Rationale: Ng et al. (2008) demonstrated that sub-acute hippocampal atrophy occurred between 4.5 and 24 months following moderate-to-severe traumatic brain injury (TBI); it remains to be determined if atrophy occurred before 24 months. Objectives: (1) to determine if sub-acute hippocampal atrophy occurs by the first year of injury; (2) to determine associated clinical and demographic variables. Methods: Ten moderate-to-severe TBI patients underwent MRI at 5 and 12 months post-injury. Glasgow Coma Scale (GCS) and demographic variables were correlated with change. Results: Significant hippocampal volume decreases were observed for right (P< 0.002, Cohen’s d= 0.34) and left (P< 0.036, Cohen’s d= 0.22) sides. GCS was significantly correlated with right (r= -0.663, P< 0.037), but not left percent hippocampal volume change (r= -0.327, P< 0.356). No significant correlations were observed for demographic variables. Conclusion: Sub-acute hippocampal atrophy occurs between 5 and 12 months post-injury and is associated with injury severity.

Animal models have yet to characterize alterations in body composition, wheel running activity, food intake, and neuroendocrine parameters, in chronic food restriction. This study investigated changes in these measures in food restricted rats, with and without access to running wheels, over four weeks. The data demonstrated that upon initiation of food restriction IGF-1 reductions paralleled loss of lean tissue while leptin levels were rapidly reduced which paralleled losses in body fat. Further, a lower limit threshold of body fat was identified, below which the correlation between leptin and fat mass was disrupted. Lastly, a decrease and plateau in body mass was mirrored by an increase and plateau in voluntary wheel activity in the food restricted population. The data suggest that there is a tight biological link between hyperactivity and body mass and that adequate nutritional support might attenuate the drive for obligate exercise even before weight is fully restored.

Recent discoveries enabled us to divide medulloblastoma into molecular sub-groups and uncover novel mutations in these tumors. However, except for superior survival of the WNT sub-group, the prognostic and therapeutic implications of these observations remain unclear. TP53 mutations which confer radioresistance revealed conflicting clinical relevance in different studies. We hypothesized that the effect of TP53 mutations on survival is modulated through molecular sub-grouping. This is especially important since therapeutic targeting of WNT can be achieved with administration of lithium. Here we first confirmed that TP53 mutant tumors confers unfavorable outcome only in SHH subgroup, but not in WNT. We demonstrated that while TP53 mutations cause radioresistance, activation of WNT/β-catenin signaling radiosensitizes medulloblastoma cells. We demonstrated that lithium activates the WNT pathway and effectively sensitize medulloblastoma cells to radiation. Furthermore, lithium did not sensitize normal neural stem cells to radiation, suggesting its potential as an effective radiosensitizer for medulloblastoma.

The purpose of this dissertation is to examine how women seek health information on the Web in relation to information source characteristics, situational characteristics, and socio-demographic characteristics. The Web is conceptualized as three facets that reflect the three main modes of seeking health information on the Web: websites; Web-based bulletin boards and chatrooms; and Web-based listservs and newsgroups. The lack of analytical research on this gendered online activity prompted this study. The conceptual framework is based primarily on theoretical foundations from two academic disciplines: information science and health sciences. The independent variables in the conceptual framework are health information need, family caregiving, perceived Web self efficacy, perceptions of the quality and accessibility of the Web as a source of health information, and socio-demographic variables. The dependent variable is intensity (frequency) of seeking health information on the Web (FSHIW). Data was collected from 264 women from November 2000 until April 2001 using a Web survey questionnaire. The participants were predominantly well educated, English-speaking Canadians. A subset of 27 survey respondents completed at least one additional component of this multi-method study. Perception of the reliability of the Web as a source of health information was identified as the key variable influencing frequency of seeking health information on the Web (FSHIW). As well, perceived information source reliability was correlated with two information source characteristics, perceived information source relevance and cognitive access. Two situational variables, health information need and family caregiving, were weakly correlated with FSHIW. Three socio-demographic variables – racial identity, household income, and occupation – affected FSHIW. Qualitative interview data, Web use journals, and recordings of Web use sessions provided a contextualized understanding of the survey data. In particular, they highlighted the importance of situational and affective relevance. To-date, very few empirical research studies have been conducted on how women seek health information on the Web. This unique multi-method study contributes to a better understanding of women’s use of the Web as a source of health information for resolving personal health problems and caring for family members by identifying key variables that affect the frequency of this online behaviour and contextualizing these variables.

Despite the establishment of heart transplantation as a life-saving therapy for children and adolescents, little research has focused on the biopsychosocial impact of the transplant process. Few studies have captured the subjective experiences of young heart transplant recipients. This program of research examined how pediatric heart transplant recipients construct their worlds and the meanings they ascribe to their transplant experience. A grounded theory approach was implemented which guided data collection and analysis. A total of twenty-seven adolescents participated in semi-structured qualitative interviews. Findings illuminate pediatric heart transplantation to be a pervasive experience, with consequent impact on physical, psychological and social well-being. Participants described various biopsychosocial processes and experiences that occurred over the course of their transplant journey. Data analysis yielded themes of quality of life reflecting notions of temporality including: 1) the pre-transplant experience – a struggle to survive, 2) the transplant surgery and hospitalization – a difficult transition and 3) the post-transplant experience – an awakening and transformation. This research identifies that heart transplantation, which may contain elements of suffering and loss, may ultimately enhance young recipients’ overall quality of life. Results reveal the possibility that adolescent heart transplant recipients not only adapt to transplantation, but also potentially experience associated growth-enhancing experiences. An emergent theoretical model is presented, with implications for practice and research.

Fundamental questions related to the locations of Cerebrospinal Spinal Fluid (CSF) absorption deficit and causes of the pressure gradients that expand the ventricles with hydrocephalus remain largely unanswered. Work in the Johnston lab over a 15 year period has demonstrated that CSF moves through the cribriform plate foramina in association with the olfactory nerves and is absorbed by a network of lymphatic vessels located within the olfactory turbinates. A kaolin-based rat model of communicating hydrocephalus was developed as a collaborative effort with Drs. McAllister, Wagshul and Li. After developing a method to quantify lymphatic CSF uptake in rats, we examined and observed that the movement of a radioactive tracer into the nasal turbinates was significantly reduced in the kaolin-injected animals compared to saline injected controls. However, it was possible that while lymphatic CSF uptake was compromised, other CSF absorption pathways may have compensated. To answer this, we measured the CSF outflow resistance (Rout) and observed it to be significantly greater in the kaolin group compared with animals receiving saline and there was a significant positive correlation between CSF Rout and ventricular volume. Nonetheless, it is not clear how impaired CSF clearance could lead to a dilation of the ventricles since the ventricular and subarachnoid compartments are in communication with one another and pressure would likely increase equally in both. At this point, we came across a theoretical paper that postulated that a drop in periventricular interstitial fluid pressure might provide an intraparenchymal pressure gradient favouring ventricular expansion. In addition, studies in non-CNS tissues indicated that a disruption of beta-1 (β1) integrin-matrix interactions could lower tissue pressure. Based on these suppositions and data, we examined if these concepts had relevance to the brain. For this, we measured pressure in the brain and observed a decline in periventricular pressures to values significantly below those monitored in the ventricular system following the injection of the anti integrin antibodies. Many of the animals developed hydrocephalus over 2 weeks post antibody injection. These data provide a novel mechanism for the generation of intraparenchymal pressure gradients that is likely contributing to ventricular expansion.

The purpose of this dissertation is to examine how women seek health information on the Web in relation to information source characteristics, situational characteristics, and socio-demographic characteristics. The Web is conceptualized as three facets that reflect the three main modes of seeking health information on the Web: websites; Web-based bulletin boards and chatrooms; and Web-based listservs and newsgroups. The lack of analytical research on this gendered online activity prompted this study. The conceptual framework is based primarily on theoretical foundations from two academic disciplines: information science and health sciences. The independent variables in the conceptual framework are health information need, family caregiving, perceived Web self efficacy, perceptions of the quality and accessibility of the Web as a source of health information, and socio-demographic variables. The dependent variable is intensity (frequency) of seeking health information on the Web (FSHIW). Data was collected from 264 women from November 2000 until April 2001 using a Web survey questionnaire. The participants were predominantly well educated, English-speaking Canadians. A subset of 27 survey respondents completed at least one additional component of this multi-method study. Perception of the reliability of the Web as a source of health information was identified as the key variable influencing frequency of seeking health information on the Web (FSHIW). As well, perceived information source reliability was correlated with two information source characteristics, perceived information source relevance and cognitive access. Two situational variables, health information need and family caregiving, were weakly correlated with FSHIW. Three socio-demographic variables – racial identity, household income, and occupation – affected FSHIW. Qualitative interview data, Web use journals, and recordings of Web use sessions provided a contextualized understanding of the survey data. In particular, they highlighted the importance of situational and affective relevance. To-date, very few empirical research studies have been conducted on how women seek health information on the Web. This unique multi-method study contributes to a better understanding of women’s use of the Web as a source of health information for resolving personal health problems and caring for family members by identifying key variables that affect the frequency of this online behaviour and contextualizing these variables.

