CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Esta dissertaÃÃo à um estudo sociolÃgico realizado com jovens acometidas por anorexia nervosa, pacientes de um serviÃo mÃdico especializado no tratamento de transtornos alimentares. Com base no depoimento de trÃs jovens, pretende-se apresentar as contradiÃÃes vivenciadas por elas no curso do tratamento mÃdico. Neste estudo investigo como as anorÃxicas produzem um corpo considerado saudÃvel pela ciÃncia mÃdica. Para tanto, conto como principal interlocutor Michel Foucault. A partir de seu conceito de resistÃncia pretendo perceber como as pacientes anorÃxicas produzem suas subjetividades ao negociarem com os saberes mÃdicos e midiÃticos de saÃde, bem-estar e beleza. à ainda interesse deste trabalho compreender como produÃÃo da identidade de gÃnero aparece no processo de renÃncia a um corpo prÃ-pÃbere para assumir um corpo sexualmente maduro. Baseada numa abordagem qualitativa e, especificamente, na prÃtica de pesquisa de campo foi possÃvel observar que a experiÃncia anorÃxica à essencialmente paradoxal. A produÃÃo do corpo anorÃxico em corpo saudÃvel exige recomposiÃÃes entre o desejo de permanecer excessivamente magra e o desejo de ficar boa. A partir dos depoimentos das anorÃxicas à possÃvel afirmar que o transtorno à uma manifestaÃÃo do desacordo entre a tentativa dessas garotas em construir um sentimento de autonomia ao controlar os impulsos alimentares e a impossibilidade de mediar a multiplicidade de discursos sobre saÃde, beleza e dietas ou de eleger apenas um desses discursos como modo de vida / This dissertation is a sociological study about young girls stricken with nervous anorexia attending a medical service that specializes in the treatment of alimentary disorders. Based on cases related by three youths, this work aims at presenting conflicting aspects that those patients had to go through during their medical treatment. It is investigated how anorexic subjects display a body that is considered healthy by medical science. To this end it was engaged as main support the work of Michel Foucault. Based on his concept of resistance, it is sought to unveil how anorexic patients produce their subjectivities in dealing with medical knowledge and information obtained from the media about health, well being and beauty. In the same fashion, this works is interested in discovering how production of genre identity appears in the process of renouncing a prepubescent body in order to adopt a sexually mature body. Based on a qualitative approach, especially from data obtained from field research, it was possible to observe that the anorexic experience is essentially a paradoxical feature. The production of an anorexic body into a healthy body requires rearrangements going from the will of keeping an excessively slender figure and the desire of obtaining cure. Based on statements from anorexic subjects it is possible to assert that the disorder is both a manisfestation of disagreement presented by these girls in their attempt at building a feeling of autonomy by reining their feeding drives and the plentiful offer of discourses about health, beauty and diets in order to elect just one of these discourses as their guidance to a way of life

Esta dissertação tem como base de estudo a análise do desempenho técnicoconstrutivo dos edifícios forenses designados pela Secretaria da Justiça e da Cidadania do Estado de São Paulo como sendo o tipo F1, que foram projetados e construídos nos anos de 1970, para comportarem apenas uma Vara Judicial e seu respectivo Cartório, e área construída de 1.121,40 m². Os edifícios objetos desta dissertação deste mestrado (tipo F1) estão situados em comarcas distantes até 200 (duzentos) quilômetros da Capital, quais sejam: Cotia, Mairiporã, Franco da Rocha, Salto, Itanhaém e Angatuba. Dentro de um raciocínio crítico foi aplicado a metodologia da análise do desempenho técnico-construtivo de edifício em função das suas patologias construtivas originadas pelas deficiências do projeto, da execução da obra, dos materiais utilizados na época de sua implantação e sua situação atual de manutenção, considerando seus reflexos e influências nos itens do desempenho dos materiais e técnicas construtivas utilizadas em cada órgão/elemento dos edifícios que serão analisados segundo os requisitos dos usuários ISO 6241. / This master thesis deals has as study base the analysis of the technicalconstructive performance of the forensic buildings assigned by the Secretariat of the Justice and the Citizenship of the State of São Paulo as being the type F1, that projected and they had been constructed in the years of 1970, to hold only one Judicial Pole and its respective Notary\'s office, and constructed area of 1.121, 40 m ². The buildings objects of this master thesis (type F1) they are situated in distant judicials district even 200 (two hundred) kilometers of the Capital, which are: Cotia, Mairiporã, Franc of the Rock, Jump, Itanhaém e Angatuba. Inside of a critical reasoning the methodology of the analysis of the technicianconstructive performance of building in function of its constructive pathologies resultant from lack and deficiencies of the design, construction, materials at the time of its implantation and its current situation of maintenance, considering its consequences and influences in the item of the performance of the materials and constructive techniques used in each agency/element of the buildings that will be analyzed according to requisite of users - ISO 6241.

