In recent decades, rates of type 2 diabetes mellitus (T2DM) and diabetic complications have reached epidemic proportions among Canadian Aboriginal people. Evidence in several populations suggests that abnormal birth weight, particularly low birth weight (LBW) and possibly high birth weight (HBW) may be linked to the development of T2DM. LBW often reflects poor maternal health/ nutritional status which may interfere with normal pancreatic development. HBW is a frequent complication of diabetic pregnancies which are associated with obesity and carbohydrate intolerance in adulthood. Since Saskatchewan Aboriginal newborns historically had higher rates of LBW, and more recently have experienced higher HBW rates, it follows that sub-optimal maternal/ fetal health may be important in the epidemic of T2DM in this population.<p> This thesis describes a case-control study that used Saskatchewan Health databases to determine the relationship between birth weight and T2DM. A sample of 846 adult diabetic Registered Indians (RI) were age and sex matched to three control groups: 1) non-diabetic RI, 2) diabetic general population (GP) subjects, and 3) non-diabetic GP subjects. RI subjects were identified as such by the provincial Health Insurance Registration File.<p> The results of this study show a significant association between HBW (> 4000 grams) and T2DM for RI people [odds ratio (OR) 1.63; 95% confidence interval (CI) 1.20, 2.24]. This association increased in strength from the middle to the latter part of this century and was found to be stronger for RI females than RI males. The comparison of birth weights within the four study groups revealed that diabetic RI (16.2%) were significantly more likely (p<0.05) than controls (10.7%,10.0%, 7.5% respectively) to have HBW. An association between LBW and T2DM (< 2500 grams) was not evident within either RI or GP sample populations.<p> The findings of this study support the hypothesis that HBW and its causes may be risk factors for T2DM among RI people. Programs to prevent gestational diabetes, and to diagnose and optimally manage diabetes during pregnancy could help to reduce rates of diabetes in future generations of Aboriginal peoples.

In recent decades, rates of type 2 diabetes mellitus (T2DM) and diabetic complications have reached epidemic proportions among Canadian Aboriginal people. Evidence in several populations suggests that abnormal birth weight, particularly low birth weight (LBW) and possibly high birth weight (HBW) may be linked to the development of T2DM. LBW often reflects poor maternal health/ nutritional status which may interfere with normal pancreatic development. HBW is a frequent complication of diabetic pregnancies which are associated with obesity and carbohydrate intolerance in adulthood. Since Saskatchewan Aboriginal newborns historically had higher rates of LBW, and more recently have experienced higher HBW rates, it follows that sub-optimal maternal/ fetal health may be important in the epidemic of T2DM in this population.<p> This thesis describes a case-control study that used Saskatchewan Health databases to determine the relationship between birth weight and T2DM. A sample of 846 adult diabetic Registered Indians (RI) were age and sex matched to three control groups: 1) non-diabetic RI, 2) diabetic general population (GP) subjects, and 3) non-diabetic GP subjects. RI subjects were identified as such by the provincial Health Insurance Registration File.<p> The results of this study show a significant association between HBW (> 4000 grams) and T2DM for RI people [odds ratio (OR) 1.63; 95% confidence interval (CI) 1.20, 2.24]. This association increased in strength from the middle to the latter part of this century and was found to be stronger for RI females than RI males. The comparison of birth weights within the four study groups revealed that diabetic RI (16.2%) were significantly more likely (p<0.05) than controls (10.7%,10.0%, 7.5% respectively) to have HBW. An association between LBW and T2DM (< 2500 grams) was not evident within either RI or GP sample populations.<p> The findings of this study support the hypothesis that HBW and its causes may be risk factors for T2DM among RI people. Programs to prevent gestational diabetes, and to diagnose and optimally manage diabetes during pregnancy could help to reduce rates of diabetes in future generations of Aboriginal peoples.

No description available.

