People's differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found ...evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal-numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31% (s.e.m.=1.8%) for verbal-numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer's disease and schizophrenia.
This Letter reports the first scientific results from the observation of antineutrinos emitted by fission products of ^{235}U at the High Flux Isotope Reactor. PROSPECT, the Precision Reactor ...Oscillation and Spectrum Experiment, consists of a segmented 4 ton ^{6}Li-doped liquid scintillator detector covering a baseline range of 7-9 m from the reactor and operating under less than 1 m water equivalent overburden. Data collected during 33 live days of reactor operation at a nominal power of 85 MW yield a detection of 25 461±283 (stat) inverse beta decays. Observation of reactor antineutrinos can be achieved in PROSPECT at 5σ statistical significance within 2 h of on-surface reactor-on data taking. A reactor model independent analysis of the inverse beta decay prompt energy spectrum as a function of baseline constrains significant portions of the previously allowed sterile neutrino oscillation parameter space at 95% confidence level and disfavors the best fit of the reactor antineutrino anomaly at 2.2σ confidence level.
This Letter reports the first measurement of the 235U $\bar{ν}$e energy spectrum by PROSPECT, the Precision Reactor Oscillation and Spectrum experiment, operating 7.9 m from the 85 MWth highly ...enriched uranium (HEU) High Flux Isotope Reactor. With a surface-based, segmented detector, PROSPECT has observed 31678±304(stat) $\bar{ν}$e-induced inverse beta decays, the largest sample from HEU fission to date, 99% of which are attributed to 235U. Despite broad agreement, comparison of the Huber 235U model to the measured spectrum produces a χ2/ndf=51.4/31, driven primarily by deviations in two localized energy regions. The measured 235U spectrum shape is consistent with a deviation relative to prediction equal in size to that observed at low-enriched uranium power reactors in the $\bar{ν}$e energy region of 5–7 MeV.
Mammalian life shows huge diversity, but most groups remain nocturnal in their activity pattern. A key unresolved question is whether mammal species that have diversified into different diel niches ...occupy unique regions of functional trait space. For 5,104 extant mammals we show here that daytime-active species (cathemeral or diurnal) evolved trait combinations along different gradients from those of nocturnal and crepuscular species. Hypervolumes of five major functional traits (body mass, litter size, diet, foraging strata, habitat breadth) reveal that 30% of diurnal trait space is unique, compared to 55% of nocturnal trait space. Almost half of trait space (44%) of species with apparently obligate diel niches is shared with those that can switch, suggesting that more species than currently realised may be somewhat flexible in their activity patterns. Increasingly, conservation measures have focused on protecting functionally unique species; for mammals, protecting functional distinctiveness requires a focus across diel niches.
Predict (www.predict.nhs.uk) is an online, breast cancer prognostication and treatment benefit tool. The aim of this study was to incorporate the prognostic effect of HER2 status in a new version ...(Predict+), and to compare its performance with the original Predict and Adjuvant!.
The prognostic effect of HER2 status was based on an analysis of data from 10 179 breast cancer patients from 14 studies in the Breast Cancer Association Consortium. The hazard ratio estimates were incorporated into Predict. The validation study was based on 1653 patients with early-stage invasive breast cancer identified from the British Columbia Breast Cancer Outcomes Unit. Predicted overall survival (OS) and breast cancer-specific survival (BCSS) for Predict+, Predict and Adjuvant! were compared with observed outcomes.
All three models performed well for both OS and BCSS. Both Predict models provided better BCSS estimates than Adjuvant!. In the subset of patients with HER2-positive tumours, Predict+ performed substantially better than the other two models for both OS and BCSS.
Predict+ is the first clinical breast cancer prognostication tool that includes tumour HER2 status. Use of the model might lead to more accurate absolute treatment benefit predictions for individual patients.
This study tests the ability of five Dynamic Global Vegetation Models (DGVMs), forced with observed climatology and atmospheric CO₂, to model the contemporary global carbon cycle. The DGVMs are also ...coupled to a fast 'climate analogue model', based on the Hadley Centre General Circulation Model (GCM), and run into the future for four Special Report Emission Scenarios (SRES): A1FI, A2, B1, B2. Results show that all DGVMs are consistent with the contemporary global land carbon budget. Under the more extreme projections of future environmental change, the responses of the DGVMs diverge markedly. In particular, large uncertainties are associated with the response of tropical vegetation to drought and boreal ecosystems to elevated temperatures and changing soil moisture status. The DGVMs show more divergence in their response to regional changes in climate than to increases in atmospheric CO₂ content. All models simulate a release of land carbon in response to climate, when physiological effects of elevated atmospheric CO₂ on plant production are not considered, implying a positive terrestrial climate-carbon cycle feedback. All DGVMs simulate a reduction in global net primary production (NPP) and a decrease in soil residence time in the tropics and extra-tropics in response to future climate. When both counteracting effects of climate and atmospheric CO₂ on ecosystem function are considered, all the DGVMs simulate cumulative net land carbon uptake over the 21st century for the four SRES emission scenarios. However, for the most extreme A1FI emissions scenario, three out of five DGVMs simulate an annual net source of CO₂ from the land to the atmosphere in the final decades of the 21st century. For this scenario, cumulative land uptake differs by 494 Pg C among DGVMs over the 21st century. This uncertainty is equivalent to over 50 years of anthropogenic emissions at current levels.
The MiniBooNE Collaboration observes unexplained electronlike events in the reconstructed neutrino energy range from 200 to 475 MeV. With 6.46x10;{20} protons on target, 544 electronlike events are ...observed in this energy range, compared to an expectation of 415.2+/-43.4 events, corresponding to an excess of 128.8+/-20.4+/-38.3 events. The shape of the excess in several kinematic variables is consistent with being due to either nu_{e} and nuover _{e} charged-current scattering or nu_{mu} neutral-current scattering with a photon in the final state. No significant excess of events is observed in the reconstructed neutrino energy range from 475 to 1250 MeV, where 408 events are observed compared to an expectation of 385.9+/-35.7 events.
In December 2019, the 13th revision of the International Geomagnetic Reference Field (IGRF) was released by the International Association of Geomagnetism and Aeronomy (IAGA) Division V Working Group ...V-MOD. This revision comprises two new spherical harmonic main field models for epochs 2015.0 (DGRF-2015) and 2020.0 (IGRF-2020) and a model of the predicted secular variation for the interval 2020.0 to 2025.0 (SV-2020-2025). The models were produced from candidates submitted by fifteen international teams. These teams were led by the British Geological Survey (UK), China Earthquake Administration (China), Universidad Complutense de Madrid (Spain), University of Colorado Boulder (USA), Technical University of Denmark (Denmark), GFZ German Research Centre for Geosciences (Germany), Institut de physique du globe de Paris (France), Institut des Sciences de la Terre (France), Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation (Russia), Kyoto University (Japan), University of Leeds (UK), Max Planck Institute for Solar System Research (Germany), NASA Goddard Space Flight Center (USA), University of Potsdam (Germany), and Université de Strasbourg (France). The candidate models were evaluated individually and compared to all other candidates as well to the mean, median and a robust Huber-weighted model of all candidates. These analyses were used to identify, for example, the variation between the Gauss coefficients or the geographical regions where the candidate models strongly differed. The majority of candidates were sufficiently close that the differences can be explained primarily by individual modeling methodologies and data selection strategies. None of the candidates were so different as to warrant their exclusion from the final IGRF-13. The IAGA V-MOD task force thus voted for two approaches: the median of the Gauss coefficients of the candidates for the DGRF-2015 and IGRF-2020 models and the robust Huber-weighted model for the predictive SV-2020-2025. In this paper, we document the evaluation of the candidate models and provide details of the approach used to derive the final IGRF-13 products. We also perform a retrospective analysis of the IGRF-12 SV candidates over their performance period (2015–2020). Our findings suggest that forecasting secular variation can benefit from combining physics-based core modeling with satellite observations.
Separation of the anomalous Nernst and spin Seebeck voltages in bilayer devices is often problematic when both layers are metallic, and the anomalous Nernst effect (ANE) becomes non-negligible. ...Co2MnSi, a strong candidate for the spin generator in spin Seebeck devices, is a predicted half-metal with 100% spin polarisation at the Fermi energy, however, typically B2 or L21 order is needed to achieve this. We demonstrate the optimisation of thin film growth of Co2MnSi on glass, where choice of deposition and annealing temperature can promote various ordered states. The contribution from the ANE is then investigated to inform future measurements of the spin Seebeck. A maximum ANE coefficient of 0.662 µV K−1 is found for an A2 disordered polycrystalline Co2MnSi film. This value is comparable to ordered Heusler thin films deposited onto single crystal substrates but obtained at a far lower fabrication temperature and material cost.
Objective Endovascular abdominal aortic aneurysm repair (EVAR) sometimes requires internal iliac artery (IIA) coverage to achieve a landing zone in the external iliac artery. The aim of this study ...was to determine complication rates following IIA exclusion. Materials and methods A systematic review of key journals was undertaken from January 1980 to April 2016. Studies detailing occlusion (using coils or plugs) or coverage of the IIA with outcome data were included. Weighted means were calculated for continuous variables. Meta-analysis was performed when comparative data were available. Quality was assessed using the GRADE system. Results Sixty-one non-randomised studies (2671 patients; 2748 IIAs) were analysed. Fifteen per cent of EVARs require IIA sacrifice. Buttock claudication (BC) occurred in 27.9% of patients, although 48.0% resolved after 21.8 months. BC rates were 32.6% with coils, 23.8% with plugs, and 12.9% with coverage alone, and less with unilateral (vs. bilateral) IIA treatment (OR 0.57, 95% CI 0.36–0.91). More proximal coil placement resulted in lower rates of BC (OR 0.12, 95% CI 0.03–0.48). Erectile dysfunction occurred in 10.2% of males, with higher rates after coiling. Type II endoleaks were more frequent after covering alone; however re-interventions were rare. Significant ischaemic events (bowel/gluteal/spinal ischaemia) were very rare. Plugs were quicker to place and required less radiation ( p < .001) than coils. GRADE scoring was very low for all outcomes. Conclusion Overall the quality of reported data on IIA sacrifice is poor. Buttock claudication and erectile dysfunction occurred frequently after IIA sacrifice. Where both options are technically possible, plugs could be considered preferential to coils, and placed as proximally in the IIA as possible.
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