VictorJuiz/thesis huggingface dataset:
Identification and in vivo Characterization of a Potential TAAR1 Antagonist
Keywords: Amphetamine
Cocaine
Homology Model
Locomotion
TAAR1
Trace Amines

TAAR1 is a G-protein coupled receptor expressed in monoaminergic regions in the brain and represents a potential novel therapeutic target for the treatment of neurological disorders. While success has been made with discovering novel selective agonists for TAAR1, only one TAAR1 antagonist has been described thus far. We used an in silico screen on a TAAR1 homology model and identified several novel agonists and potential antagonists for TAAR1. One of the identified antagonists (compound 22) was predicted to have favourable physicochemical properties that should allow it to cross the blood brain barrier. In vivo studies were therefore carried out and showed that compound 22 potentiates amphetamine- and cocaine-mediated locomotor activity, consistent with behaviours observed in Taar1-KO animals. In order to assess whether the effects of compound 22 are mediated through antagonism of TAAR1, experiments were carried out on Taar1-KO mice. Our results show that compound is also able to enhance amphetamine- and cocaine-mediated locomotor activity in Taar1-KO mice, suggesting that the in vivo effects of compound 22 are not mediated by TAAR1. In collaboration with Psychoactive Drug Screening Program at UNC-Chapel Hill, we attempted to determine the target for compound 22. PDSP results suggested several potential targets for compound 22. These include, the dopamine, norepinephrine and serotonin transporters; as well as sigma 1 and 2 receptors. Furthermore, the dopamine D2 receptor was also an initial hit in a functional assay performed by PDSP. Our follow-up studies using heterologous cell systems showed that neither DAT nor dopamine D2 dopamine receptors are targets of compound 22. Therefore, the biological target of compound 22 mediating its psychoactive effects remain unknown.
Culture, Identity and Attitudes of Adult Immigrant Learners of German in the Context of the German Integration Course
Keywords: adult education
Integrationskurs
second language acquisition

Inspired by pioneering studies in the field of adult immigrants and second language acquisition, my dissertation research seeks to bridge the classroom as an inside space and the outside as lived social reality and to draw conclusions on how the interplay of these experiences affects and is affected by aspects of culture, attitudes and identity formation. Set in the specific context of the German Integration Course, this qualitative study is based on a series of guided conversations with and the written accounts of five adult immigrants enrolled in the Integration Course in Frankfurt, Germany in 2012. I am predominantly interested in socio-psychological factors affecting the learning process, including learnersâ perspectives on learning a second language in a compulsory setting in Germany, and the influence as well as the dependence of such perspectives on their identities and as result on their learning behavior. In my work, I donâ t draw a straight line between attitudes and language achievements. Much like water refracts light and produces images, I assert that our attitudes form interpretive stances through which we explain and make sense of our experiences. This process, in turn, affects our identity work and consequently our learning behaviour in and outside the classroom. As of today, research on the linguistic development in adult immigrant learners enrolled in the German Integrationskurs and the sociocultural factors that shape it is scarce. Consequently, the present study will contribute to the small but constantly growing body of research trying to shed light on the Integration courseâ s potential and capacity to meet its own goals. My work also has the intention to contribute to modern SLA pedagogy by shedding more light on the process-oriented, socio-psychological realm of language acquisition in migration contexts.
Insights into the Impact of Med Rec Implementation at admission in Acute and Long Term Care Settings in Alberta
Keywords: Complex intervention
Fidelity measure
Medication management
Medication reconcillation
Organizational effectiveness
Organizational theory

