VictorJuiz/thesis huggingface dataset:
The Problem with Pertussis: Finding Undetected Pertussis Cases in Electronic Medical Record Primary Care (EMRPC) to Improve Data Accuracy and Burden Estimates
Keywords: Epidemiology
Infectious diseases
Public health
Public health policy
Surveillance
Vaccine-preventable diseases

Pertussis is a reportable disease in many countries and surveillance is essential, but ascertainment bias has limited data accuracy. However, the true extent of bias, and its impact on burden estimates, is unknown. Within this dissertation are three novel studies which aim to evaluate and enhance the accuracy of health data used for pertussis research in Ontario to improve burden estimates which can inform disease surveillance, health interventions, and public health policy.I used a stratified strategy to sample a reference standard from a primary care electronic medical record cohort to minimize partial verification bias while optimizing sensitivity precision. Eight hundred records were abstracted, with 208 (26.0%) definite and 261 (32.6%) possible prevalent pertussis cases. Classifications demonstrated a variety of case severities. During optimization, the predicted width of 95% confidence intervals for sensitivity ranged from 12.4% to 32.8%. I used a cohort-selected cross-sectional design to evaluate pertussis detection algorithms and reasons for lack of detection in a primary care electronic medical record database. The algorithm including all data measures achieved the highest sensitivity at 20.6%. Sensitivity increased to 100% after reclassifying symptom-only cases as non-cases, but the PPV remained low. Age at first episode was significantly associated with detection in half of the tested scenarios, and false negatives often had some history of immunization. I used Chao capture-recapture models to obtain abundance and sensitivity estimates using a dataset comprised of pertussis case report, laboratory, and health administrative data. I compared results between prevalence, incidence, and adjusted false positive case definitions. Findings demonstrated that all sources consistently fail to detect pertussis cases. Estimate validity improved after adjusting for false positives, demonstrating how capture-recapture methods can be adapted to further their utility to epidemiological research when data is biased. This research strives to improve understanding of gaps in pertussis case ascertainment and burden in Ontario while suggesting mitigation strategies. Each separate aim contributes to this effort. High quality data is essential for conducting vaccine research and effectiveness studies, in addition to evaluating immunization programs. As a result, findings from this study can help direct future research and policy towards the design of optimal public health interventions for pertussis.
An Investigation of Emotional Labour and Race in Teaching
Keywords: Black Emotional Labour
Black Teachers
Critical Race Theory
Education
Emotional Labour
Greater Toronto Area

What is Emotional Labour (EL)? Emotional labour is the process of managing and displaying emotions in the public sphere of our lives, most importantly the workplace, where emotional labour is connected to employment and is therefore done for a wage. In this doctoral thesis I explore how emotional labour is a human process that can be complicated by personal factors such as race. There were three critical questions posed in this research: (1) what is the nature of emotional labour in the work lives of Black teachers in this study? (2) how is emotional labour experienced in the work lives of Black teachers in this study? (3) what is the nature of the responses and strategies in relation to emotional labour that Black teachers in the study use in their work lives? A mixed methods design was used to gather data about the emotional labour experiences of Black teachers from two sources: (1) an online survey administered to 66 teachers from various racial groupings from the Greater Toronto Area; and (2) a series of in-depth interviews with seven Black teachers. The survey findings corroborated the experience of emotional labour for Black teachers and revealed three key concepts: racialized emotional labour (REL)—the additional emotional labour associated with being Black that prioritizes labour output; racialized emotional work (REW)—the additional emotional work associated with being Black that prioritizes human output; and white emotional privilege (WEP)—the emotional advantage gained by White teachers who are not required to engage in extra emotional labour/work attributable to race. The in-depth interviews suggested three types of teachers based on the ways they engage REL and REW: (1) Struggling to Resist; (2) Strategically Coping; and (3) Accommodating,Sticking to the Classroom, and Keeping-On. The research also provided foundational information on the development of copingstrategies among Black teachers and on the significance of spheres of interaction in the emotional experience of teachers. This complex and very rich approach gave a voice to Black teachers and focused on their personal perspectives
Leveraging CRISPR-Cas to Examine the Interplay Between Legionella pneumophila and Mobile Genetic Elements
Keywords: Bacteriophage
CRISPR-Cas
IMEX
Legionella pneumophila
Mobile genetic element