An osteological study on human skeletal remains from Maassara in Egypt. The goal of the study was to get a good picture of the health of the individuals buried in the graves at Maassara. The study was combined of nine individuals. Two from the Early Dynastic period and six individuals from the Old Kingdom. All the adult individuals have some form of pathological change. Most pathological changes are in the spine. Most pathological changes were age-related. Some of the individuals were very poorly kept and the bones were very fragile.

Les rétinites pigmentaires (RP) sont des pathologies rétiniennes cécitantes d'origine génétique caractérisées par une perte des photorécepteurs. Nous avons ciblé des formes de RP autosomique dominante consécutives à des mutations dans le gène du pigment visuel de la RHODOPSINE, du facteur d'épissage PRPF31 et du facteur de transcription impliqué dans le développement des photorécepteurs NR2E3. Les fibroblastes, issus de biopsies de peau de patients, ont été reprogrammés en cellules iPS par une technique dite non intégrative. Après stabilisation des cellules iPS, nous avons vérifié leur propriété de pluripotence et l'absence d'anomalies caryotypiques.Les cellules iPS porteuses d'une mutation sur le gène RHODOPSINE ont été différenciées dans le lignage des photorécepteurs. Nos résultats montrent que les photorécepteurs porteurs de la mutation P347L du le gène RHODOPSINE récapitulent la dégénérescence observée chez les patients.Nous montrons que les cellules de l'épithélium pigmentaire rétinien (EPR) dérivées de cellules iPS porteuses de la mutation Cys294X du gène PRPF31 présentent des problèmes d'adhésion cellulaire due à l'absence de lame basale. Leur activité de phagocytose est alors perturbée, suggérant qu'un dysfonctionnement de l'EPR pourrait être à la base de la RP causée par la mutation Cys294X du gène PRPF31. Les modèles développés nous ont permis de mieux comprendre les processus à la base de la pathogénèse de certaines RP. Ces modèles associés à des protocoles de criblage, pourraient permettre d'évaluer l'efficacité et la toxicité de nouvelles molécules pharmacologiques, mais également être utilisés pour valider des approches de thérapie génique. / Retinitis pigmentosa (RP) is an inherited retinal diseases characterized by a loss of photoreceptors. We focused specific forms of autosomal dominant RP with mutations in the rod visual pigment RHODOPSIN, the ubiquitous splicing factor PRPF31 and the transcription factor involved in the development of photoreceptors NR2E3. Fibroblasts from skin biopsies of patients were reprogrammed into iPS cells by a non-integrative approach. After stabilization of iPS cell lines, we verified their pluripotency property and the absence of karyotype abnormalities. Based on the retinal differentiation protocol, iPS cells carrying a mutation in the RHODOPSIN gene have been differentiated in the photoreceptor lineage. Our results showed that the photoreceptors expressing the mutated form of RHODOPSIN summarizing the process of degeneration observed in RP patients. We show that retinal pigment epithelium (RPE) cells derived from iPS cells carrying a mutation in the PRPF31 gene lack basal membranes and have cell adhesion disorders. Consequently, their phagocytic activity is disturbed, suggesting that a malfunction of the RPE could be the primary step of the development of RP caused by mutation Cys294X in the PRPF31 gene. The models developed from specific-patient iPS cells have enabled us to better understand the processes underlying the pathogenesis of some RP. These models associated with screening protocols could be used to evaluate the efficacy and toxicity of new pharmacologic compounds but also used to validate new gene therapy approaches.

