VictorJuiz/thesis huggingface dataset:
Effects of Infliximab Therapy on Hospitalization, Surgery and Healthcare Consumption in Crohn’s Disease: A Population Based Propensity Score Matched Analysis
Keywords: infliximab
pharmacoepidemiology

Background : The majority of patients with Crohn’s Disease (CD) will be hospitalized and receive surgery for their disease. Hospitalizations and surgical procedures account for the majority of the direct costs of CD. Purpose : Our objective was to use population-based administrative data from the province of Quebec, Canada, to estimate the effectiveness of infliximab therapy in reducing CD-related surgery, hospitalization and health care resource consumption in subjects with CD. Methods : We obtained patient level prescription data, physician billing claims and hospitalization data from the Régie de l'Assurance Maladie du Québec (RAMQ) a Canadian provincial health care provider. Subjects who were enrolled in the system for a minimum of two years and who received prescription drug benefits for each year they participated in the study were identified as being affected by CD using a validated algorithm. For each subject treated with infliximab, up to two closely matched comparison subjects were selected using propensity score methods. We compared time to first CD-related intra-abdominal surgery and hospitalization as well as total hospitalized days and physician visits between infliximab users and non-users. Results : We were able to match 319 (77%) out of the 414 infliximab users to comparison subjects using propensity score matching; 300 were matched to two infliximab non-users and 19 were matched to one non-user to create 619 matched-pair sets. Subjects who received infliximab therapy had a significantly reduced risk of experiencing a CD-related intra-abdominal surgery (HR=0.674, 95%CI 0.533-0.853, p=0.001), any hospitalization (HR=0.753, 95%CI 0.619-0.917 p=0.005), and CD-related hospitalization (HR=0.726, 95%CI 0.565-0.934 p=0.013). Infliximab users experienced lower rates of hospitalized days (RateR=0.6418, 95%CI 0.4399-0.9362; P=0.021) and gastroenterologist visits (RateR=0.810, 95% CI 0.700-0.937; P=0.005). Infliximab users and non-users had similar rates of non-gastroenterologist physician visits (RateR=0.928, 95% CI 0.851-1.057; P=0.262). Conclusion : Infliximab therapy was associated with significant reductions in CD-related intra-abdominal surgeries, hospitalizations, hospitalized days and gastroenterologist visits. Our results confirm the population-based effectiveness of infliximab beyond the ideal conditions of clinical trials.
Nod1 and Nod2 in Innate Immune Responses, Adaptive Immunity and Bacterial Infection
Keywords: Innate immunity
Bacterial infection
Inflammation