Introduction: In Canada, adverse drug events (ADEs) pose a significant public health problem. Various clinical tools have been created to mitigate ADEs and/or their impacts. Medication reconciliation (Med Rec) has been created as a clinical process intended to address the limitations associated with the use of previous clinical tools. Typically, Med Rec interventions have been implemented and evaluated at a single hospital ward and/or among vulnerable patient populations, thus limiting the generalizability of findings. In Alberta, a medication reconciliation intervention, the Medication Reconciliation Alberta (MRQA Med Rec), has been concurrently implemented in acute care hospitals and continuing care facilities with the aim of enhancing medication safety. The intervention has the potential to reduce ADE-related healthcare utilization by ensuring that all medication changes are adequately documented. Primary Objective: To evaluate the effectiveness of MRQA Med Rec in Alberta’s healthcare settings. Secondary Objectives: 1) To characterize Alberta’s healthcare institutions participating in the MRQA Med Rec intervention and compare with non-participating institutions; 2) To determine the consistency (fidelity) of MRQA Med Rec implementation by assessing the Quality Audit Bundle Compliance at Admission; 3) To evaluate whether the impact of the MRQA Med Rec intervention differs among care settings; and 4) To assess the impact of organizational factors on the effectiveness of MRQA Med Rec interventions both between and within healthcare settings. Study population: Cohort consisted of Alberta’s acute care hospital units and LTC facilities, participating in the initiative as of June 2014. Data collection: Administrative data from the following sources were linked by facility identifier: NACRS; DAD; Guide to Canadian Health facilities database; and MRQA Med Rec dataset. Data was obtained from the period between June 1st 2013 and March 31st, 2015. Analysis: Continuous variables were described with measures of central tendency and dispersion and categorical variables were described using contingency tables. Outcomes associated with ADE related healthcare utilization (ADE related ED visits and ADE related hospitalizations), consistently measured over time, were analyzed using repeated measures with the generalized linear mixed model procedures in SAS. For all parameter tests, α level was set to 0.05. Results: Alberta has 328 healthcare facilities, whereas as of June 2014, 116 healthcare organizations have implemented MRQA Med Rec including: hospitals (n=52); hospice (n=1) and publicly funded LTC facilities (n=63). MRQA Med Rec implementation in hospitals was not associated with changes in number of ADE related ED visits (p-value =0.1090) yet organizational factor analysis found that intervention’s positive effect may be more pronounced in hospitals with fewer than 50 beds (p-value
X-ray Investigations of Liquid Water Transport in Polymer Electrolyte Membrane Fuel Cell Gas Diffusion Layers
Keywords: Computed tomography
Gas diffusion layer
Liquid water transport
Polymer electrolyte membrane fuel cell
Porous medium
Synchrotron imaging

Understanding the liquid water transport behaviour in a polymer electrolyte membrane (PEM) fuel cell is key to achieving high performance. The gas diffusion layer (GDL) provides transport pathways for electrons, reactant gases, and product water. However, when liquid water accumulates within the pores of the GDL, the effective porosity of the material is decreased, resulting in a reduced effective diffusivity of reactant gases. This can lead to reactant starvation at the catalyst during high current density operation, causing significant efficiency losses. The aim of this thesis is to investigate the impact of the GDL microstructural properties on water transport in an operating fuel cell. Synchrotron X-ray radiography was used as a probing tool for identifying the water distribution in the GDL in situ. The role of the microporous layer (MPL) on liquid water management was identified through investigating in-plane water distribution in the GDL. Nanopores of the MPL reduced the amount and the size of water clusters in the GDL. Next, the influence of MPL thickness on the water accumulation in the GDL was investigated. The application of a thick MPL on the carbon fibre substrate resulted in less water content at the MPL-substrate interface than that in the GDL with a thin MPL. The effect of substrate thickness was also studied in terms of the fuel cell performance and liquid water distribution. The fuel cell incorporating a thin substrate exhibited superior electrochemical performance; however, unusual material movements were observed in the synchrotron images. It was concluded that the thin substrate was not able to provide necessary mechanical support to prevent material movements (e.g. membrane swell). Lastly, performance benefit of an MPL based on multiwall carbon nanotubes (MWCNTs) was studied. The MWCNTs additive to the MPL resulted in a high-porosity GDL compared to the conventional MPL. The high porosity region was prone to liquid water accumulation, but it also facilitated improved oxygen transport. The main findings of this thesis provide insights to fuel cell manufactures for design next generation GDLs.
Pain Assessment and Management in Pediatric Trauma
Keywords: pain
pain assessment
pain management
pediatric trauma

Background/Rationale Trauma is the leading cause of death in children over one year of age; however, research on pain assessment and management in pediatric trauma patients is scarce. Objective The aim was to determine (a) the nature and frequency of pain assessment and management practices and (b) the pain perceptions of children who have undergone a trauma and the health care professionals who provide care to them. Tenets of Critical Realism, the Gate Control Theory of pain, and developmental theory were used to examine the data. Methods A two-phased mixed methods study was conducted at a regional pediatric trauma centre. In Phase 1, pain assessment and management practices including time to administration of first analgesia (and the child and situation factors that affect them) were recorded from a retrospective chart review of pediatric trauma patients over a one-year period. Descriptive and multivariable analyses were conducted. In Phase 2, perceptions of pain management in the Emergency Department from children and health care professionals were examined through interviews. Constant comparative analysis was conducted to develop themes. Findings from Phase 1 and 2 results were triangulated. Results In Phase 1, 90/ 104 (86.5%) pediatric trauma patients had a pain assessment recorded; 60 (67%) via narrative notation and 30 (33%) with a validated pain tool. Opioid analgesia, were administered to 76/104 (73%) patients. Median (IQR) time from the traumatic event to administration of the first opioid analgesia was 99 (77-180) minutes. In Phase 2, nine children revealed their perceptions of the pain and trauma experience. Thirteen health care professionals discussed the priority of pain treatment compared to physiological stability with no standardized approach to pain treatment. Conclusion Pain assessment and management for pediatric trauma patient in the Emergency Department is suboptimal. Implications for clinical practice and research targeting interventions to improve the status of pain assessment and management are suggested. Key words: pediatric trauma, pain, pain assessment, pain management
Mighty to the End: Utilizing Military Models to Study the Structure, Composition, and Effectiveness of the Mamlūk Army
Keywords: Army
Islamic
Mamluk
Military Models
Slavery
War

This dissertation investigates the structure, composition, and effectiveness of the Mamlūk army through the use of two military models, the Diversified Army Model and the Ṣāliḥī Mamlūk Model, that dominated its organization between 1250 CE and 1517 CE. The Diversified Army Model was the dominant form of military organization in the polities of the Muslim world prior to the rise of the Mamlūk sultanate. The Ṣāliḥī Mamlūk Model came into existence in the late Ayyūbid period during the reign of al-Ṣāliḥ Ayyūb (r. 1240-1249 CE) and continued to dominate the military organization of the Mamlūk sultanate until the third reign of al-Nāṣir Muḥammad (r. 1310-1340 CE), when the Diversified army Model once again came to the fore. This period has often been viewed as one of major change or a turning point by several historians. However, there was a return to the Ṣāliḥī Mamlūk Model under several Circassian sultans and by the latter half of the sixteenth century, there was a merging of the two military models. The current study thus argues that the Mamlūk army was constantly in a state of change and that the reign of every sultan, not only that of al-Nāṣir Muḥammad, was a turning point for the military. Despite the transformations and changes in the structure and composition of the Mamlūk army, it remained a formidable force throughout the entire Mamlūk period. Through their training, the mamlūks became exceptional horsemen and proficient in the use of a variety of melee and ranged weapons. Furthermore, the slow promotion of officers (with a few exceptions), ensured that the men who rose up the ranks were seasoned and experienced soldiers. It was often from among these officers that a new sultan emerged. Finally, the Mamlūk army’s excellent track record on the battlefield demonstrates its enduring strength. This strength is signified by the fact that the sultanate’s force’s remained militarily effective and largely undefeated between the thirteenth and sixteenth centuries. The instances in which the Mamlūks suffered military defeats are few and far apart and until the Ottoman conquest of 1517 CE they quickly recovered from such setbacks.
Mobile technology and health apps: Patient and provider experiences in cardiac rehabilitation
Keywords: applications
apps
cardiac
chronic
mobile
technology

This study focused on the use of mobile health and wellness applications (apps) in chronic disease management. There are over a hundred thousand health apps available for download on public app stores. These include apps in key areas for chronic disease management such as exercise and diet. However, there is little evidence on patient use of health apps to support self-management of chronic conditions. Therefore, the study objective was to describe cardiac rehabilitation patient and provider experiences with health apps and perceived impact on self-management and the patient-provider relationship. An exploratory mixed methods design was used to gain an understanding of patient and provider perspectives and experiences. The study was conducted in a cardiac rehabilitation program in Ontario, Canada. A quantitative survey (n=242) focused on patient demographics and technology use profiles. Patient interviews (n=30) and a provider focus group (n=8) were conducted to explore perspectives on mobile technology and health app use as a part of self-management and the patient-provider relationship. Results from this study describe an aging patient population with a range of cardiac diagnoses and co-morbidities. Ninety-two percent of patients in this study used mobile technology and 50% of those with mobile technology were using health apps. Most patients and providers felt that health apps can support chronic disease management, particularly with respect to tracking progress against exercise and diet goals. Patients and providers also felt that they needed more support in using health apps and integrating them into care processes. This included the need for education on how to use apps as well as access to information on app accuracy and how to choose or recommend health apps given the large number available. Participants also emphasized the desire for health apps to connect patients and providers during and after the rehabilitation program. Health apps were mostly used by patients in the study in the absence of provider recommendations and without connectivity between patients and providers. Findings highlighted the need for health care practices to leverage and support health apps as a part of care during rehabilitation and post-discharge for patients self-managing in the community.
Role of MicroRNA-146a in Vascular Inflammation and Atherosclerosis
Keywords: Atherosclerosis
Cholesterol homeostasis
Endothelial Cells
Hematopoiesis
Inflammation
MicroRNA

Inflammation plays a vital role in acute and chronic diseases of the vasculature, including sepsis and atherosclerosis, respectively. Molecular mechanisms such as microRNAs are key regulators of signaling pathways and are important in governing the balance between physiological and pathological inflammatory responses. While numerous studies have placed miR-146a amongst the echelon of anti-inflammatory microRNAs, the role of endogenous miR-146a in vascular inflammatory diseases, including atherosclerosis, remains unknown. Therapies that directly repress vascular inflammation are expected to impede the development of sepsis and atherosclerosis. Furthermore, elevation of miR-146a expression in atherosclerotic plaques in humans and polymorphisms in the miR-146a precursor that are associated with coronary artery disease, are suggestive of a role for this microRNA in atherogenesis. Therefore, this dissertation aims to elucidate the regulation of endothelial activation by miR-146a and to determine the role of endogenous miR-146a in a mouse model of atherosclerosis. Surprising, despite the ability of this microRNA to restrain cytokine production in bone marrow-derived cells, loss of this microRNA resulted in reduced atherosclerosis. This was accompanied by hematopoietic stem cell exhaustion and a corresponding reduction in levels of circulating pro-atherogenic cells. Enhanced inflammatory signaling occurred even though circulating levels of VLDL cholesterol were diminished in these mice. Within the vasculature, miR-146a restrained endothelial activation through the regulation of transcriptional and post-transcriptional inflammatory pathways, and loss of miR-146a in the vasculature enhanced atherosclerosis. This dissertation reveals a critical function for a single microRNA in the control of the intensity of inflammatory responses to inflammatory stimuli such as hypercholesterolemia, and highlights the detrimental effects of unrestrained inflammatory signaling in multiple organs: bone marrow (hematopoietic stem cell exhaustion), spleen (extramedullary hematopoiesis and splenomegaly), liver (cholesterol homeostasis defects) and the vasculature (enhanced endothelial cell activation and monocyte recruitment). Importantly, these findings provide a further impetus to therapeutically augment miR-146a expression/function in atherosclerosis.
A Realist Evaluation of Family Navigation in Youth Mental Health and Addictions
Keywords: Evaluation
Families
Mental health
Navigation
Youth

In Canada today, many families of youth with mental health and/or addiction concerns are struggling to access the care they need. The Family Navigation Project is a service affiliated with Sunnybrook Health Sciences Centre in Toronto, Ontario, which aims to provide needs-based, family-centred system navigation to families of youth aged 13 to 26 with mental health and/or addiction concerns. The current study is a Realist Evaluation of the Family Navigation Project. The objectives of this study were a) to describe the population being served by the Family Navigation Project; b) to develop a conceptual framework for family navigation and a program theory for the Family Navigation Project; and c) to test the program theory, and refine it based on the results. This multi-phase, mixed methods study applied a Realist Evaluation framework and a cross-sectional methodological design in which both quantitative and qualitative data were collected through an online survey package in order to evaluate the sample characteristics; perception of navigation; the impact of perceived experience on family empowerment, family quality of life, and service satisfaction; and the influence of context. Data was collected from a convenience sample of 134 families seeking care on behalf of youth, who were registered with the Family Navigation Project at the time of the study. Descriptive, inferential and qualitative analyses were performed. Results indicated that the Family Navigation Project reached its target population in this sample; that families in this sample were highly satisfied with the services they received; that most families in this sample perceived care to be accessible, continuous, and family-inclusive; that this perceived experience significantly influenced family empowerment, family quality of life, and service satisfaction; and that both individual and systemic-level contexts influence experience and outcomes to varying extents. The conceptual framework and program theory were subsequently refined. Applications, contributions and limitations are noted.
Mean-Field Games and Ambiguity Aversion
Keywords: ambiguity aversion
game theory
high frequency trading
mathematical finance
mean-field games
stochastic games

This thesis focuses on incorporating the idea of ambiguity aversion into mean-field games. Intuitively, mean-field games describes the dynamics of a system with an infinite population. It is useful in approximating systems with a large population, for which an exact result is computationally intractable. By adding in ambiguity aversion, the mean-field game reflects how players in the population should act if they wish to protect themselves from model misspecification. Two applications of mean-field games are considered through two distinct approaches. The broker execution problem is investigated in a multi-agent framework containing (i) a major agent who is liquidating a large number of shares, (ii) a number of minor agents (high-frequency traders (HFTs)) who search for statistical arbitrage strategies, and (iii) noise traders who buy and sell for exogenous reasons. All optimizing agents (the broker and HFTs) trade against noise traders as well as one another. We use a mean-field game approach to solve the problem and obtain a set of decentralized feedback trading strategies for the major and minor agents. Furthermore, the mean-field game strategies have an ϵN-Nash equilibrium property where ϵN → 0 as N → ∞. The second application focuses on interbank borrowing and lending, which may induce systemic risk into financial markets. A simple model of this is to assume that log-monetary reserves are coupled, and that banks can also borrow/lend from/to a central bank. When all banks optimize their cost of borrowing and lending, this leads to a stochastic game. We account for model uncertainty by recasting the problem as a robust stochastic game and succeed in providing a strategy which leads to a Nash equilibria for both the finite game and the mean-field game limit. We prove that an ϵ-Nash equilibrium exists and show that when firms are ambiguity-averse, default probabilities can be reduced relative to their ambiguity-neutral counterparts. Finally, this thesis develops a modified stochastic maximum principle for min-max problems, and derives new existence and uniqueness results for a mean-field game with ambiguity averse players. An ϵ-Nash equilibrium is shown to exist for this class of mean-field games, and the mean-field game equations are explicitly derived in the linear-quadratic framework.