VictorJuiz/thesis huggingface dataset:
The Role of Thioredoxin Interacting Protein (TxNIP) in the Development of Diabetic Nephropathy

Thioredoxin-interacting protein (TxNIP), an endogenous inhibitor of the thiol oxidoreductase - thioredoxin, is augmented by high glucose (HG) and promotes oxidative stress. The objective of the studies in this thesis was to examine whether TxNIP contributed to diabetic nephropathy by promoting the generation of mitochondrial and total ROS and regulating the expression of Nox4. To test this, in Chapter 2, I employed mouse mesangial cells (MC) cultured from wild-type C3H and TxNIP-deficient Hcb-19 mice treated with HG. C3H MC exposed to HG elicited a significant increase in cellular and mitochondrial ROS, as well as Nox4 protein expression and NADPH oxidase activation, while Hcb-19 MC showed no response. Additionally, I revealed that the failure of HG-induced Hcb-19 MC to elevate ROS was not due to its enhanced ROS-scavenging property, but because of its inability to synthesize ROS. These results were verified with adenovirus-mediated overexpression of TxNIP in Hcb-19 MC and TxNIP knockdown with siRNA (siTxNIP) in C3H. In Chapter 3, I examined the role of TxNIP in the pathogenesis of diabetic nephropathy (DN) in vivo. For this, control TXNIP+/+ (WT), TxNIP-/- (KO) TxNIP+/- (HET) mice were rendered equally diabetic with low dose STZ. In contrast to WT, diabetes did not increase hallmarks of DN such as proteinuria, effaced/loss of podocytes, thickened glomerular basement membrane, glomerular TGF-β1, collagen IV and fibrosis (immunohistochemistry, iHC) in KO mice. Similarly, only WT diabetic mice showed a significant rise in oxidative stress (Nitrotyrosine iHC, urinary 8-hydroxy-2-deoxy-guanosine) and Nox4 protein/mRNA levels, and in inflammation (IL-1β mRNA, F4/80 iHC). Furthermore, in HG-treated cultured human podocytes, siTxNIP abolished the increased mitochondrial O2- generation and apoptosis. Chapter 4 investigates, in preliminary experiments, the cause of TxNIP-deficient cells to exhibit reduced mitochondrial glucose oxidation and ROS production. Metabolic profiling and bioenergetics of HG-treated C3H and Hcb-19 cells indicated higher glycolytic intermediates but diminished mitochondrial respiration in Hcb-19 cells, indicating an involvement of TxNIP in driving the TCA cycle for glucose oxidation and generating mitochondrial ROS. Taken together, these data indicate a direct contribution of TxNIP in the pathogenesis of DN by mediating a HG-ROS pathway.

Keywords: Diabetic Nephropathy
Mitochondria
Reactive Oxygen Species
Thioredoxin Interacting Protein
Advisor: Fantus, Ivan George
Canadian Solo Trombone Recital Repertoire: An Annotated Bibliography

The first major Canadian compositions for solo trombone were written in the 1950s, a time when Canadian concert music composers began to flourish. Since then, more than 240 Canadian works for solo trombone (including alto, tenor and bass) have been composed. This annotated bibliography is a comprehensive examination of 135 of these works, delimited to include those composed in a 60-year period from 1952 to 2012, in two subsets of the repertoire typically performed in a standard recital: music for unaccompanied trombone, and music for trombone with piano accompaniment. The performance and/or study of Canadian music is a curricular requirement in many Canadian school music programs, and the performance of Canadian works is often mandatory for recitals and solo competitions. An annotated bibliography is an important resource that allows performers, teachers and students to identify and evaluate a body of musical works. The present document responds to the demand for such a resource by musicians searching specifically for Canadian solo trombone music, and significantly expands the scope of such previous research. The works chosen for inclusion in this study are presented in five sections based on instrumentation (divided by alto, tenor or bass trombone, and by unaccompanied solos or works with piano accompaniment – at the time of writing there were no unaccompanied alto trombone solos). The information provided for each work includes point-form details (such as difficulty level, pitch range, etc.), more detailed analyses (of technical and musical characteristics, and pedagogical/performance value), supplementary information (such as premiere details, information on recordings, etc.), and musical examples. Appendices include six indexes of the included repertoire sorted according to anticipated common search parameters, a discography of CD recordings of repertoire included in the study, and publisher and composer contact information to help increase the works’ availability. This research has been undertaken with the goal of providing an indispensable resource that allows students, educators and performers to evaluate any work in the included repertoire, which will ultimately result in more frequent performances of this music, and perhaps even stimulate the composition of new works.

Keywords: bibliography
Canadian composers
Canadian music
compositions
repertoire
trombone
Advisor: Walter, Cameron
Factors Influencing Quality of Emergency Department Nurse Shift Handover

Nurse-to-nurse shift handover communication is an essential exchange of information that occurs at shift change with the purpose of ensuring that incoming nurses have necessary information to take responsibility for their patients and to provide high quality, safe care. Poor quality shift handover has been associated with adverse outcomes such as incorrect treatment, delays in diagnosis, increased length of stay, and both nurse and patient dissatisfaction. Despite an increase in the amount of handover related literature, little is known about factors that influence quality of nurse-to-nurse shift handover. The Emergency Department (ED) environment presents unique challenges for high quality handover communication as a result of unpredictability, increased volumes and rapid patient turnover. The purpose of this study was to test and refine a conceptual model of 18 factors hypothesized to influence quality of nurse-to-nurse shift handover communication in the ED. This study was conducted using a cross-sectional survey design. A total of 650 ED nurses across the Province of Ontario were invited to participate in this study. The survey included questions about demographic information as well as items and instruments to measure concepts such as staffing, triage, relationships, safety climate, interruptions, job stress, fatigue and handover format. The hypothesized conceptual model was tested using backwards stepwise multiple regression with data from a final sample of 227 participants. Following multiple regression analysis, four statistically significant predictors were retained in the final model. Together, triage flow, intrusions, safety climate and relationships explained 34% of the variance in handover quality (p

Advisor: Tourangeau, Ann
What Factors become Priorities in the Decision-making Process that Influence Administrators of Campus Space to Choose one Type of General-use Classroom over Another?

Current best practice education and design research indicated that flexible general-use teaching spaces, not inflexible row-and-column classrooms, improved student success. Research indicated inflexible classrooms inhibited progressive models of pedagogy by discouraging active learner-centered methods. The focus of this study was the inflexible general-use classroom that was the standard method of teacher-centered education. In this qualitative exploratory, descriptive case study I interviewed administrators in three Ontario Colleges of Applied Arts and Technology who were in various ways responsible for the `delivery of classrooms'. I extracted factors that influenced the decisions of participants to prioritize the inflexible classroom model and looked for reasons why the transition to supportive flexible space had been slow to emerge. Factors that stalled space changes included issues of space utilization, faculty preference, technology fatigue and effort. I also explored the colleges' historic use of inflexible classrooms, the characteristics that have maintained their use and barriers that have prevented change as well as the historic and current environmental context in which decisions about classrooms are made. The results show that administrators, for the most part reflect their learner-centered Strategic Plans. However, I discovered a gap in their understanding that inflexible teacher-centered classrooms support one pedagogy model where learner-centered pedagogies are supported by physical spaces that promote flexibility and movement. To ensure inflexible classrooms remained, administrators repeated factors containing misinformation that supported the single priority; to make the most of funding through maximization of space and schedule. Slow transition through insufficient momentum was possible because administrators did not have the design experience or skills to know better. They formed alliances and used factors to argue for the continuance of the row-and-column general-use classroom. This continuance was most evident in two of the three subject colleges. One college in the study was contemplating change while the other two were not. Emergent results showed that although best practices in design and education provided evidence that change from inflexible to flexible general-use classrooms could improve student success, environments continued to adhere to the historic standard row-and-column configuration. I hope to create the momentum for change from inflexible to flexible environments required leadership.

Keywords: Flexible classroom
Inflexible classroom
Advisor: Dietsche, Peter
Transition to Adult Health Care for Youth with Disabilities: Implications for Health Policy

This dissertation contains three papers, each on a different aspect of transition to adult healthcare for youth with disabilities. The overall aim of this dissertation research was to identify system level health care transition strategies for youth with disabilities, determine the amount and degree to which Canadian jurisdictions reflect those transition strategies in government posted documents and policy, and to understand the current status of national healthcare transition policy in Canada, the UK, and Australia. The first paper describes the results of a scoping review identifying system level strategies for policy addressing continuity of care and care transitions to adult health care for youth with disabilities. The second paper is an analysis of the match of those system level strategies to current Canadian provincial and territorial government documents and policies related to transitions to adult health care for youth with disabilities. The third paper is an analysis of international alignment and variance between Canada, the UK and Australia with respect to transitions related government policies and direction. Collectively, this dissertation research found that system level strategies in support of continuity of care and transitions to adult health care for youth with disabilities exist. The challenge of achieving effective health care transition for youth with disabilities moving from the paediatric to adult health systems is identified as an area of importance by paediatric and adult health care service providers, clients and families. However, there are considerable variances in government attention and action in addressing the issue of health care transition, and thus, variability in existing policy inclusive of transition strategies across Canada, the UK and Australia. The combined findings of these studies suggest that health system strengthening, in the area of transitions to adult health care for youth with disabilities, should be supported through health policy implementation and/or change. Policy addressing transitions to adult health care for youth with disability could drive change through: (a) bringing awareness to the issue; (b) mitigation of client-specific and system wide impacts of ineffective health care transition; and through (c) the promotion of accountability mechanisms for effective continuity of care for youth with disabilities.

Keywords: disability
health policy
transition
youth
Advisor: Verrier, Mary M
Landry, Michel D
Mobilizing Research Knowledge through Social Networks

Networks have been deemed an important knowledge mobilization (KMb) activity; however, much KMb network research fails to acknowledge the ways that relational linkages among members mediate its work. The purpose of this study is to investigate the ways in which patterns of interaction among members of an implementation support program mediate KMb activities in support of evidence-informed policy-making. This was a bounded sample where coaches (N=6) and Mental Health Leaders (MHLs; N=31) from the first two cohorts of the program were invited to participate. This descriptive case study used a sequential, explanatory mixed methods design. Phase one of the study included a survey, administered online (response rate = 97%), that included social network and attribute-based questions. Network data were analysed at multiple levels using UCINet, and SPSS was used to conduct appropriate descriptive and inferential analyses. Phase two consisted of interviews with all five coaches, and six MHLs selected based on phase one degree centrality findings. The constant comparative method was applied to the analysis of the interviews. Each network exhibited low levels of activity and reciprocal ties, and the patterns of interaction in each focused on a subset of people. Certain individuals stood out as dominant sources of research/advice/influence. Overall, coaches received significantly more relations than MHLs; however, there were two MHLs who were often sought out more than other coaches. Attributes positively associated with indegree centrality included relational capital, level of research use, and research experience. People very rarely facilitated relationships among their otherwise unconnected colleagues, and the brokering of research knowledge appeared to focus on direct connections typically maintained through the formal program. An online forum, program coaches and resources, capacity-building activities, research literacy and community were considered facilitators of KMb, whereas organizational structure, tension among system priorities, and external groups were perceived as constraints. This study describes an innovative KMb model where formal events mattered most and the key players were not always coaches. The broader context of the program mediated KMb activities, where it was not only the people within the network, but also the resources and opportunities available within it that connected research and practice.

Keywords: evidence-based policy
intermediaries
knowledge mobilization
school districts
social networks
Advisor: Anderson, Stephen E
Managing Perishability in Service Operations

We study three problems in service operations where either the supply or demand is perishable. In the first chapter, we study a perishable inventory system for items whose quality deteriorates in time, e.g., blood products. Specifically, we assume that supply and demand are driven by independent Poisson processes, units have a constant shelf-life, and unsatisfied demand is lost. We consider a threshold-based allocation policy that trades off the age and availability of allocated units. We characterize the sojourn time distribution of units in inventory and evaluate the performance of the threshold policy in terms of the distribution of the age of allocated units and the proportion of outdates and lost demand. Our numerical results demonstrate the importance of system parameters on the performance of the policy and identify important properties of the distribution of the age of allocated units. In the second chapter, we study the performance of certain practical ordering and allocation policies in reducing the age of transfused blood in hospitals while keeping the outdate and shortage rates low. We develop a data-driven (evidence-based) simulation model based on the operations of the blood bank of an acute care hospital in Hamilton, Ontario. We use empirical data to validate our model and estimate its inputs. The results suggest that by properly adjusting the ordering and allocation policies at the hospital level, a significant reduction of issue age could be achieved, without compromising availability or resulting in excessive outdates. In the third chapter, we study the rational abandonment behavior of utility-maximizing customers in the context of an observable priority queue, and identify novel pricing implications. We first characterize the equilibrium abandonment strategy of low-priority customers. We then consider pricing as a means to control the abandonment behavior and investigate its implications on system welfare and firm revenue. A distinguishing feature of our model is that in the presence of abandonment the timing of payment matters. We show that the welfare can be maximized using only a single fee charged upon service completion. In contrast, revenue maximization generally requires a combination of both an entrance and a service fee.

Keywords: Perishable inventory management
Pricing
Queueing theory
Rational abandonment
Service operations
Stochastic modeling and control
Advisor: Berman, Oded
From Genes to Communities: Effects of Habitat Change over Space and Time on Fish Diversity

Rapid habitat changes, caused by human activities within the last century, have resulted in biodiversity loss at all levels of biological organization. In light of these changes in the recent past, this thesis explores some of the effects of such changes on fish and wildlife populations, species, and communities using theoretical and empirical approaches. Using simulated genetic data, I first investigated the effects of recent population connectivity changes on the reliability of genetic inferences about connectivity. I found that, when connectivity has declined in the recent past, commonly-used genetic methods for estimating connectivity tend to overestimate current connectivity and underestimate historical connectivity. This could lead to incorrect inferences about gene flow and have negative consequences for conservation of populations and species at risk. Next, I conducted two empirical studies focusing on Canadian fishes that are threatened by habitat changes, making them excellent systems to investigate the effects of habitat change on their ecology and evolution. For Sockeye salmon populations in the Fraser River, I found that hydroelectric dams have fragmented habitats, changed connectivity among populations, and had significant effects on the ecology and evolution of some populations. Based on molecular data, I found evidence indicating very early differentiation between anadromous and resident forms of Sockeye salmon within one reservoir, where a dam has prevented the historically anadromous salmon from migrating to the ocean. In a second case study, on freshwater fish communities in northern Canadian lakes that were thought to be depauperate in biodiversity, I found higher species diversity and fish biomass than expected based on species-energy theory. My analyses indicate that fish diversity and biomass in northern lakes are not substantially lower than southern Canadian lakes. Thus, northern lakes could be important reserves of coldwater fish in light of climate change. In summary, I examined some effects of habitat change on populations, species and communities, and my thesis highlights: (i) areas for the improvement of methodologies and inferences used by conservation biologists; and (ii) specific northern communities of Canadian fishes that warrant attention to preserve Canadian fish diversity.

Keywords: Fragmentation
Genetic connectivity
Life-history
Northern Canada
Sockeye Salmon
Species-Area curve
Advisor: Rodd, Helen
Shuter, Brian J
A Computational Model of Systems Consolidation: Optimizing Memory-guided Behavior using Abstracted Hippocampal and Cortical Networks

Learning is not a isolated event, as nearly every encoding event occurs on a backdrop of previous knowledge. This idea is tightly intertwined with that of memory consolidation, which is a concept that describes the fate of memories post-encoding. After the brain encodes some episode, the encoded information undergoes a transition from hippocampal dependence to cortical dependence. Contemporary memory consolidation theories emphasize the nature of the computations that occur during this transfer, pointing to the extraction of statistical regularities, or the formation of schemas, as critical components. The work presented in this thesis analyzes memory consolidation from a computational perspective. Firstly, it describes necessary conditions for the extraction of statistical regularities across individually learned episodes, demonstrating that a consolidation-like mechanism best captures this phenomenon. Next, it probes a possible purpose of memory consolidation within a two-memory system, showing that a joint hippocampal and cortical network optimizes memory-guided behavior in a foraging-like task. Finally, some anatomical evidence is explored within the context of a major tenet of memory consolidation, namely the slow changes in interconnectivity between distributed neocortical regions during the consolidation period. The work presented in this thesis constitutes a highly comprehensive model of memory consolidation and provides a basis for further inquiry into the nuances of consolidation phenomena, such as the effects of memory interference, neurogenesis, and forgetting.

Keywords: computational model
episodic memory
hippocampus
learning
memory consolidation
semantic memory
Advisor: Frankland, Paul