Os Transtornos por Uso de Substâncias (TUS) são propostos pela Associação Norte-Americana de Psiquiatria e englobam diversas dependências químicas, incluindo o tabagismo e a dependência de crack. O uso de crack tem aumentado consideravelmente nos últimos anos, segundo dados de levantamentos brasileiros e mundiais. Com mecanismo de ação semelhante ao da cocaína, porém com efeito mais rápido, o crack é uma droga que causa grave prejuízo a seus usuários e conduz à dependência em pouco tempo. O tabagismo também é uma condição bastante prevalente no mundo inteiro, sendo que os prejuízos relacionados a esse transtorno envolvem principalmente o desenvolvimento de doenças respiratórias e câncer. Diversos trabalhos têm buscado identificar fatores de suscetibilidade a esses transtornos, sendo que estudos de associação envolvendo genes do sistema de resposta a estresse vêm ganhando importância. O eixo Hipotálamo- Pituitária-Adrenal (HPA) é o sistema de resposta a estresse mais conhecido em humanos e alvo do presente trabalho, uma vez que o funcionamento dessa cascata de sinalização da produção de cortisol pode desempenhar um papel relevante no desenvolvimento de psicopatologias. Além disso, o eixo HPA pode ser considerado um mediador da relação entre situações adversas na infância e o surgimento de TUS. O objetivo desse trabalho, portanto, é investigar o papel de polimorfismos no gene CRHR1 (que codifica o receptor tipo 1 do hormônio liberador de corticotrofina – CRH, hormônio inicial do eixo HPA) sobre o desenvolvimento e características clínicas da dependência química. Para isso, foram realizados dois estudos, envolvendo amostras de mulheres. No primeiro artigo, a partir de três amostras – (1) 136 usuárias de crack, (2) 55 tabagistas e (3) 262 voluntárias saudáveis – foram identificadas diferenças de freqüências alélicas e genotípicas do SNP rs12944712; além disso, a análise de haplótipos envolvendo tal SNP e o rs110402 revelou maior frequência do haplótipo contendo o alelo G nos dois polimorfismos nos grupos de usuárias de crack e tabagistas. No segundo artigo, foi avaliado o efeito da interação geneambiente envolvendo os mesmos polimorfismos e situações adversas na infância – estimada pela escala Childhood Trauma Questionnaire (CTQ) –sobre características clínicas da amostra de usuárias de crack, como craving e gravidade da dependência – estimados, respectivamente, pelas escalas Cocaine Selective Severity Assessment (CSSA) e Addiction Severity Index (ASI6). A análise não revelou uma interação significativa. A presente dissertação, portanto, revela um efeito do gene CRHR1 sobre o desenvolvimento de TUS, embora esse efeito pareça não se manifestar sobre a gravidade. Mais estudos são necessários visando esclarecer o real efeito do gene e do eixo HPA como um todo sobre os fenótipos e comportamentos aditivos, bem como os mecanismos subjacentes a essa relação. / The Substance Use Disorders (SUD) are proposed by the American Psychiatric Association and comprise several addictions, including tobacco and crack cocaine smoking. The prevalence of crack cocaine dependence has grown considerably, according to survey data from Brazil and worldwide. With mechanism of action similar to cocaine but with faster effect, crack is a drug that causes severe impairments to its users and leads to dependence in a short time. Tobacco smoking is also a highly prevalent condition worldwide, and the impact related to this disorder includes cancer and respiratory diseases. Several studies have attempted the identification of susceptibility factors to these disorders, and association studies involving stress response system genes have been performed. The Hypothalamic-Pituitary-Adrenal (HPA) axis is the best known stress response system, and the signaling cascade production of cortisol may play a role in the development of psychopathology. In addition, HPA axis can be considered a mediator of the relationship between early life adversity and SUD. The aim of this study is to investigate the role of polymorphisms in CRHR1 gene (encoding the corticotrophin releasing factor – CRH – receptor type 1, an initial factor in HPA axis response) on the development and clinical traits of drug dependence. Two studies were conducted on women samples. In the first article, three groups were compared - (1) 136 crack smokers, (2) 55 tobacco smokers and (3) 262 healthy volunteers. Differences in allele and genotype frequencies of the SNP rs12944712 were identified; in addition, the haplotype analysis involving this SNP and rs110402 revealed a higher frequency of the haplotype containing G allele in both polymorphisms in the groups of nicotine dependents and crack smokers. In the second article, we evaluated the effect of a gene-environment interaction involving the same polymorphisms and childhood adversity - estimated by Childhood Trauma Questionnaire (CTQ) scale – on clinical characteristics of the sample of crack users, such as craving and severity of dependence - estimated respectively by the Cocaine Selective Severity Assessment (CSSA) and Addiction Severity Index (ASI6) scales. The analysis did not reveal a significant interaction. This dissertation thus shows an effect of CRHR1 genepolymorphism on the development of SUD, although this effect does not seem to impact disorder severity. More studies are needed in order to clarify the actual effect of the gene and of the HPA axis as a whole on addictive behaviors.

Introdução: O consumo de crack tem sido alvo de grande preocupação em vista de sua expressiva expansão e dos problemas sociais e de saúde decorrentes. A cocaína na forma de crack difere das outras vias de uso principalmente pelo seu rápido início de ação, pouco tempo de efeito e alta concentração plasmática, levando a um maior impacto orgânico e a um elevado potencial de dependência. A deterioração física e cognitiva são aspectos centrais na gravidade do uso dessa droga. As taxas de infecção pelo HIV e HCV são elevadas nessa população, mas os fatores de risco associados ainda não estão claros na literatura, em particular no Brasil. Há uma busca por marcadores biológicos que possam auxiliar a avaliar o impacto físico e cerebral ocasionados pelo uso do crack. Achados recentes sugerem que as neurotrofinas cerebrais e marcadores de estresse oxidativo possam ser úteis nesse sentido. Objetivos: Avaliar a prevalência e fatores de risco associados à infecção por HIV e HCV em mulheres usuárias de crack e investigar se os níveis de BDNF, TBARS e PCC em usuários de crack, antes e após desintoxicação, diferem de controles e respectivos correlatos clínicos. Método: O artigo 1 utiliza um desenho transversal com uma amostra de conveniência de 76 mulheres com uso recente de crack. Foram coletados sangue para os testes de HIV/HCV, dados demográficos e instrumentos que avaliaram conhecimento sobre AIDS, consumo de drogas e comportamentos de risco para AIDS. No artigo 2 uma coorte com 49 usuários de crack homens foram recrutados da internação do Hospital Psiquiátrico São Pedro em Porto Alegre e 97 controles comunitários foram obtidos de um bairro pobre da cidade de Canoas (região metropolitana de Porto Alegre). O sangue para análise de BDNF (artigo 2), TBARS e PCC (resultados complementares) foi coletado no primeiro dia de internação e no dia da alta nos usuários de crack e no dia da entrevista nos controles. Nas duas amostras e nos controles os participantes tinham mais de 18 anos e realizaram teste de urina para cocaína. Resultados: No artigo 1, a prevalência de HIV entre as mulheres foi de 37,0% e de HCV de 27,7%, sendo 15,1% a prevalência de co-infecção. A análise ajustada identificou 4 anos ou menos de escolaridade como maior chance de infecção por HIV – RC 4,72 (1,49-14,99) e por HCV RC - 4,51 (1,18-17,27) e ter realizado 3 ou mais testes para HIV na vida - RC 4,26 (1,29-14,04) associado com contaminação por HIV. No artigo 2, os níveis de BDNF entre homens usuários de crack foram significativamente menores na admissão (28,6±11,0) quando comparados com os controles (39,5±10,6) e com o valor na alta hospitalar (35,6±12,3), mesmo após ajuste para as variáveis confundidoras. O valor do BDNF na alta foi um pouco menor nos usuários de crack, mas sem diferença significativa em relação aos controles. O aumento do BDNF teve associação significativa com número de dias de internação e inversa com anos de uso de crack e número de pedras de crack utilizadas no último mês. Os resultados complementares mostram que os valores médios de TBARS e PCC são semelhantes na internação e alta em relação aos controles. Contudo, o valor do TBARS na alta e a alteração durante a internação foram diretamente correlacionados com a gravidade do consumo de crack. Conclusões: Nós encontramos uma alta prevalência de contaminação por HIV e HCV entre mulheres usuárias de crack e o baixo nível educacional foi o fator de risco mais importante identificado. Em relação aos valores de BDNF em homens, foi possível identificar que este se encontra reduzido na vigência do uso de crack, com aumento na abstinência precoce, passando a ter níveis comparáveis aos controles. O aumento do BDNF e a diminuição do TBARS durante a abstinência precoce foram relacionados à menor gravidade de uso do crack. Esses achados sugerem que as variações de BDNF e TBARS após desintoxicação inicial possam ser marcadores da gravidade do uso de crack e de prognóstico, a serem investigados em futuros estudos. / Background: Crack cocaine has a been subject of great concern in view of its widespread use, as well as its increasing social and health problems. Crack cocaine differs from other administration routes primarily by its rapid onset of action, short effect and high plasma concentrations, leading to a higher organic impact and high potential for addiction. Physical and cognitive deterioration are key aspects of crack cocaine induced impairment. Rates of HIV and HCV are high in this population, but risk factors are still unclear in the literature, particularly in Brazil. There is search for biomarkers that may help identify the physical and brain injuries caused by its use. Recent findings suggest that brain neurotrophins and oxidative damage markers may be useful in this regard. Objectives: To ascertain the HIV/HCV serostatus and associated risk behaviors for infection of female crack users. To evaluated BDNF, TBARS and carbonyl levels among crack cocaine users during inpatient treatment, before and after drug withdrawal, vs. healthy controls. Clinical correlates with changes in biomarkers levels were also assessed. Method: Paper 1 is a cross-sectional study with a convenience sample of 76 female crack cocaine users. Subjects answered NIDA’s Risk Behavior Assessment and the AIDS Information Questionnaire. In addition, blood was collected from subjects for HIV/HCV tests. Blood samples for serum BDNF (paper 2), TBARS and PCC (complementary results) evaluations were collected in a cohort of 49 male crack users on the first and last days of hospitalization and in 97 healthy controls. In both samples and in the control group subjects were 18 years old or more and underwent urine tests for cocaine. Results: In paper 1, the overall prevalence of HIV was 37.0%; HCV seroprevalence was 27.7%; 15.1% of the sample was co-infected with HIV and HCV. Four years of schooling or fewer (OR 4.72 - CI 95% ((1.49-14.99)) was associated with HIV and HCV infection (OR 4.51 - CI 95% (1.18-17.27)) after multivariate logistic regression. In paper 2 BDNF levels among male crack users were significantly lower upon admission (28.6±11.0) when compared to controls (39.5±10.6) and discharge (35.6±12.3), even after adjustment for confounding variables. At discharge, BDNF levels between patients and controls were similar. Number of crack rocks used in the last 30 days and years of crack use were inversely correlated with the outcome. Complementary results show that levels of carbonyl and TBARS are similar at admission and discharge compared to controls. However, the TBARS levels at discharge and its variation rate during hospitalization were significantly correlated with the severity of crack cocaine use. Conclusions: We found a very high prevalence of HIV and HCV infection among female crack users, and low education was the most important risk factor associated with both infections. With regard to BDNF levels among men, it was reduced while using crack cocaine increased in early withdrawal reaching levels similar to control group at discharge. Rates of BDNF increase and TBARS decrease were correlated with severity of crack use. These findings suggest that the variation of BDNF and TBARS during early withdrawal may be a marker of severity of crack use.

Dissertação (mestrado)—Universidade de Brasília, Instituto de Psicologia, Programa de Pós-Graduação em Processos de Desenvolvimento Humano e Saúde, 2013. / Submitted by Jaqueline Ferreira de Souza (jaquefs.braz@gmail.com) on 2014-01-02T13:04:42Z No. of bitstreams: 1 2013_HannyaElianaHerreraCardona_Parcial.pdf: 1103268 bytes, checksum: 52bb6a86b179232c4768f82a24d83c22 (MD5) / Approved for entry into archive by Marília Freitas(marilia@bce.unb.br) on 2014-01-02T13:44:20Z (GMT) No. of bitstreams: 1 2013_HannyaElianaHerreraCardona_Parcial.pdf: 1103268 bytes, checksum: 52bb6a86b179232c4768f82a24d83c22 (MD5) / Made available in DSpace on 2014-01-02T13:44:20Z (GMT). No. of bitstreams: 1 2013_HannyaElianaHerreraCardona_Parcial.pdf: 1103268 bytes, checksum: 52bb6a86b179232c4768f82a24d83c22 (MD5) / Embora se fale muito sobre o tema no Brasil, pouco se conhece sobre a realidade do usuário de crack que busca tratamento no Sistema de Saúde. Além disso, os tratamentos costumam ser precários, e o número de pacientes que melhoram sua qualidade de vida ainda é muito pequeno e pouco documentado. Este estudo propõe-se a definir o padrão de consumo e o perfil do usuário de crack que busca tratamento no CAPS-ad do DF e analisar as formas de intervenção através do modelo de Gerenciamento de Caso, com o propósito de compreender os significados e as relações construídas por profissionais da saúde e por usuários de crack vinculados ao CAPS-ad de uma cidade-satélite do DF. Visa-se com isso contribuir com subsídios para a qualificação de profissionais da área da saúde do SUS. A realização da pesquisa deu-se em dois momentos e gerou dois níveis de análise de dados; a primeira, quantitativa e a segunda, qualitativa. O primeiro momento consistiu no levantamento de dados epidemiológicos sobre o padrão de consumo e o perfil do usuário de crack do DF, por meio dos instrumentos: Questionário de dados sociodemográficos, Questionário do Perfil de Consumo de Crack, Escala da Gravidade de Consumo de Crack, Cocaine Craving Questionnaire Brief, aplicados a 130 usuários de crack do DF que participaram do projeto “Avaliação, gerenciamento de caso e seguimento de usuários de crack que se encontram em tratamento em seis estados brasileiros”. Essas informações foram tratadas através de estatística descritiva e ajudaram a conhecer o perfil do usuário de crack que recebe tratamento no CAPS-ad, contribuindo na contextualização do fenômeno. Os dados quantitativos indicaram que os usuários de crack apresentam padrão de uso semelhante ao daqueles pertencentes às classes de menor poder aquisitivo, buscam tratamento quando encontra-se abstinentes e conscientes sobre os agravos provocados pela droga e apresentam grande suscetibilidade afetiva, sentimentos de culpa, tristeza e vergonha decorrentes de seu envolvimento com a droga. No segundo momento, foram realizadas entrevistas semiestruturadas com dois profissionais da área da saúde (Assistentes Sociais gerentes de casos treinados) e com quatro dos usuários acompanhados pelos respectivos gerentes de casos, nesse mesmo CAPS-ad. Observou-se que a adesão e o engajamento do usuário, bem como o fortalecimento de suas habilidades, não dependem somente do conhecimento técnico e teórico que o profissional possui. A adesão e o atendimento dependem também das capacidades e habilidades em acolher e estabelecer relacionamentos de confiança e vínculo terapêutico com o paciente. Além disso, a falta de articulação e enfraquecimento da rede de saúde (e desta com as demais redes de serviços) podem trazer dificuldades para o processo de reabilitação e reinserção do usuário. As implicações do estudo ressaltam a importância da qualificação dos profissionais da saúde em serviço no que tange à humanização da intervenção com os usuários de drogas, através do acolhimento, engajamento e articulação com os serviços que permitam ao indivíduo reconhecer-se como sujeito e se engajar na própria reabilitação e reinserção social. Nesse sentido, o gerenciamento de caso mostrou-se uma potente ferramenta de intervenção e acompanhamento de usuários de crack. _________________________________________________________________________________________________ ABSTRACT / Although much is said about this topic in Brazil, little is known about the reality of crack cocaine users seeking treatment in the Health System (Sistema Único de Saúde - SUS). Furthermore, treatments for crack users in Brazil tend to be precarious and the number of patients that improve their quality of life conditions is still very small, and these cases are not so well documented so far. This study aims to define the consumption pattern and profile of crack users seeking treatment in CAPS ad-DF and analyze types of intervention through the model of Case management, in order to understand the meanings and relationships constructed by health professionals and crack users linked to CAPS-ad of satellite cities of the Federal District. Its central aim is thereby to contribute to the promotion of processes of professional´s health qualification, belonging to the SUS. The research occurred in two phases and generated two-level data analysis, the first qualitative and the second of quantitative nature. In the first instance, an evaluation was carried out of epidemiological data taking into account the consumption pattern and crack user profile of the Federal District through the instruments: Sociodemographic Questionnaire, Profile of Crack Consumption Questionnaire, Severity of Crack Cocaine Consumption Scale, Cocaine Craving Questionnaire Brief Scale, applied to 130 crack users who participated in the project “Assessment, case management and accompaniment of crack users in treatment in six Brazilian states”. These data were analyzed using descriptive statistics, allowing to understand the profile of the crack users receiving treatment in the CAPS-ad, contributing thus to the contextualization of the phenomenon. Quantitative data indicate that crack use patterns are similar to those of persons belonging to lower income classes, they seek treatment when they remain abstinent and are aware of potential complications caused by the drugs, and have a great emotional sensitivity, as well as feelings of guilt, sadness, and shame arising of the relation to the drug’s use. In the second phase, semi-structured interviews were carried out with two health professionals (social workers / case managers trained) and four users accompanied by their case managers, belonging to the same ad-CAPS. It was observed that the adherence and involvement of the users, as well as strengthening their professional skills, not only depend on the technical and theoretical knowledge that the professional has. Adhesion and attention, also depend on the skills and capabilities to accept and build relationships of trust and therapeutic bond with the patient. Moreover, the lack of coordination and gradual weakening of the health network (and this with other services networks) could lead to problems in the rehabilitation and integration process of crack user. The implications of this research highlight the importance of the formation of health professionals. This formation can enable them to understand the importance of humanizing intervention with drug users through acceptance, engagement, and coordination with other services, which will allow drug users as subjects that recognize and get involved in their own rehabilitation and social reintegration. Consequently, Case management proved to be a powerful tool for intervention and accompanying of crack users.

abstract: Laboratory assessment of crack resistance and propagation in asphalt concrete is a difficult task that challenges researchers and engineers. Several fracture mechanics based laboratory tests currently exist; however, these tests and subsequent analysis methods rely on elastic behavior assumptions and do not consider the time-dependent nature of asphalt concrete. The C* Line Integral test has shown promise to capture crack resistance and propagation within asphalt concrete. In addition, the fracture mechanics based C* parameter considers the time-dependent creep behavior of the materials. However, previous research was limited and lacked standardized test procedure and detailed data analysis methods were not fully presented. This dissertation describes the development and refinement of the C* Fracture Test (CFT) based on concepts of the C* line integral test. The CFT is a promising test to assess crack propagation and fracture resistance especially in modified mixtures. A detailed CFT test protocol was developed based on a laboratory study of different specimen sizes and test conditions. CFT numerical simulations agreed with laboratory results and indicated that the maximum horizontal tensile stress (Mode I) occurs at the crack tip but diminishes at longer crack lengths when shear stress (Mode II) becomes present. Using CFT test results and the principles of time-temperature superposition, a crack growth rate master curve was successfully developed to describe crack growth over a range of test temperatures. This master curve can be applied to pavement design and analysis to describe crack propagation as a function of traffic conditions and pavement temperatures. Several plant mixtures were subjected to the CFT and results showed differences in resistance to crack propagation, especially when comparing an asphalt rubber mixture to a conventional one. Results indicated that crack propagation is ideally captured within a given range of dynamic modulus values. Crack growth rates and C* prediction models were successfully developed for all unmodified mixtures in the CFT database. These models can be used to predict creep crack propagation and the C* parameter when laboratory testing is not feasible. Finally, a conceptual approach to incorporate crack growth rate and the C* parameter into pavement design and analysis was presented. / Dissertation/Thesis / Ph.D. Civil and Environmental Engineering 2013

