Showing papers by "Queen's University Belfast published in 2014"

Biological insights from 108 schizophrenia-associated genetic loci

Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

Defining the role of common variation in the genomic and biological architecture of adult human height

Abstract: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

STOPP/START criteria for potentially inappropriate prescribing in older people: version 2

Abstract: Purpose: screening tool of older people’s prescriptions (STOPP) and screening tool to alert to right treatment (START) criteria were first published in 2008. Due to an expanding therapeutics evidence base, updating of the criteria was required. Methods: we reviewed the 2008 STOPP/START criteria to add new evidence-based criteria and remove any obsolete criteria. A thorough literature review was performed to reassess the evidence base of the 2008 criteria and the proposed new criteria. Nineteen experts from 13 European countries reviewed a new draft of STOPP & START criteria including proposed new criteria. These experts were also asked to propose additional criteria they considered important to include in the revised STOPP & START criteria and to highlight any criteria from the 2008 list they considered less important or lacking an evidence base. The revised list of criteria was then validated using the Delphi consensus methodology. Results: the expert panel agreed a final list of 114 criteria after two Delphi validation rounds, i.e. 80 STOPP criteria and 34 START criteria. This represents an overall 31% increase in STOPP/START criteria compared with version 1. Several new STOPP categories were created in version 2, namely antiplatelet/anticoagulant drugs, drugs affecting, or affected by, renal function and drugs that increase anticholinergic burden; new START categories include urogenital system drugs, analgesics and vaccines. Conclusion: STOPP/START version 2 criteria have been expanded and updated for the purpose of minimizing inappropriate prescribing in older people. These criteria are based on an up-to-date literature review and consensus validation among a European panel of experts.

Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

Abstract: Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This s ...

Choosing and using diversity indices: Insights for ecological applications from the German Biodiversity Exploratories

Abstract: Biodiversity, a multidimensional property of natural systems, is difficult to quantify partly because of the multitude of indices proposed for this purpose. Indices aim to describe general properties of communities that allow us to compare different regions, taxa, and trophic levels. Therefore, they are of fundamental importance for environmental monitoring and conservation, although there is no consensus about which indices are more appropriate and informative. We tested several common diversity indices in a range of simple to complex statistical analyses in order to determine whether some were better suited for certain analyses than others. We used data collected around the focal plant Plantago lanceolata on 60 temperate grassland plots embedded in an agricultural landscape to explore relationships between the common diversity indices of species richness (S), Shannon's diversity (H'), Simpson's diversity (D-1), Simpson's dominance (D-2), Simpson's evenness (E), and Berger-Parker dominance (BP). We calculated each of these indices for herbaceous plants, arbuscular mycorrhizal fungi, aboveground arthropods, belowground insect larvae, and P.lanceolata molecular and chemical diversity. Including these trait-based measures of diversity allowed us to test whether or not they behaved similarly to the better studied species diversity. We used path analysis to determine whether compound indices detected more relationships between diversities of different organisms and traits than more basic indices. In the path models, more paths were significant when using H', even though all models except that with E were equally reliable. This demonstrates that while common diversity indices may appear interchangeable in simple analyses, when considering complex interactions, the choice of index can profoundly alter the interpretation of results. Data mining in order to identify the index producing the most significant results should be avoided, but simultaneously considering analyses using multiple indices can provide greater insight into the interactions in a system.

Ultrafast electron dynamics in phenylalanine initiated by attosecond pulses

Abstract: In the past decade, attosecond technology has opened up the investigation of ultrafast electronic processes in atoms, simple molecules, and solids. Here, we report the application of isolated attosecond pulses to prompt ionization of the amino acid phenylalanine and the subsequent detection of ultrafast dynamics on a sub–4.5-femtosecond temporal scale, which is shorter than the vibrational response of the molecule. The ability to initiate and observe such electronic dynamics in polyatomic molecules represents a crucial step forward in attosecond science, which is progressively moving toward the investigation of more and more complex systems.

Interventions to improve the appropriate use of polypharmacy for older people

Abstract: Background Inappropriate polypharmacy is a particular concern in older people and is associated with negative health outcomes. Choosing the best interventions to improve appropriate polypharmacy is a priority, hence interest in appropriate polypharmacy, where many medicines may be used to achieve better clinical outcomes for patients, is growing. Objectives This review sought to determine which interventions, alone or in combination, are effective in improving the appropriate use of polypharmacy and reducing medication-related problems in older people. Search methods In November 2013, for this first update, a range of literature databases including MEDLINE and EMBASE were searched, and handsearching of reference lists was performed. Search terms included 'polypharmacy', 'medication appropriateness' and 'inappropriate prescribing'. Selection criteria A range of study designs were eligible. Eligible studies described interventions affecting prescribing aimed at improving appropriate polypharmacy in people 65 years of age and older in which a validated measure of appropriateness was used (e.g. Beers criteria, Medication Appropriateness Index (MAI)). Data collection and analysis Two review authors independently reviewed abstracts of eligible studies, extracted data and assessed risk of bias of included studies. Study-specific estimates were pooled, and a random-effects model was used to yield summary estimates of effect and 95% confidence intervals (CIs). The GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach was used to assess the overall quality of evidence for each pooled outcome. Main results Two studies were added to this review to bring the total number of included studies to 12. One intervention consisted of computerised decision support; 11 complex, multi-faceted pharmaceutical approaches to interventions were provided in a variety of settings. Interventions were delivered by healthcare professionals, such as prescribers and pharmacists. Appropriateness of prescribing was measured using validated tools, including the MAI score post intervention (eight studies), Beers criteria (four studies), STOPP criteria (two studies) and START criteria (one study). Interventions included in this review resulted in a reduction in inappropriate medication usage. Based on the GRADE approach, the overall quality of evidence for all pooled outcomes ranged from very low to low. A greater reduction in MAI scores between baseline and follow-up was seen in the intervention group when compared with the control group (four studies; mean difference -6.78, 95% CI -12.34 to -1.22). Postintervention pooled data showed a lower summated MAI score (five studies; mean difference -3.88, 95% CI -5.40 to -2.35) and fewer Beers drugs per participant (two studies; mean difference -0.1, 95% CI -0.28 to 0.09) in the intervention group compared with the control group. Evidence of the effects of interventions on hospital admissions (five studies) and of medication-related problems (six studies) was conflicting. Authors' conclusions It is unclear whether interventions to improve appropriate polypharmacy, such as pharmaceutical care, resulted in clinically significant improvement; however, they appear beneficial in terms of reducing inappropriate prescribing.

The timing and spatiotemporal patterning of Neanderthal disappearance

Abstract: The timing of Neanderthal disappearance and the extent to which they overlapped with the earliest incoming anatomically modern humans (AMHs) in Eurasia are key questions in palaeoanthropology. Determining the spatiotemporal relationship between the two populations is crucial if we are to understand the processes, timing and reasons leading to the disappearance of Neanderthals and the likelihood of cultural and genetic exchange. Serious technical challenges, however, have hindered reliable dating of the period, as the radiocarbon method reaches its limit at ∼50,000 years ago. Here we apply improved accelerator mass spectrometry (14)C techniques to construct robust chronologies from 40 key Mousterian and Neanderthal archaeological sites, ranging from Russia to Spain. Bayesian age modelling was used to generate probability distribution functions to determine the latest appearance date. We show that the Mousterian ended by 41,030-39,260 calibrated years bp (at 95.4% probability) across Europe. We also demonstrate that succeeding 'transitional' archaeological industries, one of which has been linked with Neanderthals (Châtelperronian), end at a similar time. Our data indicate that the disappearance of Neanderthals occurred at different times in different regions. Comparing the data with results obtained from the earliest dated AMH sites in Europe, associated with the Uluzzian technocomplex, allows us to quantify the temporal overlap between the two human groups. The results reveal a significant overlap of 2,600-5,400 years (at 95.4% probability). This has important implications for models seeking to explain the cultural, technological and biological elements involved in the replacement of Neanderthals by AMHs. A mosaic of populations in Europe during the Middle to Upper Palaeolithic transition suggests that there was ample time for the transmission of cultural and symbolic behaviours, as well as possible genetic exchanges, between the two groups.

Trust, satisfaction, and online repurchase intention: the moderating role of perceived effectiveness of E-commerce institutional mechanisms

Abstract: The effects of e-commerce institutional mechanisms on trust and online purchase have traditionally been understood in the initial online purchase context. This study extends this literature by exploring the role of e-commerce institutional mechanisms in the online repurchase context. In doing so, it responds to the emerging call for understanding the institutional context under which customer trust operates in an e-commerce environment. Specifically, this study introduces a key moderator, perceived effectiveness of e-commerce institutional mechanisms (PEEIM), to the relationships between trust, satisfaction, and repurchase intention. Drawing on the theory of organizational trust, and based on a survey of 362 returning online customers, we find that PEEIM negatively moderates the relationship between trust in an online vendor and online customer repurchase intention, as it decreases the importance of trust to promoting repurchase behavior. We also find that PEEIM positively moderates the relationship between customer satisfaction and trust as it enhances the customer's reliance on past transaction experience with the vendor to reevaluate trust in the vendor. Consistent with the predictions made in the literature, PEEIM does not directly affect trust or repurchase intention. Academic and practical implications and future research directions are discussed.

Disease associations between honeybees and bumblebees as a threat to wild pollinators

Abstract: Emerging infectious diseases (EIDs) pose a risk to human welfare, both directly and indirectly, by affecting managed livestock and wildlife that provide valuable resources and ecosystem services, such as the pollination of crops. Honeybees (Apis mellifera), the prevailing managed insect crop pollinator, suffer from a range of emerging and exotic high-impact pathogens, and population maintenance requires active management by beekeepers to control them. Wild pollinators such as bumblebees (Bombus spp.) are in global decline, one cause of which may be pathogen spillover from managed pollinators like honeybees or commercial colonies of bumblebees. Here we use a combination of infection experiments and landscape-scale field data to show that honeybee EIDs are indeed widespread infectious agents within the pollinator assemblage. The prevalence of deformed wing virus (DWV) and the exotic parasite Nosema ceranae in honeybees and bumblebees is linked; as honeybees have higher DWV prevalence, and sympatric bumblebees and honeybees are infected by the same DWV strains, Apis is the likely source of at least one major EID in wild pollinators. Lessons learned from vertebrates highlight the need for increased pathogen control in managed bee species to maintain wild pollinators, as declines in native pollinators may be caused by interspecies pathogen transmission originating from managed pollinators.

Power Scaling of Uplink Massive MIMO Systems With Arbitrary-Rank Channel Means

Abstract: This paper investigates the uplink achievable rates of massive multiple-input multiple-output (MIMO) antenna systems in Ricean fading channels, using maximal-ratio combining (MRC) and zero-forcing (ZF) receivers, assuming perfect and imperfect channel state information (CSI). In contrast to previous relevant works, the fast fading MIMO channel matrix is assumed to have an arbitrary-rank deterministic component as well as a Rayleigh-distributed random component. We derive tractable expressions for the achievable uplink rate in the large-antenna limit, along with approximating results that hold for any finite number of antennas. Based on these analytical results, we obtain the scaling law that the users' transmit power should satisfy, while maintaining a desirable quality of service. In particular, it is found that regardless of the Ricean K-factor, in the case of perfect CSI, the approximations converge to the same constant value as the exact results, as the number of base station antennas,, grows large, while the transmit power of each user can be scaled down proportionally to. If CSI is estimated with uncertainty, the same result holds true but only when the Ricean K-factor is non-zero. Otherwise, if the channel experiences Rayleigh fading, we can only cut the transmit power of each user proportionally to 1 root M. In addition, we show that with an increasing Ricean K-factor, the uplink rates will converge to fixed values for both MRC and ZF receivers.

