VictorJuiz/thesis huggingface dataset:
Genetic and Epigenetic Determinants of Tissue Factor Pathway Inhibitor Plasma Levels

Tissue factor pathway inhibitor (TFPI) regulates the intravascular formation of blood clots, and low TFPI plasma levels increase the risk of both arterial and venous thrombosis. TFPI plasma levels are also heritable, but few genes have been implicated. The objectives of my thesis were to identify genetic variants associated with TFPI plasma levels, and to integrate epigenetic data to better understand the molecular mechanisms by which these variants affect TFPI plasma levels. I started with a Human Genome Epidemiology (HuGE) review of genetic variants associated with TFPI plasma levels (manuscript 1). I meta-analyzed associations between four TFPI variants and TFPI plasma levels, and confirmed an association with rs5940 and rs7586970. I next conducted a linkage analysis of TFPI plasma levels in 251 individuals from the F5L Family Study (manuscript 2) and replicated a linkage region on chromosome 2q identified in the only genome-wide study of TFPI plasma levels reported to date. I meta-analyzed SNPs in the region across three European ancestry study samples, and implicated rs62187992 in the chromosome 2q linkage result, and in the risk of venous thromboembolism in the INVENT Collaboration dataset. Public genomic resources supported three-dimensional looping of the rs62187992 region to the promoter of IKZF2, whereas nearby whole blood DNA methylation did not mediate the association between rs62187992 and TFPI plasma levels in either the F5L Family or MARTHA studies. I last conducted a genome-wide association scan (GWAS) of TFPI plasma levels in the F5L Family Study (manuscript 3). I found that TFPI plasma level-associated SNPs were enriched in promoters and enhancers in vascular endothelial cells, a cell type that expresses TFPI, and I leveraged this enrichment in a prioritized GWAS via stratified false discovery rate control. While I did not identify novel SNPs, I nonetheless outlined a strategy for incorporating epigenetic data into prioritized GWAS. This thesis is the most comprehensive assessment of genetic risk factors for TFPI plasma levels, and integrates epigenetic data to understand biological mechanisms - a first step towards new therapies that will reduce the public health burden of thrombosis.

Keywords: coagulation
genetic epidemiology
population health
statistical genetics
thrombosis
Advisor: Gagnon, France
The Role of Social-emotional Learning Skills in Bullying Behaviour

Bullying is a serious problem in Canadian schools, with numerous consequences (see McDougall Vaillancourt, 2015). There are a number of causes and correlates (Rodkin, Espelage, Hanish, 2015), ways of assessing and defining bullying (Solberg Olweus, 2003), as well as numerous intervention programs (Ontario Ministry of Education, 2013). Due in part to these factors, the efficacy of anti-bullying programs has been modest (Ttofi Farrington, 2011). The goal of the present study was to investigate the Social-Emotional Learning (SEL) model as a framework for understanding bullying behaviour. More specifically, it explored whether the five broad SEL skills domains (i.e., self-awareness, self-management, social awareness, relationship skills, and responsible decision-making) were associated with a range of bullying behaviours (i.e., physical, verbal, social, sexual, and cyber). Participants consisted of 193 middle school students from three schools within the Greater Toronto Area (GTA). Multiple regression analyses revealed that difficulties with the self-management of anger and a high number of friends were associated with physical and verbal bullying behaviour. Poor emotional awareness and a low number of friends were associated with physical, verbal, and social targeting. Interestingly, low number of friends was also associated with physical bullying, while high number of friends was associated with cybertargeting. These findings suggest that there is significant heterogeneity amongst youth involved in bullying. While some youth involved in perpetration may need support in developing anger regulation skills, others may benefit from interventions focused on shifting peer norms supportive of bullying behaviour. Other youth may need support in developing new friendships that can protect them from ongoing targeting. The findings also suggest that gender may influence who is bullying who, and that gender specific interventions may be important. Specific interventions which can target these various findings will be briefly discussed and explored. The present study findings have shed some light on SEL variables associated with bullying. It is hoped the findings will stimulate ongoing research interest in the application of the SEL model for understanding and preventing future bullying behaviour.

Keywords: bullying
social-emotional learning
Advisor: Gillis, Roy
Development of Polylactic Acid/Cellulose Nanofiber Biocomposite Foams

The development of sustainable polymeric materials has been receiving increasing attention largely due to the rising environmental awareness and stringent governmental regulations. Biorenewable resource based biodegradable polylactic acid (PLA) is one of the most promising alternatives to petroleum-based polymers. Cellulose nanofibers (CNFs), derived from renewable resources, are being regarded as the next generation renewable reinforcements for the production of high performance biocomposites. The combination of PLA and CNFs not only endows the resulting composites with fully biodegradable feature, but also gives them significantly improved performance properties. In this context, the objective of this thesis is to develop uniform fine-cell PLA/CNF composite foams with improved mechanical properties. The material properties of PLA/CNF biocomposites, foaming mechanisms, and the mechanical properties of the composite foams were investigated. During the isothermal and non-isothermal crystallization process, CNFs, acting as effective crystal nucleating agents, enhanced the crystal nucleation density, decreased the crystallite sizes, and accelerated the crystallization of PLA. Pressurized CO2 also affect the crystallization kinetics of PLA/CNF composites significantly. The addition of CNFs increased the melt viscosity of PLA dramatically due to the formation of 3D network structure of CNFs and a good interaction between PLA and CNFs. In-situ observation revealed that CNFs were effective cell nucleating agents during foaming. Compared to the neat PLA and PLA/micro-size fiber composite foams, PLA/CNF composite foams showed a much finer and uniform cell structure. Different void fractions of PLA/CNF composite foams were obtained by altering the processing conditions. The flexural strength and modulus of the composite foams decreased with increased void fraction. Comparable specific flexural strength to the neat PLA was achieved in PLA/CNF composite foams and the toughness was increased up to 3.5 times. Notched Izod impact strength was improved by 55 % at 70 % void fraction. The addition of CNFs also improved foams' dynamic mechanical properties.

Keywords: Biocomposites
Cellulose nanofiber
Foaming
Polylactic acid
Advisor: Park, Chul B.
Sain, Mohini M.
First Trimester Sonographic Assessment of Maternal Abdominal Adiposity and Fatty Liver Disease and the development of Dysglycemia and Gestational Diabetes Mellitus

Obesity leads to insulin resistance (IR) and is part of the pathogenesis of gestational diabetes mellitus (GDM) and subsequent type 2 diabetes mellitus (T2DM) after pregnancy. Regional abdominal adipose tissue (AT) has emerged as a critical pathogenic mediator of IR and consequent metabolic dysfunction. While the mechanistic processes that characterize the pathophysiology of visceral AT (VAT) and IR remain to be elucidated, growing evidence describes the role of pro-inflammatory adipokines, free fatty acid release and changes in adipose tissue morphology that leads to ectopic fat accumulation in organs such as the liver. Hepatic fat deposition results in asymptomatic, but consequential, non-alcoholic fatty liver disease (NAFLD). Like abdominal AT, NAFLD is typically a sub-clinical state that long predates the onset of T2DM. Clinicians routinely screen for GDM in the second trimester, which may be too late to favourably impact maternal and fetal outcomes. Early risk detection might help prevent GDM and its deleterious effects. We conducted a series of prospective studies to measure maternal abdominal AT at the same time each participant underwent routine first-trimester ultrasound assessment of fetal nuchal translucency, to screen for trisomy 21. First, we demonstrated that elevated first-trimester maternal VAT and total adipose tissue (TAT) were each associated with IR at 16 weeks’ gestation. We also observed that TAT and subcutaneous adipose tissue (SAT) were more strongly associated with adiponectin at 16 weeks’ gestation than was body mass index (BMI). Second, with a larger cohort of pregnant women and using the same method of first-trimester sonographic assessment of AT, we found that the highest quartile of first-trimester VAT and TAT, each predicted IR at 24-28 weeks’ gestation, and was most significantly associated with a higher odds of GDM. Finally, we used first-trimester clinical ultrasound to assess for evidence of NAFLD, and found that the presence of one or more sonographic features of NAFLD was associated with dysglycemia and GDM at 24-28 weeks’ gestation. This body of work suggests that first-trimester sonographic assessment of maternal abdominal AT and NAFLD may each provide a novel way to identify in early pregnancy, those women at higher risk for developing GDM.

