VictorJuiz/thesis huggingface dataset:
Outcomes and Management of Type 2 Diabetes in India and China

Nearly half of all the adults with diabetes worldwide live in India and China. This thesis examines various aspects of the management and outcomes of type 2 diabetes mellitus in these populations. In India, the objective was to examine the associations between diabetes and cardiovascular mortality (due to ischemic heart disease and stroke), and between self-reported medication use and cardiovascular mortality among adults with diabetes (with or without comorbid hypertension), in a nationally representative population of India. In Hong Kong, China, the objectives were to determine how age at diagnosis and modifiable risk factors affect hospitalization rates, glycemic exposure, glycemic deterioration, and responses to oral glucose-lowering drugs. In India, diabetes was associated with double the odds of ischemic heart disease mortality and increased odds of stroke mortality. Medication use was associated with lower odds of ischemic heart disease mortality and stroke mortality in high-burden states among people with diabetes and hypertension, with no significant association among people with diabetes alone. In Hong Kong, people with young-onset type 2 diabetes had the highest hospitalization rates, and that 36.8% of bed-days before age 40 years were attributable to mental illness. The adjusted rate ratio of hospitalization was increased in young- versus usual-onset type 2 diabetes for hospitalizations due to any cause, renal causes, diabetes-related causes, cardiovascular causes, or infection. Based on model estimates, intensified risk factor control in young-onset type 2 diabetes was associated with a one-third reduction in cumulative bed-days from diagnosis until age 75 years. people with young-onset type 2 diabetes had a higher mean A1C throughout the lifespan. The cumulative glycemic exposure was >3 times higher for young-onset versus usual-onset type 2 diabetes. Younger age at diagnosis was associated with faster glycemic deterioration, while age at diagnosis ≥60 years was associated with glycemic improvement. Responses to oral glucose-lowering drugs differed by age at diagnosis. Those with young-onset type 2 diabetes had smaller A1C decrements for metformin-based combinations versus usual-onset type 2 diabetes, but greater responses to other combinations containing sulfonylureas. These findings call for better strategies and further research to improve diabetes management and outcomes in India and China.

Keywords: cardiovascular disease
China
hospitalization
India
prognosis
type 2 diabetes
Advisor: Shah, Baiju R
Factors Influencing Service Engagement of Youth in Services for Concurrent Disorders: A Mixed-methods Approach

Objective. Despite the high prevalence and negative impacts of co-occurring substance use and mental health problems (i.e., concurrent disorders) among youth (ages 14 to 24 years), the dearth of evidence-based and developmentally appropriate services for youth with concurrent disorders, and high rates of discontinuing services early among this population, little research has focused on understanding their service engagement. This dissertation employed a mixed- methods approach to understand a broad range of factors influencing engagement of youth in services for concurrent disorders. Quantitative Study. This investigation examined service engagement, as defined by attending at least five sessions, to understand how engagement changes across service stages and what client-related factors predict engagement. Three hundred and two youth presenting to an outpatient concurrent disorders service completed questionnaires investigating a variety of factors. Those found to be positively associated with service engagement included greater challenges with anxiety, depression, trauma, substance use, and emotion regulation. Identifying alcohol as the only substance of concern was negatively associated with engaging in services. Qualitative Study. This investigation allowed for a broader and more in-depth understanding of service engagement by considering client as well as service-related factors. Qualitative data were gathered from semi-structured interviews with 20 youth who had attended or were attending outpatient services for concurrent disorders. Thematic analysis revealed that youth consider engagement to be expressed in a variety of ways including attendance, participation in sessions, and actions taken between sessions. Factors – including social relationships, mental health and/or substance use challenges, readiness to change, treatment approach, and clinician characteristics – influenced service engagement. Conclusion. Youth engagement in services for concurrent disorders is more complex than just attending sessions. Behaviours during and between sessions are also important. Service engagement among this population is impacted by a variety of factors, including youth’s perspectives of services and their mental health and/or substance use challenges. It is critical that early service delivery efforts seek to understand the needs and preferences of youth in order to individualize services and promote engagement. Continued research should focus on factors influencing service engagement to help establish best practices for youth in services for concurrent disorders.

Keywords: concurrent disorders
treatment
youth
Advisor: Henderson, Joanna
“En el Lugar del Otro:” Género, Poder, Violencia y Exilio en las Novelas de Tomás Eloy Martínez

My doctoral research is focused on gender representations in the novels of Tomás Eloy Martínez. It seeks to conceptualize ways in which gender manifests itself within contexts of power, violence, and exile in order to establish Martínez’s unique approach to gendering these aspects of the human condition. Because Martínez is not commonly considered an author with a gender-centered agenda but rather representative of the postmodern writing, it is necessary to clarify the relationship between his narrative strategies and those of ‘gendered’ writing. These include feminist, queer, and new masculinity constructions. To this end, I explore contentious issues in the debate between these approaches, such as identity, subjectivity, sexuality, corporeality, and emancipation, to better understand Martínez’s strategies with regard to these proposals and uncover the theoretical meaning of his postmodern heterogeneity.My study suggests that the ways in which Martínez understands and represents gender struggles are reflective of the tense relationship between gender studies and the postmodernist paradigm. While the gendered approach translates in his novels into feminist representations of patriarchal oppression, gender violence, and masculine domination, the postmodern influences are responsible for the distortion and subversion of gender roles. The resulting hybrid discourse shows that traditional patriarchal roles serving as a metaphor for state oppression and violence coexist with the queerness that erodes authoritarian power and resemantizes gender as a result of exilic trauma. The point of convergence between gender studies and postmodernism in Martínez’s novels is the author’s overarching attention to the subjectivity of his characters. Although Martínez does not advocate for feminine, masculine, or queer subjectivity exclusively, he emphasizes the fact that violence, power, and exile are experienced by individuals as gendered beings and that experiencing these conditions may, in fact, disrupt and alter the very notion of gender. Acknowl- edging the gendered aspects of power struggles, violence, and exile, in turn, validates the authenticity of these discourses lending them a personal dimension and allowing the author to take a bolder stance on themes crucial to Latin American literature in his era.

Advisor: Sarabia, Rosa
Origin of Disease Heterogeneity in BCR-ABL1 Lymphoblastic Leukemia

BCR-ABL1 positive acute lymphoblastic leukemia (ALL) is an aggressive subtype of ALL that commonly appears in adults. Introduction of tyrosine kinase inhibitors into frontline treatments has significantly improved outcomes; however, the disease still frequently relapses and becomes refractory to targeted therapy. To understand this phenomenon, an in-depth genomic investigation, including RNA-sequencing (RNA-seq), single-cell RNA-seq, and whole-genome sequencing (WGS), of BCR-ABL1 ALL was performed. First, RNA-seq analysis identified three distinct molecular subgroups within BCR-ABL1 ALL. The first subgroup expressed higher levels of stem/myeloid genes, phenotypically resembled early-pro-B cells, and was termed ‘Aberrant Stem and Myeloid’ (ASM). The ‘Core B-lymphoid 1 and 2’ (Core-B 1/2) subgroups expressed higher levels of B-lymphoid genes and resembled pre-pro-B/pro-B cells. Clinically, ASM and Core-B 2 patients showed slower rates of achieving remission, higher relapse rates, and worse overall survival than Core-B 1. Single-cell RNA-seq revealed that ASM leukemias are highly heterogeneous and consist mostly of dormant cells, which could contribute to resistance against cytotoxic agents. Second, WGS analysis found that ASM subgroup was enriched for inactivation of HBS1L, RUNX1, and EBF1 genes, whereas Core-B 1/2 were enriched for inactivation of PAX5 and CDKN2A/B. Core-B 2 was uniquely defined by homozygous losses of IKZF1. Most focal deletions in all three subgroups were generated by RAG-mediated recombination. Tracking mutations in hematopoietic precursors and in diagnosis/relapse pairs supported that subgroups arose through secondary, stage-specific inactivation of B-lineage factors. Third, the integrated genomics approach was adapted to detect cryptic genomic lesions in complex karyotype acute myeloid leukemia. While complex karyotype leukemia is often considered a single entity, individual leukemias harboured unique driver events, such as gene fusions. Therefore, genomic analysis can effectively complement conventional cytogenetics in leukemia diagnosis. In summary, transcriptomic and genomic investigations reveal that human leukemias consist of heterogeneous subgroups that arise from acquisition of distinct genetic lesions.

