VictorJuiz/thesis huggingface dataset:
VITAMIN D AND HEALTH SERVICE UTILIZATION FOR UPPER RESPIRATORY TRACT INFECTIONS AND ASTHMA IN YOUNG CHILDREN
Keywords: Asthma
Child
Health service utilization
Nutrition
Upper respiratory tract infections
Vitamin D

Upper respiratory tract infections (URTI) and asthma are major causes of childhood morbidity. They are two of the most common reasons for children seeking health care in the outpatient and inpatient settings, posing a large burden on society and the health care system. It has been suggested that vitamin D may decrease airway inflammation and have an immune protecting effect, which may lead to a reduced risk of health service utilization (HSU) for URTI and asthma in childhood. If vitamin D has an impact on HSU for these common health issues, measures to increase vitamin D status could potentially reduce the burden of these diseases. This doctoral thesis uses observational methods to examine the relationship between 25-hydroxyvitamin D concentration in children ages 0-6 years, vitamin D supplementation during pregnancy and childhood and HSU over 2 years for URTI and asthma in childhood. Healthy children ages 0-6 years were recruited through the TARGet Kids! practice based research network from 7 primary care clinics in Toronto ON, Canada. Data from Ontario’s publicly funded health-care system was linked to TARGet Kids! data at the individual level and used to evaluate the relationship between vitamin D and HSU for URTI and asthma in childhood. I did not find statistically significant evidence to support an association between 25-hydroxyvitamin D concentration, vitamin D supplementation in pregnancy and childhood and HSU for URTI or asthma in a sample (n=2926) of healthy children ages 0-6 years that generally had adequate vitamin D concentrations. However, due to the relatively low frequency of asthma outcomes, future studies could be conducted in an asthma prevalent cohort with low 25-hydroxyvitamin D levels. Measuring asthma prevalence in young children is challenging, thus I conducted a measurement study to evaluate the agreement between the Ontario Asthma Surveillance Information System (OASIS) algorithm (a validated health services algorithm) and parent-reported asthma in children ages 1-5 years. The OASIS algorithm performed similarly to parent-reported asthma and may be a useful tool for identifying children 1-5 years of age to develop a cohort of children with a high likelihood of having asthma for inclusion into future studies.
Assessment of Potassium Focused Dietary Strategies in Individuals with Cardiovascular Disease
Keywords: Cardiovascular Disease
Heart Failure
Hypertension
Potassium

Despite the wealth of clinical data investigating the benefits of a high K+ intake, there is a lack of knowledge regarding the safety of a high K+ diet in individuals that may have disturbances in K+ homeostasis. This thesis will focus on both HTN and heart failure (HF) populations as there are several factors common to both that can predispose to hyperkalemia. In addition, the final piece of work will report on the postprandial impact of K+ intake in augmenting endothelial function and its subsequent role as a possible mechanism in driving changes in blood pressure. The overall objectives of this work were to investigate the safety of a high K+ diet in individuals that may be at risk for hyperkalemia due to medical management; and to investigate the acute changes in endothelial function after ingestion of a high and low K+ meal. We determined that: (1) high K+ diet did not cause hyperkalemia or any statistically significant or clinically relevant changes in serum K⁺ in hypertensive individuals receiving angiotensin converting enzyme inhibitors or/and angiotensin receptor blocker therapy; (2) in heart failure patients, despite increases in reported K+ consumption and accompanying changes in urinary K+ between groups, there were no overall significant changes in serum K+ concentrations. However, hyperkalemia occurred in 3 patients: 2 in the HKD group and 1 in the UD group. Based on these results, we cannot confirm the safety of consuming any amount of dietary K+ without monitoring serum K+ in patients with HF; (3) A single meal high in K+ did not improve endothelial function. This suggests that the beneficial effects of dietary K+ may not occur acutely or that a change in one nutrient, like K +, was not sufficient to improve FMD, a marker of endothelial function. In summary, these experiments provide novel information related to the safety of increasing K+ intake through K+ rich foods in populations at risk for hyperkalemia. This work also gives insight into the postprandial effects of high K+ intake on vascular function in a population likely to have endothelial dysfunction due to disease.
Race, Empire and the Making of the Global Citizen in the Ontario Curriculum (1920s-2010s)
Keywords: Canada
Curriculum
Education
Empire
Foucault
Ontario

Pedagogical approaches that emphasize the importance of creating ‘global’ citizens have been experiencing considerable momentum in the past thirty years in Canada and in other Western countries. Relying on the insights of critical race theory and postcolonial approaches in education and using Ontario’s civics and social studies curriculum as case study, this thesis questions the claims advanced by the mainstream liberal literature on Global Citizenship Education (GCE) about this approach’s benevolence and alleged break from traditional forms of citizen education based on nationalism. Instead, this dissertation demonstrates how approaches based on the idea of a global citizen reproduce a moralising liberal educational discourse in which imaginings of the moral white self (as a global citizen), the ‘other' (as a global non-citizen) and the ‘community' (Canada as a post-national entity in a globalized world) intersect, allowing for the organization of differences and similarities at an individual and collective level along racial lines. These representations, in turn, reinforce Canada's national identity as white and imperial, a discourse that traces its origins to the beginning of Canada's national project. The argument presented in this thesis is based on a Foucauldian-inspired analytical framework that treats global citizenship education not as a neutral field of knowledge, but as a discourse that shapes the ways texts, institutions and individuals can speak, write and represent a particular kind of knowledge about a topic and the ways in which they are limited in construing it. This discourse informs the teaching and learning practices adopted in GCE-infused curricula, turning these texts into technologies of power that, through what Foucault calls ‘spirals of power and pleasure', (re)create a particular modernist vision of the polity in which students can be transformed into ‘global citizens'. To demonstrate the historical continuity of the global citizenship education discourse in the Canadian context, this thesis relies on a genealogical analysis of the social studies and civics curricula in Ontario from the 1920s to today, focusing on four historical periods, each representing a distinctive phase in the evolution of the discourse around citizenship education in Canada: the interwar era (1920s-1940s); the post-war era (1950s-1960s); the Multicultural era (1970s-1980s); the post-cold war era (1990s-2010s).
A Bourdieusian Analysis of Resilience among Victimized Individuals who Smoke Crack Cocaine
Keywords: Bourdieusian research
Crack use
Persons who use drugs (PWUD)
Resilience
Victimization

Individuals who smoke crack cocaine face pervasive sources of adversity, including chronic victimization; nevertheless, in spite of such experiences many find ways to persevere. However, on trend with research in the general substance use literature, studies of crack use are preoccupied with describing and analyzing vulnerabilities and risks. Consequently, “resilience” is not a lens through which individuals who smoke crack are examined. Indeed, current psychological conceptualizations of resilience remain too narrow to recognize all the potential manifestations of resilience in the daily lives of individuals who regularly use drugs. There is a lack of studies that examine, from a resilience perspective, the practices that may protect individuals who smoke crack from victimization, or assist them in dealing with the effects of such adverse events within a high-risk environment. The primary objective of this PhD dissertation was to theoretically reconceptualize resilience using Bourdieu’s theory of practice and apply it to the particular case of victimization in crack culture. A qualitative study was conducted examining responses to victimization and the types of coping strategies utilized among thirty street-involved individuals who regularly smoke crack in a mid-sized community in Southern Ontario, Canada. Findings show that participants mobilize their capacities and resources to “rebound” from victimization in the crack field through various resilience practices. These individuals rely on their own embodied competencies and the social capital available to them through their networks, in order to avoid or deal with victimization. A focused analysis of self-blame following victimization reveals the dual nature of this practice – which often causes suffering, but also produces opportunities for agency, competency, and survivorship. By providing a theoretically-based broad definition of resilience, this research uncovers hidden, socially marginalized, misunderstood, or de-valued practices that assist street-involved individuals who smoke crack in avoiding or dealing with victimization in a challenging context.
Developing Techniques to Understand Increased Ion Complexity in the Gas Phase
Keywords: Fluorescence Spectroscopy
Gas-phase Probes
Instrument Modification
Mass Spectrometry

While ions are held in the volume of a quadrupole ion trap mass spectrometer it is possible to use gas-phase optical spectroscopy to extract intrinsic information from the trapped species. This information is unencumbered by influences and interferences that populate the condensed phase. Under these conditions, it is possible to develop an understanding of the intersection of the intra- and intermolecular influences on a molecule. Doing so by beginning at the baseline of a bare ion and building up complexity in a controlled and calculated fashion. This research aims to fill in existing knowledge gaps by monitoring the effect of discrete changes on trapped ions. Chapters 2 and 3 of this thesis focus on examining intrinsic photophysical properties from groups of common fluorescent dyes (oxazines and rhodamines). The subtle structural change of the deuteration exchange of labile hydrogens resulted in significant changes in the measured fluorescence of oxazines but minimally affected structurally related rhodamine dyes. These may function as benchmark results and enable a better understanding of the interplay between structure and quantum efficiency. In combination with computation, the new insights promise to aid the effective and deliberate design of new fluorescent probes. The fourth chapter of this thesis describes the effects of increasing the internal energy of interrogated systems; via the design, implementation, and application of an intra-vacuum heating system. Effects were monitored using optical probing in combination with heating for several systems. These effects were varied, from the subtle shifting of rhodamine emission spectra to a rejection of the gas phase effectiveness of fluorescence thermometer molecule rhodamine B, and inducing a FRET monitored conformational change in a mutant variant of ubiquitin. Using this method of purposefully added complexity (deuteration and increased internal energy) it is possible to better understand how and why these effects occur. The work in these chapters represents essential steps in taking mass spectrometry from an important tool for sensitive and selective detection to an expanded role as an important investigative space to determine the nature of the molecules we use every day.
Relative Effectiveness of Osteoporosis Treatments to Reduce Hip Fractures in Patients with Prostate Cancer on Continuous Androgen Deprivation Therapy:
Keywords: androgen deprivation therapy
fracture
osteoporosis
prostate cancer

Background: Androgen deprivation therapy (ADT) is widely used in men with advanced prostate cancer, and can lead to loss of bone mineral density (BMD) and fractures. Osteoporosis treatments are effective in improving BMD, and reducing risk of hip fractures. Given the potential benefits, risks, and widely varying costs of osteoporosis treatments in our population, we assessed the effects and cost-effectiveness of treatments. Methods: A systematic review and a network meta-analysis were conducted using randomized controlled trials (RCT) that evaluated bisphosphonates, denosumab, toremifene, and raloxifene in patients with non-metastatic prostate cancer on ADT. Outcomes included percentage change in BMD from placebo at different bone sites and incidence rates of any fractures. A cost-utility model was developed using a state transition model simulating the progression of prostate cancer, the incidence of hip fractures and an adverse event from osteoporosis treatments. The risk of fracture was conditional on BMD changes, which were modeled as the means of determining the effect of treatment on health and cost outcomes. The outcomes were predicted hip fracture incidence, quality-adjusted life years (QALYs), expected costs, and incremental cost-effectiveness ratios. Results: Thirteen RCTs were included for analysis. The largest BMD improvement compared to placebo at 12-month at femoral neck site was risedronate 6.77% (95% CrI:-6.87-20.27%). Two studies reported fractures; toremifene and denosumab studies reported improved incidence of new vertebral fracture outcome vs placebo (2.5% vs 4.9%;p
Sex Differences in the Spinal Mechanisms Underlying Chronic Pain
Keywords: Chronic Pain
Microglia
Neuropathic Pain
Rodents
Sex Differences
T cells