The last decade has been witness to a number of seminal discoveries in the field of innate immunity. The discovery that microbial molecules and endogenous danger signals can be detected by germ-line encoded receptors has changed the way we study the immune system. Indeed, the characterization of Toll in Drosophila as a sensor of microbial products in 1997 then led to the discovery of a family of Toll Like Receptors (TLRs) in mammals. TLRs are critical for the induction of inflammatory responses and the generation of a successful adaptive immune response. The array of ligands that these transmembrane proteins recognized mediates defense against bacteria, viruses, fungus and parasites, as well as, possibly, cancerous cells. In addition to this membrane-bound family of recognition proteins, two families of pattern recognition receptors have been recently shown to respond to microbial and chemical ligands within the cytosol. These represent the Nod Like Receptors (NLRs) and RIGI-like helicase receptor (RLH) families. Nod1 and Nod2 are members of the NLR family of proteins, which are responsible for the recognition of components derived from the bacterial cell wall, more precisely, moieties of peptidoglycan. As such, Nod1 and Nod2 are implicated in the recognition and the defense against bacterial pathogens. Importantly, the genes encoding these two proteins have also been linked to the etiology of several inflammatory disorders such as Crohn’s disease and asthma. In this thesis, we show that recognition of Nod1 and Nod2 ligands generates a rapid and transient inflammatory response in vivo. When co-injected with a model protein, Nod1 and Nod2 ligands exhibit adjuvant properties that lead to the generation of an antigen-specific Th2 type adaptive immune response. Surprisingly, recognition of the Nod1 ligand in non-hematopoietic cells is critical for the generation of this immune response. In contrast, TLRs classically tip the balance towards a Th1 response and interestingly, co-injection of TLR and Nod ligands synergize to generate a more potent immune response characterized by the generation of Th1, Th2 and Th17 T cell respones. To study the role of Nod1 and Nod2 in the context of a bacterial infection in vivo, we used an intestinal mouse pathogen, Salmonella enterica serovar Typhimurium. We were able to show that Nod1-deficient mice, but not Nod2-deficient mice, are more susceptible to the strain of this bacterium, which enters the host through the active pickup in the intestinal lumen by underlying myeloid cells. This sampling mechanism is mediated by a subset of dendritic cells that populate the intestinal lamina propria. Accordingly, the defect seen in Nod1-deficient mice localizes to the mucosal barrier where these dendritic cells appear to have an impaired response towards the bacteria. Taken together, these results increase our knowledge on the general role of Nod1 and Nod2 in immunity and might generate new avenues of research and potential therapeutic targets.
The Neuropsychological Mechanisms of Avoidant Coping Post Traumatic Brain Injury
Keywords: Traumatic Brain Injury
Coping
Executive Function
Affective Function

Many people who sustain traumatic brain injuries (TBI) have poor psychosocial outcomes. Previous research has indicated that poor outcomes are related to the use of avoidant coping following TBI, although the mechanisms of this relationship are not clear. The major pathological consequence of TBI is damage to the frontal lobes and/or their connections, resulting for most people in executive and/or affective dysfunction. The purpose of this dissertation study was to delineate the neuropsychological, psychiatric, personality and physiological mechanisms of avoidant coping following TBI. Controls and people with TBI completed the Baycrest Psychosocial Stress Test (BPST), where coping behaviour was observed directly, and physiological measures were recorded. Participants also completed a neuropsychological test battery, and a series of questionnaires assessing coping, psychiatric status, personality and outcomes. There were no significant differences between groups in self reported coping. However, the control and mild TBI group engaged in more planful than avoidant behaviour on the BPST. As a group, individuals with moderate-to-severe injury, in contrast, engaged in more avoidant than planful behaviour. However, analysis of individual differences in coping behaviour within the moderate-to-severe group revealed a bimodal distribution, allowing classification of people in this group as ‘planners’, or ‘avoiders’ (this distribution was not evident in the mild TBI group). Within the moderate-to-severe group, planners had better executive function, were more reactive to stress (psychologically and physiologically), performed better on the speech task during the BPST, and had greater return to productivity. However, planners also had worse psychosocial outcomes as compared to the avoiders. This was the first study, to the author’s knowledge, to examine coping behaviour during a simulated real-world stress test. Results indicate that behavioural measures of coping, such as the BPST, are more sensitive to changes in coping post TBI than are self and significant other reported questionnaires. Results also demonstrate that executive function and psychological and physiological reactivity are important factors that contribute to coping following moderate-to-severe TBI. These data raise important questions about the challenges of targeting coping through rehabilitation.
Modeling and Control of a Magnetic Fluid Deformable Mirror for Ophthalmic Adaptive Optics Systems
Keywords: Magnetic Fluid Deformable Mirror
Adaptive Optics
Retinal Imaging
Control
Modeling

Adaptive optics (AO) systems make use of active optical elements, namely wavefront correctors, to improve the resolution of imaging systems by compensating for complex optical aberrations. Recently, magnetic fluid deformable mirrors (MFDM) were proposed as a novel type of wavefront correctors that offer cost and performance advantages over existing wavefront correctors. These mirrors are developed by coating the free surface of a magnetic fluid with a thin reflective film of nano-particles. The reflective surface of the mirrors can be deformed using a locally applied magnetic field and thus serves as a wavefront corrector. MFDMs have been found particularly suitable for ophthalmic imaging systems where they can be used to compensate for the complex aberrations in the eye that blur the images of the internal parts of the eye. However, their practical implementation in clinical devices is hampered by the lack of effective methods to control the shape of their deformable surface. The research work reported in this thesis presents solutions to the surface shape control problem in a MFDM that will make it possible for such devices to become integral components of retinal imaging AO systems. The first major contribution of this research is the development of an accurate analytical model of the dynamics of the mirror surface shape. The model is developed by analytically solving the coupled system of fluid-magnetic equations that govern the dynamics of the surface shape. The model is presented in state-space form and can be readily used in the development of surface shape control algorithms. The second major contribution of the research work is a novel, innovative design of the MFDM. The design change was prompted by the findings of the analytical work undertaken to develop the model mentioned above and is aimed at linearizing the response of the mirror surface. The proposed design also allows for mirror surface deflections that are many times higher than those provided by the conventional MFDM designs. A third contribution of this thesis involves the development of control algorithms that allowed the first ever use of a MFDM in a closed-loop adaptive optics system. A decentralized proportional-integral (PI) control algorithm developed based on the DC model of the wavefront corrector is presented to deal mostly with static or slowly time-varying aberrations. To improve the stability robustness of the closed-loop AO system, a decentralized robust proportional-integral-derivative (PID) controller is developed using the linear-matrix-inequalities (LMI) approach. To compensate for more complex dynamic aberrations, an Hinf controller is designed using the mixed-sensitivity Hinf design method. The proposed model, design and control algorithms are experimentally tested and validated.
The Development and Evaluation of a Model of Time-of-arrival Uncertainty
Keywords: Uncertainty
Time-of-Arrival
Interval Estimation
Air Traffic Control
human-centred automation

Uncertainty is inherent in complex socio-technical systems such as in aviation, military, and surface transportation domains. An improved understanding of how operators comprehend this uncertainty is critical to the development of operations and technology. Towards the development of a model of time of arrival (TOA) uncertainty, Experiment 1 was conducted to determine how air traffic controllers estimate TOA uncertainty and to identify sources of TOA uncertainty. The resulting model proposed that operators first develop a library of speed and TOA profiles through experience. As they encounter subsequent aircraft, they compare each vehicle’s speed profile to their personal library and apply the associated estimate of TOA uncertainty. To test this model, a normative model was adopted to compare inferences made by human observers to the corresponding inferences that would be made by an optimal observer who had knowledge of the underlying distribution. An experimental platform was developed and implemented in which subjects observed vehicles with variable speeds and then estimated the mean and interval that captured 95% of the speeds and TOAs. Experiments 2 and 3 were then conducted and revealed that subjects overestimated TOA intervals for fast stimuli and underestimated TOA intervals for slow stimuli, particularly when speed variability was high. Subjects underestimated the amount of positive skew of the TOA distribution, particularly in slow/high variability conditions. Experiment 3 also demonstrated that subjects overestimated TOA uncertainty for short distances and underestimated TOA uncertainty for long distances. It was shown that subjects applied a representative heuristic by selecting the trained speed profile that was most similar to the observed vehicle’s profile, and applying the TOA uncertainty estimate of that trained profile. Multiple regression analyses revealed that the task of TOA uncertainty estimation contributed the most to TOA uncertainty estimation error as compared to the tasks of building accurate speed models and identifying the appropriate speed model to apply to a stimulus. Two systematic biases that account for the observed TOA uncertainty estimation errors were revealed: Assumption of symmetry and aversion to extremes. Operational implications in terms of safety and efficiency for the aviation domain are discussed.
Microsimulating Residential Mobility and Location Choice Processes within an Integrated Land Use and Transportation Modelling System
Keywords: Transportation
Urban modelling

