Background: Extensive literature has described a decrease in force output performance in the local muscle groups after static stretching, and static stretching has therefore been recommended not to be performed during warm-ups. A recent study showed evidence of a cross-over effect in regard to static stretching, i.e. non-local muscles were also affected by static stretching. This result could however be due to fatigue in the muscle groups stretched, and a fatigued condition has previously shown cross-over effects in several studies. Aim: The aim of the study was to (1) examine if upper-limb static stretching and muscle fatigue display a cross-over effect that show changes in force output in the lower limbs, and (2) if there was a difference between the effects of the static stretch protocol and the muscle fatigue protocol for the purpose of examining if fatigue is the larger factor for cross-over. Methods: Concentric maximal jump height of 15 subjects with previous strength training experience of at least one year was measured and the subjects subsequently performed both intervention protocols in a random order. After each protocol concentric jump height was measured again. The static stretch protocol consisted of a static stretch for the shoulder at an intensity of “Very hard”, 10 repetitions of 30 second stretches with 15 seconds rest in between repetitions. The muscle fatigue protocol consisted of 10 repetitions of 30 seconds isometric muscle contraction in the same position with 15 seconds rest between repetitions at an intensity of “Very hard”. The data was collected on an infra-red contact mat and differences between the mean jump heights pre- and post each protocol and between the different protocols were analyzed with pair sample t-test.   Result: Mean concentric jump height (± standard deviation, SD) was 25.31 (±9.4) cm for the baseline jumps, 23.66 (±8.89) cm post static stretch intervention jumps and 24.13 (±8.90) cm post muscle fatigue intervention jumps. This indicates a cross-over effect on force output in the legs post static stretching with a mean reduction of 1.65 cm (p=0.001). Upper-limb muscle fatigue indicated a cross-over effect on force output in the legs with a mean reduction of 1.18 cm (p=0.032). There was no statistical significance between the two protocols (p=0.146). Conclusion: The results presented a cross-over effect on both conditions. This is in line with previous research in the area. The results implicate that static stretching and muscle fatigue effects the central nervous system, which can lead to impairments in performance in non-local muscles. This can be considered in warm-up and exercise program design when force output is of great importance for performance

In this study, Gwen Gray Schwartz argues that students exhibit academic identities that do not always match their instructors' expectations for them and assumptions about them, which creates problems when second language writers enter mainstream composition classes. Using ethnographic methods, she studied three Vietnamese immigrant students from Generation 1.5 who placed into mainstream composition at a large university in the Southwest and found that while each student struggled in some ways to meet the expectations of mainstream composition, their academic identities and notions of success played a large role in how they engaged in or disassociated from the class activities and assignments. Schwartz analyzed the students' writing, and through extensive conversations with them and their mainstream composition instructors discovered that Generation 1.5 students who cross over into mainstream classes have academic identities that are complicated by their status as cross-over students--they juggle multiple languages, cultures, and school systems, all while writing in English while continuing to learn English. And while mainstream instructors do not know how to meet these students' needs, their numbers are increasing steadily across the country. Schwartz begins by complicating the term "Generation 1.5" and "ESL student" and suggests a new term, "cross-over student," to describe those students in Generation 1.5 who place into mainstream composition. Then she describes the term "academic identity" as a lens through which to examine these students' experiences in mainstream composition and their notions of success, which often are quite different from their mainstream instructors'. After extensive analysis of each student's writing, she offers solutions to the placement dilemma this group presents and provides concrete ways for mainstream instructors to better meet the needs of this student population.

This qualitative thesis examines levels of pessimism as they relate to modern and postmodern horror cinema. Beyond assumed differences in levels of pessimism between the two genres, the study also examines implicit and explicit moralization of these categories. Specifically, the study questions if postmodern horror cinema's characteristic increase in pessimism is simply a change in the genre's convention, yet a change that is irrespective of either genre's capabilities to moralize. First, the study singularly examines the conventions of each genre as it relates to levels of pessimism. Second, the study discusses works that bridge the two genres. And third, the study speculates on the future of pessimism in postmodern horror cinema, specifically examining the genre's increased reliance on a combination of narrative and documentary techniques. In addition, this study uses content analysis as its methodological framework, whereby representative works of horror cinema (the data) are subjected to in-depth personal reading and textual analysis given the levels of pessimism between the two genres (the coding) via text immersion. Nonetheless, this study should be viewed more as a guided and informed exploration of certain characteristics regarding the genres and less of a defense since the data will not be quantified.

