Colorectal cancer is the third most diagnosed cancer and second leading cause of cancer related deaths in Canada. As Ontario has the largest population in Canada, it also has great disparities in colorectal cancer incidence. The region of Timiskaming has the highest incidence for colorectal cancer, while the region of Peel has the lowest incidence for colorectal cancer in Ontario. The purpose of this study is to identify the dominant non-nutritional modifiable environmental risk factors in the region of Timiskaming compared to the region of Peel that may be associated with diverging colorectal cancer incidence rates. The three objectives of the study included performing a systematic review on available published literature, creating an assessment questionnaire tool regarding environmental exposures, and utilizing the questionnaire assessment tool within a pilot study group while expanding it into the communities of interest. Findings indicate that there are dominant non-nutritional modifiable environmental risk factors in the regions of Timiskaming and Peel that may be associated with colorectal cancer. The dominant factors identified are tobacco/smoking, alcohol use, pesticides/organochlorines, and metal toxins. Following this study, it is imperative that recommendations are directed at a community level and relate to the assessment of potential non-nutritional modifiable environmental risk factors. Future research should accompany a larger sample size, multiple participant communities, and catering of the questionnaire tool towards the communities of interest. / UOIT

The purpose of the study was to summarize the literature about geographic information systems (GIS) and its applications in childhood cancer research. The main focus was to examine how GIS has been contributing to the research of childhood leukemia and its etiology. Since this is one of the diseases that can be connected to a public health issue, a thorough exploration of different areas outside the childhood cancer area had to be considered. Areas such as epidemiology and environmental health were two of the most relevant sources of literature. The etiology behind childhood leukemia has been studied for several decades, but the risk factors that cause this disease still remain largely unknown, and the results have been inconsistent. Since the 1990's, one of the methods to identify potential spatial clusters of childhood leukemia has been the use of GIS. This software has the ability to layer multiple risk factors in relation to the diagnosed children and thereafter visualize potential clusters on a map. The evaluation of the literature resulted in five topics which included most of the studies that has utilized GIS in their research of childhood leukemia. These five topics with its connected risk factors were: electromagnetic fields, ionizing radiation, air pollution, agricultural pesticides and hazardous waste sites. Even though few of the studies showed statistic significant clusters when connecting a potential risk factor with childhood leukemia, a majority of them didn't present any evidence about a causal relationship, which indicates a need of further research.

Despite its rapid growth in recent literature, risks in project management have received limited critical attention when compared to Lean principles and total quality management. The aim of this article is to examine the ongoing dialogue within health services funders and providers concerning the relationship between project management and its relationship to hard and soft environmental risk factors. The failure of high profile projects and cost to the taxpayer is on the increase. This article argues that the lack of understanding in relation to a holistic assessment of project success factors contributes to increased risk of failure. It argues that greater emphasis is needed on placing risk relative to both operational and cultural factors, as opposed to the frequent use of prescriptive mechanistic methodologies. These changes have the potential not merely to improve the success rates of healthcare management projects, but health outcomes too.

L’objectif de cette thèse sur articles était d’identifier des facteurs de risque environnementaux (FRE) associés à la survenue et au maintien des troubles psychotiques non-affectifs, dans un contexte français. Nous nous sommes appuyé sur les modèles socio-développemental-cognitif de Howes et Murray, et de la sensibilisation. Nos résultats ont montré l’implication d’un FRE populationnel, la fragilité économique, et de plusieurs aspects d’un FRE individuel, les traumatismes infantiles, dans l’accroissement du risque de développer ou de survenue d’un trouble psychotique. Concernant l’évolution de la maladie : nous avons identifié les expériences traumatiques infantiles et la consommation de cannabis comme étant deux facteurs modificateurs du cours évolutif de la maladie. Nous avons enfin cherché à montrer les apports de la théorie de la dissociation structurelle de la personnalité, pour intégrer les résultats issus de nos deux modèles initiaux dans un cadre bio-psycho-social. Nos travaux indiquent que des FRE populationnels et individuels sont associés à la survenue et au maintien des troubles psychotiques. Ils ouvrent la voie à de nouvelles stratégies thérapeutiques. / This article thesis aimed to identify environmental risk factors (ERF) that are associated with the onset and the prognosis of non-affective psychotic disorders, in a French context. We based our work on Howes and Murray’s sociodevelopmental-cognitive model, and the sensitization model. Our results showed that one area-level environmental risk factor, namely the economic deprivation, and several aspects of childhood traumas, an individual ERF, are associated with an increased risk to develop psychotic disorders. Furthermore, we identified childhood traumas and cannabis consumption as modifier factors for these disorders. Finally, we sought to link our previous results, the two original models, and conceptual inputs from the theory of structural dissociation of personality in a coherent, clinically useful, and biopsychosocial framework. Our results suggest that both arealevel and individual environmental risk factors are involved in the onset and poor prognosis of psychotic disorders. They open perspectives for new therapeutic strategies.

