Marqueurs comportementaux et neurochimiques individuels de la prise de décision chez la souris et effets d'une dette de sommeil

Affective abilities that rely on the integrity of several neural circuits. In healthy subjects, inter-individual variability during decision-making exists due to genetic, epigenetic and environmental factors. Moreover, many psychiatric and neurobiological disorders are characterized by poor decision-making processes. Therefore, determining behavioral traits and neurobiological substrates involved in these processes is of major interest to unravel markers that could predict the emergence of neuropathologies.Based on the Iowa Gambling Task in humans, we developed a decision-making task in mice that assesses their ability to choose between several conflicting options under uncertainty. Thanks to a differential approach of mice’s behavior, we show that decision-making skills differed between mice: some mice exhibit a rigid behavior and avoid penalty (safe mice); others maintained exploratory behavior even if they took risks (risky mice); a majority of mice exhibit an intermediate behavior (average mice). We found that a combination of behavioral characteristics related to different psychopathologies in humans were specifically associated with extreme behavior in mice: safe mice exhibited a more anxious behavior, a lower prefrontal activation after the MGT than others subgroups of performance together with a lower basal rate of serotonin in the prefrontal cortex. Risky mice displayed a riskier behavior in various behavioral tasks, were less sensitive to reward, and had a lower basal rate of serotonin in the orbitofrontal cortex as well as a higher basal rate of serotonin, dopamine and noradrenaline in the hippocampus.To investigate the consequences of environmental changes on decision-making individual profiles, we performed the MGT on groups of mice either under Acute Sleep Dept (ASD) or under chronic sleep debt (CSD). We show that CSD didn't play any apparent effect but that ASD emphasized decision-making profiles: safe mice became drastically more rigid and avoided penalty; and risky mice chose systematically riskier options and developed rigid and unefficient decisions. These behavioral data could be explained by a decreased serotonin metabolism in the orbitofrontal cortex, an increase in the hippocampus and a high level of dopamine in the caudate putamen, the key brain area of habits.Therefore, in healthy inbred mice the MGT reveals individual inadapted decision-making strategies which are characterized by behavioral and neurobiological substrates exacerbated by an environmental stress. This paradigm also allows the determination of mice vulnerability to develop psychopathologies (e.g. depression, addiction) for which sleep debt could a trigger or a magnifier.La prise de décision est un processus adaptatif essentiel dont l’efficacité dépend de processus exécutifs, motivationnels, émotionnels et donc de l’intégrité de différents circuits cérébraux. Au sein d’une population saine, il existe des variabilités individuelles décisionnelles influencées par des facteurs génétiques, épigénétiques et environnementaux. De plus, de nombreuses pathologies mentales, neurobiologiques et neurodégénératives provoquent des altérations des processus décisionnels. Ainsi, déterminer des traits comportementaux et des substrats neurobiochimiques impliqués dans ce dysfonctionnement représente un intérêt majeur.Nous avons développé, chez la souris, un test de prise de décision, basé sur le test classiquement utilisé chez l’homme (l’Iowa Gambling Task), qui reproduit une situation incertaine, complexe et conflictuelle de choix : le Mouse Gambling Task (MGT). Grâce à une approche différentielle du comportement, nous avons observé des différences spontanées de capacités décisionnelles : certaines souris ont un comportement rigide et évitent toute pénalité (souris safe), d’autres ont un comportement exploratoire quitte à prendre des risques (souris risky), et une majorité des souris a un comportement intermédiaire (souris average). Nous avons ensuite révélé que les souris safe ont un comportement plus anxieux, une activation préfrontale plus faible que les autres groupes à l’issu du MGT, et un taux de sérotonine à l’état basal plus faible au niveau du cortex préfrontal. Les souris risky ont un comportement plus risqué dans plusieurs tests comportementaux et sont moins sensibles à la récompense. De plus, elles présentent un faible taux de sérotonine au niveau du cortex orbitofrontal ainsi qu’un taux de dopamine, noradrénaline et sérotonine plus important au niveau hippocampique.Afin de tester l’effet d’une modification de l’environnement sur les profils décisionnels caractérisés précédemment, nous avons réalisé le MGT sur un groupe de souris soumises soit à une dette aiguë de sommeil (DAS) soit à une dette chronique de sommeil (DCS). Nous avons alors montré qu’une DCS n’a pas d’effet sur les profils décisionnels mais qu’une DAS accentue ces profils décisionnels: les animaux safe deviennent d’autant plus rigides et évitent encore d’avantage les pénalités alors que les animaux risky choisissent systématiquement les options plus risquées, en adoptant un comportement rigide. Ces observations comportementales peuvent s’expliquer par un métabolisme sérotoninergique diminué au niveau du cortex orbitofrontal et augmenté au niveau hippocampique, ainsi que par un taux élevé de dopamine au niveau du striatum dorsal, structure cérébrale clé des processus d’automatisation.Par conséquent, le MGT permet de révéler, chez des souris consanguines saines, les caractéristiques comportementales et neurobiologiques individuelles de stratégies décisionnelles inadaptées pouvant être amplifiées par un stress environnemental. Ce modèle permettra, notamment, de déterminer les facteurs de vulnérabilité au développement de certaines psychopathologies (l’addiction et la dépression, par exemple) dont le manque de sommeil pourrait être un déclencheur ou un amplificateur