Keywords: Acute lymphoblastic leukemia
BCR-ABL1
Cell-of-origin
Disease heterogeneity
Genomics
Transcriptomics
Advisor: McPherson, John D
Notta, Faiyaz
The Making of Urban Knowledge: Ideas, Cities, Gurus

In the face of severe political, economic and environmental crises at the urban level, cities have been seen in recent decades not only as the place where these problems are created, but also as the location where they could be solved. This construction of cities as sites of both crisis and opportunity is related, at least partly, to the work of urban experts, transnational organizations, professional networks, and local agencies taking part in developing and connecting cities with ‘big ideas’ like Resilient Cities, Smart Cities and Creative Cities. To examine the making of such ideas, this dissertation develops the theoretical model of the Urban Knowledge Making Triangle, joining together three different units of analysis - Ideas, Cities, and Agents. The triangle calls to investigate how the ‘same’ idea varies over time and across places, how cities use the idea to depoliticize and re-politicize local struggles, and how human agents connect cities with the idea. To demonstrate the approach, I focus on the Creative City paradigm, which describes the shift that cities took when adjusting their economic industrial base to the information age. It also offers a formula to recover from the urban decline that many cities experienced during post-industrialization. The Creative City long-life cycle and flexible formula which is applicable to cities of different sizes and geography, make its local translations vary extensively. I use fieldwork methods to examine the making of the Creative City in Jerusalem and Toronto and the role of Richard Florida in connecting the two cities with the idea; I also use Structural Topic Modelling to draw the broader contours of arts and culture discourses using a policy corpus of the largest 26 cities in the Anglo-Saxon world. The findings demonstrate the dialectic relationship between the construction of cities as sites of crises and as sites of opportunities.

Keywords: Creative Cities
Globalization
Public Art
Science and Technology
Sociology of Ideas
Urban Studies
Advisor: Silver, Daniel
Technology to Support Informal Caregivers: Matching the Tools to the Needs from a Sex and Gender Perspective

Caregiving can be highly stressful and associated with poor mental and physical health. Technologies, including mobile and e-health applications, have been developed to address caregiver needs. Yet, although caregiving is a gendered activity, sex and gender considerations have not been incorporated systematically in understanding caregiving experiences and the design of these technologies. As such, this thesis aims to develop a tool to assist in the development of technology interventions to support caregiving by (1) synthesizing evidence on sex and gender distinctions in caregiving experiences and its physical and mental health impacts on informal caregivers, (2) examining caregiver’s knowledge, use, perceived usefulness and feature preferences of technology, and (3) exploring sex and gender influences on technology use and perceptions amongst informal caregivers. Findings from each objective are used to inform tool development. The thesis was based on three studies. The first study, a systematic review on sex and gender distinctions in caregiving experiences and its impact on informal caregivers’ physical and mental well-being, found 13 studies reporting higher caregiving burden among female caregivers. Results from the second study, a secondary analysis of a cross-sectional survey on technology needs and preferences of informal caregivers, revealed that most caregivers did not know much and had never used any technologies to assist with caregiving. Female respondents were more likely to have more knowledge about technology for caregiving while male respondents were more willing to pay higher amounts for these technologies. Findings from the third study involving semi-structured interviews with informal caregivers and technology researchers, highlighted the multi-faceted role technology can play in aiding caregiving, while at the same time draw attention to the pitfalls and drawbacks of these technologies perceived by caregivers. Together, the findings lead to the creation of the CareDATA (Caregiving Diversity and Technology Assessment) tool. It provides key considerations for incorporating sex, gender and diversity when developing technologies for caregiving. Overall, this thesis highlighted the complexities of sex, gender and diversity within the field of both caregiving experiences and technologies and represents a robust step towards the realization of more tailored technological solutions to support informal caregivers.