Les pathologies du système musculosquelettique concernant les déformations / anomalies osseuses et musculaires (e.g. paralysie cérébrale) ont un fort impact sur la qualité de vie des personnes concernées. Les objectifs de la thèse sont d’approfondir les études précédentes en intégrant la modélisation de l’incertitude des données biomécaniques et biomédicales dans les modèles de diagnostic prédictif des pathologies du système musculosquelettique. L’intervalle a été choisi pour représenter l’incertitude des données biomécaniques. Ce formalisme est simple et peu coûteux sur le plan du calcul. Les données (physiologiques, morphologiques, mécaniques et analyse du mouvement) ont été recueillies à partir de la littérature en utilisant les moteurs de recherche des articles scientifiques fiables pour établir un espace d’incertitude. La nouvelle méthode de classement (nommée US-ECM) proposée est une méthode de classement semi-supervisé qui utilise la partition crédale pour représenter les connaissances partielles sur les clusters. L’utilisation de la fonction de croyance pour représenter ces éléments de connaissance permet de les combiner d’une manière souple et robuste. De plus, l’extension de cette méthode avec un espace d’incertitude multidimensionnelle a montré la meilleure performance par rapport à la version originale. L’analyse des avis d’expert permettra d’inclure ou d’exclure les sources de données selon leurs niveaux de fiabilité. Ensuite, le modèle de regroupement (US-ECM) développé sera appliqué sur une nouvelle base de données pour évaluer l’impact de la fiabilité des données sur la performance de diagnostic. / The aim of the project is to investigate the modeling of the reliability/incertitude/imprecision of biomedical and biomechanics data (medical images, kinematics/kinetics/EMG data, etc.) and its propagation in the predictive diagnosls models of the disorders of musculoskeletal systems. These diagnosis models will be based on multimodal and multidimensional patient data (3D medical imaging, mechanical data,dinical data,etc.). The literature-based data have been collected to estabish an uncertainty space, which represents fused data from multiple sources, of morphological, mechanical, and movement analysis properties of the musculoskeletal system from multiple sources (i.e. research papers from Science Direct and Pubmed). After that,a new clustering method (US-ECM) is proposed for integrating fused data from multiple sources ln form of a multidimensional uncertainty space (US). Reliability of biomechanical data was evaluated by a fusion approach expert opinion. Reliability criteria of a data source (ie scientific paper published) focus on the technique used the acquisition protocol and measurement and the number of data. A system of questionnaires was developed to co!lect expert opinion. Then, the theory of beliet functions has been applied to merge these opinion to establish a confidence level each data source.

L’infection par le cytomégalovirus (CMV) au cours de la grossesse est fréquente et représente la première cause de pathologie neurodéveloppementale. En dépit de cette importance médicale, il n’existe à ce jour aucun traitement préventif ou curatif satisfaisant, et les mécanismes physiopathologiques mis en jeu, en particulier au niveau du cerveau foetal, restent mal connus. Des découvertes récentes sur les modèles murins d’infection cérébrale par le CMV, principalement réalisées pendant la période néonatale, ont apporté des données convergentes sur la physiopathologie de ces infections cérébrales ; notamment, le rôle joué par les cellules immunitaires périphériques dans la résolution de l’infection, et l’implication du système immunitaire cérébral (SIC) au cours du processus infectieux. Afin de compléter et préciser les résultats précédemment obtenus dans différents modèles murins, et de comprendre le rôle joué par le SIC, le premier objectif de ma thèse a consisté à mettre au point et à caractériser un nouveau modèle d’infection cérébrale par le CMV au cours du développement in utero chez le rat. Dans l'ensemble, nos résultats confirment l'altération du SIC au cours de l'infection par le CMV du cerveau en développement, et suggèrent fortement, dans ce modèle, un rôle majeur joué par le système microglie/macrophage dans l'émergence de troubles neurologiques semblables à ceux observés dans la pathologie humaine correspondante. / Cytomegalovirus (CMV) infection during pregnancy is the leading cause of neurodevelopmental disorders (polymicrogyria, microcephaly) and may lead to severe sensorineural consequences (deafness, epilepsy, cerebral palsy and hearing loss). Despite this medical importance, no preventive or curative treatment is satisfactory to date, and the pathophysiological mechanisms, notably in the fetal brain, remain poorly understood. Recent findings in murine brain CMV infection, mostly in neonatal models, have brought converging insights into the pathogenesis of these infections; the possible role played by peripheral immune cells against infection and the involvement of the brain immune system (BIS) have been proposed. The actual roles of BIS during in utero infection, and more specifically that of microglial cells and macrophages, remain unclear. In order to expand and precise the data previously obtained in the murine models, and to clarify the role of BIS, the first objective of my thesis was to design and to characterize a novel model of CMV infection during the fetal development of the rat brain. Overall, our datas confirm the altered state of BIS as a consequence of CMV infection of the developing brain, and strongly suggest, in the rat model studied here, that the microglia/macrophages system plays critical role in the pathogenesis of neurological manifestations similar to those classically seen after human congenital CMV infection.

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-04-13T17:54:47Z No. of bitstreams: 1 Arnoldo Mesquita Filho.pdf: 3369344 bytes, checksum: 1db89a5c8d8f47568c9a72abadfb5eba (MD5) / Made available in DSpace on 2018-04-13T17:54:47Z (GMT). No. of bitstreams: 1 Arnoldo Mesquita Filho.pdf: 3369344 bytes, checksum: 1db89a5c8d8f47568c9a72abadfb5eba (MD5) Previous issue date: 2018-02-28 / The study aimed to diagnose the current state of unpaved roads that were recovered by the Sustainable Development Project Microbacias II - Access to the Market of the Government of the State of São Paulo. To do so, based on consultation with the documents provided by the Coordination of Integral Technical Assistance (CATI), two roads were located in the municipality of Santa Isabel - SP. Afterwards, evaluation of the traffic conditions of these roads was applied based on subjective methodology, as proposed by Riverson et al. (1987), and objective methodology, according to Eaton and Beaucham (1995). A total of 22 sample units with extensions of 100 m each and with different areas were selected. The results of the diagnoses obtained by the different methodologies presented great divergence. Thus, for the subjective method, three classes of degrees of trafficability were found, being 36% good, 46% regular and 18% very bad. The results obtained by the objective method allowed the classification of four traffic classes, being 23% excellent, 27% very good, 23% good and 27% reasonable. They contribute, as they clarify the differences in the results of both methods and indicate the need for studies that seek to find the causes of such differences, as well as to propose adaptations to existing methods, so that, finally, the results contribute in fact to actions of the public power with ways to appropriate intervention. / O estudo teve como objetivo diagnosticar o atual estado de estradas não pavimentadas e que foram recuperadas pelo Projeto de Desenvolvimento Sustentável Microbacias II – Acesso ao Mercado do Governo do Estado de São Paulo. Para tanto, selecionou, com base em consulta aos documentos fornecidos pela Coordenadoria de Assistência Técnica Integral (CATI), duas estradas localizadas no município de Santa Isabel – SP. Na sequência, aplicou-se avaliação das condições de trafegabilidade destas estradas com base em metodologia subjetiva, conforme proposta por Riverson et al. (1987), e metodologia objetiva, de acordo com Eaton e Beaucham (1995). Foi selecionado um total de 22 unidades amostrais com extensões de 100 m cada e com áreas distintas. Os resultados dos diagnósticos obtidos pelas diferentes metodologias apresentaram grande divergência. Assim, para o método subjetivo, foram encontradas três classes de graus de trafegabilidade, sendo 36% bons, 46% regulares e 18% muito ruins. Já os resultados obtidos pelo método objetivo, permitiram a classificação de quatro classes de trafegabilidade, sendo 23% excelentes, 27% muito boas, 23% boas e 27% razoáveis. Os contribuem, uma vez que clareiam as diferenças existentes nos resultados de ambos os métodos e indicam a necessidade de estudos que busquem encontrar as causas de tais diferenças, bem como que se proponham a realizar adaptações aos métodos existentes, para que, enfim, os resultados contribuam de fato para ações do poder público com vias a adequada intervenção.

Conformément aux principes de la médecine factuelle, les guides de bonne pratique clinique (GBPC) sont élaborés dans un but d'amélioration de la qualité des soins. Pourtant, le suivi des recommandations par les médecins reste faible, même lorsqu'elles sont intégrées dans des systèmes informatisés d'aide à la décision. En effet, elles sont souvent critiquées pour leur manque de flexibilité, et leur incapacité à gérer la singularité des patients rencontrés en pratique clinique. En particulier, leur orientation monopathologique est en inadéquation avec la réalité de patients bien souvent polypathologiques. Nos travaux portent sur la proposition d'une méthode basée sur un raisonnement ontologique pour permettre la conciliation de GBPC pour la prise en charge flexible de patients polypathologiques au sein d'un système d'aide à la décision. Les bases de connaissances reposent sur des règles construites par formalisation des recommandations, dont les critères patients sont organisés par une ontologie du domaine, permettant de produire un graphe des profils cliniques structuré par généralisation. Le raisonnement ontologique permet une juste adaptation des connaissances aux niveaux d'abstraction variables de la description du patient. Cette méthode a été implémentée dans un système d'aide à la décision, appelé GO-DSS, et appliquée à la prise en charge de patients diabétiques et hypertendus, à partir des GBPC produits par la société VIDAL (VIDAL Recos). Le prototype et ses interfaces ont été évalués qualitativement par un échantillon d'utilisateurs comprenant à la fois des informaticiens avec des connaissances médicales et des médecins avec des compétences en informatique. / Clinical practice guidelines (CPGs) are elaborated according to evidence-based medicine principles in order to improve healthcare quality. However, even when they are integrated into clinical decision support systems, recommendations are poorly implemented by physicians. Indeed, CPGs are often criticized for their lack of flexibility, and their inability to handle the singularity of patients encountered in clinical practice. In particular, CPGs are usually elaborated for a single pathology whereas patients usually suffer from multiple pathologies and comorbidities. We have proposed a method based on an ontological reasoning to enable the reconciliation of single-pathology CPGs to support the flexible management of patients with multiple pathologies. Knowledge bases are made of decision rules that formalize the content of single-pathology CPGs. Patient criteria are organized by a domain ontology, which allows the generation of a generalization-ordered graph of clinical patient profiles. The ontological reasoning allows to reason at different levels of abstraction to process clinical cases described with different levels of completeness. This method has been implemented in a decision support system called GO-DSS, and applied to the management of patients suffering from both arterial hypertension and type 2 diabetes, on the basis of CPGs produced by the VIDAL company (VIDAL Recos). The prototype and its user interfaces have been qualitatively evaluated by a sample of users including both computer scientists with medical knowledge and physicians with computer skills.

