VictorJuiz/thesis huggingface dataset:
Risk Factors Associated With Opioid-Induced Toxicity: Ontogeny, Pharmacogenetics, and Drug Interactions

Opioids are an important class of drugs used for the treatment of pain. The analgesic response and opioid-induced toxicity vary widely among patients. Of serious concern is the use of opioids in susceptible populations, such as infants and their mothers. The overall objective of this thesis was to investigate the contribution of ontogeny, pharmacogenetics and drug interactions in predicting opioid-induced toxicity. This objective was addressed in four separate studies. The first study assessing whether maternal clinical factors are predictive of neonatal central nervous system (CNS) depression, revealed that the replacement of codeine by oxycodone was not safe for the mother-infant pair during breastfeeding and factors such as duration of opioid use, opioid dose, and maternal CNS depression were predictors of neonatal CNS depression. In the second study assessing whether maternal genetic variants in genes involved in the metabolism and response of oxycodone were predictive of neonatal CNS depression found that the interplay between maternal genetic and clinical factors predicted maternal and neonatal CNS depression. In the third study, the ontogeny of P-glycoprotein in the developing human blood brain barrier was assessed and found to be low in newborn infants and increased remarkably with postnatal maturation, suggesting that newborn infants have heightened sensitivity to the central effects of opioids. Lastly, the role of drug interactions in deaths attributed to codeine were investigated and revealed that the combination use of codeine with other centrally acting drugs was more toxic than codeine alone. Thus, these combinations should be avoided or at least closely monitored. Overall, the results of this research suggest that no single risk factor is associated with opioid-induced toxicity but it is the interplay among clinical factors, genetic polymorphisms, ontogeny of drug-metabolizing enzymes and relevant drug transporters, and drug interactions that will predict opioid-induced toxicity. Understanding the contribution of all these factors will allow for safer prescribing of opioids.

Keywords: Drug Interaction
Lactation
Neonate
Opioid
P-glycoprotein
Pharmacogenetics
Advisor: Gideon, Koren
In The Eyes of The Law: Survivor Experiences and Image Construction Within Sexual Assault Cases

Research has clearly documented the challenges that sexual assault survivors face within the legal system, yet little attention has been devoted to the ways in which survivors demonstrate agency during this process. The present study explored the ways in which sexual assault survivors navigate the power structures and stereotypes present within the Canadian criminal justice system, particularly during pre-trial preparatory activities and testifying experiences. Semi-structured qualitative interviews were conducted with eight adult female sexual assault survivors who testified against their assailant at a preliminary hearing or trial, as well as four service providers responsible for assisting survivors within the legal system. Data collection and analysis was informed by constructivist grounded theory (Charmaz, 2006). Findings showed that survivors' experiences testifying and interacting with defense attorneys were predominantly negative, while experiences with police and Crown Attorneys were comprised of both supportive and unsupportive aspects depending on the level of belief, support and commitment shown. Consistent with previous findings on survivor agency (e.g., Greeson Campbell, 2011), participants expressed agency through purposeful acts of both compliance and defiance with system expectations, depending on which course of action was deemed most beneficial in meeting personal goals for self-protection, system change or prosecution of the offender. Participants complied with system expectations through cooperation with legal personnel as well as deliberate mental, emotional, psychological and physical strategies to prepare themselves for testifying, including independent legal research, testimony rehearsal, psychological coping strategies, emotion management, and appearance modification. These activities were undertaken to increase personal confidence and comfort, as well as to construct stereotypically consistent images of ideal victimhood, enhance perceived credibility and assist in the prosecution effort. In addition, participants expressed agency through actions such as obtaining their own legal representation, protesting and resisting unfair or inappropriate treatment, and setting boundaries in their interactions with legal personnel. Findings indicate that even in the aftermath of serious trauma, survivors of sexual assault are able to take purposeful action to assess their own needs and shape their legal interactions and experiences in order to best meet their personal goals (Greeson Campbell, 2011; Konradi, 2007).

Keywords: Court preparation
Image Construction
Legal system
Sexual violence
Victim experience
Advisor: Lana, Stermac
A Design Methodology for Reconfigurable Milling Machine Tools and An Implementation