Humans are constantly exposed to environmental pollutants and hazardous chemicals, yet we lack effective tools for monitoring the concentrations of these substances within the body. Traditional biomonitoring programs rely on blood and urine samples, but the invasiveness of these collection methods can discourage participation and impose financial limitations. To address this, alternative human matrices are being explored to provide more convenient means of biomonitoring. One promising yet underutilized matrix is tear fluid, which is easily accessible, interfaces with ambient air, and communicates dynamically with blood, offering insights into both environmental exposures and internal physiological processes. This thesis aims to characterize and develop a method for tear-based biomonitoring by introducing a novel means of passive sampling. To this end, a sample preparation and analysis protocol was optimized for extracting, identifying, and quantifying polar and nonpolar chemicals from tear fluid passive samplers (silicone hydrogel contact lenses). To validate the passive sampling material could retain chemicals of interest, targeted approaches were developed with hydrophilic interaction liquid chromatography coupled with triple quadrupole mass spectrometry (HILIC-MS/MS) for polar metabolites and Orbitrap gas chromatography-mass spectrometry (GC-MS) for semi-volatile organic compounds. Additionally, to comprehensively characterize the chemical profile captured by the passive samplers, an optimized nontargeted workflow using high-resolution mass spectrometry was developed. Further, multiple platforms were utilized for broad coverage of chemicals, including HILIC and reverse-phase liquid chromatography (RP-LC) with quadrupole time-of-flight mass spectrometry (QTOF-MS), as well as Orbitrap GC-MS. This work lays the groundwork for a user-friendly biomonitoring approach that enables personalized chemical exposure assessment with convenient sampling. It also has the potential to facilitate larger-scale studies involving vulnerable or hard-to-reach populations. A comprehensive biomonitoring survey using tear fluid could uncover valuable insights into sources and persistence of chemical exposures and their correlations with health trends across time and regions. / Thesis / Master of Science (MSc)

Master of Science / Department of Statistics / Wei-Wen Hsu / Polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) are endocrine disrupting chemicals which can imbalance the hormonal system in the human body and lead to deleterious diseases such as diabetes, irregular menstrual cycles, endometriosis, and breast cancer. These chemicals as environmental exposures still exist in the environment and food chains and can be accumulated in human fatty tissues for many years. These chemicals can also be passed from mothers to their children through placental transfer or breastfeeding; therefore, their offspring may be at increased risk of adverse health outcomes from these inherited chemicals. However, it is still unclear how the parental association with offspring health outcomes and the inter-generational phenotypic inheritance could be affected by these chemical compounds. In this study, we mainly focus on how PCBs and DDE can affect the inheritance of Body Mass Index (BMI) across generations, as BMI is the primary health outcome (or phenotype) linked to diabetes. We propose a biometrical inheritance model to investigate the effects of PCBs and DDE on the heritability of BMI over two generations. Technically, a linear mixed effects model is developed based on the decomposition of phenotypic variance and assuming the variance of the environmental effect depends on parental exposures. The proposed model is evaluated extensively by simulations and then is applied to Michigan Fisheater Cohort data for answering the research question of interest.

Research on exposure to animals and risk of type 1 diabetes (T1D) has had conflicting results with some researchers finding that animal exposure reduces the risk of T1D and others finding no association between animal exposure and T1D. Previously conducted studies on the association between animal exposure and T1D are case-control studies that have been limited by recall bias. The purpose of this study is to investigate the association between early life animal exposure and the risk of persistent, confirmed islet autoantibodies (IA) and T1D diagnosis among an eligible cohort of genetically high T1D risk participants enrolled in the international prospective cohort study, The Environmental Determinants of Diabetes in the Young (TEDDY). It is hypothesized that children who are exposed to animals in early life will have a lower risk of developing IA and T1D than children who are not exposed to animals in early life. A total of 7,432 TEDDY participants were included in the study. The associations between early life animal exposure and the outcomes of interest were explored using Cox proportional hazards models. In order to control for confounding, a propensity score analysis was applied by three different methods: adjustment for the propensity score variable in the Cox proportional hazards model, stratification on propensity score groups, and propensity score pair matching. Early life animal exposure was not associated with diabetes autoimmunity or T1D onset in this genetically high T1D risk population. These findings were consistent across all three propensity score analysis methods and when directly adjusting for HLA type. The hypothesis that children who are exposed to animals in early life will have a lower risk of developing IA and T1D than children who are not exposed to animals in early life is not supported by this study. The results of this study suggest that there is no association between early life animal exposure and development of T1D. Performing this analysis again after longer follow-up has been completed for the study population is recommended as it may elucidate the effect of animal exposure on T1D and IA risk. Further studies are also needed on animal exposure and T1D in different types of environments (e.g., high residential density) and the effect of different types of animal exposures (e.g., species, duration) on T1D and IA risk. Additionally, studies on differences in perceptions of pets across countries could also aid the interpretation of studies on animal exposure and health outcomes.

