712 research outputs found

    Becoming an accredited medical teacher in the UK

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    Teaching and training are integral to the different, core roles of a trainee. Therefore, there is a shift in the medical profession towards credentialing teaching and training skills. Postgraduate qualifications in medical education are likely to be more important for professional development. In recent years, the number of medical education awards and training programmes has increased rapidly. This pluralism, however, may become a source of confusion for those considering enrolment on such programmes. This article summarises the nomenclature, awarding bodies, levels of qualification, programmes and positions available for those wishing to advance their educational practice. The article will focus on opportunities available to UK-based doctors and particularly for doctors in training

    Assessing the Diversity of Endogenous Viruses Throughout Ant Genomes

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    Endogenous viral elements (EVEs) can play a significant role in the evolution of their hosts and have been identified in animals, plants, and fungi. Additionally, EVEs potentially provide an important snapshot of the evolutionary frequency of viral infection. The purpose of this study is to take a comparative host-centered approach to EVE discovery in ant genomes to better understand the relationship of EVEs to their ant hosts. Using a comprehensive bioinformatic pipeline, we screened all nineteen published ant genomes for EVEs. Once the EVEs were identified, we assessed their phylogenetic relationships to other closely related exogenous viruses. A diverse group of EVEs were discovered in all screened ant host genomes and in many cases are similar to previously identified exogenous viruses. EVEs similar to ssRNA viral proteins are the most common viral lineage throughout the ant hosts, which is potentially due to more chronic infection or more effective endogenization of certain ssRNA viruses in ants. In addition, both EVEs similar to viral glycoproteins and retrovirus-derived proteins are also abundant throughout ant genomes, suggesting their tendency to endogenize. Several of these newly discovered EVEs are found to be potentially functional within the genome. The discovery and analysis of EVEs is essential in beginning to understand viral–ant interactions over evolutionary time

    Intrinsic Domain and Loop Dynamics Commensurate with Catalytic Turnover in an Induced-Fit Enzyme

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    SummaryArginine kinase catalyzes reversible phosphoryl transfer between ATP and arginine, buffering cellular ATP concentrations. Structures of substrate-free and -bound enzyme have highlighted a range of conformational changes thought to occur during the catalytic cycle. Here, NMR is used to characterize the intrinsic backbone dynamics over multiple timescales. Relaxation dispersion indicates rigid-body motion of the N-terminal domain and flexible dynamics in the I182–G209 loop, both at millisecond rates commensurate with kcat, implying that either might be rate limiting upon catalysis. Lipari-Szabo analysis indicates backbone flexibility on the nanosecond timescale in the V308–V322 loop, while the rest of the enzyme is more rigid in this timescale. Thus, intrinsic dynamics are most prominent in regions that have been independently implicated in conformational changes. Substrate-free enzyme may sample an ensemble of different conformations, of which a subset is selected upon substrate binding, with critical active site residues appropriately configured for binding and catalysis

    The Knowledge Object Reference Ontology (KORO): A formalism to support management and sharing of computable biomedical knowledge for learning health systems

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    IntroductionHealth systems are challenged by care underutilization, overutilization, disparities, and related harms. One problem is a multiyear latency between discovery of new best practice knowledge and its widespread adoption. Decreasing this latency requires new capabilities to better manage and more rapidly share biomedical knowledge in computable forms. Knowledge objects package machineĂą executable knowledge resources in a way that easily enables knowledge as a service. To help improve knowledge management and accelerate knowledge sharing, the Knowledge Object Reference Ontology (KORO) defines what knowledge objects are in a formal way.MethodsDevelopment of KORO began with identification of terms for classes of entities and for properties. Next, we established a taxonomical hierarchy of classes for knowledge objects and their parts. Development continued by relating these parts via formally defined properties. We evaluated the logical consistency of KORO and used it to answer several competency questions about parthood. We also applied it to guide knowledge object implementation.ResultsAs a realist ontology, KORO defines what knowledge objects are and provides details about the parts they have and the roles they play. KORO provides sufficient logic to answer several basic but important questions about knowledge objects competently. KORO directly supports creators of knowledge objects by providing a formal model for these objects.ConclusionKORO provides a formal, logically consistent ontology about knowledge objects and their parts. It exists to help make computable biomedical knowledge findable, accessible, interoperable, and reusable. KORO is currently being used to further develop and improve computable knowledge infrastructure for learning health systems.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143591/1/lrh210054_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143591/2/lrh210054.pd

    Time to revisit the passive overconsumption hypothesis?:Humans show sensitivity to calories in energy-rich meals

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    BACKGROUND: A possible driver of obesity is insensitivity (passive overconsumption) to food energy density (ED, kcal/g); however, it is unclear whether this insensitivity applies to all meals. OBJECTIVES: We assessed the influence of ED on energy intake (kcal) across a broad and continuous range of EDs comprised of noncovertly manipulated, real-world meals. We also allowed for the possibility that the association between energy intake and ED is nonlinear. METHODS: We completed a secondary analysis of 1519 meals which occurred in a controlled environment as part of a study conducted by Hall and colleagues to assess the effects of food ultra-processing on energy intake. To establish the generalizability of the findings, the analyses were repeated in 32,162 meals collected from free-living humans using data from the UK National Diet and Nutrition Survey (NDNS). Segmented regressions were performed to establish ED “breakpoints” at which the association between consumed meal ED and mean centered meal caloric intake (kcal) changed. RESULTS: Significant breakpoints were found in both the Hall et al. data set (1.41 kcal/g) and the NDNS data set (1.75 and 2.94 kcal/g). Centered meal caloric intake did not increase linearly with consumed meal ED, and this pattern was captured by a 2-component (“volume” and “calorie content” [biologically derived from the sensing of fat, carbohydrate, and protein]) model of physical meal size (g), in which volume is the dominant signal with lower energy-dense foods and calorie content is the dominant signal with higher energy-dense foods. CONCLUSIONS: These analyses reveal that, on some level, humans are sensitive to the energy content of meals and adjust meal size to minimize the acute aversive effects of overconsumption. Future research should consider the relative importance of volume and calorie-content signals, and how individual differences impact everyday dietary behavior and energy balance

    Insights into circovirus host range from the genomic fossil record

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    A diverse range of DNA sequences derived from circoviruses (family Circoviridae) have been identified in samples obtained from humans and domestic animals, often in association with pathological conditions. In the majority of cases, however, little is known about the natural biology of the viruses from which these sequences are derived. Endogenous circoviral elements (CVe) are DNA sequences derived from circoviruses that occur in animal genomes and provide a useful source of information about circovirus-host relationships. In this study we screened genome assemblies of 675 animal species and identified numerous circovirus-related sequences, including the first examples of CVe derived from cycloviruses. We confirmed the presence of these CVe in the germline of the elongate twig ant (Pseudomyrmex gracilis), thereby establishing that cycloviruses infect insects. We examined the evolutionary relationships between CVe and contemporary circoviruses, showing that CVe from ants and mites group relatively closely with cycloviruses in phylogenies. Furthermore, the relatively random interspersal of CVe from insect genomes with cyclovirus sequences recovered from vertebrate samples, suggested that contamination might be an important consideration in studies reporting these viruses. Our study demonstrates how endogenous viral sequences can inform metagenomics-based virus discovery. In addition, it raises doubts about the role of cycloviruses as pathogens of humans and other vertebrates

    Survival of High-Risk Pediatric Neuroblastoma Patients In a Developing Country

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    Little information is available about survival of high‐risk pediatric neuroblastoma patients in developing countries. We aimed to assess survival among high‐risk pediatric neuroblastoma patients in La Plata, Argentina. Individuals eligible for our cohort were aged4 yr at diagnosis, 54% were male, and 62% had adrenal neuroblastoma. We observed 18 deaths, and the median survival time of our study population was 1.7 yr. The five‐yr overall survival probability was 24% (95% CL: 10%, 41%). In contrast, five‐yr survival of high‐risk neuroblastoma patients ranges between 23% and 76% in developed countries. Survival among high‐risk neuroblastoma patients is generally poor regardless of geographic location, but our results illustrate dramatically worse survival for patients in a developing country. We speculate that the observed survival differences could be attenuated or eliminated with improvements in treatment and supportive care, but addressing these issues will require creative solutions because of resource limitations

    Analysis of Human Skin Tissue by Raman Microspectroscopy: Dealing with the Background

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    Raman microspectroscopy is widely used for molecular characterisation of tissue samples. Nevertheless, when working in vitro on tissue sections, the presence of a broad background to the spectra remains problematic and its removal requires advanced methods for pre-processing of the data. To date, research efforts have been primarily devoted to development of techniques of statistical analysis to extract the relevant information contained in the spectra. However, few attempts have been made to understand the origin of the background and to improve the protocols used for the collection of Raman spectra that could lead to the reduction or elimination of the background. It has been demonstrated that measurement at 785nm in water immersion significantly reduces the Raman background of both pure biochemical components and tissue sections, associating the background at 785nm with a scattering phenomenon rather than fluorescence. It is however of interest to probe the dependence of the observed background and any time evolution normally associated with photobleaching of fluorophores, under dry and immersed conditions, on the source wavelength. Using 785nm or 660nm as source, extended exposure of dried skin tissue sections to the laser results in a time dependent reduction of the background present in the Raman spectra. When working in water immersion, the overall background as well as the evolution over time is greatly reduced and the background is seen to stabilise after ~20 seconds exposure. Using 532 nm or 473 nm as source for the examination of dried tissue sections, visible photodamage of the sample limits the laser power usable for the collection of spectra to 5 mW. Immersion of the tissue sections protects against photodamage and laser powers of up to 30 mW can be used without any visible damage. Under these conditions, the background is significantly reduced and good quality Raman spectra can be recorded. By adapting the protocol usually used for the collection of Raman spectra, this study clearly demonstrates that other approaches rather than mathematical manipulation of the data can be used to deal with the intrinsic background commonly observable. Notably, the dependence of the background and its time evolution under prolonged exposure on sample environment potentially sheds light on its origin as due to sample morphology (scattering) rather than chemical content (fluorescence). Overall, the study demonstrates that, in addition to reduced background, the photostability of the samples is significantly enhanced in an immersion geometry

    Testing the Link between Functional Diversity and Ecosystem Functioning in a Minnesota Grassland Experiment

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    The functional diversity of a community can influence ecosystem functioning and reflects assembly processes. The large number of disparate metrics used to quantify functional diversity reflects the range of attributes underlying this concept, generally summarized as functional richness, functional evenness, and functional divergence. However, in practice, we know very little about which attributes drive which ecosystem functions, due to a lack of field-based tests. Here we test the association between eight leading functional diversity metrics (Rao’s Q, FD, FDis, FEve, FDiv, convex hull volume, and species and functional group richness) that emphasize different attributes of functional diversity, plus 11 extensions of these existing metrics that incorporate heterogeneous species abundances and trait variation. We assess the relationships among these metrics and compare their performances for predicting three key ecosystem functions (above- and belowground biomass and light capture) within a long-term grassland biodiversity experiment. Many metrics were highly correlated, although unique information was captured in FEve, FDiv, and dendrogram-based measures (FD) that were adjusted by abundance. FD adjusted by abundance outperformed all other metrics in predicting both above- and belowground biomass, although several others also performed well (e.g. Rao’s Q, FDis, FDiv). More generally, trait-based richness metrics and hybrid metrics incorporating multiple diversity attributes outperformed evenness metrics and single-attribute metrics, results that were not changed when combinations of metrics were explored. For light capture, species richness alone was the best predictor, suggesting that traits for canopy architecture would be necessary to improve predictions. Our study provides a comprehensive test linking different attributes of functional diversity with ecosystem function for a grassland system
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