<p>This thesis is a report of the evaluation of an industrial alcoholic rehabilitation program. The evaluation covered the years 1970 - 1974 inclusive and all those referred to the program were included in the sample.</p> <p>Since employed problem drinkers are identified by deteriorating job performance, the variables selected for investigation were directly related to job performance. Absenteeism in four categories and visits to the industrial medical clinic were compared for three years; the year before referral, the year of treatment and the year after referral. Number of accidents sustained, both occupational and non-occupational and number of suspensions incurred were compared for the year before referral and the year after referral.</p> <p>Information was collected on age, marital status, number of years employed in the industry and diagnosis of one or more selected alcohol-related conditions. Data were collected on the number of appointments scheduled and kept to determine compliance and its' relationship to outcome.</p> <p>Those win refused to enter the program are described by mean age and mean number of years worked in the industry. Those who dropped out of the program before completing one full year post-referral are described by mean age, marital status, number of dependents, mean number or years worked in the industry and the mean number of months between referral and drop-out.</p> <p>The evaluation demonstrated that the program has a 78.8% success rate. The data obtained led to the formulation of hypotheses suitable for testing in future controlled trials.</p> / Master of Science (MS)

<p>Quality of care evaluation strategies are needed for meaningful assessment of health care delivery for research, quality assurance and educational purposes.</p> <p>For the purpose of improving strategies for measuring quality of care, this thesis first reviews methodologic features of available measurement strategies as reported in the current scientific literature. Secondly it proceeds with the development of a descriptive research design to evaluate the criterion validity of a strategy for evaluating process items by comparison with comprehensive outcome measures including physical, emotional and social function. Thirdly, the development of a new strategy for measurement of interpersonal skills, which is incorporated into the process evaluation, is described.</p> <p>The objective of the study is to study patients with acute myocardial infarction in order to determine whether measurable differences in the care administered to and received by these patients result in clinically significant differences in these patient's health status six months later. Acute myocardial infarction has been chosen as a disease appropriate for the testing of this strategy because if its high incidence, its functional impact upon the patient, the variation in process management items performed by different physicians, the different clinical settings involved, the relative diagnosis and availability of an inception cohort. A community hospital setting has been selected for the reason that, compared with a teaching hospital setting, the generalisability of the study to the practice of other physicians will be greater since the majority of physicians involved in the care of patients with acute myocardial infarction work in community hospital settings.</p> / Master of Science (MS)

<p>This thesis is a study of chronic methylmercury exposure in two Indian Reserves in Northwestern Ontario - White Dog and Crassy Narrows.</p> <p>The study consists of three major divisions which are the analysis of trends in human mercury levels in the two communities from 1970 to 1978; the design of a study to examine three major research questions; and conclusions drawn from the study.</p> <p>The analysis of data from White Dog and Grassy Narrows indicate that mean human mercury levels have declined significantly in the 1970 to 1978 period. This attributed to the success of programs designed to discourage the consumption of local fish.</p> <p>A cross-sectional prevalence study is designed to address the question concerning possible neurological effects of chronic methylmercury exposure in White Dog and Grassy Narrows. A second sub-study utilizes a sample of individuals for whom early information is available on peak mercury levels to examine the question of a mercury exposure gradient. A retrospective study of stillbirths and congenital abnormalities is designed to examine the effect of prenatal exposure to methylmercury.</p> / Master of Science (MS)

<p>This thesis describes the development and preliminary assessment of social function measures applicable to noninstitutionalized children ranging from 2-14 years of age. The measures are to be used in a cohort comparison study to evaluate neonatal intensive care for under 1500 gram birth weight infants. A lack of earlier attempts to develop measures that focus specifically on the social health of children provided the motivation for creating the scales reported in this paper.</p> <p>The three major divisions of the thesis include a discussion of measurement criteria applicable to new child health scales; a content analysis and evaluation of available measures of social functioning; and the analysis of results from a pilot study designed to assess a battery of instruments created for the neonatal intensive care project.</p> <p>Emerging from this work are three social function scales. One of the scales assesses the quality of social relationships and applies to children from 2-14 years. Pilot study results suggest, however, that this scale may overlap excessively with measures of emotional function. The remaining social function scales are applicable to children from 4-14 years: they measure quantitative dimensions of social health which include friendships, interpersonal contacts and social activities.</p> / Master of Science (MS)

<p>Existing statistical measures of agreement are reviewed and organized into a series of flow charts to facilitate their selection for analysis. A subset of "useful" measures is selected on the basis of their measuring meaningful agreement, hating interpretable referent values, being subject to hypothesis testing, being hand calculable and continuous (categorical) measures having categorical (continuous) analogues. "Useful" measures for continuous data sets are all intraclass correlation coefficients, applicable to different ANOVA models depending on the assumptions involved. "Useful" measures for categories data include various chance corrected (kappa) types, sensitivity-specificity and predictive value measures. The "useful" measures are displayed in a single condensed flow chart. A strategy to evaluate the use of this flow chart is also developed.</p> / Master of Science (MS)

<p>Schistosomiasis is known to affect over 200 million people in tropical countries. It is well known to have variable manifestations in similar geographical regions. It is also known to have variable responses to treatments in different geographical regions.</p> <p>Literature on its treatment though abundant reveals no agreement on doses of drugs to be administered.</p> <p>This thesis presents a design to determine doses of a recommended drug in the treatment of haematobium schistosomiasis. Three dosage levels of niridazole (ambilhar) will be tested against a recommended dose of metrifonate. The trial will be conducted over a 12 month period and will involve infected school children in a town in Ondo State of Nigeria.</p> <p>Children will be followed up during the trial period to determine the effects of treatment on their urinary egg output.</p> / Master of Science (MS)

Obesity develops when energy intake exceeds energy expenditure. Defect in the function of brown fat and skeletal muscle, two of the major tissues that contribute towards energy expenditure, lead to the development of obesity and metabolic syndrome. Our previous findings suggest that Tyk2 deficient mice become obese and develop the metabolic syndrome. Tyk2, which is a tyrosine kinase of the JAK-STAT signaling family, is important for optimal brown development and function. Since brown fat and skeletal muscle, both are derived from the Myf5+ lineage of mesenchymal stem cells, we also characterized the role of Tyk2 in the development and function of skeletal muscle. We found that Tyk2 deficient mice do not display a structural defect in skeletal muscle development; however, the function of skeletal muscle is severely impaired in these mice. Expression of troponins, which regulate the muscle contraction and muscle creatine kinase, which regulates the levels of phosphocreatine, a major fuel for skeletal muscle, is downregulated in Tyk2 deficient mice. Skeletal muscle mitochondria also display an abnormal morphology along with decreased respiration capacity, which is a function of decreased activity of complex IV of the electron transport chain. Interestingly, Tyk2 deficient mice also exhibit an increased proportion of fast, glycolytic, Type II fibers in the skeletal muscle. Using an in-vitro system for skeletal muscle differentiation, we found that Tyk2 levels increase during differentiation, suggesting a role for Tyk2 in proper development and function of the skeletal muscle. Our previous studies suggested that a kinase-inactive (Tyk2KD) form of Tyk2 is also efficient in restoring the function of Tyk2 deficient brown fat preadipocytes. We generated transgenic mice that expressed a wild type (Tyk2WT) and kinase inactive (Tyk2 KD) form of tyk2 in brown fat and skeletal muscle under Myf5 cre and in skeletal muscle using MCK cre mice. Expression of Tyk2 using the Myf5 cre (E8.0) reverts the obese and the metabolic phenotype observed in the Tyk2 deficient mice. Interestingly, expressing Tyk2 under MCK cre (E13.0) also reverts the obese phenotype, suggesting that the temporal and spatial expression of Tyk2 is critical in regulating energy expenditure. Our studies also highlight the role of Tyk2, not as a kinase, but as a component of the transcriptional assembly regulating the expression of genes invo