Reconfigurable Machine Tools (RMTs) have been developed in response to agile manufacturing demands. The prevalent modular approach for reconfigurability, in which a machine configuration is assembled for a given part, can be a demanding task time-wise and accuracy-wise, especially for smaller-scale Reconfigurable meso-Milling Machine Tools (RmMTs). Research in the field of Parallel Kinematic Mechanisms (PKMs) has paved the way for the design of Redundant Reconfigurable Machine Tools (RRMTs) based on such accurate mechanisms. Reconfigurability in RRMTs can be manifested through topological and geometric reconfiguration, without disassembly of the structure. The main challenge in structural design of RRMTs is selecting the optimal architecture with the required level of redundancy for the set of parts at hand. The best RRMT architecture can be selected only after decisions are taken on the design variables, and the variables that manage the redundant reconfigurability. Namely, effectively locking/unlocking dof and selecting the optimal trajectory that each joint should follow. However, to date, no comprehensive design methodology addresses the challenges that are related to design of RRMTs.The objective of this Dissertation is, thus, to develop a design methodology for RRMTs. The methodology proposes an approach towards enhancing the performance of RMTs and attaining required machining conditions, while taking into account the possible inherent redundant reconfigurability of serial, parallel and hybrid mechanisms. The design process is combined from two engines: synthesis and optimization. These individual tasks, which are often solved in series, are addressed here through an integrated multi-tiered optimization-based design approach. The multi-tiered optimization comprises an iterative process that transfers decisions, which are generally taken throughout the design process, to a lower or upper tier to improve the overall result. The decisions are taken on a large number of continuous/discrete parameter's values that mutually depends upon one another in a structured manner, one that yields optimal values for a set of design variables to satisfy required process parameters. The applicability of the proposed methodology is demonstrated through a design test case of a PKM-based Redundant RmMT (RRmMT) that can attain high stiffness while satisfying the high feed-rate requirement. The design process resulted in a new 3Ă PRPRS RRmMT that can be reconfigured into several different PKMs.

Keywords: Design Methodology
Machine Tools
meso-Milling
Parallel Mechanisems
Reconfigurable
Redundant
Advisor: Beno, Benhabib
In Her Hands: Women's Educational Work at the Royal Ontario Museum, the Canadian National Exhibition and the Art Gallery of Toronto, 1900s-1950s

Women educators initiated, shaped, developed and practiced experiential, multisensory or object-based education in art galleries, exhibitions and museums in Toronto. Examining women educators' roles in developing educational programming in three sites, the Royal Ontario Museum (ROM), the Art Gallery of Toronto (now known as the Art Gallery of Ontario or AGO) and the Canadian National Exhibition (CNE), sheds light on women's work to make museums and galleries accessible to more diverse publics. Educators were white middle class women, often university educated; their work during the first half of the twentieth century in the development and practice of educational programming was geared to broader publics and ultimately resulted in institutional change. Women working in museums, galleries and exhibitions tailored their programming to: women; children and youth; newcomers to Canada and differently abled community members. By working within the gendered hierarchical structures of large cultural institutions, these educators were able to exercise their own agency and independence through the programming they developed. This gendered geneaology of museum education practice enables us to understand the history of many of the pedagogical practices in place today within these institutions. Coupled with a deeper understanding of museum education origins, this study also reveals that women played integral roles in establishing and developing educational practices that were aligned with progressive education reforms, thereby situating museums and galleries as crucial sites for these pedagogies. These learner-centered experiential pedagogies broadened museum and gallery publics and laid the groundwork for social inclusion in cultural institutions today. This study adds important recuperative historical narratives to the story of Canadian museum education and clears a space for new historical understandings of Canadian museum and exhibition practices. By historicizing museum education, and acknowledging the gendered and racialized nature of these educative spaces, this study will address how issues of access and public education have played out in the city of Toronto.

Keywords: Canada
education
history
museum
Toronto
women
Advisor: Cecilia, Morgan
Understanding and Improving the Elastic Compressive Modulus of Fibre Reinforced Soy-Based Polyurethane Foams

Soy-based polyurethane foams (PUFs) were reinforced with fibres of different aspect ratios to improve the compressive modulus. Each of the three fibre types reinforced PUF differently. Shorter micro-crystalline cellulose fibres were found embedded inside the cell struts of PUF and reinforced them. The reinforcement was attributed to be stress transfer from the matrix to the fibre by comparing the experimental results to those predicted by micro-mechanical models for short fibre reinforced composites. The reinforced cell struts increased the overall compressive modulus of the foam. Longer glass fibres (470 microns, length) provided the best reinforcement. These fibres were found to be larger than the cell diameters. The micro-mechanical models could not predict the reinforcement provided by the longer glass fibres. The models predicted negligible reinforcement because the very low modulus PUF should not transfer load to the higher modulus fibres. However, using a finite element model, it was determined that the fibres were providing reinforcement through direct fibre interaction with each other. Intermediate length glass fibres (260 microns, length) were found to poorly reinforce the PUF and should be avoided. These fibres were too short to interact with each other and were on average too large to embed and reinforce cell struts. In order to produce natural fibre reinforced PUFs in the future, a novel device was invented. The purpose of the device is to deliver natural fibres at a constant mass flow rate. The device was found to consistently meter individual loose natural fibre tufts at a mass flow rate of 2 grams per second. However, the device is not robust and requires further development to deliver a fine stream of natural fibre that can mix and interact with the curing polymeric components of PUF. A design plan was proposed to address the remaining issues with the device.

