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Background: Low 25-hydroxyvitamin D status has been associated with a higher risk of cancer in epidemiologic studies. Objective The aim of this study was to undertake a systematic review and meta-analysis of randomized clinical trials (RCTs) investigating the effect of vitamin D supplementation alone on cancer incidence and mortality. Design: A systematic review was undertaken. MEDLINE, Embase, CENTRAL, conference abstracts, and clinical trial registries were searched (last search March 2017) for RCTs investigating vitamin D supplementation alone. RCTs with ≥12 mo of follow-up and in participants with a mean or median age ≥60 y were eligible. During-study events were used as the main analysis, but after-study events were included in a secondary analysis. Subgroup analyses concerning different forms of vitamin D supplementation, 25-hydroxyvitamin D status at baseline, vitamin D dose, and exclusion of open-label trials were undertaken. Results: Thirty studies in 18,808 participants were included in the systematic review, with a median follow-up ranging from 1 to 6.2 y. The results of the meta-analysis for during-study events showed no evidence of an effect of vitamin D supplementation for cancer incidence (RR: 1.03; 95% CI: 0.91, 1.15) and cancer-related deaths (RR: 0.85; 95% CI: 0.70, 1.04). Including after-study events, the RRs were 1.02 (95% CI: 0.92, 1.13) and 0.85 (95% CI: 0.72, 1.00), respectively. These results did not appear to be affected by baseline 25-hydroxyvitamin D status, vitamin D dose, or the exclusion of open-label trials. Conclusion: We did not find evidence to suggest that vitamin D supplementation alone reduces the incidence of cancer or cancer mortality, even after including long-term follow-up results.

Phased Array Feed (PAF) technology is the next major advancement in radio astronomy in terms of combining high sensitivity and large field of view. The Focal L-band Array for the Green Bank Telescope (FLAG) is one of the most sensitive PAFs developed so far. It consists of 19 dual-polarization elements mounted on a prime focus dewar resulting in seven beams on the sky. Its unprecedented system temperature of$\sim$17 K will lead to a 3 fold increase in pulsar survey speeds as compared to contemporary single pixel feeds. Early science observations were conducted in a recently concluded commissioning phase of the FLAG where we clearly demonstrated its science capabilities. We observed a selection of normal and millisecond pulsars and detected giant pulses from PSR B1937+21., Comment: 2 pages, 3 figures, submitted for publication in the proceedings of IAU Symposium 337. Pulsar Astrophysics: The Next Fifty years

Aims Two double-blind, randomized studies were conducted to assess the tolerability, pharmacokinetics and pharmacodynamics of oral TA-8995, a new cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Methods Study 1: Subjects received single doses of TA-8995 or placebo (fasted). Doses were 5, 10, 25, 50 (fed/fasted), 100 and 150 mg (Caucasian males, 18–55 years), 25 mg (Caucasian males, > 65 years and Caucasian females, 18–55 years), 25, 50, 100 and 150 mg (Japanese males, 18–55 years). Study 2: Caucasian males (18–55 years) received 1, 2.5, 10 or 25 mg once daily TA-8995 or placebo for 21–28 days. Blood and urine for pharmacokinetics and/or pharmacodynamics were collected. Tolerability was assessed by adverse events, vital signs, electrocardiograms and laboratory safety tests. Results Peak TA-8995 concentrations occurred approximately 4 h post-dose. Mean half-lives ranged from 81 to 166 h, without an obvious dose relationship. Exposure increased less than proportionally to dose. TA-8995 was not excreted in urine. Following 2.5 to 25 mg once daily dosing, TA-8995 demonstrated nearly complete inhibition of CETP activity (92–99%), increased high density lipoprotein-cholesterol (HDL-C) by 96 to 140% and decreased low density liporotein-cholesterol (LDL-C) by 40% to 53%. There were dose-related increases in apolipoproteins A-1 and E, HDL2-C and HDL3-C, and decreases in apolipoprotein B and lipoprotein A. There was no evidence of significant effects of age, gender, ethnicity or food on pharmacokinetics or pharmacodynamics. All doses were well tolerated. Conclusions TA-8995 is a potent CETP inhibitor and warrants further investigation.

