Genome-Wide Association Study Identifies Risk Loci for Cluster Headache

OBJECTIVE: To identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways. METHODS: We carried out a genome-wide association study, where 852 UK and 591 Swedish cluster headache cases were compared with 5,614 and 1,134 controls, respectively. Following quality control and imputation, single variant association testing was conducted using a logistic mixed model, for each cohort. The two cohorts were subsequently combined in a merged analysis. Downstream analyses, such as gene-set enrichment, functional variant annotation, prediction and pathway analyses, were performed. RESULTS: Initial independent analysis identified two replicable cluster headache susceptibility loci on chromosome 2. A merged analysis identified an additional locus on chromosome 1 and confirmed a locus significant in the UK analysis on chromosome 6, which overlaps with a previously known migraine locus. The lead single nucleotide polymorphisms were rs113658130 (p = 1.92 x 10-17 , OR [95%CI] = 1.51 [1.37-1.66]) and rs4519530 (p = 6.98 x 10-17 , OR = 1.47 [1.34-1.61]) on chromosome 2, rs12121134 on chromosome 1 (p = 1.66 x 10-8 , OR = 1.36 [1.22-1.52]) and rs11153082 (p = 1.85 x 10-8 , OR = 1.30 [1.19-1.42]) on chromosome 6. Downstream analyses implicated immunological processes in the pathogenesis of cluster headache. INTERPRETATION: We identified and replicated several genome-wide-significant associations supporting a genetic predisposition in cluster headache in a genome-wide association study involving 1,443 cases. Replication in larger independent cohorts combined with comprehensive phenotyping, in relation to e.g. treatment response and cluster headache subtypes, could provide unprecedented insights into genotype-phenotype correlations and the pathophysiological pathways underlying cluster headache

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

Measurement of the electron neutrino charged-current interaction rate on water with the T2K ND280 pi(0) detector

10 pages, 6 figures, Submitted to PRDhttp://journals.aps.org/prd/abstract/10.1103/PhysRevD.91.112010© 2015 American Physical Society11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PR

The Left Hand Second to Fourth Digit Ratio (2D:4D) Does Not Discriminate World-Class Female Gymnasts from Age Matched Sedentary Girls

INTRODUCTION: The second to fourth-digit-ratio (2D:4D), a putative marker of prenatal androgen action and a sexually dimorphic trait, has been suggested to be related with sports performance, although results are not univocal. If this relation exists, it is most likely to be detected by comparing extreme groups on the continuum of sports performance. METHODS: In this study the 2D:4D ratio of world-class elite female artistic gymnasts (n = 129), competing at the 1987 Rotterdam World-Championships was compared to the 2D:4D ratio of sedentary age-matched sedentary girls (n = 129), alongside with other anthropometric characteristics including other sexually dimorphic traits such as an androgyny index (Bayer & Bayley) and Heath-Carter somatotype components (endomorphy, mesomorphy, ectomorphy) using AN(C)OVA. 2D:4D was measured on X-rays of the left hand. RESULTS: Left hand 2D:4D digit ratio in world class elite female gymnasts (0.921±0.020) did not differ significantly from 2D:4D in age-matched sedentary girls (0.924±0.018), either with or without inclusion of potentially confounding covariates such as skeletal age, height, weight, somatotype components or androgyny index. Height (161.9±6.4 cm vs 155.4±6.6 cm p<0.01), weight (53.9±7.6 kg vs 46.2 6.3 kg p<0.01), BMI (20.51±2.41 kg/m(2) vs 19.05±1.56 kg/m(2)), skeletal age (15.2±1.1 y vs 14.5±1.2 y p>0.01), somatotype components (4.0/3.0/2.9 vs 1.7/3.7/3.2 for endomorphy (p<0.01), mesomorphy (p<0.01) and ectomorphy (p<0.05) respectively) all differed significantly between sedentary girls and elite gymnasts. As expressed by the androgyny index, gymnasts have, on average, broader shoulders relative to their hips, compared to the reference sample. Correlations between the 2D:4D ratio and chronological age, skeletal age, and the anthropometric characteristics are low and not significant. CONCLUSION: Although other anthropometric characteristics of sexual dimorphism were significantly different between the two samples, the present study cannot discriminate sedentary girls from world-class female gymnasts by means of the left hand 2D:4D ratio

Role of high tibial osteotomy in chronic injuries of posterior cruciate ligament and posterolateral corner

High tibial osteotomy (HTO) is a surgical procedure used to change the mechanical weight-bearing axis and alter the loads carried through the knee. Conventional indications for HTO are medial compartment osteoarthritis and varus malalignment of the knee causing pain and dysfunction. Traditionally, knee instability associated with varus thrust has been considered a contraindication. However, today the indications include patients with chronic ligament deficiencies and malalignment, because an HTO procedure can change not only the coronal but also the sagittal plane of the knee. The sagittal plane has generally been ignored in HTO literature, but its modification has a significant impact on biomechanics and joint stability. Indeed, decreased posterior tibial slope causes posterior tibia translation and helps the anterior cruciate ligament (ACL)-deficient knee. Vice versa, increased tibial slope causes anterior tibia translation and helps the posterior cruciate ligament (PCL)-deficient knee. A review of literature shows that soft tissue procedures alone are often unsatisfactory for chronic posterior instability if alignment is not corrected. Since limb alignment is the most important factor to consider in lower limb reconstructive surgery, diagnosis and treatment of limb malalignment should not be ignored in management of chronic ligamentous instabilities. This paper reviews the effects of chronic posterior instability and tibial slope alteration on knee and soft tissues, in addition to planning and surgical technique for chronic posterior and posterolateral instability with HTO

Application of a diagnosis-based clinical decision guide in patients with neck pain

<p>Abstract</p> <p>Background</p> <p>Neck pain (NP) is a common cause of disability. Accurate and efficacious methods of diagnosis and treatment have been elusive. A diagnosis-based clinical decision guide (DBCDG; previously referred to as a diagnosis-based clinical decision rule) has been proposed which attempts to provide the clinician with a systematic, evidence-based guide in applying the biopsychosocial model of care. The approach is based on three questions of diagnosis. The purpose of this study is to present the prevalence of findings using the DBCDG in consecutive patients with NP.</p> <p>Methods</p> <p>Demographic, diagnostic and baseline outcome measure data were gathered on a cohort of NP patients examined by one of three examiners trained in the application of the DBCDG.</p> <p>Results</p> <p>Data were gathered on 95 patients. Signs of visceral disease or potentially serious illness were found in 1%. Centralization signs were found in 27%, segmental pain provocation signs were found in 69% and radicular signs were found in 19%. Clinically relevant myofascial signs were found in 22%. Dynamic instability was found in 40%, oculomotor dysfunction in 11.6%, fear beliefs in 31.6%, central pain hypersensitivity in 4%, passive coping in 5% and depression in 2%.</p> <p>Conclusion</p> <p>The DBCDG can be applied in a busy private practice environment. Further studies are needed to investigate clinically relevant means to identify central pain hypersensitivity, oculomotor dysfunction, poor coping and depression, correlations and patterns among the diagnostic components of the DBCDG as well as inter-examiner reliability, validity and efficacy of treatment based on the DBCDG.</p