Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

As William Morris Said - Strand Lamps

Strand lamps selected for inclusion in this exhibition in the Ruthin Crafts Gallery

Julius Caesar by William Shakespeare

Performance by Tyrone Guthrie Society, South Dining Hall, Queen's University, Belfast.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Finding revelation in anthropology: Alexander Winchell, William Robertson Smith and the heretical imperative

Anthropological inquiry has often been considered an agent of intellectual secularization. Not least is this so in the sphere of religion, where anthropological accounts have often been taken to represent the triumph of naturalism. This metanarrative however fails to recognise that naturalistic explanations could sometimes be espoused for religious purposes and in defence of confessional creeds. This essay examines two late nineteenth-century figures – Alexander Winchell in the United States, and William Robertson Smith in Britain – who found in anthropological analysis resources to bolster rather than undermine faith. In both cases these individuals found themselves on the receiving end of ecclesiastical censure and were dismissed from their positions at church-governed institutions. But their motivation was to vindicate divine revelation, in Winchell’s case from the physical anthropology of human origins and in Smith’s from the cultural anthropology of Semitic ritual.

The Relationship Between Laughter Intensity and Perceived Humour

There is a long history of recognizing a continuum in social signals of positive affect, with the continuum ranging from mild amusement signals to strong laughter. However there has been little systematic effort to assess what this continuum might mean. We present data that shows that incorporating intensity measures of laughter into laughter research is an important component and that there is a strong relationship between laughter intensity and humour. This may be intuitively obvious but the strength of the relationship suggests that intensity measures should be included in all laughter research.

Making randomised trials more efficient: report of the first meeting to discuss the Trial Forge platform

Randomised trials are at the heart of evidence-based healthcare, but the methods and infrastructure for conducting these sometimes complex studies are largely evidence free. Trial Forge (www.trialforge.org) is an initiative that aims to increase the evidence base for trial decision making and, in doing so, to improve trial efficiency.

This paper summarises a one-day workshop held in Edinburgh on 10 July 2014 to discuss Trial Forge and how to advance this initiative. We first outline the problem of inefficiency in randomised trials and go on to describe Trial Forge. We present participants' views on the processes in the life of a randomised trial that should be covered by Trial Forge.

General support existed at the workshop for the Trial Forge approach to increase the evidence base for making randomised trial decisions and for improving trial efficiency. Agreed upon key processes included choosing the right research question; logistical planning for delivery, training of staff, recruitment, and retention; data management and dissemination; and close down. The process of linking to existing initiatives where possible was considered crucial. Trial Forge will not be a guideline or a checklist but a 'go to' website for research on randomised trials methods, with a linked programme of applied methodology research, coupled to an effective evidence-dissemination process. Moreover, it will support an informal network of interested trialists who meet virtually (online) and occasionally in person to build capacity and knowledge in the design and conduct of efficient randomised trials.

Some of the resources invested in randomised trials are wasted because of limited evidence upon which to base many aspects of design, conduct, analysis, and reporting of clinical trials. Trial Forge will help to address this lack of evidence.

Law's Ethical, Global and Theoretical Contexts: Essays in Honour of William Twining

Law's Ethical, Global and Theoretical Contexts examines William Twining's principal contributions to law and jurisprudence in the context of three issues which will receive significant scholarly attention over the coming decades. Part I explores human rights, including torture, the role of evidence in human rights cases, the emerging discourse on 'traditional values', the relevance of 'Southern voices' to human rights debates, and the relationship between human rights and peace agreements. Part II assesses the impact of globalization through the lenses of sociology and comparative constitutionalism, and features an analysis of the development of pluralistic ideas of law in the context of privatization. Finally, Part III addresses issues of legal theory, including whether global legal pluralism needs a concept of law, the importance of context in legal interpretation, the effect of increasing digitalization on legal theory, and the utility of feminist and postmodern approaches to globalization and legal theory.

Establishing the validity of English GP Patient Survey items evaluating out-of-hours care

Background A 2014 national audit used the English General Practice Patient Survey (GPPS) to compare service users’ experience of out-of-hours general practitioner (GP) services, yet there is no published evidence on the validity of these GPPS items. Objectives Establish the construct and concurrent validity of GPPS items evaluating service users’ experience of GP out-of-hours care. Methods Cross-sectional postal survey of service users (n=1396) of six English out-of-hours providers. Participants reported on four GPPS items evaluating out-of-hours care (three items modified following cognitive interviews with service users), and 14 evaluative items from the Out-of-hours Patient Questionnaire (OPQ). Construct validity was assessed through correlations between any reliable (Cochran's α>0.7) scales, as suggested by a principal component analysis of the modified GPPS items, with the ‘entry access’ (four items) and ‘consultation satisfaction’ (10 items) OPQ subscales. Concurrent validity was determined by investigating whether each modified GPPS item was associated with thematically related items from the OPQ using linear regressions. Results The modified GPPS item-set formed a single scale (α=0.77), which summarised the two-component structure of the OPQ moderately well; explaining 39.7% of variation in the ‘entry access’ scores (r=0.63) and 44.0% of variation in the ‘consultation satisfaction’ scores (r=0.66), demonstrating acceptable construct validity. Concurrent validity was verified as each modified GPPS item was highly associated with a distinct set of related items from the OPQ. Conclusions Minor modifications are required for the English GPPS items evaluating out-of-hours care to improve comprehension by service users. A modified question set was demonstrated to comprise a valid measure of service users’ overall satisfaction with out-of-hours care received. This demonstrates the potential for the use of as few as four items in benchmarking providers and assisting services in identifying, implementing and assessing quality improvement initiatives.