Molecular simulation of chevrons in confined smectic liquid crystals

Chevron structures adopted by confined smectic liquid crystals are investigated via molecular dynamics simulations of the Gay-Berne model. The chevrons are formed by quenching nematic films confined between aligning planar substrates whose easy axes have opposing azimuthal components. When the substrates are perfectly smooth, the chevron formed migrates rapidly towards one of the confining walls to yield a tilted layer structure. However, when substrate roughness is included, by introducing a small-amplitude modulation to the particle- substrate interaction well-depth, a symmetric chevron is formed which remains stable over sufficiently long runtimes for detailed structural information, such as the relevant order parameters and director orien- tation, to be determined. For both smooth and rough boundaries, the smectic order parameter remains non-zero across the entire chevron, implying that layer identity is maintained across the chevron tip. Also, when the surface-stabilised chevron does eventually revert to a tilted layer structure, it does so via surface slippage, such that layer integrity is maintained throughout the chevron to tilted layer relaxation process. </p

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Ultraluminous Infrared Galaxies

Ever since their discovery in the 1970's, UltraLuminous InfraRed Galaxies (ULIRGs; classically Lir>10^12Lsun) have fascinated astronomers with their immense luminosities, and frustrated them due to their singularly opaque nature, almost in equal measure. Over the last decade, however, comprehensive observations from the X-ray through to the radio have produced a consensus picture of local ULIRGs, showing that they are mergers between gas rich galaxies, where the interaction triggers some combination of dust-enshrouded starburst and AGN activity, with the starburst usually dominating. Very recent results have thrown ULIRGs even further to the fore. Originally they were thought of as little more than a local oddity, but the latest IR surveys have shown that ULIRGs are vastly more numerous at high redshift, and tantalizing suggestions of physical differences between high and low redshift ULIRGs hint at differences in their formation modes and local environment. In this review we look at recent progress on understanding the physics and evolution of local ULIRGs, the contribution of high redshift ULIRGs to the cosmic infrared background and the global history of star formation, and the role of ULIRGs as diagnostics of the formation of massive galaxies and large-scale structures.Comment: Review article, published in "Astrophysics Update 2 - topical and timely reviews on astronomy and astrophysics". Ed. John W. Mason. Springer/Praxis books. ISBN: 3-540-30312-X. 53 pages, 5 figures. Higher quality figures available on reques

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Desk study on the impact of increasing numbers of women doctors on the medical workforce

SIGLEAvailable from British Library Document Supply Centre-DSC:m00/48051 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

GPs in the workplace: does gender matter?

The differing status of men and women in a society affects their experience both as patients and as providers of health care. This article examines the influence gender issues have upon the role of doctors and the running of health care services in an increasingly feminized workforce. It aims to raise awareness of the medicolegal aspects involved, including opportunities for GPs to improve gender equity in the workplace