VictorJuiz/thesis huggingface dataset:
Pathophysiologic Mechanisms, Prevention and Treatment of Antibody Independent Transfusion Related Acute Lung Injury

A key component of the ability to resuscitate or revive badly injured or ill patients involves transfusion of blood products. Though blood products offer incredible capacity to benefit patients in need, they are not without risk. Though infrequent, in 1 in 5000 transfusions, one of the most lethal (mortality ≈ 10%) and thus serious adverse events associated with receiving a blood transfusion is transfusion related acute lung injury (TRALI). TRALI causes chest infiltrates and hypoxia in part due to lung endothelial cell barrier disruption. Mechanistically, TRALI involves pathogenic antibodies or biological response modifiers (such as sphingolipids) from donor blood which damage transfusion recipients’ lungs. Antibody-mediated TRALI rates have fallen since interventions to reduce the amounts of antibodies in donated blood have been initiated. Antibody-independent-TRALI is hard to identify, let alone eliminate. To gain insights into antibody-independent-TRALI we elected to study platelet mediated TRALI. Platelets, especially those stored for extended periods prior to transfusion represent the highest risk cellular blood products for causing TRALI. We hypothesize that aged platelets are especially injurious due to key distinctions: 1) they contain more of the acid sphingomyelinase (ASM) derived sphingolipid ceramide (known to cause lung injury) and 2) have increased production of extracellular vesicles (EVs; small sub-cellular particles released from platelets during storage which we propose to mediate TRALI). TRALI’s low clinical incidence means studying this condition prospectively at the bedside is very challenging. As a result, we developed a novel murine platelet antibody-independent-TRALI model of TRALI as well as an in vitro human pulmonary microvascular endothelial cell injury model. Within these models we show that aged (stored 5-7 days), not fresh (stored 1 day) platelets or platelet EVs are able to mediate TRALI through an ASM/ceramide dependent mechanism. Present treatment of TRALI involves supportive care with oxygen and positive pressure ventilation. Our study offers pathophysiologic insights which may translate into novel therapies, for example inhibition of ASM during platelet storage or supplementation of the barrier-protective sphingolipid sphingosine-1-phosphate (S1P) within aged platelets may prove effective strategies to prevent or even treat antibody-independent-TRALI.

Keywords: ceramide
extracellular vesicles
lung injury
sphingosine-1-phosphate
transfusion-related acute lung injury
Advisor: Kuebler, Wolfgang M
Semple, John W
Youth Artists for Justice: Examining Participation in Social Movements and Envisioning Futures through Applied Theatre

This study examines how racialized, socioeconomically under-resourced secondary school-age youth in Toronto conceptualize their current and future roles within contemporary social movements and the larger political sphere. This collaborative ethnodrama action research study, Youth Artists for Justice, involved 12 participants ages 15-20, consisting mainly of racialized, socioeconomically under-resourced youth. The study expands understanding of how youth envision and enact political participation within the current context of ongoing racism in this neoliberal era. A goal of the program was to garner within these particular youth a sense of hope and capacity to conceptualize and enact their political agency. This research contributes to scholarly discourses of drama methodology and secondary school-age youth participation in social movements by examining how ethnodrama as a methodology supports youth in further developing theories of change, envisioning their own potential political roles, and entering into participation on their terms. Applied theatre practices in this study created space to honour and to apply counter-hegemonic knowledges, to embrace and mobilize emotional expression, to disrupt power, to enrich collective agency, and to perform a public performance with political efficacy. Findings show the need to attend to the sense of existential displacement and foreboding that many youth participants reported experiencing when envisioning the future. Another major finding points to how the Toronto youth participants, through the theatre-making processes, related to the embodiment of solidarity. In this study, devised theatre work with marginalized youth serves as a means of analyzing, experiencing, and modeling solidarity and its strategic importance as a modality for countering systemic injustice. Using a critical youth studies and applied theatre lens, this research expands discourse on how youth desire and strategize the means by which to enact both major structural change and local movement-building outside of neoliberal structures.