Microglia-neuronal signalling has been critically implicated in mediating pain hypersensitivity associated with peripheral nerve injury (PNI). PNI causes upregulation of the purinergic receptor P2X4 (P2X4R) on microglia, which elicits brain-derived neurotrophic factor release (BDNF). BDNF acts on spinal dorsal horn neurons, leading to enhancement of NMDA receptor (NMDAR) activity and downregulation of the potassium chloride cotransporter KCC2. Together, these neuronal changes cause hyperexcitability of lamina I neurons which transmit pain information to the brain. Unfortunately, the P2X4R-BDNF-NMDAR/KCC2 framework was delineated through experiments employing exclusively male rodents. This sex bias in subject inclusion is rampant in preclinical pain research. Here, we found that disrupting microglial P2X4R-BDNF signalling, which blocked pain hypersensitivity in males, had no effect in females. Thus, we concluded that microglia-neuronal signalling does not contribute to neuropathic pain hypersensitivity in female mice. Furthermore, we found that females lacking T cells, which are critical mediators of adaptive immunity, ‘switched’ to using the microglial-dependent pathway. These findings suggest that T cells may play an analogous role to microglia in females with pain hypersensitivity. Our qPCR and flow cytometry experiments indicated that this sexual dimorphism appears to be dependent on a lack of increased P2X4R activity in females after nerve injury. Additionally, we found that modulators of microglia functioning attenuated CFA-induced hypersensitivity in males only, demonstrating that a sexually dimorphic role for microglia also exists in inflammatory pain. We also demonstrated that this sex difference in pain signalling likewise occurs in rats, thus there is conservation of this phenomenon between different rodent species. Further, we showed that nerve injury downregulated KCC2 in both sexes, and pharmacologically targeting KCC2 or NMDARs rescued pain hypersensitivity in females and males. Thus, despite sexually dimorphic immune pain signalling, NMDARs and KCC2 contribute to pain hypersensitivity in both sexes. Therefore, neuronal mechanisms downstream of microglia are convergent between the sexes, which reveal that pain hypersensitivity is degenerate, in that multiple processes can lead to the same pathological change. Our findings demonstrate that future development of drug therapies for chronic pain should target non-degenerate mechanisms and highlight the importance of including female subjects in preclinical pain research.
Development of a Hybrid Brain-Computer Interface Based on Imagined Speech Using Electroencephalography and Near-Infrared Spectroscopy
Keywords: brain-computer interfaces
classification
electroencephalography
functional near-infrared spectroscopy
imagined speech
machine learning

The primary goal of brain-computer interface (BCI) research is to provide communication capabilities for individuals with severe motor impairments. However, using BCIs for communication can be nonintuitive, often requiring the performance of a conversation-irrelevant task. The primary objective of this research was to propose an intuitive BCI based on imagined speech tasks and investigate the reliability of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) signals, separately, in detecting these tasks. The secondary objective was to develop a hybrid EEG-fNIRS BCI based on speech tasks, leveraging the advantages of each measurement modality. In the first study, EEG signals were used to classify three different mental tasks: unconstrained rest or the mental repetition of the words “yes” or “no”. An average offline binary (“yes” versus “no”) and ternary classification accuracies of 63% and 54% were reached across participants, respectively. These results were validated in a second study using two online BCIs, one to differentiate between rest and “no” and the other between “yes” and “no”, which yielded average online accuracies of 76% and 69%, respectively. The third study consisted of two phases. In the first phase, a 3-class online BCI based on imagined speech (“yes”, “no” and rest) was developed using fNIRS and yielded an average online ternary classification accuracy of 64%. EEG data were collected from participants but were not analyzed in this phase. In the second phase of this study, the collected EEG data were used to develop a multi-class hybrid fNIRS-EEG offline BCI. An average ternary classification accuracy of 69% was attained, exceeding accuracies of BCIs based on EEG or fNIRS alone. These studies demonstrate that imagined speech is a promising activation task for selected users. Concurrent neuroelectric and hemodynamic measurements can improve BCI classification accuracy and information transfer rate when using imagined speech as the activation task.
Metabolic Engineering of Lyase-Based Biosynthetic Pathways for Non-Natural Chemical Production
Keywords: Aldolase
Butanediol
Lyase
Metabolic Engineering
Synthetic Biology
Systems Biology

