Genome-wide association analysis identifies susceptibility loci for migraine without aura

Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 x 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 x 10(-4); combined P = 7.06 x 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 x 10(-4); combined P = 1.17 x 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 x 10(-8) and P = 0.02; combined P = 3.86 x 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.

Variation in BMPR1B, TGFRB1 and BMPR2 and control of dizygotic twinning

Genes in the TGF9 signaling pathway play important roles in the regulation of ovarian follicle growth and ovulation rate. Mutations in three genes in this pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and the bone morphogenetic protein receptor B 1 (BMPRB1), influence dizygotic (DZ) twinning rates in sheep. To date, only variants in GDF9 and BMP15, but not their receptors transforming growth factor ss receptor 1 (TGFBR1), bone morphogenetic protein receptor 2 (BMPR2) and BMPR1B, have been investigated with respect to their roles in human DZ twinning. We screened for rare and novel variants in TGFBR1, BMPR2 and BMPR1B in mothers of dizygotic twins (MODZT) from twin-dense families, and assessed association between genotyped and imputed variants and DZ twinning in another large sample of MODZT. Three novel variants were found: a deep intronic variant in BMPR2, and one intronic and one non-synonymous exonic variant in BMPRB1 which would result in the replacement of glutamine by glutamic acid at amino acid position 294 (p.Gln294Glu). None of these variants were predicted to have major impacts on gene function. However, the p.Gln294Glu variant changes the same amino acid as a sheep BMPR1B functional variant and may have functional consequences. Six BMPR1B variants were marginally associated with DZ twinning in the larger case-control sample, but these were no longer significant once multiple testing was taken into account. Our results suggest that variation in the TGF9 signaling pathway type II receptors has limited effects on DZ twinning rates in humans.

Sitting-time and 9-year all-cause mortality in older women

Background Studies of mid-aged adults provide evidence of a relationship between sitting-time and all-cause mortality, but evidence in older adults is limited. The aim is to examine the relationship between total sitting-time and all-cause mortality in older women. Methods The prospective cohort design involved 6656 participants in the Australian Longitudinal Study on Women's Health who were followed for up to 9 years (2002, age 76–81, to 2011, age 85–90). Self-reported total sitting-time was linked to all-cause mortality data from the National Death Index from 2002 to 2011. Cox proportional hazard models were used to examine the relationship between sitting-time and all-cause mortality, with adjustment for potential sociodemographic, behavioural and health confounders. Results There were 2003 (30.1%) deaths during a median follow-up of 6 years. Compared with participants who sat <4 h/day, those who sat 8–11 h/day had a 1.45 times higher risk of death and those who sat ≥11 h/day had a 1.65 times higher risk of death. These risks remained after adding sociodemographic and behavioural covariates, but were attenuated after adjustment for health covariates. A significant interaction (p=0.02) was found between sitting-time and physical activity (PA), with increased mortality risk for prolonged sitting only among participants not meeting PA guidelines (HR for sitting ≥8 h/day: 1.31, 95% CI 1.07 to 1.61); HR for sitting ≥11 h/day: 1.47, CI 1.15 to 1.93). Conclusions Prolonged sitting-time was positively associated with all-cause mortality. Women who reported sitting for more than 8 h/day and did not meet PA guidelines had an increased risk of dying within the next 9 years.

Sleep and self-regulation from birth to 7 years: A retrospective study of children with and without ADHD at 8-9 years

Objective To examine mean level differences, and longitudinal and reciprocal relations among behavioral sleep problems, emotional dysregulation, and attentional regulation across early childhood for children with and without ADHD at 8-9 years. Method This study used data from Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) – Infant Cohort (n = 4109 analyzed). Children with and without ADHD were identified at age 8-9 years via parent-report of ADHD diagnosis and the 5-item Inattention-Hyperactivity subscale from the Strengths and Difficulties Questionnaire. Maternal report of child sleep problems and self-regulation was collected at 0-1, 2-3, 4-5 and 6-7 years of age. ANOVA was used to compare mean level differences in sleep problems, emotional and attentional regulation by ADHD group. Longitudinal structural equation modeling examined the relations among sleep and self-regulation across time in children with and without ADHD. Results Children with ADHD had persistently elevated levels of sleep problems (from infancy) and emotional and attentional dysregulation compared to controls (from 2-3 years of age). Sleep problems, emotional dysregulation, and attentional regulation were stable over time for both groups. Sleep problems were associated with greater emotional dysregulation two years later from 2-3 years of age for both groups, which in turn was associated with poorer attentional regulation. There was no direct relationship between sleep problems and later attentional regulation. Conclusion Sleep problems in children with and without ADHD are associated with emotional dysregulation, which in turn contributes to poorer attentional functioning. This study highlights the importance of assessing and managing sleep problems in young children.

