Background: Childhood excess weight and family food insecurity are food-system related public health problems that exist in Canada. Since both relate to issues of food accessibility and availability, which have elements of “place”, they may share common risk factors in the local environment that are amenable to intervention. In this area of research, the literature derives mostly from a US context, and there is a dearth of high quality evidence, specifically from longitudinal studies. Objectives: The main objectives of this thesis were to examine the adjusted associations between the place factors: material deprivation, social deprivation, social cohesion, disorder, and living location, with change in child BMI Z-score and with change in family food insecurity status in a Canadian cohort of children. Methods: The Québec Longitudinal Study of Child Development was used to meet the main objectives of this thesis. Response data from six collection cycles (4 – 10 years of age) were used in three main analyses. The first analysis examined change in child BMI Z-score as a function of the place factors using mixed models regression. The second analysis examined change in child BMI Z-score as a function of place factors using group-based trajectory modeling. The third and final analysis examined change in family food insecurity status as a function of the place factors using generalized estimating equations. Results: Social deprivation, social cohesion and disorder were strongly and positively associated with family food insecurity, increasing the odds by 45-76%. These place factors, on the other hand, were not consistently associated with child weight status. Material deprivation was not important for either outcome, except for a slight positive association in the mixed models analysis of child weight status. Living location was not important in explaining family food insecurity. On the other hand, it was associated with child weight status in both analyses, but the nature of the relationship is still unclear. Conclusions: Results do not suggest that addressing similar place factors may alleviate both child excess weight and family food insecurity. More high quality longitudinal and experimental studies are needed to clarify relationships between the local environment and child weight status and family food insecurity.

Improving the estimation efficiency has always been one of the important aspects in statistical modelling. Our goal is to develop new statistical methodologies yielding more efficient estimators in the analysis of longitudinal data. In this thesis, we consider two different approaches, empirical likelihood and jointly modelling the mean and variance, to improve the estimation efficiency. In part I of this thesis, empirical likelihood-based inference for longitudinal data within the framework of generalized linear model is investigated. The proposed procedure takes into account the within-subject correlation without involving direct estimation of nuisance parameters in the correlation matrix and retains optimality even if the working correlation structure is misspecified. The proposed approach yields more efficient estimators than conventional generalized estimating equations and achieves the same asymptotic variance as quadratic inference functions based methods. The second part of this thesis focus on the joint mean-variance models. We proposed a data-driven approach to modelling the mean and variance simultaneously, yielding more efficient estimates of the mean regression parameters than the conventional generalized estimating equations approach even if the within-subject correlation structure is misspecified in our joint mean-variance models. The joint mean-variances in parametric form as well as semi-parametric form has been investigated. Extensive simulation studies are conducted to assess the performance of our proposed approaches. Three longitudinal data sets, Ohio Children’s wheeze status data (Ware et al., 1984), Cattle data (Kenward, 1987) and CD4+ data (Kaslowet al., 1987), are used to demonstrate our models and approaches.

In this thesis we are interested in generalized estimating equations (GEE). First, we introduce the term of generalized linear model, on which generalized estimating equations are based. Next we present the methos of pseudo maximum likelyhood and quasi-pseudo maximum likelyhood, from which we move on to the methods of generalized estimating equations. Finally, we perform simulation studies, which demonstrates the theoretical results presented in the thesis. 1

