Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population

Background Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2) gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry. Methods We genotyped four single nucleotide polymorphisms (SNPs) of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372) in 831 subjects with diabetes and 437 control subjects. Results The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 – 1.56, p = 1.96 × 10-3). For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p ≤ 1.04 × 10-7). Conclusion Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

<b>Background</b> Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. <p></p> <b>Methods</b> 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. <p></p> <b>Results</b> People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. <p></p> <b>Conclusion</b> People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation

Changing gender roles and attitudes and their implications for well-being around the new millennium

<b>Purpose</b><p></p> Given evidence that gender role attitudes (GRAs) and actual gender roles impact on well-being, we examine associations between GRAs, three roles (marital status, household chore division, couple employment) and psychological distress in working-age men and women. We investigate time-trends reflecting broader social and economic changes, by focusing on three age groups at two dates.<p></p> <b>Methods</b><p></p> We used British Household Panel Survey data from 20- to 64-year-olds in heterosexual couple households in 1991 (N = 5,302) and 2007 (N = 6,621). We examined: levels of traditional GRAs according to gender, age, date, household and employment roles; associations which GRAs and roles had with psychological distress (measured via the GHQ-12); whether psychological distress increased when GRAs conflicted with actual roles; and whether any of these associations differed according to gender, age or date.<p></p> <b>Results</b><p></p> Gender traditionalism was lower among women, younger people, those participating in 2007 and in ‘less traditional’ relationships and households. Psychological distress was higher among those with more traditional GRAs and, particularly among men, for those not employed, and there was some evidence of different patterns of association according to age-group. There was limited evidence, among women only, of increased psychological distress when GRAs and actual roles conflicted and/or reductions when GRAs and roles agreed, particularly in respect of household chores and paid employment.<p></p> <b>Conclusions</b><p></p> Although some aspects of gender roles and attitudes (traditionalism and paid employment) are associated with well-being, others (marital status and household chores), and attitude-role consistency, may have little impact on the well-being of contemporary UK adults.<p></p&gt

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals

Cluster analysis of protein array results via similarity of Gene Ontology annotation

BACKGROUND: With the advent of high-throughput proteomic experiments such as arrays of purified proteins comes the need to analyse sets of proteins as an ensemble, as opposed to the traditional one-protein-at-a-time approach. Although there are several publicly available tools that facilitate the analysis of protein sets, they do not display integrated results in an easily-interpreted image or do not allow the user to specify the proteins to be analysed. RESULTS: We developed a novel computational approach to analyse the annotation of sets of molecules. As proof of principle, we analysed two sets of proteins identified in published protein array screens. The distance between any two proteins was measured as the graph similarity between their Gene Ontology (GO) annotations. These distances were then clustered to highlight subsets of proteins sharing related GO annotation. In the first set of proteins found to bind small molecule inhibitors of rapamycin, we identified three subsets containing four or five proteins each that may help to elucidate how rapamycin affects cell growth whereas the original authors chose only one novel protein from the array results for further study. In a set of phosphoinositide-binding proteins, we identified subsets of proteins associated with different intracellular structures that were not highlighted by the analysis performed in the original publication. CONCLUSION: By determining the distances between annotations, our methodology reveals trends and enrichment of proteins of particular functions within high-throughput datasets at a higher sensitivity than perusal of end-point annotations. In an era of increasingly complex datasets, such tools will help in the formulation of new, testable hypotheses from high-throughput experimental data

A quantitative PCR (TaqMan) assay for pathogenic Leptospira spp

BACKGROUND: Leptospirosis is an emerging infectious disease. The differential diagnosis of leptospirosis is difficult due to the varied and often "flu like" symptoms which may result in a missed or delayed diagnosis. There are over 230 known serovars in the genus Leptospira. Confirmatory serological diagnosis of leptospirosis is usually made using the microscopic agglutination test (MAT) which relies on the use of live cultures as the source of antigen, often performed using a panel of antigens representative of local serovars. Other techniques, such as the enzyme linked immunosorbent assay (ELISA) and slide agglutination test (SAT), can detect different classes of antibody but may be subject to false positive reactions and require confirmation of these results by the MAT. METHODS: The polymerase chain reaction (PCR) has been used to detect a large number of microorganisms, including those of clinical significance. The sensitivity of PCR often precludes the need for isolation and culture, thus making it ideal for the rapid detection of organisms involved in acute infections. We employed real-time (quantitative) PCR using TaqMan chemistry to detect leptospires in clinical and environmental samples. RESULTS AND CONCLUSIONS: The PCR assay can be applied to either blood or urine samples and does not rely on the isolation and culture of the organism. Capability exists for automation and high throughput testing in a clinical laboratory. It is specific for Leptospira and may discriminate pathogenic and non-pathogenic species. The limit of detection is as low as two cells

Search for ZZ and ZW Production in ppbar Collisions at sqrt(s) = 1.96 TeV

We present a search for ZZ and ZW vector boson pair production in ppbar collisions at sqrt(s) = 1.96 TeV using the leptonic decay channels ZZ --> ll nu nu, ZZ --> l l l' l' and ZW --> l l l' nu. In a data sample corresponding to an integrated luminosity of 194 pb-1 collected with the Collider Detector at Fermilab, 3 candidate events are found with an expected background of 1.0 +/- 0.2 events. We set a 95% confidence level upper limit of 15.2 pb on the cross section for ZZ plus ZW production, compared to the standard model prediction of 5.0 +/- 0.4 pb.Comment: 7 pages, 2 figures. This version is accepted for publication by Phys. Rev. D Rapid Communication

Measurement of the Cross Section for Prompt Diphoton Production in p-pbar Collisions at sqrt(s) = 1.96 TeV

We report a measurement of the rate of prompt diphoton production in $p\bar{p}$ collisions at $\sqrt{s}=1.96 ~\hbox{TeV}$ using a data sample of 207 pb$^{-1}$ collected with the upgraded Collider Detector at Fermilab (CDF II). The background from non-prompt sources is determined using a statistical method based on differences in the electromagnetic showers. The cross section is measured as a function of the diphoton mass, the transverse momentum of the diphoton system, and the azimuthal angle between the two photons and is found to be consistent with perturbative QCD predictions.Comment: 7 pages, 3 figures,revtex4. Version accepted by PRL, but with cross section tables i

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO