1,061,482 research outputs found

    No Evidence for Dark Energy Dynamics from a Global Analysis of Cosmological Data

    Full text link
    We use a variant of principal component analysis to investigate the possible temporal evolution of the dark energy equation of state, w(z). We constrain w(z) in multiple redshift bins, utilizing the most recent data from Type Ia supernovae, the cosmic microwave background, baryon acoustic oscillations, the integrated Sachs-Wolfe effect, galaxy clustering, and weak lensing data. Unlike other recent analyses, we find no significant evidence for evolving dark energy; the data remains completely consistent with a cosmological constant. We also study the extent to which the time-evolution of the equation of state would be constrained by a combination of current- and future-generation surveys, such as Planck and the Joint Dark Energy Mission.Comment: 6 pages, 5 figure

    Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

    Get PDF
    Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

    Decellularization and Delipidation Protocols of Bovine Bone and Pericardium for Bone Grafting and Guided Bone Regeneration Procedures

    Get PDF
    The combination of bone grafting materials with guided bone regeneration (GBR) membranes seems to provide promising results to restore bone defects in dental clinical practice. In the first part of this work, a novel protocol for decellularization and delipidation of bovine bone, based on multiple steps of thermal shock, washes with detergent and dehydration with alcohol, is described. This protocol is more effective in removal of cellular materials, and shows superior biocompatibility compared to other three methods tested in this study. Furthermore, histological and morphological analyses confirm the maintenance of an intact bone extracellular matrix (ECM). In vitro and in vivo experiments evidence osteoinductive and osteoconductive properties of the produced scaffold, respectively. In the second part of this study, two methods of bovine pericardium decellularization are compared. The osmotic shock-based protocol gives better results in terms of removal of cell components, biocompatibility, maintenance of native ECM structure, and host tissue reaction, in respect to the freeze/thaw method. Overall, the results of this study demonstrate the characterization of a novel protocol for the decellularization of bovine bone to be used as bone graft, and the acquisition of a method to produce a pericardium membrane suitable for GBR applications

    Evidence-based prescribing: combining network meta-analysis with multicriteria decision analysis to choose among multiple drugs

    Get PDF
    What is the drug of choice for condition x? is among the most commonly asked questions in primary care.1 Reflecting the complexity of prescribing decisions, answering this question requires a difficult trade-off between the benefits and harms of multiple drugs for a given condition. The principles of evidence-based medicine suggest that prescribing decisions should be guided by an objective benchmark, namely scientific evidence.2 Such evidence is particularly important when choosing a first-line treatment among multiple alternatives. Unfortunately, existing clinical evidence on benefits and harms is rarely adequate to inform prescribing decisions. A randomized controlled trial comparing all relevant drugs would provide such information. However, clinical trials are often designed for regulatory purposes and, therefore, include selective patient populations and do not include all available comparator drugs.3,4 To obtain insight into the comparative benefits and harms of multiple drugs, prescribers turn to summaries of evidence to discern the most promising drugs from their less effective comparators. Recent methods used to synthesize existing evidence provide much-needed information on the comparative benefits and harms of multiple drugs. Network meta-analysis is one such method that allows for the combination of direct and indirect evidences from randomized trials, facilitating the comparison of all relevant drugs even when they are not directly compared with each other in clinical trials.5 The recent surge in the number of network meta-analyses in the general medical literature is a testament to the increasing need for comparative evidence in prescribing decisions

    The Complex Demographic History and Evolutionary Origin of the Western Honey Bee, Apis Mellifera.

    Get PDF
    The western honey bee, Apis mellifera, provides critical pollination services to agricultural crops worldwide. However, despite substantial interest and prior investigation, the early evolution and subsequent diversification of this important pollinator remain uncertain. The primary hypotheses place the origin of A. mellifera in either Asia or Africa, with subsequent radiations proceeding from one of these regions. Here, we use two publicly available whole-genome data sets plus newly sequenced genomes and apply multiple population genetic analysis methods to investigate the patterns of ancestry and admixture in native honey bee populations from Europe, Africa, and the Middle East. The combination of these data sets is critical to the analyses, as each contributes samples from geographic locations lacking in the other, thereby producing the most complete set of honey bee populations available to date. We find evidence supporting an origin of A. mellifera in the Middle East or North Eastern Africa, with the A and Y lineages representing the earliest branching lineages. This finding has similarities with multiple contradictory hypotheses and represents a disentangling of genetic relationships, geographic proximity, and secondary contact to produce a more accurate picture of the origins of A. mellifera. We also investigate how previous studies came to their various conclusions based on incomplete sampling of populations, and illustrate the importance of complete sampling in understanding evolutionary processes. These results provide fundamental knowledge about genetic diversity within Old World honey bee populations and offer insight into the complex history of an important pollinator

    Drawing together multiple lines of evidence from assessment studies of hydropeaking pressures in impacted rivers

    Get PDF
    Hydropeaking has negative effects on aquatic biota, but the causal relationships have not been studied extensively, especially when hydropeaking occurs in combination with other environmental pressures. The available evidence comes mainly from case studies demonstrating river-specific effects of hydropeaking that result in modified microhabitat conditions and lead to declines in fish populations. We used multiple lines of evidence to attempt to strengthen the evidence base for models of ecological response to flow alteration from hydropeaking. First, we synthesized evidence of ecological responses from relevant studies published in the scientific literature. We found considerable evidence of the ecological effects of hydropeaking, but many causal pathways are poorly understood, and we found very little research on the interactive effects of hydropeaking and other pressures. As a 2nd line of evidence, we used results from analyses of large-scale data sets. These results demonstrated the extent to which hydropeaking occurs with other pressures, but did not elucidate individual or interactive effects further. Thus, the multiple lines of evidence complemented each other, but the main result was to identify knowledge gaps regarding hydropeaking and a consequent pressing need for novel approaches, new questions, and new ways of thinking that can fill them.© 2017 by The Society for Freshwater Science.publishedVersio

    Organizational Commitment: Do Workplace Practices Matter?

    Get PDF
    Using nationally-representative linked employer-employee data for Britain this paper considers whether employers are able to influence the organizational commitment (OC) of their employees through the practices they deploy. We examine the association between OC and two broad groups of HRM practices emphasised in two different strands of the literature, namely "High-Performance Workplace Practices" (HPWPs) and practices associated with "Perceived Organizational Support" (POS). We consider their associations with mean workplace-level OC and individual employees' OC. Although employers may be able to engender greater OC on the part of their employees, the practices that do so are not those emphasized in the HPWP literature, with the exception of consultation and the involvement of employees in decision-taking. POS practices fare a little better but, again, the findings are far from unequivocal. Furthermore, those practices that are 'effective' in engendering higher OC such as tolerance of absence, recruiting on 'values' and allowing employees to make decisions, tend to have a fairly low incidence in British workplaces. There is, however, one finding which chimes with the ideas underpinning the HPWP literature, namely that there are returns to the use of practices in combination. Analyses of both mean workplace-level OC and individual employee OC find an independent positive association between OC and the deployment of multiple practices in combination. This evidence is consistent with practices having synergies, as emphasised in some of the HPWP literature.high performance, organizational commitment, perceived organizational support
    • 

    corecore