Exercícios de força com intensidade preferida ou prescrita resultam em efeitos analgésicos semelhantes em pacientes com FM, sugerindo que o modelo de treinamento deve ser recomendado para melhorar a aderência ao exercício. O objetivo foi comparar o efeito de sessões de exercícios de força com intensidade preferida e prescrita na dor de pacientes com FM. De forma aleatória, as mulheres do sexo feminino (n = 32, idade 20-55 anos) foram submetidas às seguintes sessões de exercício: i) prescrição padrão (STD, 6 x 10 repetições com 60% de uma repetição máxima); ii) carga auto-selecionada com número fixo de repetições (SS); iii) carga auto-selecionada com volume total correspondente ao volume STD (SS-VM); e iii) carga auto-selecionada com um número livre de repetições até atingir o escore 7 na Escala de Percepção ao esforço (SS-PSE). A dor foi avaliada através da Escala Visual Analógica (EVA) e do Questionário de Dor de McGill Short-Form (SF-MPQ) antes imediatamente após e 24, 48, 72 e 96 horas após as sessões de exercícios de força. O humor, escala de afetividade ao exercício e a PSE da sessão também foram medidos. A intensidade foi significativamente menor em SS, SS-VM, SS-PSE do que em STD, enquanto o volume total, humor, afetividade ao exercício e PSE não tiveram diferença entre as sessões. As pontuações de VAS também aumentaram imediatamente após todas as sessões de exercício (p < 0,0001) e, em seguida, reduziram significativamente após 48, 72, 96 h (p < 0,0001), permanecendo elevada em relação aos prévalores. Os valores de SF-MPQ aumentaram significativamente imediatamente após todas as sessões de exercício de resistência (p = 0,025), depois diminuíram gradualmente ao longo do tempo, atingindo os níveis basais às 24 h. Não houve efeito de interação significativa para a dor. As sessões de exercício de força prescrita e preferida não foram capaz de induzir analgesia em pacientes com FM, sugerindo que os modelos de exercícios de força que levem a menores intensidades percebidas podem ser necessários para superar essa resposta anormal nesta síndrome / Preferable and prescribed resistance exercises result similar analgesic effects in FM patients suggesting that the training model should be recommended to improve exercise adherence. Compare the effect of preferred and prescribed resistance exercises on pain in FM patients. In a randomized cross-over fashion, FM female patients (n = 32, age 20-55 years) underwent the following exercise sessions: i) standard prescription (STD; 6 x 10 repetitions at 60% of one-maximum repetition); ii) self-selected load with fixed number of repetitions (SS); iii) self-selected load with total volume matched for STD volume (SS-VM); and iii) self-selected load with a free number of repetitions until achieving score 7 in the rating of perceived exertion (SS-RPE). Pain was assessed through the Visual Analogic Scale (VAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) before and 0, 24, 48, 72 and 96 hours after the resistance exercise sessions. Mood, affective valence scale and session RPE were also measured. Intensity was significantly lower in SS, SS-VM, SS-RPE than in STD, whereas total volume, mood, affective and RPE were comparable between the sessions. VAS scores equally increased immediately after all the exercise sessions (p < 0.0001), and then significantly reduced after 48, 72, 96 h (p < 0.0001), remaining elevated as compared to pre-values. SF-MPQ values significantly increased immediately after all the resistance exercise sessions (p = 0.025), then gradually reduced across time, reaching baseline levels at 24 h. There was no significant interaction effect for pain. Prescribed and preferable resistance exercise equally failed to induce analgesia in FM patients, suggesting that resistance exercise models leading to lower perceived intensities might be needed to overcome this dysfunctional response in this syndromes

