VictorJuiz/thesis huggingface dataset:
Biodegradable Polyurethane Hydrogels for Sustained Growth Factor Delivery Intended for Treatment of Ischemic Conditions

The development of a treatment for ischemic conditions has been hindered by the lack of appropriate growth factor delivery vehicles, the limited number of effective agents, and the inability to assess the efficacy of the agent in clinical trials. An MRI-trackable injectable microsphere growth factor delivery vehicle, containing low-inflammatory polyurethanes, referred to as D-PHI polymers, is proposed for treating ischemic conditions in this thesis. The carriers were developed with the design challenge that growth factors have short half-lives in the body but are necessary for a few weeks to ensure cell survival, proliferation, and migration. In order to avoid rapid uptake by phagocytic cells and to facilitate the extracellular delivery of growth factors, microspheres of specific sizes and morphologies were fabricated. The chemistry of the D-PHI polymer was modified to achieve a fast bioresorption rate, whereby it can be quickly reabsorbed once the growth factor has been released. In order to predict the biodegradation of a family of novel crosslinked D-PHI hydrogels, an accelerated erosion test was developed. In vitro methods for evaluating the encapsulation, stability, and release of proteins from such hydrogels were developed and validated. Specific steps were taken to maintain the activity of the protein (i.e. vascular endothelial growth factor (VEGF)) during fabrication, storage, and use of the growth factor carriers. A sustained release of VEGF was observed over a two-week period from the hydrogels, and the released VEGF increased the proliferation of cells. To dampen the inflammation associated with a foreign body response in tissue and prepare it for revascularization, polyurethane-based D-PHI materials were used. These materials exhibited inherent immune-modulatory properties. For the purpose of tracking the hydrogel in rodents non-invasively, an MRI contrast agent was developed. The T1 contrast of manganese porphyrins bound to hydrogels was measured using this strategy. This thesis contributed to the development of an injectable polyurethane D-PHI hydrogel, which facilitates the slow release of pro-angiogenic VEGF and provides a versatile MRI-active platform. The combination of these technologies can provide a specific set of growth factor carriers that may be applied to the treatment of ischemic conditions and other soft tissue injuries where pro-regenerative immune control is important.

Keywords: Biodegradation
Biomaterial
Growth Factor Carrier
Hydrogel
Immune response
MRI
Advisor: Santerre, Paul J
Cheng, Margaret Hai-Ling
Enduring Effects of Early Life Inflammation on Stress-related Microglial, Neuronal and Behavioral phenotypes

Inflammatory early life stressors, including maternal obesity via high-fat diet (mHFD) and neonatal infections, are increasingly recognized as contributing factors to the development of mood and cognition-related disorders. In parallel, rodent models of mHFD and neonatal infection exhibit behaviors associated with these disorders, particularly increased anxiety. These animals also exhibit neuroinflammation and altered stress-related gene expression, including glucocorticoid receptor (GR), potential drivers of their altered behavior. Epidemiological studies indicate that neonates born to mothers with obesity have a higher likelihood of developing neonatal infections, however effects on offspring health resulting from the combination of these stressors have yet to be investigated. GR expression in neurons and microglia regulate anxiety behaviors and their densities can influence this regulation. Microglia, neuro-immune cells, orchestrate neuroinflammation with functions ranging from resting state surveillance to activated state phagocytosis. Whether dysregulated cell-specific GR expression, densities and microglial overactivation, characterizable by morphology, explains the neuroinflammation and heightened anxiety phenotypes found previously also remains to be elucidated. The aims of this thesis were to 1) characterize immediate and persistent phenotypes resulting from the combined and independent effects of mHFD and neonatal lipopolysaccharide (nLPS) exposure and 2) delineate cell-specific contributions to altered GR and immune gene expression in key brain regions regulating anxiety. Firstly, juvenile rats with combined but not independent exposures to mHFD+nLPS exhibited altered stress-related transcript abundances in the ventral hippocampus (vHPC) in a manner conducive to potentiating neural stress responses. Surprisingly, mHFD+nLPS juvenile offspring displayed normalized spatial memory behavior and dorsal hippocampal gene expression in contrast to offspring with independent exposures. Secondly, corresponding with potentiating neural stress responses, independent exposures to mHFD or nLPS decreased neuronal densities, GR colocalization and increased microglial densities, activation and toll-like receptor 4 colocalization in the vHPC and amygdala subregions at adulthood, with similar findings in mHFD+nLPS females. Surprisingly, adult mHFD+nLPS males displayed normalization in behavior and the neural features examined, with effects similar to that of controls. As markers of microglial overactivation have been found in human studies of various neuropsychiatric diseases, these findings suggest that maternal obesity and neonatal infections heighten the risk for their development by way of microglial pathology.

Advisor: McGowan, Patrick O
Robotic Manipulation of Embryos for Blastocyst Evaluation

Infertility is a global public health issue, affecting 15% of couples worldwide. In in vitro fertilization (IVF) treatment, blastocyst evaluation is routinely conducted to select Day 5/6 embryos (so-called blastocysts) that are free of chromosomal aneuploidy and have high reproductive potential. Standard blastocyst evaluation involves morphological evaluation using 2D images and blastocyst biopsy for genetic testing. Current clinical practice of morphological evaluation lacks complete 3D morphological information, leading to controversial and erroneous evaluation results for blastocyst selection. Manual biopsy in clinics suffers from inconsistency and large damage to both blastocysts and biopsied trophectoderm (TE) cells, which reduces the reproductive potential for fetus development and is detrimental to the subsequent genetic testing. To achieve blastocyst evaluation with high accuracy and minimal invasiveness, this thesis focused on (1) developing a 3D morphology measurement technique for morphological evaluation of blastocysts, and (2) developing, for the first time, a robotic system for blastocyst biopsy with minimal invasiveness. A spherical rotation scale invariant feature transform (SR-SIFT) algorithm was developed to build the 3D surface model of a blastocyst, and a U-Net with generalized Dice loss was designed for robust and accurate segmentation of TE and inner cell mass (ICM) of the blastocyst. Based on the 3D surface model and segmentation results, the 3D morphological parameters of the entire blastocyst were measured. A decision tree was developed using the 3D morphological parameters as the input to accurately predict the euploid condition of a blastocyst for embryo selection. To reduce the cell damage in biopsy procedure for genetic testing, a U-Net with modified Dice loss was designed to detect TE cell junctions for laser cutting, and an integral-based adaptive controller was developed to update the varying system parameters in real time and dynamically compensated for the cell position error during biopsy. These robotic techniques improve the evaluation accuracy and minimize the invasiveness to blastocysts. The high performance enables the techniques to standardize the evaluation criteria of human blastocysts in IVF clinics.

Advisor: Sun, Yu
Perpetuating Precarity in Theory and in Practice: A Case Study of Work-integrated Learning in the Non-profit Sector in Northern Canada

Work-integrated learning (WIL) is a process of curricular experiential education within a workplace or practical setting and is believed to give students “the skills and experiences they need to start a well-paying career after they graduate” (Trudeau, 2017). WIL is portrayed as a win-win, yet this research suggests that WIL perpetuates precarity and deepens inequalities between students, between different types of employers, and between geographic regions. Using the Human Development and Capabilities Approach (HDCA), this study investigated how eight diverse non-profit organizations (NPOs) in northern Canada are positioned to support students to develop personal agency through WIL. Most WIL research is urban-centric, focused on for-profit industries and framed within Human Capital Theory (HCT), making this study an outlier. Using a case study approach underpinned by critical and social realism to inform research methods, this study explores the ways in which WIL enables and constrains the development of agency at individual, social, and institutional levels. The role of learning partners, the structure of WIL and the presence of social actors (industry associations, regulatory bodies, and unions) were examined as conversion factors. The research is based on semi-structured interviews with twelve non-profit staff and volunteers, ten faculty and administrators, and institutional document analysis. Content analysis was implemented by organization to identify themes. The research shows inconsistencies in current approaches to WIL. While NPOs are committed to student development, theoretical fragmentation within non-profit contexts combined with constraints in the post-secondary environment compromise student learning. Students and learning partners are poorly prepared and equipped for WIL. Furthermore, the increasingly precarious positioning of NPOs within the labour market threatens their ability to offer students (future) decent work. The institutional and policy environments that undergird WIL do not acknowledge the distinctness of non-profit organizations within a neoliberal economy and this makes invisible other dimensions that affect decent work, such as the regulatory environment, collectivization, and the “contracting regime.” To ensure well-paying jobs, these factors must be addressed. This research also recommends that WIL be evaluated with greater emphasis on social and institutional conversion factors, and that future studies of WIL use HDCA, rather than HCT.

Keywords: experiential education
human capital theory
human development and capabilities approach
inequality
non-profit organization
work-integrated learning
Advisor: Wheelahan, Leesa
Amīr ʿAbd al-Qādir al-Jazāʾirī (d. 1883): Mystical Hermeneutics, Theology and Metaphysics in His Kitāb al-Mawāqif (“The Book of Mystical Halts”)

