Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGFβ1) gene in knee and hip osteoarthritis

Introduction: The objective was to investigate potential gene-environment interaction between body mass index (BMI) and each of eight TGFβ1 polymorphisms in knee and hip osteoarthritis (OA). Methods: We conducted a case-control study of Caucasian men and women aged 45 to 86 years from Nottingham, United Kingdom (Genetics of OA and Lifestyle (GOAL) study). Cases had clinically severe symptoms and radiographic knee or hip OA; controls had no symptoms and no radiographic knee/hip OA. We used logistic regression to investigate the association of TGFβ1 polymorphisms and OA when stratifying by BMI. Knee and hip OA were analyzed separately with adjustment for potential confounders. Additive and multiplicative interactions were examined. Results: 2,048 cases (1,042 knee OA, 1,006 hip OA) and 967 controls were studied. For hip OA, the highest risk was in overweight (BMI ≥25 kg/m2) individuals with the variant allele of single-nucleotide polymorphism (SNP) rs1800468 (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.55, 3.15). Evaluation of gene-environment interaction indicated significant synergetic interaction (relative excess risk due to interaction (RERI) = 0.93, synergy index (SI) = 4.33) with an attributable proportion due to interaction (AP) of 42% (AP = 0.42; 95% CI 0.16, 0.68). Multiplicative interaction was also significant (OR for interaction (ORINT) = 2.27, P = 0.015). For knee OA, the highest risk was in overweight individuals with homozygous genotype 11 of SNP rs2278422 (OR = 6.95, P < 0.001). In contrast, the variant allele indicated slightly lower risks (OR = 4.72, P < 0.001), a significant antagonistic interaction (RERI = -2.66, SI = 0.59), AP = -0.56 (95%CI -0.94, -0.17) and a significant multiplicative interaction (ORINT = 0.47, P = 0.013). Conclusion: TGFβ1 gene polymorphisms interact with being overweight to influence the risk of large joint OA

Cryogenic Fluid Management Technology for Moon and Mars Missions

In support of the U.S. Space Exploration Policy, focused cryogenic fluid management technology efforts are underway within the National Aeronautics and Space Administration. Under the auspices of the Exploration Technology Development Program, cryogenic fluid management technology efforts are being conducted by the Cryogenic Fluid Management Project. Cryogenic Fluid Management Project objectives are to develop storage, transfer, and handling technologies for cryogens to support high performance demands of lunar, and ultimately, Mars missions in the application areas of propulsion, surface systems, and Earth-based ground operations. The targeted use of cryogens and cryogenic technologies for these application areas is anticipated to significantly reduce propellant launch mass and required on-orbit margins, to reduce and even eliminate storage tank boil-off losses for long term missions, to economize ground pad storage and transfer operations, and to expand operational and architectural operations at destination. This paper organizes Cryogenic Fluid Management Project technology efforts according to Exploration Architecture target areas, and discusses the scope of trade studies, analytical modeling, and test efforts presently underway, as well as future plans, to address those target areas. The target areas are: liquid methane/liquid oxygen for propelling the Altair Lander Ascent Stage, liquid hydrogen/liquid oxygen for propelling the Altair Lander Descent Stage and Ares V Earth Departure Stage, liquefaction, zero boil-off, and propellant scavenging for Lunar Surface Systems, cold helium and zero boil-off technologies for Earth-Based Ground Operations, and architecture definition studies for long term storage and on-orbit transfer and pressurization of LH2, cryogenic Mars landing and ascent vehicles, and cryogenic production via in situ resource utilization on Mars

Relative importance of herd-level risk factors for probability of infection with paratuberculosis in Irish dairy herds

Control of paratuberculosis is challenging due to the relatively poor performance of diagnostic tests, a prolonged incubation period, and protracted environmental survival. Prioritization of herd-level interventions is not possible because putative risk factors are often not supported by risk factor studies. The objective for this study was to investigate the relative importance of risk factors for an increased probability of herd paratuberculosis infection. Risk assessment data, comprehensive animal purchase history, and diagnostic test data were available for 936 Irish dairy herds. Both logistic regression and a Bayesian β regression on the outcome of a latent class analysis were conducted. Population attributable fractions and proportional reduction in variance explained were calculated for each variable in the logistic and Bayesian models, respectively. Routine use of the calving area for sick or lame cows was found to be a significant explanatory covariate in both models. Purchasing behavior for the previous 10 yr was not found to be significant. For the logistic model, length of time calves spend in the calving pen (25%) and routine use of the calving pen for sick or lame animals (14%) had the highest attributable fractions. For the Bayesian model, the overall R2 was 16%. Dry cow cleanliness (7%) and routine use of the calving area for sick or lame cows (6%) and had the highest proportional reduction in variance explained. These findings provide support for several management practices commonly recommended as part of paratuberculosis control programs; however, a large proportion of the observed variation in probability of infection remained unexplained, suggesting other important risks factors may exist

The Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP): Overview and description of models, simulations and climate diagnostics

The Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP) consists of a series of time slice experiments targeting the long-term changes in atmospheric composition between 1850 and 2100, with the goal of documenting composition changes and the associated radiative forcing. In this overview paper, we introduce the ACCMIP activity, the various simulations performed (with a requested set of 14) and the associated model output. The 16 ACCMIP models have a wide range of horizontal and vertical resolutions, vertical extent, chemistry schemes and interaction with radiation and clouds. While anthropogenic and biomass burning emissions were specified for all time slices in the ACCMIP protocol, it is found that the natural emissions are responsible for a significant range across models, mostly in the case of ozone precursors. The analysis of selected present-day climate diagnostics (precipitation, temperature, specific humidity and zonal wind) reveals biases consistent with state-of-the-art climate models. The model-to-model comparison of changes in temperature, specific humidity and zonal wind between 1850 and 2000 and between 2000 and 2100 indicates mostly consistent results. However, models that are clear outliers are different enough from the other models to significantly affect their simulation of atmospheric chemistry

When the working day is through: The end of work as identity?

This article seeks to present a counter-case to the ‘end of work thesis’ advocated by writers such as Beck, Sennett and Bauman. It argues that work remains a significant locus of personal identity and that the depiction by these writers of endemic insecurity in the workplace is inaccurate and lacks empirical basis. The article draws upon case study data to illustrate how, across a range of workplaces, work remains an importance source of identity, meaning and social affiliation

Genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase C gene

Neuropathic pain-like joint symptoms (NP) are seen in a proportion of individuals diagnosed with osteoarthritis (OA) and post total joint replacement (TJR). In this study, we performed a genome-wide association study (GWAS) using NP as defined by the painDETECT questionnaire (score >12 indicating possible NP) in 613 post-TJR participants recruited from Nottinghamshire (UK). The prevalence of possible NP was 17.8%. The top four hits from the GWAS and two other biologically relevant single-nucleotide polymorphisms (SNPs) were replicated in individuals with OA and post TJR from an independent study in the same area (N=908) and in individuals from the Rotterdam Study (N=212). Three of these SNPs showed effect sizes in the same direction as in the GWAS results in both replication cohorts. The strongest association upon meta-analysis of a recessive model was for the variant allele in rs887797 mapping to the protein kinase C alpha (PRKCA) gene odds ratio (OR)possNP=2.41 (95% CI 1.74–3.34, P=1.29 × 10−7). This SNP has been found to be associated with multiple sclerosis and encodes a functional variant affecting splicing and expression of the PRKCA gene. The PRKCA gene has been associated with long-term potentiation, synaptic plasticity, chronic pain and memory in the literature, making this a biologically relevant finding