The differential impact of oxytocin receptor (OXTR) genotypes on the risk of autism spectrum disorder (ASD) and resulting social communication deficits

Background: Autism spectrum disorder (ASD) is multifactorial and is likely the result of complex interactions between multiple environmental and genetic factors. Recently, it has been suggested that each symptom cluster of the disorder, such as poor social communication, may be mediated by different genetic influences. Genes in the oxytocin pathway, which mediates social behaviours in humans, have been studied with single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR) being implicated in ASD. This thesis examines the presence of different oxytocin receptor genotypes, and their associations with ASD and resulting social communication deficits. Methods: The relationship between four OXTR variants and ASD was evaluated in 607 ASD simplex (SPX) families. Cases were compared to their unaffected siblings using a conditional logistic approach. Odds ratios and associated 95 percent confidence intervals were obtained. A second sample of 235 individuals with a diagnosis of ASD was examined to evaluate whether these four OXTR variants were associated with social communication scores on the Autism Diagnostic Interview – Revised (ADI-R). Parameter estimates and associated 95 percent confidence intervals were generated using a linear regression approach. Multiple testing issues were addressed using false discovery adjustments. Results: The rs53576 AG genotype was significantly associated with a lower risk of ASD (OR = 0.707, 95% CI: 0.512-0.975). A single genotype (AG) provided by the rs2254298 marker was found to be significantly associated with higher social communication scores (Parameter estimate = 1.833, SE = 0.762, p = 0.0171). This association was also seen in a Caucasian only and mothers as the respondent samples. No association was significant following false discovery rate adjustments. Conclusion: The findings from these studies provide limited support for the role of OXTR SNPs in ASD, especially in social communication skills. The clinical significance of these associations remains unknown, however, it is likely that these associations do not play a role in the severity of symptoms associated with ASD. Rather, they may be important in the appearance of social deficits due to the rs2254298 markers association with enlarged amygdalas.

The Impact of Geographic Mobility on Canadian Military families and their Children’s Access Special Education Services

To achieve academic success, children with learning-related disabilities often receive special education supports at school. Currently, Canada does not have a federal department or integrated national system of education. Instead, each province and territory has a separate department or ministry that is responsible for the organization and delivery of education, including special education, at the elementary level. At the macro (national) level, inclusive education is the policy across Canada. However, each province and territory has its own legislation, definitions, and policies mandating special education services. These variations result in little consistency at the micro (individual school) level. Differences between eligibility requirements, supports offered, and delivery methods may present challenges for highly mobile families who must navigate new special education systems on behalf of their children with medical or learning challenges. One of the defining features of the Canadian military lifestyle is geographic mobility. As a result, many families are tasked with navigating new school systems for their children, a task that may be more difficult when children require special education services. The purpose of this study is to explore the impact of geographic mobility on Canadian military families and their children’s access to special education services. The secondary objective was to gain insight into supports that helped facilitate access to services, as well as supports that participants believe would have helped facilitate access. A qualitative approach, interpretive phenomenological analysis (IPA), was employed due to of its focus on individuals’ experiences and their understandings of a particular phenomenon. IPA allowed participants to reflect on the significance of their experiences, while the researcher engaged with these reflections to make sense of the meanings associated with their experiences. Nine semi-structured interviews were conducted with civilian caregivers who have a child with special education needs. An interview guide and probes were used to elicit rich, detailed, first-person accounts of their experiences navigating new special education systems. The main themes that emerged from the participants’ combined experiences addressed the emotional components of experiencing a transition, factors that may facilitate access to special education services, and career implications associated with accessing and maintaining special education services. Findings from the study illustrate that Canadian families experience many, and often times severe, barriers to accessing special education services after a posting. Furthermore, the impacts reported throughout the study echo the existing American literature on geographic mobility and access to special education services. Building on the literature, this study also highlights the need for further research exploring factors that create unique barriers to access in a Canadian context, resulting from the current special education climate, military policies, and military family support services.

SIGNIFICANCE OF HEAT DISSIPATION IN THE CATHODE CATALYST LAYER ON THE LIFETIME AND RELIABILITY OF POLYMER ELECTROLYTE FUEL CELLS

To study the dissipation of heat generated due to the formation of pinholes that cause local hotspots in the catalyst layer of the Polymer Electrolyte Fuel Cell, a two-phase non-isothermal model has been developed by coupling Darcy’s law with heat transport. The domain under consideration is a section of the membrane electrode assembly with a half-channel and a half-rib. Five potential locations where a pinhole might form were analyzed: at the midplane of the channel, midway between the channel midplane and the channel wall, at the channel or rib wall, midway between the rib midplane and the channel wall, at the midplane of the rib. In the first part of this work, a preliminary thermal model was developed. The model was then refined to account for the two-phase effects. A sensitivity study was done to evaluate the effect of the following properties on the maximum temperature in the domain: Catalyst layer thermal conductivity, the Microporous layer thermal conductivity, the anisotropy factor of the Catalyst layer thermal conductivity, the Porous transport layer porosity, the liquid water distribution and the thickness of the membrane and porous layers. Accounting for the two-phase effects, a slight cooling effect was observed across all hotspot locations. The thermal properties of the catalyst layer were shown to have a limited impact on the maximum temperature in the catalyst layer of new fuel cells without pinhole. However, as hotspots start to appear, thermal properties play a more significant role in mitigating the thermal runaway.