Gene-gene Interaction Analyses for Atrial Fibrillation

Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in a

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

14 p.Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change

Aligning the CMS Muon Chambers with the Muon Alignment System during an Extended Cosmic Ray Run

Peer reviewe

Controls on dryland mountain landscape development along the NW Saharan desert margin: Insights from Quaternary river terrace sequences (Dadès River, south-central High Atlas, Morocco)

This study documents river terraces from upstream reaches of the Dad es River, a major fluvial system draining the south-central High Atlas Mountains. Terraces occur as straths with bedrock bases positioned at 10 m altitudinal intervals up to 40 m (T1-T5) above the valley floor, becoming less common between 50 and 140 m. The rock strength, stratigraphy and structure of the mountain belt influences terrace distribution. Terraces are absent in river gorges of structurally thickened limestone; whilst welldeveloped, laterally continuous terraces (T1-T4) form along wide valleys occupying syncline structures dominated by weaker interbedded limestone-mudstone. Terrace staircases develop in confined canyons associated with weaker lithologies and influence from structural dip and stratigraphic configuration. Terraces comprise a bedrock erosion surface overlain by fluvial conglomerates, rare overbank sands and colluvium. This sequence with some OSL/IRSL age control, suggests terrace formation over a 100 ka climate cycle with valley floor aggradation during full glacials and incision during glacial-interglacial transitions. This integrates with other archives (e.g. lakes, glaciers, dunes), appearing typical of landscape development along the NW Saharan margin south of the High Atlas, and similar to patterns in the western-southern Mediterranean. The 100 ka climate cycle relationship suggests that the terrace sequence documents Late-Middle Pleistocene landscape development. Consistent altitudinal spacing of terraces and their distribution throughout the orogen suggests sustained base-level lowering linked to uplift-exhumation of the High Atlas. Low incision rates (<0.2 mm a 1) and general absence of terrace deformation suggests dominance of isostatically driven base-level lowering with relief generation being Early Pleistocene or older.National Geographic research grant (8609-09

Pulmonary Function and Blood DNA Methylation A Multiancestry Epigenome-Wide Association Meta-analysis

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function. Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics. Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate,,0.025) in relation to FEV1, FVC, or FEV1/FVC, including 1,240 novel and 73 also related to chronic obstructive pulmonary disease (1,787 cases). We found 294 CpGs unique to European or African ancestry and 395 CpGs unique to never or ever smokers. The majority of significant CpGs correlated with nearby gene expression in blood. Findings were enriched in key regulatory elements for gene function, including accessible chromatin elements, in both blood and lung. Sixty-nine implicated genes are targets of investigational or approved drugs. One example novel gene highlighted by integrative epigenomic and druggable target analysis is TNFRSF4. Mendelian randomization and colocalization analyses suggest that epigenome-wide association study signals capture causal regulatory genomic loci. Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

A new Taxonomy of Continuous Global Optimization Algorithms

Surrogate-based optimization and nature-inspired metaheuristics have become the state of the art in solving real-world optimization problems. Still, it is difficult for beginners and even experts to get an overview that explains their advantages in comparison to the large number of available methods in the scope of continuous optimization. Available taxonomies lack the integration of surrogate-based approaches and thus their embedding in the larger context of this broad field. This article presents a taxonomy of the field, which further matches the idea of nature-inspired algorithms, as it is based on the human behavior in path finding. Intuitive analogies make it easy to conceive the most basic principles of the search algorithms, even for beginners and non-experts in this area of research. However, this scheme does not oversimplify the high complexity of the different algorithms, as the class identifier only defines a descriptive meta-level of the algorithm search strategies. The taxonomy was established by exploring and matching algorithm schemes, extracting similarities and differences, and creating a set of classification indicators to distinguish between five distinct classes. In practice, this taxonomy allows recommendations for the applicability of the corresponding algorithms and helps developers trying to create or improve their own algorithms

Behavior-based neuroevolutionary training in reinforcement learning

In addition to their undisputed success in solving classical optimization problems, neuroevolutionary and population-based algorithms have become an alternative to standard reinforcement learning methods. However, evolutionary methods often lack the sample efficiency of standard value-based methods that leverage gathered state and value experience. If reinforcement learning for real-world problems with significant resource cost is considered, sample efficiency is essential. The enhancement of evolutionary algorithms with experience exploiting methods is thus desired and promises valuable insights. This work presents a hybrid algorithm that combines topology-changing neuroevolutionary optimization with value-based reinforcement learning. We illustrate how the behavior of policies can be used to create distance and loss functions, which benefit from stored experiences and calculated state values. They allow us to model behavior and perform a directed search in the behavior space by gradient-free evolutionary algorithms and surrogate-based optimization. For this purpose, we consolidate different methods to generate and optimize agent policies, creating a diverse population. We exemplify the performance of our algorithm on standard benchmarks and a purpose-built real-world problem. Our results indicate that combining methods can enhance the sample efficiency and learning speed for evolutionary approaches