Resource use data by patient report or hospital records: Do they agree?

Background: Economic evaluations alongside clinical trials are becoming increasingly common. Cost data are often collected through the use of postal questionnaires; however, the accuracy of this method is uncertain. We compared postal questionnaires with hospital records for collecting data on physiotherapy service use. Methods: As part of a randomised trial of orthopaedic medicine compared with orthopaedic surgery we collected physiotherapy use data on a group of patients from retrospective postal questionnaires and from hospital records. Results: 315 patients were referred for physiotherapy. Hospital data on attendances was available for 30% (n = 96), compared with 48% (n = 150) of patients completing questionnaire data (95% Cl for difference = 10% to 24%); 19% (n = 59) had data available from both sources. The two methods produced an intraclass correlation coefficient of 0.54 (95% Cl 0.31 to 0.70). However, the two methods produced significantly different estimates of resource use with patient self report recalling a mean of 1.3 extra visits (95% Cl 0.4 to 2.2) compared with hospital records. Conclusions: Using questionnaires in this study produced data on a greater number of patients compared with examination of hospital records. However, the two data sources did differ in the quantity of physiotherapy used and this should be taken into account in any analysi

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Image-based Cohesive Element Modelling of Low Temperature Crack Propagation in Alloy 82 Weld Metal

Exposure of Alloy 82 welds to hydrogen containing, de-oxygenated aqueous environments at temperatures below 150°C can result in embrittlement, manifested by a significant reduction of its resistance to cracking. The embrittlement is brought about by nano-scale niobium and titanium rich carbonitrides at grain boundaries which act as hydrogen traps. The presence of stresses may then result in low temperature crack propagation (LTCP).The work reported in this paper provides a better understanding of the effect of grain boundary micro- and meso-structure on LTCP susceptibility. The grain boundary morphology of an Alloy 82 weld microstructure was characterised using image analysis methods, and microstructure-faithful grain boundary profiles imported into Abaqus Finite Element (FE) software. A 2D model of the grain boundary meso-structure was generated using cohesive elements to simulate intergranular LTCP. Stress-assisted diffusion was used to calculate the rate of hydrogen ingress along grain boundaries. Changes in local hydrogen concentrations were then used to obtain the failure energy of each cohesive element. This controls the energy required to advance a crack locally. Grain boundary morphology, crystallography, and coverage of intergranular precipitates can also be included in the cohesive element model.The model was compared to in-situ observations of crack propagation in fatigue pre-cracked Alloy 82 microstructures exposed to 54C hydrogenated water. A windowed-autoclave test facility in conjunction with slow strain rate testing was used to observe a propagating crack along grain boundary segments. Digital image correlation (DIC) was then employed to estimate local crack growth rates and obtain fracture pathway information. Results obtained by in-situ observations were then used to calibrate cohesive model parameters. Post-mortem fractographic assessment was carried to out to determine modes of failure

Reading, Trauma and Literary Caregiving 1914-1918: Helen Mary Gaskell and the War Library

This article is about the relationship between reading, trauma and responsive literary caregiving in Britain during the First World War. Its analysis of two little-known documents describing the history of the War Library, begun by Helen Mary Gaskell in 1914, exposes a gap in the scholarship of war-time reading; generates a new narrative of "how," "when," and "why" books went to war; and foregrounds gender in its analysis of the historiography. The Library of Congress's T. W. Koch discovered Gaskell's ground-breaking work in 1917 and reported its successes to the American Library Association. The British Times also covered Gaskell's library, yet researchers working on reading during the war have routinely neglected her distinct model and method, skewing the research base on war-time reading and its association with trauma and caregiving. In the article's second half, a literary case study of a popular war novel demonstrates the extent of the "bitter cry for books." The success of Gaskell's intervention is examined alongside H. G. Wells's representation of textual healing. Reading is shown to offer sick, traumatized and recovering combatants emotional and psychological caregiving in ways that she could not always have predicted and that are not visible in the literary/historical record

(Micro)evolutionary changes and the evolutionary potential of bird migration

Seasonal migration is the yearly long-distance movement of individuals between their breeding and wintering grounds. Individuals from nearly every animal group exhibit this behavior, but probably the most iconic migration is carried out by birds, from the classic V-shape formation of geese on migration to the amazing nonstop long-distance flights undertaken by Arctic Terns Sterna paradisaea. In this chapter, we discuss how seasonal migration has shaped the field of evolution. First, this behavior is known to turn on and off quite rapidly, but controversy remains concerning where this behavior first evolved geographically and whether the ancestral state was sedentary or migratory (Fig. 7.1d, e). We review recent work using new analytical techniques to provide insight into this topic. Second, it is widely accepted that there is a large genetic basis to this trait, especially in groups like songbirds that migrate alone and at night precluding any opportunity for learning. Key hypotheses on this topic include shared genetic variation used by different populations to migrate and only few genes being involved in its control. We summarize recent work using new techniques for both phenotype and genotype characterization to evaluate and challenge these hypotheses. Finally, one topic that has received less attention is the role these differences in migratory phenotype could play in the process of speciation. Specifically, many populations breed next to one another but take drastically different routes on migration (Fig. 7.2). This difference could play an important role in reducing gene flow between populations, but our inability to track most birds on migration has so far precluded evaluations of this hypothesis. The advent of new tracking techniques means we can track many more birds with increasing accuracy on migration, and this work has provided important insight into migration's role in speciation that we will review here

The emerging structure of the Extended Evolutionary Synthesis: where does Evo-Devo fit in?

The Extended Evolutionary Synthesis (EES) debate is gaining ground in contemporary evolutionary biology. In parallel, a number of philosophical standpoints have emerged in an attempt to clarify what exactly is represented by the EES. For Massimo Pigliucci, we are in the wake of the newest instantiation of a persisting Kuhnian paradigm; in contrast, Telmo Pievani has contended that the transition to an EES could be best represented as a progressive reformation of a prior Lakatosian scientific research program, with the extension of its Neo-Darwinian core and the addition of a brand-new protective belt of assumptions and auxiliary hypotheses. Here, we argue that those philosophical vantage points are not the only ways to interpret what current proposals to ‘extend’ the Modern Synthesis-derived ‘standard evolutionary theory’ (SET) entail in terms of theoretical change in evolutionary biology. We specifically propose the image of the emergent EES as a vast network of models and interweaved representations that, instantiated in diverse practices, are connected and related in multiple ways. Under that assumption, the EES could be articulated around a paraconsistent network of evolutionary theories (including some elements of the SET), as well as models, practices and representation systems of contemporary evolutionary biology, with edges and nodes that change their position and centrality as a consequence of the co-construction and stabilization of facts and historical discussions revolving around the epistemic goals of this area of the life sciences. We then critically examine the purported structure of the EES—published by Laland and collaborators in 2015—in light of our own network-based proposal. Finally, we consider which epistemic units of Evo-Devo are present or still missing from the EES, in preparation for further analyses of the topic of explanatory integration in this conceptual framework

Statistical power considerations in genotype-based recall randomized controlled trials

Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for genemetformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a metformin transported encoding locus. We then calculated statistical power for interactions between genetic risk scores (GRS), metformin treatment and intensive lifestyle intervention (ILI) given a range of sampling frames, clinical trial sample sizes, interaction effect estimates, and allele frequencies; outcomes were type 2 diabetes incidence (time-to-event) and change in small LDL particles (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR (participants recruited from the extremes of a GRS distribution) and conventional sampling (participants recruited without explicit emphasis on genetic characteristics). We further examined the influence of outcome measurement error on statistical power. Under most simulated scenarios, GBR trials have substantially higher power to observe gene-drug and gene-lifestyle interactions than same-sized conventional RCTs. GBR trials are becoming popular for validation of gene-treatment interactions; our analyses illustrate the strengths and weaknesses of this design

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA