The z=0.0912 and z=0.2212 Damped Lyman Alpha Galaxies Along the Sight-Line Toward the Quasar OI 363

New optical and infrared observations along the sight-line toward the quasar OI 363 (0738+313) are presented and discussed. Excluding systems which lack confirming UV spectroscopic observations of the actual Lyman alpha line, this sight-line presently contains the two lowest-redshift classical damped Lyman alpha (DLA) quasar absorption line systems known (i.e. with N(HI) \ge 2 x 10^{20} atoms cm^{-2}), one at z(abs)=0.0912 and the other at z(abs)=0.2212. The z=0.09 DLA galaxy appears to be an extended low surface brightness galaxy which is easily visible only in infrared images and shows rich morphological structure. Subtraction of the quasar nuclear and host light yields L_K \approx 0.08L_K* at z=0.09. The impact parameter between the galaxy and quasar sight-line is very small, b<3.6 kpc (<2 arcsec), which makes measurements difficult. The z=0.22 DLA galaxy is an early-type dwarf with a K-band luminosity of L_K \approx 0.1L_K* at impact parameter b=20 kpc. In general, these results serve to support mounting evidence that DLA galaxies are drawn from a wide variety of gas-rich galaxy types. (Abridged)Comment: 27 pages, 6 figures, 2 in color. Submitted to Ap

Genome-wide gene by environment study of time spent in daylight and chronotype identifies emerging genetic architecture underlying light sensitivity

Study Objectives: Light is the primary stimulus for synchronizing the circadian clock in humans. There are very large interindividual differences in the sensitivity of the circadian clock to light. Little is currently known about the genetic basis for these interindividual differences.Methods: We performed a genome-wide gene-by-environment interaction study (GWIS) in 280 897 individuals from the UK Biobank cohort to identify genetic variants that moderate the effect of daytime light exposure on chronotype (individual time of day preference), acting as “light sensitivity” variants for the impact of daylight on the circadian system.Results: We identified a genome-wide significant SNP mapped to the ARL14EP gene (rs3847634; p &lt; 5 × 10−8), where additional minor alleles were found to enhance the morningness effect of daytime light exposure (βGxE = −.03, SE = 0.005) and were associated with increased gene ARL14EP expression in brain and retinal tissues. Gene-property analysis showed light sensitivity loci were enriched for genes in the G protein-coupled glutamate receptor signaling pathway and genes expressed in Per2+ hypothalamic neurons. Linkage disequilibrium score regression identified Bonferroni significant genetic correlations of greater light sensitivity GWIS with later chronotype and shorter sleep duration. Greater light sensitivity was nominally genetically correlated with insomnia symptoms and risk for post-traumatic stress disorder (PTSD).Conclusions: This study is the first to assess light as an important exposure in the genomics of chronotype and is a critical first step in uncovering the genetic architecture of human circadian light sensitivity and its links to sleep and mental healt

A novel method for radiotherapy patient identification using surface imaging

Performing a procedure on the wrong patient or site is one of the greatest errors that can occur in medicine. The addition of automation has been shown to reduce errors in many processes. In this work we explore the use of an automated patient identification process using optical surface imaging for radiotherapy treatments. Surface imaging uses visible light to align the patient to a reference surface in the treatment room. It is possible to evaluate the similarity between a daily set-up surface image and the reference image using distance to agreement between the points on the two surfaces. The higher the percentage overlapping points within a defined distance, the more similar the surfaces. This similarity metric was used to intercompare 16 left-sided breast patients. The reference surface for each patient was compared to 10 daily treatment surfaces for the same patient, and 10 surfaces from each of the other 15 patients (for a total of 160 comparisons per patient), looking at the percent of points overlapping. For each patient, the minimum same-patient similarity score was higher than the maximum different-patient score. For the group as a whole a threshold was able to classify correct and incorrect patients with high levels of accuracy. A 10-fold cross-validation using linear discriminant analysis gave cross-validation loss of 0.0074. An automated process using surface imaging is a feasible option to provide nonharmful daily patient identification verification using currently available technology

The impact of Mendelian sleep and circadian genetic variants in a population setting

Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants in these genes with extreme sleep conditions were usually based on clinically ascertained families, and their effects when identified in the population are unknown. We aimed to determine the effects of these variants on sleep traits in large population-based cohorts. We performed genetic association analysis of variants previously reported to be causal for Mendelian sleep and circadian conditions. Analyses were performed using 191,929 individuals with data on sleep and whole-exome or genome-sequence data from 4 population-based studies: UK Biobank, FINRISK, Health-2000-2001, and the Multi-Ethnic Study of Atherosclerosis (MESA). We identified sleep disorders from self-report, hospital and primary care data. We estimated sleep duration and timing measures from self-report and accelerometery data. We identified carriers for 10 out of 12 previously reported pathogenic variants for 8 of the 10 genes. They ranged in frequency from 1 individual with the variant in CSNK1D to 1,574 individuals with a reported variant in the PER3 gene in the UK Biobank. No carriers for variants reported in NPSR1 or PER2 were identified. We found no association between variants analyzed and extreme sleep or circadian phenotypes. Using sleep timing as a proxy measure for sleep phase, only PER3 and CRY1 variants demonstrated association with earlier and later sleep timing, respectively; however, the magnitude of effect was smaller than previously reported (sleep midpoint similar to 7 mins earlier and similar to 5 mins later, respectively). We also performed burden tests of protein truncating (PTVs) or rare missense variants for the 10 genes. Only PTVs in PER2 and PER3 were associated with a relevant trait (for example, 64 individuals with a PTV in PER2 had an odds ratio of 4.4 for being "definitely a morning person", P = 4x10(-8); and had a 57-minute earlier midpoint sleep, P = 5x10(-7)). Our results indicate that previously reported variants for Mendelian sleep and circadian conditions are often not highly penetrant when ascertained incidentally from the general population.Peer reviewe

CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids

Mutations in the colony stimulating factor 1 receptor

Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment