Objective: To describe the walking characteristics of a sample of ambulatory subjects with sub-acute incomplete spinal cord injury (iSCI). Methods: 52 subjects were included in a secondary analysis of clinical and spatiotemporal measures of walking. The study sample was described as a whole and subsequently divided into subgroups on the basis of 3 clinical factors (etiology, severity, and neurological level of injury) and 4 gait factors (gait aid, velocity, symmetry, and variability). Results: Clinical and spatiotemporal parameters were highly variable across the study population. Sub–groups with unique gait features were best identified by velocity and variability. Conclusions: Spatiotemporal measures of walking provide augmented description of walking in the sub-acute iSCI population. Sub-grouping by gait factors warrants further investigation with respect to their ability to act as predictors and modifiers of treatment effect.

Aerobic exercise such as cycling is known to elicit a post-exercise hypotensive (PEH) response. However, it is not known if swim exercise produces a similar effect in normotensive individuals. We tested the hypothesis that an acute bout of swimming would elicit a PEH response that is less compared to an equivalent bout of cycling. 10 trained and 11 untrained normotensive (SBP/DBP < 120/80 mmHg) individuals (23±1 years) underwent 30 min intensity-matched cycling and swimming sessions to assess changes in BP and cardiovascular responses. While PEH was similar between modalities within groups, the magnitude and temporality of change in BP following swimming was significantly different (p < 0.01) between groups, with untrained participants showing a significant PEH response. Attenuation of PEH in trained individuals was reflective of a significant increase in sympathetic outflow and slower vagal reactivation, suggesting training in an aquatic environment leads to alterations in post-exercise BP regulatory mechanisms.

This thesis explores health technology innovation within indigenous enterprises in China, India, and Brazil. The main discussions are presented in five papers/manuscripts. The first is a case study of Brazil’s health biotechnology sector. It concludes that systemic tensions between the country’s public and private sectors may be detracting from its overall innovative success. The second paper gauges vaccine and medicinal innovation within enterprises in the stated countries by analyzing new technologies in their pipelines or on the market. It concludes that that a growing number of health enterprises in these countries are tackling more technologically challenging and costly innovations. The third paper explores how national institutions and industry globalization interact to shape commitments to new drug and vaccine innovations by enterprises in the three countries. It concludes that; a) the introduction of pharmaceutical product patent regimes has had a modest impact on entrepreneurial attempts to develop new technologies, b) key challenges that diminish patent incentives tend to be institutional in nature and, c) the increasingly globalized nature of health product innovation limits what countries can achieve independently. The fourth paper analyzes key issues and trends in health biotechnology firms’ transition to innovation in China, India, Brazil, and South Africa. It concludes that this transition often entails greater integration into the global system. The fifth paper ponders the implications for global health of the emerging market firms’ transition to innovation. It concludes that these enterprises have the potential to simultaneously address global health needs while exploiting global markets, provided support mechanisms are put in place to enable product development for the poorest market segments. This research suggests that to succeed in biopharmaceutical innovation, nations need to adjust scientifically, sectorally and globally all at the same time. Also, that national governments and the global health community need to enhance engagement of emerging market enterprises in related efforts.

Bone disease and fractures are common in men and women with chronic kidney disease (CKD). The etiology of fractures in CKD is multi-factorial; identifying risk factors for fracture is important in CKD, so that patients who are at high risk can be treated before they fracture. The majority of studies have focused on risk factors associated with fracture in patients with stage 5 CKD on dialysis–there is a need for studies in pre-dialysis CKD. Three novel, non-radiological factors were assessed in 211 men and women with stage 3-5 CKD: cytokines osteoprotegerin (OPG) and receptor activator of nuclear factor kappa beta ligand (RANKL); tests of neuromuscular function including the timed up and go (TUG), 6 minute walk (6MW), and grip strength; and daily activity levels by accelerometry. Fractures were defined as self-reported low-trauma fractures since the age of 40 and/or prevalent vertebral fractures identified by morphometry. Logistic regression and receiver operating characteristic curves (ROC) were performed using STATA version 11.0. Those with fractures had elevated OPG compared to those without fractures (9.37±4.23 vs. 8.13±3.04 pmol/L, p=0.03), however, after adjusting for age OPG did not differ by fracture status. After adjusting for age, weight, and sex, impairments in both the TUG and 6MW tests were associated with fractures (TUG odds ratio (OR): 1.68, 95% confidence interval (CI): 1.40-2.02; 6MW OR: 0.53, 95% CI: 0.52-0.54). The diagnostic tests characteristics of the TUG and 6MW tests were excellent; both could discriminate fracture status (TUG AUROC: 0.90, 95% CI: 0.84-0.95; 6MW AUROC: 0.87, 95% CI: 0.84-0.95). Overall, subjects were primarily sedentary. After adjusting for stage of CKD, increased sedentary activity and decreased light intensity activity could discriminate fracture status (sedentary AUROC: 0.72, 95% CI: 0.56 to 0.87; light activity AUROC: 0.71, 95% CI: 0.55 to 0.87). In conclusion, non-radiological, novel factors including the TUG, the 6MW, and daily activity, but not OPG or RANKL were able to discriminate fracture status in men and women with stage 3-5 CKD.

A qualitative research study was conducted with people who had participated as healthy subjects in phase I drug trials at commercial research facilities, in order to develop a better understanding of their perspective regarding research participation. The participants were recruited using online advertisements posted on the University of Toronto student website (www.my.utoronto.ca) and NOW Magazine online. Thirty-one subjects were interviewed. The audiotaped interviews were transcribed and analyzed using grounded theory methods. A grounded theory was developed that describes the process of participation and the main factors affecting the experience of participation, from the perspective of healthy subjects. The theory, called Making Participation Work, explains how healthy subjects frame participation as an income earning opportunity, and how this framing shapes their behaviour with regard to participation. Participants expressed a range of attitudes about the experience of participation, from very positive to very negative. The main factor affecting the experience is the perceived net burden, which is in turn affected by the degree to which subjects find personal control over their participation. Net burden and finding personal control were both affected by the degree to which subjects felt valued by research staff, and by whether subjects had trust in the research enterprise. Although subjects framed participation as work, the relationship with the study doctors and nurses was viewed as clinical. Most subjects are generally trusting that participation in phase I drug trials is safe. These findings suggest that models of research participation assuming participation motivated by altruism or potential therapeutic benefit cannot accommodate the attitudes and behaviours of healthy subjects in phase I drug trials. New models must be developed which account for the framing of participation as work, while being sensitive to the trust that healthy subjects place in the research enterprise.

Introduction: In the palliative care literature there has been debate over the occurrence and the desirability of the rationalization of palliative care. The discussion is based mostly on opinion, anecdote and argument. Little discussion is based on research, or is specific to Canada. Considering this question of rationalization, this thesis asks whether Canadian palliative care ethics has changed, and if so in what regard. Methods: Discourse analysis was used to evaluate texts and interviews from early and late Canadian palliative care. Based on expression, influence and comprehensiveness, two key texts were identified from each of the early and late periods of palliative care. Ten interviews were conducted with Canadian palliative care pioneers practicing across these periods. These interviews were semi-structured, and were based on the background literature and the textual analysis. Results: Analysis of the textual data led to the descriptive themes of person, profession and well-being. These themes, when compared across the early and late periods, generated three themes of process. Analysis of the interview data generated three similar themes of process. The themes of process from the textual and interview data were similar enough to generate three overall themes of process – routinization, medicalization, and professionalization.

Introduction: In the palliative care literature there has been debate over the occurrence and the desirability of the rationalization of palliative care. The discussion is based mostly on opinion, anecdote and argument. Little discussion is based on research, or is specific to Canada. Considering this question of rationalization, this thesis asks whether Canadian palliative care ethics has changed, and if so in what regard. Methods: Discourse analysis was used to evaluate texts and interviews from early and late Canadian palliative care. Based on expression, influence and comprehensiveness, two key texts were identified from each of the early and late periods of palliative care. Ten interviews were conducted with Canadian palliative care pioneers practicing across these periods. These interviews were semi-structured, and were based on the background literature and the textual analysis. Results: Analysis of the textual data led to the descriptive themes of person, profession and well-being. These themes, when compared across the early and late periods, generated three themes of process. Analysis of the interview data generated three similar themes of process. The themes of process from the textual and interview data were similar enough to generate three overall themes of process – routinization, medicalization, and professionalization.

This study examined right-ventricular-pulmonary arterial (RV-PA) coupling and pulmonary vascular mechanics during acute exercise in 12 middle-aged men with a long-standing history of endurance training. Subjects underwent simultaneous right-heart catheterization and echocardiography, with measures obtained at steady state heart rates of 100, 130 and 150 beats/min. Subjects were highly trained and displayed RV remodeling of endurance-trained athletes. During exercise at 100 beats/min, systolic, diastolic, and mean pulmonary artery pressure increased significantly from rest, as did pulmonary capillary wedge pressure. The slope of pooled mean pulmonary pressure indexed to cardiac output was 1.436 mmHg⋅min-1⋅L-1 with a distensibility index of 0.112 ± 0.048 mmHg-1. The pulmonary arterial elastance-RV end-systolic elastance ratio (Ea:Ees) decreased from rest to exercise at 130 beats/min (P < 0.01). These results suggest that Ea:Ees becomes favourable for RV function during exercise, indicative of a pulmonary vasculature that is highly distensible and well matched to RV output.

In Ontario, the organs of deceased donors are usually allocated to those recipients who are ranked highest on the province’s waiting list for transplant surgery. However, on rare occasion, a donor, or the donor’s family, will request that an organ be given to a designated recipient or designated group of recipients. The ethical acceptability of these so-called “directed donations” of organs from deceased donors is debated in the transplant literature. The purpose of this study was to elicit the views of a group of transplant professionals in Ontario on the question, “Under what circumstances, if any, should a donor or the donor’s family be allowed to choose the recipient of the organ?” Qualitative in-depth interviews were conducted with 14 Ontario transplant professionals from a range of clinical disciplines. An analysis of these interviews revealed several practical and ethical considerations that the transplant professionals believed to be important in assessing the acceptability of directed donations.

In Ontario, the organs of deceased donors are usually allocated to those recipients who are ranked highest on the province’s waiting list for transplant surgery. However, on rare occasion, a donor, or the donor’s family, will request that an organ be given to a designated recipient or designated group of recipients. The ethical acceptability of these so-called “directed donations” of organs from deceased donors is debated in the transplant literature. The purpose of this study was to elicit the views of a group of transplant professionals in Ontario on the question, “Under what circumstances, if any, should a donor or the donor’s family be allowed to choose the recipient of the organ?” Qualitative in-depth interviews were conducted with 14 Ontario transplant professionals from a range of clinical disciplines. An analysis of these interviews revealed several practical and ethical considerations that the transplant professionals believed to be important in assessing the acceptability of directed donations.