EDF souhaite conforter la justification de l’intégrité des cuves de réacteurs nucléaires à eau pressurisée, basées sur l’amorçage de fissure, par le concept d’arrêt de fissure. L'objectif de la thèse est de consolider les travaux de prévision de l’arrêt des fissures fragiles dans l’acier de cuve. Des essais d'arrêt de fissure isothermes réalisés entre -150°C et -50°C sur des éprouvettes CT et sur des anneaux en compression ont été analysés. Les analyses fractographiques montrent que la propagation et l’arrêt de fissure se produisent en clivage même si de la déchirure ductile précède la propagation instable de fissure. Un critère local d’arrêt de fissure fragile est appliqué lors de calculs par éléments finis en élastoviscoplasticité et en dynamique : la rupture se produit si la contrainte principale maximale est égale à une contrainte critique. Ce critère permet de bien prédire les vitesses de propagation ainsi que les longueurs de fissure à l’arrêt. La contrainte critique augmente avec la température en relation avec les signes de dissipation observés sur les surfaces de rupture. Une dépendance du critère à la géométrie est observée. Elle peut être liée aux hypothèses de calculs réalisés en bidimensionnel. L’étude de la dynamique de la structure montre que le phénomène d’arrêt de fissure est fortement lié à la dynamique globale de la structure : l’arrêt et la fermeture de la fissure interviennent simultanément. / EDF wants to complete the assessment of reactor pressure vessels usually based on crack initiation concept by crack arrest concept. The work aims at improving the knowledge of cleavage crack arrest in reactor pressure vessel steel. For that purpose, isothermal crack arrest experiments were performed for temperatures ranging from –150°C up to –50°C on compact tensile specimens and on pre-cracked rings submitted to compressive loading. Fractographic observations revealed that the whole crack propagation and arrest occurs by cleavage even if ductile tearing occurs before initiation of the unstable crack propagation. A local cleavage crack arrest criterion is applied in finite element computations carried out in elastoviscoplasticity and in full dynamics: the crack propagates since the largest principal stress reaches a critical stress. The application of this criterion on the experiments leads to a good prediction of the crack speed and of the crack length and shows that the critical stress increases with the temperature in relation with dissipation features observed on the fracture surfaces. Dependence to the geometry is observed; it can be due to the assumption used for the 2D computations. The study of the structural dynamic shows that the crack arrest phenomenon is very linked to the global dynamics of the structure: crack arrest and crack closure occur approximately at the same time.

L’objectif de cette thèse est de comprendre les micro-mécanismes physiques de propagation et d’arrêt de fissure de clivage dans l’acier de cuve 16MND5 et de proposer un modèle de prédiction robuste et physiquement fondé, en s’appuyant sur une campagne d’essais de rupture fragile sur éprouvettes de laboratoire finement instrumentées, associée à la modélisation numérique de ces essais. Dans un premier temps, des expériences ont été menées sur des éprouvettes CT25 de différentes épaisseurs à cinq températures (-150°C, -125°C, -100°C, -75°C, -50°C). Des trajets de fissures rectilignes et branchées (deux fissures se développant de manière quasi-symétrique) ont été observés. Pour estimer la vitesse de propagation, une caméra ultra-rapide a été utilisée, associée à la mise au point d’un protocole expérimental permettant d’observer la face de l’éprouvette dans l’enceinte thermique, sans givrage. Des observations à 500 000 images.s-1 ont permis de caractériser finement la vitesse instantanée de la fissure sur le ligament complet de la CT (~25 mm). En parallèle, pour pouvoir analyser les essais et l’impact de la viscosité sur la réponse mécanique autour de la fissure, le comportement élasto-viscoplastique du matériau a été étudié jusqu’à une vitesse de déformation de 104 s-1 pour les températures étudiées. La méthode des éléments finis étendus (X-FEM) a été utilisée dans le code de calcul CAST3M pour modéliser la propagation de fissure. Les simulations numériques associent l’approche locale de la rupture en dynamique non linéaire et un critère de propagation en contrainte critique de type RKR à une distance caractéristique. Les travaux réalisés ont permis de confirmer la forme du critère proposé par Prabel à -125°C, et d’identifier les dépendances de ce critère à la température et à la vitesse de déformation. A partir d’analyses numériques en 2D et 3D, un critère multi-température fonction croissante de la vitesse de déformation est proposé. Des modélisations prédictives ont permis de valider le critère sur deux géométries d’éprouvettes (CT et anneau) en mode I à différentes températures. Des observations MEB et des analyses 3D au microscope optique montrent que le mécanisme de rupture est le clivage associé à des zones de cisaillement ductile entre les différents plans de fissuration. L’étude de la fraction surfacique des marches de cisaillement et des contraintes de fermeture associées tend à justifier le critère mis en place. Un modèle analytique est proposé permettant de justifier le critère déduit des modélisations numériques. Ce modèle considère que les ligaments retiennent la lèvre de la fissure et induisent donc des contraintes de fermeture au niveau de la pointe de fissure qu’il faut compenser pour atteindre la contrainte de clivage effective en pointe de fissure. Cette résistance des ligaments est directement reliée à la loi de comportement du matériau et justifie la dépendance du critère de rupture identifié à la vitesse de déformation. Enfin, les branchements de fissure ont été analysés via le dépouillement des vidéos obtenues avec la caméra rapide qui mettent en évidence un amorçage initial rectiligne, puis un amorçage de fissures multiples de part et d’autre du plan de fissure qui conduisent à l’arrêt de la fissure initiale, l’une de ces fissures ‘secondaires’ conduisant ensuite à la rupture de l’éprouvette. Les rôles essentiels de l’épaisseur et du chargement dans ce mécanisme de branchement sont soulignés. L’augmentation de l’épaisseur réduit la fréquence d’apparition de ce mécanisme et finit même par l’annuler. Logiquement l’intensité du chargement doit être suffisamment importante pour créer cette zone plastique étendue : les essais qui présentent une propagation rectiligne sont les essais pour lesquels les chargements à l’amorçage sont les plus faibles. / The purpose of this PhD thesis is to understand physical mechanisms of cleavage crack propagation and arrest in the 16MND5 PWR vessel steel and to propose a robust predicting model based on a brittle fracture experimental campaign of finely instrumented laboratory specimens associated with numerical computations. First, experiments were carried out on thin CT25 specimens at five temperatures (-150°C, -125°C, - 100°C, -75°C, -50°C). Two kinds of crack path, straight or branching path, have been observed. To characterize crack propagation and to measure crack speed, a high-speed framing camera system was used, combined with the development of an experimental protocol which allowed to observe CT surface without icing inside the thermal chamber and on the specimen. The framing camera (520 000 fps) has allowed to have a very accurate estimation of crack speed on the complete ligament of CT (~ 25 mm). Besides, to analyse experiments and to study the impact of viscosity on the mechanical response around the crack tip, the elastic-viscoplastic behavior of the ferritic steel has been studied up to a strain rate of 104 s-1 for the tested temperatures.The eXtended Finite Element Method (X-FEM) was used in CAST3M FE software to model crack propagation. Numerical computations combine a local non linear dynamic approach with a RKR type fracture stress criterion to a characteristic distance. The work carried out has confirmed the form of the criterion proposed by Prabel at -125°C, and has identified the dependencies of the criterion on temperature and strain rate. From numerical analyzes in 2D and 3D, a multi-temperature fracture stress criterion, increasing function of the strain rate, was proposed. Predictive modeling were used to confirm the identified criterion on two specimen geometries (CT and compressive ring) in mode I at different temperatures. SEM observations and 3D analyzes made with optical microscope showed that the fracture mechanism was the cleavage associated with ductile shear zones between the different planes of cracking. The study of the surface fraction of ductile shear zones and associated closing stress tends to justify the established criterion. An analytical model is proposed to justify the criterion deduced from numerical modeling. This model assumes that the ligaments hold the crack lips and therefore induce closing stress at the crack tip which has to be compensated to achieve the effective cleavage stress at the crack tip. This resistance of ligaments is directly related to the mechanical behavior of the material and justifies the dependence of fracture stress criterion with strain rate. Lastly, the crack branching was analyzed thanks to movies obtained with the high-speed camera. The cleavage crack propagates in a straight way over few millimeters. Then, new cracks appear on both sides of the initial crack lips which leads to the arrest of the initial crack. One of the new cracks leads to the failure of the CT specimen. The essential role of the thickness and loading on this branching mechanism is emphasized. The increased thickness reduces the frequency of occurrence of this mechanism and eventually even cancel. Low thicknesses lead to more extensive plasticity at the crack tip and generates the germs for the triggering of secondary cracks that appear. Logically, the intensity of loading must be large enough to create this extended plastic zone : the experiments with a straight path are the tests for which the initial loadings are the lowest.

