Recent work has demonstrated that some functional categories of the genome contribute disproportionately to the heritability of complex diseases. Here we analyze a broad set of functional elements, ...including cell type-specific elements, to estimate their polygenic contributions to heritability in genome-wide association studies (GWAS) of 17 complex diseases and traits with an average sample size of 73,599. To enable this analysis, we introduce a new method, stratified LD score regression, for partitioning heritability from GWAS summary statistics while accounting for linked markers. This new method is computationally tractable at very large sample sizes and leverages genome-wide information. Our findings include a large enrichment of heritability in conserved regions across many traits, a very large immunological disease-specific enrichment of heritability in FANTOM5 enhancers and many cell type-specific enrichments, including significant enrichment of central nervous system cell types in the heritability of body mass index, age at menarche, educational attainment and smoking behavior.
Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing ...estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are the lack of availability of individual-level genotype data and widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique-cross-trait LD Score regression-for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap. We use this method to estimate 276 genetic correlations among 24 traits. The results include genetic correlations between anorexia nervosa and schizophrenia, anorexia and obesity, and educational attainment and several diseases. These results highlight the power of genome-wide analyses, as there currently are no significantly associated SNPs for anorexia nervosa and only three for educational attainment.
The injection and mixing of contaminant mass into the fuel in inertial confinement fusion (ICF) implosions is a primary factor preventing ignition. ICF experiments have recently achieved an ...alpha-heating regime, in which fusion self-heating is the dominant source of yield, by reducing the susceptibility of implosions to instabilities that inject this mass. We report the results of unique separated reactants implosion experiments studying pre-mixed contaminant as well as detailed high-resolution three-dimensional simulations that are in good agreement with experiments. At conditions relevant to mixing regions in high-yield implosions, we observe persistent chunks of contaminant that do not achieve thermal equilibrium with the fuel throughout the burn phase. The assumption of thermal equilibrium is made in nearly all computational ICF modeling and methods used to infer levels of contaminant from experiments. We estimate that these methods may underestimate the amount of contaminant by a factor of two or more.
Habitat selection studies facilitate assessing and predicting species distributions and habitat connectivity, but habitat selection can vary temporally and among individuals, which is often ignored. ...We used GPS telemetry data from 96 Gray wolves (Canis lupus) in the western Great Lakes region of the USA to assess differences in habitat selection while wolves exhibited resident (territorial) or non-resident (dispersing or floating) movements and discuss implications for habitat connectivity. We used a step-selection function (SSF) to assess habitat selection by wolves exhibiting resident or non-resident movements, and modeled circuit connectivity throughout the western Great Lakes region. Wolves selected for natural land cover and against areas with high road densities, with no differences in selection among wolves when resident, dispersing, or floating. Similar habitat selection between resident and non-resident wolves may be due to similarity in environmental conditions, when non-resident movements occur largely within established wolf range rather than near the periphery or beyond the species range. Alternatively, non-resident wolves may travel through occupied territories because higher food availability or lower human disturbance outweighs risks posed by conspecifics. Finally, an absence of differences in habitat selection between resident and non-resident wolf movements may be due to other unknown reasons. We recommend considering context-dependency when evaluating differences in movements and habitat use between resident and non-resident individuals. Our results also provide independent validation of a previous species distribution model and connectivity analysis suggesting most potential wolf habitat in the western Great Lakes region is occupied, with limited connectivity to unoccupied habitat.
Salt contamination of lakes, due to the application of winter de-icing salts on roads, presents a significant environmental challenge in the “salt belt” region of eastern North America. The research ...reported here presents the first deployment of a previously published proxy tool based on Arcellinida (testate lobose amoebae) for monitoring road salt contamination. The research was conducted at Silver Lake in Eastern Ontario, a 4-km-long lake with the heavily traveled Trans-Canada Highway (HWY 7) transiting the entire southern shore. The lake showed elevated conductivity (297–310 µS/cm) and sub-brackish conditions (0.14–0.15 ppt). Sodium levels were also elevated near the roadside (median Na = 1020 ppm). Cluster analysis and nonmetric multidimensional scaling results revealed four distinct Arcellinida assemblages: “Stressed Cool Water Assemblage (SCWA),” “Deep Cold Water Assemblage (DCWA),” both from below the 8-m thermocline, and the shallower water “Shallow Water Assemblage 1 (SWA-1)” and “Shallow Water Assemblage 2 (SWA-2)”. Redundancy analysis showed a minor response of Arcellinida to road salt contamination in shallower areas of the lake, with confounding variables significantly impacting assemblage distribution, particularly beneath the thermocline (e.g., water temperature, water depth, sediment runoff from catchment Ti, sediment geochemistry Ca, S). The results of this study indicate that the trophic structure of the lake has to date only been modestly impacted by the cumulative nature of road salt contamination. Nonetheless, the Silver Lake results should be considered of concern and warrant continued arcellinidan biomonitoring to gauge the ongoing and long-term effects of road salt on its ecosystem.