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<p>Postpartum depression has become a major public health concern for women within a specific time period after delivery. Depression is possibly associated with some risk factors such as socioeconomic status, social support, maternal mental and physical health, and history of anxiety. TOMIS III, funded by the Canadian Institutes of Health Research, is a prospective cohort to study the associations between delivery method and health and health resource utilization.</p> <p>Clinically, we investigated the associations between mode of delivery and outcome of postnatal depression, maternal and infant health, and we implied the risk predictors for outcomes by statistical methodology of marginal model with generalized estimating equations (GEE). Statistically, a variety of regression models, namely, generalized linear mixed effect model (GLMM), hierarchical generalized linear model (HGLM) and Bayesian hierarchical model were applied for this analysis and results were compared with GEEs. Some imputation strategies, namely, mean imputation, last observation carrying forward (LOCF), hot-deck imputation and multiple imputation were employed for handling missing values in this study.</p> <p>Analysis results demonstrated that there was no statistically significant association between mode of delivery and postpartum depression [OR 0.99, 95% CI (0.73, 1.34)]. However, the development of postpartum depression was found to be associated with low income, low mental and physical health functioning, lack of social support, the low number of unmet learning needs in hospital, and English or French spoken at home. Results were consistent for all regression models but GEE provided the best fit and an excellent discriminative ability. GEE models were constructed on different datasets imputed by mean, LOCF, hot-deck and multiple imputation, and LOCF was recommended to handle the missing data in this longitudinal study.</p> <p>Analyses on the outcome of maternal health and infant health stated that method of delivery had a statistically significant influence on maternal health but no significant impact on infant health. Risks of maternal health problems were associated with cesarean delivery, good/fair/poor infant health, low maternal mental and physical health functioning, lack of care for maternal mental health, and good/fair/poor health before pregnancy. Risks of infant health problems were associated with good/fair/poor maternal health before pregnancy and after discharge, inadequate care or help for infant health, fair/poor community services after discharge, low maternal mental health functioning, non-English or non-French spoken at home, and mothers born outside of Canada.</p> / Master of Science (MSc)

Neste trabalho, apresentamos as equações de estimação generalizadas desenvolvidas por Liang e Zeger (1986), sob a ótica da teoria de funções de estimação apresentada por Godambe (1991). Essas equações de estimação são obtidas para os modelos lineares generalizados (MLGs) considerando medidas repetidas. Apresentamos também um processo iterativo para estimação dos parâmetros de regressão, assim como testes de hipóteses para esses parâmetros. Para a análise de resíduos, generalizamos para dados com medidas repetidas algumas técnicas de diagnóstico usuais em MLGs. O gráfico de probabilidade meio-normal com envelope simulado é uma proposta para avaliarmos a adequação do ajuste do modelo. Para a construção desse gráfico, simulamos respostas correlacionadas por meio de algoritmos que descrevemos neste trabalho. Por fim, realizamos aplicações a conjuntos de dados reais. / In this work, we consider the generalized estimation equations developed by Liang and Zeger (1986) focusing the theory of estimating functions presented by Godambe (1991). These estimation equations are an extension of generalized linear models (GLMs) to the analysis of repeated measurements. We present an iterative procedure to estimate the regression parameters as well as hypothesis testing of these parameters. For the residual analysis, we generalize to repeated measurements some diagnostic methods available for GLMs. The half-normal probability plot with a simulated envelope is useful for diagnosing model inadequacy and detecting outliers. To obtain this plot, we consider an algorithm for generating a set of nonnegatively correlated variables having a specified correlation structure. Finally, the theory is applied to real data sets.

Neste trabalho, apresentamos as equações de estimação generalizadas desenvolvidas por Liang e Zeger (1986), sob a ótica da teoria de funções de estimação apresentada por Godambe (1991). Essas equações de estimação são obtidas para os modelos lineares generalizados (MLGs) considerando medidas repetidas. Apresentamos também um processo iterativo para estimação dos parâmetros de regressão, assim como testes de hipóteses para esses parâmetros. Para a análise de resíduos, generalizamos para dados com medidas repetidas algumas técnicas de diagnóstico usuais em MLGs. O gráfico de probabilidade meio-normal com envelope simulado é uma proposta para avaliarmos a adequação do ajuste do modelo. Para a construção desse gráfico, simulamos respostas correlacionadas por meio de algoritmos que descrevemos neste trabalho. Por fim, realizamos aplicações a conjuntos de dados reais. / In this work, we consider the generalized estimation equations developed by Liang and Zeger (1986) focusing the theory of estimating functions presented by Godambe (1991). These estimation equations are an extension of generalized linear models (GLMs) to the analysis of repeated measurements. We present an iterative procedure to estimate the regression parameters as well as hypothesis testing of these parameters. For the residual analysis, we generalize to repeated measurements some diagnostic methods available for GLMs. The half-normal probability plot with a simulated envelope is useful for diagnosing model inadequacy and detecting outliers. To obtain this plot, we consider an algorithm for generating a set of nonnegatively correlated variables having a specified correlation structure. Finally, the theory is applied to real data sets.

Les études cliniques permettent de mesurer de nombreuses variables répétées dans le temps. Lorsque l'objectif est de les relier à un critère clinique d'intérêt, les méthodes de régularisation de type LASSO, généralisées aux Generalized Estimating Equations (GEE) permettent de sélectionner un sous-groupe de variables en tenant compte des corrélations intra-patients. Les bases de données présentent souvent des données non renseignées et des problèmes de mesures ce qui entraîne des données manquantes inévitables. L'objectif de ce travail de thèse est d'intégrer ces données manquantes pour la sélection de variables en présence de données longitudinales. Nous utilisons la méthode d'imputation multiple et proposons une fonction d'imputation pour le cas spécifique des variables soumises à un seuil de détection. Nous proposons une nouvelle méthode de sélection de variables pour données corrélées qui intègre les données manquantes : le Multiple Imputation Penalized Generalized Estimating Equations (MI-PGEE). Notre opérateur utilise la pénalité group-LASSO en considérant l'ensemble des coefficients de régression estimés d'une même variable sur les échantillons imputés comme un groupe. Notre méthode permet une sélection consistante sur l'ensemble des imputations, et minimise un critère de type BIC pour le choix du paramètre de régularisation. Nous présentons une application sur l'arthrose du genoux où notre objectif est de sélectionner le sous-groupe de biomarqueurs qui expliquent le mieux les différences de largeur de l'espace articulaire au cours du temps. / Clinical studies enable us to measure many longitudinales variables. When our goal is to find a link between a response and some covariates, one can use regularisation methods, such as LASSO which have been extended to Generalized Estimating Equations (GEE). They allow us to select a subgroup of variables of interest taking into account intra-patient correlations. Databases often have unfilled data and measurement problems resulting in inevitable missing data. The objective of this thesis is to integrate missing data for variable selection in the presence of longitudinal data. We use mutiple imputation and introduce a new imputation function for the specific case of variables under detection limit. We provide a new variable selection method for correlated data that integrate missing data : the Multiple Imputation Penalized Generalized Estimating Equations (MI-PGEE). Our operator applies the group-LASSO penalty on the group of estimated regression coefficients of the same variable across multiply-imputed datasets. Our method provides a consistent selection across multiply-imputed datasets, where the optimal shrinkage parameter is chosen by minimizing a BIC-like criteria. We then present an application on knee osteoarthritis aiming to select the subset of biomarkers that best explain the differences in joint space width over time.

Dentre as possíveis propostas encontradas na literatura estatística para analisar dados oriundos de estudos com observações correlacionadas, estão os modelos condicionais e os modelos marginais. Diversas técnicas têm sido propostas para a análise de diagnóstico nesses modelos. O objetivo deste trabalho é apresentar algumas das técnicas de diagnóstico disponíveis para os dois tipos de modelos e avaliá-las por meio de estudos de simulação. As técnicas apresentadas também foram aplicadas em um conjunto de dados reais. / Conditional and marginal models are among the possibilities in statistical literature to analyze data from studies with correlated observations. Several techniques have been proposed for diagnostic analysis in these models. The objective of this work is to present some of the diagnostic techniques available for both modeling approaches and to evaluate them by simulation studies. The presented techniques were also applied in a real dataset.

Dentre as possíveis propostas encontradas na literatura estatística para analisar dados oriundos de estudos com observações correlacionadas, estão os modelos condicionais e os modelos marginais. Diversas técnicas têm sido propostas para a análise de diagnóstico nesses modelos. O objetivo deste trabalho é apresentar algumas das técnicas de diagnóstico disponíveis para os dois tipos de modelos e avaliá-las por meio de estudos de simulação. As técnicas apresentadas também foram aplicadas em um conjunto de dados reais. / Conditional and marginal models are among the possibilities in statistical literature to analyze data from studies with correlated observations. Several techniques have been proposed for diagnostic analysis in these models. The objective of this work is to present some of the diagnostic techniques available for both modeling approaches and to evaluate them by simulation studies. The presented techniques were also applied in a real dataset.