2,902 research outputs found

    Measurement error in a multi-level analysis of air pollution and health: a simulation study.

    Get PDF
    BACKGROUND: Spatio-temporal models are increasingly being used to predict exposure to ambient outdoor air pollution at high spatial resolution for inclusion in epidemiological analyses of air pollution and health. Measurement error in these predictions can nevertheless have impacts on health effect estimation. Using statistical simulation we aim to investigate the effects of such error within a multi-level model analysis of long and short-term pollutant exposure and health. METHODS: Our study was based on a theoretical sample of 1000 geographical sites within Greater London. Simulations of "true" site-specific daily mean and 5-year mean NO2 and PM10 concentrations, incorporating both temporal variation and spatial covariance, were informed by an analysis of daily measurements over the period 2009-2013 from fixed location urban background monitors in the London area. In the context of a multi-level single-pollutant Poisson regression analysis of mortality, we investigated scenarios in which we specified: the Pearson correlation between modelled and "true" data and the ratio of their variances (model versus "true") and assumed these parameters were the same spatially and temporally. RESULTS: In general, health effect estimates associated with both long and short-term exposure were biased towards the null with the level of bias increasing to over 60% as the correlation coefficient decreased from 0.9 to 0.5 and the variance ratio increased from 0.5 to 2. However, for a combination of high correlation (0.9) and small variance ratio (0.5) non-trivial bias (> 25%) away from the null was observed. Standard errors of health effect estimates, though unaffected by changes in the correlation coefficient, appeared to be attenuated for variance ratios > 1 but inflated for variance ratios < 1. CONCLUSION: While our findings suggest that in most cases modelling errors result in attenuation of the effect estimate towards the null, in some situations a non-trivial bias away from the null may occur. The magnitude and direction of bias appears to depend on the relationship between modelled and "true" data in terms of their correlation and the ratio of their variances. These factors should be taken into account when assessing the validity of modelled air pollution predictions for use in complex epidemiological models

    Network Analysis of Host-Virus Communities in Bats and Rodents Reveals Determinants of Cross-Species Transmission

    Get PDF
    Bats are natural reservoirs of several important emerging viruses. Cross-species transmission appears to be quite common among bats, which may contribute to their unique reservoir potential. Therefore, understanding the importance of bats as reservoirs requires examining them in a community context rather than concentrating on individual species. Here, we use a network approach to identify ecological and biological correlates of cross-species virus transmission in bats and rodents, another important host group. We show that given our current knowledge the bat viral sharing network is more connected than the rodent network, suggesting viruses may pass more easily between bat species. We identify host traits associated with important reservoir species: gregarious bats are more likely to share more viruses and bats which migrate regionally are important for spreading viruses through the network. We identify multiple communities of viral sharing within bats and rodents and highlight potential species traits that can help guide studies of novel pathogen emergence

    GATA2 regulates the erythropoietin receptor in t(12;21) ALL.

    Get PDF
    The t(12;21) (p13;q22) chromosomal translocation resulting in the ETV6/RUNX1 fusion gene is the most frequent structural cytogenetic abnormality in children with acute lymphoblastic leukemia (ALL). The erythropoietin receptor (EPOR), usually associated with erythroid progenitor cells, is highly expressed in ETV6/RUNX1 positive cases compared to other B-lineage ALL subtypes. Gene expression analysis of a microarray database and direct quantitative analysis of patient samples revealed strong correlation between EPOR and GATA2 expression in ALL, and higher expression of GATA2 in t(12;21) patients. The mechanism of EPOR regulation was mainly investigated using two B-ALL cell lines: REH, which harbor and express the ETV6/RUNX1 fusion gene; and NALM-6, which do not. Expression of EPOR was increased in REH cells compared to NALM-6 cells. Moreover, of the six GATA family members only GATA2 was differentially expressed with substantially higher levels present in REH cells. GATA2 was shown to bind to the EPOR 5'-UTR in REH, but did not bind in NALM-6 cells. Overexpression of GATA2 led to an increase in EPOR expression in REH cells only, indicating that GATA2 regulates EPOR but is dependent on the cellular context. Both EPOR and GATA2 are hypomethylated and associated with increased mRNA expression in REH compared to NALM-6 cells. Decitabine treatment effectively reduced methylation of CpG sites in the GATA2 promoter leading to increased GATA2 expression in both cell lines. Although Decitabine also reduced an already low level of methylation of the EPOR in NALM-6 cells there was no increase in EPOR expression. Furthermore, EPOR and GATA2 are regulated post-transcriptionally by miR-362 and miR-650, respectively. Overall our data show that EPOR expression in t(12;21) B-ALL cells, is regulated by GATA2 and is mediated through epigenetic, transcriptional and post-transcriptional mechanisms, contingent upon the genetic subtype of the disease

    Reporting of factorial trials of complex interventions in community settings: a systematic review

