1,287 research outputs found

    Mutations in the E2 glycoprotein and the 3\u27 untranslated region enhance chikungunya virus virulence in mice

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    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes debilitating musculoskeletal pain and inflammation and can persist for months to years after acute infection. Although studies of humans and experimentally infected animals suggest that CHIKV infection persists in musculoskeletal tissues, the mechanisms for this remain poorly understood. To evaluate this further, we isolated CHIKV from the serum of persistently infected Rag1 -/- mice at day 28. When inoculated into naive wild-type (WT) mice, this persistently circulating CHIKV strain displayed a capacity for earlier dissemination and greater pathogenicity than the parental virus. Sequence analysis revealed a nonsynonymous mutation in the E2 glycoprotein (E2 K200R) and a deletion within the 3' untranslated region (3'-UTR). The introduction of these changes into the parental virus conferred enhanced virulence in mice, although primary tropism for musculoskeletal tissues was maintained. The E2 K200R mutation was largely responsible for enhanced viral dissemination and pathogenicity, although these effects were augmented by the 3'- UTR deletion. Finally, studies with Irf3/Irf7 -/- and Ifnar1 -/- mice suggest that the E2 K200R mutation enhances viral dissemination from the site of inoculation independently of interferon regulatory factor 3 (IRF3)-, IRF7-, and IFNAR1-mediated responses. As our findings reveal viral determinants of CHIKV dissemination and pathogenicity, their further study should help to elucidate host-virus interactions that determine acute and chronic CHIKV infection

    Improving the normalization of complex interventions: measure development based on normalization process theory (NoMAD): study protocol

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    <b>Background</b> Understanding implementation processes is key to ensuring that complex interventions in healthcare are taken up in practice and thus maximize intended benefits for service provision and (ultimately) care to patients. Normalization Process Theory (NPT) provides a framework for understanding how a new intervention becomes part of normal practice. This study aims to develop and validate simple generic tools derived from NPT, to be used to improve the implementation of complex healthcare interventions.<p></p> <b>Objectives</b> The objectives of this study are to: develop a set of NPT-based measures and formatively evaluate their use for identifying implementation problems and monitoring progress; conduct preliminary evaluation of these measures across a range of interventions and contexts, and identify factors that affect this process; explore the utility of these measures for predicting outcomes; and develop an online usersā€™ manual for the measures.<p></p> <b>Methods</b> A combination of qualitative (workshops, item development, user feedback, cognitive interviews) and quantitative (survey) methods will be used to develop NPT measures, and test the utility of the measures in six healthcare intervention settings.<p></p> <b>Discussion</b> The measures developed in the study will be available for use by those involved in planning, implementing, and evaluating complex interventions in healthcare and have the potential to enhance the chances of their implementation, leading to sustained changes in working practices

    Chapter F of the International Code of Nomenclature for algae, fungi, and plants as approved by the 11th International Mycological Congress, San Juan, Puerto Rico, July 2018

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    A revised version of Chapter F of the International Code of Nomenclature for algae, fungi, and plants is presented, incorporating amendments approved by the Fungal Nomenclature Session of the 11th International Mycological Congress held in San Juan, Puerto Rico in July 2018. The process leading to the amendments is outlined. Key changes in the San Juan Chapter F are (1) removal of option to use a colon to indicate the sanctioned status of a name, (2) introduction of correctability for incorrectly cited identifiers of names and typifications, and (3) introduction of option to use name identifiers in place of author citations. Examples have been added to aid the interpretation of new Articles and Recommendations, and Examples have also been added to the existing Art. F.3.7 concerning the protection extended to new combinations based on sanctioned names or basionyms of sanctioned names (which has been re-worded), and to Art. F.3.9 concerning typification of names accepted in the sanctioning works

    Large Language Models for Granularized Barrett's Esophagus Diagnosis Classification

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    Diagnostic codes for Barrett's esophagus (BE), a precursor to esophageal cancer, lack granularity and precision for many research or clinical use cases. Laborious manual chart review is required to extract key diagnostic phenotypes from BE pathology reports. We developed a generalizable transformer-based method to automate data extraction. Using pathology reports from Columbia University Irving Medical Center with gastroenterologist-annotated targets, we performed binary dysplasia classification as well as granularized multi-class BE-related diagnosis classification. We utilized two clinically pre-trained large language models, with best model performance comparable to a highly tailored rule-based system developed using the same data. Binary dysplasia extraction achieves 0.964 F1-score, while the multi-class model achieves 0.911 F1-score. Our method is generalizable and faster to implement as compared to a tailored rule-based approach

    Making Sense of a New Transport System: An Ethnographic Study of the Cambridgeshire Guided Busway

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    An increase in public transport use has the potential to contribute to improving population health, and there is growing interest in innovative public transport systems. Yet how new public transport infrastructure is experienced and integrated (or not) into daily practice is little understood. We investigated how the Cambridgeshire Guided Busway, UK, was used and experienced in the weeks following its opening, using the method of participant observation (travelling on the busway and observing and talking to passengers) and drawing on Normalization Process Theory to interpret our data. Using excerpts of field notes to support our interpretations, we describe how the ease with which the new transport system could be integrated into existing daily routines was important in determining whether individuals would continue to use it. It emerged that there were two groups of passengers with different experiences and attitudes. Passengers who had previously travelled frequently on regular bus services did not perceive the new system to be an improvement; consequently, they were frustrated that it was differentiated from and not coherent with the regular system. In contrast, passengers who had previously travelled almost exclusively by car appraised the busway positively and perceived it to be a novel and superior form of travel. Our rich qualitative account highlights the varied and creative ways in which people learn to use new public transport and integrate it into their everyday lives. This has consequences for the introduction and promotion of future transport innovations. It is important to emphasise the novelty of new public transport, but also the ways in which its use can become ordinary and routine. Addressing these issues could help to promote uptake of other public transport interventions, which may contribute to increasing physical activity and improving population health. Ā© 2013 Jones et al

    Porewater Carbonate Chemistry Dynamics in a Temperate and a Subtropical Seagrass System

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    Seagrass systems are integral components of both local and global carbon cycles and can substantially modify seawater biogeochemistry, which has ecological ramifications. However, the influence of seagrass on porewater biogeochemistry has not been fully described, and the exact role of this marine macrophyte and associated microbial communities in the modification of porewater chemistry remains equivocal. In the present study, carbonate chemistry in the water column and porewater was investigated over diel timescales in contrasting, tidally influenced seagrass systems in Southern California and Bermuda, including vegetated (Zostera marina) and unvegetated biomes (0ā€“16 cm) in Mission Bay, San Diego, USA and a vegetated system (Thallasia testudinium) in Mangrove Bay, Ferry Reach, Bermuda. In Mission Bay, dissolved inorganic carbon (DIC) and total alkalinity (TA) exhibited strong increasing gradients with sediment depth. Vertical porewater profiles differed between the sites, with almost twice as high concentrations of DIC and TA observed in the vegetated compared to the unvegetated sediments. In Mangrove Bay, both the range and vertical profiles of porewater carbonate parameters such as DIC and TA were much lower and, in contrast to Mission Bay where no distinct temporal signal was observed, biogeochemical parameters followed the semi-diurnal tidal signal in the water column. The observed differences between the study sites most likely reflect a differential influence of biological (biomass, detritus and infauna) and physical processes (e.g., sediment permeability, residence time and mixing) on porewater carbonate chemistry in the different settings

    Measurement of Biodiversity (MoB): A method to separate the scale-dependent effects of species abundance distribution, density, and aggregation on diversity change

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    Little consensus has emerged regarding how proximate and ultimate drivers such as productivity, disturbance and temperature may affect species richness and other aspects of biodiversity. Part of the confusion is that most studies examine species richness at a single spatial scale and ignore how the underlying components of species richness can vary with spatial scale. We provide an approach for the measurement of biodiversity that decomposes changes in species rarefaction curves into proximate components attributed to: (a) the species abundance distribution, (b) density of individuals and (c) the spatial arrangement of individuals. We decompose species richness by comparing spatial and nonspatial sample- and individual-based species rarefaction curves that differentially capture the influence of these components to estimate the relative importance of each in driving patterns of species richness change. We tested the validity of our method on simulated data, and we demonstrate it on empirical data on plant species richness in invaded and uninvaded woodlands. We integrated these methods into a new r package (mobr). The metrics that mobr provides will allow ecologists to move beyond comparisons of species richness in response to ecological drivers at a single spatial scale toward a dissection of the proximate components that determine species richness across scales

    Violent and victimized bodies: sexual violence policy in England and Wales

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    This paper uses the notion of the body to frame an archaeology of sexual violence policy in England and Wales, applying and developing Pillowā€™s ideas. It argues that the dominant construction is of sexual violence as an individualized crime, with the solution being for a survivor to report, and with support often instrumentalized in relation to criminal justice objectives. However, criminal justice proceedings can intensify or create further trauma for sexual violence survivors. Furthermore, in addition to criminalizing the violent body and supporting the victimized one, there is a need for policy to produce alternative types of bodies through preventative interventions. Much sexual violence is situated within (hetero) sexual dynamics constructing a masculine aggressor and a feminine body which eventually yields. Prevention must therefore focus on developing embodied boundaries, and narratives at the margins of policy could underpin such efforts
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