L’amélioration du pronostic des pathologies chroniques à début pédiatrique s’est accompagnée d’un nombre grandissant de patients atteignant l’âge adulte. Cependant, l’adolescence et l’entrée dans la vie adulte est une période de multiples changements et de crises, pouvant être à l’origine de rupture avec le système de soins et de complications médicales. Dans cette thèse, j’ai tout d’abord décrit les hospitalisations et la mortalité des jeunes ayant été déclarés en affection de longue durée (ALD) avant 14 ans (N=1752), en comparaison à des jeunes sans pathologie chronique (N=52346). Pour cela, une cohorte rétrospective (2005-2014) a été reconstruite à partir de l’échantillon généraliste des bénéficiaires de l’Assurance maladie. Environ 3% des jeunes de 14 ans avaient déjà été déclarés en ALD. Les profils de mortalité par sexe et les tendances par âge de l’incidence des hospitalisations étaient différents de ceux de la population générale du même âge, en particulier après 18 ans, où l’on observait une chute de l’incidence des hospitalisations. Ensuite, à partir de ces mêmes données, j’ai montré que le pronostic de ces jeunes malades, y compris la mortalité, était associé à la précarité sociale, mesurée par la couverture maladie universelle complémentaire, montrant ainsi que la gratuité des soins à laquelle ces jeunes ont droit dans le système de santé français ne permettait pas de compenser les inégalités sociales dans cette population. Enfin, à un moment ou un autre, ces jeunes sont transférés vers un service d’adultes. Ce passage est un moment crucial dans leur suivi, qui peut être à l’origine d’une discontinuité du suivi médical. Des programmes de transition sont mis en place progressivement pour préparer et accompagner ce transfert. J’ai réalisé une revue systématique de la littérature (23 études) qui a montré qu’il existait deux aspects de la continuité des soins au moment de ce transfert : l’engagement (premier contact) et le maintien dans le suivi en service d’adultes. Cette analyse a également mis en exergue la pauvreté des études existant actuellement pour évaluer les programmes de transition en termes de continuité des soins. Finalement, ces résultats soulèvent de nombreuses questions, notamment les stratégies d’adaptation de ces jeunes vis-à-vis des situations à haut risque et le rôle du transfert en service d’adultes sur le comportement des patients, le pronostic et les pratiques cliniques. Des études incluant largement l’ensemble des jeunes atteints d’une pathologie chronique, intégrant notamment des facteurs liés à l’organisation des soins, liés à la pathologie, individuels et familiaux, devraient être encouragées. / The prognosis of childhood-onset chronic conditions has improved, such that more patients now reach adulthood. However, adolescence and entry into adulthood is a critical period that may be associated with poor outcomes, including gaps in care continuity and medical complications. Here, I first described hospitalization and mortality rates in youths registered for a long-term disease (LTD) before the age of 14 (N=1,752), relative to those with no LTD (N=52,346). A retrospective cohort (2005-2014) was built from a sample of the French national health insurance database, called Echantillon généraliste des Bénéficiaires. Approximately 3% of 14-year-old youths had been registered for a LTD. The mortality patterns by gender and the trend in hospitalization rates by age were different from those in the general population of the same age, especially after reaching the age of 18, which was followed by a fall in hospitalization rates. Then, using the same data, I showed that the prognosis of these youths living with a chronic disease, including mortality, was associated with low socio-economic level, as measured by being covered by Couverture Maladie Universelle Complementaire, a public complementary health insurance offering free access to care, delivered on the basis of very low househould incomes. Hence, overcoming financial barriers did not offset social health inequalities in this population. At last, one day, these youths have to be transferred to adult care. Moving to adult care is a critical time in patients’ follow-up that may lead to discontinuity in medical care. Transition programs are being gradually implemented, to prepare and smooth the transfer and support youths during this period. I performed a systematic review of literature (23 studies) that highlighted two aspects of continuity of care during transfer: engagement (first contacts) and retention in adult care once the first contact has been established. This review also emphasized the paucity of knowledge to evaluate transition programs in terms of care continuity. Finally, the results of this PhD raises many issues that need to be addressed, including coping strategies of young patients with high risk situations, and the role of transfer to adult care on patient behavior, prognosis and clinical practices. Studies involving patients with a large spectrum of severe chronic diseases, including factors related to healthcare organization, related to the disease, individual and familial, should be encouraged.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.