Exercícios de força com intensidade preferida ou prescrita resultam em efeitos analgésicos semelhantes em pacientes com FM, sugerindo que o modelo de treinamento deve ser recomendado para melhorar a aderência ao exercício. O objetivo foi comparar o efeito de sessões de exercícios de força com intensidade preferida e prescrita na dor de pacientes com FM. De forma aleatória, as mulheres do sexo feminino (n = 32, idade 20-55 anos) foram submetidas às seguintes sessões de exercício: i) prescrição padrão (STD, 6 x 10 repetições com 60% de uma repetição máxima); ii) carga auto-selecionada com número fixo de repetições (SS); iii) carga auto-selecionada com volume total correspondente ao volume STD (SS-VM); e iii) carga auto-selecionada com um número livre de repetições até atingir o escore 7 na Escala de Percepção ao esforço (SS-PSE). A dor foi avaliada através da Escala Visual Analógica (EVA) e do Questionário de Dor de McGill Short-Form (SF-MPQ) antes imediatamente após e 24, 48, 72 e 96 horas após as sessões de exercícios de força. O humor, escala de afetividade ao exercício e a PSE da sessão também foram medidos. A intensidade foi significativamente menor em SS, SS-VM, SS-PSE do que em STD, enquanto o volume total, humor, afetividade ao exercício e PSE não tiveram diferença entre as sessões. As pontuações de VAS também aumentaram imediatamente após todas as sessões de exercício (p < 0,0001) e, em seguida, reduziram significativamente após 48, 72, 96 h (p < 0,0001), permanecendo elevada em relação aos prévalores. Os valores de SF-MPQ aumentaram significativamente imediatamente após todas as sessões de exercício de resistência (p = 0,025), depois diminuíram gradualmente ao longo do tempo, atingindo os níveis basais às 24 h. Não houve efeito de interação significativa para a dor. As sessões de exercício de força prescrita e preferida não foram capaz de induzir analgesia em pacientes com FM, sugerindo que os modelos de exercícios de força que levem a menores intensidades percebidas podem ser necessários para superar essa resposta anormal nesta síndrome / Preferable and prescribed resistance exercises result similar analgesic effects in FM patients suggesting that the training model should be recommended to improve exercise adherence. Compare the effect of preferred and prescribed resistance exercises on pain in FM patients. In a randomized cross-over fashion, FM female patients (n = 32, age 20-55 years) underwent the following exercise sessions: i) standard prescription (STD; 6 x 10 repetitions at 60% of one-maximum repetition); ii) self-selected load with fixed number of repetitions (SS); iii) self-selected load with total volume matched for STD volume (SS-VM); and iii) self-selected load with a free number of repetitions until achieving score 7 in the rating of perceived exertion (SS-RPE). Pain was assessed through the Visual Analogic Scale (VAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) before and 0, 24, 48, 72 and 96 hours after the resistance exercise sessions. Mood, affective valence scale and session RPE were also measured. Intensity was significantly lower in SS, SS-VM, SS-RPE than in STD, whereas total volume, mood, affective and RPE were comparable between the sessions. VAS scores equally increased immediately after all the exercise sessions (p < 0.0001), and then significantly reduced after 48, 72, 96 h (p < 0.0001), remaining elevated as compared to pre-values. SF-MPQ values significantly increased immediately after all the resistance exercise sessions (p = 0.025), then gradually reduced across time, reaching baseline levels at 24 h. There was no significant interaction effect for pain. Prescribed and preferable resistance exercise equally failed to induce analgesia in FM patients, suggesting that resistance exercise models leading to lower perceived intensities might be needed to overcome this dysfunctional response in this syndromes

INTRODUÇÃO: Em um cenário de mudanças climáticas, o delineamento da associação e dos mecanismos de efeito entre fatores de risco ambientais, como temperatura e poluição, e saúde tornou-se foco de diversos estudos epidemiológicos. À medida que a exposição à poluição e às condições meteorológicas ocorre de forma simultânea, além do efeito isolado, devemos buscar compreender a interação entre tais fatores, observando se atuam como modificadores de efeito. O presente estudo caracterizou o efeito da temperatura e da poluição do ar, isolado e sinérgico, na mortalidade, a partir de dados secundários. MÉ- TODOS: Três tipos de metodologias foram aplicadas para avaliar a associação isolada da temperatura média e da concentração média diária de poluentes (MP10, NO2, O3) na mortalidade de indivíduos acima dos 40 anos por doenças cardiovasculares e na mortalidade de indivíduos acima dos 60 anos por doenças respiratórias, na cidade de São Paulo - Brasil entre 1998 e 2008. As estimativas de risco relativo produzidas em análises case-crossover com pareamento temporal bidirecional e com pareamento pelo fator confundidor, i.e. temperatura média ou poluente, foram comparadas aos resultados de uma análise tradicional de séries temporais. Para avaliar o efeito sinérgico entre os fatores de risco, interpretamos representações gráficas de superfícies geradas em modelos bivariados. RESULTADOS: Não foram observadas diferenças entre os resultados das análises case-crossover e da análise de séries temporais. Para mortalidade cardiovascular, estimou-se uma mudança percentual no risco relativo devido a um aumento de 10 ug/m3 na concentração do MP10 e do NO2, respectivamente, de 0,85% (0,45-1,25) e 0,26% (0,04-0,48). O aumento percentual no risco de mortalidade respiratória foi de 1,60% (0,74-2,46) e 1,29% (0,46-2,12), respectivamente para MP10 e O3. O efeito da temperatura foi analisado através das funções ajustadas para parametrizar sua relação com a mortalidade. O padrão observado para mortalidade cardiovascular foi de U-shaped. Para mortalidade respiratória foi de J-espelhado, identificando maior risco relativo em temperaturas altas. As análises case-crossover confirmaram que a associação positiva parametrizada para os poluentes não sofre confusão da temperatura, bem como a curva parametrizada para a temperatura não sofre confusão dos níveis de poluentes na análise de séries temporais. As figuras 3D produzidas pelo modelo bivariado ilustraram a dinâmica interativa entre os fatores de risco. O efeito na mortalidade cardiovascular é positivo em baixas concentrações de NO2 e de O3 combinadas com baixas temperaturas. A dimensão deste efeito é comparável ao efeito de altas concentrações em altas temperaturas. Para mortalidade respiratória, a combinação dos fatores mostra um padrão intuitivo de simples somatória dos efeitos. CONCLUSÕES: Métodos analíticos, como o método case-crossover, com controles mais intrínsecos do que parametrizações para variáveis confundidoras, produziram estimativas de risco relativo na mortalidade semelhantes às geradas na análise tradicional de séries temporais. A simultaneidade de exposição a diferentes níveis de fatores ambientais, como temperatura e poluição, pode gerar condições de efeito combinado tão preocupantes quanto as previstas para extremas concentrações / INTRODUCTION : In a climate change scenario, the description of the association and of the pathophysiological mechanisms linking environmental risk factors, such as temperature and air pollution, and health has been the focus in several epidemiological studies. Exposure to air pollution and weather conditions occurs simultaneously, therefore, in addition to the isolated effect, factors interactions and modification effects are key issue. The present study characterized the effect of temperature and air pollution, both isolated and synergistic effects, on mortality, from secondary data. METHODS: Three methods were applied to evaluate the association of average temperature and average daily concentration of pollutants (PM10, NO2, O3) on mortality caused by cardiovascular diseases among individuals over 40 years old and on mortality caused by respiratory diseases among individuals over 60 years old, in the city of Sao Paulo - Brazil, from 1998 to 2008 . We compared the estimates of relative risk produced in several case-crossover approaches, time-stratified bidirectional and matched by the confounding factor, i.e. average temperature or pollutant, to the results of a traditional time-series analysis. The risk factors synergistic effect was evaluated by the graphical interpretation of response surfaces generated by bivariate models. RESULTS: No statistical differences were observed between the results from the case-crossover and time-series analyses . The relative risk percent changes for cardiovascular mortality associated with an increase of 10 ug/m3 in the 24-h average concentrations of PM10 and NO2 are, respectively, 0.85% (0.45-1.25) and 0.26% (0.04-0.48). The percentage increase in the risk of respiratory mortality was 1.60% (0.74- 2.46) and 1.29% (0.46-2.12), respectively, for PM10 and O3. The effect of temperature was analyzed by smooth functions plots. The pattern observed for cardiovascular mortality was U-shaped. For respiratory mortality, the smooth function was J-shaped horizontal flipped, identifying higher relative risk at hot temperatures. The case-crossover analyzes confirmed that the positive association parameterized for pollutants is unlikely to be caused by confounding by temperature, as well as the parametric curve for temperature is unlikely to be caused by confounding by pollutant levels in time-series analysis. The bivariate model surface plots illustrated the dynamic interaction within the risk factors. The effect on cardiovascular mortality is positive at low concentrations of NO2 and O3 in combination with cold temperatures. The magnitude of this effect is comparable to the effect of high concentrations at hot temperatures. For respiratory mortality, the combination of risk factors is simple summation of effects, with no effect modifications of the original patterns. CONCLUSIONS: Analytical methods such as case-crossover method, controlled for confounding variables by design, produced estimates of relative risk in mortality similar to those generated in the traditional time-series analysis. The simultaneous exposure to several levels of environmental factors, such as temperature and air pollution, may represent conditions as harmful as the predicted to extreme concentrations, due to the combined effect

INTRODUÇÃO: Em um cenário de mudanças climáticas, o delineamento da associação e dos mecanismos de efeito entre fatores de risco ambientais, como temperatura e poluição, e saúde tornou-se foco de diversos estudos epidemiológicos. À medida que a exposição à poluição e às condições meteorológicas ocorre de forma simultânea, além do efeito isolado, devemos buscar compreender a interação entre tais fatores, observando se atuam como modificadores de efeito. O presente estudo caracterizou o efeito da temperatura e da poluição do ar, isolado e sinérgico, na mortalidade, a partir de dados secundários. MÉ- TODOS: Três tipos de metodologias foram aplicadas para avaliar a associação isolada da temperatura média e da concentração média diária de poluentes (MP10, NO2, O3) na mortalidade de indivíduos acima dos 40 anos por doenças cardiovasculares e na mortalidade de indivíduos acima dos 60 anos por doenças respiratórias, na cidade de São Paulo - Brasil entre 1998 e 2008. As estimativas de risco relativo produzidas em análises case-crossover com pareamento temporal bidirecional e com pareamento pelo fator confundidor, i.e. temperatura média ou poluente, foram comparadas aos resultados de uma análise tradicional de séries temporais. Para avaliar o efeito sinérgico entre os fatores de risco, interpretamos representações gráficas de superfícies geradas em modelos bivariados. RESULTADOS: Não foram observadas diferenças entre os resultados das análises case-crossover e da análise de séries temporais. Para mortalidade cardiovascular, estimou-se uma mudança percentual no risco relativo devido a um aumento de 10 ug/m3 na concentração do MP10 e do NO2, respectivamente, de 0,85% (0,45-1,25) e 0,26% (0,04-0,48). O aumento percentual no risco de mortalidade respiratória foi de 1,60% (0,74-2,46) e 1,29% (0,46-2,12), respectivamente para MP10 e O3. O efeito da temperatura foi analisado através das funções ajustadas para parametrizar sua relação com a mortalidade. O padrão observado para mortalidade cardiovascular foi de U-shaped. Para mortalidade respiratória foi de J-espelhado, identificando maior risco relativo em temperaturas altas. As análises case-crossover confirmaram que a associação positiva parametrizada para os poluentes não sofre confusão da temperatura, bem como a curva parametrizada para a temperatura não sofre confusão dos níveis de poluentes na análise de séries temporais. As figuras 3D