L’objectif de la thèse est la prédiction de la propagation et de l’arrêt de fissure de clivage dans un acier de cuve de type 16MND5 par un critère local en contrainte critique, calculé en pointe de fissure. Les travaux précédents ont montré que le mécanisme de rupture était du clivage,associé à des zones de cisaillement ductile entre les différents plans de fissuration. Ceci explique la dépendance de la contrainte critique de rupture à la vitesse de déformation en pointe de fissure du fait du comportement visqueux des aciers ferritiques aux vitesses de propagation considérées. Cette thèse consiste à optimiser la méthode numérique mise en oeuvre pour simuler la propagation dynamique de fissure, identifier et valider un critère local de propagation et d’arrêt sur des chargements thermomécaniques complexes, rendre compte des trajets de fissuration variés, et approfondir les connaissances sur les micro-mécanismes physiques de la rupture pour renforcer le contenu physique du critère utilisé.L’identification du critère de propagation et d’arrêt a été faite par la simulation numérique des essais de rupture fragile réalisés sur des éprouvettes CT25 à quatre températures (-150°C, -125°C, -100°C et -75°C). La méthode des éléments finis étendus (X-FEM) a été utilisée dans le code de calcul CAST3M pour ces modélisations. Les résultats des analyses en 2D et 3D ont montré que la contrainte critique de rupture augmentait avec la vitesse de déformation plastique et ils ont donc permis d’établir un critère de propagation et d’arrêt basé sur cette contrainte.Une formulation analytique du critère a été développée pour justifier le critère identifié. La contrainte critique du critère a été considérée comme la somme de la contrainte critique de clivage et de la contrainte générée par la déformation des ligaments (ponts de matières résistants sollicités en cisaillement) en arrière du front de la fissure. Afin de quantifier ce phénomène, des mesures de caractérisations des ligaments ont été effectuées sur les faciès de rupture et sur les coupes transversales des éprouvettes. Le profil de contrainte sur les lèvres de la fissure, généré par les ligaments tendant à résister à l’ouverture de la fissure, a été calculé à l’aide de modélisations éléments finis de multifissures représentatives de la géométrie réelle de la fissure observée sur une coupe transversale. Ceci a permis d’obtenir la contribution de l’effort des ligaments à la contrainte critique en pointe de fissure, et de développer ensuite une formulation analytique pour la contrainte critique. La courbe de la formulation analytique présente un très bon accord avec le critère empirique identifié.Afin de tester la pertinence de ce critère, la prédiction de la propagation et de l’arrêt de fissure a d’abord été menée sur des essais isothermes, à la fois sur des éprouvettes CT25 (la fissure étant sollicitée en mode I) et ensuite sur des anneaux fissurés sollicités en mode mixte. Les résultats numériques des prédictions ont présenté une bonne cohérence avec les expériences.Ceci montre la pertinence du critère sous chargement isotherme. Pour étudier la propagation et l’arrêt de fissure sous choc thermique, un essai a ensuite été réalisé sur un anneau fissuré. Le chargement pour l’essai est plus complexe avec un couplage des chargements mécaniques et thermiques. La prédiction par le critère a été effectuée en 2D et en 3D. Les résultats prédits sont de bonne qualité en termes de cinétique de propagation et de longueur de fissure à l’arrêt. Ceci complète la validation du critère sous chargement thermomécanique.En parallèle, des expériences ont été menées sur des éprouvettes CT25 rallongées (de même hauteur qu’une CT25 mais de largeur double), présentant une bifurcation de la trajectoire de la fissure. [...] / The purpose of this PhD study is to predict the propagation and arrest of cleavage cracks in a French PWR vessel steel (16MND5). This is accomplished through use of a local criterion based on the critical stress calculated ahead of crack tip. Previous work has shown that fracture mechanism was cleavage associated with the ductile shear zone between the different planes of cracking. Thus, the critical stress at crack tip depends on stain rate. This thesis consists ofnumerical optimization, identification and validation of a local criterion based on experimentswhich have complex thermomechanical loads. The criterion accounts for various crack paths,deepening the knowledge about micro mechanisms during crack propagation in order to justify the established criterion.Criterion identification was carried out by using numerical simulations of tension tests performed on CT (Compact Tension) specimens at four different temperatures (-150°C, -125°C,-100°C and -75°C). The eXtended Finite Element Method (X-FEM) was used in CAST3M FEsoftware to model dynamic crack propagation and arrest. The analysis results in 2D and 3Dshowed that the critical stress at crack tip increased with the inelastic strain rate. Therefore, acriterion based on the critical stress was established. An analytical model was developed to justify the identified criterion. The critical stress givenby the local criterion was considered as the sum of the critical cleavage stress and the stress generated by the deformation of ligaments behind the crack tip. In order to quantify this phenomenon, measurements of ligaments’ characteristics have been performed on facture surfaces and on cross-sections of the specimens. The stress profile of the crack lips generated by ligaments was calculated by modeling of multi-cracks on specimen’s cross-section. The contribution of stress generated by ligaments to the critical stress at crack tip was obtained with this method, and then the analytical model of the critical stress was developed. The results of this analytical model is in good agreement with the empirical criterion identified.In order to test the validity of the identified criterion, the prediction of the crack propagation and arrest by the criterion was first performed for isothermal tests. It was performed both onCT25 specimens (crack was solicited in mode I) and on ring specimens in mixed mode loadingwhich were carried out at three different temperatures. The numerical results of prediction were in good agreement with experiments. They showed the validity of the criterion for experiments under isothermal loading for two different specimen geometries. In order to test the validity of criterion for the situation of thermal shock, experiments were carried out on ring specimens. At first, one ring specimen was cooled down to -150°C, and then hot water (≈90°C) was injected through the inner side of the ring specimen. At the same time of thermal shock, this specimen was submitted to a mechanical compressive loading (-750kN). The prediction of crack propagation and arrest by the criterion for this situation was calculated in both 2D and 3D. The predicted results were in good agreement with experiments for both crack speed and crack length. This confirmed that the criterion is relevant to predict the crack propagation and arrest for thermal shock.In parallel, some experiments were performed on extended CT25 specimens (same height but double the width of the CT25 specimen). The crack path on this kind of specimen was curved.A statistical effect by a random selection in the propagation direction was introduced to takeinto account the instability during the crack propagation. The numerical results correctlyreproduce the curvature and the dispersion of the crack paths.

Submitted by Isaac Francisco de Souza Dias (isaac.souzadias@ufpe.br) on 2015-05-18T18:35:07Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE Déborah Daniella Diniz Fonsêca.pdf: 1243075 bytes, checksum: d4fcba13348615fafe873d10016ce007 (MD5) / Made available in DSpace on 2015-05-18T18:35:07Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE Déborah Daniella Diniz Fonsêca.pdf: 1243075 bytes, checksum: d4fcba13348615fafe873d10016ce007 (MD5) Previous issue date: 2014-12-17 / FACEPE / OBJETIVO: Avaliar o perfil sociodemográfico, a saúde bucal e a soro prevalência dos vírus HIV, HCV e HBV em usuários de crack. MATERIAIS E MÉTODOS: Pesquisa transversal composta por 94 usuários de crack. Para avaliação da saúde bucal foram utilizados os índices CPOD, CPI, avaliação do fluxo salivar, xerostomia e presença de lesão oral. A sorologia para HIV, HCV e HBV foi realizada para estimar a soro prevalência. Para comparar se houve diferença estatística significante nos valores médios, os dados foram submetidos ao teste de normalidade de Kolmogorov-Smirnov e Shapiro-Wilk. RESULTADOS: A maioria da amostra composta por homens, média de 33,4 anos. Índice CPOD médio 13,2 com 77,7% apresentando prevalência muito alta. Para o CPI, 46% dos sextantes avaliados apresentaram sangramento, presença de cálculo, bolsas periodontais e sextantes excluídos. 5 (5,3%) pacientes apresentaram lesões potencialmente malignas incluindo leucoplasia, eritroplasia e carcinoma in situ. 23 (24,5%) usuários apresentaram hipossalivação e 56 (59,6%) relataram xerostomia. 6 (6,4%), 2 (2,1%), 49 (52,1%) soro positivos para os vírus HIV, HCV e HBV (anti-HBCTotal), respectivamente, nenhuma positividade para o antígeno HBsAg. CONCLUSÕES: Usuários apresentaram baixo nível socioeconômico e de escolaridade, saúde bucal deficiente, risco aumentado para lesões potencialmente malignas como leucoplasia e eritroplasia, fluxo salivar normal, presença de xerostomia e risco aumentado para infecção pelos vírus HIV, HCV e HBV. RELEVÂNCIA CLÍNICA: Achados importantes na Odontologia e Saúde Pública, permitindo um maior conhecimento da população estudada e um fortalecimento de políticas públicas de atenção à saúde desses pacientes com abordagem multiprofissional.

Submitted by Isaac Francisco de Souza Dias (isaac.souzadias@ufpe.br) on 2015-10-21T18:27:24Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_Conferida.pdf: 772985 bytes, checksum: 23f7d52c97c90334611f2febe39f126d (MD5) / Made available in DSpace on 2015-10-21T18:27:24Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_Conferida.pdf: 772985 bytes, checksum: 23f7d52c97c90334611f2febe39f126d (MD5) Previous issue date: 2014-04-28 / CAPES / Esta pesquisa se insere na área de conhecimento dos estudos sobre sexualidade em interface com questões de gênero e geração. Nosso objetivo foi analisar as vivências sexuais de mulheres jovens usuárias de crack e as repercussões de tais práticas em suas vidas. Partimos da perspectiva do construcionismo social que compreende a organização eminentemente social do mundo a partir das práticas discursivas. Para construir e analisar os dados, utilizamos a Análise Crítica do Discurso, que foca sua atenção nas relações de poder presentes nos discursos. Primeiramente, debatemos os aspectos gerais do uso de crack, enfatizando a feminização de tal uso e políticas públicas que atuam junto aos usuárias/os. Posteriormente, discutimos questões relativas à juventude, gênero e sexualidade, que atravessam a vida das usuárias, considerando-as sujeitos de direitos sexuais e direitos reprodutivos. Buscamos desenvolver um olhar interseccional por todo trabalho. A partir da abordagem qualitativa, realizamos a pesquisa em serviço de tratamento intensivo para usuários de álcool e outras drogas da cidade do Recife. Utilizamos observações participantes e entrevista semiestruturada com 03 mulheres jovens entre 18 e 29 anos. Os diários de campo nos auxiliaram nas considerações desenvolvidas sobre a instituição e políticas públicas. Observamos que as jovens viveram em bairros marcados por violência e tráfico, em contextos de dificuldade de acesso à saúde, educação, lazer e habitação, configurando uma condição de vida marcada pela miséria e exclusão social. Neste cenário, elas iniciaram o uso de crack e, por algumas vezes utilizarem o corpo para conseguirem droga, vivenciaram situações de risco, seja por agravos à sexualidade ou por violência física. Por vergonha de assumirem que vivem sua sexualidade ou que são usuárias de crack, dificilmente elas chegam às unidades de saúde, ficando desassistidas. Percebemos que há distanciamento e indiferença das relações em contexto familiar. As jovens têm planos positivos para suas vidas após a saída da instituição, entretanto, observamos a ausência de projetos profissionais. Acreditamos que uma abordagem psicossocial que as ajude a descobrir atividades que possam, minimamente, contribuir para a construção de independência financeira colabora na quebra dos ciclos de uso, indicando que este é um importante ponto a se investir no período de tratamento.

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