This research investigates motivational and procedural aspects of households’ long-term decisions of residential locations. The main goal of the research is to develop microbehavioural models of location processes in order to implement this critical land use component within a microsimulation-based model of Integrated Land Use, Transportation and Environment (ILUTE). The research takes a disaggregate and longitudinal approach to develop the models, which is consistent with the real-world decision-making process of households concerning their movements from one residence to another over time. It identifies two sequential model components to represent households’ relocation behaviour: (1) a model of household residential mobility that determines whether a household decides to become active in the housing market, and (2) a (re) location choice model. Both components are empirically investigated using retrospective surveys of housing careers. For the residential mobility decision, the research tests continuous-time hazard duration models and discrete-time panel logit models, and attempts to capture heterogeneity effects due to repeated choices within both modelling techniques. A discrete-time random parameter model is selected for implementation within ILUTE since it incorporates time-varying covariates. Assuming a sequential decision process, this mobility decision model is linked to the (re) location choice model that establishes preference orderings for each active household for a given set of dwelling units that it considers to relocate within the housing market. A unique feature of the (re) location model developed in this research is that it incorporates reference dependence that explicitly recognizes the role of the status quo and captures asymmetric responses towards gains and losses in making location choice decisions. The research then estimates an asking price model, which is used to generate base prices for active dwellings to interact with active households through a market clearing process within a microsimulation environment. A multilevel model that simultaneously accounts for both temporal and spatial heterogeneity is developed in this research using multi-period property transaction data. Finally, this research simulates evolution of households’ location choices for a twenty-year period (1986-2006) and compares the results against observed location patterns.
Interactions of Cancer Stem Cells and Tumor Vasculature
Keywords: cancer stem cell
angiogenesis

In recent years, research in the area of cancer stem cells has spiked tremendously. Numerous investigators have found that several types of cancers contain a subpopulation of tumor cells that display many defining characteristics of normal tissue stem cells, including multipotent differentiation potential, long-term self-renewal capacity, and expression of molecular markers of stemness. Most importantly, these cancer stem cells (CSCs) have very high tumor initiating potential, a finding that has led to the development of the cancer stem cell model for tumor progression. This model suggests that tumors are organized in a developmental hierarchy (similar to healthy tissue), with long-term tumor progression being driven by self-renewing CSCs at the top of the hierarchy. The CSC model represents a significant shift in our understanding of tumor progression, and as such, it may be possible to expand our knowledge of other aspects of tumor biology by re-examining them in the context of the CSC model. My work focuses on investigating interactions between CSCs and the tumor vasculature. Previous work has demonstrated heterogeneity in the proangiogenic potential of cells in a tumor. Considering the possibility that angiogenesis may be driven by specific subsets of tumor cells, I investigated the contribution of the CSC fraction to tumor angiogenesis. Comparing tumors with low or high CSC fractions, I have found that CSCs contribute to tumor vascular development through promotion of endothelial cell activity and recruitment of bone marrow-derived proangiogenic cells, mediated in part by vascular endothelial growth factor (VEGF) and stromal-derived factor 1 (SDF1). Since some tissue stem cells are known to reside in a vascular niche, I investigated the possibility that CSCs may also be supported by blood vessels in the tumor microenvironment, and that consequently CSCs may be targeted by disruption of tumor vasculature with antiangiogenic therapy. By testing multiple antiangiogenic therapeutic strategies, I have found that antiangiogenic therapy sensitizes CSCs to the effects of cytotoxic chemotherapy. Taken together, my work demonstrates a bi-directional relationship in which CSCs promote tumor vascular development, and tumor vasculature supports and protects CSCs. This work has implications for our understanding of CSC biology, tumor angiogenesis and antiangiogenic therapy, and provides insight into strategies for targeting the critical CSC population.
The Identity Myth: Constructing the Face in Technologies of Citizenship
Keywords: Face Recognition, biometrics, identity, identification, facialization

