To obtain a better understanding of the pharmacokinetic and/or pharmacodynamic characteristics of an investigated treatment, clinical data is often analysed with nonlinear mixed effects modelling. The developed models can be used to design future clinical trials or to guide individualised drug treatment. Missing data is a frequently encountered problem in analyses of clinical data, and to not venture the predictability of the developed model, it is of great importance that the method chosen to handle the missing data is adequate for its purpose. The overall aim of this thesis was to develop methods for handling missing data in the context of nonlinear mixed effects models and to compare strategies for handling missing data in order to provide guidance for efficient handling and consequences of inappropriate handling of missing data. In accordance with missing data theory, all missing data can be divided into three categories; missing completely at random (MCAR), missing at random (MAR) and missing not at random (MNAR). When data are MCAR, the underlying missing data mechanism does not depend on any observed or unobserved data; when data are MAR, the underlying missing data mechanism depends on observed data but not on unobserved data; when data are MNAR, the underlying missing data mechanism depends on the unobserved data itself. Strategies and methods for handling missing observation data and missing covariate data were evaluated. These evaluations showed that the most frequently used estimation algorithm in nonlinear mixed effects modelling (first-order conditional estimation), resulted in biased parameter estimates independent on missing data mechanism. However, expectation maximization (EM) algorithms (e.g. importance sampling) resulted in unbiased and precise parameter estimates as long as data were MCAR or MAR. When the observation data are MNAR, a proper method for handling the missing data has to be applied to obtain unbiased and precise parameter estimates, independent on estimation algorithm. The evaluation of different methods for handling missing covariate data showed that a correctly implemented multiple imputations method and full maximum likelihood modelling methods resulted in unbiased and precise parameter estimates when covariate data were MCAR or MAR. When the covariate data were MNAR, the only method resulting in unbiased and precise parameter estimates was a full maximum likelihood modelling method where an extra parameter was estimated, correcting for the unknown missing data mechanism's dependence on the missing data. This thesis presents new insight to the dynamics of missing data in nonlinear mixed effects modelling. Strategies for handling different types of missing data have been developed and compared in order to provide guidance for efficient handling and consequences of inappropriate handling of missing data.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / Apesar dos progressos recentes do setor de saneamento básico no Brasil, muitas dificuldades ainda precisam ser superadas. A desigualdade no acesso a esses serviços bem como a fragmentação das políticas públicas e a ausência de marco regulatório podem ser citados como os principais desafios no setor. Este estudo tem por objetivo analisar os determinantes da cobertura de saneamento básico no Brasil, com base na Pesquisa Nacional de Saneamento Básico de 1989 e 2000 e nos Censos demográficos de 1991 e 2000 elaborados pelo Instituto Brasileiro de Geografia e Estatística (IBGE). A fim de estimar tanto os fatores que determinam a existência de esgotamento sanitário nos domicílios de um município (modelo de variável dependente limitada) quanto os fatores que indicam a proporção de domicílios cobertos por esgotamento sanitário (modelo Double-Hurdle), foram utilizadas variáveis de demanda, variáveis de oferta, variáveis institucionais e variáveis de controle na estimação de um modelo. Como resultado, observou-se, por exemplo, que a variável renda per capita municipal não é estatisticamente significativa no primeiro modelo mas o é no segundo, o que parece indicar, por um lado, que a existência de bolsões de pobreza é mais importante do que o nível médio de renda do município no caso da determinação da existência de esgotamento sanitário em um município mas, por outro lado, que a renda per capital é o principal determinante na expansão da rede de esgoto. Por fim, o estudo provou que avanços podem ser feitos no que tange os condicionantes políticos que parecem afetar de forma desproporcional e desigual os gastos dos municípios com esgotamento sanitários. / Despite some progress authorities have been promoting in the past few years, many difficulties remain in the Brazilian basic sanitation sector. The inequality in access to those public services, the non-coordinated public policies and the absence of an efficient regulatory framework are the main challenges to the sector. This study analyses the factors behind the basic sanitation coverage in Brazil, based on the Pesquisa Nacional de Saneamento Básico 1989/2000 (1989 and 2000 National Survey of Basic Sanitation) and the Censo Demográfico 1991/2000 (1991 and 2000 Demographic Census), both published by the Instituto Brasileiro de Geografia e Estatística (IBGE). Two models were built in a way to estimate the factors that determine the installation of sanitary sewer services in Brazilian houses and the factors that explain the ratio of houses covered by sanitary sewer services in Brazilian cities - the first, a limited dependent variable model, and the second a Double-Hurdle model, both using demand, supply, institutional and control variables. An important result, for example, is that the variable income per capita is not statistically significant for the first model but it is for the second, which seems to indicate, on one hand, that the fact that exists many bolsões de pobreza (communities of concentrated poverty) are more important than the city basic level of income in the case of determining the installation of sanitary sewer services in Brazilian houses but, on the other hand, that income per capita is the main factor in the sewer services expansion. At last, progress can be made by studding more carefully the political effects that seems to affect disproportionally and unequally cities expenses with sewer services.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / Apesar dos progressos recentes do setor de saneamento básico no Brasil, muitas dificuldades ainda precisam ser superadas. A desigualdade no acesso a esses serviços bem como a fragmentação das políticas públicas e a ausência de marco regulatório podem ser citados como os principais desafios no setor. Este estudo tem por objetivo analisar os determinantes da cobertura de saneamento básico no Brasil, com base na Pesquisa Nacional de Saneamento Básico de 1989 e 2000 e nos Censos demográficos de 1991 e 2000 elaborados pelo Instituto Brasileiro de Geografia e Estatística (IBGE). A fim de estimar tanto os fatores que determinam a existência de esgotamento sanitário nos domicílios de um município (modelo de variável dependente limitada) quanto os fatores que indicam a proporção de domicílios cobertos por esgotamento sanitário (modelo Double-Hurdle), foram utilizadas variáveis de demanda, variáveis de oferta, variáveis institucionais e variáveis de controle na estimação de um modelo. Como resultado, observou-se, por exemplo, que a variável renda per capita municipal não é estatisticamente significativa no primeiro modelo mas o é no segundo, o que parece indicar, por um lado, que a existência de bolsões de pobreza é mais importante do que o nível médio de renda do município no caso da determinação da existência de esgotamento sanitário em um município mas, por outro lado, que a renda per capital é o principal determinante na expansão da rede de esgoto. Por fim, o estudo provou que avanços podem ser feitos no que tange os condicionantes políticos que parecem afetar de forma desproporcional e desigual os gastos dos municípios com esgotamento sanitários. / Despite some progress authorities have been promoting in the past few years, many difficulties remain in the Brazilian basic sanitation sector. The inequality in access to those public services, the non-coordinated public policies and the absence of an efficient regulatory framework are the main challenges to the sector. This study analyses the factors behind the basic sanitation coverage in Brazil, based on the Pesquisa Nacional de Saneamento Básico 1989/2000 (1989 and 2000 National Survey of Basic Sanitation) and the Censo Demográfico 1991/2000 (1991 and 2000 Demographic Census), both published by the Instituto Brasileiro de Geografia e Estatística (IBGE). Two models were built in a way to estimate the factors that determine the installation of sanitary sewer services in Brazilian houses and the factors that explain the ratio of houses covered by sanitary sewer services in Brazilian cities - the first, a limited dependent variable model, and the second a Double-Hurdle model, both using demand, supply, institutional and control variables. An important result, for example, is that the variable income per capita is not statistically significant for the first model but it is for the second, which seems to indicate, on one hand, that the fact that exists many bolsões de pobreza (communities of concentrated poverty) are more important than the city basic level of income in the case of determining the installation of sanitary sewer services in Brazilian houses but, on the other hand, that income per capita is the main factor in the sewer services expansion. At last, progress can be made by studding more carefully the political effects that seems to affect disproportionally and unequally cities expenses with sewer services.

nÃo hà / Este estudo buscou demonstrar o comportamento do nÃvel de acidente de trabalho na construÃÃo civil, para o ano de 2011, para os Estados da RegiÃo Nordeste. Depois de rÃpida exposiÃÃo acerca dos aspectos histÃricos e legislaÃÃo brasileira sobre o acidente de trabalho, foi estimado um modelo a partir dos dados da RAIS, divulgados pelo MinistÃrio do Trabalho e Emprego. Estudando o acidente de trabalho, em nÃmeros, verificou-se que as variÃveis sexo, idade, salÃrio, experiÃncia, escolaridade, raÃa e setor de atividade possuem relaÃÃo direta com o acidente de trabalho, sendo o tema de muita importÃncia, em decorrÃncia dos infortÃnios e, tambÃm, do curto despendido pelo Estado. / This study sought to demonstrate the behavior of the level of work-related accident in civil construction, for the year 2011, for the States of the Northeast Region. After a quick exposure about the historical aspects and Brazilian legislation on the work accident, was estimated a model from the RAIS data, published by the Ministry of Labor and Employment. Studying the work accident, in numbers, it was found that the variables sex, age, salary, experience, educational level, race and sector of activity have direct relation with the work accident, being the subject of so much importance, as a result of mishaps and, also, the short spent by State.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

No description available.

No description available.