Keywords: Composite Materials
Foam Manufacturing
Foam Mechanics
Natural Fibre
Polyurethane Foams
Advisor: Mark, T Kortschot
Methods for Sparse Functional Data

The primary aim of this thesis is to study methods for the analysis of sparse functional data. Since this type of data is observed infrequently and irregularly for each subject, even simple descriptive statistics such as the mean and covariance must be reformulated. In the first part of this thesis, we study a related but more challenging problem of recovering the underlying functional trajectories when the subjects are genetically correlated. The key idea is to reconstruct the trajectories by using the Karhunen-Love expansion of a random function with a data-driven eigenbasis. In the second part of this thesis, we study effective dimension reduction for regression of a scalar response on a sparse functional predictor. Our proposal estimates the effective dimension reduction space under the presence of sparse functional data, which has the important property that the projection of the functional predictor onto it contains as much information on the response as the functional predictor itself. We derive our estimator's asymptotic properties and study its finite sample performance. Lastly, we consider extensions of our effective dimension reduction procedure for the classification of sparse functional data.

Keywords: Dimension reduction
Functional principal components
Smoothing
Sparse functional data
Advisor: Fang, Yao
The Social Relations of Accessibility: Explicating the Work of Accommodation for Students with Mental Health Problems in University

Providing accessible education for students with mental health problems is an important aspect of social inclusion, as it increases educational attainment, subsequent employment opportunity and community participation. In universities, accommodations are provided where necessary with the intent of ensuring equal opportunity for all students. Despite the availability of accommodations, students with mental health problems continue to experience difficulty achieving academic success, suggesting a disjuncture between accommodations and their expected favourable outcomes within the social organization of the university. This Institutional Ethnography explores the social organization of university accessibility for students with mental health problems. Sixteen students with mental health problems and eight staff members of a large university in an urban setting participated in interviews focusing on the processes of seeking and implementing accommodations. I explored institutional texts for their ability to coordinate the actions of people in this setting, as the social organization of this university is informed by numerous texts that guide participants' work. Data analysis focused on asking questions of the data and mapping work processes, in order to develop an understanding of the social organization of accessibility and accommodation for these students. In the findings, I map and explicate what I have termed an "institutional accessibility mechanism", the set of work and texts that guide the university's social relations around accommodation and accessibility. These social relations involved staff and student work processes that maintained the mechanism and preserved institutional relations. Through the Institutional Accessibility Mechanism, the university appeared to place a focus on accommodation over accessibility and created work for individual students seeking access. This Mechanism also operated under assumptions of mental wellness and presented challenges for students with mental health problems. These findings have important implications for the development of higher education policies, which can enable students with mental health problems to have better chances of success in their academic endeavours. Promoting the inclusion of students with mental health problems in university can improve their educational and employment opportunities and further the prosperity of society as a whole.

Keywords: Accessibility
Accommodation
Higher education
Inclusion
Institutional Ethnography
Mental health
Advisor: Bonnie, Kirsh
HLA-B27-specific Immune Response to Influenza is Critically Dependent on ERAP-1 and on MHC-I Allelic Co-dominant Expression

Genetic studies have demonstrated that both the HLA-B27 and endoplasmic reticulum aminopeptidase (ERAP) are contributing factors to the pathogenesis of ankylosing spondylitis (AS). In my studies I have used HLA transgenic (Tg) mice to examine the contribution of HLA-B7 and ERAP1 to the HLA-B27-mediated immune response to influenza (flu) infection, results of which could be used as proof of principle for AS. Influenza infection affects millions of individuals worldwide annually. Because of the well-established HLA allele-specific epitope recognition, I used flu infection in HLA Tg mice deficient of endogenous MHC-I expression; i.e., H2-D-/-, H2-K-/- or double knock out (DKO) in a proof-of-concept strategy to define the details of first, the interaction of HLA-B7 and HLA-B27 and secondly, the contribution of ERAP to allele-specific immunodominance. Immunodominance during a viral infection is influenced by many factors. To assess whether co-expression of HLA-B7 and HLA-B27 would influence the immune response in double HLA Tg mice, I created double Tg B7/B27 mice with intact ERAP expression on a DKO background. Following flu infection, the dominant anti-viral CTL responses was surprisingly directed predominantly at the B7-restricted NP418-426 epitope while the CTL response to the B27-restricted NP383-391 epitope was significantly reduced. Using chimeras and flu-specific tetramer staining I showed that the reduced B27/NP383-391 CTL response in B7/B27 Tg mice was due to negative selection of T cells specific to NP383-391 recognition. Secondly, recent genome-wide association studies (GWAS) with AS patients have shown that loss-of-function genetic variants of ERAP1 are protective, and that this relationship is seen exclusively in B27+ patients. To investigate these interactions in an in vivo model, I created single Tg B7 and B27 mice in the absence of ERAP. Following flu infection the B27/NP383-391 CTL response was reduced in B27/ERAP-/- Tg mice compared to B27/ERAP+/+ mice. No difference in the CTL response to the B7/NP418-426 epitope was observed between the B7/ERAP-/- and B7/ERAP+/+ mice. This is the first in vivo validation of the gene-gene interaction between B27 and ERAP1 which had been suggested by prior genetic studies.

Keywords: Ankylosing Spondylitis
ERAP
HLA-B27 and HLA-B7
HLA Transgenic Mice
Immunodominance
Influenza Infection
Advisor: Robert, D Inman Dr.
Primate-Plant Interactions in the Tropical Dry Forests of Northwestern Madagascar: Seed Dispersal and Sensory Ecology of Eulemur fulvus.

Fruiting plants and frugivores are involved in a complex set of interactions. Frugivores rely on fruiting plants as critical food resources, while fruiting plants rely on frugivores for seed dispersal services. Here, I measure the interrelatedness of brown lemurs (Eulemur fulvus) and the endemic fruits they disperse in the tropical dry forests of Ankarafantsika National Park, northwestern Madagascar. I analyze fruit traits across all fruits consumed by brown lemurs over the course of one year of behavioral study of three groups of habituated, individually identifiable brown lemurs. Using non-invasive genetic sampling, I determine that brown lemurs are dichromatic, or red-green color blind. Using spectroscopy, I quantify fruit color, and model it according to the brown lemur dichromatic phenotype and known optical morphology. I additionally quantify fruit puncture resistance using a modified force gauge and fruit odor using XAD filtration and gas chromatography-mass spectrometry. I determine that many ripe fruits colors are conspicuous to brown lemurs against a background of leaves, and that ripe fruits are significantly different chromatically from unripe fruits. I also determine that ripe fruit odors are significantly higher in ripe versus unripe fruits, and that during foraging, fruit odor and fruit size are the two strongest determinants of brown lemur foraging behavior and efficiency. Understanding the degree of fruit-frugivore interrelatedness is critical in the dry forests of Madagascar, where habitat and species loss is proceeding at a rapid pace.

Advisor: Shawn, M Lehman
Measuring the Inboard Side Scrape-off Layer of DIII-D Plasmas using Swing-probes

The scrape-off layer (SOL) plasma of a tokamak often has a complicated spatial dependence. The temperatures, densities and flow speeds can vary significantly on the same magnetic flux tube at different poloidal locations. To fully understand the plasma variation, we must make active measurements along the full length of the flux tubes by expanding our diagnostic capability to include the critically under-diagnosed inboard side. To accomplish this, a new pair of in-situ reciprocating Mach probes called Swing-Probes have been developed and deployed on the DIII D centerpost. This design is unique in that the probe swings vertically through the SOL plasma, taking measurements along a 180° arc with a 20 cm radius. Two electrodes maintain a Mach-pair orientation throughout the swing and provide measurements of saturation current, electron temperature, and parallel flow speeds. The probes can handle very high heat fluxes and have taken measurements up to the Last Closed Flux Surface (LCFS) in high-powered H-Mode at 10 MW. The Swing-Probe temperature and density measurements have been verified against the floor Langmuir probes, the core Thomson scattering and the divertor Thomson scattering systems in DIII-D for conditions where poloidal variation are expected to be small. Measurements have been taken across a wide range of plasma conditions and provide informative relationships between the plasma parameters at the entrance of the inner divertor and the crown of the plasma.The low-turbulence plasmas on the inboard scrape-off layer make it possible to clearly quantify the sheath-expansion around Langmuir probes. An I-V fitter has been developed which can account for sheath-expansion in a theoretically consistent way, improving the reliability of Langmuir probe data analysis. In an inner-wall limited experiment in DIII-D requested by ITER, the Swing-Probes made the first Langmuir probe measurements of an enhanced heat flux feature just outside the LCFS. These measurements match those made using infrared camera images of the centerpost in DIII-D and in other tokamaks and confirm that this feature should be accounted for in the designs of plasma facing surfaces in ITER.

Keywords: DIII-D
Langmuir Probe
Nuclear Fusion
plasma
scrape-off-layer
tokamak
Advisor: Peter, C Stangeby