In this thesis, I describe a series of studies of the prevalence, causes, and management of asthma in the Pacific. The core study of the thesis is Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). The ISAAC study is the largest worldwide epidemiological study on asthma prevalence and was established partly in response to the increases in asthma prevalence in most parts of the world over the last two to three decades. The ISAAC Phase I study found large variations in asthma prevalence globally, but no Pacific countries were involved. Thus, the situation in the Pacific was relatively unknown due to lack of standardised studies on prevalence and time trends. The burden and impact of other non-communicable diseases such as cardiovascular and other metabolic disorder on the other hand have been the target of various studies in the Pacific for the past few decades The ISAAC Phase III study was therefore conducted in eight Pacific countries to address the above issues, as well as to enhance Pacific participation and contribution to international research on the causes and control of asthma. The collaboration also served the purpose of encouraging and strengthening health research capacity in the Pacific. The ISAAC Phase III study was followed by an asthma self-management intervention trial conducted in Tonga by the ISAAC Tonga study team. Methods The work presented in this thesis involved: (i) the conduct of the ISAAC Phase III study in the six Pacific islands of Tokelau, Samoa, Fiji Islands, Tonga, Niue and the Cook Islands, as well as the incorporation into the analysis of data that had already been collected in French Polynesia and New Caledonia; (ii) analysis of the data from an environmental asthma risk factor questionnaire which was included in the ISAAC survey in three countries (Samoa, Fiji and Tokelau); (iii) the conduct of the Tonga Asthma Self-management Study which was intended to assess whether the introduction of asthma education, including asthma self-management plans, would reduce morbidity from asthma. Results A total of 20,876 13-14 year olds, in the eight countries involved, participated in the ISAAC Phase III survey, with an overall response rate of 92%. The survey showed that there was considerable variation in the prevalence of asthma symptoms between the eight countries, ranging from 5.8% for current wheeze in Samoa to 16.2% in Tonga. Tokelau reported the highest prevalence (19.7%) for current wheeze, but the number of participants was relatively small. The prevalences of asthma symptoms among Pacific children in the Pacific were lower than those reported for Pacific, Māori and European children living in New Zealand from a previous study (ISAAC Phase I) conducted ten years earlier using the same methodology. The prevalence of 'asthma ever' in Pacific children living in the Pacific was also lower than that found among Pacific, Māaori and European children in New Zealand. The ISAAC Phase III environmental questionnaire data was collected in Samoa, Fiji and Tokelau. The analyses indicated that the major factors associated with current wheeze (across the three countries) were paracetamol use in the previous year (odds ratio (OR) = 1.36, 95% CI 1 15-1.61), the use of open fires for cooking (OR = 1.34,95% CI 1.13-1.58), lack of physical activity as indicated by television viewing more than 3 hours per day (OR = 1.24,95% CI 1.04-1.47), regular meat consumption (OR = 1.30,95% CI 1.09-1.54) and regular cereal consumption (OR = 1.29,95% CI 1.07-1.54). However, these risk factors were not particular strong, and did not account for a large proportion of asthma cases (i.e. they had relatively low population attributable risks). The asthma self-management plan intervention study resulted in significant improvements in asthma morbidity and the management of asthma among individuals and the service provision. The success of the introduction of the self-management plan, in the context of an asthma clinic, was reflected by improvement in measures of asthma morbidity, such as peak expiratory flow rates and nights woken with asthma or coughing. There was also a reduction in the requirement for acute medical treatment, indicated by a decrease in emergency department hospital visits for asthma and hospital admissions. The programme was so successful that the intervention study evolved into a full regular asthma clinic for the main island of Tonga. It is now intended that the asthma self-management programme will be extended throughout the rest of Tonga, through the primary health care system. Conclusions The ISAAC Phase IIII survey has shown that, although there is a significant level of morbidity, asthma prevalence in Pacific countries is lower than those among Pacific people in New Zealand. Together with the large variations in prevalence between the six Pacific countries that participated, this further lends support for the role of environmental risk factors in asthma. The availability of data on eight countries using a standardised methodology also provides useful information on the burden of asthma in the Pacific that is comparable to other countries regionally and internationally as well as forming a basis for ascertaining trends in the future. The crucial role of asthma self-management plans in asthma management is supported by the findings of the Tonga study, and its implementation is essential in the resource-scarce Pacific health setting. The collaborative nature of ISAAC in the Pacific has further raised awareness of the need for capacity building and creating networks and environments that enhance health research in areas other than asthma. The study has also nurtured an environment and network that encourages and strengthens the establishment of health research as one of the vital tools for achieving better health.

This thesis looks at risk factors for multiple sclerosis (MS), a chronic, degenerative autoimmune disease which is usually diagnosed between the ages of 20 and 50 years. It is estimated to affect over 100,000 people in the UK. The research setting was Orkney and Shetland, two archipelagos situated north of mainland Scotland, and both of which have very high MS prevalence as do other countries at high latitudes. I examine genetic and environmental risk factors in Orkney and Shetland using multiple methods over four studies. I also review the vitamin D and UV exposure literatures as these are risk factors pertinent to MS in Orkney and Shetland. After devoting three chapters to introducing the purpose of the thesis, MS, and Orkney and Shetland, in the fourth chapter, I aim to establish whether the birthplace of cases show any spatial, temporal, or spatiotemporal clustering. Evidence of these kinds of clustering may indicate that there are environmental risk factors present in some areas or that were present over particular periods, which raise risk of developing MS. Although I find statistically significant temporal, spatial, and spatiotemporal clustering in Orkney, and a spatial cluster in Shetland, for multiple reasons these results need to be interpreted with caution. I conclude that the clusters are very likely to be artefacts. Furthermore, there are multiple possible alternative explanations for such clusters that could not be explored by the available data. Chapter 5 examines the heritability of MS in Orkney and Shetland to estimate the proportion of phenotypic variance attributable to additive genetic effects. I also look at the birthplaces of ancestors of cases and controls to see if any locations contribute a greater amount of ancestral DNA to the gene pool of modern MS cases, which I term ‘genetic clustering’. In Orkney I obtained a heritability estimate of 0.36 (95% CI -0.26, 0.98); in Shetland this estimate was 0.20 (95% CI -1.88, 2.28). These modest estimates are consistent with the heritability literature. The genetic clustering analyses highlight two Orkney registration districts, Kirkwall and Westray, which earlier studies identified as areas of MS clustering. I also identify three Shetland registration districts, however these locations had not shown any evidence of clustering in earlier studies. Again, I advise caution in interpreting results, particularly as all the error bars across registration districts overlap. Chapter 6 presents a scoping review to map the literature and identify evidence of an association between vitamin D and UV exposure with MS. In methodically searching the literature, I identify a large and heterogeneous evidence base comprising multiple observational, intervention, and genetic studies. Overall, many studies support an association between vitamin D deficiency and MS. There is also evidence for an association between UV exposure and MS, although UV exposure is considerably less explored than vitamin D. I finally identify gaps in the literature and make suggestions for future research. In Chapter 7 I aim to compare vitamin D levels in Orkney and mainland Scotland, and establish the determinants of vitamin D status in Orkney. I firstly compare mean vitamin D and prevalence of deficiency in cross-sectional data from studies in Orkney and mainland Scotland. I secondly use multivariable regression to identify factors associated with vitamin D levels in Orkney. I find that mean (standard deviation) vitamin D is significantly higher in Orkney compared to mainland Scotland (35.3 (18.0) and 31.7 (21.2), respectively), and prevalence of severe deficiency is lower in Orkney (6.6% to 16.2% p = 1.1 x 10-15). Factors associated with higher vitamin D in Orkney include older age, farming occupations and foreign holidays. I conclude that although mean vitamin D levels are higher in Orkney compared to mainland Scotland, there is substantial variation within the Orkney population which may influence MS risk. Chapter 8 examines the correlates and determinants of UVB exposure in Shetland. I firstly construct correlation matrices to visualise how 1) personal characteristics such as sex, occupation, and skin type, 2) physical activity, and 3) body weight and fat, correlate with UVB exposure. I then use multivariable regression to identify factors associated with UVB exposure in Shetland. I run two multivariable models. The first includes the full sample size where activity data were measured by questionnaires. The second includes both questionnaire physical activity data and step-count data from pedometers, however as only a subset of participants had been supplied with pedometers, this analysis comprises a smaller sample size. I find that the amount of skin exposed was most strongly correlated with UVB exposure. Step count and activity minutes were also moderately positively correlated, and indoor occupations moderately negatively correlated, with UVB exposure. The regression analysis using the full sample with questionnaire activity data found that factors associated with greater UVB exposure were age and ambient UVB, while working indoors was significantly associated with lower UVB exposure. The model including the pedometer data found that found that age, total steps, and the amount of ambient UVB were significantly associated with greater UVB exposure. I conclude that atmospheric conditions, working outdoors and older age are important factors in UVB exposure in Shetland. It remains to be seen how UVB exposure translates to vitamin D levels in Shetland. I found evidence for environmental and genetic risk factors for MS in Orkney and Shetland. The two environmental risk factors, vitamin D deficiency and reduced UV exposure, are more likely to affect the younger population who are still within their lifetime risk of developing MS.

would like to thank my thesis supervisor, Dr Devendra Amre, for his guidance. I would also like to extend my gratitude to the CHU Ste-Justine Research Center and the Ste-Justine Foundation, as well as the Department of Biomedical Sciences of the University of Montreal, for their generous support. / L'importance des déterminants génétiques de la maladie de Crohn (MC) chez l'enfant est bien connue, mais nos connaissances sur la contribution des facteurs de risque environnementaux demeurent limitées. Parmi les facteurs de risque du déclenchement de la MC chez l'adulte, figure le tabac. Le lien entre le tabagisme actif et le déclenchement de la MC a été maintes fois démontré. Cependant, les études menées jusqu'à présent sur l'influence de la fumée secondaire sur le déclenchement de la MC chez l'enfant ne sont pas consistantes, et ont souvent montré des résultats contradictoires. Le principal objectif de notre étude était donc de déterminer l'influence de l'exposition à la fumée secondaire pendant la grossesse et durant l'enfance sur le déclenchement de la MC chez l'enfant. Méthodes: Nous avons mené une étude cas-témoins auprès d'enfants caucasiens. Les cas avaient reçu un diagnostic de MC avant l'âge de 20 ans à la clinique de gastroentérologie pédiatrique du CHU-Sainte-Justine de Montréal (n=132), et les témoins (n=131) ont été sélectionnés parmi les patients du service de gastroentérologie ou d'orthopédie du même hôpital, sans histoire de maladie chronique intestinale. Nous avons apparié les cas et les témoins selon le moment du diagnostic (± 3 mois) et leur lieu de résidence (à l'aide du code postal). L'information sur l'exposition à la fumée secondaire au cours de la grossesse et durant l'enfance, ainsi que les autres facteurs de risque ont été colligés à l'aide d'un questionnaire. L'analyse des déterminants du déclenchement de la MC a été faite par régression logistique pour estimer le ratio de cote (RC) ainsi que les intervalles de confiance correspondant (IC95%). Résultats: L'âge moyen (± ET) des cas était légèrement plus élevé que celui des témoins (12,7 ± 4,0 vs. 11,4 ± 4,7; p=0,01). Le sexe était réparti de manière égale entre les groupes. L’histoire familiale s'est avérée significativement associée à la MC (p=0,01). La régression logistique multivariée n'a montré aucun lien statistiquement significatif entre le tabagisme de la mère pendant la grossesse et la MC, en comparant les mères qui ont fumé pendant la grossesse avec celles qui n’ont fumé ni pendant la / positively associated with the disease. In children, there is interest in understanding whether passive exposure to environmental tobacco smoke (ETS) could confer similar risks. However, current studies have provided inconsistent results. The major objective of our study was thus to comprehensively ascertain whether ETS exposure during pregnancy and childhood was associated with the risk of developing CD in children. Methods: We carried out a case-control study based on Caucasian children diagnosed with CD (n=132) prior to age 20 at a pediatric gastroenterology clinic in Montreal (CHU-Sainte-Justine). Controls (n=131) were children having visited the orthopedic or gastroenterology clinics, who did not have a past/current history of IBD, were diagnosed within ± 3 months of case diagnosis and resided in the same geographic area (based on the first 3 digits of the postal code) as the cases. Information on ETS during and post-pregnancy and other potential risk factors for CD was acquired using a structured questionnaire. Associations between ETS and CD were analyzed using unconditional logistic regression. Odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were estimated. Results: The mean age (±SD) of the cases 12.7 (±4.0) was slightly higher than the controls (11.4±4.7) (p-value=0.01). Gender was equally distributed between the groups. Family history was positively associated with CD (p-value=0.01). Multivariate logistic regression did not reveal any association with CD when mothers who smoked during pregnancy were compared to those who neither smoked during pregnancy nor post-pregnancy (OR=1.55, 95% CI=0.84-2.86). Paternal smoking during pregnancy was also not associated with risk of CD (OR=0.95, 95% CI=0.33-2.75). Exposure of ETS to the child during childhood via maternal smoking appeared to increase risk (OR=3.54, 95% CI=0.71-17.57) but the risks were not iv significant. Paternal smoking during childhood also appeared to enhance risk of CD, in particular when the parents also smoked during pregnancy (OR=2.52, 95% CI=1.11-5.72). Conclusions: ETS exposure per se during pregnancy does not seem to confer risks of CD in children. However, ETS exposure during childhood either from maternal or paternal smoking appears to contribute to risk of CD in the child. Further studies are required to validate these associations.

Philosophiae Doctor - PhD / Background: A subtype of inflammatory bowel disease, Crohn' s disease is thought to represent a complex interaction between environmental factors, a defective immune system, the gastrointestinal microbiome and genetic' susceptibility; however; the-prevalence of different susceptibility mutations appears to vary between population groups, implying distinctions in disease pathogenesis or risk. Vitamin D, signaling through the vitamin D receptor, appears to have numerous effects on the immune system, and deficiency has been shown to playa role in both the pathogenesis and severity of experimental inflammatory bowel disease. However, the literature surrounding the association between vitamin D concentrations and disease severity in Crohn's disease is limited, and no such literature exists in South Africa. Furthermore, a paucity of data exists on the racial variability of Crohn' s disease phenotype in the Western Cape population of South Africa, as well as environmental factors in childhood associated with future Crohn's disease development. Aims: The three primary aims of the study were to investigate: 1) the racial variability of, Crohn's disease phenotype, defined by the Montreal classification scheme, as well as Crohn's disease behavior, using predefined definitions, stratified as 'complicated' or 'uncomplicated', based on a cross-sectional study design; 2) the association between childhood environmental exposures and the subsequent development of Crohn's disease, with specific emphasis on the timing of exposure, based on a case-control study design; and 3) the association between serum 25(OH)D concentration with Crohn's disease activity, measured by the Harvey Bradshaw Index, based on a cross-sectional study design; in this process, various vitamin D thresholds for predicting a high disease activity score were investigated, and the serum 25(OH)D concentrations were compared with those of the healthy controls to evaluate the prevalence of vitamin D deficiency. Design: This was a case control study, as well as two cross-sectional evaluations of the case control study data, of all consecutive Crohn's disease patients (ages 18-70 years) seen between September 2011 and January 2013 during their normally scheduled appointments at Schuur Hospital and Tygerberg Hospital. Control subjects for the study were