Over the last century, images of faces have become integral components of many institutional identification systems. A driver’s licence, a passport and often even a health care card, all usually feature prominently images representing the face of their bearer as part of the mechanism for linking real-world bodies to institutional records. Increasingly the production, distribution and inspection of these documents is becoming computer-mediated. As photo ID documents become ‘enhanced’ by computerization, the design challenges and compromises become increasingly coded in the hierarchy of gazes aimed at individual faces and their technologically mediated surrogates. In Western visual culture, representations of faces have been incorporated into identity documents since the 15th century when Renaissance portraits were first used to visually and legally establish the social and institutional positions of particular individuals. However, it was not until the 20th century that official identity documents and infrastructures began to include photographic representations of individual faces. This work explores photo ID documents within the context of “the face,”—a theoretical model for understanding relationships of power coded using representations of particular human faces as tokens of identity. “The face” is a product of mythology for linking ideas of stable identity with images of particular human beings. This thesis extends the panoptic model of the body and contributes to the understanding of changes posed by computerization to the norms of constructing institutional identity and interaction based on surrogates of faces. The exploration is guided by four key research questions: What is “the face”? How does it work? What are its origins (or mythologies)? And how is “the face” being transformed through digitization? To address these questions this thesis weaves ideas from theorists including Foucault, Deleuze and Lyon to explore the rise of “the face” as a strategy for governing, sorting, and classifying members of constituent populations. The work re-examines the techno-political value of captured faces as identity data and by tracing the cultural and techno-political genealogies tying faces to ideas of stable institutional identities this thesis demonstrates face-based identity practices are being improvised and reconfigured by computerization and why these practices are significant for understanding the changing norms of interaction between individuals and institutions.
Ionizing Radiation Exposure and Risk of Gastrointestinal Cancer: A Study of the Ontario Uranium Miners
Keywords: Epidemiology
Uranium Miners
Cancer
Ionizing Radiation
Esophageal
Stomach
Colorectal

Rationale/Objective: Excess lung cancer risks associated with exposure to inhaled radon decay products among uranium miners has well been established. Although ingestion is also a potentially important route of exposure, the relationship between ingested radon decay products and gastrointestinal cancer risks are not well examined. The objective of this study is to determine the relationship between exposure to radon decay products and the incidence and mortality of gastrointestinal (esophagus, stomach, and colorectal) cancer among men employed as uranium miners in Ontario. Secondly, to determine whether the duration of exposure (dose rate), years since last exposure and age at first exposure modify these associations. Methods: A cohort of miners who had ever worked in an Ontario uranium mine between 1954 and 1996 was created using the Mining Master File and the National Dose Registry. Cumulative radon exposures measured in Working Level Months (WLM) were previously estimated for each miner. Cancer diagnoses (1964-2004) and cancer deaths (1954-2004) occurring in Ontario were determined by probabilistic record linkage with the Ontario Cancer Registry. To calculate person-years at risk, non-cancer deaths were also ascertained from the Ontario mortality file for the period between 1954 and 2004. Poisson regression methods for grouped data were used to estimate the relative risks (RR) and 95% Confidence Intervals (CI) by exposure level. Results/Conclusions: The final cohort consisted of 28,273 Ontario uranium miners. By the end of 2004, 34 miners had been diagnosed with esophageal cancer, 86 with stomach cancer, and 359 with colorectal cancer. There were 40 deaths due to esophageal cancer, 69 from stomach cancer, and 176 from colorectal cancer. When comparing the highest cumulative exposure category (>40 WLM) to the referent group (0 WLM), significant increases in both stomach (RRIncidence= 2.30, 95% CI;1.02-5.17 and RRMortality=2.90, 95% CI;1.11-7.63) and colorectal cancers (RRIncidence =1.56, 95% CI;1.07-2.27 and RRMortality =1.74, 95% CI;1.01-2.99) after adjusting for age at risk and period effects. However, no relationships were observed for esophageal cancer. Suggestive evidence of modifying effects of these associations by duration of employment (dose rate) and years since last exposure for colorectal cancer was also observed.