Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions

Randomized Controlled Trial of Proactive Web-Based Alcohol Screening and Brief Intervention for University Students

Background: University students drink more heavily than their nonstudent peers and are often unaware that their drinking is risky and exceeds normative levels. We tested the efficacy of a proactive Web-based alcohol screening and brief intervention program. Methods: A randomized controlled trial was conducted at an Australian university in 2007. Invitations were sent to 13 000 undergraduates (age range, 17-24 years) to complete a Web-based Alcohol Use Disorders Identification Test. Of 7237 students who responded, 2435 scored in the hazardous/harmful range (≥8) and were randomized, and 2050 (84%) completed at least 1 follow-up assessment. Intervention was 10 minutes of Web-based motivational assessment and personalized feedback. Controls received only screening. Follow-up assessments were conducted at 1 and 6 months with observers and participants blinded to allocation. Outcome measures were drinking frequency, typical occasion quantity, overall volume, number of personal problems, an academic problems score, prevalence of binge drinking, and prevalence of heavy drinking. Results: Mean (SD) baseline Alcohol Use Disorders Identification Test scores for control and intervention groups were 14.3 (5.1) and 14.2 (5.1), respectively. After 1 month, participants receiving intervention drank less often (rate ratio [RR], 0.89; 95% confidence interval [CI], 0.83-0.94), smaller quantities per occasion (RR, 0.93; 95% CI, 0.88-0.98), and less alcohol overall (RR, 0.83; 95% CI, 0.78-0.90) than did controls. Differences in alcohol-related harms were nonsignificant. At 6 months, intervention effects persisted for drinking frequency (RR, 0.91; 95% CI, 0.85-0.97) and overall volume (RR, 0.89; 95% CI, 0.82-0.96) but not for other variables. Conclusion: Proactive Web-based screening and intervention reduces drinking in undergraduates, and such a program could be implemented widely

Indirect Monitoring of Frequencies of a Multiple Span Bridge Using Data Collected from an Instrumented Train: A Field Case Study

In this paper, a field study is carried out to monitor the natural frequencies of Malahide viaduct bridge which is located in the north of Dublin. The bridge includes a series of simply supported spans, two of which collapsed in 2009 and were replaced. The replaced spans are stiffer than most of the others and these differences resulted in higher natural frequencies. An indirect bridge monitoring approach is employed in which acceleration responses from an instrumented train are used to estimate the natural frequencies of each span of the viaduct showing the locations of the two replaced spans with higher stiffness. For the indirect approach, an Ensemble Empirical Mode Decomposition (EEMD)-based Hilbert Huang Transform (HHT) technique is employed to identify the natural frequency of each span. This is carried out by analysing the Instantaneous Frequencies (IFs) from the calculated intrinsic mode functions. The average of the IFs calculated using 41 runs of the instrumented train (with varying carriage mass and speed for each run) are used to estimate the natural frequencies. To assess the feasibility of the indirect approach, a bespoke set of direct measurements was taken using accelerometers attached successively on each span of the viaduct. The free and forced vibrations from each span are used to estimate the first natural frequencies. The frequencies obtained from drive-by measurements are compared to those from direct measurements which confirms the effectiveness of indirect approaches. In addition, the instantaneous amplitudes of the drive-by signals are used to indicate the location of the stiffer spans. Finally, the accuracy and robustness of the indirect approaches for monitoring of multi span bridges are discussed

Body image and quality of life in adolescents with craniofacial conditions

© Copyright 2017 American Cleft Palate-Craniofacial Association. Objective: To evaluate body image in adolescents with and without craniofacial conditions and to examine relationships between body image and quality of life. Design: Case-control design. Setting: A pediatric hospital's craniofacial center and primary care practices. Participants: Seventy adolescents with visible craniofacial conditions and a demographically matched sample of 42 adolescents without craniofacial conditions. Main Outcome Measure: Adolescents completed measures of quality of life and body image including satisfaction with weight, facial and overall appearance, investment in appearance (importance of appearance to self-worth), and body image disturbance (appearance-related distress and impairment in functioning). Results: Adolescents with craniofacial conditions reported lower appearance investment (P < .001) and were more likely to report concerns about facial features (P < .02) compared with nonaffected youth. Females in both groups reported greater investment in appearance, greater body image disturbance, and lower weight satisfaction compared with males (P < .01). Within both groups, greater body image disturbance was associated with lower quality of life (P < .01). The two groups did not differ significantly on measures of quality of life, body image disturbance, or satisfaction with appearance. Conclusions: Body image and quality of life in adolescents with craniofacial conditions are similar to nonaffected youth. Relationships between body image and quality of life emphasize that appearance perceptions are important to adolescents' well-being regardless of whether they have a facial disfigurement. Investment in one's appearance may explain variations in body image satisfaction and serve as an intervention target, particularly for females

Dinheiro, poder e sexo Money, power, and sex

A crença generalizada de que o dinheiro corrompe a intimidade bloqueia nossa capacidade de descrever e explicar como dinheiro, poder, e sexo, de fato, interagem. A crença oposta - de que o sexo funciona como uma mercadoria como qualquer outra - não é melhor para ajudar descrições e explicações. A intersecção de sexo, dinheiro e poder, de fato, gera confusão e conflito, mas isso ocorre precisamente porque os participantes estão simultaneamente negociando relações interpessoais delicadas e responsáveis e marcando diferenças entre essas relações e outras com as quais elas poderiam ser fácil e perigosamente confundidas. Na vida cotidiana, as pessoas lidam com essas dificuldades com um conjunto de práticas que poderíamos chamar de "Boas Combinações".<br>Widespread beliefs that money corrupts intimacy block our ability to describe and explain how money, power, and sex actually interact. The opposite belief - that sex operates like an ordinary market commodity - serves description and explanation no better. The intersection of sex, money, and power, does indeed generate confusion and conflict, but that is precisely because participants are simultaneously negotiating delicate, consequential, interpersonal relations and marking differences between those relations and others with which they could easily and dangerously be confused. In everyday social life, people deal with these difficulties by relying on a set of practices we can call good matches

Quantifying the Effects of 16p11.2 Copy Number Variants on Brain Structure: A Multisite Genetic-First Study

International audienceBackground: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure.Methods: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV.Results: Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen's d > 1), the superior and middle temporal gyri (deletion duplication; -0.5 > Cohen's d > -1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results.Conclusions: The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially