The aim with our study was to understand former addict´s experience of social networks from the Lewi Pethrus foundation (LP foundation) aftercare. The method we have used is qualitative semi-structured interviews. We have interviewed eight persons, four men and four women. They have all been in contact with the LP foundation and are today drug free. The result of the study has shown that the fellowship, in the different social networks have been very important to maintain a drug free life. A feeling of affinity, being seen, feel supported and trusted, experience that someone believe in you, has been the most regarded in the social networks. The contact with the LP foundation and the church appeared to have a significant role in the LP foundation and the church appeared to have a significant role in the LP foundation aftercare to create new social networks. Having a job or study is also a key to build new relationships and is something that the LP foundations aftercare has contributed to. Our study also showed the necessity to break up with old friends from the time when they were addicts, who had a negative influence. Furthermore it was vital to re-establish the relationship with their children and also with their siblings.

Les maladies cardiovasculaires représentent la première cause de morbidité et mortalité dans le monde. L'athérosclérose, qui conduit à l'obstruction des artères, est à l'origine de 50% des décès dans les sociétés industrialisées. La rupture d'une plaque d'athérosclérose dite vulnérable entraîne de nombreuses complications qui, en fonction du territoire artériel considéré, vont de l'accident vasculaire cérébral à l'infarctus du myocarde. Pour pallier ce problème de santé publique majeur, l'enjeu clinique et en particulier diagnostic repose sur la prévention de ces complications cardiovasculaires dans une population à haut risque comme à l'île de la Réunion, qui se caractérise par une incidence élevée d'atteintes vasculaires et de mortalité associée. Or, il n'existe aucune technique d'imagerie permettant la détection précoce des plaques d'athérosclérose vulnérables. La médecine nucléaire possède une grande sensibilité et pourrait offrir des outils diagnostics performants permettant d'évaluer la formation de ces plaques. Parmi tous les biomarqueurs tissulaires et circulants produits lors de l'athérogenèse, nous avons choisi la Lp-PLA2 (phospholipase A2 associée aux lipoprotéines), enzyme associée aux processus inflammatoires (produite par les monocytes et macrophages) et transportée par les lipoprotéines, comme cible de l'athérosclérose en imagerie TEP (Tomographie par Émission de Positons). Nos travaux ont permis la synthèse puis le radiomarquage d'un puissant inhibiteur cette enzyme : le Darapladib, ainsi que d'analogues. Nous avons réussi à obtenir le 18F-Darapladib afin d'étudier son accumulation dans des modèles murin et ex vivo humain de plaques d’athérome. / Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Atherosclerosis, which leads to the obstruction of large arteries, represents 50% of deaths in industrialized societies. Rupture of a vulnerable atherosclerotic plaque can lead to several complications which, depending on the site, can cause stroke or myocardial infarction.To address this public health issue, there is a real need to develop new diagnostic tools to prevent these cardiovascular complications in a high risk population in Reunion island. However, no potent tool is available to doctors in order to predict the formation of vulnerable atherosclerotic plaques. Nuclear medicine with its high sensibility could offer new powerful diagnostic tools in order to assess vulnerable atheroma formation. Among all biomarkers available to the scientific community, we chose Lp-PLA2 (Lipoprotein-associated phospholipase A2) which is an enzyme associated to inflammatory processes (produced by monocytes and macrophages) as a target for PET (Positron Emission Tomography) imaging of atherosclerosis.Our work describes the radiolabelling of a potent inhibitor of this enzyme: Darapladib and associated analogs. We were able to perform its radiolabelling and to study its potential accumulation in atheroma murin models and in ex vivo human endarterectomy pieces.

Introdução: A obesidade se caracteriza como um processo oxidativo e inflamatório, que predispõe adolescentes, de modo precoce, a eventos até recentemente pouco frequentes nessa faixa etária. Assim, a ação da enzima Fosfolipase A associada às lipoproteínas (Lp-PLA ), que reduz fosfolipídios oxidados e gera lisofosfolipídios, bem como a disponibilidade de antioxidantes plasmáticos, representam um importante tema de pesquisa no contexto cardiovascular. Objetivo: Verificar se a atividade da LP-PLA 2 2 e a concentração de antioxidantes lipossolúveis se associam com os principais marcadores de risco cardiovascular em adolescentes. Métodos: Duzentos e quarenta e dois adolescentes (10 a 19 anos), de ambos os sexos foram distribuídos, segundo o índice de massa corporal (IMC), em três grupos: Eutróficos (n=77), Sobrepeso (n=82) e Obesos (n=83). A amostra foi caracterizada através de parâmetros sócio-econômicos, estado de saúde, uso de medicamentos, antedecentes familiares de doenças crônicas e prática de atividade física. Foram avaliados ainda os dados antropométricos (peso, altura e composição corporal - bioimpedância), e o consumo alimentar por meio de três recordatórios 24 h. A partir de uma amostra de sangue coletada após jejum (12h), realizaram-se as análises da atividade da Lp-PLA , LDL(-) e seus auto-anticorpos, perfil lipídico (colesterol total, LDL-C, HDL-C e triglicerídeos), tamanho da HDL, proteína transportadora de éster de colesterol (CETP), ácidos graxos não esterificados (NEFAs), adipocitocinas, assim como antioxidantes (retinol, licopeno, -tocoferol e -caroteno) no plasma. Resultados: Artigo 1: Lp-PLA maybe an important cardiovascular biomarker in obese adolescents. Verificou-se que o perfil lipídico, insulina, HOMA-IR (resistência à insulina) e LDL(-) evidenciaram um maior risco cardiovascular nos adolescentes obesos. A atividade da enzima Lp-PLA 2 mostrou uma variação proporcional ao IMC, circunferência da cintura e porcentagem de gordura. Essa tendência foi, ainda, reforçada pelas associações positivas entre a enzima e HOMA-IR, glicose, insulina e as variáveis lipídicas. Adicionalmente, associação negativa foi encontrada para ApoAI. As associações mais relevantes foram observadas para ApoB e Apo B / Apo AI (=0,293; P<0,001, =0,343; P<0,001, respectivamente). O melhor modelo preditor para a atividade da enzima incluiu Apo B/Apo AI (= 0,327; P<0,001), tamanho da HDL (=-0,326; P<0,001), circunferência da cintura (=0,171; P=0,006) e glicose (= 0,119; P=0,038). A análise de Odds Ratio mostrou que a mudança de uma unidade na razão entre Apo B/Apo AI esteve associada a 73.5 maior risco para elevada atividade de Lp-PLA 2 . Conclusão: A enzima Lp-PLA , em adolescentes, varia em função do estado nutricional e está relacionada a vários marcadores de risco cardiovascular, especialmente a Apo B/Apo AI. Assim, a atividade da enzima pode representar um importante biomarcador de risco cardiovascular na adolescência. Artigo 2: Antioxidant, and inflammatory aspects of phospholipase A 2 associated to lipoprotein (Lp-PLA ): A review. Esta revisão descreve os principais aspectos relacionados à enzima Lp-PLA 2 e seu impacto no perfil inflamatório e oxidativo da doença aterosclerótica. Artigo 3: Plasma antioxidants, but not the dietary ones, are associated with cardiometabolic risk in adolescents. Neste artigo, observou-se que 2 os antioxidantes -caroteno, licopeno, retinol e -tocoferol variam em função do IMC. Verificou-se que -caroteno e -tocoferol apresentaram valores reduzidos para o grupo obeso em comparação ao eutrófico e ao sobrepeso. Para o -caroteno, verificou-se que essa diferença pôde ser observada inclusive quando comparados sobrepesos e eutróficos. Quando esses antioxidantes foram ajustados pelo colesterol total ou pelo LDL-C essas diferenças se mantiveram. Correlações importantes foram obtidas entre os antioxidantes ajustados por colesterol ou por LDL-C e as variáveis de risco cardiometabólico (perfil lipídico (colesterol total e frações, CETP), resistência à insulina (HOMA-IR, insulina, glicose) e LDL(-)). A obesidade representou um importante fator para a existência dessas correlações, pois após o ajuste por IMC foram reduzidas. Apesar desses resultados, os antioxidantes availados pelo recordatório de 24h não apresentaram nenhuma correlação com os fatores de risco cardiometabólico. Conclusão: Antioxidantes plasmáticos estão relacionados ao risco cardiometabólico em adolescentes, sendo que o IMC desempenha um papel importante para a existência dessas correlações. Tais biomarcadores representam uma