Secondary prevention in the clinical management of patients with cardiovascular diseases. Core components, standards and outcome measures for referral and delivery: A Policy Statement from the Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation. Endorsed by the Committee for Practice Guidelines of the European Society of Cardiology

Abstract: Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic burden both in western and developing countries, in which this burden is increasing in close correlation to economic growth Health authorities and the general population have started to recognize that the fight against these diseases can only be won if their burden is faced by increasing our investment on interventions in lifestyle changes and prevention There is an overwhelming evidence of the efficacy of secondary prevention initiatives including cardiac rehabilitation in terms of reduction in morbidity and mortality However, secondary prevention is still too poorly implemented in clinical practice, often only on selected populations and over a limited period of time The development of systematic and full comprehensive preventive programmes is warranted, integrated in the organization of national health systems Furthermore, systematic monitoring of the process of delivery and outcomes is a necessity Cardiology and secondary prevention, including cardiac rehabilitation, have evolved almost independently of each other and although each makes a unique contribution it is now time to join forces under the banner of preventive cardiology and create a comprehensive model that optimizes long term outcomes for patients and reduces the future burden on health care services These are the aims that the Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation has foreseen to promote secondary preventive cardiology in clinical practice

Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease

Abstract: Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.

Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial

Abstract: Summary Background Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range α-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases. Methods In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2:1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Findings Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo. Symptomatic skeletal events occurred in 202 (33%) of 614 patients in the radium-223 group and 116 (38%) of 307 patients in the placebo group. Time to first symptomatic skeletal event was longer with radium-223 than with placebo (median 15·6 months [95% CI 13·5–18·0] vs 9·8 months [7·3–23·7]; hazard ratio [HR]=0·66, 95% CI 0·52–0·83; p=0·00037). The risks of external beam radiation therapy for bone pain (HR 0·67, 95% CI 0·53–0·85) and spinal cord compression (HR=0·52, 95% CI 0·29–0·93) were reduced with radium-233 compared with placebo. Radium-223 treatment did not seem to significantly reduce the risk of symptomatic pathological bone fracture (HR 0·62, 95% CI 0·35–1·09), or the need for tumour-related orthopaedic surgical intervention (HR 0·72, 95% CI 0·28–1·82). Interpretation Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases. Funding Algeta and Bayer HealthCare Pharmaceuticals.

Multipair Full-Duplex Relaying With Massive Arrays and Linear Processing

Abstract: We consider a multipair decode-and-forward relay channel, where multiple sources transmit simultaneously their signals to multiple destinations with the help of a full-duplex relay station. We assume that the relay station is equipped with massive arrays, while all sources and destinations have a single antenna. The relay station uses channel estimates obtained from received pilots and zero-forcing (ZF) or maximum-ratio combining/maximum-ratio transmission (MRC/MRT) to process the signals. To significantly reduce the loop interference effect, we propose two techniques: i) using a massive receive antenna array; or ii) using a massive transmit antenna array together with very low transmit power at the relay station. We derive an exact achievable rate expression in closed-form for MRC/MRT processing and an analytical approximation of the achievable rate for ZF processing. This approximation is very tight, particularly for a large number of relay station antennas. These closed-form expressions enable us to determine the regions where the full-duplex mode outperforms the half-duplex mode, as well as to design an optimal power allocation scheme. This optimal power allocation scheme aims to maximize the energy efficiency for a given sum spectral efficiency and under peak power constraints at the relay station and sources. Numerical results verify the effectiveness of the optimal power allocation scheme. Furthermore, we show that, by doubling the number of transmit/receive antennas at the relay station, the transmit power of each source and of the relay station can be reduced by 1.5 dB if the pilot power is equal to the signal power, and by 3 dB if the pilot power is kept fixed, while maintaining a given quality of service.

Accountability and the Promise of Performance: In Search of the Mechanisms

Abstract: In an effort to determine the basis for the assumed relationship between accountability and performance that pervades much of contemporary administrative reform efforts, this paper applies a "social mechanisms" approach to elaborate the factors that might be involved in account giving and various forms of administrative performance. This search for mechanisms indicates that the relationship is paradoxical and either spurious or so contingent as to raise questions regarding administrative reforms based on it. Various theoretical approaches for dealing with the relationship are considered.

Cosmological Constraints from Measurements of Type Ia Supernovae Discovered During the First 1.5 Yr of the Pan-STARRS1 Survey

Abstract: We present griz P1 light curves of 146 spectroscopically confirmed Type Ia supernovae (SNe Ia; 0.03 < z < 0.65) discovered during the first 1.5 yr of the Pan-STARRS1 Medium Deep Survey. The Pan-STARRS1 natural photometric system is determined by a combination of on-site measurements of the instrument response function and observations of spectrophotometric standard stars. We find that the systematic uncertainties in the photometric system are currently 1.2% without accounting for the uncertainty in the Hubble Space Telescope Calspec definition of the AB system. A Hubble diagram is constructed with a subset of 113 out of 146 SNe Ia that pass our light curve quality cuts. The cosmological fit to 310 SNe Ia (113 PS1 SNe Ia + 222 light curves from 197 low-z SNe Ia), using only supernovae (SNe) and assuming a constant dark energy equation of state and flatness, yields $w=-1.120^{+0.360}_{-0.206}\hbox{(Stat)} ^{+0.269}_{-0.291}\hbox{(Sys)}$. When combined with BAO+CMB(Planck)+H 0, the analysis yields $\Omega _{\rm M}=0.280^{+0.013}_{-0.012}$ and $w=-1.166^{+0.072}_{-0.069}$ including all identified systematics. The value of w is inconsistent with the cosmological constant value of –1 at the 2.3σ level. Tension endures after removing either the baryon acoustic oscillation (BAO) or the H 0 constraint, though it is strongest when including the H 0 constraint. If we include WMAP9 cosmic microwave background (CMB) constraints instead of those from Planck, we find $w=-1.124^{+0.083}_{-0.065}$, which diminishes the discord to <2σ. We cannot conclude whether the tension with flat ΛCDM is a feature of dark energy, new physics, or a combination of chance and systematic errors. The full Pan-STARRS1 SN sample with ~three times as many SNe should provide more conclusive results.

Validity of the Global Physical Activity Questionnaire (GPAQ) in assessing levels and change in moderate-vigorous physical activity and sedentary behaviour

Abstract: Background: Feasible, cost-effective instruments are required for the surveillance of moderate-to-vigorous physical activity (MVPA) and sedentary behaviour (SB) and to assess the effects of interventions. However, the evidence base for the validity and reliability of the World Health Organisation-endorsed Global Physical Activity Questionnaire (GPAQ) is limited. We aimed to assess the validity of the GPAQ, compared to accelerometer data in measuring and assessing change in MVPA and SB. Methods: Participants (n = 101) were selected randomly from an on-going research study, stratified by level of physical activity (low, moderate or highly active, based on the GPAQ) and sex. Participants wore an accelerometer (Actigraph GT3X) for seven days and completed a GPAQ on Day 7. This protocol was repeated for a random sub-sample at a second time point, 3–6 months later. Analysis involved Wilcoxon-signed rank tests for differences in measures, Bland-Altman analysis for the agreement between measures for median MVPA and SB mins/day, and Spearman’s rho coefficient for criterion validity and extent of change. Results: 95 participants completed baseline measurements (44 females, 51 males; mean age 44 years, (SD 14); measurements of change were calculated for 41 (21 females, 20 males; mean age 46 years, (SD 14). There was moderate agreement between GPAQ and accelerometer for MVPA mins/day (r = 0.48) and poor agreement for SB (r = 0.19). The absolute mean difference (self-report minus accelerometer) for MVPA was �0.8 mins/day and 348.7 mins/day for SB; and negative bias was found to exist, with those people who were more physically active over-reporting their level of MVPA: those who were more sedentary were less likely to under-report their level of SB. Results for agreement in change over time showed moderate correlation (r = 0.52, p = 0.12) for MVPA and poor correlation for SB (r =�0.024, p = 0.916). Conclusions: Levels of agreement with objective measurements indicate the GPAQ is a valid measure of MVPA and change in MVPA but is a less valid measure of current levels and change in SB. Thus, GPAQ appears to be an appropriate measure for assessing the effectiveness of interventions to promote MVPA.

Changing the intellectual climate

Abstract: Calls for more broad-based, integrated, useful knowledge now abound in the world of global environmental change science. They evidence many scientists' desire to help humanity confront the momentous biophysical implications of its own actions. But they also reveal a limited conception of social science and virtually ignore the humanities. They thereby endorse a stunted conception of 'human dimensions' at a time when the challenges posed by global environmental change are increasing in magnitude, scale and scope. Here, we make the case for a richer conception predicated on broader intellectual engagement and identify some preconditions for its practical fulfilment. Interdisciplinary dialogue, we suggest, should engender plural representations of Earth's present and future that are reflective of divergent human values and aspirations. In turn, this might insure publics and decision-makers against overly narrow conceptions of what is possible and desirable as they consider the profound questions raised by global environmental change.

Reducing implicit racial preferences: I. A comparative investigation of 17 interventions.

Abstract: Many methods for reducing implicit prejudice have been identified, but little is known about their relative effectiveness. We held a research contest to experimentally compare interventions for reducing the expression of implicit racial prejudice. Teams submitted 17 interventions that were tested an average of 3.70 times each in 4 studies (total N = 17,021), with rules for revising interventions between studies. Eight of 17 interventions were effective at reducing implicit preferences for Whites compared with Blacks, particularly ones that provided experience with counterstereotypical exemplars, used evaluative conditioning methods, and provided strategies to override biases. The other 9 interventions were ineffective, particularly ones that engaged participants with others' perspectives, asked participants to consider egalitarian values, or induced a positive emotion. The most potent interventions were ones that invoked high self-involvement or linked Black people with positivity and White people with negativity. No intervention consistently reduced explicit racial preferences. Furthermore, intervention effectiveness only weakly extended to implicit preferences for Asians and Hispanics.

Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States

Abstract: Objective To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences. Design Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US. Setting General population. Participants 26 018 men and women aged 50-79 years Main outcome measures All-cause, cardiovascular, and cancer mortality. Results 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses. Conclusions Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.

Experimental reconstruction of work distribution and study of fluctuation relations in a closed quantum system.

Abstract: We report the experimental reconstruction of the nonequilibrium work probability distribution in a closed quantum system, and the study of the corresponding quantum fluctuation relations. The experiment uses a liquid-state nuclear magnetic resonance platform that offers full control on the preparation and dynamics of the system. Our endeavors enable the characterization of the out-of-equilibrium dynamics of a quantum spin from a finite-time thermodynamics viewpoint.

AVEC 2014: 3D Dimensional Affect and Depression Recognition Challenge

Abstract: Mood disorders are inherently related to emotion. In particular, the behaviour of people suffering from mood disorders such as unipolar depression shows a strong temporal correlation with the affective dimensions valence, arousal and dominance. In addition to structured self-report questionnaires, psychologists and psychiatrists use in their evaluation of a patient's level of depression the observation of facial expressions and vocal cues. It is in this context that we present the fourth Audio-Visual Emotion recognition Challenge (AVEC 2014). This edition of the challenge uses a subset of the tasks used in a previous challenge, allowing for more focussed studies. In addition, labels for a third dimension (Dominance) have been added and the number of annotators per clip has been increased to a minimum of three, with most clips annotated by 5. The challenge has two goals logically organised as sub-challenges: the first is to predict the continuous values of the affective dimensions valence, arousal and dominance at each moment in time. The second is to predict the value of a single self-reported severity of depression indicator for each recording in the dataset. This paper presents the challenge guidelines, the common data used, and the performance of the baseline system on the two tasks.

