The association of parity with osteoarthritis and knee replacement in the Multicenter Osteoarthritis Study

SummaryObjectiveWe evaluated the association of parity to both risk of knee replacement (KR) and knee osteoarthritis (OA).DesignThe NIH-funded Multicenter Osteoarthritis Study (MOST) is a longitudinal observational study of persons age 50–79 years with either symptomatic knee OA or at elevated risk of disease. Baseline and 30-month knee radiographic OA (ROA) was defined as Kellgren/Lawrence (K/L) grade ≥2 or KR. Women were grouped based by number of births: 0; 1 (reference group); 2; 3; 4; and 5 or more. We examined the relation of parity to the incidence over 30 months of ROA and KR using a Poisson regression model. Generalized estimating equations (GEE) were used to control for correlation between two knees within a subject. We adjusted for age, BMI, race, education, occupation, baseline estrogen use, clinical site, injury, and for KR analyses WOMAC pain and use of pain medication.ResultsAmong 1618 women who reported parity information, mean age was 62.6 years, mean BMI 30.7 kg/m2, mean WOMAC pain subscale score 3.7 at baseline. There were 115 KRs and 134 cases of incident knee ROA over 30 months. The relative risk of incident KR was 2.7 times as high (95% CI: 1.0, 7.3) and relative risk of incident knee ROA was 2.6 times as high (95% CI: 1.2, 5.3) among women with five to 12 children compared with those with one birth.ConclusionParity in women at risk for OA is associated with both incident ROA and KR, particularly for those with more than four children

Bounded and unitary elements in pro-C^*-algebras

A pro-C^*-algebra is a (projective) limit of C^*-algebras in the category of topological *-algebras. From the perspective of non-commutative geometry, pro-C^*-algebras can be seen as non-commutative k-spaces. An element of a pro-C^*-algebra is bounded if there is a uniform bound for the norm of its images under any continuous *-homomorphism into a C^*-algebra. The *-subalgebra consisting of the bounded elements turns out to be a C^*-algebra. In this paper, we investigate pro-C^*-algebras from a categorical point of view. We study the functor (-)_b that assigns to a pro-C^*-algebra the C^*-algebra of its bounded elements, which is the dual of the Stone-\v{C}ech-compactification. We show that (-)_b is a coreflector, and it preserves exact sequences. A generalization of the Gelfand-duality for commutative unital pro-C^*-algebras is also presented.Comment: v2 (accepted

DXA-derived hip shape is related to osteoarthritis:findings from in the MrOS cohort

BF conducted this research whilst on a clinical research primer fellowship awarded by the Elizabeth Blackwell Institute, University of Bristol, UK. This study was funded by Arthritis Research UK project grant ref 20244. CG is funded by Arthritis Research UK grant ref 20000. The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: R01 AR052000, K24 AR048841, U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128.Peer reviewedPostprin

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs49654

Aligning simulation models: A case study and results

This paper develops the concepts and methods of a process we will call “alignment of computational models” or “docking” for short. Alignment is needed to determine whether two models can produce the same results, which in turn is the basis for critical experiments and for tests of whether one model can subsume another. We illustrate our concepts and methods using as a target a model of cultural transmission built by Axelrod. For comparison we use the Sugarscape model developed by Epstein and Axtell.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44707/1/10588_2005_Article_BF01299065.pd

Recent sarcopenia definitions—prevalence, agreement and mortality associations among men: findings from population‐based cohorts

Background The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health-related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. Methods White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4–6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength <27 kg and ALM index <7.0 kg/m2), SDOC (grip strength <35.5 kg and gait speed <0.8 m/s) and Modified SDOC (grip strength <35.5 kg and gait speed <1.0 m/s). Cohen's kappa statistic was used to assess agreement between original definitions (EWGSOP2 and SDOC). Presence versus absence of sarcopenia according to each definition in relation to mortality risk was examined using Cox regression with adjustment for age and weight; estimates were combined across cohorts using random-effects meta-analysis. Results Mean (SD) age of participants (n = 9170) was 74.3 (4.9) years; 5929 participants died during a mean (SD) follow-up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (κ = 0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I2: 0.0%]; SDOC [2.75 (2.28, 3.31), I2: 0.0%]; and Modified SDOC [1.93 (1.54, 2.41), I2: 58.3%]. Conclusions There was low prevalence and poor agreement among recent sarcopenia definitions in community-dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance

Statistical shape modeling of the hip and the association with hip osteoarthritis: a systematic review

Objective: To summarize available evidence on the association between hip shape as quantified by statistical shape modeling (SSM) and the incidence or progression of hip osteoarthritis. Design: We conducted a systematic search of five electronic databases, based on a registered protocol (available: PROSPERO CRD42020145411). Articles presenting original data on the longitudinal relationship between radiographic hip shape (quantified by SSM) and hip OA were eligible. Quantitative meta-analysis was precluded because of the use of different SSM models across studies. We used the Newcastle–Ottawa Scale (NOS) for risk of bias assessment. Results: Nine studies (6,483 hips analyzed with SSM) were included in this review. The SSM models used to describe hip shape ranged from 16 points on the femoral head to 85 points on the proximal femur and hemipelvis. Multiple hip shape features and combinations thereof were associated with incident or progressive hip OA. Shape variants that seemed to be consistently associated with hip OA across studies were acetabular dysplasia, cam morphology, and deviations in acetabular version (either excessive anteversion or retroversion). Conclusions: Various radiographic, SSM-defined hip shape features are associated with hip OA. Some hip shape features only seem to increase the risk for hip OA when combined together. The heterogeneity of the used SSM models across studies precludes the estimation of pooled effect sizes. Further studies using the same SSM model and definition of hip OA are needed to allow for the comparison of outcomes across studies, and to validate the found associations

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Combination of searches for WW, WZ, and ZZ resonances in pp collisions at s=8 TeV with the ATLAS detector

The ATLAS experiment at the CERN Large Hadron Collider has performed searches for new, heavy bosons decaying to WW, WZ and ZZ final states in multiple decay channels using 20.3 fb-1 of pp collision data at s=8 TeV. In the current study, the results of these searches are combined to provide a more stringent test of models predicting heavy resonances with couplings to vector bosons. Direct searches for a charged diboson resonance decaying to WZ in the ℓνℓ'ℓ' (ℓ=μ, e), ℓℓqq-, ℓνqq- and fully hadronic final states are combined and upper limits on the rate of production times branching ratio to the WZ bosons are compared with predictions of an extended gauge model with a heavy W' boson. In addition, direct searches for a neutral diboson resonance decaying to WW and ZZ in the ℓℓqq-, ℓνqq-, and fully hadronic final states are combined and upper limits on the rate of production times branching ratio to the WW and ZZ bosons are compared with predictions for a heavy, spin-2 graviton in an extended Randall-Sundrum model where the Standard Model fields are allowed to propagate in the bulk of the extra dimension