This paper describes MUSTANG 2, a 338 element focal plane array that is being built for the Green Bank Telescope. Each element consists of a profiled feedhorn coupled to two transition edge sensor bolometers, one for each polarization. Initial deployment will be with 32 detectors, but once fully populated, MUSTANG 2 will be capable of mapping a $$8'\times 8'$$ area to $$23~\upmu $$ Jy in 1 h with good image fidelity on angular scales from $$9''$$ to $$6'$$ . As well as an instrument overview, the choice of bandpass and the design of the feeds, detectors and readout are given.

The Collaboration for Astronomy Signal Processing and Electronics Research (CASPER) has been working for a decade to reduce the time and cost of designing, building and deploying new digital radio-astronomy instruments. Today, CASPER open-source technology powers over 45 scientific instruments worldwide, and is used by scientists and engineers at dozens of academic institutions. In this paper, we catalog the current offerings of the CASPER collaboration, and instruments past and present built by CASPER users and developers. We describe the ongoing state of software development, as CASPER looks to support a broader range of programming environments and hardware and ensure compatibility with the latest vendor tools.

IntroductionGoal-setting is recommended for patients with multimorbidity, but there is little evidence to support its use in general practice.ObjectiveTo assess the feasibility of goal-setting for patients with multimorbidity, before undertaking a definitive trial.Design and settingCluster-randomised controlled feasibility trial of goal-setting compared with control in six general practices.ParticipantsAdults with two or more long term health conditions and at risk of unplanned hospital admission.InterventionsGeneral practitioners (GPs) underwent training and patients were asked to consider goals before an initial goal-setting consultation and a follow-up consultation 6 months later. The control group received usual care planning.Outcome measuresHealth-related quality of life (EQ-5D-5L), capability (ICEpop CAPability measure for Older people), Patient Assessment of Chronic Illness Care and healthcare use. All consultations were video-recorded or audio-recorded, and focus groups were held with participating GPs and patients.ResultsFifty-two participants were recruited with a response rate of 12%. Full follow-up data were available for 41. In the goal-setting group, mean age was 80.4 years, 54% were female and the median number of prescribed medications was 13, compared with 77.2 years, 39% female and 11.5 medications in the control group. The mean initial consultation time was 23.0 min in the goal-setting group and 19.2 in the control group. Overall 28% of patient participants had no cognitive impairment. Participants set between one and three goals on a wide range of subjects, such as chronic disease management, walking, maintaining social and leisure interests, and weight management. Patient participants found goal-setting acceptable and would have liked more frequent follow-up. GPs unanimously liked goal-setting and felt it delivered more patient-centred care, and they highlighted the importance of training.ConclusionsThis goal-setting intervention was feasible to deliver in general practice. A larger, definitive study is needed to test its effectiveness.Trial registration numberISRCTN13248305; Post-results.

Background Standing invoked change in QT interval has been identified as a promising autonomic maneuver for the assessment of QT/QTc prolongation in patients with underlying heart abnormalities or as a positive control in healthy volunteers for drug studies. Criticism for its more widespread use is the high variability in reported results and the need for a more standardized methodology with defined normal ranges. Methods Forty healthy male subjects underwent continuous ECG collection on the day before dosing in a double-blind, placebo-controlled, randomized, single ascending dose trial. A brisk supine to standing (3 minutes) response was conducted at three time points. Results were grouped by treatment cohort or assessed as a pooled group at each time point. Maximum time and median change from baseline (ΔTmaxQTcF, ΔQTcF) were calculated for each individual over sequential 30-second periods staggered by 5 seconds. Results Maximum ΔQTcF at all time points and in all groups was significant (i.e., the lower bound of 90% CI was > 5 milliseconds) which is the ICH E14 regulatory requirement for a positive control. Variability of the time to maximum response was also reduced 9-fold by the third time period. Conclusions Standing invoked ΔQTcF can be utilized to validate the sensitivity of a study for assessment of the QT interval effect of drugs in early development. The methodology may be used to further improve its diagnostic use of long QT syndromes by reducing the variability and allowing adequate definition of normal limits.