Legionella pneumophila is a Gram-negative, intracellular bacterium and an accidental human pathogen. Much of the research to date has focused on L. pneumophila's ability to cause disease, and while this is important for developing treatments, studying the factors that influence its environmental persistence is critical to mitigating future outbreaks of disease. To this end, I focused on leveraging the CRISPR-Cas adaptive immune system to examine the impact that mobile genetic elements could have on L. pneumophila. I provided bioinformatic and experimental evidence to support the hypothesis that plasmid-based CRISPR-Cas systems are likely circulated by horizontal gene transfer, then leveraged by the bacterium to strengthen and restore its defences against environmental threats. Next, I expanded on our lab's previous work to generate a comprehensive, bioinformatic catalogue of the mobile genetic elements that L. pneumophila encounters in its environment. Using an expanded catalogue of CRISPR spacer sequences and a custom bioinformatics workflow, I showed that one or more lytic gokushoviruses and the prophage-like Legionella mobile element-1 (LME-1) are frequently encountered by L. pneumophila, providing the first evidence that the bacterium is challenged by lytic phages in the environment. In light of my findings, I re-visited the hypothesis that LME-1 could form phage-like particles under one or more experimental conditions, as opposed to being a phage remnant. I used transmission electron microscopy to show that under axenic growth conditions in rich media, LME-1 could form podophage-like particles, and that these particles were abolished in LME-1 mutants. I also showed that the LME-1 genome was protected from DNase treatment in extracellular fractions, and that a Xer recombinase, XerL, was implicated in LME-1 excision. Finally, I designed and validated a new assay to assess if the LME-1 phage-like particle is required for transfer between Legionella strains. Taken together, the data presented in my graduate research thesis highlight the role that mobile genetic elements could have on L. pneumophila's environmental persistence, and provide avenues for future research to mitigate outbreaks of Legionnaires' disease.
Oxime Click-crosslinked Cryogels to Quantify and Target Tumour-associated Macrophage Invasion in Hodgkin Lymphoma
Keywords: drug screening
gelatin
hyaluronan
hydrogel
lymphoma
tumour-associated macrophage

Hodgkin lymphoma (HL) cancer cells account for less than 5% of the tumour microenvironment, yet drug screening and treatment strategies typically focus on targeting malignant cells. Tumour-associated macrophages (TAMs) are associated with poor prognosis and resistance to therapy; however, there remains an unmet need for a suitable pre-clinical model to identify macrophage-targeting therapeutics. We analyzed the HL extracellular matrix (ECM) in primary tumours and found a high abundance of hyaluronic acid, collagen, and fibronectin, which guided the design of our HL-tumour mimetic hydrogel: a cryogel comprised of gelatin, hyaluronan, and fibronectin-derived peptides crosslinked using oxime click chemistry. Primary human macrophages seeded thereon migrated to a greater depth in cryogels with greater porosity and pore size; with fibronectin-derived peptides enhancing macrophage migration. We then studied classically and alternatively activated polarized macrophages in these cryogels. While IL-4/IL-13-stimulated, alternatively-activated macrophages invaded more than IFNgamma +LPS-stimulated, pro-inflammatory macrophages, both states adopted a combination of matrix-metalloproteinase (MMP)-dependent and independent invasion mechanisms. We then studied the effect of HL co-culture on macrophage invasion and found that HL direct co-culture and HL conditioned media promoted macrophage invasion into cryogels to the same extent. HL CM-induced invasion was associated with a unique polarization phenotype and upregulation of matrix-metalloproteinase 9 (MMP9) activity. In an invasion inhibitor screen of 25 drugs, we identified 5 drug hits that significantly reduced HL TAM invasion; one of these drug hits, currently approved for treating autoimmune diseases, both decreased invasion and enhanced the percentage of M1-like, anti-neoplastic/pro-inflammatory macrophages; another has demonstrated recent success in HL clinical trials. Collectively, we have designed a platform to study TAMs in HL and 1) reveal immune effects of drugs currently under clinical investigation, 2) suggest the repurposing of approved drugs to treat HL, and 3) ultimately bridge the gap between standard 2D drug screening and complex clinical readouts.
Healthcare Professional Association Agency in Preparing for Complex Technological Interventions: A Multiple-case Study of Artificial intelligence in Radiation Medicine and Medical Imaging
Keywords: artificial intelligence
complex intervention
health professions
medical imaging
professional identity
radiation medicine

As artificial intelligence (AI) is increasingly integrated in healthcare, associated impact on employment, education, ethics, and professional regulation requires consideration. It is incumbent on healthcare professional associations (HPAs) to assist their memberships in preparing for related change. HPAs hold a unique role in establishing the socio-cultural, normative, and regulative elements of healthcare professions. An exploratory multiple-case study approach was employed to consider how, when faced with AI as a disruptive technology, HPAs engage in sense-making and legitimation of the change in order to support their membership in preparing for future practice.Normalization process theory (NPT) suggests behavioural constructs required for complex change, providing a novel lens through which to consider the agency of macro-level actors in practice change. Four HPAs were studied, selected for early consideration of AI technologies in their fields. Data collection involved key-informant interviews and document review, focusing on sense-making, engagement, coordinated action, and reflexive monitoring work of the HPA. Concept coding allowed for inductive framing of individual case narratives and subsequent cross-case analysis. Concepts were then mapped against NPT constructs. Eighteen interviews were conducted and documents spanning 2013 to 2020 were reviewed. Eleven coding categories and 25 subconcepts were identified, spanning perceived impact of AI, perspectives on prevalent mindsets, roles of HPAs in preparing their membership, including changing education needs. The HPAs studied engaged in work that aligned with NPT in varying ways, with perceived roles in education, advocacy, and leadership. Emergent trends across the four HPAs suggested three factors that might influence engagement in work that aligned with NPT; factors related to the organization, those related to the profession, and those related to the innovation in question. All HPAs acknowledged AI’s impact on practice in medical imaging and radiation medicine, while some saw it as more of a disruptive force and assigned it greater priority in the organizations. Conceptualizations of the potential threat to the profession and the HPA’s role in supporting members in navigating that future landscape were also key insights gleaned through this work. This research suggests how healthcare professions are engaging at the macro level in the implementation and normalization work related to AI, and shed light on nuanced perspectives on AI of groups that would interface with it.
Availability and Accessibility of Primary Care for Community Dwelling Persons with Dementia
Keywords: access
dementia
primary care

This thesis comprises a description and analysis of access to primary care (PC) for community dwelling persons living with dementia (PLWD) in Ontario. PLWD benefit from PC for diagnosis, management, and connection to specialists and community supports, however, PC physicians and services are not equitably distributed in Ontario. The Patient Centred Accessibility Framework was used to define access and guide this thesis. Population-level health administrative databases were used to create a cross-section of community dwelling persons with prevalent, physician diagnosed dementia. To understand supply, demand, and realized access of community dwelling PLWD, the first objective used the cross-sectional study group described above, and semi-structured key informant interviews in a convergent mixed methods design. Access to PC in rural and urban areas was compared, finding that rural areas included a higher proportion of PLWD compared to urban areas, and that there was a larger supply of physicians in urban areas. Qualitatively, I explored how PC providers provide care and perceive supply and demand of health and community services for PLWD. Identified themes emphasized the different types of challenges in rural and urban settings. In objective two, I quantified the association between house calls (availability), travel time to PC physician (geographic accessibility), appropriateness (continuity of care) and emergency department (ED) use. I used regression analyses to measure the association in the study group, followed by stratification by urban and rural residence of PLWD. Results indicated that longer travel time to PC physician was associated with higher likelihood of ED use in urban settings. In the third objective, I measured the association between travel time, house calls, and continuity of care, and distress of caregivers of PLWD. Regression analyses of the entire study group were conducted, then the group was stratified by sex. Results demonstrated a positive association between having a physician who conducts house calls and caregiver distress. Findings from this thesis emphasize challenges in urban and rural access to PC, identifying potential for improving health use and outcomes among PLWD. These findings are relevant for clinicians, administrators, and policy makers working to improve access to PC in Ontario.
Creative Becomings: Explicit Fanfiction, Reinventing Adolescence, and Queer Relationality
Keywords: Adolescence
Fan studies
Fanfiction
Pop Culture
Queer Studies
Youth Studies

This dissertation is an interdisciplinary study into the experiences of adolescent fans in online fan spaces, particularly as they interact with sexually explicit fanfiction. Drawing together the threads of queer theory, adolescent sexuality, critical race theory, and fan studies, I use debates about teenagers and access to pornographic fanfiction as a starting point for a wider consideration of queer adolescent fans, the generative capacity of fan creative writing, particularly of the pornographic sort, and the relationality between adult and teenage fans. Working from Jen Gilbert’s (2007) provocation that “rather than trying to extricate youth from risk, for adolescence to occur, a risk must be taken ... tolerating this view of adolescence as development will require something more of adults and sex educators: the risk of relationality” (50), I explore sexually explicit fanfiction written and read by teenagers which puts adults and adolescents into direct conversations about desire and sexuality. Given the moral panics about teenagers accessing sexual information and engaging with sexual narratives online, as well as discourses that cast any adult engaging in conversations about sexuality with teenagers outside of an institutional setting as inherently predatory, I question what fandom and sexually explicit fanfiction might offer us in terms of alternative forms of “growing up” and relationality outside of the discourses of protection and education. I thus draw on theories of storytelling, play, digital space, and sideways growth to explore how/if fandom can offer a more generative way of looking at teenage experiences in the digital realm. Working from an understanding of fanfiction as collective, intertextual, and generative storytelling, each chapter of my dissertation involves discourse analysis and a close reading of a mix of fan-generated texts, from fanfiction (including some of my own early writing) to the debates, discussions, and creative engagements with fanfiction stories on the Archive of Our Own, Tumblr, and Twitter. In looking beyond moral panics, and the dual impulses to educate and to protect, I seek to consider what kind of creative work teenagers can generate and what this work can do – both for teenagers and for adults who interact with them.
South Asian Low-sodium sTudy (SALT): A Multi-Method Approach
Keywords: Hypertension
Knowledge Attitude and Behavior
Low-Sodium Diet
Nursing
Pilot Randomized Controlled Trial
South Asian

Background: Hypertension (HTN) is prevalent in South Asian Canadians (SAC), and dietary sodium is the primary contributing factor. The overall goal of the South Asian Low-sodium sTudy (SALT) is to describe contextual factors and determine the feasibility of implementing a six-week low sodium community-based dietary intervention to improve outcomes in SAC with stage one HTN. Methods: SALT is a multi-method study consisting of a pilot randomized controlled trial (RCT) and a cross-sectional survey. Following ethics approval, participants with stage one HTN were randomized to a usual care group or an intervention group. Participants in the usual care group received the HTN Canada booklet and those in the intervention group received the SALT Intervention (culturally specific manual, five online modules, five weekly telephone calls). The Sodium Calculator, health literacy assessment short-form, Asian Indian Dietary Acculturation Measure (AIDAM), Knowledge, Attitude, and Behaviour (KAB) survey were utilized. A non-probability sample of SAC over 18 years was recruited for the survey. Results: A total of 292 SAC participated in blood pressure (BP) screenings, 35 (12%) were eligible for the pilot RCT. Of these, 23 (65.7%) consented. Results demonstrated some feasibility in terms of recruitment, retention, acceptability and one of the four components of intervention engagement. Participants lacked sodium-related knowledge and had positive changes in their attitudes toward lowering dietary sodium. Linear Mix Models found a significant effect of time but no effect for the group or group-by-time interaction in BP and a significant effect of group (p=0.044) and no effect of time (p=0.861) and group-by-time interaction for urinary sodium (p=0.0263). A total of 354 SAC completed the cross-sectional survey. Survey results suggest that SAC has a mean sodium intake of 2,117±1896 mg/day, and most of the respondents were concerned about their sodium intake but lacked sodium-related knowledge. Conclusion: The finding of the SALT study suggests that SAC consume a higher than Adequate Intake recommendation of sodium; they are concerned about their sodium intake but lack the knowledge for behaviour change. Results of the pilot RCT suggest that a six-week low sodium community-based dietary intervention is feasible and a larger RCT is warranted.
Exploring Neural Stem Cell Activation in Recovery Strategies to Treat Neonatal Brain Injury
Keywords: constraint-induced movement therapy
hypoxia ischemia
metformin
neural stem cell lineage
neural stem cells
primitive neural stem cell

Harnessing neural stem cells and their progeny—together termed neural precursor cells (NPCs)—as a source of replacement cells after injury is a promising strategy for neural repair. I explored if endogenous NPC activation underlies recovery after neonatal stroke using two approaches: the drug metformin, and the neurorehabilitation strategy constraint-induced movement therapy (CIMT).Expansion of the NPC pool correlates with improved functional outcomes following neonatal stroke, and treatment with the drug metformin has been shown to expand the NPC pool and improve motor behaviour. To explore the role of activated NPCs in the metformin-mediated recovery, I used a GFAP-TK mouse model and designed a strategy to ablate the largest pool of neural stem cells (NSCs) in the postnatal brain in vivo, the definitive neural stem cells (dNSCs). A ~90% depletion of dNSCs in vivo is insufficient to prevent metformin-mediated sensorimotor and cognitive recovery following neonatal stroke. An increase in proliferating neuroblasts (DCX+Ki67+ cells) was observed in the NSC niche after stroke+ablation+metformin, suggesting neuroblast activation may underlie metformin-mediated recovery. Rehabilitation has been shown to confer improved motor outcomes after stroke. We designed a CIMT approach to treat mice following neonatal stroke which involved the administration of Botox injections to induce paralysis in the unaffected forelimb. I designed a CIMT approach in neonatal mice using Botox injections to induce paralysis in the unaffected forelimb at a time when NPC expansion is observed and asked if there was a correlation between NPC activation and CIMT-mediated recovery. CIMT improved motor function post-stroke and NPC activation was not observed at the time of recovery. Recovery was consistent with increased proliferation of microglia/macrophages in the cortex, suggesting that modulating microglia activity may play an important role in the CIMT-induced recovery. Using the novel paradigm developed in my first aim, NSC depletion studies revealed a novel NSC population in the neonatal and adult brain. I characterized the population and found it to be an intermediate neural stem cell (iNSC) between two well characterized populations in the neural stem cell lineage. This discovery redefines the neural stem cell lineage and may inform novel strategies to promote brain repair.
Distributed (Generalized) Nash Equilibrium Seeking in the Partial-Decision Information Setting
Keywords: Control Theory
Distributed Systems
Game Theory
Monotone Operators
Optimization

We consider the problem of distributed (Generalized) Nash Equilibrium seeking over networks. In this setting, agents have limited information about the other agents' actions and communicate locally over a communication graph to learn these actions. We start by first formulating the (Generalized) Nash Equilibrium problem and then present a method for solving the (Generalized) Nash Equilibrium problem under the most commonly used assumptions in the literature. From this starting point, we suggest four different research directions to extend the results: relaxing the game-map assumption, dealing with adversaries in the communication network, relaxing the communication graph assumptions, and improving scalability. We then present algorithms that deal with each one of these research problems.