Metabolic engineering efforts have led to the development of bioprocesses implemented at an industrial scale for the production of natural and non-natural chemicals. However, several challenges need to be addressed in order to develop more bioprocesses that can reduce our reliance on petroleum-based feedstocks. One area of improvement is to expand the types of chemicals that can be produced. Often, the limitation lies in the unavailability of known enzymes to catalyze steps in novel biosynthetic pathways. This thesis investigates the application of carbon-carbon bond-forming enzymes in biosynthetic pathways to produce chemicals from renewable resources. In addition, this thesis provides insights into aldehyde metabolism in microbes by elucidating side reactions that need to be addressed in order to utilize aldehyde-associated reactions. First, we demonstrated the production of a non-natural chemical, 1,3-butanediol, from glucose in Escherichia coli using an aldolase-based pathway that also produced acetaldehyde via pyruvate decarboxylase. By combining strain and pathway engineering strategies, 1,3-butanediol reached a titer of 2.4 g/L and 11 % of the maximum theoretical yield from glucose in strain BD24. We suspected that a combination of challenges remained in the engineered strain including poor NADPH balancing and carboligation activity of pyruvate decarboxylase resulting in acetoin and 2,3-butanediol production. Therefore, we designed an alternative acetaldehyde production module from glucose, using an acetylating acetaldehyde dehydrogenase in attempt to prevent acetoin production. In combination with a metabolic model-guided approach, we identified gene knockouts that could further improve 1,3-butanediol yield on glucose. Deleting the following genes predicted by the model: ilvB, pykF, sfcA, and sthA led to the highest 1,3-butanediol yield in our study (16.8 % of the maximum theoretical yield). Finally, we demonstrated the tuning of 2,3-butanediol isomer production in E. coli using a shorter and novel pathway via the carboligation activity on acetaldehyde to produce acetoin. The final strain BD38 led to the production of 2S,3S-butanediol directly from glucose with a yield of 21 % of the maximum theoretical yield. Harnessing the potential of lyases, including aldolases and carboligases, has led to the production of a non-natural chemical, 1,3-butanediol, and a non-inherent chemical, 2S,3S-butanediol, in E. coli.
The Influence of Fantastical Discourse Context on Young Children's Online Sentence Comprehension
Keywords: Development
Discourse
Eye tracking
Generic language
Semantics
Sentence comprehension

Real-time eye-movement measures were used to ask how a fantastical discourse context competes with stored representations of real-world events to influence moment-by-moment interpretation of a story by 7-year-old children and adults. Listeners heard stories about fantastical characters such as witches, who performed unusual actions such as eating keys. Results from Chapter 2 demonstrate that 7-year-olds were less effective at bypassing stored real-world knowledge during real-time interpretation than adults. Nevertheless, an effect of discourse context on comprehension was still apparent. In Chapter 3, the effect of generic language on children’s and adults’ performance was examined. Generic language implies a type of universal truth that applies to categories, and may therefore enhance the salience of fantastical information in listeners’ mental representations of story events. When stories referred either to the actions of an individual, using non-generic language (e.g., ‘Wendy the witch has keys for her lunch’) or used generic language to attribute these actions to a category (‘Witches have…’), adults used discourse-based information, whereas children relied on stored semantic knowledge during real-time comprehension regardless of language type. Contrary to expectation, children were less able to override their stored semantic knowledge when they heard generic than when they heard non-generic language. When stories referred to novel fantastical creatures about which listeners possessed no background information, children were able to integrate information from the discourse and generic language supported their performance, whereas adults’ performance degraded across both language types. I conclude that generic language is more supportive of children’s than of adults’ use of a fantastical discourse context during anticipatory language processing, and that children interpret unusual actions by familiar fantastical characters about whom they already possess background information as violations of their prior knowledge. I also examine the relation between listeners’ performance and individual variation in their cognitive skills.