14 research outputs found

    Relationship between bacterial strain type, host biomarkers, and mortality in clostridium difficile infection

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    Background: Despite substantial interest in biomarkers, their impact on clinical outcomes and variation with bacterial strain has rarely been explored using integrated databases. Methods: From September 2006 to May 2011, strains isolated from Clostridium difficile toxin enzyme immunoassay (EIA)-positive fecal samples from Oxfordshire, United Kingdom (approximately 600 000 people) underwent multilocus sequence typing. Fourteen-day mortality and levels of 15 baseline biomarkers were compared between consecutive C. difficile infections (CDIs) from different clades/sequence types (STs) and EIA-negative controls using Cox and normal regression adjusted for demographic/clinical factors. Results: Fourteen-day mortality was 13% in 2222 adults with 2745 EIA-positive samples (median, 78 years) vs 5% in 20 722 adults with 27 550 EIA-negative samples (median, 74 years) (absolute attributable mortality, 7.7%; 95% CI, 6.4%-9.0%). Mortality was highest in clade 5 CDIs (25% [16 of 63]; polymerase chain reaction (PCR) ribotype 078/ST 11), then clade 2 (20% [111 of 560]; 99% PCR ribotype 027/ST 1) versus clade 1 (12% [137 of 1168]; adjusted P <. 0001). Within clade 1, 14-day mortality was only 4% (3 of 84) in ST 44 (PCR ribotype 015) (adjusted P =. 05 vs other clade 1). Mean baseline neutrophil counts also varied significantly by genotype: 12.4, 11.6, and 9.5 × 109 neutrophils/L for clades 5, 2 and 1, respectively, vs 7.0 × 109 neutrophils/L in EIA-negative controls (P <. 0001) and 7.9 × 109 neutrophils/L in ST 44 (P =. 08). There were strong associations between C. difficile-type-specific effects on mortality and neutrophil/white cell counts (rho = 0.48), C-reactive-protein (rho = 0.43), eosinophil counts (rho =-0.45), and serum albumin (rho =-0.47). Biomarkers predicted 30%-40% of clade-specific mortality differences. Conclusions: C. difficile genotype predicts mortality, and excess mortality correlates with genotype-specific changes in biomarkers, strongly implicating inflammatory pathways as a major influence on poor outcome after CDI. PCR ribotype 078/ST 11 (clade 5) leads to severe CDI; thus ongoing surveillance remains essential

    The Role of Gemcitabine in the Treatment of Cholangiocarcinoma and Gallbladder Cancer: A Systematic Review

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    BACKGROUND: Cholangiocarcinoma and gallbladder cancer are difficult to treat curatively. The treatment of choice is surgery, dependent on detection at a resectable stage. No chemotherapy or radiotherapy options have shown substantial activity. Gemcitabine has demonstrated response in similar cancers. Considering the lack of treatment options for cholangiocarcinoma and gallbladder cancer, a systematic review of the evidence on gemcitabine use for these indications was performed

    Decadal-scale morphological adjustment of a lowland tropical river

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    Compared with temperate regions, much less is known about the dynamics of tropical river systems. Tropical rivers are typically characterised by pronounced seasonal changes in precipitation, large sediment loads and high rates of lateral channel migration across often very low-gradient and densely populated floodplains. Understanding the controls on channel migration or change is integral to our ability to fully predict and build resilience against flood risk and wider river-related hazards. Here, we analyse channel and confluence migration over the last ~40 years along a ~85 km reach of the Cagayan River and one of its tributaries, the Pinacanauan de Ilagan (Luzon, Philippines) using optical satellite imagery captured during this period. Combining this with spatial variations in channel pattern, valley width and new bed material grain size data, we demonstrate that sediment transport and deposition are key drivers of the observed tropical channel morphodynamics in this region. The high sediment supply generated in the catchment headwaters (by mass-wasting of hillslopes triggered especially in typhoons) results in high aggradation rates and channel widening on the lower gradient alluvial plain. We suggest that this aggradation enhances local confluence and lateral channel migration rates, which can reach &gt;300 m per decade, and that lateral migration rates of tropical rivers are typically greater than those of temperate rivers. Channel morphodynamics have implications for how to best manage these types of tropical river systems, where hard bank protection structures may result in a complex geomorphic response and flood risk mapping may need to include assessment of sensitivity to varying channel position and topography

    Hybridization of electronic states in quantum dots through photon emission

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    4 páginas, 5 figuras.The self-assembly of semiconductor quantum dots has opened up new opportunities in photonics. Quantum dots are usually described as 'artificial atoms', because electron and hole confinement gives rise to discrete energy levels. This picture can be justified from the shell structure observed as a quantum dot is filled either with excitons1 (bound electron–hole pairs) or with electrons2. The discrete energy levels have been most spectacularly exploited in single photon sources that use a single quantum dot as emitter3, 4, 5, 6. At low temperatures, the artificial atom picture is strengthened by the long coherence times of excitons in quantum dots7, 8, 9, motivating the application of quantum dots in quantum optics and quantum information processing. In this context, excitons in quantum dots have already been manipulated coherently10, 11, 12. We show here that quantum dots can also possess electronic states that go far beyond the artificial atom model. These states are a coherent hybridization of localized quantum dot states and extended continuum states: they have no analogue in atomic physics. The states are generated by the emission of a photon from a quantum dot. We show how a new version of the Anderson model that describes interactions between localized and extended states can account for the observed hybridization.This work was funded by the DFG, EPSRC and The Royal Society.Peer reviewe

    Sources and Characteristics of Summertime Organic Aerosol in the Colorado Front Range: Perspective from Measurements and WRF-Chem Modeling

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    Abstract. The evolution of organic aerosols (OAs) and their precursors in the boundary layer (BL) of the Colorado Front Range during the Front Range Air Pollution and Photochemistry Éxperiment (FRAPPÉ, July–August 2014) was analyzed by in situ measurements and chemical transport modeling. Measurements indicated significant production of secondary OA (SOA), with enhancement ratio of OA with respect to carbon monoxide (CO) reaching 0.085±0.003 µg m−3 ppbv−1. At background mixing ratios of CO, up to  ∼  1.8 µg m−3 background OA was observed, suggesting significant non-combustion contribution to OA in the Front Range. The mean concentration of OA in plumes with a high influence of oil and natural gas (O&amp;G) emissions was  ∼  40 % higher than in urban-influenced plumes. Positive matrix factorization (PMF) confirmed a dominant contribution of secondary, oxygenated OA (OOA) in the boundary layer instead of fresh, hydrocarbon-like OA (HOA). Combinations of primary OA (POA) volatility assumptions, aging of semi-volatile species, and different emission estimates from the O&amp;G sector were used in the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) simulation scenarios. The assumption of semi-volatile POA resulted in greater than a factor of 10 lower POA concentrations compared to PMF-resolved HOA. Including top-down modified O&amp;G emissions resulted in substantially better agreements in modeled ethane, toluene, hydroxyl radical, and ozone compared to measurements in the high-O&amp;G-influenced plumes. By including emissions from the O&amp;G sector using the top-down approach, it was estimated that the O&amp;G sector contributed to  &lt;  5 % of total OA, but up to 38 % of anthropogenic SOA (aSOA) in the region. The best agreement between the measured and simulated median OA was achieved by limiting the extent of biogenic hydrocarbon aging and consequently biogenic SOA (bSOA) production. Despite a lower production of bSOA in this scenario, contribution of bSOA to total SOA remained high at 40–54 %. Future studies aiming at a better emissions characterization of POA and intermediate-volatility organic compounds (IVOCs) from the O&amp;G sector are valuable

    SARS-CoV-2 antibody prevalence, titres and neutralising activity in an antenatal cohort, United Kingdom, 14 April to 15 June 2020

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    SARS-CoV-2 IgG screening of 1,000 antenatal serum samples in the Oxford area, United Kingdom, between 14 April and 15 June 2020, yielded a 5.3% seroprevalence, mirroring contemporaneous regional data. Among the 53 positive samples, 39 showed in vitro neutralisation activity, correlating with IgG titre (Pearson's correlation p<0.0001). While SARS-CoV-2 seroprevalence in pregnancy cohorts could potentially inform population surveillance, clinical correlates of infection and immunity in pregnancy, and antenatal epidemiology evolution over time need further study
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