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Se trata de una tesis doctoral presentada en la modalidad compendio de publicaciones. En ella, se presenta una línea de trabajo de investigación mediante la presentación sucesiva de tres artículos ya publicados en diferentes revistas de impacto en el ámbito de las enfermedades infecciosas. Los trabajos presentados en esta tesis nacen de una necesidad clínica patente en nuestra asistencia a los pacientes con infección por VIH, ya que el uso clínico de maraviroc, un antagonista del correceptor de quimiocinas CCR5, se veía dificultado por la necesidad de conocer el tropismo vírico y los métodos disponibles para ello eran caros, complejos y con problemas de interpretación. Por ello, el primer trabajo de la presente tesis fue diseñar una herramienta clínica más sencilla rápida y barata que los métodos disponibles hasta entonces; además, esta herramienta clasificaba al paciente en sensible al fámaco o no, más allá de un resultado categórico de tropismo. Este objetivo se abordó en el primer artículo publicado en "Journal of Antimicrobial Chemotherapy" en 2009. Posteriormente, realizamos un análisis de comparación entre nuestra herramienta clínica y el método fenotípico estándar de oro para determinar el tropismo vírico, con el onjetivo de alertar sobre las implicaciones clínicas que podrían tener tasas de discrepancia entre ambos métodos superiores al 15%. Este segundo objetivo se en el segundo artículo publicado en "Antiviral Research" en 2011. Por último, nos interesaba conocer cuál era la eficacia y seguridad de maraviroc asociado a diferentes antirretrovirales en nuestra cohorte de pacientes, masivamente coinfectada por virus de la hepatitis C, y en diferentes escenarios clínicos. Además, en la mayoría de estos pacientes se decidió iniciar tratamiento con maraviroc a través de la herramienta clínica previamente diseñada. Este tercer objetivo se abordó en el último trabajo publicado en "Current HIV Research" en 2010. Los resultados obtenidos en estos tres trabajos permiten extraer las siguientes conclusiones: 1. Una herramienta clínica que permite determinar la sensibilidad clínica a maraviroc es un método sencillo y eficaz para considerar a un paciente candidato a recibir tratamiento con maraviroc. 2. Se observan tasas de discrepancia entre esta herramienta clínica y los métodos fenotípicos superiores al 15%, lo que puede tener importantes repercusiones clínicas. 3. Un régimen antirretroviral con maraviroc es eficaz y seguro en diferentes escenarios clínicos, asociado a diferentes antirretrovirales y en una población con elevada tasa de coinfección por virus de la hepatitis C. Premio Extraordinario de Doctorado US

This study examined coping skills and experiences of childhood abuse and neglect in four groups of offenders (i.e., those who have committed Sexual (SO), Violent (VO), Violent and Sexual (VSO), and Other offences), and in two subgroups of sexual offenders (i.e., child molesters and perpetrators against peers/adults). The study also sought to determine whether coping skills predicted the severity of sexual offending, as gauged by the number of victims, the degree of victim-offender physical contact, and the variety of sexually abusive behaviours. Archival data on 471 adolescent males from two correctional facilities in Michigan were used. Coping was assessed using the Youth Coping Index, while abuse variables were assessed using the Childhood Trauma Questionnaire and the Sexual Abuse Exposure Questionnaire. Biased responding was controlled for using Paulhus's Social Desirability Index. Multiple regression analyses failed to detect a relationship between coping styles and the severity of sexual offending. SO and non-SO showed no differences in their reliance on masturbatory coping, but VO were more likely to use aggression as a means of coping than those who committed nonviolent offenses. A 2 x 2 MANCOVA found that experiences of childhood Sexual Abuse, Emotional Abuse and Neglect, Physical Abuse and Coping using Incendiary Communication and Tension Management were higher in SO than in those who committed non-sexual offences. Non-sexual offenders were more likely to report Coping using Positive Appraisal and Problem Solving. VO obtained higher scores on Physical Neglect and Coping using Incendiary Communication and Tension Management than those who committed non-violent offenses. Logistic regression analysis indicated that Sexual Abuse predicted SO status, and Physical Neglect and Coping using Incendiary Communication and Tension Management predicted VO status. Child molesters reported more experiences of Physical Neglect than perpetrators against peers/adults, but the two types of sexual offenders did not differ on the other predictors. The implications of these findings for clinical work and research are discussed.Dept. of Psychology. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2004 .U545. Source: Dissertation Abstracts International, Volume: 66-02, Section: B, page: 1188. Adviser: Steve Hibbard. Thesis (Ph.D.)--University of Windsor (Canada), 2004.

Dept. of Mathematics and Statistics. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1973 .C365. Source: Dissertation Abstracts International, Volume: 62-13, Section: A. Thesis (Ph.D.)--University of Windsor (Canada), 1974.

This study was developed to address the problem of the high rates of suicidality found among street youth. Semi-structured interviews were conducted with 80 street youth in agencies and on the streets of Toronto and Vancouver. Participants described the meanings suicide held for them and their understandings of the phenomenon of suicide among street youth. Qualitative analysis of the interviews revealed themes of worthlessness, loneliness, hopelessness, and most centrally the feeling of being 'trapped' that form the construct of suicide held by the participants. These idioms of distress were situated within the context of the street life that included social stigma and oppression, and drug abuse. Recommendations are made for working with these youth. Additionally, it is suggested that a more socially active approach be taken to increase awareness of the issues of street youth, who are largely overlooked and maligned in public forums and social policy.Dept. of Psychology. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2001 .K535. Source: Dissertation Abstracts International, Volume: 63-04, Section: B, page: 2062. Adviser: Michael Kral. Thesis (Ph.D.)--University of Windsor (Canada), 2001.

Par une approche supramoléculaire, des architectures radiales hétéro-poly-métalliques ont été réalisées pour des applications en photosynthèse artificielle et en magnétisme moléculaire. Dans une première partie, la synthèse et la caractérisation (spectroscopie UV-vis, émission, électrochimique, DRX) de complexes de ruthénium(II), possédant une gamme de ligands polypyridines, ont été réalisées. Les calculs théoriques ont été effectués afin de soutenir l’interprétation des propriétés photophysiques. Ces complexes, présentant un certain nombre de pyridines externes, ont servi de cœur à des architectures à base de rhénium tris-carbonyles (pour les effets d’antenne), et de cobaloximes (pour les propriétés catalytiques). Les nucléarités obtenues varient de 2 à 7 selon le cœur utilisé. Ces systèmes ont été engagés dans des cycles de photo-production de dihydrogène, démontrant une meilleure efficacité que la référence du domaine, le [Ru(bpy)3]2+. La seconde partie concerne l’étude de couples de métaux de transition, construits à partir de briques polycyanométallates, ou de lanthanides pontés par des ligands oxamides. Ces approches « complexes comme ligand » puis « assemblages comme ligand » permettent d’obtenir des systèmes de haute nucléarité, présentant des propriétés de molécule-aimant ou des effets magnéto-caloriques (à base de CrNi, GdCu, DyCu). Des propriétés photomagnétiques ont été observées sur les couples RuCu et MoCu, pouvant servir de commutateurs moléculaires dans des systèmes complexes. Enfin, une structure hétéro-tétra-métallique trifonctionnelle a été obtenue contenant à la fois un commutateur MoCu, une entité molécule-aimant CuTb et un complexe de ruthénium. By a supramolecular strategy, radial hetero-poly-metallic architectures were obtained for applications in artificial photosynthesis and molecular magnetism. The first part is devoted to the synthesis, as well as the photophysical characterization (UV-vis absorption, emission, electrochemistry, X-ray diffraction) of ruthenium(II) complexes bearing a wide range of polypyridine ligands. Theoretical calculations were performed to support the interpretation of the photophysical properties. Through their pendant pyridine moieties, these complexes were used as core of architectures, bearing rhenium tris-carbonyl (for antenna effects), and cobaloximes (for catalytic properties) complexes. The nuclearities obtained vary from two to seven according to the core involved. These systems were engaged in photo-production of hydrogen, demonstrating more efficient systems than the reference in the field, the archetypal [Ru(bpy)3]2+. The second part concerns the study of transition metal couples, built on polycyanometallate cores, or oxamide-bridged lanthanide-based assemblies. These “complex as ligand” and “assemblies as ligand” approaches allow us to obtain high nuclearity systems on which we seek single molecule magnet (SMM) properties or good magnetocaloric effect (based on CrNi, GdCu, DyCu). Photo-magnetic properties have been studied on the RuCu and MoCu couples, which can serve as molecular switches in complex systems. Finally, a tri-functional hetero-tetra-metallic architecture was obtained containing a MoCu switch, a CuTb SMM entity, and a ruthenium complex.

Due to scientific and technological advancements, investigations in modern medicine are producing more measurement data than ever before. Since a large amount of information exists, and it is also being produced at ever-increasing rates, no single person can digest all current knowledge of diseases. Data collected from large patient cohorts may contain valuable knowledge of diseases, which could be useful to clinicians when making diagnoses or choosing treatments. Making use of the large volumes of data in clinical decision-making requires ancillary help from information technologies, but such systems have not yet become widely available. This thesis addresses the challenge by proposing a computer-based decision support method that is suited to clinical use. This thesis presents the Disease State Index (DSI), a supervised machine learning method intended for the analysis of patient data. The DSI comprehensively compares patient data with previously diagnosed cases with or without a disease. Based on this comparison, the method provides an estimate of the state of disease progression in the patient. Interpreting the DSI is made possible by its visual counterpart, the Disease State Fingerprint (DSF), which allows domain experts to gain a comprehensive view of patient data and the state of the disease at a quick glance. In the design and development of these methods, both performance and applicability in clinical use were taken into account equally. Alzheimer's disease (AD) is a slowly progressing neurodegenerative disease and one of the largest social and economic burdens in the world today, and it will continue to be so in the future. Studies with large patient cohorts have significantly improved our knowledge of AD during the last decade. This information should be made extensively available at memory clinics to maximize the benefits for diagnostics and treatment of the disease. The DSI and DSF methods proposed in this thesis were studied in the early diagnosis of AD and as a measure of disease progression in six original publications. The methods themselves and their implementation within a clinical decision support system, the PredictAD tool, were quantitatively evaluated with regard to their performance and potential benefits in clinical use. The results show that the methods and clinical decision support tool based on these methods can be used to follow disease progression objectively and provide earlier diagnoses of AD. These, in turn, could improve treatment efficacy due to earlier interventions and make drug trials more efficient by allowing better patient selection.

Knowledge of ecological and life-history traits over ontogeny for long-lived migratory marine species is vital to creating effective conservation and management strategies, however these details are often difficult to obtain. Incrementally growing biomineralized structures, such as elasmobranch vertebrae, are metabolically stable and provide the potential to investigate changes in spatial and trophic ecology over ontogeny. In the present dissertation, chemical tracer analysis (δ13C, δ15N, and Δ14C) and opportunistic sightings data are used to address data deficiencies for a threatened marine predator (white shark, Carcharodon carcharias).

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

The global HIV/AIDS pandemic has emerged alongside a changing world order marked by the growing power and authority of business, new constraints on public authority and policy autonomy, and new global hierarchies, inequalities, and contradictory tendencies. These conditions have helped midwife new configurations of public and private power, authority, and relations and shaped normative and operating environments for global health governance. In these contexts, public-private partnerships emerged as an institutional experiment, ostensibly to address health governance gaps and failures, including access to HIV and AIDS medicines in the global South. This study investigates the growth and roles of private authority in health governance through the lens of four case studies of public-private partnerships intended to enhance access to HIV and AIDS medicines in the global South. The study reveals that public-private partnerships in health emerged from this history as institutional experiments, yet not convincingly as functionalist responses to governance gaps and failures. The history demonstrates that private business actors opted to engage in partnerships in the contexts of a convergence of social, political, and commercial pressures, and normative and structural transformations in the world order. The case study partnerships emerged as accommodation or trasformismo strategies which offered concessions in an attempt to neutralise and co-opt social contestation around treatment access, without succumbing to demands for deeper structural and legislative reforms. These strategies offer bilateral, narrow, and tactical contributions in a framework of poor design, governance, accountability, and equity considerations and obligations, and are ultimately unconvincing in their commitment or capacity to expand access to HIV and AIDS medicines. Ultimately, public-private partnerships in health present practical, strategic, and normative consequences that necessitate new approaches to reform and/or serious reconsideration of their role and prospects in global health governance. Doctor of Philosophy (PhD)