Exploiting the beta distribution-based reputation model in recommender system

Reputation systems are employed to measure the quality of items on the Web. Incorporating accurate reputation scores in recommender systems is useful to provide more accurate recommendations as recommenders are agnostic to reputation. The ratings aggregation process is a vital component of a reputation system. Reputation models available do not consider statistical data in the rating aggregation process. This limitation can reduce the accuracy of generated reputation scores. In this paper, we propose a new reputation model that considers previously ignored statistical data. We compare our proposed model against state-of the-art models using top-N recommender system experiment.

Influence of interleukin-1 beta on platelet-poor plasma clot formation: A potential impact on early bone healing

Objectives Hematoma quality (especially the fibrin matrix) plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β) on fibrin clot formation from platelet-poor plasma (PPP). Methods Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG), blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM), confocal microscopy (CM), turbidity, and clot lysis assays. Results The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β) compared to the control group without IL-1β (543.8 ± 205.8). Maximal turbidity was observed in the control group. IL-1β (500 pg/mL) treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05). The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers. Conclusion IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

Crime Justice and Social Democracy: Proceedings of the 3rd International Conference, 9-10 July 2015

We are pleased to present these selected papers from the proceedings of the 3rd Crime, Justice and Social Democracy International Conference, held in July 2015 in Brisbane, Australia. Over 350 delegates attended the conference from 19 countries. The papers collected here reflect the diversity of topics and themes that were explored over three days. The Crime, Justice and Social Democracy International Conference aims to strengthen the intellectual and policy debates concerning links between justice, social democracy, and the reduction of harm and crime, through building more just and inclusive societies and proposing innovative justice responses. In 2015, attendees discussed these issues as they related to ideas of green criminology; indigenous justice; gender, sex and justice; punishment and society; and the emerging notion of ‘Southern criminology’. The need to build global connections to address these challenges is more evident than ever and the conference and these proceedings reflect a growing attention to interdisciplinary, novel, and interconnected responses to contemporary global challenges. Authors in these conference proceedings engaged with issues of online fraud, queer criminology and law, Indigenous incarceration, youth justice, incarceration in Brazil, and policing in Victoria, Australia, among others. The topics explored speak to the themes of the conference and demonstrate the range of challenges facing researchers of crime, harm, social democracy and social justice and the spaces of possibility that such research opens. Our thanks to the conference convenor, Dr Kelly Richards, for organising such a successful conference, and to all those presenters who subsequently submitted such excellent papers for review here. We would also particularly like to thank Jess Rodgers for their tireless editorial assistance, as well as the panel of international scholars who participated in the review process, often within tight timelines.

8-13 Hz fluctuations in rectal pressure are an objective marker of clitorally-induced orgasm in women

Orgasm is a subjective experience accompanied by involuntary muscle contractions. We hypothesized that orgasm in women would be distinguishable by frequency analysis of a perineal muscle-derived signal. Rectal pressure, an index of perineal muscle activity, was measured continuously in 23 healthy women during different sexual tasks: receiving clitoral stimulation, imitation of orgasm, and attempt to reach orgasm, in which case the women were asked to report whether orgasm had been reached ("orgasm") or not ("failed orgasm attempt"). We performed spectral analysis on the rectal pressure data and calculated the spectral power in the frequency bands delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-25 Hz). The most significant and most important difference in spectral power between orgasm and both control motor tasks (imitation of orgasm and failed orgasm attempt) was found in the alpha band. An objective rule based on spectral power in the alpha band recognized 94% (29/31) of orgasms and correctly labeled 69% (44/64) of all orgasm attempts as either successful or failed. Because outbursts of alpha fluctuations in rectal pressure only occurred during orgasm and not during voluntary imitation of orgasm or failed attempts, we propose that they represent involuntary contractions of muscles in the rectal vicinity. This is the first objective and quantitative measure that has a strong correspondence with the subjective experience of orgasm.

