Response times for visually guided saccades in persons with Parkinson's disease : a meta-analytic review

Individuals with Parkinson's disease (PD) show marked impairments in their ability to generate self-initiated, or “voluntary”, saccadic eye movements. Investigations of visually guided, or “reflexive”, saccades have, on the other hand, produced inconclusive results with studies showing response times (RTs) in persons with PD that are slower, faster, or indistinguishable from those of controls. We performed a meta-analysis to establish whether there are consistent effects of PD on the metrics of visually guided saccades. Combining results across 47 studies we found that reflexive saccades are overall initiated more slowly in persons with PD than in controls, however, this analysis also revealed considerable heterogeneity across studies. Step-wise meta-regression, using eleven potential predictors, subsequently showed that differences in mean RT between controls and persons with PD may arise due to aspects of experimental design. In particular, mean target eccentricity was shown to impact substantially on RTs such that persons with PD predictably initiate saccades faster than controls at small target eccentricities, while responding more slowly for large target eccentricities. Changes in eye-tracking and display equipment over the period covered by the review were also found to have impacted on the pattern of results obtained. We conclude that a, previously unsuspected, eccentricity effect could explain why the saccadic eye movements of persons with PD are sometimes found to be “hyper-reflexive” compared to controls, and suggest that this effect may arise due to PD-induced changes in both peripheral perceptual processing and in central executive mechanisms involving the basal ganglia

Free-electron laser results from the Advanced Test Accelerator

PALADIN is a 10.6-..mu..m FEL amplifier experiment operating at the Lawrence Livermore National Laboratory's Advanced Test Accelerator, an induction linear accelerator designed to produce a 45-MeV, 10-kA electron beam. With a 15-m long wiggler, PALADIN demonstrated 27 dB of exponential gain from a 14-kW input signal. With a 5-MW input signal, the amplifier saturated after 10 dB of gain. The exponentially growing signal in the unsaturated amplifier was clearly seen to be gain guided by the electron beam. 7 refs., 8 figs

Schottky barrier heights at polar metal/semiconductor interfaces

Using a first-principle pseudopotential approach, we have investigated the Schottky barrier heights of abrupt Al/Ge, Al/GaAs, Al/AlAs, and Al/ZnSe (100) junctions, and their dependence on the semiconductor chemical composition and surface termination. A model based on linear-response theory is developed, which provides a simple, yet accurate description of the barrier-height variations with the chemical composition of the semiconductor. The larger barrier values found for the anion- than for the cation-terminated surfaces are explained in terms of the screened charge of the polar semiconductor surface and its image charge at the metal surface. Atomic scale computations show how the classical image charge concept, valid for charges placed at large distances from the metal, extends to distances shorter than the decay length of the metal-induced-gap states.Comment: REVTeX 4, 11 pages, 6 EPS figure

A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe