This research examines the activation of the Rapid Response Team (RRT) through the Early Warning Score (EWS) model as a system of predicting adverse event outcomes. Modeling the input parameters of this system concluded that although conventional parameters associated with EWSs were predictive,the most predictive clinical and laboratory parameters are those of hematological and nephritic function, related to the model of multi-organ system decompensation. Upon examining different EWSs, the Modified Early Warning Score exhibited superior operating characteristics, however, it was not statistically different than other common EWSs from literature. Accounting for temporal features of the dataset shows that the International Normalized Ratio is the most predictive parameter, however, the hazard model exhibits poor discriminative ability. Therefore, clinically, parameters outside the EWS models are predictive of the outcomes in question, and their incorporation into future policy would serve to better inform the prevention of adverse events.

Purpose: Patients’ perspectives of informed consent for chiropractic care have not been investigated. This study explored how patients of chiropractors perceived the exchange of risk information during informed consent. Methods: Interviews were conducted with 26 participants, recruited from chiropractic clinics. Interview transcripts were analyzed using a constant comparative method of analysis. Findings: Participants experienced informed consent as an on-going process where risk perceptions were shaped throughout four distinct stages. In the first stage information acquired prior to arriving at the clinic for treatment shaped perceptions of risk. In the second stage participants assessed the perceived competence of the practitioners. Participants then signed the consent form and discussed the risks with t heir practitioner. Finally, they communicated with their practitioners during treatment to ensure their pain threshold was not crossed. Conclusion: These findings suggest that patients perceive informed consent as a social process involving on-going communication with their practitioners.

Introduction: Currently, there are no specific pharmacological treatments for sepsis-induced acute respiratory distress syndrome (ARDS). And mesenchymal stem cells (MSCs) have shown reparative potential in both sepsis and ARDS. Objectives: To determine the role of MSC administration in the modulation of pulmonary host-responses to sepsis via differential regulation of regulatory microRNAs (miRNAs/miRs). Methods: MicroRNA and mRNA profiling was performed to identify differential expression. Quantitative real time polymerase chain reaction (qRT-PCR), trans-endothelial electrical resistance (TEER) measurements, and luciferase activity assay were used. Results: MicroRNA expression was examined in Human Pulmonary Microvascular Endothelial Cells (HPMECs). One miRNA – miR-193b-5p, targets occludin, a tight junction protein associated with endothelial leakage. A specific regulatory relationship between miR-193b-5p and occludin was identified. The loss in endothelial integrity was rescued when miR-193b-5p inhibitor was transfected. Conclusion: miR-193b-5p is a suppressor of occludin. Studying transcriptional changes allows identification of therapeutically relevant mediators for ARDS/ALI treatment.

Introduction: Currently, there are no specific pharmacological treatments for sepsis-induced acute respiratory distress syndrome (ARDS). And mesenchymal stem cells (MSCs) have shown reparative potential in both sepsis and ARDS. Objectives: To determine the role of MSC administration in the modulation of pulmonary host-responses to sepsis via differential regulation of regulatory microRNAs (miRNAs/miRs). Methods: MicroRNA and mRNA profiling was performed to identify differential expression. Quantitative real time polymerase chain reaction (qRT-PCR), trans-endothelial electrical resistance (TEER) measurements, and luciferase activity assay were used. Results: MicroRNA expression was examined in Human Pulmonary Microvascular Endothelial Cells (HPMECs). One miRNA – miR-193b-5p, targets occludin, a tight junction protein associated with endothelial leakage. A specific regulatory relationship between miR-193b-5p and occludin was identified. The loss in endothelial integrity was rescued when miR-193b-5p inhibitor was transfected. Conclusion: miR-193b-5p is a suppressor of occludin. Studying transcriptional changes allows identification of therapeutically relevant mediators for ARDS/ALI treatment.

This study investigates the use of five broad accountability mechanisms by gathering the perceptions of charities involved in the Canadian effort to reduce under-5 mortality abroad. While annual deaths in children under the age of 5 declined from an estimate of over 24.0 million in 1960 to under 8.0 million in 2010, mortality reduction goals have been established and missed for decades. As worldwide economies worsen, the amount of funds available for development assistance can be expected to decrease. This study seeks to determine if having accountability mechanisms is perceived to improve organizational behaviour, results and/or reduce costs. It uses a mixed methods approach including: a literature review to gain an understanding of accountability, effectiveness, development and under-5 mortality; key informant interviews to gain an understanding of funders, charities and development; a survey to gather the information required to answer the research questions; and a multiple-case study to gain a better appreciation of how accountability is used and to gather evidence of survey responses. The study investigates: which accountability mechanisms charities have, why they have them and the associated accountability holders; standards body memberships; the relationship between accountability mechanisms and various organizational characteristics; and the perceived effects of accountability mechanisms on organizational behaviour, results and costs. The survey finds that: charities say that they adopt accountability mechanisms because it is a good management practice that is perceived to improve organizational behaviour and results while not incurring costs in excess of the benefits; charities are more likely to adopt accountability mechanisms due to internal pressures than external pressures; the use of accountability mechanisms increases with organization size; and there is a greater difference in use of accountability mechanisms between small and large charities than there is between medium and large charities. The multiple-case study confirms the survey results. This study fills a gap in the literature by providing a Canadian perspective on the use of accountability mechanisms and the relationships amongst them and their perceived effects on organizational behaviour, results and costs. As economic burdens increase, increased accountability may lead to improved results even with fewer dollars.

This study investigates the use of five broad accountability mechanisms by gathering the perceptions of charities involved in the Canadian effort to reduce under-5 mortality abroad. While annual deaths in children under the age of 5 declined from an estimate of over 24.0 million in 1960 to under 8.0 million in 2010, mortality reduction goals have been established and missed for decades. As worldwide economies worsen, the amount of funds available for development assistance can be expected to decrease. This study seeks to determine if having accountability mechanisms is perceived to improve organizational behaviour, results and/or reduce costs. It uses a mixed methods approach including: a literature review to gain an understanding of accountability, effectiveness, development and under-5 mortality; key informant interviews to gain an understanding of funders, charities and development; a survey to gather the information required to answer the research questions; and a multiple-case study to gain a better appreciation of how accountability is used and to gather evidence of survey responses. The study investigates: which accountability mechanisms charities have, why they have them and the associated accountability holders; standards body memberships; the relationship between accountability mechanisms and various organizational characteristics; and the perceived effects of accountability mechanisms on organizational behaviour, results and costs. The survey finds that: charities say that they adopt accountability mechanisms because it is a good management practice that is perceived to improve organizational behaviour and results while not incurring costs in excess of the benefits; charities are more likely to adopt accountability mechanisms due to internal pressures than external pressures; the use of accountability mechanisms increases with organization size; and there is a greater difference in use of accountability mechanisms between small and large charities than there is between medium and large charities. The multiple-case study confirms the survey results. This study fills a gap in the literature by providing a Canadian perspective on the use of accountability mechanisms and the relationships amongst them and their perceived effects on organizational behaviour, results and costs. As economic burdens increase, increased accountability may lead to improved results even with fewer dollars.

Shiga toxin-producing E. coli (STEC) comprise a group of pathogenic organisms that elaborate a family of protein exotoxins known as Shiga toxins (Stxs). Intestinal infection with these organisms may lead to hemorrhagic colitis and hemolytic uremic syndrome, a life-threatening condition characterized by thrombocytopenia, non-immune hemolytic anemia, and acute renal failure. Vascular endothelial damage is believed to be a key initiating event in Stx-mediated diseases. At the molecular level, these toxins depurinate human 28S rRNA and inhibit translation. In addition, at concentrations that only minimally affect global protein synthesis, they have been found to alter expression of specific target genes. To better understand the endothelial damage induced by Stx, we investigated the global effects of Stx on endothelial gene expression, and defined a specific group of genes whose expression was altered by the toxin. Of interest, the CXCR4/CXCR7/SDF-1 chemokine pathway, a pathway central to vascular biology, was activated by Stx. In vitro studies demonstrated that Stx enhanced both transcript levels of these molecules, as well as their association with ribosomes. To define the relevance of these findings in vivo, a mouse model was established and key changes were noted in plasma and tissue content of CXCR4/CXCR7/SDF-1 following Stx exposure. Inhibition of CXCR4/SDF-1 interaction decreased indices of endothelial activation and organ injury and improved animal survival. Importantly, in children infected with E. coli O157:H7, plasma SDF-1 levels were significantly elevated in individuals who progressed to hemolytic uremic syndrome. A second pathway critical to endothelial health and function is VEGF signaling. Of interest, our endothelial gene expression analyses revealed changes in this pathway in vitro. VEGF mRNA association with cellular polyribosomes increased following Stx treatment. Further studies in vivo demonstrated decreased cardiac function and blood pressure, and increased vascular permeability in specific tissues. VEGF, an important inducer of vascular permeability, increased in mouse plasma. Additionally, altered mRNA expression was observed in key organs, such as the kidney and heart, following Stx challenge. Inhibition of VEGF significantly improved survival of animals treated with Stx, indicating that VEGF plays a role in Stx-mediated pathogenesis. Moreover, in vitro studies demonstrated that Stx-mediated endothelial permeability was attenuated in the presence of a VEGF inhibitor. Taken together, these data indicate that E. coli-derived Stxs induce pathological changes in two pathways key to vascular biology. These pathways represent novel targets for the development of preventative and therapeutic strategies for complications associated with Shiga toxin-producing E. coli infection.

This study characterized the effects of two anti-diabetic drugs, a thiazolidinedione (TZD) and a Dipeptidyl Peptidase-4 (DPP-4) inhibitor on bone quality in a glucose intolerant mouse model. Bone quality in a DPP-4 -/- mouse model was also examined. Bone quality was evaluated through densitometry, mechanical testing and techniques to assess remodeling, structural and mineral properties. TZD treatment negatively affected trabecular mechanical properties in male, female and ovariectomized female (OVX) mice. Male mice exhibited the greatest effect due to TZD treatment with reduced vertebral vBMD, trabecular structure and bone formation. DPP-4 inhibitor treatment improved vertebral vBMD and trabecular architecture in female mice but improvements were lost in females following OVX. Male, female and OVX mice experienced increased trabecular mineralization due to DPP-4 inhibitor treatment. Genetic inactivation of DPP-4 did not produce a major bone phenotype in male and female mice but lead to reduced femoral geometry and mechanics in OVX mice.

Health system restructuring combined with the preferences of palliative care recipients to be cared for at home has lead to a shift in the delivery of care from the hospital to the home setting. An analysis was conducted on five main home-based palliative care health service components: home-based nurse visits, home personal support worker visits, home-based physician visits, ambulatory physician visits, and other ambulatory and home-based visits. First, we assessed the proportion of total cost associated with the main services at different time points over the palliative care trajectory. Second we examined the socio-demographic and clinical factors that predict the propensity and intensity of service use, using a two-part model. The results suggest that the greatest contributor to the total cost of home-based palliative care was personal support worker visits, followed by nurse visits. The regression analysis revealed that patient age as well as functional status most often predicted health service use.

Background: Variation exists in quality of life (i.e., utility) estimates depending on the utility elicitation method utilized. Using the EQ-5D, VAS, and HUI-III, the aim of this thesis was to determine whether these measures adequately capture HRQOL in a CRC population and assess the relationship between utility estimates generated. Methods: A mixed methods study design was employed to collect health status scores and interview data from a sample of 50 CRC patients in Toronto, Ontario. Results: Mean utility scores between the EQ-5D and HUI-III were identical at 0.76 (95% CI), with an overall VAS score of 0.72 (95% CI). Conclusion: The fact that the EQ-5D and HUI-III resulted in identical mean utility scores provides assurance for future studies using these tools in CRC. However, many factors that CRC patients identify as important to their HRQOL are not captured by these instruments. These findings have implications for informing economic evaluations.