Genome-wide association studies of the self-rating of effects of ethanol (SRE).

The level of response (LR) to alcohol as measured with the Self-Report of the Effects of Alcohol Retrospective Questionnaire (SRE) evaluates the number of standard drinks usually required for up to four effects. The need for a higher number of drinks for effects is genetically influenced and predicts higher risks for heavy drinking and alcohol problems. We conducted genome-wide association study (GWAS) in the African-American (COGA-AA, N = 1527 from 309 families) and European-American (COGA-EA, N = 4723 from 956 families) subsamples of the Collaborative Studies on the Genetics of Alcoholism (COGA) for two SRE scores: SRE-T (average of first five times of drinking, the period of heaviest drinking, and the most recent 3 months of consumption) and SRE-5 (the first five times of drinking). We then meta-analyzed the two COGA subsamples (COGA-AA + EA). Both SRE-T and SRE-5 were modestly heritable (h2 : 21%-31%) and genetically correlated with alcohol dependence (AD) and DSM-IV AD criterion count (rg : 0.35-0.76). Genome-wide significant associations were observed (SRE-T: chromosomes 6, rs140154945, COGA-EA P = 3.30E-08 and 11, rs10647170, COGA-AA+EA P = 3.53E-09; SRE-5: chromosome13, rs4770359, COGA-AA P = 2.92E-08). Chromosome 11 was replicated in an EA dataset from the National Institute on Alcohol Abuse and Alcoholism intramural program. In silico functional analyses and RNA expression analyses suggest that the chromosome 6 locus is an eQTL for KIF25. Polygenic risk scores derived using the COGA SRE-T and SRE-5 GWAS predicted 0.47% to 2.48% of variances in AD and DSM-IV AD criterion count in independent datasets. This study highlights the genetic contribution of alcohol response phenotypes to the etiology of alcohol use disorders

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P < 0.001), age, bisphosphonate use, and rodding (P < 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Development and stability of Th17 cells in ovarian cancer requires nitric oxide and endogenous NOS2 activity in cancer-associated CD4+ T cells

Th17 cells play reciprocal roles in different forms and at different stages of cancer. We report that the presence of Th17 cells in ovarian cancer ascites correlates with local expression of nitric oxide synthase-2 (NOS2). Furthermore, the development of RORγt+IL-23R+IL-17+ Th17 cells from human naive-, memory- or tumor-infiltrating CD4+ T cells critically depends on NO and endogenous NOS2 induced in CD4+ T cells by Th17-inducing cytokines (IL-1β/IL-6/IL-23) or by cancer-associated IL-1β/IL-6/IL-23/NO-producing MDSCs. Inhibition of NOS2 or its downstream cGMP/cGK signaling pathway abolishes de novo induction of Th17 cells. Moreover, even short-term blockade of NOS/cGMP suppresses the IL-17 production by established Th17 cells isolated from ovarian cancer patients, demonstrating the novel key role of NOS/cGMP in Th17 cell physiology and providing for new therapeutic targets to manipulate Th17- and NOS/cGMP-associated immunity in precancerous lesions and advanced cancer

Mental Contrasting With Implementation Intentions Reduces Drinking When Drinking Is Hazardous: An Online Self-Regulation Intervention

Introduction. Drinking alcohol has detrimental health consequences, and effective interventions to reduce hazardous drinking are needed. The self-regulation intervention of Mental Contrasting with Implementation Intentions (MCII) promotes behavior change across a variety of health behaviors. In this study, we tested if online delivery of MCII reduced hazardous drinking in people who were worried about their drinking. Method. Participants (N = 200, female = 107) were recruited online. They were randomized to learn MCII or solve simple math problems (control). Results. Immediately after the intervention, participants in the MCII condition (vs. control) reported an increased commitment to reduce drinking. After 1 month, they reported having taken action measured by the Readiness to Change drinking scale. When drinking was hazardous (Alcohol Use Disorders Identification Test ≥ 8, n = 85), participants in the MCII condition indicated a decreased number of drinking days, exp(β) = 0.47, CI (confidence interval) [−1.322, −.207], p = .02, and drinks per week, exp(β) = 0.57, CI [0.94, 5.514], p = .007, compared with the control condition. Discussion. These findings demonstrate that a brief, self-guided online intervention (Mdn = 28 minutes) can reduce drinking in people who worry about their drinking. Our findings show a higher impact in people at risk for hazardous drinking. Conclusion. MCII is scalable as an online intervention. Future studies should test the cost-effectiveness of the intervention in real-world settings

Taking into account sensory knowledge: the case of geo-techologies for children with visual impairments

This paper argues for designing geo-technologies supporting non-visual sensory knowledge. Sensory knowledge refers to the implicit and explicit knowledge guiding our uses of our senses to understand the world. To support our argument, we build on an 18 months field-study on geography classes for primary school children with visual impairments. Our findings show (1) a paradox in the use of non-visual sensory knowledge: described as fundamental to the geography curriculum, it is mostly kept out of school; (2) that accessible geo-technologies in the literature mainly focus on substituting vision with another modality, rather than enabling teachers to build on children's experiences; (3) the importance of the hearing sense in learning about space. We then introduce a probe, a wrist-worn device enabling children to record audio cues during field-trips. By giving importance to children's hearing skills, it modified existing practices and actors' opinions on non-visual sensory knowledge. We conclude by reflecting on design implications, and the role of technologies in valuing diverse ways of understanding the world

Physicians' attitudes about obesity and their associations with competency and specialty: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Physicians frequently report negative attitudes about obesity which is thought to affect patient care. However, little is known about how attitudes toward treating obese patients are formed. We conducted a cross-sectional survey of physicians in order to better characterize their attitudes and explore the relationships among attitudes, perceived competency in obesity care, including report of weight loss in patients, and other key physician, training, and practice characteristics.</p> <p>Methods</p> <p>We surveyed all 399 physicians from internal medicine, pediatrics, and psychiatry specialties at one institution regarding obesity care attitudes, competency, including physician report of percent of their patients who lose weight. We performed a factor analysis on the attitude items and used hierarchical regression analysis to explore the degree to which competency, reported weight loss, physician, training and practice characteristics explained the variance in each attitude factor.</p> <p>Results</p> <p>The overall response rate was 63%. More than 40% of physicians had a negative reaction towards obese patients, 56% felt qualified to treat obesity, and 46% felt successful in this realm. The factor analysis revealed 4 factors–<it>Physician Discomfort/Bias, Physician Success/Self Efficacy, Positive Outcome Expectancy</it>, and <it>Negative Outcome Expectancy</it>. Competency and reported percent of patients who lose weight were most strongly associated with the <it>Physician Success/Self Efficacy </it>attitude factor. Greater skill in patient assessment was associated with less <it>Physician Discomfort/Bias</it>. Training characteristics were associated with outcome expectancies with newer physicians reporting more positive treatment expectancies. Pediatric faculty was more positive and psychiatry faculty less negative in their treatment expectancies than internal medicine faculty.</p> <p>Conclusion</p> <p>Physician attitudes towards obesity are associated with competency, specialty, and years since postgraduate training. Further study is necessary to determine the direction of influence and to explore the impact of these attitudes on patient care.</p

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts