62 research outputs found

    Novel genetic loci associated with hippocampal volume

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    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

    Effect of priming interval on reactogenicity, peak immunological response, and waning after homologous and heterologous COVID-19 vaccine schedules: exploratory analyses of Com-COV, a randomised control trial

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    Background: Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca). Methods: Com-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020–005085–33). Findings: Between Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77–89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2–ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second dose, with geometric mean ratios of 1·4 (95% CI 1·1–1·8) for homologous BNT162b2, 1·5 (1·2–1·9) for ChAdOx1 nCoV-19–BNT162b2, 1·6 (1·3–2·1) for BNT162b2–ChAdOx1 nCoV-19, and 2·4 (1·7–3·2) for homologous ChAdOx1 nCoV-19. At 6 months post-second dose, anti-spike IgG geometric mean concentrations fell to 0·17–0·24 of the 28-day post-second dose value across all eight study groups, with only homologous BNT162b2 showing a slightly slower decay for the 12-week versus 4-week interval in the adjusted analysis. The rank order of schedules by humoral response was unaffected by interval, with homologous BNT162b2 remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals compared with their 4-week counterparts. 12-week schedules for homologous BNT162b2 and ChAdOx1 nCoV-19–BNT162b2 were up to 80% less reactogenic than 4-week schedules. Interpretation: These data support flexibility in priming interval in all studied COVID-19 vaccine schedules. Longer priming intervals might result in lower reactogenicity in schedules with BNT162b2 as a second dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines using these novel platforms might benefit from schedules with long intervals. Funding: UK Vaccine Taskforce and National Institute for Health and Care Research

    A ETNOECOLOGIA EM PERSPECTIVA: ORIGENS, INTERFACES E CORRENTES ATUAIS DE UM CAMPO EM ASCENSÃO

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    Assessment of hydrodynamic simulation results for eco-hydraulic and eco-hydrological applications: a spatial semivariance approach

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    Output from a three-dimensional numerical flow model (SSIIM) is used in conjunction with high-resolution topographic and velocity data to assess such models for eco-hydraulic applications in river channel design and habitat appraisal. A new methodology for the comparison between field measurement and model output is detailed. This involves a comparison between conventional goodness-of-fit approaches applied to a spatially structured (riffle and pool) sample of model and field data, and a relaxation method based upon the spatial semivariance of model/field departures. Conventional assessment indicates that the model predicts point-by-point velocity characteristics on a 0·45 m mesh to within ±0·1 m s-1 over 80% of the channel area at low flow, and 50% of the area at high in-bank flow. When a relative criterion of model fit is used, however, the model appears to perform less well: 60-70% of channel area has predicted velocities that depart from observed velocities by more than 10%. Regression analysis of observed and predicted velocities gives more cause for optimism, but all of these conventional indicators of goodness of fit neglect important spatial characteristics of model performance. Spatial semivariance is a means of supplementing model appraisal in this respect. In particular, using the relaxation approach, results are greatly improved: at a high in-bank flow, the model results match field measurements to within 0·1 m s-1 for more than 95% of the total channel area, provided that model and field comparisons are allowed within a radius of approximately 1 m from the original point of measurement. It is suggested that this revised form of model assessment is of particular relevance to eco-hydraulic applications, where some degree of spatial and temporal dynamism (or uncertainty) is a characteristic. The approach may also be generalized to other environmental science modelling applications where the spatial attributes of model fits are of interest

    Realism in geomorphology

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    Book synopsis: Process and Form in Geomorphology marks a turning point in geomorphological research. Stoddart has brought together a team of the leading international experts to offer important new studies into the processes, theory and history of landforms, and to present a framework for taking research forward into the new millenium. Illustrated throughout, Process and Form in Geomorphology takes up the challenges of the research agenda set by Richard Chorley and offers fresh insights into his unique contribution
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