The scope of this paper is to identify the experience, attitudes and impressions of health care professionals (HCPs) in addressing the needs of women patients suffering from intimate partner violence (IPV). In-depth interviews were conducted with 14 doctors and 11 nurses in Ribeirão Preto. Results show that there is an 'apparent invisibility' of IPV, the convenience of a tacit compact of silence about such violence on the part of women and HCPs. We studied the reasons given by HCPs for failing to deal with IPV. We also addressed the health service facility context, and the diversity of the professioinals' responses to violence, with indications of the emergence of a more proactive and positive stance. Qualitative data analysis highlights previous survey findings. A positive response from HCPs shows that there is perhaps some change from a narrow, medically-focused model of health care, to a more broadly defined social model.Objetivos: Identificar a experiência, as atitudes e os sentimentos dos profissionais de saúde (PS) quando abordam as necessidades de mulheres que sofrem violência do parceiro íntimo (VPI). Método: Foram realizadas entrevistas em profundidade com 14 médicos e 11 enfermeiras em Ribeirão Preto. Resultados: Há uma aparente invisibilidade e a conveniência de um acordo tácito de silêncio por parte da mulher e do PS; exploramos as razões dadas por eles para esta inabilidade em atender VPI. Também abordamos o contexto dos serviços de saúde, a diversidade de respostas dos profissionais e a emergência uma postura mais proativa e positiva. Discussão: A análise qualitativa realça os resultados de um inquérito prévio. Uma resposta positiva mostra que talvez haja algumas mudanças de perspectiva de um modelo medicalizado de cuidado à saúde para um modelo mais abrangente ou integral que define saúde como social.

Contains fulltext : 126103.pdf (Publisher’s version ) (Open Access) In the UK, prostate cancer (PC) is the most common cancer in men. A diagnosis can be confirmed only following a prostate biopsy. Many men find themselves with an elevated prostate-specific antigen (PSA) level and a negative biopsy. The best way to manage these men remains uncertain.To assess the diagnostic accuracy of magnetic resonance spectroscopy (MRS) and enhanced magnetic resonance imaging (MRI) techniques [dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted MRI (DW-MRI)] and the clinical effectiveness and cost-effectiveness of strategies involving their use in aiding the localisation of prostate abnormalities for biopsy in patients with prior negative biopsy who remain clinically suspicious for harbouring malignancy.Databases searched--MEDLINE (1946 to March 2012), MEDLINE In-Process & Other Non-Indexed Citations (March 2012), EMBASE (1980 to March 2012), Bioscience Information Service (BIOSIS; 1995 to March 2012), Science Citation Index (SCI; 1995 to March 2012), The Cochrane Library (Issue 3 2012), Database of Abstracts of Reviews of Effects (DARE; March 2012), Medion (March 2012) and Health Technology Assessment database (March 2012).Types of studies: direct studies/randomised controlled trials reporting diagnostic outcomes. Index tests: MRS, DCE-MRI and DW-MRI. Comparators: T2-weighted magnetic resonance imaging (T2-MRI), transrectal ultrasound-guided biopsy (TRUS/Bx). Reference standard: histopathological assessment of biopsied tissue. A Markov model was developed to assess the cost-effectiveness of alternative MRS/MRI sequences to direct TRUS-guided biopsies compared with systematic extended-cores TRUS-guided biopsies. A health service provider perspective was adopted and the recommended 3.5\% discount rate was applied to costs and outcomes.A total of 51 studies were included. In pooled estimates, sensitivity [95\% confidence interval (CI)] was highest for MRS (92\%; 95\% CI 86\% to 95\%). Specificity was highest for TRUS (imaging test) (81\%; 95\% CI 77\% to 85\%). Lifetime costs ranged from £3895 using systematic TRUS-guided biopsies to £4056 using findings on T2-MRI or DCE-MRI to direct biopsies (60-year-old cohort, cancer prevalence 24\%). The base-case incremental cost-effectiveness ratio for T2-MRI was

Aim To evaluate the evidence for denosumab for the treatment of bone metastases secondary to solid tumours and, using a network meta-analysis, indirectly compare denosumab with bisphosphonates and best supportive care. Data sources MEDLINE (1948 to April 2011), EMBASE (1980 to March 2011), Cochrane Library (all sections) (issue 1, 2011) and Web of Science with Conference Proceedings (1970 to May 2011) and additional meeting abstracts (2010 and 2011) were searched. Study eligibility, participants and interventions Only randomised controlled trials assessing denosumab, bisphosphonates or best supportive care in patients with bone metastases from any solid tumour were included. Synthesis Direct evidence comparing denosumab and zoledronic acid was assessed for breast cancer, prostate cancer and other solid tumours. Denosumab was compared with pamidronate and best supportive care through a network meta-analysis for each tumour type. The primary outcomes were time to first skeletal related event (SRE) and time to first and subsequent SRE. Secondary outcomes were skeletal morbidity rate, pain, quality of life (QoL) and overall survival. Results Denosumab was found to be more effective in delaying the time to first SRE and reducing the risk of first and subsequent SRE compared to zoledronic acid, placebo and pamidronate. In breast and prostate cancer, denosumab was effective in reducing skeletal morbidity rate compared with placebo. The lack of published data on pain and QoL meant that firm conclusions could not be made. Denosumab did not appear to have an affect on overall survival. Limitations Network meta-analyses are subject to uncertainties and potential biases. Conclusions Denosumab is effective in preventing SRE, but the effect on pain and QoL is unclear.

The human electrophysiological and pharmacological properties of XEN-D0101 were evaluated to assess its usefulness for treating atrial fibrillation (AF). XEN-D0101 inhibited Kv1.5 with an IC50 of 241 nM and is selective over non-target cardiac ion channels (IC50 Kv4.3, 4.2 μM; hERG, 13 μM; activated Nav1.5, >100 μM; inactivated Nav1.5, 34 μM; Kir3.1/3.4, 17 μM; Kir2.1, >>100 μM). In atrial myocytes from patients in sinus rhythm (SR) and chronic AF, XEN-D0101 inhibited non-inactivating outward currents (Ilate) with IC50 of 410 and 280 nM, respectively, and peak outward currents (Ipeak) with IC50 of 806 and 240 nM, respectively. Whereas Ilate is mainly composed of IKur, Ipeak consists of IKur and Ito. Therefore, the effects on Ito alone were estimated from a double-pulse protocol where IKur was inactivated (3.5 µM IC50 in SR and 1 µM in AF). Thus, inhibition of Ipeak is because of IKur reduction and not Ito. XEN-D0101 significantly prolonged the atrial action potential duration at 20%, 50%, and 90% of repolarization (AF tissue only) and significantly elevated the atrial action potential plateau phase and increased contractility (SR and AF tissues) while having no effect on human ventricular action potentials. In healthy volunteers, XEN-D0101 did not significantly increase baseline- and placebo-adjusted QTc up to a maximum oral dose of 300 mg. XEN-D0101 is a Kv1.5/IKur inhibitor with an attractive atrial-selective profile.

Cardiovascular disease (CVD) is a major cause of mortality accounting for 27% of deaths in the UK in 2014 and is a great cost to the UK economy, estimated to be £15.2 billion in 2015.1 Lipid modification is important as there is a positive correlation between the incidence of CVD and cholesterol levels.2 There is substantial evidence of benefit in prescribing statins to all patients for secondary prevention of CVD and for primary prevention in many of those patients with higher CVD risk.3 A Cochrane review in 2013 included 18 randomised controlled trials of statin prescribing for primary prevention and reported a reduction in all-cause mortality (odds ratio [OR] 0.86, 95% confidence interval [CI] = 0.79 to 0.94), with the number needed to treat to prevent one death over 5 years being 96 and an acceptable cost-effectiveness.3 The Cholesterol Treatment Trialists’ Collaboration (CTTC) trial performed a meta-analysis of individual patient data from 27 randomised controlled trials and reported in 2012 that statin therapy reduces the risk of major vascular events even in patients with 5-year CVD risks of 10% 10-year risk of developing CVD. This guidance was revised from a >20% risk in 2014 and a >30% risk in 2010.4 …

How landscape context influences density-dependent processes is important, as environmental heterogeneity can confound estimates of density dependence in demographic parameters. Here we evaluate 19 populations in a shoaling temperate reef fish (Trachinops caudimaculatus) metapopulation within a heterogeneous seascape (Port Phillip Bay, Australia) to show empirically that shelter availability and population density interact to influence juvenile mortality, growth and condition. Although heterogeneity in shelter availability obscured the underlying patterns of density dependence in different ways, the combination of habitat and its interaction with density were two to six times more important than density alone in explaining variation in demographic parameters for juveniles. These findings contradict many small-scale studies and highlight the need for landscape-scale observations of how density dependence interacts with resource availability and competition to better understand how demographic parameters influence the dynamics of metapopulations in heterogeneous environments.

Background Asthma prevalence has increased world-wide especially in children; thus there is a need to develop new therapies that are safe and effective especially for patients with severe/refractory asthma. CD4+ T cells are thought to play a central role in disease pathogenesis and associated symptoms. Recently, TRPV1 has been demonstrated to regulate the activation and inflammatory properties of CD4+ cells. The aim of these experiments was to demonstrate the importance of CD4+ T cells and the role of TRPV1 in an asthma model using a clinically ready TRPV1 inhibitor (XEN-D0501) and genetically modified (GM) animals. Methods Mice (wild type, CD4 −/− or TRPV1 −/−) and rats were sensitised with antigen (HDM or OVA) and subsequently topically challenged with the same antigen. Key features associated with an allergic asthma type phenotype were measured: lung function (airway hyperreactivity [AHR] and late asthmatic response [LAR]), allergic status (IgE levels) and airway inflammation. Results CD4+ T cells play a central role in both disease model systems with all the asthma-like features attenuated. Targeting TRPV1 using either GM mice or a pharmacological inhibitor tended to decrease IgE levels, airway inflammation and lung function changes. Conclusion Our data suggests the involvement of TRPV1 in allergic asthma and thus we feel this target merits further investigation.

TA-8995 is a potent inhibitor of cholesteryl ester transfer protein (CETP) with beneficial effects on lipids and lipoproteins. The effect of TA-8995 on cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, and HDL subparticle distribution is largely unknown. To assess the effect of the CETP inhibitor TA-8995 on ABCA1- and non-ABCA1-driven CEC and on HDL particle distribution. Total, non-ABCA1-, and ABCA1-specific CEC from J774 cells and HDL subclass distribution assessed by two-dimensional gel electrophoresis were measured at baseline and after 12-week treatment in 187 mild-dyslipidemic patients randomized to placebo, 1 mg, 5 mg, 10 mg TA-8995, or 10 mg TA-8995 combined with 10 mg rosuvastatin (NCT01970215). Compared with placebo, total, non-ABCA1-, and ABCA1-specific CEC were increased dose dependently by up to 38%, 72%, and 28%, respectively, in patients randomized to 10 mg of TA-8995. PreBeta-1 HDL, the primary acceptor for ABCA1-driven cholesterol efflux, was increased by 36%. This increase in preBeta-1 HDL correlated significantly with the total and the ABCA1-driven CEC increase, whereas the high-density lipoprotein cholesterol (HDL-C) increase did not. TA-8995 dose dependently increased not only total and non-ABCA1-specific CEC but also ABCA1-specific CEC and preBeta-1 HDL particle levels. These findings suggest that TA-8995 not only increases HDL-C levels but also promotes functional properties of HDL particles. This CETP inhibitor-driven preBeta-1 HDL increase is an important predictor of both ABCA1 and total CEC increase, independent of HDL-C increase. Whether these changes in HDL particle composition and functionality have a beneficial effect on cardiovascular outcome requires formal testing in a cardiovascular outcome trial

Predicting the consequences of predator biodiversity loss on prey requires an understanding of multiple predator interactions. Predators are often assumed to have independent and additive effects on shared prey survival; however, multiple predator effects can be non-additive if predators foraging together reduce prey survival (risk enhancement) or increase prey survival through interference (risk reduction). In marine communities, juvenile reef fish experience very high mortality from two predator guilds with very different hunting modes and foraging domains-benthic and pelagic predator guilds. The few previous predator manipulation studies have found or assumed that mortality is independent and additive. We tested whether interacting predator guilds result in non-additive prey mortality and whether the detection of such effects change over time as prey are depleted. To do so, we examined the roles of benthic and pelagic predators on the survival of a juvenile shoaling zooplanktivorous temperate reef fish, Trachinops caudimaculatus, on artificial patch reefs over 2 months in Port Phillip Bay, Australia. We observed risk enhancement in the first 7 days, as shoaling behaviour placed prey between predator foraging domains with no effective refuge. At day 14 we observed additive mortality, and risk enhancement was no longer detectable. By days 28 and 62, pelagic predators were no longer significant sources of mortality and additivity was trivial. We hypothesize that declines in prey density led to reduced shoaling behaviour that brought prey more often into the domain of benthic predators, resulting in limited mortality from pelagic predators. Furthermore, pelagic predators may have spent less time patrolling reefs in response to declines in prey numbers. Our observation of the changing interaction between predators and prey has important implications for assessing the role of predation in regulating populations in complex communities.

Bariatric surgery can provide efficient weight loss and improvement in obesity-related co-morbidities in adults. Laparoscopic adjustable gastric banding (LAGB) comprised 30.3% of all bariatric procedures between 2009 and 2010 in the UK. This review evaluates the level 1 evidence for change in co-morbidities, quality of life (QoL) and weight provided by LAGB compared with other bariatric procedures.Systematic literature search of MEDLINE, EMBASE and CENTRAL (1988 to May 2011) was performed. Only randomised controlled trials (RCTs) were included. Studies with non-surgical comparators, open gastric banding procedures or adolescent participants were excluded. Primary outcome was change in co-morbidities. Secondary outcomes included QoL, weight loss, complications, operation time and length of stay.Five RCTs met the inclusion criteria. Vertical banded gastroplasty, sleeve gastrectomy and gastric bypass were compared to LAGB. Co-morbidities were reported in two studies and QoL in one. LAGB was comparable to other procedures for both of these outcomes. All five trials showed LABG to be effective in weight loss, however all comparative procedures resulted in greater weight loss. Operative time and length of hospital stay were significantly shorter with LAGB. Short-term complications were found to be consistently lower in the LAGB group. Evidence was divided with respect to long-term complications.Co-morbidities and QoL are poorly reported and showed no difference between LAGB and other bariatric procedures. Evidence suggests that LAGB is not the most effective surgical procedure to reduce weight. LAGB is associated with lower early complications and shorter operative time and length of stay, and therefore may be preferable to patients.

Background Intraoperative cholangiography (IOC) is used to detect choledocholithiasis and identify or prevent bile duct injury. The aim of this study was systematically to review the randomized clinical trials of IOC for these two indications. Methods MEDLINE, Embase, the Cochrane Library, clinicaltrials.gov and the World Health Organization database of clinical trials were searched systematically (January 1980 to February 2011) to identify trials. Two authors performed the literature search and extracted data independently. Primary endpoints were bile duct injury and retained common bile duct (CBD) stones diagnosed at any stage after surgery. Preliminary meta-analysis was undertaken, but the trials were too methodologically heterogeneous and the outcome events too infrequent to allow meaningful meta-analysis. Results Eight randomized trials were identified including 1715 patients. Six trials assessed the value of routine IOC in patients at low risk of choledocholithiasis. Two trials randomized all patients (including those at high risk) to routine or selective IOC. Two cases of major bile duct injury were reported, and 13 of retained CBD stones. No trial demonstrated a benefit in detecting CBD stones. IOC added a mean of 16 min to the total operating time. Conclusion There is no robust evidence to support or abandon the use of IOC to prevent retained CBD stones or bile duct injury. Level 1 evidence for IOC is of poor to moderate quality. None of the trials, alone or in combination, was sufficiently powered to demonstrate a benefit of IOC. Further small trials cannot be recommended.

The Scottish Intercollegiate Guideline Network (SIGN) published Postoperative Management in Adults in 2004, advocating post-operative assessments to optimize post-operative care. Our aim was to improve post-operative assessments in a surgical high-dependency unit (HDU).

Voiding dysfunction (VD) is relatively common following suburethral tape insertion. Our study aimed to identify perioperative variables that predict VD. Women who underwent suburethral tapes (TVT(TM) and TVT-O(TM)), either as sole procedure or with a concomitant prolapse repair, were studied retrospectively. The primary outcome was women requiring catheterisation and/or re-catheterisation in the postoperative period. A total of 319 women underwent suburethral tapes within the study period: 256 case notes (80.2%) were available for review and 40/256 women (15.6%) developed postoperative VD. No preoperative urinary symptoms were associated with postoperative VD. Univariate analysis demonstrated three variables associated with VD: average flow rate (Q-ave) ≤5th centile (odds ratio (OR) 2.3, 95% CI 1.2-6.5, p = 0.016), a combination of Q-ave and maximum flow rate (Q-max) ≤5th centile (OR 2.8, 95% CI 1.1-6.9, p = 0.030) and concomitant prolapse procedure (OR 3.6, 95% CI 1.5-8.9, p = 0.005). Following multivariate logistic regression Q-ave ≤5th centile and concomitant prolapse procedure showed the strongest association with VD.

