VictorJuiz/thesis huggingface dataset:
Using Laboratory-Confirmed Outcomes to Study Pediatric Influenza and Influenza Vaccine Epidemiology in Ontario

Annual epidemics of seasonal influenza continue to cause substantial morbidity in young children. Influenza is among several respiratory viruses that cause illness in children, in addition to a large burden on the healthcare system and society, but is the only one for which a vaccine is available. In this dissertation, I present three studies regarding the epidemiology of influenza in children under the age of five years using a novel approach of linking laboratory and health administrative data in Ontario. In a systematic review and meta-analysis of children presenting to healthcare who are tested for influenza, I found that 20% (95%CI 15%-25%) have laboratory-confirmed influenza, with variation across subgroups. I found that influenza represents a large overall burden of disease and a substantial proportion of healthcare encounters for respiratory illnesses. In a retrospective cohort study, I compared the characteristics, outcomes, and relative severity of illness of children who were hospitalized and tested for influenza A, influenza B, and respiratory syncytial virus (RSV) and were positive for only a single virus. I found that in-hospital outcomes and post-discharge healthcare utilization in children with no identified comorbidities were similar by virus type, but post-discharge healthcare utilization was higher for those with influenza in those with underlying comorbidities. I observed similar severity of illness, based on in-hospital outcomes, and cost of hospitalization between viruses. In a test-negative study, I estimated vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations in children aged 6-59 months for the 2010-11 to 2013-14 seasons. I found that overall, VE was 51% (95%CI 38%-61%) for any vaccination, with variation by vaccination status (full vs. partial), season, age group, and subtype. These results indicate that large numbers of pediatric hospitalizations resulting from influenza infection could be prevented by promoting seasonal influenza vaccination each year. Overall, these results contribute to our understanding of pediatric respiratory viruses in Ontario, with each individual chapter adding to our knowledge regarding burden, severity, and prevention of influenza infection. These results can inform families, clinicians, public health practitioners, and policy makers in order to help reduce the impact of annual influenza infection in young children.

Keywords: epidemiology
influenza
pediatric
respiratory viruses
vaccine effectiveness
Advisor: Kwong, Jeffrey C
Contributions in Uncertainty Quantification Towards Reliability-based Rock Engineering Design

This thesis contributes to two distinct but related problems in contemporary rock engineering design which arise in the context of developing limit states design (LSD) protocols. In doing so, it identifies the discrepancies between geotechnical limit states design standards and customary rock engineering design procedures. These discrepancies are shown to be classified as (i) difficulties regarding definition of limit state functions stemming from model uncertainty, and (ii) parameter uncertainties stemming from lack of sufficient quantitative data. With regards to (i) above, this thesis demonstrates the existence of a significant component of neglected and unquantifiable model uncertainty in rock engineering, embodied in the form of various subjective-qualitative schemes (e.g. RMR, Q and GSI) commonly used in rock engineering. We suggest that the term “nebulous models” better describes the role of such schemes in engineering design, and discuss how their common application is a major obstacle to achieving rock engineering LSD, overcoming which requires community-wide efforts and a fundamental change in mindset. This thesis continues to discuss (ii) above in more detail. We introduce Bayesian data analysis (BDA) which allows logical augmentation of data with information from other sources (i.e. relevant historical data and expert knowledge) as a potential solution to the problem of limited data in rock engineering. Limiting our investigation to analysis of intact rock strength data, we develop Bayesian regression models that accommodate variability of strength data, and characterize the to-date neglected associated strength parameter uncertainties. We particularly address simultaneous analysis of tensile and compressive strength data. Furthermore, we propose a hierarchical Bayesian model for meta-analysis of rock strength data which results in shrinkage of uncertainty of estimated parameters. We further discuss how the results of this model may be used to augment future data. Also, this thesis develops a quantile regression model for obtaining strength curves that comply with LSD standard definitions of characteristic values. Finally, Bayesian regression analysis is used to reveal and characterize a neglected statistical property of strength of strongly anisotropic rock, namely, unequal variance with respect to loading direction. This thesis concludes with suggestions for the research required to further develop rock engineering LSD.

Keywords: Bayesian data analysis
Intact Rock Strength
Limit States Design
Reliability-based Design
Rock Engineering Design
Uncertainty Quantification
Advisor: Harrison, John P
A population-based evaluation of long-term outcomes following major burn injury

Introduction: Advances in critical care and the regionalization of burn care have resulted in a significant decrease in mortality after burn injury such that most burn-injured patients are expected to survive. This thesis aimed to evaluate and characterize long-term outcomes following major burn injury. Methods: Using linked health administrative data, we identified adults who sustained major burn injury during 2003-2014. First, we evaluated temporal changes in the incidence and in-hospital mortality of burn injury. We then estimated five-year risk-adjusted rates and principal causes of emergency department visits and readmissions. A self-matched longitudinal cohort study was performed to compare rates of mental illness-related healthcare utilization in the 3 years before and after burn. Finally, a matched cohort study was performed to estimate 5-year mortality after burn. Results: The incidence of burn injury remained stable over time, and significant reductions in the overall in-hospital mortality rate occurred; the odds of death in 2010-2013 were significantly lower than 2003-2006 (odds ratio (OR) 0.39, 95% CI 0.25-0.61). In the five years after discharge from the index burn admission, 70% of patients had >1 emergency department (ED) visit, and 30% had an unplanned readmission. The principal cause of healthcare utilization was unintentional injury, followed by mental illness and respiratory disease. Patients who received burn center care had significantly lower rates of ED visits (rate ratio 0.64, 95% CI 0.56-0.73) and readmissions (hazard ratio 0.77, 95% CI 0.65-0.92). Burn injury was not associated with a higher rate of mental health visits compared to the pre-injury period (RR 0.97, 95% CI 0.78-1.20), but was associated with a two-fold increase in self-harm (RR 1.95 (95% CI 1.15-3.33). Five-year mortality after burn injury was 11%, compared to 4% among matched controls. The hazard ratio was greatest during the first year after discharge (HR 4.15, 95% CI 3.17-5.42). Conclusions: Burn injury confers a physical and psychological impact up to five years after discharge, associated with high rates of healthcare utilization and increased late mortality compared to matched controls. Further development of consolidated and focused burn care, and improved mental healthcare, offer an opportunity to improve outcomes after burn injury.

Keywords: burns
epidemiology
health services research
outcomes
Advisor: Nathens, Avery B
Jeschke, Marc G
Cooperative Interference Mitigation in Wireless Cellular Networks

In this thesis, we explore potentials of cooperative communication at receivers' side in the downlink of wireless cellular networks for interference mitigation and signal enhancement. We investigate two regimes of latency and reliability of communication: one for providing high long-term average user rates for supporting a quality of service that is suitable for human visual and auditory perception, and the other for providing an ultrareliable low-latency machine-type wireless communication for streaming information in control applications. We consider three different models of cooperative communication. First, we study deploying a multi-antenna relay node that provides a nearby cell-edge user with extra dimensions over an out-of-band relaying link. We model this scenario by a Gaussian multiple-input multiple-output (MIMO) relay channel with correlated noise across relay and destination antennas, and analyze the capacity of this channel. This type of relay deployment is most effective when the number of receive antennas is small and the number of relay antennas is large enough. Second, we study deploying a multi-antenna half-duplex amplify-and-forward relay node that simultaneously provides multiple cell-edge users with extra dimensions. We show that the optimized relaying significantly improves the long-term average rates of cell-edge users, even after accounting for the extra bandwidth required for half-duplex relaying, provided that the relay is equipped with sufficiently many antennas. Third, we study cooperation among receivers for combating fading and mitigating interference for ultrareliable low-latency wireless communication. We consider multiple interfering broadcasts from controllers to their corresponding actuators. The recently-proposed Occupy CoW protocol efficiently exploits the spatial diversity of distributed receivers for combating deep fading. It consists of two consecutive phases: the broadcast phase and the cooperation phase. However, it avoids interference by orthogonalization; hence, its required bandwidth for achieving ultrareliability is not scalable in network size. We observe that full frequency reuse in the broadcast phase with successive interference cancellation notably improves the scalability of this protocol. We propose two schemes depending on whether interference cancellation or interference avoidance is implemented in the cooperation phase, and show that both outperform Occupy CoW, each in its own preference region.

Advisor: Yu, Wei
'Borders...Are No Longer at the Border': High-skilled Labour Migration, Discourses of Skill and Contemporary Canadian Nationalism

This dissertation explores the constitutive relationship between immigration and nationalism as manifest in the high skilled labour market of post-liberalization (post 1960s) Canada. I show that as skilled immigration became crucial for Canadian national prosperity, a simultaneous rise in discourses of skill deficit rendered actively recruited immigrants as deficient worker subjects. Unfolding in the decades following liberalization, persistent discourses of deficit - refracted through a systemic privileging of Canadian/Western skills and training (understood as both tangible credentials and intangible soft/cultural skills) - constructed the figure of the immigrant as a prototypically skill-deficient subject struggling to integrate into the Canadian labour market, and by extension, to the larger Canadian society. Scholarship on labour market integration has frequently seen the issue as an example of policy level and administrative disjuncture. In contrast, I argue that skilled immigrants’ marginalization in the labour market of the very nation that recruited them as vital for national prosperity creates a gap between immigrants’ juridical and substantive membership. It is systematic and socio-politically productive. I conduct a critical discourse analysis of post-liberalization skilled immigration policies and related texts (government commissioned reports, press releases, ministerial speeches, and policy backgrounders) and show how the nation state continues to be an exclusive space where immigrants’ welcome is contingent and conditional on their ability to approximate an amorphous and contested Canadianness. I argue that it is through the mobilization of deficit discourses that the post-liberalization state negotiated its increasing reliance on immigrant labour with the historically racially conceptualized criteria for national membership. In the post- liberalization global hierarchy of nation states, the dynamics of welcome (as labour) and expulsion (from membership) allowed Canada to open up the national space to the raceless meritocracy of the best and the brightest, while continuing to re-align it along racial lines. This dissertation makes three key interventions: 1) it repositions the high skilled labour market – typically considered unfettered by practices of racialized nationalism - as a key site for its exercise in post-liberalization era, 2) it argues that training/learning discourses in this context are better seen as nationalist discourses subsumed within the discriminatory notion of Canadian experience, and finally, 3) it proposes a dialogue between scholarships on Canadian nationalism and immigrants’ labour market integration as the conceptual disconnect between these is analytically costly for our understanding of post-liberalization Canadian nationalism.

Keywords: discourse analysis
high skilled labour migration
knowledge economy
national membership
settler nationalism
skill deficit
Advisor: Mirchandani, Kiran
The Modern Moon: Studies of recent lunar chronology and links to future sample-return missions

The Moon acts as a time capsule for events in our region of the Solar System. The combination of returned lunar samples, lunar meteorites, orbital and lander data have allowed a fundamental understanding of the formation and history of the Moon and the inner Solar System. With the lack of returned samples from other planetary bodies, the lunar bombardment rate is used as the basis of modeled crater production functions for other planetary bodies. Thus, having a more constrained lunar chronology is critical in providing more precise surface ages, as well as anchoring the bombardment rate in our region of the Solar System. The first chapter of my thesis focuses on refining the recent lunar chronology by using the rockiness of craters’ ejecta as a proxy for their age. Using this method, I have dated all craters with diameters 10 km, younger than roughly one billion years. This new dataset suggests that the lunar bombardment rate has increased by a factor of ~2.6 in the past ~290 million years. In comparing the lunar craters with terrestrial ones, it is evident that both impact rates follow the same trend. Thus, the dearth of large terrestrial craters between ~290-650 Myr is most likely an implication of an implied lower past impact flux, rather than preservation bias. Additionally, I use high-resolution images from the Lunar Reconnaissance Orbiter to compare rock populations resulting from impact craters of similar sizes and ages across different terrains and compare their evolution over time. As craters age, they become less rocky and my results show that rocks of all sizes in their ejecta diminish in number at the same rate, regardless of their location on the Moon. These results further imply that regolith thickness variations do not strongly affect impact production of rocks for craters 10 km in diameter. Lastly, through a study for exploration of the lunar south polar region, this thesis provides information for future sample collection locations on the Moon in order to obtain a more precise lunar chronology, which could then be extended to other planetary bodies in the Solar System.

Keywords: cratering
moon
regolith formation
remote sensing
Advisor: Ghent, Rebecca R
Improving Land-Use Based Estimation of Traffic-Related Air Pollution by Extending Models over Space and Time

Land-use regression (LUR) modeling is used to predict traffic-related air pollution (TRAP) at the urban-scale; which makes it a common tool for estimating exposure in health studies. However, these models are developed for a specific time and geographic area. This can lead to inaccurate exposure assessments when TRAP estimations are required for past or future years, or in cities beyond the model’s geographic area. This research used mobile sampled data to identify ways to improve the accuracy of model estimations when predicting exposure across time and space. Mobile measurements were separated into three resolved concentrations (local, neighbourhood- and regional- background) based on the spline of minimums method, a time-series approach. Associations between concentrations and land-use data (proximity to highways, industries, parks) were stronger for resolved than unresolved concentrations. To more accurately model observed concentration patterns across a wider geographic area, LUR models were developed from these resolved concentrations. For most air pollutants (ultrafine particles, nitrogen dioxide and nitric oxide), the resolved models were better able to assess exposure than unresolved models (those developed with total ambient concentrations) when they were spatially extended to areas bordering the model’s geographic area. Furthermore, these improvements in the resolved models’ estimations were observed for similar and different land-use practices between the model’s geographic area and bordering areas. Traditional LUR models contain only spatial predictor variables and these can be backcasted or forecasted through linear scaling for past or future exposure estimates. Spatiotemporal are another type of model that contain both spatial and temporal predictor variables; these can estimate past or future concentrations by updating the temporal predictor variables (wind speed, temperature, reference monitor concentrations) within the model. This research found that spatiotemporal models were better able to estimate observed concentration patterns in present-day and historic concentrations, but backcasting of spatial models showed more accurate historical estimates. In addition, this work developed hybrid land-use models (coupling machine learning techniques and land-use data) that were used to estimate historical concentrations. The hybrid models were better able to estimate present-day exposure than traditional LUR models, however, LUR models were better able to assess historical exposure.

Advisor: Evans, Greg J
Super-Resolved Microscopy as a Tool to Unveil Intracellular Structure in Biological Systems

We have employed a combination of super-resolution microscopy techniques to explore the spatial redistribution of the heat-stable nucleoid structuring (H-NS) protein within E. coli in response to high osmolarity. H-NS is an abundant nucleoid association protein in gram-negative bacteria and plays a dual role as a global gene regulator and nucleoid organizer. By imaging the spatial organization of H-NS, we hoped to gain insight into its complicated role in osmoadaptation. While we saw no effect on the spatial organization of H-NS in osmotically stressed, exponentially growing cells, we observed a profound rearrangement of H-NS proteins in osmotically stressed, stationary phase cells. In this case, H-NS was dynamically translocated towards the cell periphery, over the course of 5-10 minutes, and appears to be excluded from a tightly condensed chromosome. While the mechanism remains elusive, we were able to connect this response to the overall superhelicity of the bacterial chromosome. By inhibiting DNA gyrase in exponential phase, we were able to observe a very similar reorganization of H-NS, and chromosomal collapse, that we previously observed only in stationary phase. This behavior implies that the superhelicity of the chromosome plays a role in regulating osmoadaptation. To perform these studies, owing to the small size of bacteria and the diffraction limit of light, we established an optical setup on which we can conduct one- or two-color PALM or dSTORM in three-dimensions. These single-molecule localization microscopy (SMLM) methods can achieve a resolution of roughly 20 nm. In addition, we developed image-processing tools to reconstruct accurate SMLM images and studied the photo-physics of various photo-switchable fluorophores to confirm their suitability for high-resolution SMLM. Further applications of these methods and developments are discussed herein.

Advisor: Milstein, Joshua N
Enhancement of peripheral nerve regeneration with controlled local release of Tacrolimus (FK506)

Despite substantial improvements in microsurgical techniques, patients with peripheral nerve injuries rarely recover fully. FK506, an FDA approved immunosuppressant, improves functional recovery and reinnervation following peripheral nerve injury in animal models. However, systemically delivered FK506 causes undesirable global immunosuppression. We have therefore engineered a biodegradable local delivery system for FK506 using fibrin gel as a drug reservoir that can be placed at a site of nerve injury. We used our FK506 delivery system to enhance nerve regeneration in clinically applicable models of nerve injuries. We further investigated the mechanism of action by which local FK506 promoted peripheral nerve regeneration. In the first aim of this study, the drug delivery system was engineered to provide sustained and controlled release of bioactive FK506. Moreover, the optimal local FK506 dose delivered to the peripheral nerve tissue was investigated in a three-dimensional organotypic system. In the second aim, we demonstrated the efficacy of local FK506 release from the delivery system on enhancing axon regeneration and functional recovery in clinically applicable models of nerve injury in rats. We documented the biodistribution of FK506 within the nervous system in vivo following the drug release from the delivery system implanted at the site of nerve repair. In the third aim, the neuroregenerative mechanism of action for the local FK506 administration was investigated both in vitro and in vivo. The analysis of FK506 binding proteins (FKBP)s’ localization within the peripheral nerve in vivo suggested Schwann cells containing FKBP52 at the site of nerve injury and repair can be a cellular target for the locally applied FK506. FKBP52 was further confirmed to be a molecular target for the FK506 mediated neuroregeneration effect in vitro. In the studies presented in this thesis, we demonstrated the local application of FK506 using our engineered drug delivery system resulted in superior axon regeneration while preventing the toxicity of systemic FK506 that has prevented clinicians from using FK506 routinely for treating peripheral nerve injuries. The findings in this study provide compelling evidence that the tested FK506 delivery system can provide a new and effective clinical solution for treatment of peripheral nerve injury.

Keywords: Biomaterial
FK506
Drug delivery
Nerve injury
Nerve regeneration
Rat model
Regenerative medicine
Advisor: Borschel, Gregory H
Gordon, Tessa