Heparin versus 0.9% sodium chloride intermittent flushing for the prevention of occlusion in long term central venous catheters in infants and children: A systematic review

Background Around the world, guidelines and clinical practice for the prevention of complications associated with central venous catheters (CVC) vary greatly. To prevent occlusion, most institutions recommend the use of heparin when the CVC is not in use. However, there is debate regarding the need for heparin and evidence to suggest normal saline may be as effective. The use of heparin is not without risk, may be unnecessary and is also associated with increased costs. Objectives To assess the clinical effects (benefits and harms) of heparin versus normal saline to prevent occlusion in long-term central venous catheters in infants, children and adolescents. Design A Cochrane systematic review of randomised controlled trials was undertaken. - Data sources: The Cochrane Vascular Group Specialised Register (including MEDLINE, CINAHL, EMBASE and AMED) and the Cochrane Register of Studies were searched. Hand searching of relevant journals and reference lists of retrieved articles was also undertaken. - Review Methods: Data were extracted and appraisal undertaken. We included studies that compared the efficacy of normal saline with heparin to prevent occlusion. We excluded temporary CVCs and peripherally inserted central catheters. Rate ratios per 1000 catheter days were calculated for two outcomes, occlusion of the CVC, and CVC-associated blood stream infection. Results Three trials with a total of 245 participants were included in this review. The three trials directly compared the use of normal saline and heparin. However, between studies, all used different protocols with various concentrations of heparin and frequency of flushes. The quality of the evidence ranged from low to very low. The estimated rate ratio for CVC occlusion per 1000 catheter days between the normal saline and heparin group was 0.75 (95% CI 0.10 to 5.51, two studies, 229 participants, very low quality evidence). The estimated rate ratio for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37, two studies, 231 participants; low quality evidence). Conclusions It remains unclear whether heparin is necessary for CVC maintenance. More well-designed studies are required to understand this relatively simple, but clinically important question. Ultimately, if this evidence were available, the development of evidenced-based clinical practice guidelines and consistency of practice would be facilitated.

Identification of IDUA and WNT16 phosphorylation-related non-synonymous polymorphisms for bone mineral density in meta-analyses of genome-wide association studies

Protein phosphorylation regulates a wide variety of cellular processes. Thus, we hypothesize that single-nucleotide polymorphisms (SNPs) that may modulate protein phosphorylation could affect osteoporosis risk. Based on a previous conventional genome-wide association (GWA) study, we conducted a three-stage meta-analysis targeting phosphorylation-related SNPs (phosSNPs) for femoral neck (FN)-bone mineral density (BMD), total hip (HIP)-BMD, and lumbar spine (LS)-BMD phenotypes. In stage 1, 9593 phosSNPs were meta-analyzed in 11,140 individuals of various ancestries. Genome-wide significance (GWS) and suggestive significance were defined by α = 5.21 × 10–6 (0.05/9593) and 1.00 × 10–4, respectively. In stage 2, nine stage 1–discovered phosSNPs (based on α = 1.00 × 10–4) were in silico meta-analyzed in Dutch, Korean, and Australian cohorts. In stage 3, four phosSNPs that replicated in stage 2 (based on α = 5.56 × 10–3, 0.05/9) were de novo genotyped in two independent cohorts. IDUA rs3755955 and rs6831280, and WNT16 rs2707466 were associated with BMD phenotypes in each respective stage, and in three stages combined, achieving GWS for both FN-BMD (p = 8.36 × 10–10, p = 5.26 × 10–10, and p = 3.01 × 10–10, respectively) and HIP-BMD (p = 3.26 × 10–6, p = 1.97 × 10–6, and p = 1.63 × 10–12, respectively). Although in vitro studies demonstrated no differences in expressions of wild-type and mutant forms of IDUA and WNT16B proteins, in silico analyses predicts that WNT16 rs2707466 directly abolishes a phosphorylation site, which could cause a deleterious effect on WNT16 protein, and that IDUA phosSNPs rs3755955 and rs6831280 could exert indirect effects on nearby phosphorylation sites. Further studies will be required to determine the detailed and specific molecular effects of these BMD-associated non-synonymous variants. © 2015 American Society for Bone and Mineral Research.