Keywords: Applied Theatre
Arts Education
Marginalized Youth
Participatory Politics
Social Movements
Youth Studies
Advisor: Gallagher, Kathleen
A Situational Analysis of Women in Higher Education Leadership Positions in Kenya

A Situational Analysis of Women in Higher Education Leadership Positions in Kenya Doctor of Philosophy (2019) Evelyn Jeruiyot Kipkosgei Department of Social Justice Education University of Toronto ABSTRACT Gender imbalance among senior university academics is an acknowledged problem in many countries, including Kenya. This thesis gives a situational analysis of women academics in senior leadership positions in institutions of higher education in Kenya. This study sought to determine the requisite attributes that propelled women to higher management positions in institutions of higher education in Kenya; to identify strategies adopted by women to attain leadership in higher education in Kenya; and to explore the lessons that can be drawn from the experiences of women in higher education leadership positions in Kenya. The research is anchored in feminist and leadership theories. The study uses data collected from 18 participants in senior leadership ranks derived through purposive and snowballing sampling technique across 32 public universities. A qualitative approach of in-depth semi-structured interviews aided by a questionnaire was used to collect primary data whereas secondary data was obtained by document analysis. Preliminary findings indicate that success largely depends on a combination of individual’s initiatives, institutional structures, and governmental interventions. Results indicated that women success in leadership positions at higher education institutions in Kenya is attributable to individual paradigm shifts, external networks, pro-women movements, and enforceable affirmative action plans. Strategies employed by women to attain leadership were identified as continuous education, determination and tenacity, performativity, goodwill, and the use of role models and mentors. Major attributes to emulate were: defining marks of leadership and identity, collaboration, spirituality, and performativity. It was concluded that women in this study merited their success since they possessed the required qualifications and experience. They had the ambition, drive, and patience to succeed against all odds. Going by their small numbers in managerial positions, there seems to be other underlying factors over and above qualifications that affect women career mobility. The study recommended an urgent and deliberate effort to address structural and sociocultural hurdles constricting the upward mobility of women. Recommendations include formulation of implementable affirmative action policies and introduction of egalitarianism in education curriculum. It is recommended that women get trained on to negotiation skills which exclude counterproductive confrontational approaches.

Advisor: Wane, Njoki N
Structural Characterization of Prion Protein Misfolding using Proteins from Resistant Species and Antibodies

Transmissible spongiform encephalopathies are a group of infectious and currently untreatable neurological diseases of humans and farmed and wild animals, that are caused by a unique pathogenic mechanism – misfolding of the cellular prion protein (PrP). PrP is primarily expressed in the nervous system. It is highly conserved among mammals and has orthologs in other vertebrates. The mature PrP is a GPI-anchored glycoprotein attached to the outer leaflet of the plasma membrane. It has two main structural domains. The N-terminal half is flexible and contains four or more metal binding sites. The C-terminal half is folded into a unique prion fold composed of two short β-strands and three α-helices. The misfolding of PrP leads to a poorly understood and aggregation-prone prion species rich in β-sheets. A number of pathologic mutations have been identified, mostly in the C-terminal domain. Some species, such as horses or chicken are considered resistant to prion diseases. To further our understanding of PrP’s pathologic conversion I explored two main areas. Firstly, I determined the crystal structure of the C-terminal, folded domains of horse PrP at 1.08 Å and of chicken PrP at 1.7 Å resolution. Both structures show a typical prion fold and a disordered highly conserved helix-2 helix-3 loop which was structured in crystal structures of PrPs from other species. Secondly, I showed that the β-sheet-rich octameric PrP induced by intermediate urea concentrations at low pH is stable at least for 80 days upon urea removal and is recognized by several antibodies. I determined the crystal structure of PRB7 Fab, a putative β-PrP-specific antibody. This antibody however did not show any binding to PrP or its proposed epitope peptide in the tested conditions. Antibodies D18, P and AMF-1c-120 showed a highly pH-dependant binding to β-octamers. While D18 Fab did not bind β-octamers at low pH, P Fab formed a stoichiometric 1:1 complex with β-PrP octamer, even at pH 4.5. This thesis describes structural features of PrP that may contribute to resistance to prion diseases in some species and provides a roadmap for the antibody-mediated crystallization of the misfolded PrP.

Keywords: crystallography
misfolding
neurodegeneration
prion protein
prions
structural biology
Advisor: Pai, Emil F
Empathy in Education: A Narrative Study into Practicing Teachers’ Experiences

This dissertation interweaves a study of how empathy is understood and talked about with an account of practicing teachers’ experiences. While empathy has long been proposed by educational thinkers as the remedy to social conflicts and divisions, it is also understood in myriad, and at times contradictory, ways. The ambiguity of the term does not seem to lessen empathy’s discursive cachet, however. And since the lack of clear or widely accepted conceptualization is no obstacle to empathy’s flourishing as an educational ideal, I propose that what empathy does (or what educators think it does) is much more important than what empathy is. Thinking of what empathy “does” – of what we are hoping for when we invoke it – frames empathy’s operation as a set of promises. Pedagogies of empathy and their interpretation by teachers thus become sites of examination for issues of systemic injustice in the education system. In fact, I suggest that behind most invocations of empathy are pressing systemic issues, unaddressed. I propose that while an uncomplicated “one-size-fits-all” model of decontextualized, prosocial, and teachable empathy is unlikely to be effective for students and teachers, neither is a model based primarily on teachers’ individual emotional responses to their students.