Background Life expectancy in the UK stopped increasing in 2010. To identify possible causes, we explored changes in life expectancy by age, sex, and condition. Methods Using the Global Burden of Disease (GBD) study 2016, we determined estimates of life expectancy, death rates, and premature mortality (years of life lost [YLL]) from 1990 to 2016 in the UK by sex and age. Annual change in YLL and death rates were calculated for the following leading causes of premature death in 2016: ischaemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, dementia, lower respiratory tract infections, colorectal and breast cancers, self-harm, and diseases due to alcohol use and related diseases. Findings Combined mean improvements in life expectancy were 0·26% per year (75·72–80·99) and death rates were 0·98% (195427·59–154351·73) from 1990 to 2010; improvements stalled after 2010. The slowdown was seen across all age groups and in both sexes, with a slightly more marked slowdown in men (0·04%, 72·85–78·92) than in women (0·03%, 78·47–82·86). The conditions that showed the greatest changes in YLL since 2010 were ischaemic heart disease, stroke, lower respiratory tract infections, and lung and colon cancer. YLL reduction rates from ischaemic heart disease fell from 2·94% (205098·90–84411·42) to 1·77% (84411·42–75449·83) per year and stroke 2·03% (78921·56–46918·77) to 1·17% (46918·77–43638·12). YLL rates from lung and colon cancer increased in the over 85 year age group with lung cancer at 1·03% (5718·47–6072·65) per year and colon cancer 0·44% (5423·75–5568·14). YLL rates from lower respiratory tract infections increased 1·25% (27984·06–30086·93) per year after 2010 following yearly reductions for the previous 16 years. The YLL rate for lower respiratory tract infections increased more in England than in the other three UK countries. Interpretation The slowdown in UK life expectancy since 2010 appears to have been driven largely by declining improvements in YLL from ischaemic heart disease and stroke, with increasing YLL from lower respiratory tract infections and cancer also contributing. Further research is needed into the causes of these condition-specific changes, including the effects of austerity and international comparisons to explore the extent to which further improvements in life expectancy are biologically possible. Funding None.

Identifying and conserving sites with consistently high settlement is necessary for pro- tecting recruitment of coastal fish populations. We investigated the initial settlement patterns of coastally spawned juvenile fish entering 4 temperate estuaries with narrow entrances (

We review the status of marine shellfish ecosystems formed primarily by bivalves in Australia, including: identifying ecosystem-forming species, assessing their historical and current extent, causes for decline and past and present management. Fourteen species of bivalves were identified as developing complex, three-dimensional reef or bed ecosystems in intertidal and subtidal areas across tropical, subtropical and temperate Australia. A dramatic decline in the extent and condition of Australia’s two most common shellfish ecosystems, developed by Saccostrea glomerata and Ostrea angasi oysters, occurred during the mid-1800s to early 1900s in concurrence with extensive harvesting for food and lime production, ecosystem modification, disease outbreaks and a decline in water quality. Out of 118 historical locations containing O. angasi-developed ecosystems, only one location still contains the ecosystem whilst only six locations are known to still contain S. glomerata-developed ecosystems out of 60 historical locations. Ecosystems developed by the introduced oyster Crasostrea gigas are likely to be increasing in extent, whilst data on the remaining 11 ecosystem-forming species are limited, preventing a detailed assessment of their current ecosystem-forming status. Our analysis identifies that current knowledge on extent, physical characteristics, biodiversity and ecosystem services of Australian shellfish ecosystems is extremely limited. Despite the limited information on shellfish ecosystems, a number of restoration projects have recently been initiated across Australia and we propose a number of existing government policies and conservation mechanisms, if enacted, would readily serve to support the future conservation and recovery of Australia’s shellfish ecosystems.

Previous research (e.g., Woodward & Baxter, 1997) found that Standards-based mathematics teaching provides marginal or no benefits for low achievers, in contrast with positive effects for middle and high ability students. A randomized quasi-experiment in 52 Canadian schools found that low achieving grade 7 and 8 students who received support consisting of placement on a learning continuum, instruction focused on their specific learning needs, and concrete materials to represent mathematical constructs, benefited from teaching that emphasized construction over transmission of knowledge. Treatment students showed small but statistically significant improvements over controls in student achievement, and controversially, in mathematical beliefs, and attitudes. The latter finding raised issues of the appropriate balance between Type I and Type II error in educational research.

