A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents

Introduction. Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation across adolescence. Methods. Mega-analysis of pooled genetically informative data on smoking initiation was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N=19 313 pairs) between age 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the US, Europe and Australia. Results. Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of smoking initiation across developed countries. The estimate of additive genetic contributions to liability of smoking initiation increased from approximately 15% to 45% from age 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to smoking initiation at age 13 (70%) and gradually less by age 19 (40%). Conclusions. Both additive genetic and shared environmental factors significantly contribute to variance in smoking initiation throughout adolescence. The present study, the largest genetic epidemiological study on smoking initiation to date, found consistent results across 11 studies for the etiology of smoking initiation. Environmental factors, especially those shared by siblings in a family, primarily influence smoking initiation variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. IMPLICATIONS: This is the first study to find evidence of genetic factors in liability to smoking initiation at ages as young as 12. It also shows the strongest evidence to date for decay of effects of the shared environment from early adolescence to young adulthood. We found remarkable consistency of twin correlations across studies reflecting similar etiology of liability to initiate smoking across different cultures and time periods. Thus familial factors strongly contribute to individual differences in who starts to smoke with a gradual increase in the impact of genetic factors and a corresponding decrease in that of the shared environment

The Roots of Autism and ADHD Twin Study in Sweden (RATSS)

Neurodevelopmental disorders affect a substantial minority of the general population. Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environment-phenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders. This article describes the design, recruitment, data collection, measures, collected pairs' characteristics, as well as ongoing and planned analyses in RATSS. Potential gains of the study comprise the identification of environmentally mediated biomarkers, the emergence of candidates for drug development, translational modeling, and new leads for prevention of incapacitating outcome

The Roots of Autism and ADHD Twin Study in Sweden (RATSS)

Neurodevelopmental disorders affect a substantial minority of the general population. Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environment-phenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders. This article describes the design, recruitment, data collection, measures, collected pairs' characteristics, as well as ongoing and planned analyses in RATSS. Potential gains of the study comprise the identification of environmentally mediated biomarkers, the emergence of candidates for drug development, translational modeling, and new leads for prevention of incapacitating outcome

A community-based lifestyle and weight loss intervention promoting a Mediterranean-style diet pattern evaluated in the stroke belt of North Carolina: the Heart Healthy Lenoir Project

Abstract Background Because residents of the southeastern United States experience disproportionally high rates of cardiovascular disease (CVD), it is important to develop effective lifestyle interventions for this population. Methods The primary objective was to develop and evaluate a dietary, physical activity (PA) and weight loss intervention for residents of the southeastern US. The intervention, given in eastern North Carolina, was evaluated in a 2 year prospective cohort study with an embedded randomized controlled trial (RCT) of a weight loss maintenance intervention. The intervention included: Phase I (months 1–6), individually-tailored intervention promoting a Mediterranean-style dietary pattern and increased walking; Phase II (months 7–12), option of a 16-week weight loss intervention for those with BMI ≥ 25 kg/m2 offered in 2 formats (16 weekly group sessions or 5 group sessions and 10 phone calls) or a lifestyle maintenance intervention; and Phase III (months 13–24), weight loss maintenance RCT for those losing ≥ 8 lb with all other participants receiving a lifestyle maintenance intervention. Change in diet and PA behaviors, CVD risk factors, and weight were assessed at 6, 12, and 24 month follow-up. Results Baseline characteristics (N = 339) were: 260 (77 %) females, 219 (65 %) African Americans, mean age 56 years, and mean body mass index 36 kg/m2. In Phase I, among 251 (74 %) that returned for 6 month follow-up, there were substantial improvements in diet score (4.3 units [95 % CI 3.7 to 5.0]), walking (64 min/week [19 to 109]), and systolic blood pressure (−6.4 mmHg [−8.7 to −4.1]) that were generally maintained through 24 month follow-up. In Phase II, 138 (57 group only, 81 group/phone) chose the weight loss intervention and at 12 months, weight change was: −3.1 kg (−4.9 to −1.3) for group (N = 50) and −2.1 kg (−3.2 to −1.0) for group/phone combination (N = 75). In Phase III, 27 participants took part in the RCT. At 24 months, weight loss was −2.1 kg (−4.3 to 0.0) for group (N = 51) and −1.1 kg (−2.7 to 0.4) for combination (N = 72). Outcomes for African American and whites were similar. Conclusions The intervention yielded substantial improvement in diet, PA, and blood pressure, but weight loss was modest. Trial registration clinicaltrials.gov Identifier: NCT0143348

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

A genetic investigation of sex bias in the prevalence of attention-deficit/hyperactivity disorder

Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish populationregister data (N=77,905 cases, N=1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that females with ADHD may be at especially high risk of certain comorbid developmental conditions (i.e. autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score (PRS) analysis did not support a higher burden of ADHD common risk variants in female cases (OR=1.02 [0.98-1.06], p=0.28). In contrast, epidemiological sibling analyses revealed that the siblings of females with ADHD are at higher familial risk of ADHD than siblings of affected males (OR=1.14, [95% CI: 1.11-1.18], p=1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence

Concepts fondamentaux d'une iconologie. Étude des présupposés philosophiques de la méthode historique d'Erwin Panofsky

L étude des concepts fondamentaux de l iconologie permet de dégager la conception de l art, de l histoire et de la création qu elle implique. L examen de l analyse iconographique, des formations par analogie et de la critique du formalisme de Wölfflin permet de réviser l idée selon laquelle l intellectualisme de Panofsky le conduirait à méconnaître la spécificité du visuel. La mise au jour des torsions que l iconologue fait subir au concept de forme symbolique clarifie la question du néo-kantisme et pose celle de l usage de concepts (philosophiques) par l historien. Le propre de la démarche historienne ressort aussi de l analyse du concept rieglien de Kunstwollen qui engage la théorie de la création, la définition de l art, son autonomie et la légitimité de l iconologie. Celle-ci passe également par la résolution d une tension entre le souci d écarter toute approche esthétique ou normative de l objet d art et la nécessaire prise en compte de sa spécificité épistémologique et pratique. Enfin le concept d habitus et la refonte des notions d influences et de tradition lèvent l antinomie entre liberté créatrice et nécessité historique. L usage du modèle dialectique (hégélien) de l histoire relève d un choix de méthode et d une prise de distance par rapport à Warburg dont les concepts centraux sont détournés.The study of the fundamental concepts of iconology enables us to identify the idea of art, of history and of creation it presupposes and also to rethink the traditional interpretation which is made of it. The analysis of the iconographical moment, of the creation by analogy and of the criticism of Wölfflin s formalism challenges the idea that Panofsky supposedly fails to recognize the implacability of the visual aspect. As for Panofsky s thesis of Neo-Kantianism, it is based on resorting to the concept of symbolic form. But the twisting it undergoes is relevant of the unique way in which the historian resorts to (philosophical) concepts. The distinguishing feature of the historical approach also emerges from the study of the Rieglian Kunstwollen concept which involves the theory of creation, the definition and the autonomy of art, and the legitimacy of iconology. This legitimacy also emerges from the solving of the tension between the desire to turn down any esthetical or normative approach of the objet d art, and the necessity to take its epistemological and practical specificity into account. The historian s will to be objective and the transformation of the taste-based judgment into the knowledge-based judgment it seems to imply are also questioned. Finally, the concept of habitus and the transformation of the notions of influence and tradition remove the antinomy between creative freedom and historical necessity. The use of the dialectic (Hegelian) model of history is a choice of method and implies that Panofsky voluntarily stands back from Warburg s philosophy, the key concepts of which are thus embezzled.PARIS4-Bib. électronique (751059905) / SudocSudocFranceF

L'œil et l'objectif (la psychologie de la perception à l'épreuve du style cinématographique (1945-1965))

En faisant du monde un objet déployé sous le regard du spectateur, le dispositif cinématographique semble mettre le film à la disposition de la science de la perception, qui pourrait alors rendre compte de cet objet spécifique en tous ses éléments, et même le plus inassignable son style. La psychologie expérimentale peut alors devenir un instrument d analyse privilégié dans l étude des films, précisément parce que, comme eux, elle suppose un dispositif dualiste de perception. Il s agit alors de déterminer dans quelle mesure la psychologie de la perception notamment la Gestalttheorie est susceptible d éclairer le style au cinéma : si elle semble pertinente quand le film revêt l apparence d un objet à distance, elle achoppe et trouve ses limites quand elle cherche à analyser un style qui renoue avec notre présence au monde et brouille la distinction de l objectif et du subjectif.Films turn the world into an object that visually unfurls in front of the audience. In doing so, the filmmaking device seems to put films at the disposal of the science of perception. This science could very well, then, capture all the elements of this specific object, even the most elusive one: style. Therefore, experimental psychology can be used as a preferred tool for film analysis, as it presupposes, as all films do, that perception is a dualistic device. Our task is then to sort out how exactly the psychology of perception (and more particularly the Gestalttheorie) may throw some light on filmmaking style. On one hand, psychology of perception does clarify style, when it acts like an object: kept at a good distance. But, on the other hand, its limitations become evident when style is more about the way we actually inhabit the world, and when it tends to blur the distinction between subjectivity and objectivity.PARIS4-Bib. électronique (751059905) / SudocSudocFranceF