Active Contour-Based Segmentation of Head and Neck with Adaptive Atlas Selection

This paper presents automated segmentation of structuresin the Head and Neck (H\&N) region, using an activecontour-based joint registration and segmentation model.A new atlas selection strategy is also used. Segmentationis performed based on the dense deformation fieldcomputed from the registration of selected structures inthe atlas image that have distinct boundaries, onto thepatient's image. This approach results in robustsegmentation of the structures of interest, even in thepresence of tumors, or anatomical differences between theatlas and the patient image. For each patient, an atlasimage is selected from the available atlas-database,based on the similarity metric value, computed afterperforming an affine registration between each image inthe atlas-database and the patient's image. Unlike manyof the previous approaches in the literature, thesimilarity metric is not computed over the entire imageregion; rather, it is computed only in the regions ofsoft tissue structures to be segmented. Qualitative andquantitative evaluation of the results is presented.

Adherence to and effectiveness of highly active antiretroviral treatment for HIV infection: assessing the bidirectional relationship.

BACKGROUND: It is well established that high adherence to HIV-infected patients on highly active antiretroviral treatment (HAART) is a major determinant of virological and immunologic success. Furthermore, psychosocial research has identified a wide range of adherence factors including patients' subjective beliefs about the effectiveness of HAART. Current statistical approaches, mainly based on the separate identification either of factors associated with treatment effectiveness or of those associated with adherence, fail to properly explore the true relationship between adherence and treatment effectiveness. Adherence behavior may be influenced not only by perceived benefits-which are usually the focus of related studies-but also by objective treatment benefits reflected in biological outcomes. METHODS: Our objective was to assess the bidirectional relationship between adherence and response to treatment among patients enrolled in the ANRS CO8 APROCO-COPILOTE study. We compared a conventional statistical approach based on the separate estimations of an adherence and an effectiveness equation to an econometric approach using a 2-equation simultaneous system based on the same 2 equations. RESULTS: Our results highlight a reciprocal relationship between adherence and treatment effectiveness. After controlling for endogeneity, adherence was positively associated with treatment effectiveness. Furthermore, CD4 count gain after baseline was found to have a positive significant effect on adherence at each observation period. This immunologic parameter was not significant when the adherence equation was estimated separately. In the 2-equation model, the covariances between disturbances of both equations were found to be significant, thus confirming the statistical appropriacy of studying adherence and treatment effectiveness jointly. CONCLUSIONS: Our results, which suggest that positive biological results arising as a result of high adherence levels, in turn reinforce continued adherence and strengthen the argument that patients who do not experience rapid improvement in their immunologic and clinical statuses after HAART initiation should be prioritized when developing adherence support interventions. Furthermore, they invalidate the hypothesis that HAART leads to "false reassurance" among HIV-infected patients.

AT-RISK ALCOHOL USE IN YOUNG ADULTS - EFFECTIVENESS AND MECHANISMS OF BRIEF MOTIVATIONAL INTERVENTION AS A PRIMARY AND SECONDARY PREVENTION MEASURE

SummaryThe alcohol use of adolescents and young adults is one of the world's most important and costliest health problems. Particularly, binge drinking (i.e. drinking an important amount of alcohol in one occasion) among young people increase the risk of detrimental consequences such as blackouts, injuries, at-risk sexual behaviors, involvement in violent acts, academic failure, and suicide attempts. In countries with mandatory conscription mechanisms, such as Switzerland, the army provides a unique opportunity to reach a large portion of this high risk population. We used this sample to evaluate the prevalence of binge drinking among young men, to test the efficacy of brief motivational interventions (BMI) as a primary and secondary preventive measure, and to examine the mechanisms underlying BMI in this age group.We showed that binge drinking among young French-speaking Swiss men is less of an exception than it is the norm. Of those using alcohol, 75.5% had a binge drinking episode at least monthly, and 69.3% of all consumption reported in a one-week diary was due to binge drinking days.We used two different inclusion modes to evaluate the success of alcohol BMI. In the first randomized controlled trial, inclusion relied on a random selection of conscripts. BMI efficacy was evaluated in a sample of conscripts who visited the army recruitment centre that is potentially generalizable to the entire population. In the second randomized controlled trial, we included subjects voluntarily participating in BMI. This venue might be more realistic for young adults; it is more akin to the MI spirit, in which it is crucial for individuals to control their own decisions.Regarding BMI efficacy as a secondary prevention measure (i.e. to help decrease alcohol use among at-risk drinkers, defined here as those having a binge drinking episode at least monthly), it was effective among randomly selected at-risk drinkers, whereas it was not effective among at-risk drinkers who voluntarily showed up. Individuals who showed interest in BMI had more severe patterns of alcohol use, which may have made change more difficult and calls for treatment that is more intensive. BMI demonstrated a 20% reduction in weekly alcohol use among randomly selected participants, indicating potential interest in BMI implementation within similar community settings.Regarding BMI efficacy as a primary prevention measure (i.e. to help maintain low levels of use among low-risk drinkers), it had significant protective effects among low-risk drinkers voluntarily showing up whereas it was not effective among low-risk drinkers randomly selected. This suggests that BMI might help young individuals keep their drinking at low levels, especially when they are interested in discussing their alcohol use. Therefore, BMI has potentially promising uses in primary prevention efforts. The content of these interventions for low-risk drinkers who do not seek BMI on their own should be further evaluated.BMI mechanisms were addressed since little is known about exactly which elements of it work, or which of the counselor and subject communication behaviors are most effective in triggering behavior changes. The causal chain hypothesis developed in the motivational interviewing (MI) theory was followed, and it was found that counselor behaviors consistent with the MI approach (MICO) were significantly more likely to be followed by participant language in favor of change (change talk, CT), while behaviors inconsistent with MI (MIIN) were significantly less likely to do so. Several CT dimensions measured during BMI (particularly Ability, Desire, and Need to change) were predictive of change in alcohol use. Our findings lend strong support for the use of MICO behaviors and the avoidance of MIIN behaviors in eliciting CT, and point out that particular attention should be paid to the utterances in several sub-dimensions of CT and to the strength of expression, since these are good indicators of potential actual behavior change in future.RésuméLa consommation d'alcool chez les adolescents et les jeunes adultes est un des problèmes de santé les plus importants et les plus coûteux dans le monde. En particulier, les consommations importantes d'alcool en une occasion (binge drinking) parmi les jeunes adultes ont été liées à des conséquences telles que pertes de connaissance, accidents et blessures, comportements sexuels à risque, violences, difficultés scolaires et tentatives de suicide. Les pays qui, comme la Suisse, connaissent un processus de recrutement obligatoire pour l'armée offrent une opportunité unique d'atteindre une large portion de cette population à hauts risques. Nous avons utilisé cet échantillon pour évaluer la prévalence du binge drinking parmi les jeunes hommes, pour tester l'efficacité de l'intervention brève motivationnelle (IBM) comme mesure de prévention primaire et secondaire, et pour examiner les mécanismes sous-tendant ce type d'interventions.La première partie de cette étude montre que le binge drinking est moins une exception que la norme parmi les jeunes hommes suisses francophones. 75.5% des personnes consommant de l'alcool avaient au moins un épisode de binge drinking par mois et 69.3% du total des boissons alcoolisées reportées comme consommation de la semaine précédant le questionnaire avaient été consommées lors d'épisodes de binge drinking.Pour évaluer l'efficacité de l'IBM dans ce cadre, nous avons utilisé deux modes d'inclusion. Dans une première étude randomisée contrôlée, nous avons inclus des personnes sélectionnées au hasard parmi toutes celles se présentant au centre de recrutement, créant ainsi un groupe potentiellement représentatif de l'ensemble du collectif. Dans la deuxième étude randomisée contrôlée, nous avons inclus des sujets se présentant volontairement pour recevoir une IBM, prendre des volontaires pouvant être plus proche de la réalité et plus proche de l'esprit motivationnel dans lequel il est crucial que l'individu contrôle ses décisions.En regardant l'IBM comme mesure de prévention secondaire (c'est-à-dire aider à diminuer la consommation d'alcool chez les consommateurs à risque, définis ici comme au moins un épisode de binge drinking par mois), l'IBM était efficace lorsque les participants étaient inclus au hasard et inefficace lorsqu'ils étaient volontaires. Les jeunes hommes volontaires pour un IBM avaient un mode de consommation particulièrement sévère qui pourrait être plus difficile à changer et nécessiter un traitement plus intensif. Parmi les personnes sélectionnées au hasard, l'IBM permettait une diminution de 20% de la consommation hebdomadaire d'alcool, montrant l'intérêt potentiel d'une implémentation de ce type de mesures dans des contextes communautaires similaires.En ce qui concerne l'IBM comme mesure de prévention primaire (c'est-à-dire aider à maintenir une consommation à bas risque chez les consommateurs à bas risque), l'IBM avaient un effet protectif significatif parmi les jeunes hommes volontaires pour une IBM, mais pas d'effet chez ceux sélectionnés au hasard. Ces résultats suggèrent que l'IBM pourrait aider de jeunes personnes à maintenir un niveau de consommation à bas risque si celles-ci s'intéressent à discuter cette consommation et aurait ainsi un potentiel intéressant comme mesure de prévention primaire. Le contenu de l'IBM pour des consommateurs à bas risque non-volontaires pour une IBM devra encore être évalué.Nous avons ensuite examiné les mécanismes de l'IBM car son fonctionnement est encore peu expliqué et les comportements de l'intervenant et du sujet les plus à même de provoquer le changement ne sont pas bien définis. En suivant l'hypothèse d'une chaine causale développée dans la littérature de l'entretien motivationnel (EM), nous avons pu montrer qu'un discours en faveur du changement chez le sujet était plus probable après des comportements de l'intervenant recommandés dans l'EM et moins probable après des comportements à éviter dans l'EM ; et que plusieurs dimensions de ce discours en faveur du changement (notamment la capacité, le désir et le besoin de changer) prédisaient un changement effectif dans la consommation d'alcool. Ces résultats encouragent donc à utiliser des comportements recommandés dans l'EM pour favoriser un discours en faveur du changement. Ils montrent aussi qu'une attention particulière doit être portée à la fréquence et à la force avec laquelle sont exprimées certaines dimensions de ce discours car ceux-ci indiquent un potentiel changement effectif de comportement.Résumé vulgariséLa consommation d'alcool chez les adolescents et les jeunes adultes est un des problèmes de santé les plus importants et les plus coûteux dans le monde. En particulier, les consommations importantes d'alcool en une occasion (binge drinking) parmi les jeunes adultes augmentent fortement les risques de conséquences telles que pertes de connaissance, accidents et blessures, comportements sexuels à risque, violences, difficultés scolaires et tentatives de suicide. Les pays qui, comme la Suisse, connaissent un processus de recrutement obligatoire pour l'armée offrent une opportunité unique d'atteindre une large portion de cette population à hauts risques. Nous avons utilisé cet échantillon pour évaluer l'importance du phénomène de binge drinking, pour tester l'efficacité de l'intervention brève motivationnelle (IBM) comme mesure de prévention de la consommation à risque d'alcool, et pour examiner comment fonctionne ce type d'interventions.La première partie de cette étude montre que le binge drinking est moins une exception que la norme parmi les jeunes hommes suisses francophones. Trois quart des personnes consommant de l'alcool avaient au moins un épisode de binge drinking par mois. Presque 70% du total des boissons alcoolisées consommées durant la semaine précédant le questionnaire avaient été consommées lors d'épisodes de binge drinking.Nous avons ensuite mené deux études pour évaluer l'efficacité de l'IBM dans ce cadre. Dans une première étude, nous avons sélectionné des personnes au hasard parmi toutes celles se présentant au centre de recrutement, créant ainsi un groupe potentiellement représentatif de l'ensemble du collectif. Dans la deuxième étude, nous avons inclus toutes les personnes se présentant volontairement pour recevoir une IBM, prendre des volontaires pouvant être plus proche de la réalité et plus proche de l'approche motivationnelle dans laquelle il est crucial que l'individu contrôle ses décisions. Dans les deux études, nous testions l'efficacité de l'IBM comme mesure de prévention primaire et secondaire (voir ci-dessous).En regardant l'IBM comme mesure de prévention secondaire (c'est-à-dire aider à diminuer la consommation d'alcool chez les consommateurs à risque, définis ici comme au moins un épisode de binge drinking par mois), l'IBM était efficace lorsque les participants étaient inclus au hasard et inefficace lorsqu'ils étaient volontaires. Les jeunes hommes volontaires pour un IBM avaient un mode de consommation particulièrement sévère qui pourrait être plus difficile à changer et nécessiter un traitement plus intensif. Parmi les personnes sélectionnées au hasard, l'IBM permettait une diminution de 20% de la consommation hebdomadaire d'alcool, montrant l'intérêt potentiel de la mise en place de ce type de mesures dans des contextes communautaires similaires.En ce qui concerne l'IBM comme mesure de prévention primaire (c'est-à-dire aider à maintenir une consommation à bas risque chez les consommateurs à bas risque), l'IBM avaient un effet protectif parmi les jeunes hommes volontaires pour une IBM, mais pas d'effet chez ceux sélectionnés au hasard. Ces résultats suggèrent que l'IBM pourrait aider de jeunes personnes à maintenir un niveau de consommation à bas risque si celles-ci s'intéressent à discuter de cette consommation. Le contenu de l'IBM pour des consommateurs à bas risque non-volontaires pour une IBM devra encore être évalué.Nous avons ensuite examiné le fonctionnement de l'IBM et cherché quels comportements de l'intervenant et du jeune homme pouvaient être les plus à même d'amener à un changement dans la consommation. Nous avons pu montrer que 1) un discours en faveur du changement chez le jeune homme était plus probable après des comportements de l'intervenant recommandés dans l'approche motivationnelle et moins probable après des comportements non-recommandés ; et 2) plusieurs dimensions de ce discours en faveur du changement (notamment la capacité, le désir et le besoin de changer) prédisaient un changement effectif dans la consommation d'alcool. Ces résultats encouragent donc à utiliser des comportements recommandés dans l'EM pour favoriser un discours en faveur du changement. Ils montrent aussi qu'une attention particulière doit être portée à certaines dimensions de ce discours car celles-ci indiquent un potentiel changement effectif de comportement.

Insights from insects about adaptive social information use.

Copying others can greatly improve individual fitness and is fundamental for the organisation of societies. Yet in some situations it is better to ignore social information and either explore the world individually or use personal information obtained through prior experience. Insects provide excellent models to study the strategic use of social information, but insights from recent research have rarely been viewed in the light of social learning strategies. Here we discuss how insects tailor their reliance on social information to those circumstances for which it is most beneficial, and suggest that insects and vertebrates use similar information-use strategies. We highlight future research avenues, including the use of molecular tools to study the genetic and genomic basis of social information use.

The cost effectiveness of pharmacological smoking cessation therapies in developing countries: a case study in the Seychelles

OBJECTIVE: To examine the incremental cost effectiveness of the five first line pharmacological smoking cessation therapies in the Seychelles and other developing countries. DESIGN: A Markov chain cohort simulation. SUBJECTS: Two simulated cohorts of smokers: (1) a reference cohort given physician counselling only; (2) a treatment cohort given counselling plus cessation therapy. INTERVENTION: Addition of each of the five pharmacological cessation therapies to physician provided smoking cessation counselling. MAIN OUTCOME MEASURES: Cost per life-year saved (LYS) associated with the five pharmacotherapies. Effectiveness expressed as odds ratios for quitting associated with pharmacotherapies. Costs based on the additional physician time required and retail prices of the medications. RESULTS: Based on prices for currently available generic medications on the global market, the incremental cost per LYS for a 45 year old in the Seychelles was 599 US dollars for gum and 227 dollars for bupropion. Assuming US treatment prices as a conservative estimate, the incremental cost per LYS was significantly higher, though still favourable in comparison to other common medical interventions: 3712 dollars for nicotine gum, 1982 dollars for nicotine patch, 4597 dollars for nicotine spray, 4291 dollars for nicotine inhaler, and 1324 dollars for bupropion. Cost per LYS increased significantly upon application of higher discount rates, which may be used to reflect relatively high opportunity costs for health expenditures in developing countries with highly constrained resources and high overall mortality. CONCLUSION: Pharmacological cessation therapy can be highly cost effective as compared to other common medical interventions in low mortality, middle income countries, particularly if medications can be procured at low prices.

What is the value of forensic science? : an overview of the effectiveness of forensic science in the Australian criminal justice system project

Forensic science is increasingly relied upon by law enforcement to assist in solvingcrime and gaining convictions, and by the judicial system in the adjudication ofspecific criminal cases. However, the value of forensic science relative to the workinvolved and the outcome of cases has yet to be established in the Australiancontext. Previous research in this area has mainly focused on the science andtechnology, rather than examining how people can use forensic services/science tothe best possible advantage to produce appropriate justice outcomes. This fiveyearproject entails an investigation into the effectiveness of forensic science inpolice investigations and court trials. It aims to identify when, where and howforensic science can add value to criminal investigations, court trials and justiceoutcomes while ensuring the efficient use of available resources initially in theVictorian and the ACT criminal justice systems and ultimately across Australiaand New Zealand. This paper provides an overview of the rationale and aims ofthe research project and discusses current work-in-progress.

A Randomized Controlled Trial of the Effectiveness of Computer-Assisted Cognitive Remediation (CACR) in Adolescents with Psychosis or at High Risk of Psychosis.

Background: Computer assisted cognitive remediation (CACR) was demonstrated to be efficient in improving cognitive deficits in adults with psychosis. However, scarce studies explored the outcome of CACR in adolescents with psychosis or at high risk. Aims: To investigate the effectiveness of a computer-assisted cognitive remediation (CACR) program in adolescents with psychosis or at high risk. Method: Intention to treat analyses included 32 adolescents who participated in a blinded 8-week randomized controlled trial of CACR treatment compared to computer games (CG). Cognitive abilities, symptoms and psychosocial functioning were assessed at baseline and posttreatment. Results: Improvement in visuospatial abilities was significantly greater in the CACR group than in CG. Other cognitive functions, psychotic symptoms and psychosocial functioning improved significantly, but at similar rates, in the two groups. Conclusion: CACR can be successfully administered in this population; it proved to be effective over and above CG for the most intensively trained cognitive ability.

The evolution, maintenance and adaptive function of genetic colour polymorphism in birds.

The hypothesis that ornaments can honestly signal quality only if their expression is condition-dependent has dominated the study of the evolution and function of colour traits. Much less interest has been devoted to the adaptive function of colour traits for which the expression is not, or is to a low extent, sensitive to body condition and the environment in which individuals live. The aim of the present paper is to review the current theoretical and empirical knowledge of the evolution, maintenance and adaptive function of colour plumage traits for which the expression is mainly under genetic control. The finding that in many bird species the inheritance of colour morphs follows the laws of Mendel indicates that genetic colour polymorphism is frequent. Polymorphism may have evolved or be maintained because each colour morph facilitates the exploitation of alternative ecological niches as suggested by the observation that individuals are not randomly distributed among habitats with respect to coloration. Consistent with the hypothesis that different colour morphs are linked to alternative strategies is the finding that in a majority of species polymorphism is associated with reproductive parameters, and behavioural, life-history and physiological traits. Experimental studies showed that such covariations can have a genetic basis. These observations suggest that colour polymorphism has an adaptive function. Aviary and field experiments demonstrated that colour polymorphism is used as a criterion in mate-choice decisions and dominance interactions confirming the claim that conspecifics assess each other's colour morphs. The factors favouring the evolution and maintenance of genetic variation in coloration are reviewed, but empirical data are virtually lacking to assess their importance. Although current theory predicts that only condition-dependent traits can signal quality, the present review shows that genetically inherited morphs can reveal the same qualities. The study of genetic colour polymorphism will provide important and original insights on the adaptive function of conspicuous traits.

Genital Chlamydia trachomatis: understanding the roles of innate and adaptive immunity in vaccine research.

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide, and despite significant advances in chlamydial research, a prophylactic vaccine has yet to be developed. This Gram-negative obligate intracellular bacterium, which often causes asymptomatic infection, may cause pelvic inflammatory disease (PID), ectopic pregnancies, scarring of the fallopian tubes, miscarriage, and infertility when left untreated. In the genital tract, Chlamydia trachomatis infects primarily epithelial cells and requires Th1 immunity for optimal clearance. This review first focuses on the immune cells important in a chlamydial infection. Second, we summarize the research and challenges associated with developing a chlamydial vaccine that elicits a protective Th1-mediated immune response without inducing adverse immunopathologies.

Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors.