Statin therapy, fitness, and mortality risk in middle-aged hypertensive male veterans

BACKGROUND Hypertension often coexists with dyslipidemia, accentuating cardiovascular risk. Statins are often prescribed in hypertensive individuals to lower cardiovascular risk. Higher fitness is associated with lower mortality, but exercise capacity may be attenuated in hypertension. The combined effects of fitness and statin therapy in hypertensive individuals have not been assessed. Thus, we assessed the combined health benefits of fitness and statin therapy in hypertensive male subjects. METHODS Peak exercise capacity was assessed in 10,202 hypertensive male subjects (mean age = 60.4±10.6 years) in 2 Veterans Affairs Medical Centers. We established 4 fitness categories based on peak metabolic equivalents (METs) achieved and 8 categories based on fitness status and statin therapy. RESULTS During the follow-up period (median = 10.2 years), there were 2,991 deaths. Mortality risk was 34% lower (hazard ratio (HR) = 0.66; 95% confidence interval (CI) = 0.59–0.74; P \u3c 0.001) among individuals treated with statins compared with those not on statins. The fitness-related mortality risk association was inverse and graded regardless of statin therapy status. Risk reduction associated with exercise capacity of 5.1–8.4 METs was similar to that observed with statin therapy. However, those achieving ≥8.5 METs had 52% lower risk (HR = 0.48; 95% CI = 0.37–0.63) when compared with the least-fit subjects (≤5 METs) on statin therapy. CONCLUSIONS The combination of statin therapy and higher fitness lowered mortality risk in hypertensive individuals more effectively than either alone. The risk reduction associated with moderate increases in fitness was similar to that achieved by statin therapy. Higher fitness was associated with 52% lower mortality risk when compared with the least fit subjects on statin therapy

Percutaneous Catheter Dilatation of Benign Ureteroenteric Anastomotic Strictures Followed or not by Retrograde Transconduit Placement of a Catheter: Long Term Results

BACKGROUND: We report our experience on multiple balloon dilatations for benign ureteroenteric anastomotic strictures after total cystectomy and urinal deviation by ileal conduit, followed or not by retrograde placement of a permanent catheter through the stoma of the ileal conduit. PATIENTS AND METHODS: Patients were classified in two groups: Group A included patients treated only by multiple balloon dilatations and Group B patients in whom multiple dilatations were followed by retrograde insertion of a permanent catheter through the stoma of the ileal conduit, which then had to be replaced regularly. Records of survival and patency rates were recorded. RESULTS: Twenty patients with 24 benign ureteroenteric anastomotic strictures referred to radiology department. Long-term results were available in only 15 patients, who finally included in the study. In Group A long term follow-up was achieved in five patients. Mean primary patency time of stenoses (interval between initial dilatation and recurrence) was 33.2 months. This time-period proved to be the same as the survival time of Group A patients, since all five patients eventually succumbed to the underlying disease or other reasons. In Group B, 6 patients are still alive and 4 patients eventually succumbed to the underlying disease or other reasons. Mean primary patency time of stenoses was 38.1 months. CONCLUSIONS: Balloon dilatations of benign ureteroenteric anastomotic strictures, due to radical cystectomy and urinal deviation by ileal conduit, were technically successful in all cases. Patency rate was comparable in the two study groups. However, regular catheter replacement through the ileal conduit is well tolerated and gives a sense of security to both patient and physician