melhor maneira de estimar a influência de um padrão dietético sobre o risco cardiometabólico em adolescentes do que a avaliação do inquérito alimentar / Introduction: Obesity is characterized as an oxidative and inflammatory process, which precociously predisposes adolescents to events until recently uncommon in this age group. Thus, the action of Lipoprotein-associated phospholipase A (LpPLA ), which reduces oxidized phospholipids and generates lysophospholipids, as well as the availability of plasma antioxidants, represent important subjects of cardiovascular research. Objetive: To evaluate if the activity of Lp-PLA 2 and the concentration of fat-soluble antioxidants are associated with the most important cardiovascular risk markers in adolescents. Methods: 242 adolescents (10 to 19 years old), from both sexes, were distributed according to Body mass index (BMI) in three groups: Health Weigth (HW, n=77), Overweigth (OV, n=82) and Obeses (OB, n=83). The sample was characterized by socioeconomic parameters, health condition, use of medications, family history of chronic diseases and physical activity. It were evaluated also the anthropometric data (weigth, heigth, body composition - bioimpedance) and the food intake through three 24h-recall. From a blood sample collected after fasting (12h), were analized the Lp-PLA activity, the levels of LDL(-) and it antibodies, the lipid profile (total cholesterol, LDL-C, HDL-C and triglycerides), HDL-size, Non-Esterified Fatty Acids (NEFAs), Cholesteryl Ester Transfer Protein (CETP), adipocytokines, as well as plasma antioxidants (retinol, licopene, -tocopherol e -carotene). Results: Article 1: Lp-PLA as an important biomarker of cardiovascular risk in obese adolescents. It was observed that the lipid profile, the insulin, the HOMA-IR (insulin resistance) and the LDL(-) represented a higher cardiovascular risk in obese adolescents. The activity of Lp-PLA 2 has shown a variation proportional to BMI, waist circumference and fat mass percentage. This tendency was reinforced by positive associations of the enzyme with HOMA-IR, glucose, insulin and lipid variables. Additionaly, a negative association was observed for Apo AI. The most relevant associations were observed for ApoB and Apo B / Apo AI (=0,293; P<0,001, =0,343; P<0,001, respectively). The best predictor model for the enzyme activity included Apo B/Apo AI (= 0,327; P<0,001), HDLsize (=-0,326; P<0,001), waist circumference (=0,171; P=0,006) and glucose (= 0,119; P=0,038). The Odds Ratio analysis showed that the change of one unit in the ratio of Apo B/Apo AI was related to a 73.5 times higher risk of elevated Lp-PLA activity. Conclusion: The enzyme Lp-PLA , in adolescents, varies in function of the nutritional status and it is related to several cardiovascular risk markers, especially to Apo B/Apo AI. Thus, this enzyme activity may represent an important biomarker of cardiovascular risk in adolescence. Article 2: Antioxidant and inflammatory aspects of phospholipase A 2 2 associated to lipoprotein (Lp-PLA ): a review. This review describes the main aspects related to the enzime Lp-PLA 2 and its impact to inflammatory and oxidative profiles of atherosclerotic disease. Article 3: Plasma antioxidants, but not the dietary ones, are associated with cardiometabolic risk in 2 adolescents. It was observed that the antioxidants -carotene, licopene, retinol and -tocopherol vary in function of BMI. It was verified that -carotene and - tocopherol presented reduced values for the OB group in comparison with the HW and OV groups. For -carotene, it was observed that this difference was also verified when OB and OV were compared. These differences remained alike when the antioxidants were adjusted by total cholesterol or by LDL-C. Important correlations were obtained between the antioxidants adjusted by total cholesterol or by LDL-C, and cardiometabolic risk variables (lipid profile (total cholesterol and fractions, CETP), insulin resistance (HOMA-IR, insulin, glucose) and LDL(-)). The obesity represented an important factor to the occurrence of these correlations, since they were reduced after BMI adjustment. Despite these results, the antioxidants evaluated by 24h-diet recall did not show any correlations with cardiometabolic risk. Conclusion: Plasma antioxidants are related to cardiometabolic risk in adolescents, where the BMI represents an important factor. These biomarkers are better than the food intake to estimate the influence of a dietary pattern on the cardiometabolic risk in adolescents

No description available.

[pt] Esta dissertação de mestrado aborda um estudo aprofundado do artigo [2]. No Capítulo 2, são introduzidas as definições e conceitos fundamentais necessários para a análise teórica subsequente. Uma proposição é demonstrada, estabelecendo a existência de uma expansão de Taylor para funções em um determinado espaço, enfatizando o papel do expoente de Escauriaza. O capítulo continua apresentando dois lemas que relacionam subsoluções e supersoluções em termos de viscosidade e propriedades de normas. A primeira versão do lema considera a relação entre a dimensão do espaço e a norma, enquanto a segunda versão utiliza o expoente de Escauriaza para obter resultados mais refinados. Também são apresentados dois resultados que explicam a relação entre diferentes noções de soluções viscosas e sua conexão com os espaços de Sobolev. As propriedades dos operadores de Pucci são discutidas como conclusão deste capítulo. No Capítulo 3, a dissertação estabelece a definição da geometria da fronteira do domínio em questão. Em seguida, um importante lema é demonstrado, estabelecendo a existência de soluções fortes em um determinado espaço, explorando a regularidade das funções envolvidas com base nesse lema. Os conceitos de super-diferenciabilidade e sub-diferenciabilidade são introduzidos, desempenhando um papel crucial na compreensão do comportamento das soluções viscosas e suas relações com derivadas de ordem superior. Um resultado geral que amplia essas definições é apresentado. Duas versões em que a função u é duas vezes super-diferenciável são discutidas, considerando o espaço Ld e posteriormente o espaço Lp , de modo que p menor que d. A dissertação prossegue demonstrando a relação entre sub-solução Lp-viscosidade e sub-solução Lp-forte quando u pertence a um espaço específico. Em seguida, é mostrado que os limites uniformes de soluções também são soluções. Por fim, é apresentado o resultado principal da dissertação, demonstrando a unicidade das soluções fortes. / [en] This master s thesis delves into an in-depth study of the article [2]. Chapter2 begins by introducing fundamental definitions and concepts essential forthe subsequent theoretical analysis. A proposition is then demonstrated,establishing the existence of a Taylor expansion for functions in a givenspace, emphasizing the role of the Escauriaza exponent.The chapter proceeds to present two lemmas that relate subsolutions andsupersolutions in terms of viscosity and properties of norms. The firstversion of the lemma considers the relationship between the dimension ofspace and the norm, while the second version uses the Escauriaza exponentto obtain more refined results. Two results are shown to explain that explainthe relationship between different notions of viscous solutions and theirconnection with Sobolev spaces.The properties of the Pucci operators are discussed at the conclusion of thischapter. Chapter 3 begins by establishing the definition of the boundarygeometry of the domain in question. An important lemma is demonstrated,which establishes the existence of strong solutions in a given space andexplores the regularity of the functions involved based on this lemma.The concepts of superdifferentiability and subdifferentiability areintroduced, playing a crucial role in understanding the behavior of viscoussolutions and their relationships with higher order derivatives. A generalresult that extends these definitions is presented. The dissertation discussestwo versions wherein the function u is twice super-differentiable, consideringthe space Ld and later the space Lp, so that p less than d.The dissertation goes on to demonstrate the relationship between Lp-viscosity sub-solution and Lp-strong sub-solution when u belongs to aspecific space. Next, it is shown that the uniform limits of solutions arealso solutions. Finally, the main result of the dissertation is presented,demonstrating the uniqueness of strong solutions.

Theodor Adorno verkündete, das Model von Kurt Weill lasse sich nicht wiederholen. Seine Bühnenwerke wurden trotzdem zum unvermeidlichen Präzedenzfall für Komponisten auf beiden Seiten des Atlantiks. Diese Promotionsarbeit erkundet insbesondere die Rolle seiner formalen Innovationen im Musiktheater von Marc Blitzstein und Leonard Bernstein. Dabei haben die Komponisten seinem ästhetischen Beitrag zur amerikanischen Tradition entweder wiederstanden oder ihn heruntergespielt. Komparative Analysen aufgrund von Harold Blooms „Anxiety of Influence“ und anderen intertextuellen Methoden decken auf, dass die Grundsätze von Weills Opernreform eine einheimische Bewegung von anspruchsvollem, sozial-engagierten Musiktheater katalysierten. Die folgende Studie richtet den Fokus auf Werke, die verschiedene Phasen seiner Mission vertreten, die Gattung der Oper zu erneuern, eine Entwicklung, die sich von der Urform in Die Dreigroschenoper bis zum Musical Play (Lady in the Dark) und zur Broadway Opera (Street Scene) erstreckt. Blitzstein und Bernstein wiederum überwanden die formalen Grenzen zwischen Oper und Musical mit The Cradle Will Rock, Regina, Trouble in Tahiti, Candide und West Side Story, teil einer kurzlebigen Bewegung in Amerika des zwanzigsten Jahrhunderts. Dieselbe überschnitt sich mit einer Renaissance für Weills deutschsprachige Werke im Anschluss an die Premiere von Blitzsteins Übersetzung The Threepenny Opera unter Bernsteins Leitung. Das unveröffentlichte A Pray by Blecht, für welches Bernstein sich an Stephen Sondheim und Jerome Robbins, seine Kooperationspartner in West Side Story, wieder angeschlossen hat, vertieft den Bezug von Bernsteins Musiktheater-Ästhetik auf Weill. / Theodor Adorno famously proclaimed that the model of Kurt Weill could not be repeated. His stage works nevertheless set an inescapable precedent for composers on both sides of the Atlantic. My dissertation explores how Weill’s formal innovations in particular laid the groundwork for the music theater of Marc Blitzstein and Leonard Bernstein although they either resisted or downplayed his aesthetic contribution to American tradition. Comparative analysis based on Harold Bloom’s Anxiety of Influence and other modes of intertextuality reveal that the principles of Weill’s opera reform would catalyze an indigenous movement in sophisticated, socially engaged music theatre. The following study focuses on works that represent different phases of his mission to renew the genre of opera, evolving from the Urform (original or primitive form) in Die Dreigroschenoper to the musical play (Lady in the Dark) and Broadway Opera (Street Scene). Blitzstein and Bernstein in turn defied the formal boundaries between opera and musical theater with The Cradle Will Rock, Regina, Trouble in Tahiti, Candide and West Side Story, part of a short-lived movement in mid-twentieth century America that coincided with a renaissance for Weill’s German-period works following the premiere of Blitzstein’s translation, The Threepenny Opera, under Bernstein’s baton. The unpublished A Pray by Blecht, – for which Bernstein rejoined Stephen Sondheim and Jerome Robbins, his collaborators on West Side Story, – deepens the connection of Bernstein’s music theater aesthetic to Weill.

A computational study aimed at improving the understanding of rotating instability in the LP steam turbine last stage working under low flow rate conditions is described in this thesis. A numerical simulation framework has been developed to investigate into the instability flow field. Two LP model turbine stages are studied under various flow rate conditions. By using the 2D simulations as reference and comparing the results to those of the 3D simulations, the basic physical mechanism of rotating instability is analysed. The pressure ratio characteristics across the rotor row tip are found to be crucial to the inception of rotating instability. The captured instability demonstrates a 2D mechanism based on the circumferential variation of unsteady separation flow in the rotor row. The 3D tip clearance flow is found not a necessary cause of the instability onset. Several influential parameters on the instability flow are also investigated by a set of detailed studies on different turbine configurations. The results show that the instability flow pattern and characteristics can be altered by the gap distance between the stator and rotor row, the rotor blading and the stator row stagger angle. Some flow control approaches are proposed based on the observations, which may also serve as design reference. The tip region 3D vortex flow upstream to the rotor row is also captured by the simulations under low flow rate conditions. Its appearance is found to be able to suppress the inception of rotating instability by disrupting the interaction between the rotor separation flow and the incoming flow. Finally, some recommendations for further work are proposed.

