585 research outputs found

    Interplay between genome-wide implicated genetic variants and environmental factors related to childhood antisocial behavior in the UK ALSPAC cohort

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    We investigated gene-environment (G x E) interactions related to childhood antisocial behavior between polymorphisms implicated by recent genome-wide association studies (GWASs) and two key environmental adversities (maltreatment and smoking during pregnancy) in a large population cohort (ALSPAC). We also studied the MAOA candidate gene and addressed comorbid attention-deficit/hyperactivity disorder (ADHD). ALSPAC is a large, prospective, ethnically homogeneous British cohort. Our outcome consisted of mother-rated conduct disorder symptom scores at age 7;9 years. G x E interactions were tested in a sex-stratified way (alpha = 0.0031) for four GWAS-implicated variants (for males, rs4714329 and rs9471290; for females, rs2764450 and rs11215217), and a length polymorphism near the MAOA-promoter region. We found that males with rs4714329-GG (P = 0.0015) and rs9471290-AA (P = 0.0001) genotypes were significantly more susceptible to effects of smoking during pregnancy in relation to childhood antisocial behavior. Females with the rs11215217-TC genotype (P = 0.0018) were significantly less susceptible to effects of maltreatment, whereas females with the MAOA-HL genotype (P = 0.0002) were more susceptible to maltreatment effects related to antisocial behavior. After adjustment for comorbid ADHD symptomatology, aforementioned G x E's remained significant, except for rs11215217 x maltreatment, which retained only nominal significance. Genetic variants implicated by recent GWASs of antisocial behavior moderated associations of smoking during pregnancy and maltreatment with childhood antisocial behavior in the general population. While we also found a G x E interaction between the candidate gene MAOA and maltreatment, we were mostly unable to replicate the previous results regarding MAOA-G x E's. Future studies should, in addition to genome-wide implicated variants, consider polygenic and/or multimarker analyses and take into account potential sex stratification

    Telecommunications. He received a BSc in Aerospace

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    2010, he was a Principal Engineer (Algorithms) at SigNav Pty Ltd where he worked for 15 years on GPS embedded firmware and algorithm development. He also worked at Auspace Ltd for 3 years as a Software Systems Engineer