The therapeutic efficacy of anticancer chemotherapies may depend on dendritic cells (DCs), which present antigens from dying cancer cells to prime tumor-specific interferon-gamma (IFN-gamma)-producing T lymphocytes. Here we show that dying tumor cells release ATP, which then acts on P2X(7) purinergic receptors from DCs and triggers the NOD-like receptor family, pyrin domain containing-3 protein (NLRP3)-dependent caspase-1 activation complex ('inflammasome'), allowing for the secretion of interleukin-1beta (IL-1beta). The priming of IFN-gamma-producing CD8+ T cells by dying tumor cells fails in the absence of a functional IL-1 receptor 1 and in Nlpr3-deficient (Nlrp3(-/-)) or caspase-1-deficient (Casp-1(-/-)) mice unless exogenous IL-1beta is provided. Accordingly, anticancer chemotherapy turned out to be inefficient against tumors established in purinergic receptor P2rx7(-/-) or Nlrp3(-/-) or Casp1(-/-) hosts. Anthracycline-treated individuals with breast cancer carrying a loss-of-function allele of P2RX7 developed metastatic disease more rapidly than individuals bearing the normal allele. These results indicate that the NLRP3 inflammasome links the innate and adaptive immune responses against dying tumor cells.

Cost-effectiveness of surgery in low- and middle-income countries: a systematic review.

BACKGROUND: There is increasing interest in provision of essential surgical care as part of public health policy in low- and middle-income countries (LMIC). Relatively simple interventions have been shown to prevent death and disability. We reviewed the published literature to examine the cost-effectiveness of simple surgical interventions which could be made available at any district hospital, and compared these to standard public health interventions. METHODS: PubMed and EMBASE were searched using single and combinations of the search terms "disability adjusted life year" (DALY), "quality adjusted life year," "cost-effectiveness," and "surgery." Articles were included if they detailed the cost-effectiveness of a surgical intervention of relevance to a LMIC, which could be made available at any district hospital. Suitable articles with both cost and effectiveness data were identified and, where possible, data were extrapolated to enable comparison across studies. RESULTS: Twenty-seven articles met our inclusion criteria, representing 64 LMIC over 16 years of study. Interventions that were found to be cost-effective included cataract surgery (cost/DALY averted range US$5.06-$106.00), elective inguinal hernia repair (cost/DALY averted range US$12.88-$78.18), male circumcision (cost/DALY averted range US$7.38-$319.29), emergency cesarean section (cost/DALY averted range US$18-$3,462.00), and cleft lip and palate repair (cost/DALY averted range US$15.44-$96.04). A small district hospital with basic surgical services was also found to be highly cost-effective (cost/DALY averted 1 US$0.93), as were larger hospitals offering emergency and trauma surgery (cost/DALY averted US$32.78-$223.00). This compares favorably with other standard public health interventions, such as oral rehydration therapy (US$1,062.00), vitamin A supplementation (US$6.00-$12.00), breast feeding promotion (US$930.00), and highly active anti-retroviral therapy for HIV (US$922.00). CONCLUSIONS: Simple surgical interventions that are life-saving and disability-preventing should be considered as part of public health policy in LMIC. We recommend an investment in surgical care and its integration with other public health measures at the district hospital level, rather than investment in single disease strategies.

THE USEFUL SIDE OF AMBIVALENCE: Ambivalent attitudes can be adaptive and socially valued