Keywords: Adiposity
Gestational Diabetes
Insulin Resistance
Maternal Obesity
non-alcoholic fatty liver disease
Advisor: Ray, Joel G
Nathens, Avery B
Writing for Ecological Understanding

Thomas Berry (1999) and John Vaillant (2015) agree that the central question of our times involves considering the natural, nonhuman world and the human place in it. Ecological understanding can be defined as this awareness. This work examines ecological understanding in terms of writing pedagogy for adult learners, considering how narrative ways of teaching and learning supports ecological understanding in adult learners; and how writing can serve as a learning response to environmental and ecological issues. The methodology approaches these questions by paying attention to students’ voices about their learning and by examining student-authored work through Buell’s (1995) ecocritical lens. Interviews with educators also contribute. Robert Yagelski’s (2011) ontological approach to writing views the act as one that “both shapes and reflects our sense of who we are in relation to the world around us” (p.3). This work furthers this theory, which views the primary benefits to the self occurring solely during the act of composition, by moving towards an ontological theory of writing for ecological understanding that considers the entire writing process as shaping the self, including the editing process and a pedagogy that encourages publication of student-authored peer models. This new ontology culminates in Seven Principles for Teaching Writing for Ecological Understanding, two of which are: First-person creative nonfiction and other genres serve as solid entry points for students into the topic of the environment.; Cultivation of the naïve narrator well serves environmental writing. One methodological refinement is to focus on students’ work and then ask them to consider their own work from their point of view. Further questions include: Does a predisposition towards writing for ecological understanding develop in childhood and, if so, can it be offset by experiential writing pedagogy?; How do peer model texts affect the learning of adult students who employ them?

Keywords: ecological understanding and ecological identity
environmental autobiography
environmental narrative nonfiction journalism
expressive writing composition pedagogy
peer model texts and student authorship
transformative adult learning
Advisor: Knowles, Gary
A Phase 1 Study of a Kolb-influenced, High Fidelity Simulation Intervention Implemented to Improve Nursing Students' Use of a Conflict Resolution Skill

Interpersonal task-related conflict that arises within nursing practice can contribute to issues regarding patient safety. Exposure to conflict within practice occurs as soon as the undergraduate nursing student’s first clinical placement. Yet studies have shown that students, as well as practitioners, are not utilizing a conflict management style conducive to safe patient care. Few educational interventions have incorporated the teaching of conflict resolution skills to nursing students. Therefore, a high fidelity simulation intervention (two scenarios, each followed by a debriefing session) was developed and refined to teach the two-challenge rule to Year 2 nursing students. The Medical Research Council Framework informed the intervention’s design and refinement strategy, while Kolb’s Experiential Learning Theory provided the foundation to implement the entire, refined intervention. A Phase 1 study with two successive components, refinement and single-group post-test, was conducted to determine the feasibility for a future randomized controlled trial (RCT) of this high fidelity simulation intervention. Forty eligible Year 3 nursing students participated in the refinement phase during a 2-week period. For the single-group post-test component, 35 Year 2 nursing students participated in the entire, refined high fidelity simulation intervention which included a 5-week spacing period. The refinement strategy improved the high fidelity simulation intervention’s overall design features. For Scenario 1, the Simulation Design Scale (SDS) mean score reached a high on Day 5 of 4.86 (SD = 0.14) in contrast to a score of 3.45 (SD = 0.17) on Day 1. For Scenario 2, the SDS specific mean score was 4.75 (SD = 0.16) on Day 5, which represented a mean score increase of 1.01 from the score on Day 1. Of the Year 2 students who participated in the refined intervention, 88.7% rated its quality at 4 or higher on the Educational Practices Questionnaire. Year 2 nursing students (82.9%) also rated their satisfaction and self-confidence after participating in the entire refined intervention at 4 or higher on the Satisfaction and Self-Confidence in Learning scale. Additionally, the Year 2 students utilized the two-challenge rule 74.3% of the time after participating in the second high fidelity simulation scenario. Overall, the results of the Phase 1 study were favourable and will contribute to planning a future RCT.

Keywords: conflict resolution
Kolb's Theory of Experiential learning
nursing students
refinement strategy
simulation design
simulation education
Advisor: Dubrowski, Adam
Basic Psychological Needs and the Facilitation of Integrative Processes: A Personality Neuroscience Approach

Research has shown that people's abilities to develop and act from an integrated sense of self are facilitated by fulfillment of the basic psychological needs for competence, relatedness, and autonomy. However, few studies have examined the neurophysiological processes that support the integrative functions of need fulfillment. In the present research, I therefore used neuroscience methods to examine the neural correlates of need fulfillment. In the first study, I used event-related potentials to examine the association between need fulfillment and conflict negativity (CN), a measure of conflict during personal decision making. Participants completed a decision-making task in which they made a series of forced choices according to their personal preferences. The degree of decisional conflict was manipulated on the basis of participants' unique preference ratings for the target stimuli. Results indicated that people reporting higher levels of need fulfillment exhibited larger CN amplitudes in high- relative to low-conflict situations; by contrast, people reporting lower levels of need fulfillment exhibited CN amplitudes that poorly discriminated the decision situations. In the second study, I used functional near-infrared spectroscopy to examine the association between need fulfillment and activity within the medial prefrontal cortex (MPFC), a key region involved in self-referential processing. Young adults were asked to reflect on their personal characteristics in the remembered past, perceived present, and imagined future. Results indicated that people reporting higher levels of need fulfillment exhibited similarly high levels of right-MPFC activity across the three self-reflection conditions; by contrast, people reporting lower levels of need fulfillment exhibited elevated right-MPFC activity only when reflecting upon their current characteristics. Together, these two studies suggest that need fulfillment may promote integrated self-functioning by increasing people's receptivity to and processing of events that challenge their abilities to make efficient, self-congruent choices and by increasing the integration of temporally distant self-representations.

Keywords: anterior cingulate cortex
basic psychological needs
functional near-infrared spectroscopy
medial prefrontal cortex
self-determination theory
self-integration
Advisor: Fournier, Marc A
John Duns Scotus on the Role of the Moral Virtues

This dissertation examines the account of the role of moral virtue in human action put forward by John Duns Scotus (c. 1266-1308). Various issues related to Scotus’s account of moral virtue have received scholarly attention in recent years, notably the discussions in the late thirteenth century concerning the nature of human freedom and how it led to the view, adopted by Scotus, that moral virtues are habits (i.e. acquired dispositions) that pertain specifically to the faculty of free will, rather than to the human soul’s various powers of action, as some medieval philosophers maintained. The present work builds on such studies by examining how Scotus’s radical account of freedom drastically circumscribes the role that is possible for moral virtues. Scotus maintains that we are, as free rational beings, always able in principle to judge correctly what is the right action and to act freely according to that judgment; moreover, a free choice to follow right reason is sufficient for a human act to qualify as morally good, regardless of any habitual inclinations we might have or lack. Thus, while moral virtue inclines an agent to acts that would be morally good if accompanied by right reasoning, this inclination in itself has no moral character, nor does it cause the resulting act to be morally good. Scotus therefore denies that the moral virtues have an essential explanatory role in the account of how and why an action is morally good, and they do not play an essential role in his ethical theory.

Keywords: freedom of the will
habit
John Duns Scotus
medieval philosophy
moral psychology
moral virtue
Advisor: King, Peter
PickavĂŠ, Martin
How to Refer to Abstract Objects

Consider the statement “7 + 5 = 12”. It appears to be true. Moreover, it appears to entail that something is identical to 7 + 5. But this thing that is identical to 7 + 5 does not appear to be located in space or time – where and when would we find it? Nor does it appear to enter into any causal interactions – what causes can influence it, and what events has it produced? Mathematical platonism is the view that all these intuitive appearances are correct: many of our mathematical statements are true statements about non-spatiotemporal and non-causal objects, or as philosophers say, abstract objects. Mathematical platonism stands in direct tension with many contemporary theories about how our thoughts and utterances can be about mind-independent objects, as most of those theories explain how we can think and speak about such objects in causal terms. This observation gives rise to the following argument, which I call the 'semantic argument against mathematical platonism'. For our any one of our expressions to refer to an object o, it must be possible for o to stand in at least one causal relation. It is impossible for abstract mathematical objects to stand in causal relations. Therefore reference to abstract mathematical objects is impossible. But if reference to abstract mathematical objects is impossible, then hardly any of our mathematical statements are true – at least when read at face value. This substantially undermines mathematical platonism. This dissertation defends mathematical platonism against the semantic argument. It has four chapters and a brief conclusion. I ultimately describe a package of views that may allow the platonist to resist the semantic argument. In particular this package of views allows the platonist to claim that not only can we refer to abstract mathematical objects, but we can refer singularly to them. Hence not only are apparent mathematical truths like “7 + 5 = 12” indeed true, but they say what they appear to say.

Keywords: Metaphysics
Philosophy of Language
Philosophy of Mathematics
Advisor: Dickie, Imogen
Kremer, Philip
Liquid Film Formation by Spray Droplet Impact on a Solid Surface

Formation of liquid films through the deposition of droplets and spray onto a solid surface was studied experimentally. Experiments were done to observe the coalescence of highly viscous liquid droplets (87 wt% glycerin-in-water solutions) deposited onto a flat, solid steel plate. Droplets were deposited sequentially in straight lines or square droplet arrays. Droplet center-to-center distance was varied and the final dimensions of lines and sheets measured from photographs. When overlapping droplets were deposited surface tension forces pulled impacting droplets towards those already on the surface, a phenomena known as drawback. At large overlaps droplets deposited in a line or square array coalesced to form a circular film. When the droplet center-to-center distance increased, leading to less interaction, long, thin lines and square sheets were formed. As overlap was further decreased lines and sheets became discontinuous. A simple model was developed to predict the conditions under which rupture occurred. The lowest droplet overlap ratio (defined as droplet overlap distance divided by droplet spread diameter) at which a continuous liquid film could be formed was 位 = 0.293. Further studies with a pneumatic droplet generator that put down multiple droplets simultaneously confirmed this finding. In addition, spray experiments also exhibited the drawback effect during droplet coalescence and showcased the need to spray small droplets with large overlap in order to form a uniform thin film. Bubble entrapment and escape from sprayed paint films of different thickness was analyzed and the number, diameter and velocity of air bubbles were determined. Bubbles were observed to escape from both upward and downwards facing surfaces. Concentration gradients due to solvent evaporation in a paint film create surface tension variations that drive Marangoni flows, which bring bubbles to the paint surface. An analytical one-dimensional model of solvent diffusion was used to calculate solvent concentration variations in the paint film and the Marangoni number.

Keywords: Bubble Entrapment
Drawback
Droplet Coalescence
Liquid Film Rupture
Marangoni Flows
Paint Drying
Advisor: Chandra, Sanjeev