O atual modelo de desenvolvimento econômico, que tem como uma de suas bases a acentuada produção de bens de consumo, é responsável pelo aumento crescente de riscos ambientais que incidem nas questões de saúde das populações. Esse modelo é também responsável por um aumento na geração de resíduos sólidos, considerado um dos problemas ambientais emergentes com significativos impactos para a saúde humana. O crescimento na geração de resíduos vem sendo acompanhado por um aumento considerável no número de catadores de material reciclável, que encontram nessa atividade uma estratégia de sobrevivência. Esse grupo de trabalhadores encontra-se potencialmente exposto a maiores riscos no campo da saúde em função de sua ocupação. Na presente investigação, avaliaram-se os níveis de exposição aos metais cádmio (Cd), chumbo (Pb), mercúrio (Hg) e níquel (Ni) em catadores de material reciclável de quatro cooperativas na Região Metropolitana de São Paulo (RMSP) e os resultados foram comparados com estudos de biomonitoramento também realizados na RMSP .Foram coletadas amostras de sangue de 226 indivíduos (IC:95%, precisão 6%) e aplicados questionários para o levantamento de características associadas às concentrações de metais e à presença de valores acima dos Valores de Referência (VR) definidos por estudos de biomonitoramento. As concentrações médias de Cd (MA: 0,47 ug/L; MG: 0,34 ug/L) foram quase quatro vezes superiores às apontadas no estudo de referência e 24,3% dos indivíduos apresentaram concentrações de Cd acima dos VR. As concentrações médias de Pb (MA: 39,13 ug/L; MG: 34,11 ug/L) foram 1,4 vezes superiores às da população de referência e 10,6% dos indivíduos apresentaram concentrações de Pb acima do VR. As concentrações médias de Hg (MA: 1,46 ug/L; MG: 0,94 ug/L) não foram significativamente diferentes da população de referência, porém 4,9% dos indivíduos apresentaram concentrações de Hg acima do VR. As concentrações médias de níquel (Ni) (MA:3,3 ug/L; MG:1,89 ug/L) apresentaram grande variabilidade, não sendo possível realizar inferências sobre os níveis de exposição. Os resultados encontrados apontam para uma maior exposição ao Cd entre os catadores, possivelmente relacionada ao trabalho com a reciclagem, porém as fontes específicas não puderam ser determinadas por este estudo. Os resultados apontam também uma maior exposição ao Pb, porém de menor magnitude, o que pode estar relacionado com a condição socioeconômica e maior percentual de tabagistas na população do estudo e não necessariamente com a ocupação que exercem / The current model of economic development, which has as one of its bases a constant increase in production and consumption, is responsible for the intensification of environmental risks that can compromise a population\'s health. This model is also responsible for the continued growth in waste generation which is accompanied by a considerable increase in the number of recyclable materials collectors, who find in this activity a survival strategy. This population group that has for decades played an important role in solid waste management, now has greater exposures to health risks due to their daily activity. In the present study, the levels of exposure to the metals cadmium (Cd), lead (Pb), mercury (Hg) and nickel (Ni) were evaluated in recyclable materials collectors from four cooperatives in the Metropolitan Region of São Paulo (MRSP). Blood samples were collected from 226 individuals (CI: 95%, accuracy 6%) and the results were compared with other biomonitoring studies from MRSP. Questionnaires were applied to obtain information regarding variables that could influence the blood levels of the metals under study. The mean concentrations of Cd found (AM: 0.47 ug/L; GM: 0.34 ug/L) were almost four times that the ones found in the reference study and 24,3% of the individuals presented Cd concentrations above the Reference Values (RV). The mean concentrations of Pb in the collectors (AM: 39.13 ug/L; GM: 34.11 ug/L) were also significantly higher than the mean concentration in the reference study population (about 1.4 times) and 10,6% of the collectors presented Pb concentrations above the RV. The mean concentrations of mercury (AM: 1.46 ug/L; GM: 0.94 ug/L) were not significantly higher than the mean concentration found in the reference study. The concentration of Ni presented a large variability, so it was not possible to make inferences about the exposure to this metal. This study indicates that recyclable materials collectors have a greater exposure to Cd when compared with the general population, and this is possibly related to the work developed by these individuals, even though the sources could not be determined by this study. It also indicated that the collectors have a greater exposure to Pb, but the magnitude of the results might be explained by the socioeconomic characteristics and the larger amount of smokers among the sampled population

O atual modelo de desenvolvimento econômico, que tem como uma de suas bases a acentuada produção de bens de consumo, é responsável pelo aumento crescente de riscos ambientais que incidem nas questões de saúde das populações. Esse modelo é também responsável por um aumento na geração de resíduos sólidos, considerado um dos problemas ambientais emergentes com significativos impactos para a saúde humana. O crescimento na geração de resíduos vem sendo acompanhado por um aumento considerável no número de catadores de material reciclável, que encontram nessa atividade uma estratégia de sobrevivência. Esse grupo de trabalhadores encontra-se potencialmente exposto a maiores riscos no campo da saúde em função de sua ocupação. Na presente investigação, avaliaram-se os níveis de exposição aos metais cádmio (Cd), chumbo (Pb), mercúrio (Hg) e níquel (Ni) em catadores de material reciclável de quatro cooperativas na Região Metropolitana de São Paulo (RMSP) e os resultados foram comparados com estudos de biomonitoramento também realizados na RMSP .Foram coletadas amostras de sangue de 226 indivíduos (IC:95%, precisão 6%) e aplicados questionários para o levantamento de características associadas às concentrações de metais e à presença de valores acima dos Valores de Referência (VR) definidos por estudos de biomonitoramento. As concentrações médias de Cd (MA: 0,47 ug/L; MG: 0,34 ug/L) foram quase quatro vezes superiores às apontadas no estudo de referência e 24,3% dos indivíduos apresentaram concentrações de Cd acima dos VR. As concentrações médias de Pb (MA: 39,13 ug/L; MG: 34,11 ug/L) foram 1,4 vezes superiores às da população de referência e 10,6% dos indivíduos apresentaram concentrações de Pb acima do VR. As concentrações médias de Hg (MA: 1,46 ug/L; MG: 0,94 ug/L) não foram significativamente diferentes da população de referência, porém 4,9% dos indivíduos apresentaram concentrações de Hg acima do VR. As concentrações médias de níquel (Ni) (MA:3,3 ug/L; MG:1,89 ug/L) apresentaram grande variabilidade, não sendo possível realizar inferências sobre os níveis de exposição. Os resultados encontrados apontam para uma maior exposição ao Cd entre os catadores, possivelmente relacionada ao trabalho com a reciclagem, porém as fontes específicas não puderam ser determinadas por este estudo. Os resultados apontam também uma maior exposição ao Pb, porém de menor magnitude, o que pode estar relacionado com a condição socioeconômica e maior percentual de tabagistas na população do estudo e não necessariamente com a ocupação que exercem / The current model of economic development, which has as one of its bases a constant increase in production and consumption, is responsible for the intensification of environmental risks that can compromise a population\'s health. This model is also responsible for the continued growth in waste generation which is accompanied by a considerable increase in the number of recyclable materials collectors, who find in this activity a survival strategy. This population group that has for decades played an important role in solid waste management, now has greater exposures to health risks due to their daily activity. In the present study, the levels of exposure to the metals cadmium (Cd), lead (Pb), mercury (Hg) and nickel (Ni) were evaluated in recyclable materials collectors from four cooperatives in the Metropolitan Region of São Paulo (MRSP). Blood samples were collected from 226 individuals (CI: 95%, accuracy 6%) and the results were compared with other biomonitoring studies from MRSP. Questionnaires were applied to obtain information regarding variables that could influence the blood levels of the metals under study. The mean concentrations of Cd found (AM: 0.47 ug/L; GM: 0.34 ug/L) were almost four times that the ones found in the reference study and 24,3% of the individuals presented Cd concentrations above the Reference Values (RV). The mean concentrations of Pb in the collectors (AM: 39.13 ug/L; GM: 34.11 ug/L) were also significantly higher than the mean concentration in the reference study population (about 1.4 times) and 10,6% of the collectors presented Pb concentrations above the RV. The mean concentrations of mercury (AM: 1.46 ug/L; GM: 0.94 ug/L) were not significantly higher than the mean concentration found in the reference study. The concentration of Ni presented a large variability, so it was not possible to make inferences about the exposure to this metal. This study indicates that recyclable materials collectors have a greater exposure to Cd when compared with the general population, and this is possibly related to the work developed by these individuals, even though the sources could not be determined by this study. It also indicated that the collectors have a greater exposure to Pb, but the magnitude of the results might be explained by the socioeconomic characteristics and the larger amount of smokers among the sampled population

No description available.

Cette thèse a pour but d'améliorer les connaissances concernant les techniques d'analyse de données et certains modèles bayésiens dans le domaine de l'étude des inégalités sociales et environnementales de santé. À l'échelle géographique de l'IRIS sur les agglomérations de Paris, Marseille, Lyon et Lille, l'événement sanitaire étudié est la mortalité infantile dont on cherchera à expliquer le risque avec des données socio-économiques issues du recensement et des expositions environnementales comme la pollution de l'air, les niveaux de bruit et la proximité aux industries polluantes, au trafic automobile ou aux espaces verts. Deux volets principaux composent cette thèse. Le volet analyse de données détaille la mise au point d'une procédure de création d'indices socio-économiques multidimensionnels et la conception d'un package R l'implémentant, puis la création d'un indice de multi-expositions environnementales. Pour cela, on utilise des techniques d'analyse de données pour synthétiser l'information et fournir des indicateurs composites utilisables directement par les décideurs publics ou dans le cadre d'études épidémiologiques. Le second volet concerne les modèles bayésiens et explique le modèle « BYM ». Celui-ci permet de prendre en compte les aspects spatiaux des données et est mis en oeuvre pour estimer le risque de mortalité infantile. Dans les deux cas, les méthodes sont présentées et différents résultats de leur utilisation dans le contexte ci-dessus exposés. On montre notamment l'intérêt de la procédure de création d'indices socio-économiques et de multi-expositions, ainsi que l'existence d'inégalités sociales de mortalité infantile dans les agglomérations étudiées / The purpose of this thesis is to improve the knowledge about and apply data mining techniques and some Bayesian model in the field of social and environmental health inequalities. On the neighborhood scale on the Paris, Marseille, Lyon and Lille metropolitan areas, the health event studied is infant mortality. We try to explain its risk with socio-economic data retrieved from the national census and environmental exposures such as air pollution, noise, proximity to traffic, green spaces and industries. The thesis is composed of two parts. The data mining part details the development of a procedure of creation of multidimensional socio-economic indices and of an R package that implements it, followed by the creation of a cumulative exposure index. In this part, data mining techniques are used to synthesize information and provide composite indicators amenable for direct usage by stakeholders or in the framework of epidemiological studies. The second part is about Bayesian models. It explains the "BYM" model. This model allows to take into account the spatial dimension of the data when estimating mortality risks. In both cases, the methods are exposed and several results of their usage in the above-mentioned context are presented. We also show the value of the socio-economic index procedure, as well as the existence of social inequalities of infant mortality in the studied metropolitan areas