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Standards for the reporting of factorial randomised trials remain to be established. We aimed to review the quality of reporting of methodological aspects of published factorial trials of complex interventions in community settings.</p> <p>Methods</p> <p>We searched MEDLINE, EMBASE, PsychInfo and the Cochrane Controlled Trials Register to identify factorial randomised trials of complex interventions in community settings from January 2000 to August 2009. We also conducted a citation search of two review papers published in 2003. Data were extracted by two reviewers on 22 items relating to study design, analysis and presentation.</p> <p>Results</p> <p>We identified 5941 unique titles, from which 116 full papers were obtained and 76 were included in the review. The included trials reflected a broad range of target conditions and types of intervention. The median sample size was 400 (interquartile range 191-1001). Most (88%) trials employed a 2 × 2 factorial design. Few trials (21%) explicitly stated the rationale for using a factorial design. Reporting of aspects of design, analysis or presentation specific to factorial trials was variable, but there was no evidence that reporting of these aspects was different for trials published before or after 2003. However, for CONSORT items that apply generally to the reporting of all trials, there was some evidence that later studies were more likely to report employing an intention-to-treat (ITT) approach (78% vs 52%), present appropriate between-group estimates of effect (88% vs 63%), and present standard errors or 95% confidence intervals for such estimates (78% vs 56%). Interactions between interventions and some measure of the precision associated with such effects were reported in only 14 (18%) trials.</p> <p>Conclusions</p> <p>Reports of factorial trials of complex interventions in community settings vary in the amount of information they provide regarding important methodological aspects of design and analysis. This variability supports the extension of CONSORT guidelines to include the specific reporting of factorial trials.</p

    Why do Particle Clouds Generate Electric Charges?

    Full text link
    Grains in desert sandstorms spontaneously generate strong electrical charges; likewise volcanic dust plumes produce spectacular lightning displays. Charged particle clouds also cause devastating explosions in food, drug and coal processing industries. Despite the wide-ranging importance of granular charging in both nature and industry, even the simplest aspects of its causes remain elusive, because it is difficult to understand how inert grains in contact with little more than other inert grains can generate the large charges observed. Here, we present a simple yet predictive explanation for the charging of granular materials in collisional flows. We argue from very basic considerations that charge transfer can be expected in collisions of identical dielectric grains in the presence of an electric field, and we confirm the model's predictions using discrete-element simulations and a tabletop granular experiment

    Next-Generation Sequencing Reveals Significant Bacterial Diversity of Botrytized Wine

    Get PDF
    While wine fermentation has long been known to involve complex microbial communities, the composition and role of bacteria other than a select set of lactic acid bacteria (LAB) has often been assumed either negligible or detrimental. This study served as a pilot study for using barcoded amplicon next-generation sequencing to profile bacterial community structure in wines and grape musts, comparing the taxonomic depth achieved by sequencing two different domains of prokaryotic 16S rDNA (V4 and V5). This study was designed to serve two goals: 1) to empirically determine the most taxonomically informative 16S rDNA target region for barcoded amplicon sequencing of wine, comparing V4 and V5 domains of bacterial 16S rDNA to terminal restriction fragment length polymorphism (TRFLP) of LAB communities; and 2) to explore the bacterial communities of wine fermentation to better understand the biodiversity of wine at a depth previously unattainable using other techniques. Analysis of amplicons from the V4 and V5 provided similar views of the bacterial communities of botrytized wine fermentations, revealing a broad diversity of low-abundance taxa not traditionally associated with wine, as well as atypical LAB communities initially detected by TRFLP. The V4 domain was determined as the more suitable read for wine ecology studies, as it provided greater taxonomic depth for profiling LAB communities. In addition, targeted enrichment was used to isolate two species of Alphaproteobacteria from a finished fermentation. Significant differences in diversity between inoculated and uninoculated samples suggest that Saccharomyces inoculation exerts selective pressure on bacterial diversity in these fermentations, most notably suppressing abundance of acetic acid bacteria. These results determine the bacterial diversity of botrytized wines to be far higher than previously realized, providing further insight into the fermentation dynamics of these wines, and demonstrate the utility of next-generation sequencing for wine ecology studies

    Electrically-driven phase transition in magnetite nanostructures

    Full text link
    Magnetite (Fe3_{3}O4_{4}), an archetypal transition metal oxide, has been used for thousands of years, from lodestones in primitive compasses[1] to a candidate material for magnetoelectronic devices.[2] In 1939 Verwey[3] found that bulk magnetite undergoes a transition at TV_{V} \approx 120 K from a high temperature "bad metal" conducting phase to a low-temperature insulating phase. He suggested[4] that high temperature conduction is via the fluctuating and correlated valences of the octahedral iron atoms, and that the transition is the onset of charge ordering upon cooling. The Verwey transition mechanism and the question of charge ordering remain highly controversial.[5-11] Here we show that magnetite nanocrystals and single-crystal thin films exhibit an electrically driven phase transition below the Verwey temperature. The signature of this transition is the onset of sharp conductance switching in high electric fields, hysteretic in voltage. We demonstrate that this transition is not due to local heating, but instead is due to the breakdown of the correlated insulating state when driven out of equilibrium by electrical bias. We anticipate that further studies of this newly observed transition and its low-temperature conducting phase will shed light on how charge ordering and vibrational degrees of freedom determine the ground state of this important compound.Comment: 17 pages, 4 figure

    The plate-to-rod transition in trabecular bone loss is elusive.

    Get PDF
    Changes in trabecular micro-architecture are key to our understanding of osteoporosis. Previous work focusing on structure model index (SMI) measurements have concluded that disease progression entails a shift from plates to rods in trabecular bone, but SMI is heavily biased by bone volume fraction. As an alternative to SMI, we proposed the ellipsoid factor (EF) as a continuous measure of local trabecular shape between plate-like and rod-like extremes. We investigated the relationship between EF distributions, SMI and bone volume fraction of the trabecular geometry in a murine model of disuse osteoporosis as well as from human vertebrae of differing bone volume fraction. We observed a moderate shift in EF median (at later disease stages in mouse tibia) and EF mode (in the vertebral samples with low bone volume fraction) towards a more rod-like geometry, but not in EF maximum and minimum. These results support the notion that the plate to rod transition does not coincide with the onset of bone loss and is considerably more moderate, when it does occur, than SMI suggests. A variety of local shapes not straightforward to categorize as rod or plate exist in all our trabecular bone samples
    corecore