Detailed electrocardiographic (ECG) support was provided to a first-in-man, single-ascending-dose study that included 6 cohorts of 8 male volunteers each. In each cohort, 6 and 2 subjects received active compound and placebo, respectively. Long-term 12-lead ECGs were obtained on baseline day -1, dosing day 1, and day 2. Automatic QT-interval measurements were made at 63 time points (28 at baseline and 35 on treatment). Based on QT/RR distribution, 20% of measurements were visually verified. Baseline-corrected time-matched DeltaQTc values were obtained at 35 postdose time points. Placebo subjects of all cohorts were pooled. When 2 cohorts of the lowest, middle, and highest doses were pooled (12 subjects per active treatment group), the spreads of placebo-corrected DeltaDeltaQTc values were within the regulatory requirements (single-sided 95% confidence interval

The Green Bank Telescope is a large flexible structure, requiring rms tracking error ≤ 3 arcseconds against internal and external disturbances. We design an extended state observer (ESO) based controller in various configurations to improve tracking performance and increase disturbance rejection. The controllers are simulated with an experimentally validated model of the GBT. Through the simulations, the response of ESO based controllers and legacy PID controller are compared using time and frequency domain responses. We show that the ESO based controller when implemented in both position and velocity loop can give significant improvement in tracking performance and better disturbance rejection without increase in controller output.Copyright © 2015 by ASME

When Robert Fleetcroft and colleagues attempted a systematic review of the treatment of heart failure, they were unable to answer their research question because of poor reporting and non-disclosure of data. And yet the necessary studies had been done. Here they discuss their experience and possible solutions

Background Seven-day opening in primary care is a key policy for the UK government. However, it is unclear if weekend opening will meet patients’ needs or lead to additional demand. Aim To identify patient groups most likely to use weekend opening in primary care. Design and setting The General Practice Patient Survey 2014, which sampled from all general practices in England, was used. Method Logistic regression was used to measure the associations between perceived benefit from seeing or speaking to someone at the weekend and age, sex, deprivation, health conditions, functioning, work status, rurality, and quality of life. Results Out of 881 183 participants who responded to the questionnaire, 712 776 (80.9%) did not report any problems with opening times. Of the 168 407 responders (19.1%) who reported inconvenient opening times, 73.9% stated that Saturday opening, and 35.8% Sunday opening, would make it easier for them to see or speak to someone. Only 2.2% of responders reported that Sunday, but not Saturday, opening would make it easier for them. Younger people, those who work full time, and those who could not get time off work were more likely to report that weekend opening would help. People with Alzheimer’s disease, learning difficulties, or problems with walking, washing, or dressing were less likely to report that weekend opening would help. Conclusion Most people do not think they need weekend opening, but it may benefit certain patient groups, such as younger people in full-time work. Sunday opening, in addition to Saturday, is unlikely to improve access.

Background Access to general practices may be an important determinant of emergency admissions for asthma, as early treatment of exacerbations has been shown to prevent deterioration. Aim To determine whether access to primary care is associated with emergency admissions for asthma. Design and setting Cross-sectional analysis of data from English practices in 2010–2011. Method Negative binomial regression was used to explore the associations between emergency admissions for asthma and seven measures of patient-reported access to general practice services taken from the GP Patient Survey, controlled for the characteristics of practice populations. Incidence rate ratios (IRR) were calculated for each association. Results In total 7806 (95%) of practices had data for all variables. There were 3 134 106 patients with asthma, and there were 55 570 emergency admissions with asthma. Admission rates were lower in practices with a higher composite access score (adjusted IRR for 10% change in variable 0.679, 95% CI = 0.665 to 0.708). Admissions were higher in those practices with higher proportions of the practice population who were white, and in practices with lower performance in the Quality and Outcomes Framework indicator ‘asthma review in past 15 months’ (Asthma 6). Assuming these associations were causal, a higher access score of 10% was associated with a decrease of 17 837 admissions per year for these practices. Conclusion Practices with higher patient-reported access had lower rates of emergency admissions for asthma. Policymakers should consider improving access to primary care as one potential way to help prevent emergency hospital admissions for asthma.