We extend the theory of perturbations of KMS states to some class of unbounded perturbations using noncommutative Lp-spaces. We also prove certain stability of the domain of the Modular Operator associated to a ||.||p-continuous state. This allows us to define an analytic multiple-time KMS condition and to obtain its analyticity together with some bounds to its norm. The main results are Theorem 5.1.15, Theorem 5.1.16 and Corollary 5.1.18. Apart from that, this work contains a detailed review, with minor contributions due to the author, starting with the description of C*-algebras and von Neumann algebras followed by weights and representations, a whole chapter is devoted to the study of KMS states and its physical interpretation as the states of thermal equilibrium, then the Tomita-Takesaki Modular Theory is presented, furthermore, we study analytical properties of the modular operator automorphism group, positive cones and bounded perturbations of states, and finally we start presenting multiple versions of noncommutative Lp-spaces. / Apresentamos uma extensão da teoria de perturbações de estados KMS para uma classe de operadores ilimitados através dos espaços Lp não-comutativos. Além disso, provamos certa estabilidade do domínio do Operador Modular de um estado ||.||p-contínuo o que nos permite escrever a condições KMS para tempos múltiplos e obter sua analiticidade junto com majorantes para sua norma. Os principais resultados são o Teorema 5.1.15, o Teorema 5.1.16 e o Corolário 5.1.18. Além disso, nesse trabalho fazemos uma detalhada revisão, com contribuições menores devidas ao autor, começamos com uma descrição de álgebras C* e álgebras de von Neumann, seguida por pesos e representações, um capítulo inteiro é dedicado ao estudo de estados KMS e sua interpretação como estados de equilíbrio térmico, depois apresentamos a Teoria Modular de Tomita-Takesaki, além disso, estudamos as propriedades de analiticidade do grupo de automorfismo modular, cones positivos e perturbações de estados e finalmente, começamos a apresentar múltiplas versões dos espaços Lp não comutativos.

We extend the theory of perturbations of KMS states to some class of unbounded perturbations using noncommutative Lp-spaces. We also prove certain stability of the domain of the Modular Operator associated to a ||.||p-continuous state. This allows us to define an analytic multiple-time KMS condition and to obtain its analyticity together with some bounds to its norm. The main results are Theorem 5.1.15, Theorem 5.1.16 and Corollary 5.1.18. Apart from that, this work contains a detailed review, with minor contributions due to the author, starting with the description of C*-algebras and von Neumann algebras followed by weights and representations, a whole chapter is devoted to the study of KMS states and its physical interpretation as the states of thermal equilibrium, then the Tomita-Takesaki Modular Theory is presented, furthermore, we study analytical properties of the modular operator automorphism group, positive cones and bounded perturbations of states, and finally we start presenting multiple versions of noncommutative Lp-spaces. / Apresentamos uma extensão da teoria de perturbações de estados KMS para uma classe de operadores ilimitados através dos espaços Lp não-comutativos. Além disso, provamos certa estabilidade do domínio do Operador Modular de um estado ||.||p-contínuo o que nos permite escrever a condições KMS para tempos múltiplos e obter sua analiticidade junto com majorantes para sua norma. Os principais resultados são o Teorema 5.1.15, o Teorema 5.1.16 e o Corolário 5.1.18. Além disso, nesse trabalho fazemos uma detalhada revisão, com contribuições menores devidas ao autor, começamos com uma descrição de álgebras C* e álgebras de von Neumann, seguida por pesos e representações, um capítulo inteiro é dedicado ao estudo de estados KMS e sua interpretação como estados de equilíbrio térmico, depois apresentamos a Teoria Modular de Tomita-Takesaki, além disso, estudamos as propriedades de analiticidade do grupo de automorfismo modular, cones positivos e perturbações de estados e finalmente, começamos a apresentar múltiplas versões dos espaços Lp não comutativos.

We consider the survivable network design problem - the problem of designing, at minimum cost, a network with edge-connectivity requirements. As special cases, this problem encompasses the Steiner tree problem, the traveling salesman problem and the k-connected network design problem. We establish a property, referred to as the parsimonious property, of the linear programming (LP) relaxation of a classical formulation for the problem. The parsimonious property has numerous consequences. For example, we derive various structural properties of these LP relaxations, we present some algorithmic improvements and we perform tight worstcase analyses of two heuristics for the survivable network design problem.