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Two main theories of neural atypicality have been postulated in autism. One theory proposes that autism can be explained as the result of atypical patterns of hypo and hyper functional connectivity (FC) within and between brain areas. A complementary theory suggests that atypical functional communication in autism could result from an altered ratio between excitatory and inhibitory input (E:I imbalance). These theories have been previously explored as they might apply to all individuals with a behavioral diagnosis. However, given the multiscale heterogeneity characterizing autism, different subsets of individuals with autism may display different patterns of functional connectivity atypicalities and E:I imbalance. This thesis sets out to explore how neural atypicalities in connectivity and E:I imbalance might be differentially expressed in subsets of the autistic population. To this end, two empirical investigations were conducted. First, the connectivity hypothesis was explored by investigating whether behaviorally-defined subtypes were associated with different patterns of FC atypicalities. Behaviorally-defined subtypes were obtained by stratifying autistic individuals based on their relative balance between social communication (SC) and restricted and repetitive behaviors (RRBs) core symptom domains. This approach yielded three behaviorally-based subtypes: SC>RRB, SCRRB displayed hypoconnectivity between somatomotor and perisylvian circuitry, while subtypes SC=RRB showed hypoconnectivity between somatomotor and visual association areas and hyperconnectivity between medial motor and anterior salience networks. Finally, these subtype-specific FC alterations were shown to be enriched for partially distinct genetic mechanisms, some of which related to excitatory-inhibitory neurons and astrocytes. In a second study, the EI imbalance hypothesis was explored by investigating whether autism subtypes could be identified based on an E:I-sensitive metric computed from electroencephalographic (EEG) data. Specifically, the Hurst exponent (H) – a metric that has been shown to be affected by changes in excitatory input – was computed on EEG time-series data, obtained in two resting state conditions of eyes open and closed. H-based clustering revealed two E:I-based neurosubtypes across conditions with opposing patterns of E:I imbalance compared to neurotypical controls. Autism neurosubtype 1 showed on-average higher H values, while neurosubtype 2 displayed on-average lower H. These opposing E:I balance patterns were present globally across the brain, with the limited exception of an orthogonal larger decrease in H in non-frontal electrodes in neurosubtype 2. Finally, investigation at the behavioral level identified distinct multivariate brain-behavior relationships between age, intelligence, autistic traits and H. Taken together, these empirical findings demonstrate that the two major theories of neural atypicality in autism – FC alteration and E:I imbalance – do not apply equally to all individuals with a behavioral diagnosis. Rather, different subtypes of autism exist that display contrasting patterns of neural atypicality compared to typically-developing individuals. These contrasting patterns might be driven by differentially altered primary or compensatory E:I mechanisms shaping distinct atypical cortical organizations within the subtypes. Interestingly, the relationship between specific neural atypicalities and variability at the behavioral and genetic level is, however, subtle across the subtypes. This limited multiscale association could suggest that heterogeneity in autism might be due to the presence, within the larger population, of subtype-specific mosaic-like patterns of atypicalities at the behavioral and biological level. Further research is required to thoroughly characterize how these levels map onto one another within the subtypes and determine the pathophysiological mechanisms driving their development.

Ce mémoire analyse l'évolution de la polarisation des revenus au Canada entre 1973 et 2003. Nous utilisons à cette fin les indices de Duclos, Esteban et Ray (DER) et de Wolfson. Les résultats tendent premièrement à démontrer que l'évolution de la polarisation des revenus du marché semble suivre un mouvement généralement contracyclique. Deuxièmement, on observe depuis 30 ans un phénomène de croissance de la polarisation des revenus du marché au Canada. Finalement, bien que le rôle joué par le régime d'impôts et de transferts sur la polarisation soit très différent entre la décennie de 1980 et celle de 1990, le régime d'impôts et de transferts semble neutraliser ou du moins atténuer la croissance et les fluctuations de cette dernière, ce qui se traduit par une polarisation des revenus après impôts qui varie nettement moins au cours du cycle économique et, généralement parlant, au fil du temps.

Dans un plan stratifié, le calcul des bornes de strates peut se faire de plusieurs façons. On peut se fier à un jugement personnel et séparer les unités de la population en se basant sur la distribution de la variable de stratification. D’autres méthodes scientifiques et rigoureuses donnent un meilleur résultat, dont les algorithmes de cum √f, Sethi et Kosak. Pour les populations asymétriques, telles que retrouvées dans les enquêtes entreprises, l’utilisation d’une strate recensement permet de diminuer la taille d’échantillon et donner des estimations plus fiables. Parfois, la variable de stratification utilisée dans l’élaboration du plan de sondage ne garantit pas l’obtention de la précision cible pour toutes les variables d’intérêt de l’enquête. Utiliser la variable d’intérêt la plus difficile à estimer, comme variable de stratification, permet de garantir un CV cible minimal pour toutes les autres variables, mais engendre des grandes tailles d’échantillon. / In a stratified sampling design, the calculation of the stratum boundaries can be done in several ways. We can rely on personal judgment and separate the units of the population based on the distribution of the stratification variable. Other scientific and rigorous methods give a better result, including the algorithms of cum √f, Sethi and Kosak. For asymmetric populations, as found in the business surveys, the use of a census stratum reduces the sample size and gives more reliable estimates. Univariate methods, those that use a single stratification variable in calculating the boundaries, do not guarantee that the target precision will be obtained for all the variables of interest in the survey. Using the variable of interest that is the most difficult to estimate, as a stratification variable, makes it possible to guarantee a minimum target CV for all the other variables, but generates large sample sizes.

Yes / Introduction: Between 2009/2010 and 2019/2020, England witnessed an increase in suspected head and neck cancer (sHNC) referrals from 140 to 404 patients per 100 000 population. 1 in 10 patients are not seen within the 2-week target, contributing to patient anxiety. We will develop a pathway for sHNC referrals, based on the Head and Neck Cancer Risk Calculator. The evolution of a patient-reported symptom-based risk stratification system to redesign the sHNC referral pathway (EVEREST-HN) Programme comprises six work packages (WPs). This protocol describes WP1 and WP2. WP1 will obtain an understanding of language to optimise the SYmptom iNput Clinical (SYNC) system patient-reported symptom questionnaire for sHNC referrals and outline requirements for the SYNC system. WP2 will codesign key elements of the SYNC system, including the SYNC Questionnaire, and accompanying behaviour change materials. Methods and analysis: WP1 will be conducted at three acute National Health Service (NHS) trusts with variation in service delivery models and ensuring a broad mixture of social, economic and cultural backgrounds of participants. Up to 150 patients with sHNC (n=50 per site) and 15 clinicians (n=5 per site) will be recruited. WP1 will use qualitative methods including interviews, observation and recordings of consultations. Rapid qualitative analysis and inductive thematic analysis will be used to analyse the data. WP2 will recruit lay patient representatives to participate in online focus groups (n=8 per focus group), think-aloud technique and experience-based codesign and will be analysed using qualitative and quantitative approaches. Ethics and dissemination: The committee for clinical research at The Royal Marsden, a research ethics committee and the Health Research Authority approved this protocol. All participants will give informed consent. Ethical issues of working with patients on an urgent cancer diagnostic pathway have been considered. Findings will be disseminated via journal publications, conference presentations and public engagement activities. / This work was supported by NIHR Programme Grants for Applied Research (grant number: NIHR202862).

Suicide is a significant public health issue in the US. Despite national and international prioritization since 1996, little definitive progress has been made in terms of identification and intervention in cases of elevated suicide risk. Forty percent of those who died by suicide attended an emergency department within a year of death. Therefore, universal suicide risk screening in emergency departments could prove a vital component to a national suicide prevention strategy. The present study empirically evaluated the universal suicide risk screening program recently implemented at Parkland Health and Hospital System. The sample consisted of patients over 18 years of age (N=333,855; Mage=42.7, 32% male) screened as part of routine clinical care from May 4th, 2015, through November 3rd, 2015. The Parkland Algorithm for Suicide Screening (PASS) is part of a clinical decision support system for responses to Columbia - Suicide Severity Rating Scale Clinical Practice Screener (C-SSRS) items, leading to an automated clinical response via three suicide risk stratification levels: no action for no risk identified, psychiatric social worker assessment for moderate risk identified, and psychiatrist/psychologist interview for high risk identified. The present study used receiver operating characteristic (ROC) curve analysis, which found the PASS predicted disposition (z=30.46, p<.001, AUC=.78, CI95=.77, .81). This study also evaluated the cutpoints separating suicide risk stratification and levels of clinical response. The results supported the first cutpoint and highlighted a need for additional data to address the second cutpoint. The results of the present study suggest that the universal suicide risk screening program at Parkland Health and Hospital System is an important step toward addressing suicide prevalence in the US.

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À l’aide des données du recensement canadien de 2006, ce mémoire examine les assortiments éducationnels des couples exogames immigrants-natifs à titre d’indicateur de stratification sociale. Premièrement, les résultats tirés de régressions logistiques multinomiales confirment la présence d’échange (social status exchange : Merton 1941; Davis 1941) entre les natifs et les immigrants, c’est-à-dire qu’un immigrant est davantage susceptible de s’unir avec un natif s’il est plus scolarisé que ce dernier. Ces résultats supportent l’existence d’une stratification sociale entre les immigrants et les natifs. Deuxièmement, l’analyse révèle que l’échange apparait chez les immigrants des deux sexes ayant au moins un baccalauréat, alors que chez les moins scolarisés l’échange ne ressort que chez les hommes. Troisièmement, chez les immigrants de minorité visible, l’échange perdure de la première à la deuxième génération d’immigrant, alors que parmi ceux n’appartenant pas à une minorité visible, l’échange ne concerne que les immigrants de première génération. / Using the 2006 Canadian census data, this thesis examines the educational assortative mating of exogamous couples formed of an immigrant and a native as an indicator of social stratification. First, results from multinomial logistic regression confirm the presence of exchange (status exchange: Merton 1941; Davis 1941) between natives and immigrants, meaning that an immigrant is more susceptible to have native spouse if his education level is higher than the native’s. These results support the existence of a social stratification between natives and immigrants. Second, the analysis reveals that exchange appears for immigrants of both sexes that have at least a bachelor degree, whereas for immigrants that are less educated, exchange is only apparent with men. Third, for immigrants of visible minorities, exchange is present for immigrant of first and second generation, whereas for immigrants who are not of a visible minorities, exchange only appears for first generation immigrants.

Pour franchir les prochaines étapes réglementaires, une des solutions adoptées par les constructeurs automobiles est la dépollution à la source par des nouveaux concepts de combustion. Une piste d’étude est le moteur à charge homogène allumé par compression, le moteur HCCI. Le défi majeur est de contrôler le phasage de la combustion lors des transitions. Or, l’ozone est un additif prometteur de la combustion. La première partie de ce travail est consacrée au développement d’un modèle 0D physique de la combustion dans le moteur HCCI à l’aide d’une approche statistique basée sur une fonction de densité de probabilité (PDF) de la température. Pour cela, un modèle de variance d’enthalpie est développé. Après la validation expérimentale du modèle, il est utilisé pour développer des cartographies du moteur HCCI avec et sans ajout de l’ozone afin d’évaluer le gain apporté par cet actuateur chimique en terme de charge et régime. La deuxième partie porte sur le contrôle du phasage de combustion par ajout d’ozone. Une étude de simulation est effectuée où des lois de commandes sont appliquées sur un modèle orienté contrôle. Les résultats montrent que l’ajout d’ozone permet de contrôler cycle-à-cycle le phasage de la combustion. En parallèle, une étude expérimentale sur un banc moteur est facilitée grâce à un système d’acquisition des paramètres de combustion (Pmax, CA50) en temps réel, développé au cours de cette étude. En intégrant les lois de commande par ajout d’ozone dans le calculateur du moteur (ECU), les résultats expérimentaux montrent la possibilité de contrôler non seulement cycle-à-cycle le phasage de la combustion par ajout d’ozone lors des transitions mais aussi de stabiliser le phasage de la combustion d’un point instable. / To pass the next legislator steps, one of the alternative solutions proposed for the depollution at the source by new concepts of combustion. One of proposed solution is the Homogeneous Charge Compression Ignition (HCCI) engine. The major challenge is to control combustion phasing during transitions. Ozone is promising additive to combustion. During this work, a 0D physical model is developed based on temperature fluctuations inside the combustion chamber by using Probability Density Function (PDF) approach. For this, an enthalpy variance model is developed to be used in Probability Density Function (PDF) of temperature. This model presents a good agreement with the experiments. It is used to develop HCCI engine map with and without ozone addition in order to evaluate the benefit of using ozone in extending the map in term of charge-speed. The second part deals with control the combustion phasing by ozone addition. A Control Oriented Model (COM) coupled with control laws demonstrates the possibility to control combustion phasing cycle-to-cycle. Thereafter, an experimental test bench is developed to prove this possibility. A real time data acquisition system is developed to capture combustion parameters (Pmax, CA50). By integrating control laws into Engine Control Unit (ECU), results demonstrate not only the controllability of combustion phasing cycle-to-cycle during transitions but also to stabilize it for an instable operating point.

Les gyres subtropicaux sont au coeur des changements observés au cours des dernières décennies. On y observe entre la surface et la pycnocline permanente une augmentation du contenu thermique de l’océan. La pycnocline permanente délimite un important réservoir de chaleur et joue un rôle majeur en empêchant la chaleur accumulée en surface d’atteindre les profondeurs de l’océan. La pycnocline permanente est donc d’un intérêt important dans un contexte de changement climatique. Pour la première fois et grâce au réseau de données Argo, nous avons été capables de déterminer les propriétés de la pycnocline permanente. L’objectif de cette thèse est de déterminer la structure de la pycnocline permanente et d’étudier sa variabilité au cours des dernières décennies. Une méthode de détermination objective de la pycnocline permanente a été développée. Cette méthode a d’abord été appliquée à l’océan Atlantique nord avec les données Argo puis à l’océan global. Une structure complexe de la pycnocline permanente a été mise en évidence avec de fortes différences d’un gyre à l’autre. La pycnocline permanente est la plus profonde et la plus épaisse dans le gyre subtropical nord Atlantique. Cela explique que le gyre subtropical nord Atlantique soit le plus grand réservoir de chaleur au monde. Ensuite, les relations entre la variabilité du contenu de chaleur et les propriétés de la pycnocline permanente ont été étudiées en s’appuyant sur des réanalyses océaniques. Au cours des dernières décennies, un réchauffement important de l’océan a été observé et particulièrement dans l’océan Atlantique nord. Ce réchauffement est principalement dominé par un approfondissement des isopycnes. Les déplacements verticaux des isopycnes induisent des changements dans la stratification et affectent les propriétés de la pycnocline permanente (profondeur et densité potentielle). / Subtropical gyres are central to the observed climate changes throughout the last decades. It is observed between the surface and the permanent pycnocline an intense increase in the ocean heat content. The permanent pycnocline delineates thus an important heat reservoir. The permanent pycnocline has a major role in preventing heat to reach the deep ocean and it thus of a relative importance in the context of climate change. For the first time and thanks to the development of the Argo array, we have been able to characterize the observed structure of the permanent pycnocline. The objective of this PhD thesis is to investigate the structure of the permanent pycnocline and its variability over the last decades. We developed an objective method to characterize the properties of the permanent pycnocline. This method has been first applied to the North Atlantic Ocean with Argo data and then to the global ocean. A complex structure of the permanent pycnocline emerges with strong differences from one gyre to another. The permanent pycnocline is found to be the deepest and the thickest in the North Atlantic subtropical gyre. It implies that the North Atlantic subtropical gyre is the largest heat reservoir on Earth. Then, ocean reanalyses have been used to investigate the changes in the permanent pycnocline properties in the North Atlantic subtropical gyre. Over the last decades, there is a strong warming of the upper ocean, especially in the North Atlantic subtropical gyre. The warming in the ocean is dominated by the heaving of isopycnal surfaces. This heaving strongly affects the depths of isopycnals and the stratification. This in turn affects the properties of the permanent pycnocline, especially its depth and potential density.