Keywords: empathy
empathy pedagogy
teacher narratives
Advisor: Boler, Megan
Biomedical Refusal: Pediatric Decision-making and the Settler State

This dissertation focuses on a recent case in which an 11-year-old Mohawk girl (whom I call Lyra) attempted, along with her family, to refuse chemotherapy in favor of Haudenosaunee healing practices. Drawing from 3 years of fieldwork, I unpack Lyra’s case at two interrelated levels. At the micro level, I foreground the lived experience of Lyra and her family, as well as the clan mothers, healers, clinicians, and state agents who became entangled in her care. I paint a thick picture of the decision to resist treatment and then of sticking to and living with that decision – one that illuminates the way participants’ moral worlds, discursive practices, and local epistemologies came together to shape their decision-making. At a macro level, I illuminate the sociocultural mechanisms and ideologies that structure “choice” in pediatric decision-making. Young people like Lyra who resist treatment reveal an intricate legal and medical infrastructure that dictates who is seen as capable of making medical decisions and who is not. Throughout I attend to the complex ways Indigenous sovereignty is asserted in settler states.

Keywords: Ethics of Childhood
Ethnography
Pediatric Bioethics
Relational Autonomy
Settler Colonialism
Subjectivity and Resistance
Advisor: Volpe, Richard
Functional Polyester Materials for Manipulation of the Cellular Microenvironment

Polyester materials are used in many biomedical applications, including tissue engineering scaffolds and a variety of biomedical devices. Given their degradability and well understood chemical synthesis, these materials serve as a strong platform to develop polymers that impact cell microenvironments. Here, we describe the development of polyesters that exhibit inherent modulation of (a) mechanical properties to mimic the extracellular matrix of cardiac tissue and (b) incorporate a biomimetic moiety of mammalian immunity to support infection prevention and integration at the material surface. Using polycondensation techniques, incorporation of unsaturated carbonyl groups allowed for controllable molding and crosslinking to generate material constructs with intricate designs and highly tunable elasticity that matched that of cardiac tissue. Mechanical behaviour was controllable according to synthesis conditions. This supported maturity of engineered tissue constructs, which was further enhanced with incorporation of carbon nanotubes into elastic material scaffolds to support electrical cell communication. In biomaterial application, inflammation and infection at the biomaterial surface limits integration. To tackle this, itaconate was incorporated into material backbones to impart biomimetic small molecule modulation with hydrolytic degradation release. Quantifiable release of the small molecule from multiple polyester material chemistries was observed, suggesting material potential as a long-term drug delivery depot. Itaconate containing materials demonstrated the modulation of activated macrophage inflammatory behaviour and prevention of bacterial growth in vitro. Material implantation presented similar outcomes, with reduced mortality with bacterial loading and minimized immune infiltration following material injection into the peritoneum. Using scalable polyester synthesis techniques, we have demonstrated the power of instructive biomaterial technologies as functional modulators of the cell microenvironment.

Advisor: Radisic, Milica
Vox Populi: Organized Crime, Media Politics, and Subaltern Publicity in Contemporary Naples, Southern Italy

This dissertation investigates the organized crime sponsored mediascape of Naples, Southern Italy, through the ethnographic analysis of the "neomelodic" media industry. Neomelodic folk-pop songs and local TV shows constitute a main form of media entertainment among the current Neapolitan lower-classes. These cultural productions aim to depict the experience of the local poor, specifically those involved with the Camorra: a criminal organization that is also a major investor in the neomelodic mediascape. With this in mind, this dissertation explores the neomelodic media industry as a cultural, aesthetic, and politico-economic platform of informal governmentality, which attempts to reconcile the Neapolitan subaltern publics with the political violence managed by local Camorra networks versus the unaccountability of the Italian state toward its social peripheries. Complementing historical insights with ethnographic data collected amid neomelodic sites of cultural production, this dissertation shows that Camorra-mediated subaltern politics parallel the neoliberal policies engendering the populist take-over of the post-Berlusconian Italian state over the national media industries since the mid-1990s. These policies, in fact, turned Italian national media into platforms of informal engagement with the public sphere, which served the local subaltern as self-exploitative tools of socio-economic mobility and indirect governmentality. Through this comparison, this dissertation ultimately shows how the politics enacted by contemporary criminal cartels and the neoliberal state are articulated in tension with each other, since they hinge on similar logics of mediation. Together, they deploy an interactive regime of subaltern publicity, which reproduces historical conditions of social inequality while turning them into mediacratic forms of agency and populist reinterpretations of power and violence.

Keywords: Italy
Media Studies
Neoliberism
Organized Crime
Political anthropology
Subaltern Politics
Advisor: Muehlebach, Andrea
Song, Jesook
Assessing Indigenous Food Systems and Cultural Knowledges Among Smallholder Farmers in Ghana: Towards Environmental Sustainability Education and Development

Suleyman Mohammed Demi Doctor of Philosophy Department of Social Justice Education, Ontario Institute for Studies in Education University of Toronto 2019 Abstract Africa is expected to experience elevated temperatures and frequent drought that will decrease crop yields by half (Boko et al., 2007). Unpredictable weather patterns negatively impact Indigenous food systems (IFSs) across Africa, including Ghana. This study sought to (a) examine Indigenous food production practices among smallholder farmers in Ghana; (b) investigate how cultural knowledge(s) offer pedagogical lessons in environmental sustainability education in Ghanaian schools; (c) identify specific environmental challenges and adaptation strategies confronting smallholder farmers in their food production activities and their implications on IFSs and farmersʼ livelihoods; and (c) identify the implications of development as understood by smallholder farmers on IFSs. The study is grounded in three theoretical frameworks: political ecology, anti-colonial theory, and Indigenous knowledge (IK) perspectives. The mixed-methods study surveyed 136 participants and selected 105 for in-depth interviews and focus group discussions in addition to workshops, participant observations, and document analysis. Quantitative data were analyzed using SPSS 24 and Excel while coding and thematization using NVivo software for qualitative data. Results indicate that although smallholder farmers use considerable IK in in their farming practices with Indigenous food crops—including soil and seed selection, food processing and preservation, management of various diseases, and adaptation to adverse environmental conditions—IK is seldom taught in schools. The study further indicates farmers face numerous environmental challenges including prolonged drought, deforestation, indiscriminate grazing, and misuse of agrochemicals, resulting in acute water shortages, extinction of Indigenous food crops, and increases in poor health and social insecurity. Participants understand development as any happenings in human life both negative and positive be it on a personal, community, or nationwide scale. The study recommends that civil society and farmer groups should demand the government of Ghana to improve its meteorological resources and services for greater precision in weather forecasting and better support farmers in growing both Indigenous and new varieties of crops. Research institutions should identify Indigenous sciences that can be included in the science curriculum to augment Western-based sciences.

Keywords: Development
Education
Environment
Food system
Indigenous knowledge
sustainability
Advisor: Dei, George J.S
Immunotherapy for Alzheimer’s Disease: IVIg Delivery to the Hippocampus in a Mouse Model of Amyloidosis

Alzheimer’s disease (AD) is characterized by cognitive decline, neuronal degeneration and pathologies, which include toxic amyloid beta peptides (Aβ) and tau. To date, there is no cure for AD and therapies are only symptomatic. A Phase III clinical trial using intravenous immunoglobulins (IVIg) - natural antibodies collected from the plasma of healthy blood donors and shown to reduce AD-related pathologies in mouse models - recently failed to prevent cognitive decline in people living with AD. IVIg treatment efficacy may be suboptimal due to the blood-brain barrier (BBB), which restricts the bioavailability of IVIg to the brain. We propose to address this problem by administering IVIg intravenously combined with focused ultrasound (FUS) to temporarily increase BBB permeability. Our hypothesis is that IVIg will enter FUS-targeted hippocampi, promote neurogenesis and decrease amyloid pathology in the TgCRND8 (Tg) mouse model of amyloidosis. In 3-month-old Tg mice, we found that the hippocampal bioavailability of IVIg was increased by 7-fold with FUS. Within one week, IVIg was cleared from the hippocampus. We discovered that two weekly treatments of IVIg with FUS promoted hippocampal neurogenesis by 3-fold compared to IVIg-alone, significantly increasing both the proliferation and survival of neural progenitor cells in the dentate gyrus. Compared to IVIg-alone, IVIg-FUS also increased pro-neurogenic cytokine interleukin-2 in the serum and decreased pro-inflammatory cytokine tumor necrosis factor alpha in the hippocampus. Aβ pathology was significantly decreased by IVIg-FUS, IVIg-alone and FUS-alone treatments. The findings in this thesis point to the benefits of coupling IVIg therapy with FUS to enhance its bioavailability and engage neuronal systems, in addition to reducing Aβ pathology and modulating the inflammatory environment. Compared to traditional intravenous administration of IVIg and other amyloid targeted antibodies, brain targeted IVIg treatment using FUS could provide greater benefits in the treatment of AD.

Keywords: Alzheimer's disease
Amyloidosis
Focused Ultrasound
Inflammation
Intravenous Immunoglobulin
Neurogenesis
Advisor: Aubert, Isabelle
Hynynen, Kullervo