Over the past twenty years the incidence of both childhood acute lymphoblastic leukaemia (ALL) and type 1 diabetes have risen in many developed countries, including New Zealand. Although the explanations for this increase and the precise aetiology of both diseases remain unclear, environmental factors are thought to be important. One factor receiving increasing attention is the role of infections introduced through population mixing. However, previous studies on this topic show mixed results and population mixing itself tends to be under-theorised. Furthermore, this issue has not been adequately assessed in New Zealand, a country characterised by high levels of population mobility. In this research, a variety of population mixing measures for small areas in New Zealand were developed. National data on ALL registrations were obtained from the New Zealand Cancer Registry, and regional type 1 diabetes data were obtained from the Canterbury Diabetes Register for the Canterbury Region of the South Island. The analyses were undertaken in three stages. First, standardised incidence ratios of each disease were examined at different geographical and temporal scales, between areas of differing socioeconomic status, and in urban and rural New Zealand. Second, cluster analysis was employed to test for spatial-temporal clustering of the two diseases. Finally, multivariate regression analyses were utilised to investigate the association between each disease and the various measures of population mixing at the area-level. The results reveal similarities in the geographical epidemiology of childhood ALL and type 1 diabetes in New Zealand. The majority of the findings were suggestive of an infectious aetiology for both diseases. In addition, higher incidence of both diseases was observed in areas which increased the most in population mixing over short time periods (6/7 years). Furthermore, raised type 1 diabetes incidence was also associated with high population mixing in early life.

Aim: A wealth of quantitative literature exists exploring the adjustment of children and young people with Type 1 Diabetes Mellitus. However, results are often confusing and contradictory, at least partly due to studies using different definitions and measures. Studies have been criticised for over relying on parental reports and failing to consider young people’s own perceptions. Furthermore, they have often conceptualised adjustment as an outcome, rather than exploring the process involved. Additionally, although peers are considered to play an important role in young people’s lives, their role in young people’s adjustment to living with diabetes has rarely been examined. To address this gap, this study attempted to gain a rich understanding of young people’s experiences of adjusting to life with diabetes and explore how they feel their peers have contributed to this process, with the hope of informing clinical practice and improving support to young people and their families. Method: A qualitative approach was chosen and six young females aged 12 – 15 with a diagnosis of Type 1 diabetes were interviewed using semi-structured interviews. Interpretative Phenomenological Analysis was used to analyse the transcripts. Results: Five main themes emerged from participants’ accounts: Developing a balanced relationship with diabetes; the uncomfortable position of difference; grappling with the fall out of diabetes; making diabetes more bearable; and the role of parents and friends. The findings are discussed in relation to the relevant literature. Clinical implications, methodological limitations and directions for future research are presented. Conclusions: This study provided an insight into the complex and dynamic process of young people’s adjustment to life with Type 1 diabetes. It highlighted the challenges and struggles they faced as a result of their diagnosis and the different strategies they employed to manage these. It also emphasised the valuable role both parents and friends provide in supporting young people with their illness.

Type 1 diabetes (T1D) is characterised by an absolute insulin deficiency resulting from the chronic and progressive destruction of pancreatic β-cells by the immune system cells. Continuous subcutaneous insulin infusion (CSII) is becoming a popular technique for insulin delivery among T1D patients. Exercise is known to exert anti-inflammatory effects and metabolic control. Therefore it was of interest to study this in T1D using CSII. The objectives of this thesis were to further understanding of the effect of exercise on blood glucose, hemoglobin A1c, lipids, insulin and inflammatory markers in healthy and T1D volunteers. Three studies have been investigated where the diabetic volunteers used multi daily injections (MDI) or CSII. Firstly a survey was conducted aimed to investigate the effect of exercise on T1D patients using CSII therapy. The second study examined the acute and chronic effects of resistance and cardio exercise at moderate intensity on inflammatory markers such as IL-6, IL-1β, TNF-α and IFN-γ in healthy and T1D using MDI or CSII. Finally, a study was undertaken to find out the effects of chronic moderate intensity exercise on lipids profile and glycaemic control in healthy and T1D using MDI or CSII. The statistical analysis of the survey showed that CSII therapy for T1D had a significant reduction on A1c, insulin requirement and improvement of lipids profile compared to MDI. Moreover, majority of CSII users (63%) rarely suffered from hypoglycemia during exercise. The second study demonstrated that acute and chronic exercises have a positive impact on the inflammatory markers among CSII users e.g. in CSII users statistically significant increase in IL-6 and TNF-α levels were observed (P=0.014 and P=0.001 respectively). The last study showed that lipids profile, total daily insulin units were improved and A1c levels were significantly reduced in CSII as well as MDI groups after 6 weeks of exercise. T1D affects major organs e.g. heart, kidneys, blood vessels etc. However, good glycaemic control can reduce the risk of diabetes complications. This study suggested that CSII therapy along with exercise can maintain the BG level close to normal, as all 5 participants of the study showed an improvement in their BG levels after exercise.

Objectives: Systematic review: This article presents a systematic review of studies evaluating the evidence for mobile phone-based interventions with adolescents who have Type 1diabetes. Studies were critically appraised and findings synthesised with the aim of answering the question: do mobile phone technologies facilitate improved outcomes in adolescents who have Type 1diabetes? Empirical research study: Diabetes research has indicated an association between attachment security and metabolic control as well as increased prevalence of mental health difficulties in diabetes populations. There is limited research with an adolescent Type 1 diabetes population. The current study aimed to examine attachment, emotional distress and self-esteem in an adolescent Type 1 diabetes population in relation to metabolic control and quality of life. The current study also aimed to evaluate the impact of ‘wellbeing text-messaging support’ with the same population. Method: Systematic review: A systematic search strategy was employed to identify relevant studies. An electronic database search, combined with a hand search of key journals and reference sections of key papers, was undertaken. Methodological quality was determined using an idiosyncratic measure including information relating to study design, sample size, interventions and statistical analyses. A narrative synthesis was performed due to the heterogeneity of the sample. Empirical research study: 60 participants aged between 12-18 years old who had a diagnosis of Type 1 diabetes for over 12 months took part. A longitudinal questionnaire design was used to collect data using five validated psychological measures. HbA1c was used as a measure of metabolic control. Text-messaging comprised a wellbeing module delivered daily over a three-week period. Results: Systematic review: 12 eligible studies were identified. One achieved a rating of ‘very good’, two a rating of ‘good’ and the remaining nine were pilot and/or feasibility studies, of whom four received a rating of ‘fair’ and ‘five received a rating of ‘poor’ methodological quality. Results indicated limited good quality evidence which included improved adherence and self-efficacy and mixed results in relation to metabolic control. Limitations identified included the use of small, convenience samples and short study duration. Empirical research study: High levels of fearful attachment security predicted poorer metabolic control and poorer quality of life, and high levels of emotional distress predicted poorer quality of life. ‘Wellbeing text-messaging support’ resulted in significantly improved quality of life. Conclusion: Systematic review: There is limited evidence that mobile phone technology has consistently improved outcomes in adolescents with Type 1 diabetes. Due to the number of pilot or feasibility studies and predominantly poor/fair quality of the current literature, and the heterogeneity of the sample, only tentative conclusions can be drawn, thus highlighting the need for further research. Empirical research study: Adolescent attachment style and emotional distress may be assessed as part of routine diabetes care in order to identify individuals who are potentially most at risk of failing to engage with diabetes health care. This can subsequently impact negatively on metabolic control and/or quality of life. These findings highlight the importance of clinical psychology input in paediatric diabetes teams. Further research in relation to text-messaging support was recommended.

Epithelial Ovarian Cancer (EOC) kills more women annually in the United Kingdom than any other gynaecological cancer. Survival rates for women diagnosed with EOC have not improved over the past 30 years, due to the often advanced stage at presentation, where widespread intra-peritoneal dissemination has occurred. The natural history of the disease remains uncertain but the ovarian surface epithelium (OSE) is a strong candidate for the tissue of origin. The OSE undergoes cyclical damage and repair in women of reproductive age following ovulation, which can be considered an acute inflammatory event. Factors that prevent ovulation (pregnancy, breastfeeding and contraceptive pill use) also protect against the development of EOC. Previously published data show that the OSE is able to upregulate the enzyme 11-beta hydroxysteroid dehydrogenase type 1 (11βHSD1) in response to inflammation, the enzyme responsible for converting inactive cortisone to anti-inflammatory cortisol. This thesis hypothesises that 11βHSD isozymes are deregulated in ovarian cancer; that the peritoneal surface epithelium (PSE) is indistinguishable from the OSE in its response to inflammation and should be considered a potential source of some “ovarian cancers”; and finally that the expression of the tumour suppressor gene OPCML (OPioid binding Cell adhesion Molecule-Like) is altered by inflammation. These hypotheses were examined at three levels. Firstly, primary cultures of EOC were established, and glucocorticoid metabolism and the response to inflammation was compared to normal OSE. Results from these investigations reveal that the11βHSD1 response to IL-1α stimulation is impaired in EOC compared to normal OSE at the mRNA level but there is no significant difference when 11βHSD1 enzyme activity is measured in these tissues. When basal levels of 11βHSD1, 11βHSD2 and COX2 are compared amongst untreated samples of EOC and OSE, there was a significant correlation between 11βHSD1 and COX2 mRNA expression (P<0.001). 11βHSD2 mRNA expression was significantly higher in the EOC specimens compared to OSE (P<0.05). Secondly the response to inflammation was compared in primary cultures of human peritoneal surface epithelial (PSE) cells and OSE. The data suggest that the mRNA response to inflammation was similar in OSE and PSE, but that the 11βHSD1 enzyme activity was reduced in PSE (P<0.05), which may result in differences in tissue healing. Finally, the effect of inflammation on the expression of the ovarian cancer associated tumour suppressor gene (TSG), OPCML (OPioid binding Cell adhesion Molecule-Like) and the other members of the IgLON family, was examined in OSE. These results suggest that OPCML mRNA expression can be induced by IL-1α, an effect that is inhibited by cortisol.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Unga vuxna typ 1 diabetiker i åldern 18-29 år har inte optimal diabetes-behandling. Insulin saknas och glukos kan inte transporteras till kroppens celler. Egenvård måste ske i form av insulintillförsel, regelbundna måltiderna och blodsockerkontroller. Behandlingsmålet är ett normalt liv och hindrande av långtidskomplikationer. Syftet med litteraturöversikten var att beskriva hinder och möjligheter av betydelse för egenvård hos unga vuxna med diabetes typ 1. Systematisk litteraturöversikt i tre olika databaser resulterade i elva vetenskapliga artiklar. Två kategorier framkom: Hinder och resurser för egenvård, vilka delades i subkategorierna vårdrelation vid transition, kommunikation vid transition, sociala relationer och patientens autonomi. Livet förändras i många avseenden i åldern 18-29 år. Det egna ansvarstagandet, autonomin och delaktigheten påverkas av bristande rutin, ostrukturerad livsstil, stress, dåliga vanor, felprioriteringar och bristande motivation. Patientens kontroll av sjukdom och egenvård är en viktig inre resurs som kan stärkas genom fortsatt utbildning, vilket resulterar i ökad delaktighet. Överföring mellan vårdgivare och tillgänglighet måste förbättras. Sjuksköterskans kunskap om samband mellan egenvårdsförmåga och motivationshöjande terapimetoder måste fördjupas och vidare forskning för att hitta åtgärder som främjar egenvården måste göras. / Young adult type 1 diabetics aged 18-29 do not have optimal diabetes treatment. Insulin is missing and glucose can not be transported to the body's cells. Self-care such as insulin administration, regular meals and bloodsugar controls must be done. The treatment goal is normal life and prevention of long-term complications. The purpose of the literature review was to describe obstacles and possibilities of self-care in young adults with type 1 diabetes. Systematic literature review in three different databases resulted in eleven scientific articles. Two categories emerged: Obstacles and resources for self-care, which were divided into subcategories care relationship at transition, communication at transition, social relations and patient autonomy. Life is changing in many respects between the ages of 18 and 29. Responsibility, autonomy and participation are affected by lack of routine, unstructured lifestyle, stress, bad habits, bad priorities and lack of motivation. The patient's control over disease and self-care is an important internal resource that can be strengthened through continuing education, resulting in increased participation. Transfers between healthcare providers and accessibility must be improved. Nursing knowledge about self-reliance and motivational therapy methods needs to be deepened and further research to find actions that promote selfesteem must be done.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Streptococcus suis est une bactérie encapsulée causant des pertes économiques majeures dans l’industrie porcine en provoquant la méningite et la septicémie chez le porc. C’est aussi un important agent zoonotique. Depuis de nombreuses années de recherche sur des vaccins, aucun n’est efficace et commercialement disponible. En effet, les bactérines (bactéries entières inactivées) autogènes sont les plus couramment utilisées sur le terrain, mais demeurent avec des résultats controversés. Pourtant, S. suis exprime de nombreux composants immunogéniques pouvant être potentiellement utilisés pour des vaccins sous-unitaires. Cependant, tester la capacité immunogénique de ces nombreux candidats vaccinaux ainsi qu’évaluer le meilleur adjuvant pour la formulation d’un vaccin contre S. suis est un processus long et onéreux qui requiert l’utilisation d’un nombre élevé d’animaux. En effet, les essais vaccinaux contre S. suis débutent par un premier dépistage chez la souris pour ensuite être testés chez le porc. Il est donc nécessaire de développer des stratégies permettant d’avancer et de faciliter la recherche. Dans cette optique, un système in vitro a été développé utilisant des cellules dendritiques (DC) différenciées à partir des cellules souches de la moelle osseuse de fémur de porc. Ce modèle permettra l’analyse des candidats vaccinaux et de leur potentiel immunogénique ainsi que l’évaluation préliminaire des adjuvants. Ce système in vitro pourrait réduire le nombre d’animaux utilisés pour les essais précliniques en délivrant des connaissances immunologiques fondamentales sur les formulations de vaccins testés, dont ceux retenus mériteront une étude approfondie chez l’animal. Pour développer ce modèle in vitro, l’utilisation de plusieurs cultures de DCs, dérivées des cellules souches de la moelle osseuse de 10 porcelets différents, ont été utilisées afin de tenir compte du polymorphisme génétique de chacun. Différents composants antigéniques de S. suis, dont leurs pouvoirs immunogéniques ont déjà été évalués lors des essais vaccinaux, ont été choisis. Parmi eux, une protéine de surface de S. suis a été sélectionnée : l’énolase. In vivo, elle a été reconnue comme ayant une forte immunogénicité, cependant la protection conférée par cette protéine dépend de l’adjuvant utilisé dans la formulation vaccinale. La capsule polysaccharidique (CPS) de S. suis, l’antigène le plus exposé en surface de la bactérie et en première ligne de contact avec le système immunitaire, est le deuxième antigène à être sélectionné pour cette étude. Étant donné la faible immunogénicité de la CPS, reliée à sa nature polysaccharidique, un prototype glycoconjugué a été précédemment développé dans notre laboratoire et son effet protecteur a été validé chez le porc. Le glycoconjugué et ses dérivées ont aussi fait l’objet de cette présente étude. Finalement, la capacité des DCs à répondre à des bactérines a aussi été évaluée. Différentes catégories d’adjuvants ont été sélectionnées (Poly I:C, Quil A, Alhydrogel 2%, TiterMax Gold et Stimune) et leurs effets ont été comparés. L’activation des DCs a été évaluée par la production de cytokines de type 1 (IL-12 et TNF-α) et de type 2 (IL-6). Il a été observé que les adjuvants intensifiaient l’activation des DCs par une augmentation de production des cytokines par rapport aux antigènes seuls. De plus, il a été constaté que les DCs distinguaient un adjuvant de type 1 ou de type 2 par l’observation d’un profil cytokinique spécifique à chaque type de réponse suite à leur activation par les adjuvants combinés aux différents antigènes. Il a aussi été constaté que l’ampleur de la production de cytokines variait selon la nature de l’antigène présent avec les adjuvants. Enfin, il a été noté que les DCs répondaient différemment selon la nature chimique des antigènes. En conclusion, ce système in vitro a permis d’évaluer la capacité immunogénique de candidats vaccinaux, mais aussi de présélectionner les meilleurs adjuvants favorisant la réponse immunitaire désirée contre S. suis. À cette fin, ce modèle pourrait permettre la réduction du nombre d’animaux utilisés en test préclinique, en permettant une présélection des candidats vaccinaux à tester in vivo ou en fournissant des connaissances scientifiques additionnelles sur des choix des candidats cibles. Sur le long terme, ce modèle facilitera la découverte des vaccins sous-unitaires contre S. suis. / Streptococcus suis, an encapsulated bacterium, is a major swine pathogen and an important zoonotic agent mainly causing septicemia and meningitis. Despite decades of vaccine research, no effective vaccine is currently commercially available. Indeed, autogenous bacterins (whole inactivated bacteria) are the most commonly used vaccines in the field; however, their protective capacity remains controversial. Nevertheless, S. suis expresses many immunogenic constituents that may have potential as sub-unit vaccines. However, testing the immunogenic potential of the many S. suis candidates and appropriate adjuvants is a long and costly process requiring the use of many animals. Indeed, studies of vaccines against S. suis start with a first screening in mice prior to evaluation in pigs. Therefore, it is necessary to develop strategies to advance and facilitate the research. Hence, an in vitro porcine bone marrow-derived dendritic cell (DC) culture was developed as a model for screening vaccine candidates, evaluation of their immunogenicity, and assessment of the best(s) adjuvant(s) to be used. This model could reduce the number of animals used in pre-clinical trials by providing fundamental immunological knowledge on selected vaccine formulations that would deserve further analysis in animal trials. To develop this model, porcine bone marrow-derived DC cultures from 10 different pigs were used to take into account the genetic polymorphism of individual animals. Different antigenic components of S. suis, the immunogenic properties of which have already been evaluated in vaccine trials, were selected. Among them, a surface protein of S. suis was selected: enolase. In vivo, this protein has been recognized as having high immunogenicity; however, the protection conferred by this protein depends on the adjuvant used in the vaccine formulation. The S. suis capsular polysaccharide (CPS), the most exposed antigen on the surface of the bacterium and the first line of contact with the immune system, is the second antigen selected for this study. Given the low immunogenicity of CPS, linked to its polysaccharide nature, a prototype glycoconjugate vaccine was previously developed in our laboratory and its protective effect validated in pigs. This glycoconjugate and its derivatives have also been the subject of this study. Finally, the ability of DCs to respond to bacterins was also evaluated. Different categories of adjuvants (Poly I:C, Quil A, Alhydrogel 2%, TiterMax Gold, and Stimune) were compared. The activation of DCs was evaluated by the production of type 1 (IL-12 and TNF-α) and type 2 (IL-6) cytokines. It was observed that adjuvants amplify DC activation as demonstrated by an increase of cytokine production when compared to the antigen alone. Moreover, DCs distinguish type 1 or 2 adjuvants in combination with different S. suis antigens, according to the cytokine profile observed. It has also been found that the extent of cytokine production varies depending on the nature of the antigen present with the adjuvants. Finally, it was observed that DCs respond differently depending on the chemical nature of the antigens. In conclusion, this in vitro model allows the evaluation of the immunogenic potential of vaccine candidates while also screening for adjuvants favoring the desired immune response against S. suis. Therefore, this model could permit a reduction in the number of animals used in pre-clinical trials by allowing a preselection of candidates to be tested in vivo or by providing additional scientific knowledge as a basis for the target choices. As a result, the list of candidates to be screened in the natural host in vivo would be reduced, facilitating the discovery of a subunit vaccine against S. suis.