Examining paleoclimate-driven changes of elemental contaminants, such as Arsenic (As), increases the understanding of the mobility and fate of elements under a warming climate scenario. To ...characterize the variability in As sequestration in the sediments of a freshwater system in response to decadal- to centennial-scale climate oscillations, a freeze-core (CON01) was recovered from Control Lake, Northwest Territories. Radiocarbon dating of 13 bulk-organic samples provided temporal reference to core depth. Sediment geochemistry was determined using Itrax X-ray fluorescence core-scanning (Itrax-XRF). Elemental concentrations were measured on a sub-set of samples using ICP-MS after multi-acid (MA) digestion to assess the accuracy of Itrax-XRF results through a multivariate log-ratio (MLC) calibration. Comparison of Itrax-XRF to ICP-MS using the MLC in ItraXelerate software show Pearson's R2 values >0.75, with the exception of As (R2 = 0.44). MLC-calibrated Itrax-XRF elemental data were centered log-ratio (CLR) transformed to eliminate issues related to data closure. During the ca. 3300-yr sedimentary record, moderate-strength negative correlations between AsCLR and KCLR (Spearman's ρ = −0.38, p-value < 0.001, n = 785), and AsCLR and TiCLR, (Spearman's ρ = −0.52, p-value < 0.001, n = 785) suggest that As is primarily sequestered in sediments during intervals of warmer temperatures and higher productivity. Proxies for sediment particle size (TiCLR, KCLR) and As concentration (AsCLR) were examined for response to quasi-periodic climate oscillations using spectral analysis. Significant periodicities were observed with approximately 4–13, 30–60, 90–120, and 160–280 yr periods in TiCLR, KCLR, and AsCLR records. These frequencies are interpreted as corresponding to the North Atlantic Oscillation and/or 8–14-yr Schwabe sunspot cycles, 30–60-yr Pacific Decadal Oscillation, and centennial-scale solar cycles (e.g., 90-yr Gleissberg cycle; 205-yr Suess cycle). Coeval occurrence of these periodicities revealed through wavelet analysis of Control Lake geochemistry data suggests that these climate cycles only impact Control Lake when they occur concurrently.
•Itrax-XRF analysis of a sediment core from NT, Canada, provided sub-decadal geochemical data.•Wavelet and spectral analyses reveal 9–13, 30–60, 100, and 200 yr periodicities in data.•Periodicities correspond to known PDO, AO/NAO, and decadal to centennial solar cycles.•Higher As occurred during warmer intervals with high lake productivity.
Site fidelity is thought to provide increased fitness through familiarity with the distribution of forage, protective cover, breeding and offspring rearing sites, and predators. For moose (Alces ...alces (Linnaeus, 1758)), previous research has documented fidelity at varying spatial scales. Our objective was to build on this knowledge and assess fidelity by adult female moose in two areas of central Ontario, Canada (Algonquin Provincial Park (APP) and Wildlife Management Unit 49 (WMU49)). We used global positioning system data to generate mean weekly locations for collared moose, then measured the distance between paired weekly locations among consecutive years to evaluate site fidelity. We tested for effects of study area, biological season, moose age, and reproductive status using generalized linear mixed models. Moose demonstrated stronger site fidelity in WMU49, an area with more anthropogenic disturbance, than the protected area, APP. Fidelity was weakest in the winter, but was similar among other seasons and was independent of maternal age and the presence of a calf. Our study highlights the need to consider the scale of site fidelity relative to habitat management. Actions aimed at supporting moose populations might benefit more by protecting habitat classes selected by moose rather than specific sites used by individuals.
Electrical impedance tomography (EIT) is an attractive method for clinically monitoring patients during mechanical ventilation, because it can provide a non-invasive continuous image of pulmonary ...impedance which indicates the distribution of ventilation. However, most clinical and physiological research in lung EIT is done using older and proprietary algorithms; this is an obstacle to interpretation of EIT images because the reconstructed images are not well characterized. To address this issue, we develop a consensus linear reconstruction algorithm for lung EIT, called GREIT (Graz consensus Reconstruction algorithm for EIT). This paper describes the unified approach to linear image reconstruction developed for GREIT. The framework for the linear reconstruction algorithm consists of (1) detailed finite element models of a representative adult and neonatal thorax, (2) consensus on the performance figures of merit for EIT image reconstruction and (3) a systematic approach to optimize a linear reconstruction matrix to desired performance measures. Consensus figures of merit, in order of importance, are (a) uniform amplitude response, (b) small and uniform position error, (c) small ringing artefacts, (d) uniform resolution, (e) limited shape deformation and (f) high resolution. Such figures of merit must be attained while maintaining small noise amplification and small sensitivity to electrode and boundary movement. This approach represents the consensus of a large and representative group of experts in EIT algorithm design and clinical applications for pulmonary monitoring. All software and data to implement and test the algorithm have been made available under an open source license which allows free research and commercial use.
Various methods exist to monitor wildlife populations and estimate trends in their distribution and abundance. For American beaver (Castor canadensis), aerial surveys provide a means to obtain ...abundance data over large areas and typically involve observers searching watercourses and shorelines for active beaver presence. Here, we describe a systematic aerial photographic census we designed and executed in autumn to quantify annual beaver colony abundance on the 184‐km2 Michipicoten Island, Ontario, from 2015 to 2019. Aerial photographs were stitched together into orthophotomosaics after each census and visually searched for beaver food caches, with each food cache representing an independent beaver colony. Our methods revealed that beaver colony abundance declined substantially from a peak of 6.1 colonies/km2 in 2015, the highest reported across North America, to 0.4 colonies/km2 in 2018. Beaver abundance remained low through 2019. Although photographing the entire isolated study area required relatively little time and effort, even when beaver density was very high, post‐census processing work was time‐consuming. Lessons learned will improve efficiencies of our future censuses and aid other researchers. Our method is advantageous over traditional aerial wildlife surveys in that it provides a digital and visual record that can be used for additional analyses.
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