En s'inspirant de la littérature récente qui a dépeint l'ambivalence comme étant adaptative et en lien avec des comportements stratégiques, cette thèse examine le versant utile des attitudes ambivalentes. Elle met tout d'abord en évidence que son expression peut-être sciemment contrôlée et mise en avant pour des raisons d'auto-présentation. De plus, elle démontre que les individus peuvent présenter une attitude ambivalente afin de gagner l'approbation sociale sur un objet d'attitude controversé alors que l'inverse a été observé sur des objets consensuels (Première ligne de recherche). Cette thèse a également révélé que l'expression d'attitudes ambivalentes pouvait amener à être valorisé socialement. En effet, contrairement à des attitudes plus tranchées (pro-normatives ou contre-normatives), les attitudes ambivalentes ont été évaluées de façon plus importante sur la dimension de l'utilité sociale (une dimension qui indique la compétence d'autrui ou encore la propension à évoluer dans la hiérarchie sociale). La valorisation de l'ambivalence n'est apparue que sur la dimension de l'utilité sociale et non sur la dimension de la désirabilité sociale (une dimension qui indique la sympathie d'autrui ainsi que la propension à être apprécié socialement). De plus, ce résultat a été observé sur des thèmes controversés et non sur des thèmes consensuels (Seconde ligne de recherche). Dans l'ensemble cette thèse soutient une approche de l'ambivalence comme donnant lieu à des bénéfices. Elle peut également ouvrir la voie à l'étude de l'ambivalence en lien avec la pensée critique. - Drawing on the recent literature that portrayed ambivalence as being adaptive and linked with strategic behaviors, this thesis examines the useful side of ambivalent attitudes. It first revealed that the expression of ambivalent attitudes could be controlled and purposely displayed for self-presentational concerns. Furthermore, it demonstrated that people could put ambivalence forward to gain social approval when expressing it on controversial social issues, whereas the opposite was true on consensual social issues (First line of research). The thesis also revealed that the expression of ambivalent attitudes could lead to be socially valued. Indeed, contrary to clear-cut attitudes (either pro-normative or counter-normative attitudes), ambivalent attitudes have been evaluated the highest on the social utility dimension (a dimension indicating people's competence as well as the extent to which they are likely to climb in social hierarchy). The valorization of ambivalent attitudes only appeared on social utility and not on social desirability (a dimension indicating people's niceness as well as the extent to which they are likely to be socially appreciated). This effect was true on controversial social issues but not on consensual ones (Second line of research). Overall, this thesis provides support for an approach that conceives attitudinal ambivalence as leading to benefits. It also may open avenues for the study of ambivalence in relation with critical thinking.

Cardiac raptor deletion impairs adaptive hypertrophy, alters metabolic gene expression and causes heart failure in mice

Background: Mammalian target of rapamycin (mTOR), a central regulator of cell growth, is found in two structurally and functionally distinct multiprotein complexes called mTOR complex (mTORC)1 and mTORC2. The specific roles of each of these branches of mTOR signaling have not been dissected in the adult heart. In the present study, we aimed to bring new insights into the function of cardiac mTORC1-mediated signaling in physiological as well as pathological situations.Methods: We generated mice homozygous for loxP-flanked raptor and positive for the tamoxifen-inducible Cre recombinase (MerCreMer) under control of the α- myosin heavy chain promoter. The raptor gene encodes an essential component of mTORC1. Gene ablation was induced at the age of 10-12 weeks, and two weeks later the raptor cardiac-knockout (raptor-cKO) mice started voluntary cagewheel exercise or were subjected to transverse aortic constriction (TAC) to induce pressure overload.Results: In sedentary raptor-cKO mice, ejection fractions gradually decreased, resulting in significantly reduced values at 38 days (P < 0.001). Raptor-cKO mice started to die during the fifth week after the last tamoxifen injection. At that time, the mortality rate was 36% in sedentary (n = 11) and 64% in exercising (n = 14) mice. TAC-induced pressure overload resulted in severe cardiac dysfunction already at earlier timepoints. Thus, at 7-9 days after surgery, ejection fraction and fractional shortening values were 22.3% vs 43.5% and 10.2% vs 21.5% in raptor-cKO vs wild-type mice, respectively. This was accompanied by significant reductions of ventricular wall and septal thickness as well as an increase in left ventricular internal diameter. Moreover, ventricular weight to tibial length ratios were increased in wild-type, but not in the raptor-cKO TAC mice. Together, this shows that raptor-cKO mice rapidly developed dilated cardiomyopathy without going through a phase of adaptive hypertrophy. Expression of ANP and β-MHC was induced in all raptor-cKO mice irrespective of the cardiac load conditions. Consistent with reduced mTORC1 activity, phosphorylation of ribosomal S6 kinase and 4E-BP1 was blunted, indicating reduced protein synthesis. Moreover, expression of multiple genes involved in the regulation of energy metabolism was altered, and followed by a shift from fatty acid to glucose oxidation.Conclusion: Our study suggests that mTORC1 coordinates protein and energy metabolic pathways in the heart. Moreover, we demonstrate that raptor is essential for the cardiac adaptation to increased workload and importantly, also for normal physiological cardiac function.