Exercise Capacity and All-Cause Mortality in African American and Caucasian Men With Type 2 Diabetes

OBJECTIVE - The purpose of this study was to assess the association between exercise capacity and mortality in African Americans and Caucasians with type 2 diabetes and to explore racial differences regarding this relationship. RESEARCH DESIGN AND METHODS - African American (n = 1,703; aged 60 ± 10 years) and Caucasian (n = 1,445; aged 62 ± 10 years) men with type 2 diabetes completed a maximal exercise test between 1986 and 2007 at the Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, California. Three fitness categories were established (low-, moderate-, and high-fit) based on peak METs achieved. Subjects were followed for all-cause mortality for 7.3 ± 4.7 years. RESULTS - The adjusted mortality risk was 23% higher in African Americans than in Caucasians (hazard ratio 1.23 [95% CI 1.1-1.4]). A graded reduction in mortality risk was noted with increased exercise capacity for both races. There was a significant interaction between race and METs (P \u3c 0.001) and among race and fitness categories (P \u3c 0.001). The association was stronger for Caucasians. Each 1-MET increase in exercise capacity yielded a 19% lower risk for Caucasians and 14% for African Americans (P \u3c 0.001). Similarly, the risk was 43% lower (0.57 [0.44- 0.73]) for moderate-fit and 67% lower (0.33 [0.22-0.48]) for high-fit Caucasians. The comparable reductions in African Americans were 34% (0.66 [0.55-0.80]) and 46% (0.54 [0.39-0.73]), respectively. CONCLUSIONS - Exercise capacity is a strong predictor of all-cause mortality in African American and Caucasian men with type 2 diabetes. The exercise capacity-related reduction in mortality appears to be stronger and more graded for Caucasians than for African Americans. © 2009 by the American Diabetes Association

Finding Semantically Related Videos in Closed Collections

Modern newsroom tools offer advanced functionality for automatic and semi-automatic content collection from the web and social media sources to accompany news stories. However, the content collected in this way often tends to be unstructured and may include irrelevant items. An important step in the verification process is to organize this content, both with respect to what it shows, and with respect to its origin. This chapter presents our efforts in this direction, which resulted in two components. One aims to detect semantic concepts in video shots, to help annotation and organization of content collections. We implement a system based on deep learning, featuring a number of advances and adaptations of existing algorithms to increase performance for the task. The other component aims to detect logos in videos in order to identify their provenance. We present our progress from a keypoint-based detection system to a system based on deep learning

Detecting Manipulations in Video

This chapter presents the techniques researched and developed within InVID for the forensic analysis of videos, and the detection and localization of forgeries within User-Generated Videos (UGVs). Following an overview of state-of-the-art video tampering detection techniques, we observed that the bulk of current research is mainly dedicated to frame-based tampering analysis or encoding-based inconsistency characterization. We built upon this existing research, by designing forensics filters aimed to highlight any traces left behind by video tampering, with a focus on identifying disruptions in the temporal aspects of a video. As for many other data analysis domains, deep neural networks show very promising results in tampering detection as well. Thus, following the development of a number of analysis filters aimed to help human users in highlighting inconsistencies in video content, we proceeded to develop a deep learning approach aimed to analyze the outputs of these forensics filters and automatically detect tampered videos. In this chapter, we present our survey of the state of the art with respect to its relevance to the goals of InVID, the forensics filters we developed and their potential role in localizing video forgeries, as well as our deep learning approach for automatic tampering detection. We present experimental results on benchmark and real-world data, and analyze the results. We observe that the proposed method yields promising results compared to the state of the art, especially with respect to the algorithm’s ability to generalize to unknown data taken from the real world. We conclude with the research directions that our work in InVID has opened for the future