    Sight Distance Standards Based On Observational Data Risk Evaluation Of Passing

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    The paper presents an application of a reliability analysis for evaluating the risk associated with passing sight distance (PSD) standards in terms of the expected probability of noncompliance. Calculation of PSD is required to determine where drivers can safely execute passing maneuvers. Traditional PSD standards are based on deterministic, theoretical models, which are calibrated with conservative percentile values for uncertain design inputs to account for uncertainty. The PSD standards do not provide information about the risk of deviation from them. Reliability analysis is a technique that is based on limit state design and that accounts for the propagation of variability from input random parameters to the design outputs. A total of 1,098 passing maneuvers were observed on several two-lane highways in Spain; two data collection methodologies were used: external observations and an instrumented vehicle. The most significant factors affecting PSD were impeding-vehicle speed, passing-vehicle acceleration, and head-ways between impeding and passing vehicles. A uniform acceleration model described the passing-vehicle trajectory. The characterized input parameters and the passing model were used to perform a reliability analysis. The results showed the probability of noncompliance in different scenarios, defined as the proportion of cases in which the required PSD would exceed the available sight distance. American and Spanish PSD standards were evaluated. Geometric design standards presented a probability of noncompliance of about 0.15, whereas some marking standards had a probability of noncompliance exceeding 0.85. These standards may be associated with higher risk levels if they are followed by drivers. As well, PSD risk levels were not consistent for different design speeds, since they underestimated operating speed at some locationsThis paper was developed as a result of a mobility study at the University of British Columbia funded by the Erasmus Mundus Program of the European Commission under the Transatlantic Partnership for Excellence in Engineering project. The authors thank the Spanish Ministry of Economy and Competitiveness, which subsidized the research project, and the Spanish Directorate General of Traffic, Spanish Ministry of Public Works, Valencia Regional Department of Transport, and Valencia province road department for their collaboration during the field study.Llorca Garcia, C.; Moreno Chou, AT.; Sayed, T.; García García, A. (2014). Sight Distance Standards Based On Observational Data Risk Evaluation Of Passing. Transportation research record. 2404:18-26. doi:10.3141/2404-03S18262404Ismail, K., & Sayed, T. (2009). Risk-based framework for accommodating uncertainty in highway geometric design. Canadian Journal of Civil Engineering, 36(5), 743-753. doi:10.1139/l08-146Ismail, K., & Sayed, T. (2010). Risk-Based Highway Design. Transportation Research Record: Journal of the Transportation Research Board, 2195(1), 3-13. doi:10.3141/2195-01Richl, L., & Sayed, T. (2006). Evaluating the Safety Risk of Narrow Medians Using Reliability Analysis. Journal of Transportation Engineering, 132(5), 366-375. doi:10.1061/(asce)0733-947x(2006)132:5(366)Harwood, D. W., Gilmore, D. K., & Richard, K. R. (2010). Criteria for Passing Sight Distance for Roadway Design and Marking. Transportation Research Record: Journal of the Transportation Research Board, 2195(1), 36-46. doi:10.3141/2195-05Wang, Y., & Cartmell, M. P. (1998). New Model for Passing Sight Distance on Two-Lane Highways. Journal of Transportation Engineering, 124(6), 536-545. doi:10.1061/(asce)0733-947x(1998)124:6(536)Polus, A., Livneh, M., & Frischer, B. (2000). Evaluation of the Passing Process on Two-Lane Rural Highways. Transportation Research Record: Journal of the Transportation Research Board, 1701(1), 53-60. doi:10.3141/1701-07Llorca, C., & García, A. (2011). Evaluation of Passing Process on Two-Lane Rural Highways in Spain with New Methodology Based on Video Data. Transportation Research Record: Journal of the Transportation Research Board, 2262(1), 42-51. doi:10.3141/2262-05Carlson, P., Miles, J., & Johnson, P. (2006). Daytime High-Speed Passing Maneuvers Observed on Rural Two-Lane, Two-Way Highway: Findings and Implications. Transportation Research Record: Journal of the Transportation Research Board, 1961, 9-15. doi:10.3141/1961-02Llorca, C., Moreno, A. T., García, A., & Pérez-Zuriaga, A. M. (2013). Daytime and Nighttime Passing Maneuvers on a Two-Lane Rural Road in Spain. Transportation Research Record: Journal of the Transportation Research Board, 2358(1), 3-11. doi:10.3141/2358-01Easa, S. M. (1993). Reliability‐Based Design of Intergreen Interval at Traffic Signals. Journal of Transportation Engineering, 119(2), 255-271. doi:10.1061/(asce)0733-947x(1993)119:2(255)Selvanathan, E. A., & Selvanathan, S. (1994). The demand for transport and communication in the United Kingdom and Australia. Transportation Research Part B: Methodological, 28(1), 1-9. doi:10.1016/0191-2615(94)90027-2Easa, S. M. (2000). Reliability Approach to Intersection Sight Distance Design. Transportation Research Record: Journal of the Transportation Research Board, 1701(1), 42-52. doi:10.3141/1701-06Ibrahim, S. E.-B., & Sayed, T. (2011). Developing safety performance functions incorporating reliability-based risk measures. Accident Analysis & Prevention, 43(6), 2153-2159. doi:10.1016/j.aap.2011.06.006Khoury, J. E., & Hobeika, A. G. (2007). Assessing the Risk in the Design of Passing Sight Distances. Journal of Transportation Engineering, 133(6), 370-377. doi:10.1061/(asce)0733-947x(2007)133:6(370)Khoury, J. E., & Hobeika, A. G. (2012). Integrated Stochastic Approach for Risk and Service Estimation: Passing Sight Distance Application. Journal of Transportation Engineering, 138(5), 571-579. doi:10.1061/(asce)te.1943-5436.0000366Kim, S., & Choi, J. (2013). Effects of preceding geometric conditions on operating speed consistency of multilane highways. Canadian Journal of Civil Engineering, 40(6), 528-536. doi:10.1139/cjce-2012-005