produzidas pelo modelo bivariado ilustraram a dinâmica interativa entre os fatores de risco. O efeito na mortalidade cardiovascular é positivo em baixas concentrações de NO2 e de O3 combinadas com baixas temperaturas. A dimensão deste efeito é comparável ao efeito de altas concentrações em altas temperaturas. Para mortalidade respiratória, a combinação dos fatores mostra um padrão intuitivo de simples somatória dos efeitos. CONCLUSÕES: Métodos analíticos, como o método case-crossover, com controles mais intrínsecos do que parametrizações para variáveis confundidoras, produziram estimativas de risco relativo na mortalidade semelhantes às geradas na análise tradicional de séries temporais. A simultaneidade de exposição a diferentes níveis de fatores ambientais, como temperatura e poluição, pode gerar condições de efeito combinado tão preocupantes quanto as previstas para extremas concentrações / INTRODUCTION : In a climate change scenario, the description of the association and of the pathophysiological mechanisms linking environmental risk factors, such as temperature and air pollution, and health has been the focus in several epidemiological studies. Exposure to air pollution and weather conditions occurs simultaneously, therefore, in addition to the isolated effect, factors interactions and modification effects are key issue. The present study characterized the effect of temperature and air pollution, both isolated and synergistic effects, on mortality, from secondary data. METHODS: Three methods were applied to evaluate the association of average temperature and average daily concentration of pollutants (PM10, NO2, O3) on mortality caused by cardiovascular diseases among individuals over 40 years old and on mortality caused by respiratory diseases among individuals over 60 years old, in the city of Sao Paulo - Brazil, from 1998 to 2008 . We compared the estimates of relative risk produced in several case-crossover approaches, time-stratified bidirectional and matched by the confounding factor, i.e. average temperature or pollutant, to the results of a traditional time-series analysis. The risk factors synergistic effect was evaluated by the graphical interpretation of response surfaces generated by bivariate models. RESULTS: No statistical differences were observed between the results from the case-crossover and time-series analyses . The relative risk percent changes for cardiovascular mortality associated with an increase of 10 ug/m3 in the 24-h average concentrations of PM10 and NO2 are, respectively, 0.85% (0.45-1.25) and 0.26% (0.04-0.48). The percentage increase in the risk of respiratory mortality was 1.60% (0.74- 2.46) and 1.29% (0.46-2.12), respectively, for PM10 and O3. The effect of temperature was analyzed by smooth functions plots. The pattern observed for cardiovascular mortality was U-shaped. For respiratory mortality, the smooth function was J-shaped horizontal flipped, identifying higher relative risk at hot temperatures. The case-crossover analyzes confirmed that the positive association parameterized for pollutants is unlikely to be caused by confounding by temperature, as well as the parametric curve for temperature is unlikely to be caused by confounding by pollutant levels in time-series analysis. The bivariate model surface plots illustrated the dynamic interaction within the risk factors. The effect on cardiovascular mortality is positive at low concentrations of NO2 and O3 in combination with cold temperatures. The magnitude of this effect is comparable to the effect of high concentrations at hot temperatures. For respiratory mortality, the combination of risk factors is simple summation of effects, with no effect modifications of the original patterns. CONCLUSIONS: Analytical methods such as case-crossover method, controlled for confounding variables by design, produced estimates of relative risk in mortality similar to those generated in the traditional time-series analysis. The simultaneous exposure to several levels of environmental factors, such as temperature and air pollution, may represent conditions as harmful as the predicted to extreme concentrations, due to the combined effect

No description available.

Au cours des études de survie, certains facteurs ayant un rôle pronostique peuvent être inobservés ou indisponibles. Dans le cadre des essais cliniques randomisés où deux groupes de traitement sont comparés par un modèle de Cox, « l’oubli » de tels facteurs dans le modèle entraîne une sous-estimation en valeur absolue de l’effet du traitement. L’objectif de la thèse est de préciser le rôle de différents déterminants de ce biais et de suggérer l’utilisation de méthodes pouvant le réduire, avec un intérêt particulier pour les essais de prévention à l'infection VIH où de tels facteurs peuvent exister. L’effet des principaux facteurs pouvant influencer le biais est précisé dans une première partie de la thèse. Si certains facteurs sont connus de longue date, d’autres, comme la durée de l’essai n’ont, à notre connaissance, pas été étudiés. L’approche utilisée repose sur l’utilisation d’un « vrai » modèle de type à risques proportionnels. Dans ce modèle, l’effet des covariables « oubliées » est résumé par l’introduction dans l’expression du risque instantané d’un terme aléatoire de « fragilité » propre à chaque sujet. Le biais cherché est calculé comme la limite asymptotique, sous le modèle marginal correspondant au « vrai » modèle, du rapport des risques instantanés déduit du modèle de Cox n’incluant pas la fragilité. Les résultats montrent une nette augmentation du biais, en valeur absolue, avec la durée de l’essai. Cette augmentation est particulièrement marquée pour des distributions de fragilité continues comme celles pouvant être rencontrées en pratique, par rapport à des fragilités binaires. Par ailleurs, les résultats antérieurs de la littérature sont confirmés et précisés. Dans un second temps, les conséquences d’une variation de la fragilité au cours du temps sur le biais sont recherchées. Plus précisément, la situation envisagée est celle qui est rencontrée dans les essais de prévention contre le VIH effectués auprès de populations « instables » vis-à-vis du risque, comme les jeunes ou les prostituées en Afrique sub-saharienne. Ces populations montrent une hétérogénéité comportementale liée aux changements de partenaires sexuels dont le statut VIH est par ailleurs inconnu. Il s’agit d’évaluer le biais en présence d’une telle fragilité « intermittente » au moyen de simulations reflétant les situations réelles. Les résultats montrent que le biais dû à l’omission de la fragilité dans l’analyse, bien qu’inférieur au biais obtenu dans le cas d’une fragilité constante au cours du temps, reste significatif et doit être considéré. Les différentes fragilités générées au cours du suivi sont soit indépendantes entre elles, soit corrélées. Enfin, dans le cas d’une fragilité supposée constante au cours du temps, l’intérêt de l’utilisation d’un essai en « cross-over » est recherché. Dans un tel essai, les sujets exempts d’évènement après un temps de suivi donné changent de groupe de traitement. Dans le cadre des essais de prévention VIH, Auvert & al [2011] ont montré en particulier une diminution du biais avec un schéma en cross-over comparativement à un schéma parallèle classique, en utilisant une fragilité catégorielle dans une étude de simulation. Buyze & Goetghebeur [2011] ont également montré les avantages du cross-over, en particulier concernant l’efficacité relative d’un test de comparaison des deux groupes, en utilisant une fragilité de distribution gamma ou log-normale. Ces résultats sont précisés en calculant formellement le biais asymptotique dans l’estimation du risque relatif pour les différentes distributions possibles de la fragilité omise, continue ou catégorielle. Les résultats obtenus sont nettement en faveur du cross-over, avec une diminution du biais entre 60% et 90% et une amélioration de l’efficacité du test. Le temps de changement de groupe optimal est également recherché. Il apparaît que celui-ci dépend essentiellement de la durée le l'essai et de la valeur de l'effet traitement. / In survival analysis, some prognostic factors can be unobserved or unavailable. In randomized clinical trials framework where two treatment groups are compared in the Cox model setting, the omission of such factors in the model leads to an under-estimation in absolute value of the treatment effect. The aim of the project is to better understand the determinants of this bias and to suggest the use of methods that could reduce it, with a particular interest in HIV prevention trials where such factors are likely to exist. In a first step, the role of the main determinants of the bias is highlighted. While some of them have long been identified, others like trial duration have never been considered to our knowledge. The bias was calculated as the asymptotic limit of the maximum likelihood estimator of the treatment effect when the analysis is done following a proportional hazard model which no takes into account the frailty. The results show a clear increase of the bias in absolute value with the trial duration. This increase is especially marked with continuous frailty distributions, such as those which can be encountered in practice, compared to binary frailties. Also, some previous results have been confirmed. In a second step, a frailty depending on time is considered, as it can be encountered in HIV clinical trials including “unstable” population about infection risk, as prostitutes or young people in sub-Saharan Africa. These populations present a behavioral heterogeneity linked to the change of partner whose the HIV status is unknown. The bias is estimated using a transient frailty with a simulation study reflecting real-life situations. The results show that when the frailty is regenerated during the follow-up, the bias caused by its omission, although lower than the bias obtained with a time-independent frailty, stays significant and has to be considered. The different frailties generated during the follow-up are independent or correlated. Finally, with a “stable” population whose the frailty can be supposed constant over time, the interest of the use of the “cross-over” is searched. In such trial, the subjects which have not presented the event after a given time of follow-up, change of treatment group. In HIV prevention trials framework, Auvert & al. (2011) have particularly shown a decrease of the bias with a cross-over design comparatively to a parallel design, using a categorized frailty in a simulation study. Buyze & Goetghebeur (2011) have also shown the advantages of the cross-over, particularly about the relative efficiency of the comparison test of the two treatment groups, using gamma or log-normal frailty distributions. These results are specified calculating explicitly the asymptotic bias of the hazard ratio estimate for different possible distributions of the omitted frailty, continuous or categorized. The obtained results are clearly in favor of the cross-over, with a decrease of the bias between 60% et 90% and a significant improvement of the efficiency of the comparison test. The optimal switch time and its prognostic factors are searched. It appears that it essentially depends on the trial duration and is little affected by the frailty distribution or the value of the treatment effect.

A hiperacusia e o zumbido representam alterações na percepção dos sons, estando freqüentemente associados. Ambos refletem um estado de hiperatividade da via auditiva, gerado por alterações na plasticidade neuronal geralmente associadas à super estimulação ou deprivação sensorial. A hiperacusia refere-se a uma disfunção na percepção da intensidade de sons externos, o zumbido refere-se à percepção de um som interno que não tem uma fonte geradora externa. Afetam adultos e crianças e podem ocasionar limitações na qualidade de vida. Ainda são muito negligenciados por otorrinolaringologistas e pediatras, apesar da sua presença não ser incomum na infância. Delineamos um estudo populacional transversal randomizado entre crianças de 5 a 12 anos cujo objetivo principal foi estimar a prevalência da hiperacusia e do zumbido. O objetivo secundário foi avaliar a associação a possíveis fatores de risco e a causalidade entre os sintomas. Foram avaliadas 506 crianças em ambiente escolar. Os dados foram coletados por meio de questionário aos pais ou responsáveis, entrevista com as crianças, otoscopia e testes auditivos. A classificação dos resultados seguiu critérios previamente estabelecidos. Participaram 240 meninas (47,4%) e 266 meninos (52,6%), idade média 9.46 anos (DP= 2.09). Os limiares auditivos foram classificados como normais em 81%, disacusia de grau mínimo/leve em 14% e disacusia de grau moderado/ profundo em 4% das crianças. A prevalência da sensação de zumbido foi 37,5%, incômodo com zumbido 19,6% e hiperacusia 3,2%. Os fatores de risco foram analisados por um modelo de regressão multivariado. Em relação ao zumbido, os fatores associados foram: idade, gênero, perda auditiva, história de exposição aos sons e cinetose. Para a hiperacusia, o único fator de risco encontrado foi a perda auditiva leve na orelha esquerda. A presença de hiperacusia demonstrou ser o maior fator de risco associado ao incomodo com o zumbido / Hyperacusis and tinnitus are altered states of sound perception and are frequently associated. Both reflect a hyperactivity of the auditory pathway as an expression of neural plasticity which is often triggered by over stimulation or deprivation of sensorial stimuli. Hyperacusis is a dysfunction on loudness perception of external sounds and tinnitus a perception of an internal sound without an external source. They might affect adults and children causing interference on quality of life. They are still neglected by otolaryngologysts and pediatricians. A prospective cross sectional study was designed to estimate tinnitus and hyperacusis prevalence and evaluate association to possible risk factors and causality among them. Children from 5 to 12 years of age were evaluated in the school environment. Data was collected searching parental information, children\'s interview, otoscopy and audiometric tests. The symptoms were classified according to previous established criteria. The final sample counted on 240 girls and 266 boys, mean age 9.46 (SD= 2.09). Hearing thresholds were classified as normal in 81%, minimum to mild hearing loss in 14% and moderate to profound hearing loss in 4% of the children. Prevalence of tinnitus sensation was found to be 37.5%, tinnitus suffering 19.6% and hyperacusis 3.2%. Age, gender, hearing loss, history of noise exposure and motion sickness were risk factors to tinnitus. Left ear hearing loss was a risk factor for hyperacusis. The presence of hyperacusis demonstrated to be the highest risk factor to tinnitus suffering