approach described in this paper may be used with results from the GenomeLab SNPstream instrument for high-throughput SNP genotyping. The overall correlation with manual revision was 0.844. The approach can be applied to a quality review of results from other high-throughput fluorescent-based biochemical assays in a high-throughput mode

Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis without known PsA compared with the general population after adjusting for traditional cardiovascular risk factors.A population-based longitudinal cohort study from 1994 to 2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the UK. Patients aged 18-89 years of age with PsA, RA or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents and the composite outcome (MACE). Cox proportional hazards models were used to calculate the HRs for each outcome adjusted for traditional risk factors. A priori, we hypothesised an interaction between disease status and disease-modifying antirheumatic drug (DMARD) use.Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=81 573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in patients with PsA not prescribed a DMARD (HR 1.24, 95% CI 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95% CI 1.28 to 1.50, DMARD: HR 1.58, 95% CI 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95% CI 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95% CI 1.17 to 1.73).Cardiovascular risk should be addressed with all patients affected by psoriasis, PsA or RA.American College of Rheumatology R01HL089744 K24AR064310 Clinical and Translational Science Award at the University of Pennsylvania from the National Center for Research Resources 8UL1TR000003 American College of Rheumatology Research and Education Foundation NIH K23AR063764 Doris Duke Charitable Foundation Center for Clinical Epidemiology and Biostatistics Icelandic Research Fund 120433021 R01AG025152 K23HL097151-0

Risk Factors for Diagnosis of Psoriatic Arthritis, Psoriasis, Rheumatoid Arthritis, and Ankylosing Spondylitis : A Set of Parallel Case-control Studies

Funding Information: This work was supported in part by the National Institutes of Health (NIH), Grant K23 AR063764, to the principal investigator AO, and internal funds from the University of Pennsylvania. MD was supported by the NIH, Grant K23 AR06912701. 1E. Meer, BA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; 2T. Thrastardottir, MPH, T.J. Love, MD, PhD, Department of Medicine/Rheumatology, University of Iceland and Landspitali, Reykjavik, Iceland; 3X. Wang, MD, Y. Chen, PhD, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; 4M. Dubreuil, MD, Department of Medicine/Rheumatology, Boston University, Boston, Massachusetts, USA; 5J.M. Gelfand, MD, MSCE, Department of Biostatistics, Epidemiology and Informatics, and Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; 6A. Ogdie, MD, MSCE, Department of Biostatistics, Epidemiology and Informatics, and Department of Medicine/ Rheumatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. JMG has served as a consultant for BMS, Boehringer Ingelheim, Lilly, Janssen Biologics, Novartis, UCB (DSMB), Neuroderm (DSMB), Dr. Reddy’s Labs, Pfizer, and Sun Pharma, receiving honoraria; receives research grants (to the Trustees of the University of Pennsylvania) from AbbVie, Boehringer Ingelheim, Janssen, Novartis, Celgene, Ortho Dermatologics, and Pfizer; and received payment for continuing medical education work related to psoriasis that was supported indirectly by Lilly, Ortho Dermatologics, and Novartis. JMG is a co-patent holder of resiquimod for treatment of cutaneous T-cell lymphoma, is a Deputy Editor for the Journal of Investigative Dermatology, receiving honoraria from the Society for Investigative Dermatology, and is a member of the Board of Directors for the International Psoriasis Council, receiving no honoraria. TJL has received reimbursement from Celgene for speaking about guidelines for the treatment of psoriatic arthritis. AO has served as a consultant for AbbVie, Amgen, BMS, Celgene, Corrona, Global Health Living Foundation, Janssen, Lilly, Novartis, Pfizer, and Takeda, and has received grants to the University of Pennsylvania from Pfizer and Novartis and to Forward from Amgen; her husband has received royalties from Novartis. EM, TT, MD, XW, and YC declare no conflicts of interest relevant to this article. Address correspondence to Dr. A. Ogdie, University of Pennsylvania, Division of Rheumatology, 3400 Civic Center Blvd., Philadelphia, PA 19104, USA. Email: [email protected]. Accepted for publication July 16, 2021. Publisher Copyright: © 2022 The Journal of Rheumatology.Objective. To compare potential risk factors for the diagnosis of psoriatic arthritis (PsA), psoriasis (PsO), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Methods. Four parallel case-control studies were conducted within The Health Improvement Network using data between 1994 and 2015. Patients with PsA, PsO, RA, or AS were identified using validated code lists and matched to controls on age, sex, practice, and year. Risk factors were selected in the time prior to diagnosis. Multivariable logistic regression models were constructed for each disease using automated stepwise regression to test potential risk factors. Results. Patients with incident PsA (n = 7594), PsO (n = 111,375), RA (n = 28,341), and AS (n = 3253) were identified and matched to 75,930, 1,113,345, 283,226, and 32,530 controls, respectively. Median diagnosis age was 48 (IQR 38–59), 43 (IQR 28–60), 60 (IQR 48–71), and 41 (IQR 32–54) years, respectively. In multivariable models, there were some shared and some differing risk factors across all 4 diseases: PsA was associated with obesity, pharyngitis, and skin infections; PsA and PsO were associated with obesity and moderate alcohol intake; PsA and AS were associated with uveitis; and PsA and RA were associated with preceding gout. Both RA and AS were associated with current smoking, former moderate drinking, anemia, osteoporosis, and inflammatory bowel disease. All shared former or current smoking as a risk factor; statin use was inversely associated with all 4 diseases. Conclusion. Shared and different risk factors for PsA, PsO, RA, and AS were identified. Statin use was inversely associated with all 4 conditions.Peer reviewe