This dissertation examines the Sufi revivalist theology of Amīr ʿAbd al-Qādir al-Jazāʾirī (d. 1883) through a close study of his magnum opus, Kitāb al-Mawāqif fi baʿḍ ishārāt al-Qurʾān ilā’l-asrār wa-l-maʿārif (“The Book of Mystical Halts Concerning Some Subtle Qurʾānic Allusions to The Esoteric Mysteries and Divine Truths”). Although considerable research has been conducted on ʿAbd al-Qādir’s political resistance against the French colonial invasion of Algeria, his enormous influence on nineteenth-century Sufi revivalist discourse remains understudied and poorly understood. Over the past decades, however, a small but growing niche of scholars begun to pay closer attention to ʿAbd al-Qādir’s Sufi mystical teachings. The literature on Kitāb al-Mawāqif, however, is conspicuously scarce. We only have scattered essays on some salient themes that emerge in Kitāb al-Mawāqif or the influence of Ibn ʿArabī’s (d. 1249) mystical doctrines on ʿAbd al-Qādir’s thought. As the first in-depth study of Kitāb al-Mawāqif, my dissertation fills a long-existing gap in modern scholarship. By closing examining the Sufi Qurʾānic hermeneutics, mystical theology and revivalist discourse of ʿAbd al-Qādir, I offer a deeper glimpse into his mystical universe and his unique contributions to early modern Sufi revivalist discourse. As I argue, ʿAbd al-Qādir develops his Sufi revivalist discourse against the backdrop of his critique of Ashʿarī scholastic rationalism (kalām). Rather than turning to rationalism for answers, he seeks to curb what he considers a subversive Islamic rationalism that competes rather than submits to the authority of Revelation and Sufi mystical knowledge.

Keywords: Ash'arism
Islamic Reform
Metaphysics
Modernity
Qur'an
Sufism
Advisor: Saleh, Walid A
Sample-Complexity Optimality Under Local Differential Privacy and Related Models

This work explores the sample complexity of estimation and learning tasks under local differential privacy (LDP), an especially strong approach to differential privacy which does not rely on any trusted party to guarantee privacy. We give a new characterization of the sample complexity of answering statistical (linear) queries under non-interactive LDP in terms of the $\fnorminf$ norm, showing that a slight generalization of the well-studied factorization mechanism achieves, in polynomial time, nearly optimal sample complexity for each specific workload of queries. These results are obtained by leveraging information theoretic bounds for LDP and applying them together with geometric techniques which allow us to construct hard distributions for answering statistical queries. We extend these ideas to obtain characterizations of both agnostic learning and and agnostic refutation under non-interactive LDP in terms of the $\fnorminf$ norm, and derive, by consequence, a sample-complexity equivalence between the two tasks. We also give a characterization of realizable refutation in terms of a factorization norm which we define. A matching upper boud is given for realizable refutation, implying that realizable refutability implies realizable learning. We explore other techniques for obtaining characterizations of local privacy tasks, including an approach which combines a mutual information bound for differential privacy with an information complexity lower bound borrowed from communication theory. We also consider relationships between local privacy and data-access models which turn out to be closely related. In particular, we demonstrate an equivalence between the sample complexity of learning under sequential LDP and the sample complexity of learning under single-intrusion pan-privacy. Finally, we demonstrate an equivalence between the sample complexity of agnostic learning under non-interactive LDP and the query complexity of agnostic learning under the adaptive correlational statistical query model.

Keywords: differential privacy
estimation
information complexity
learning
local
Advisor: Nikolov, Aleksandar
Pitassi, Toniann
Examining the Relationship Between the Natural Environment and Outcomes Related to the Mental Health and Well-Being of Residents and Care Staff in Long-Term Care Homes

Introduction: Natural environments (NEs) in healthcare design are thought to promote health. However, empirical research on the NE in long term care (LTC) has been limited; the degree of rigour is mixed, focusing mostly on residents, with little research on care staff (e.g., personal support workers and nurses). Aims: The aim of this investigation is to examine the relationships between the NE and the mental health and well-being of residents and care staff in LTC homes using a rigorously developed survey to standardize an approach to the evaluation of the NE in LTC homes. The three research questions (RQ) addressed are (1) How is the NE conceptualized in healthcare literature? (2) How can the NE design, usage and exposure be evaluated rigorously in LTC homes? (3) What are the associations between the NE and the MH&WB in residents and care staff? Methods: This is a cross-sectional, Multiphase Mixed Method study which included a scoping review, a modified Delphi technique, cognitive debriefing interviews, psychometric evaluations, and multilevel modelling. Key findings: A conceptual framework was developed that comprised five interdependent themes on the NE in healthcare, relating to its definitions, processes, usages, people’s opinions, and effects—all of which are shaped by the NE’s physical and programmatic design. The framework informed the development of the Natural Environment Survey for Long-Term Care (NESL), comprised of three parts: evaluating NE design, residents’ NE usage and exposure, and care staff’s NE usage, exposure, and perception. The application of the NESL in 83 units across 27 LTC homes identified statistically significant associations between the NE and residents’ responsive behaviour in secure units and between the NE and care staff’s work-related stress, burnout, and turnover intention in secure and non-secure units. Significance: The framework complements the conceptual work on the NE to date and emphasizes NE’s complementarity to the biomedical healthcare system. The NESL advances research by providing a strong conceptual and empirical base for future development and standardization. Findings from this research are likely generalizable to LTC settings in other jurisdictions and have potential utility for researchers and decision-makers who are transforming LTC.

Keywords: long-term care
natural environment
nurses
nursing home
personal support workers
residents
Advisor: Berta, Whitney WB
Verderber, Stephen SV
Quality of Care and Long-term Outcomes of Active Surveillance: Gaining Insights from Population-level Perspectives

Active surveillance (AS) for low-risk prostate cancer (PC) is evolving as an internationally recognized standard of care and is recognized by major urological associations as a preferred treatment option. AS is increasingly used worldwide, yet research on variations of quality of care during AS is lacking, and compliance with AS guidelines is largely unknown at the population level. The aims of this research were to develop quality indicators (QIs) for AS, evaluate the quality of care for patients on AS using those QIs, and estimate long-term oncological outcomes after initial AS. A first study aimed to develop national consensus-based system-level QIs for evaluation of AS care among patients with low-risk PC. A second study aimed to critically apply QIs to examine/understand quality of care during AS at the population level. A third study aimed to evaluate long-term oncological outcomes at the population level in patients who received initial AS. This thesis establishes a foundation on which to measure and monitor the quality of care for AS patients at the population level. We developed 20 comprehensive structure-process-outcome-based QIs for measuring quality of AS care. Further, by applying these AS QIs to a large Canadian population database, we identified current gaps in the quality of AS care. The findings suggest that process of care QIs measured at PC diagnosis and during eligibility assessment for AS were improving in recent years; however, considerable variation appeared with many process indicators during the AS follow-up phase. Finally, our third study is one of the first to measure long-term oncological outcomes of AS using population-level data compared with initial treatment. Among men diagnosed with low-risk PC and managed with AS, the results suggest excellent 10- and 15-year metastasis-free survival, overall survival, and PC-specific mortality, similar to published observational studies from academic centres. However, at a population level, AS was associated with slightly worse long-term metastasis-free survival, overall survival and PC-specific mortality compared with initial treatment. These results should help clinicians and policy makers understand the impact of AS on long-term outcomes after widespread adoption.

Keywords: Active surveillance
Long-term outcome
Population-based study
Prostate cancer
Quality indicator
Quality of care
Advisor: Dr. Alibhai, MD, MSc, FRCPC, Shabbir M.H.
The Role of Retinoic Acid Signaling in Development of the Human Embryonic Hematopoietic System

The developing embryo harbours multiple waves of hematopoiesis that differ in not only their spatial and temporal properties, but also in their capacity to generate specific lineages of differentiated progeny. The hematopoietic stem cell (HSC), which is uniquely positioned at the head of the hematopoietic hierarchy and is capable of clonal multilineage differentiation potential, is restricted to the definitive hematopoietic program of the developing embryo. As HSCs exhibit both self-renewal and engraftment capability following transplantation, they represent a highly-coveted cell type in regenerative medicine with immense therapeutic value. The challenge with using human pluripotent stem cells (hPSCs) as a strategy for generation of HSCs ex vivo is the unintended heterogeneity of hematopoietic progenitors deriving from different embryonic blood programs that are otherwise spatio-temporally segregated in vivo. Accordingly, elucidating the different signaling pathways relevant for specification of these distinct hematopoietic programs is fundamental to improving directed differentiation protocols. Here, we model definitive hematopoietic development using a small-molecule and growth factor based hPSC differentiation approach in the context of a novel transgenic line that reports for expression of ALDH1A2 (the gene for RALDH2). Specifically, we show that ALDH1A2 expression is a marker of definitive, and not primitive, hematopoietic KDR+CD184+ mesoderm. Additionally, ALDH1A2 is the only ALDH isoform implicated at the definitive mesoderm stage. Kinetic analyses revealed that there are multiple waves of RALDH2 expression during mesoderm maturation and that retinoic acid (RA) signaling activation in the second wave acts via a non-cell autonomous mechanism to reveal its latent hematopoietic potential. Specifically, this WNT-driven hematopoietic mesoderm has RA-dependent multilineage erythroid, myeloid, and T lymphoid potential, and genetic deletion of ALDH1A2 abrogates the hematopoietic potential of this mesoderm. The RA-dependent T lymphoid population differs from its RA-independent KDR+CD184- mesoderm-derived counterpart, in that the former generates cord blood-like TCRV?1+ cells within the TCR?? subset. Collectively, the characterization of this WNT-driven RA-dependent definitive hematopoiesis represents an advance towards the goal of directed differentiation of hPSCs towards HSCs.

Advisor: Keller, Gordon M