    COMPULS:Design of a multicenter phenotypic, cognitive, genetic, and magnetic resonance imaging study in children with compulsive syndromes

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    Background: Compulsivity, the closely linked trait impulsivity and addictive behaviour are associated with several neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive compulsive disorder (OCD). All three disorders show impaired fronto-striatal functioning, which may be related to altered glutamatergic signalling. Genetic factors are also thought to play an important role in the aetiology of compulsivity-related disorders. Methods: The COMPULS study is a multi-center study designed to investigate the relationship between the traits compulsivity, impulsivity, and, to a lesser extent, addictive behaviour within and across the neurodevelopmental disorders ADHD, ASD, and OCD. This will be done at the phenotypic, cognitive, neural, and genetic level. In total, 240 participants will take part in COMPULS across four different sites in Europe. Data collection will include diagnostic interviews, behavioural questionnaires, cognitive measures, structural, functional and spectral neuroimaging, and genome-wide genetic information. Discussion: The COMPULS study will offer the unique opportunity to investigate several key aspects of compulsivity across a large cohort of ADHD, ASD and OCD patients

    The correlation of RNase A enzymatic activity with the changes in the distance between Nepsilon2-His12 and N delta1-His119 upon addition of stabilizing and destabilizing salts.

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    The effect of stabilizing and destabilizing salts on the catalytic behavior of ribonuclease A (RNase A) was investigated at pH 7.5 and 25 degrees C, using spectrophotometric, viscometric and molecular dynamic methods. The changes in the distance between N(epsilon2) of His(12) and N(delta1) of His(119) at the catalytic center of RNase A upon the addition of sodium sulfate, sodium hydrogen sulfate and sodium thiocyanate were evaluated by molecular dynamic methods. The compactness and expansion in terms of Stokes radius of RNase A upon the addition of sulfate ions as kosmotropic salts, and thiocyanate ion as a chaotropic salt, were estimated by viscometric measurements. Enzyme activity was measured using cytidine 2', 3'-cyclic monophosphate as a substrate. The results from the measurements of distances between N(epsilon2) of His(12) and N(delta1) of His(119) and Stokes radius suggest (i) that the presence of sulfate ions decreases the distance between the catalytic His residues and increases the globular compactness, and (ii) that there is an expansion of the enzyme surface as well as elongation of the catalytic center in the presence of thiocyanate ion. These findings are in agreement with activity measurements

    The First Episode Rapid Early Intervention for Eating Disorders - Upscaled study: Clinical outcomes

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    BACKGROUND: First Episode Rapid Early Intervention for Eating Disorders (FREED) is a service model and care pathway for emerging adults aged 16 to 25‐years with a recent onset eating disorder (ED) of <3 years. A previous single‐site study suggests that FREED significantly improves clinical outcomes compared to treatment‐as‐usual (TAU). The present study (FREED‐Up) assessed the scalability of FREED. A multi‐centre quasi‐experimental pre‐post design was used, comparing patient outcomes before and after implementation of FREED in participating services. METHODS: FREED patients (n = 278) were consecutive, prospectively ascertained referrals to four specialist ED services in England, assessed at four time points over 12 months on ED symptoms, mood, service utilization and cost. FREED patients were compared to a TAU cohort (n = 224) of similar patients, identified retrospectively from electronic patient records in participating services. All were emerging adults aged 16–25 experiencing a first episode ED of <3 years duration. RESULTS: Overall, FREED patients made significant and rapid clinical improvements over time. 53.2% of FREED patients with anorexia nervosa reached a healthy weight at the 12‐month timepoint, compared to only 17.9% of TAU patients (X2 [1, N = 107] = 10.46, p < .001). Significantly fewer FREED patients required intensive (i.e., in‐patient or day‐patient) treatment (6.6%) compared to TAU patients (12.4%) across the follow‐up period (X2 [1, N = 40] = 4.36, p = .037). This contributed to a trend in cost savings in FREED compared to TAU (−£4472, p = .06, CI −£9168, £233). DISCUSSION: FREED is robust and scalable and is associated with substantial improvements in clinical outcomes, reduction in inpatient or day‐patient admissions, and cost‐savin
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