SDSS J115517.35+634622.0: A Newly Discovered Gravitationally Lensed Quasar

We report the discovery of SDSSJ115517.35+634622.0, a previously unknown gravitationally lensed quasar. The lens system exhibits two images of a $z = 2.89$ quasar, with an image separation of 1{\farcs}832 \pm 0.007 . Near-IR imaging of the system reveals the presence of the lensing galaxy between the two quasar images. Based on absorption features seen in the Sloan Digital Sky Survey (SDSS) spectrum, we determine a lens galaxy redshift of $z = 0.1756$. The lens is rather unusual in that one of the quasar images is only 0{\farcs}22\pm0{\farcs}07 ($\sim 0.1 R_{\rm eff}$) from the center of the lens galaxy and photometric modeling indicates that this image is significantly brighter than predicted by a SIS model. This system was discovered in the course of an ongoing search for strongly lensed quasars in the dataset from the SDSS.Comment: 18 pages, 6 figures. Accepted for publication in A

The Sloan Digital Sky Survey Quasar Lens Search. II. Statistical lens sample from the third data release

We report the first results of our systematic search for strongly lensed quasars using the spectroscopically confirmed quasars in the Sloan Digital Sky Survey (SDSS). Among 46,420 quasars from the SDSS Data Release 3 (~4188 deg^2), we select a subsample of 22,683 quasars that are located at redshifts between 0.6 and 2.2 and are brighter than the Galactic extinction-corrected i-band magnitude of 19.1. We identify 220 lens candidates from the quasar subsample, for which we conduct extensive and systematic follow-up observations in optical and near-infrared wavebands, in order to construct a complete lensed quasar sample at image separations between 1" and 20" and flux ratios of faint to bright lensed images larger than 10^(−0.5). We construct a statistical sample of 11 lensed quasars. Ten of these are galaxy-scale lenses with small image separations (~ 1"-2") and one is a large separation (15") system which is produced by a massive cluster of galaxies, representing the first statistical sample of lensed quasars including both galaxy- and cluster-scale lenses. The Data Release 3 spectroscopic quasars contain an additional 11 lensed quasars outside the statistical sample

The Sloan Digital Sky Survey Quasar Lens Search. III. Constraints on Dark Energy from the Third Data Release Quasar Lens Catalog

We present cosmological results from the statistics of lensed quasars in the Sloan Digital Sky Survey (SDSS) Quasar Lens Search. By taking proper account of the selection function, we compute the expected number of quasars lensed by early-type galaxies and their image separation distribution assuming a flat universe, which is then compared with 7 lenses found in the SDSS Data Release 3 to derive constraints on dark energy under strictly controlled criteria. For a cosmological constant model (w=-1) we obtain \Omega_\Lambda=0.74^{+0.11}_{-0.15}(stat.)^{+0.13}_{-0.06}(syst.). Allowing w to be a free parameter we find \Omega_M=0.26^{+0.07}_{-0.06}(stat.)^{+0.03}_{-0.05}(syst.) and w=-1.1\pm0.6(stat.)^{+0.3}_{-0.5}(syst.) when combined with the constraint from the measurement of baryon acoustic oscillations in the SDSS luminous red galaxy sample. Our results are in good agreement with earlier lensing constraints obtained using radio lenses, and provide additional confirmation of the presence of dark energy consistent with a cosmological constant, derived independently of type Ia supernovae.Comment: 9 pages, 3 figures, 2 tables, accepted for publication in A

Distribution of Mycobacterium ulcerans in Buruli Ulcer Endemic and Non-Endemic Aquatic Sites in Ghana

Mycobacterium ulcerans, the causative agent of Buruli ulcer, is an emerging environmental bacterium in Australia and West Africa. The primary risk factor associated with Buruli ulcer is proximity to slow moving water. Environmental constraints for disease are shown by the absence of infection in arid regions of infected countries. A particularly mysterious aspect of Buruli ulcer is the fact that endemic and non-endemic villages may be only a few kilometers apart within the same watershed. Recent studies suggest that aquatic invertebrate species may serve as reservoirs for M. ulcerans, although transmission pathways remain unknown. Systematic studies of the distribution of M. ulcerans in the environment using standard ecological methods have not been reported. Here we present results from the first study based on random sampling of endemic and non-endemic sites. In this study PCR-based methods, along with biofilm collections, have been used to map the presence of M. ulcerans within 26 aquatic sites in Ghana. Results suggest that M. ulcerans is present in both endemic and non-endemic sites and that variable number tandem repeat (VNTR) profiling can be used to follow chains of transmission from the environment to humans. Our results suggesting that the distribution of M. ulcerans is far broader than the distribution of human disease is characteristic of environmental pathogens. These findings imply that focal demography, along with patterns of human water contact, may play a major role in transmission of Buruli ulcer

Patterns and rates of exonic de novo mutations in autism spectrum disorders

Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified1,2. To identify further genetic risk factors, we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n= 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant and the overall rate of mutation is only modestly higher than the expected rate. In contrast, there is significantly enriched connectivity among the proteins encoded by genes harboring de novo missense or nonsense mutations, and excess connectivity to prior ASD genes of major effect, suggesting a subset of observed events are relevant to ASD risk. The small increase in rate of de novo events, when taken together with the connections among the proteins themselves and to ASD, are consistent with an important but limited role for de novo point mutations, similar to that documented for de novo copy number variants. Genetic models incorporating these data suggest that the majority of observed de novo events are unconnected to ASD, those that do confer risk are distributed across many genes and are incompletely penetrant (i.e., not necessarily causal). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5 to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favor of CHD8 and KATNAL2 as genuine autism risk factors

Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls

We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD. © 2013 Liu et al

The severity of pandemic H1N1 influenza in the United States, from April to July 2009: A Bayesian analysis

Background: Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. Methods and Findings: We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data - medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York - were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-96lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5-17 y. sCHR appears to be lowest in persons aged 5-17; our data were too sparse to allow us to determine the group in which it was the highest. Conclusions: These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.published_or_final_versio

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes