VictorJuiz/thesis huggingface dataset:
Contextualizing the Crisis in the Hospital Discharge Process for People Experiencing Homelessness in Toronto, Canada: “Danger and Opportunity”

Canadian scholarship shows higher rates of hospital readmission among homeless than housed populations, signaling that their health needs are not being met post-discharge. The discharge process is meant to ensure patients’ care is transitioned to the community and is recognized by communities and homelessness researchers as a critical point of transition; yet little research has examined this process from acute physical care services. This exploratory qualitative study aimed to characterize the hospital discharge process for people experiencing homelessness when discharged from general medicine in Toronto, Canada. Informed by critical realism, it explains how and why discharging homeless patients remains a challenge. Semi-structured in-depth interviews were held with 16 hospital workers involved in the discharge process from three urban hospitals, six shelter workers who receive discharged patients, and 11 key informants with expertise in homelessness and healthcare. Results broadly characterize the process, situating inadequate discharges as a consequence of the failure of multiple systems on which the discharge process relies: barriers to publicly-funded systems, and silos and gaps between these systems. Further findings shed light on contextual influences of two features of the discharge process. First, finding an appropriate discharge destination was challenged by historical and contemporary social and economic contexts that triggered the adoption of efficiency and accountability measures in hospitals, and eligibility and exclusion criteria in shelters. Second, within the legal context of health information protection in Ontario, knowledge sharing between hospitals and shelters was complicated by the concept of circle of care that excludes shelter workers from the discharge process. Certain geographic and organizational contexts have activated the development of institutional- and individual-level relationships between some hospitals and shelters or their workers, which improved knowledge sharing. Despite the agency exhibited by our participants, the discharge process was marred by uneven power dynamics between hospitals and shelters and a service gap where neither hospitals nor shelters are responsible for the wellbeing of homeless patients post-discharge. Future research should centre the voices of people experiencing homelessness who go through the discharge process and adopt an intersectional analysis to better understand how the discharge process is shaped by patients’ intersecting social locations.

Keywords: context
critical realism
discharge planning
discharge process
homelessness
qualitative
Advisor: Di Ruggiero, Erica
Hwang, Stephen W
Observing and Describing the Sigmoidal Growth of Bone Anchorage from Endosseous Healing with Empirical Models

The concept of endosseous healing creating a secondary biologic stability is firmly established in the dental literature, but mathematical growth curves have not been used to describe the resultant increase in bone anchorage (BA). This work investigates the hypothesis that the effect of implant surface topography on BA can be quantified using the appropriate empirical model and that increases in BA follow a sigmoidal growth curve with features that are consistent with the three general phases of endosseous healing: the lag phase with osteoconduction, the growth phase with de novo bone formation, and the plateau phase with remodeling. BA of rectangular implants placed in rat femora were tested in both shear and tension. Initial anchorage measurements taken at 5-days occurred after the lag phase, but growth and plateau phases were apparent in the data and could be measured using the asymptotic model. Testing method was found to significantly affect the peak BA and the inclusion of nanotopography on a microtopographically complex surface significantly decreased the required healing time. The effect of nanotopography was found to be greater than the effect of surface chemistry or hydrophilicity. Cylindrical and threaded implants were tested in torsion after being placed in rat tibiae for up to 6 months. By taking BA measurements at 3-days after placement the lag phase could be observed, enabling the fitting of sigmoidal functions with the logistic function producing the best fit. This allowed for the description of the peak anchorage, inflection point, and healing time. By differentiating between the phases of endosseous healing it was found that implant topography had a significant effect on de novo bone formation but not remodeling. This work has shown the three phases of increasing BA, related the increase of BA to bone formation, and found that curve fitting is an effective means of comparing different implant designs with respect to BA achieved through endosseous healing.

Keywords: Bone
Empirical Modeling
Implants
Advisor: Davies, John E.
Identifying Host-adaptive Genomic Signatures in the Pseudomonas syringae Species Complex

Pseudomonas syringae is a diverse bacterial species complex capable of causing disease on various crop and wild plant species. Despite the relatively high number of affected crops, an understanding of the genetic basis allowing P. syringae to promote disease on many of these hosts is lacking. My goal was to identify genomic signatures from P. syringae genomes associated with adaptation to distinct types of hosts. I hypothesized that such signatures were overrepresented in pathogens from a given host, and that they could be extracted when compared to genome data from non-pathogens. Using statistical approaches such as GWAS and machine learning, I identified five plasmid-borne type III secreted effectors (T3SEs) and 32 other plasmid-borne genes strongly associated with isolation from diseased coffee plants. We then showed that isolates lacking this plasmid exhibit reduced growth on coffee leaves, suggesting that these genes play an important role on coffee colonization by P. syringae. Furthermore, I employed machine learning techniques to investigate if we could use genomic data to predict P. syringae virulence on bean and found that our model could predict virulence with high accuracy (mean absolute error = 0.05). I functionally validated the model by predicting virulence for 16 strains and found that 15 (94%) had virulence levels within the bounds of estimated predictions, demonstrating the power of machine learning for predicting host-specific adaptation. Finally, I also identified specific T3SE gain and loss events potentially associated with bean adaptation and showed that the loss of the HopAZ1 T3SE contributed to this process. Its presence reduced the growth of the strong kidney bean pathogen P. syringae pathovar phaseolicola 1448A on bean. Altogether, my thesis shows that pathogen genomes contain a written history of past evolutionary events associated with adaptation to specific hosts. Such signatures can be unraveled by applying statistical approaches to next-generation sequencing data.

Keywords: Comparative genomics
Genome-Wide Association Studies
Host adaptation
Machine learning
Pseudomonas syringae
Advisor: Guttman, David S
Historical Thinking in Ontario Secondary Schools: A Multiple Case Study

In recent decades, history and education scholars in the Western world have argued for a constructivist approach to disciplinary thinking in history, known as historical thinking. This generated a large body of scholarship and many curriculum revisions. In Canada, these included the articulation of six historical thinking concepts designed to operationalize historical thinking for the classroom. Four of these concepts were embedded into the 2013 secondary school history curriculum in Ontario, the context of this present study. Yet, there has been little classroom-based empirical research exploring how teachers implement and enact historical thinking, generally, and historical thinking concepts, specifically. The present study asks: How do Ontario secondary school history teachers, who conceptually and practically embrace historical thinking as their approach to teaching history, understand and implement the Ontario history curriculum? Multiple-case study methodology was used, with the participation of four history teachers. Data for each case was generated by a survey, three interviews, two think-aloud activities, five classroom observations, document analysis of lesson plans, student and teaching resources, and assessments. The results revealed teachers’ different interpretations and expressions of the Ontario history curriculum. Two pedagogical profiles emerged. In one, teachers understood historical thinking concepts as skills for developing students’ critical thinking, as a transferable generic skill. Historical thinking was a means to this end. In the other profile, teachers used historical thinking concepts as critical inquiry lenses for creating new knowledge about history; they used historical thinking to help students understand history as a process of interpreting humanity and society over time. Historical thinking was its own end. These results support other studies in suggesting that there is no singular pedagogical approach for delivering a secondary school curricula. The particular contribution of this study, however, is in its detailed descriptions and analysis of how and why teachers negotiate between curriculum imperatives and their own teaching philosophy, and how they adapt their knowledge and understanding of historical thinking to do so. This study concludes by exploring the implications of this research for curriculum implementation, for teaching practice, for teacher education (both pre-service and in-service), for curriculum development, and further classroom-based research.

Keywords: Historical Thinking
Historical Thinking Concepts
History Education
History Teaching
Advisor: Sandwell, Ruth
Linking Polar Bear Physiology and Ecology via Models of Their Energetics

Polar bears require a sea ice platform to access and capture energy-rich marine prey. Climate warming is lengthening summer ice-free periods, forcing polar bears to survive increasingly longer periods of food deprivation while also leaving less time to accumulate body energy stores through on-ice periods. Dynamic energy budget (DEB) models have been used to estimate physiological and demographic impacts of sea ice loss for polar bears, accurately reflecting declines in body condition, reproduction and survival already observed in several subpopulations. To date, data limitations have restricted assessments to the effects of increased summer ice-free periods on the reproduction and survival of adult bears. My thesis increases our understanding of polar bear energetics by developing and refining models for estimating the energy polar bears have stored in lipid and protein reserves, developing new methods for collecting polar bear energetics data, and by exploring how polar bears acquire energy-draining parasites. In Chapter 2, I used data from dissected polar bears to develop a body composition model that separately estimates protein and lipid energy storage, expanding the applicability of the polar bear DEB framework to conditions where the molecular composition of energy storage changes rapidly (i.e., feeding). In Chapter 3, I developed and tested a method for morphometric data collection from captive polar bears using crate training. Sequential straight line body length measurements of captive bears showed no difference in precision compared to those collected from wild polar bears, opening new avenues for collecting physiological data necessary for further DEB development. In Chapter 4, I applied energy budget and demographic arguments to establish marine prey muscle tissue as the most likely transmission pathway of the parasite Trichinella nativa to polar bears. Understanding how polar bears acquire parasites facilitates understanding how changes in diet might affect parasite load, and thus, polar bear energetics. My thesis highlights the power of implementing novel methodologies while concurrently repurposing existing data and rethinking traditional collections to better understand difficult-to-observe processes like energy acquisition or disease transmission. As human-driven environmental change continues to push ecosystems beyond regularly observed extremes, methods enabling predictions of unobservable phenomena using measurable variables are invaluable.

Keywords: climate change
energetics
modelling
parasites
polar bears
Advisor: Molnár, Péter K
The Transgenerational Effects of a Dpaminergic Drug on the Behaviour and Morphology of the Trinidadian guppy (Poecilia reticulata)

Maternal effects are ubiquitous, but paternal effects, the nongenetic influence of fathers on their offspring, were traditionally thought to be limited to animal species with paternal care/investment, however, there is now evidence that fathers can influence their offspring via nongenetic factors (interactions with females, modifications to sperm/ejaculate). There is also limited evidence that both maternal and paternal effects can span several generations, i.e. they can be transgenerational, but it is not yet clear if this phenomenon is generalizable across taxa. For my dissertation, I asked if there were parental and transgenerational effects of a dopaminergic drug (the psychostimulant methylphenidate hydrochloride (MPH), known as Ritalin or Concerta) on Trinidadian guppies. I selected MPH because it is highly prescribed for the treatment of Attention-deficit/hyperactivity disorder and, given its pharmacology, it was predicted that it could cause transgenerational effects; despite this, the paternal and transgenerational effects of MPH were unknown. I found that MPH treatment had significant effects on the behaviour of first-generation males, and the morphology of first-generation males and females. I also found that some of these effects persisted across generations. First, MPH treatment directly affected male mating behaviours, with downstream effects on the behaviour of offspring; there was evidence that paternal effects were mediated by females for the offspring of control fathers, but, not for the offspring of MPH-treated fathers, suggesting nongenetic modifications to sperm as a potential mechanism. I also describe transgenerational effects of MPH in later generations and observed that behavioural effects of MPH were transmitted through the paternal, but not maternal, line to male and female great-grandoffspring—a generation that was not directly exposed to MPH. For morphological traits (body size and male colouration), I observed that both maternal and paternal treatment affected some offspring and grandoffspring morphological traits, highlighting the importance of exploring maternal and paternal effects in tandem. Taken together, this research is the first to demonstrate that MPH can cause transgenerational effects, which highlights the need to consider parental and transgenerational effects in studies of human health and the responses of natural populations to anthropogenic effects (e.g. exposure to pollutants, climate change).

Keywords: Dopamine
Epigenetics
Guppy
Paternal effects
Ritalin
Transgenerational effects
Advisor: Rodd, Helen
The Development of Xeno-free Culture Substrates for Long-term Culture of Human Pluripotent Stem Cells

Human pluripotent stem cells (hPSCs) are subject to a highly dynamic microenvironment in the developing embryo, replete with a wide range of biochemical and biophysical cues. Given the transitory and complex nature of pluripotency, efforts to fully understand the factors that maintain hPSCs in vitro can be leveraged for tissue engineering and regenerative medicine applications. In vitro culture methods for hPSCs have largely relied on xenogenic and non-chemically defined culture substrates, namely basement membrane extracts (eg., Matrigel and Geltrex) and supportive feeder layers, while xeno-free culture substrates that support high levels of proliferation and pluripotent marker expression are currently lacking. In this thesis, the role of substrate stiffness and extracellular matrix (ECM) composition in maintaining hPSC pluripotency and proliferation was explored. We first developed a high throughput matrix microarray screening platform capable of tightly controlling substrate stiffness and ECM protein composition. Proof-of-concept screening with this platform identified several non-intuitive matrix and substrate stiffness combinations capable of supporting hPSC pluripotency in long term culture. Subsequently, we employed a bioinformatics and mass spectrometry screening approach to identify novel ECM factors that support hPSC pluripotency. These factors were screened using a design of experiments (DOE) screening strategy on our matrix microarray where we identified a novel matrix condition that outperformed Geltrex in long term culture. Cells grown on this substrate in chemically defined conditions exhibited improved cell survival, increased proliferation, and greater expression of pluripotency factors compared to Geltrex. Through RNA-Seq and phosphoproteome arrays, we determined that an increase in AKT signalling ostensibly drove the observed increase in pluripotency and proliferation on our novel substrate. In summary, the integration of a combinatorial microarray screening platform and statistical modeling facilitated the study of the effect of substrate stiffness and ECM composition on hPSC pluripotency. The optimal hPSC culture substrate developed in this work could be used to permit massive expansion of hPSCs in chemically defined conditions for tissue engineering and regenerative medicine applications. This screening approach can also be applied to other cells to optimally guide cell phenotype.

Advisor: Simmons, Craig A
Identification of Androgen-regulated Genes in a Breast Carcinoma Cell Line, BT474, using Transcriptomic and Proteomic Techniques

Breast cancer (BCa) is the second most common cancer worldwide and the most prevalent cancer in women. The majority of BCa cases are positive for the estrogen receptor (ER+, 80%), and progesterone receptor (PR+, 65%), whereas some express human epidermal growth factor receptor 2 (HER2+, 20%). The androgen receptor (AR) is also found to be expressed in 77% of patients with invasive BCa and is now considered a promising biomarker and therapeutic target for BCa. However, the biological significance of androgens (A) and the AR in BCa remains unclear. Thus, in this study, the BT474 cell line was used as cell line model because it is an ER+PR+AR+ BCa cell line with high response to androgen treatment. The main purpose of this work was to investigate the effect of androgens in this cell line at the transcriptomic and proteomic level. The first step was to perform a pilot study using the androgenic hormones (dihydrotestosterone and norgestrel) to identify the expression of androgen-related molecules, using RNA sequencing and stable isotope labelling by amino acids in cell culture (SILAC)-based proteomics. As a second step, the effects of dihydrotestosterone and progesterone hormone were examined in a more precise way to identify potential androgen-regulated genes and molecular pathways that are involved in BCa pathology, using the same techniques. Thirtly, validation of candidate mRNAs and proteins was perfomed using qRT-PCR and parallel reaction monitoring (PRM)-based proteomics, respectively. Lastly, verification of the expression of selected androgen-regulated genes was assessed in other BCa cell lines. The high expression of kallikrein 3 (KLK3), also known as prostate specific antigen (PSA), under androgen stimulation, was used as a positive control for all experiments. Several known and unknown androgen-regulated genes were identified. Pathway analysis revealed that androgen stimulation changed the abundance of proteins involved in lipid metabolism, cell cycle, and estrogen-dependent processes known to be associated with BCa progression. The validated results from these orthogonal techniques contribute to the overall knowledge of AR’s role and significance in BCa. Furthermore, new androgen-regulated genes identified through this work may be considered for further investigation as biomarkers or target molecules for personalized treatments.

Keywords: Androgen Receptor
Breast Cancer
Proteomics
RNA Sequencing
Advisor: DIAMANDIS, ELEFTHERIOS EPD
Legislation of Structural Violence, Inequities, and Social Injustices? An Institutional Ethnography of the social organization of HIV Healthcare and Treatment for African, Caribbean, and Black (ACB) People Living with HIV in Canada

Biomedical HIV discourses demonstrate that people living with HIV on antiretroviral treatment (ART) can achieve undetectable viral load or a state of undetectability, which is fundamental for optimizing health outcomes, decreasing mortality and morbidity, and preventing HIV transmission. Despite the biomedical breakthroughs and the global and national commitment to end HIV/AIDS, African, Caribbean, and Black (ACB) people remain structurally disadvantaged, marginalized and experience disproportionate burden of HIV. The way that HIV healthcare and treatment are organized has significant implications for ACB people. This dissertation research draws on institutional ethnography (IE) to explore how ACB people access HIV healthcare and treatment given the social context and their actualities. Through the lens of structural violence, this IE illuminates invisible and taken-for-granted harmful effects of laws, policies and institutional practices organizing and regulating healthcare access and delivery in Ontario, Canada. The research explicates how laws, policies, and institutional practices shape Black people’s day-to-day lives in ways that constrain their ability to access and engage in HIV healthcare, adhere to ART, and reach undetectability. This research uses data obtained through semi-structured interviews with Black people living with HIV (n=20) and fifteen health workers (n=15), including physicians, nurses, pharmacists, frontline workers, and health policy actors, and textual analysis of biomedical HIV/AIDS discourses, and legislative and human right frameworks. The inquiry begins from the experiences of ACB people seeking HIV healthcare and explores the struggles they encounter accessing care within Canada’s healthcare system. This inquiry demonstrates that standardized biomedical HIV discourses, which are presented as “best practices,” ignore and obscure forms of structural violence that perpetuate inequities and violate individual and population right to health. The dissertation unmasks a multi-axial model of violence, inequities, social injustices, and suffering that constrain Black people’s ability to enter the healthcare system, access HIV healthcare, adhere to ART, reach undetectability, and achieve optimal health outcomes and quality life, and therefore undermining public health and global HIV response efforts of ending HIV and contributing to the pathologization of Black people. Actioning Black Health provides a human rights, equity and social justice informed operational framework for facilitating HIV healthcare and treatment interventions.

Keywords: African
Caribbean and Black people
HIV care cascade
HIV healthcare
Inequities
Social injustice
Structural violence
Advisor: Grace, Daniel