identified from the same populations giving rise to the Crohn's disease cases. An investigator-administrated questionnaire was used to identify numerous demographic and lifestyle variables, as well as childhood environmental exposures during three age intervals; 0-5, 6-10 and 11-18 years. Clinical variables at diagnosis and time of study enrolment were determined via a review of medical and pharmacy records, as well as clinical examination by the consulting gastroenterologist. Serum 25(OH)D was measured using the SIEMENS ADIVA Centaur® XP Vitamin D Immunoassay [Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA]. Vitamin D status was classified as either 'deficient' or 'sufficient', and was analyzed in 2 ways: ~20 ng/mL versus ~21 ng/mL; and ~29 ng/mL versus ~30 ng/mL, respectively. One year after study completion, a total of 40 (10%) randomly selected participants from the cohort completed the interviewer-administered questionnaire for a second time. A kappa statistic was used in order to measure the agreement between repeated data for the questionnaire. Only data pertaining to the three age intervals (0-5, 6-10 and 11-18 years) was extracted in this process. Results: One hundred and ninety four Crohn's disease patients and 213 controls meeting our inclusion criteria were identified; 35 (18%) and 19 (9%) were White, 152 (78%) and 177 (83%) were Coloured, and 7(4%) and 17 (8%) were South African Black, respectively. No subjects reported being of Asian or Indian ethnicity. Overall, 125 (31%) of the cohort were male. On multiple logistic regression analysis, Coloured Crohn's disease patients were significantly more likely to develop 'complicated' Crohn's disease (60% versus 9%, P = 0.023) during the disease course when compared to White Crohn's disease patients. In addition, significantly more White subjects had successfully discontinued cigarette smoking at study enrolment (31% versus 7% reduction, P = 0.02). No additional interracial differences were found. A low proportion inflammatory bowel diseases family history was observed among the Coloured and Black subjects. When evaluating childhood environmental exposures, multiple logistic regression analysis showed that during the age interval 6-10 years, never having consumed unpasteurized milk [(OR = 6.43; 95% Cl, 3.02-14.81), (K =0.79; 95% Cl, 0.39-1.00)] and never having a donkey, horse, sheep or cow on the property [(OR = 3.10; 95% Cl, 1.42-7.21), (K = 0.84; 95% Cl, 0.12-1.00)], significantly increased the risk of developing future Crohn's disease. During the age interval 11-18 years, an independent risk-association was identified for; never having consumed unpasteurized milk (OR = 2.60; 95% Cl, 1.17-6.10) and second-hand cigarette smoke exposure (OR = 1.93; 95% Cl, 1.13-3.35). For the vitamin Danalysis, 186 Crohn's disease patients and 199 control subjects met the study inclusion criteria. Overall, 113 (29%) of the cohort were male. Forty four percent of the cohort had a deficient vitamin D concentration (::;20 ng/ml.), no participants had severely deficient vitamin D concentrations, and 26% of the cohort had sufficient vitamin D concentrations (:::30 ng/mL). Fifty-three percent of the controls and 34% of the cases had vitamin D concentrations ::;20 ng/mL (P < 0.001). On multiple logistic regression analysis, higher Harvey Bradshaw Index scores and not having taken vitamin D supplementation in the six months prior to enrolment were identified as independent predictors of vitamin D deficiency in Crohn's disease patients; defined either as ::;20 ng/mL, or as ::;29 ng/mL (P < 0.001). Compared to patients with Harvey Bradshaw Index <5, those with Harvey Bradshaw Index 2:8 were 2.5-times more likely to have vitamin D concentrations ::;21 ng/mL (PR = 2.5; 95% Cl, 1.30-6.30). The risk was similar, though not as high, if deficiency was defined as ::;29ng/ml. (PR = 2.0; 95% Cl, 1.20-3.50). Conclusions: Coloured Crohn's disease patients were significantly more likely to develop 'complicated' Crohn's disease over time when compared to White Crohn's disease patients. Limited microbial exposures and exposure to second-hand cigarette smoke during childhood is associated with future development Crohn's diseases. However the inconsistencies between each age interval with regards to the identified risk factors may imply that the effect of different viruses or bacteria on the development of immune structures varies according to the timing of exposure. The finding that lower serum 25(OH)D was associated with moderate to severe Crohn's disease activity suggests that this patient population may benefit from vitamin D supplementation in order to achieve, or maintain a serum 25(OH)D concentration of at least 30 ng/mL.

(Truncated abstract) The aims of this thesis are: (i) To estimate the prevalence of psychiatric illness among persons with intellectual disability and, conversely, the prevalence of intellectual disability among persons with a psychiatric illness; (ii) To describe the disability and service utilisation profile of persons with conjoint disorder; (iii) To examine, in particular, intellectual disability co-occurring with schizophrenia; and (iv) To explore the role of hereditary and environmental (specifically obstetric) risk factors in the aetiology of (i) intellectual disability and (ii) intellectual disability co-occurring with psychiatric illness. This thesis has a special interest in the relationship between intellectual disability and schizophrenia. Where data and sample sizes permit, it explores that relationship at some depth and has included sections on the putative nature of the link between intellectual disability and schizophrenia in the introductory and discussion chapters. To realise its objectives, the thesis comprises a core study focusing on aims (i) – (iii) and a supplementary study whose focus is aim (iv). It also draws on work from an ancillary study completed prior to the period of candidacy...This thesis found that, overall, 31.7% of persons with an intellectual disability had a psychiatric illness; 1.8% of persons with a psychiatric illness had an intellectual disability. The rate of schizophrenia, but not bipolar disorder or unipolar major depression, was greatly increased among cases of conjoint disorder: depending on birth cohort, 3.7-5.2% of individuals with intellectual disability had co-occurring schizophrenia. Down syndrome was much less prevalent among conjoint disorder cases despite being the most predominant cause of intellectual disability while pervasive developmental disorder was over-represented. Persons with conjoint disorder had a more severe clinical profile including higher mortality rates than those with a single disability. The supplementary study confirmed the findings in the core body of work with respect to the extent of conjoint disorder, its severity, and its relationship with pervasive development disorder and Down syndrome. Moreover, the supplementary study and the ancillary influenza study indicated a role for neurodevelopmental insults including obstetric complications in the adverse neuropsychiatric outcomes, with timing of the insult a potentially critical element in defining the specific outcome. The supplementary study also added new information on familiality in intellectual disability. It found that, in addition to parental intellectual disability status and exposure to labour and delivery complications at birth, parental psychiatric status was an independent predictor of intellectual disability in offspring as well as a predictor of conjoint disorder. In conclusion, the facility to collect and integrate records held by separate State administrative health jurisdictions, and to analyse them within the one database has had a marked impact on the capacity for this thesis to estimate the prevalence of conjoint disorder among intellectually disabled and psychiatric populations, and to understand more about its clinical manifestations and aetiological underpinnings.

Type 1 diabetes (T1D) is an autoimmune disease that destroys the bodies’ insulin producing beta-cells. The disease is understood to be triggered in genetically susceptible individuals by environmental factors. While the genetic side of the etiological model has to some degree been uncovered, there is no clear understanding of which environmental factors play a role in the disease process. Several hypotheses claim to explain the development of T1D, of which enteroviral infections show the most promise. According to this hypothesis high prevalence of enteroviral infections would also mean high incidence rates of T1D. This study focused on four Nordic countries (Denmark, Finland, Norway and Sweden) that as late as 2017 were found in the top 10 countries for incidence rate of childhood-onset T1D in the world. Incidence rates of T1D and prevalence of enteroviruses were mapped and geographically analyzed according to the principles of spatial epidemiology, after which correlation coefficients were calculated. In doing so the study tried to answer to which extent the prevalence of enteroviruses could explain the regional variations in T1D. For all countries no significant correlation was found, but increasing sample size, by grouping countries, showed considerably different outcomes with a small positive correlation in the case of Norway and Finland.