Simvastatin in the Acute Respiratory Distress Syndrome

Abstract: BACKGROUND Studies in animals and in vitro and phase 2 studies in humans suggest that statins may be beneficial in the treatment of the acute respiratory distress syndrome (ARDS). This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS. METHODS In this multicenter, double-blind clinical trial, we randomly assigned (in a 1:1 ratio) patients with an onset of ARDS within the previous 48 hours to receive enteral simvastatin at a dose of 80 mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator-free days to day 28. Secondary outcomes included the number of days free of nonpulmonary organ failure to day 28, mortality at 28 days, and safety. RESULTS The study recruited 540 patients, with 259 patients assigned to simvastatin and 281 to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P = 0.21) or days free of nonpulmonary organ failure (19.4±11.1 and 17.8±11.7, respectively; P = 0.11) or in mortality at 28 days (22.0% and 26.8%, respectively; P = 0.23). There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug. CONCLUSIONS Simvastatin therapy, although safe and associated with minimal adverse effects, did not improve clinical outcomes in patients with ARDS. (Funded by the U.K. National Institute for Health Research Efficacy and Mechanism Evaluation Programme and others; HARP-2 Current Controlled Trials number, ISRCTN88244364.)

Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial

Abstract: Summary Background Primary results from the phase 3 ALSYMPCA trial showed that radium-223 dichloride (radium-223), a targeted α-emitter, improved overall survival compared with placebo and was well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases. We did a prespecified subgroup analysis from ALSYMPCA to assess the effect of previous docetaxel use on the efficacy and safety of radium-223. Methods In the phase 3, randomised, double-blind ALSYMPCA trial, patients with symptomatic castration-resistant prostate cancer, at least two symptomatic bone metastases, no known visceral metastases, and who were receiving best standard of care were randomly assigned (2:1) via an interactive voice response system to receive six injections of radium-223 (50 kBq/kg intravenously) or matching placebo, with one injection given every 4 weeks. Patients had either received previous docetaxel treatment or were unsuitable for or declined docetaxel; previous docetaxel use (yes or no) was a trial stratification factor. We investigated the effect of previous docetaxel use on radium-223 treatment for the primary endpoint of overall survival, the main secondary efficacy endpoints, and safety. Efficacy analyses were done for the intention-to-treat population; safety analyses were done for the safety population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Findings Randomisation took place between June 12, 2008, and Feb 1, 2011. 526 (57%) of 921 randomly assigned patients had received previous docetaxel treatment (352 in the radium-223 group and 174 in the placebo group) and 395 (43%) had not (262 in the radium-223 group and 133 in the placebo group). Radium-223 prolonged median overall survival compared with placebo, irrespective of previous docetaxel use (previous docetaxel use, hazard ratio [HR] 0·70, 95% CI 0·56–0·88; p=0·002; no previous docetaxel use, HR 0·69, 0·52–0·92; p=0·01). The benefit of radium-223 compared with placebo was seen in both docetaxel subgroups for most main secondary efficacy endpoints; risk for time to time to first symptomatic skeletal event was reduced with radium-223 versus placebo in patients with previous docetaxel use, but the difference was not significant in those with no previous docetaxel use. 322 (62%) of 518 patients previously treated with docetaxel had grade 3–4 adverse events, compared with 205 (54%) of 383 patients without docetaxel. Patients who had previously been treated with docetaxel had a higher incidence of grade 3–4 thrombocytopenia with radium-223 than with placebo (31 [9%] of 347 patients vs five [3%] of 171 patients), whereas the incidence was similar between treatment groups among patients with no previous docetaxel use (seven [3%] of 253 patients vs one [1%] of 130 patients). The incidences of grade 3–4 anaemia and neutropenia were similar between the radium-223 and placebo groups within both docetaxel subgroups. Interpretation Radium-223 is effective and well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases, irrespective of previous docetaxel use. Funding Algeta ASA and Bayer HealthCare Pharmaceuticals.