Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students

Background: Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk. Methods: We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h2SNP) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults. Results: Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h2SNP estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample. Conclusions: These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification

Maximizing information : a machine learning approach for analysis of complex nanoscale electromechanical behavior in defect-rich PZT films

F.Z. and B.J.R. gratefully acknowledge support from the China Scholarship Council and Science Foundation Ireland (US-Ireland R&D Partnership Programme (SFI/14/US/I3113) and Career Development Award (SFI/17/CDA/4637) with support from the Sustainable Energy Authority of Ireland). A.N. gratefully acknowledges support from the Engineering and Physics Sciences Research Council (EPSRC) through grants EP/R023751/1 and EP/L017008/1. A.K. gratefully acknowledges support from Department of Education and Learning NI through grant USI-082 and Engineering and Physical Sciences Research Council via grant EP/S037179/1. K.W., Y.Y., and N.B.G. gratefully acknowledge support from the US National Science Foundation through grant CMMI-1537262 and DMR-1255379. K.W. and N.B.G. also acknowledge support through DMR-2026976. This publication has emanated from research supported in part by a grant from Science Foundation Ireland under Grant numbers SFI/14/US/I3113 and SFI/17/CDA/4637.Scanning Probe Microscopy (SPM) based techniques probe material properties over microscale regions with nanoscale resolution, ultimately resulting in investigation of mesoscale functionalities. Among SPM techniques, piezoresponse force microscopy (PFM) is a highly effective tool in exploring polarization switching in ferroelectric materials. However, its signal is also sensitive to sample-dependent electrostatic and chemo-electromechanical changes. Literature reports have often concentrated on the evaluation of the Off-field piezoresponse, compared to On-field piezoresponse, based on the latter's increased sensitivity to non-ferroelectric contributions. Using machine learning approaches incorporating both Off- and On-field piezoresponse response as well as Off-field resonance frequency to maximize information, switching piezoresponse in a defect-rich Pb(Zr,Ti)O3 thin film is investigated. As expected, one major contributor to the piezoresponse is mostly ferroelectric, coupled with electrostatic phenomena during On-field measurements. A second component is electrostatic in nature, while a third component is likely due to a superposition of multiple non-ferroelectric processes. The proposed approach will enable deeper understanding of switching phenomena in weakly ferroelectric samples and materials with large chemo-electromechanical response.Publisher PDFPeer reviewe

Barriers to Infectious Disease Care among Lesbians1

Despite the considerable number of women in the United States who identify as lesbian, few data exist that address lesbians' health needs. The Institute of Medicine emphasized that data on sexually transmitted infections, Pap smear screening, and cervical dysplasia among lesbians were needed to guide clinical practice, policy development, and patient education. Use of surveillance data for this purpose is limited because risk classifications exclude same-gender sex among women or subsume it under behavior considered as higher risk. However, sexual transmission of human papillomavirus, HIV, Treponema pallidum, and Trichomonas vaginalis between women has been reported. Data indicate that lesbians receive routine Pap smear screening less frequently than is optimal. Moreover, lesbians commonly report previous pregnancy, induced abortion, and hormonal contraceptive use. Education of lesbians and their care providers should counter assumptions that sex between women confers no risk for transmission of sexually transmitted infections, and lesbians should receive Pap smears according to current guidelines

Sum rules and dualities for generalized parton distributions: is there a holographic principle?

To leading order approximation, the physical content of generalized parton distributions (GPDs) that is accessible in deep virtual electroproduction of photons or mesons is contained in their value on the cross-over trajectory. This trajectory separates the t-channel and s-channel dominated GPD regions. The underlying Lorentz covariance implies correspondence between these two regions through their relation to GPDs on the cross-over trajectory. This point of view leads to a family of GPD sum rules which are a quark analogue of finite energy sum rules and it guides us to a new phenomenological GPD concept. As an example, we discuss the constraints from the JLab/Hall A data on the dominant u-quark GPD H. The question arises whether GPDs are governed by some kind of holographic principle.Comment: 45 pages, 4 figures, Sect. 2 reorganized for clarity. Typos in Eq. (20) corrected. 4 new refs. Matches published versio

Climate warming, marine protected areas and the ocean-scale integrity of coral reef ecosystems

Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the 1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure, diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales, with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance. This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should be integrated into existing management frameworks and combined with policies to improve system-wide resilience to climate variation and change

A time study of physicians' work in a German university eye hospital to estimate unit costs.

BACKGROUND: Technical efficiency of hospital services is debated since performance has been heterogeneous. Staff time represents the main resource in patient care and its inappropriate allocation has been identified as a key factor of inefficiency. The aim of this study was to analyse the utilisation of physicians' work time stratified by staff groups, tasks and places of work. A further aim was to use these data to estimate resource use per unit of output. METHODS: A self-reporting work-sampling study was carried during 14-days at a University Eye Hospital. Staff costs of physicians per unit of output were calculated at the wards, the operating rooms and the outpatient unit. RESULTS: Forty per cent of total work time was spent in contact with the patient. Thirty per cent was spent with documentation tasks. Time spent with documentation tasks declined monotonically with increasing seniority of staff. Unit costs were 56 € per patient day at the wards, 77 € and 20 € per intervention at the operating rooms for inpatients and outpatients, respectively, and 33 € per contact at the outpatient unit. Substantial differences in resources directly dedicated to the patient were found between these locations. CONCLUSION: The presented data provide unprecedented units costs in inpatient Ophthalmology. Future research should focus on analysing factors that influence differences in time allocation, such as types of patients, organisation of care processes and composition of staff

Characterization of Coding Synonymous and Non-Synonymous Variants in ADAMTS13 Using Ex Vivo and In Silico Approaches

Synonymous variations, which are defined as codon substitutions that do not change the encoded amino acid, were previously thought to have no effect on the properties of the synthesized protein(s). However, mounting evidence shows that these “silent” variations can have a significant impact on protein expression and function and should no longer be considered “silent”. Here, the effects of six synonymous and six non-synonymous variations, previously found in the gene of ADAMTS13, the von Willebrand Factor (VWF) cleaving hemostatic protease, have been investigated using a variety of approaches. The ADAMTS13 mRNA and protein expression levels, as well as the conformation and activity of the variants have been compared to that of wild-type ADAMTS13. Interestingly, not only the non-synonymous variants but also the synonymous variants have been found to change the protein expression levels, conformation and function. Bioinformatic analysis of ADAMTS13 mRNA structure, amino acid conservation and codon usage allowed us to establish correlations between mRNA stability, RSCU, and intracellular protein expression. This study demonstrates that variants and more specifically, synonymous variants can have a substantial and definite effect on ADAMTS13 function and that bioinformatic analysis may allow development of predictive tools to identify variants that will have significant effects on the encoded protein