Policy making bodies are increasingly highlighting the important role innovation can play in African development─not only to spur economic growth but also to deliver locally relevant, affordable products and services to African populations. The health sector is one area where innovation is most needed; however, we know very little about the capacity of African countries to innovate in this area. At the same time, a range of conceptual questions have arisen in the academic literature as to the very definition of innovation in an African context, and specifically, the applicability of the National Innovation System (NIS) to African countries. Through detailed case study research of science-based health firms in South Africa, of the NIS health system of Ghana, and by comparing these data with data collected in Uganda and Tanzania, I shed light on these questions from an empirical perspective. I find that science-based health innovation is a complex field, and whilst institutions can help or hinder its viability, the current state of health innovation in SSA can be attributed primarily to individual entrepreneurs with strong networks, who are taking risks in a largely non-enabling environment. I find that, more important for innovation, is the ability to access global knowledge–through appropriate policies and strong partnerships–and the capacity to apply it locally. For this, tacit knowledge, or “learning-by-doing,”’ to respond to consumer demand and achieve regional product penetration, is vital. My results show that the traditional focus on knowledge - or science-heavy innovation - will simply not capture the true extent of health innovation in SSA countries. Furthermore, science-based health innovation is clearly not one thing, and it is, for example, important to understand how plant medicine innovation fit in. The aims, intentions, and impacts of African health research on the countries themselves are rather vague, which constrains innovation at all levels.

Policy making bodies are increasingly highlighting the important role innovation can play in African development─not only to spur economic growth but also to deliver locally relevant, affordable products and services to African populations. The health sector is one area where innovation is most needed; however, we know very little about the capacity of African countries to innovate in this area. At the same time, a range of conceptual questions have arisen in the academic literature as to the very definition of innovation in an African context, and specifically, the applicability of the National Innovation System (NIS) to African countries. Through detailed case study research of science-based health firms in South Africa, of the NIS health system of Ghana, and by comparing these data with data collected in Uganda and Tanzania, I shed light on these questions from an empirical perspective. I find that science-based health innovation is a complex field, and whilst institutions can help or hinder its viability, the current state of health innovation in SSA can be attributed primarily to individual entrepreneurs with strong networks, who are taking risks in a largely non-enabling environment. I find that, more important for innovation, is the ability to access global knowledge–through appropriate policies and strong partnerships–and the capacity to apply it locally. For this, tacit knowledge, or “learning-by-doing,”’ to respond to consumer demand and achieve regional product penetration, is vital. My results show that the traditional focus on knowledge - or science-heavy innovation - will simply not capture the true extent of health innovation in SSA countries. Furthermore, science-based health innovation is clearly not one thing, and it is, for example, important to understand how plant medicine innovation fit in. The aims, intentions, and impacts of African health research on the countries themselves are rather vague, which constrains innovation at all levels.

Athlete-centred coaching is proposed to enhance performance (Lyle, 2002), develop life skills (Kidman &amp; Lombardo, 2010), and prevent athlete maltreatment (Kerr &amp; Stirling, 2008). Despite the consistent recommendation, very little is known empirically about athlete-centred coaching, the extent to which it is implemented, or athletes&rsquo; experiences with this style of coaching. The purpose of this study therefore was to examine recently retired elite athletes&rsquo; perspectives on their most athlete-centred coach. Semi-structured interviews were conducted with eight male and female recently retired Olympians. The findings of this study provided mixed evidence for coaching behaviours characterized as athlete-centred coaching as defined within the literature. Specifically, at least half of the coaches did not use stimulating questions, one of the most central athlete-centred tenets. Explanations for the mixed findings are discussed and a continuum of athlete-centred coaching is proposed. Lastly, suggestions for future research and practical implications are presented.