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.

The sociolinguistic stratification of a connected speech process - The case of the T to R rule in the Black Country

This paper examines the connected speech process described by Wells (1982b) as the T to R rule in the West Midlands speech variety associated with the Black Country. The T to R rule is well known as a linguistic marker of local varieties of the middle and far north of England. Less well understood is its position in the phonological systems of Midlands varieties. Varieties of the Midlands of England are underresearched in comparison with varieties of the north, and what is known about the application of the T to R rule in this transitional dialect area is correspondingly nebulous. This paper focuses on the Black Country area, and examines the possible outputs in the contexts which give rise to /t/ becoming [?] in local varieties of the north. I examine the written and spoken evidence which suggests that the T to R rule does indeed operate in the Black Country variety. My analysis focuses on possible phonetic outcomes of the T to R rule across time. In my conclusion, I discuss briefly the possibility that, lying on a bundle of isoglosses separating north from south, the variety of the Black Country reflects this in that a T to [?] rule, rather than a T to R rule, is the dominant output of this connected speech process in the Black Country.

Characterization of the hairpin vortex solution in plane Couette flow

Quantitative evidence that establishes the existence of the hairpin vortex state (HVS) in plane Couette flow (PCF) is provided in this work. The evidence presented in this paper shows that the HVS can be obtained via homotopy from a flow with a simple geometrical configuration, namely, the laterally heated flow (LHF). Although the early stages of bifurcations of LHF have been previously investigated, our linear stability analysis reveals that the root in the LHF yields multiple branches via symmetry breaking. These branches connect to the PCF manifold as steady nonlinear amplitude solutions. Moreover, we show that the HVS has a direct bifurcation route to the Rayleigh-Bénard convection. © 2010 The American Physical Society.