Dermal wound healing proliferative phase is a complicated physiological process in which many growth factors, cell types and matrix components participate. The process must be well coordinated to restore the structural and functional integrity of tissue injured. Many disorders interrupting healing process result in abnormal healing such as chronic wounds or excessive scarring. Mathematical modeling has been used to investigate many aspects of wound healing. Angiogenesis is pertinent for dermal wound healing since the cellular activities involved in tissue repair requires oxygen and nutrients to be delivered to the wound site. By using a hybrid agent-based model, we investigated the interactive dynamics of vasculature growth and collagen network growth. Our model further examine the effects of tissue oxygen tension (hypoxia, normoxia, hyperoxia) on healing process. Wound contraction is generally beneficial for the overall healing since it reduces the wound size thus reduces the chance to be infected. However, contraction going overboard may result in excessive scarring. Our model seeks to investigate the source of driving force during early and late stage of wound contraction. For the first time, skin is modeled as a fiber-reinforced anisotropic soft tissue. The effects of a dynamically orienting collagen matrix on the contraction process are thus shown. The simulation results of the model agree with the hypothesis that scar formation is the byproduct of collagen fiber synthesis and alignment in the presence of the tensile stress field generated by a wound contraction process. Multi-scale modeling is illuminating because it can help explain the phenomena at tissue level by the subcellular level events. We built a multi-scale model of general wound healing proliferative phase by embedding a TGFbeta pathway to each fibroblasts. The subcellular level model is an ODE system and the cellular level model is a hybrid agent-based model of fibroblast migration, proliferationg and collagen production. Our model clearly shows how varying mechanics of the subcellular level system results in varying tissue level pattern (collagen orientation and cell population distribution). The model can be further extended to incorporate subcellular events relating to angiogenesis and wound contraction.

Despite external bilateral symmetry, the internal organs of vertebrates are asymmetrically arranged. The development of Left-Right (LR) asymmetry is dependent on the activity of a ciliated organ known as the Kupffer’s vesicle (KV) or the embryonic node, in zebrafish and mouse, respectively. Cilia beating within the KV are essential to generate a counterclockwise flow of fluid, which leads to left-sided Ca2+ elevation. Ca2+ is a crucial morphogenic second messenger during vertebrate development. Ca2+ elevation activates targets, such as CaMK-II, which is also known as the multifunctional Ca2+/calmodulin-dependent protein kinase. Studies have linked CaMK-II to secretion (mediated through synapsin I) and to bipolar spindle formation in mammalian cells, among other cellular functions. In mammals, CaMK-II is encoded by four genes: α, β, δ, and γ. In zebrafish, like other teleost fish, gene duplication has yielded eight genes (α, αKAP, β1, β2, δ1, δ2, γ1, and γ2), which are transcriptionally active during the first 72 hours post fertilization (hpf). This dissertation has demonstrated that suppression of at least three of these CaMK-II genes disrupts proper LR-axis formation. In particular, knockdown of γ1 and αKAP CaMK-II dramatically affects southpaw (spaw) expression in the Lateral Plate Mesoderm (LPM). Interestingly, activated CaMK-II (P-CaMK-II) appears transiently in cells on the left side of the KV following Ca2+ elevation, and prior to spaw expression in the LPM. These findings indicate a role for CaMK-II in the processing or secretion of Spaw to the left LPM. In addition, cilia length and number are diminished in all three morphants, suggesting a role for CaMK-II in the process of ciliogenesis. CaMK-II is a binding partner of Kif2C, a Kinesin 13 member. Kinesin 13 members control flagellar length in Chlamydomonas, the blue-green algae and protists. The roles of Kif2C in zebrafish have never been explored, but could potentially explain cilia shortening seen in CaMK-II morphants. Zebrafish has served as an excellent model organism for the determination of the relative contributions of calcium signaling CaMK-II and Kif2C to the cellular and molecular mechanisms of LR-axis formation.

This thesis concerns the estimation of extreme quantiles on a dose-response curve. It focuses on the Robbins-Monro and up-and-down procedures. Simulation studies run in search of the LD15 and LD30 using a variety of methods suggest that the Robbins-Monro procedure is optimal in terms of Monte Carlo MSE and bias. The up-and-down procedure's performance differs in many cases only slightly from that of the Robbins-Monro process, therefore indicating its value as a practical alternative to the Robbins-Monro process for extreme-quantile estimation.