Keywords: Caregiving
Diversity
Gender
Older Adults
Technology
Advisor: Colantonio, Angela
Brain Synchronization with Electroencephalography (EEG) for Children/Youth with Disabilities, their Parents, and Neurologic Music Therapists

Research investigating ‘physiological empathy’ in neurodevelopmental and pediatric neurorehabilitation settings is very limited. Previous research has suggested that music may be a potent language to drive interpersonal synchronization, at both socio-emotional and neurophysiological levels. The most practical approach to study neurophysiological synchrony is via electroencephalographic (EEG) hyperscanning, which is the measurement of activity in two or more brains simultaneously. We carried out two empirical studies using EEG hyperscanning to investigate the neural mechanisms of real-time social interactions in children with neurodevelopmental disorders during music and storytelling (as a comparison condition) conditions. In the first study, we investigated interbrain synchronization in a “youth with cerebral palsy-mother” (YM) dyad and a “youth-therapist” (YT) dyad. We found significantly higher interbrain synchronization during music condition only in the YM dyad, possibly due to music familiarity, and maternal cognitive-empathy and emotional predisposition. In addition, interbrain synchronization occurred in empathy-related frequency bands (delta: 0-3 Hz) in the YM dyad and in cognition-related frequency bands (alpha: 8-15 Hz) in the YT dyad. Both YM and YT dyad also experienced synchronization in empathy-related brain regions. The findings in the first study established the feasibility of using interbrain synchronization as an objective measurement of socio-emotional responses in a youth with CP. Thus, in the second study, we extended our protocol to include an expanded sample, comprising of both verbal and non-verbal children with CP or autism spectrum disorders (ASD) to confirm the presence of interbrain synchronization in both dyads. Additionally, we explored the directionality of interbrain synchronization and its correlation to measures of behavioral empathy. Patterns of interbrain synchronization similar to those of the first study were observed. In terms of directionality, we found a significantly higher directed coupling from adult (mother or music therapist) to child compared to the coupling from child to adult, potentially due to adult anticipation of child responses and lower child propensity for synchrony. In sum, this thesis lays the foundation for follow-on research that seeks to understand the socio-emotional responses of children with neurodevelopmental disorders, and thereby guide parental care and care provider intervention.

Advisor: Thaut, Michael
Chau, Tom
Towards an Understanding of the Chemical Formation Pathways of Polycyclic Aromatic Hydrocarbons (PAHs) in Sooting Flames

Combustion of hydrocarbons inadvertently produces soot which has detrimental effects on both health and environment. Polycyclic Aromatic Hydrocarbons (PAHs) play a central role in soot formation. Several chemical pathways have been predicted to explain the growth of PAH growth during combustion like sequential addition of small species (C1, C2, C3), reactions between aromatic radicals and reactions of Resonantly Stabilised Radicals (RSRs) with another RSR or PAH. These pathways have been developed based on the experimental trends. However, the experimental dataset available in the literature is limited especially for coflow diffusion flames. As a result, a chemical mechanism developed based on the experimental results of one fuel or flame configuration can not explain the PAH growth for other fuels or burner configuration. The uncertainty increases as the PAHs grow larger and depart from the gas-phase. Some studies suggest that this departure starts as PAHs containing 13-16 rings are formed. Other studies suggest that the medium-sized PAHs (containing four or five rings) depart from the gas-phase to form soot. This thesis presents an extensive and comprehensive database comprising of PAHs, soot volume fraction, temperature and soot morphology for aliphatic and aromatic fuels in a coflow diffusion flame. The thesis describes the relationship between the fuel structure and the PAH formation pathways. The potential global chemical pathways for PAH growth discussed here can help in developing more comprehensive and accurate chemical mechanisms. The experimental results show that for aliphatic fuels, PAH growth takes place mainly by sequential addition. For alkylated aromatic, the growth of PAHs take place by the reactions between RSRs, reactions between aromatic radicals and hydrogenation of PAHs followed by addition of methyl radicals. The thesis also discusses the surface chemistry of particulates. The surface composition of the young soot is dominated by medium-sized PAHs and is similar to the gas-phase in its vicinity. With the increase in flame temperature or degree of maturity of the particles, medium-sized PAHs desorb from the surface of the particles into the gas-phase. Large PAHs are dominant only on the surface of the mature particles suggesting that these PAHs might be growing on the surface.

Keywords: combustion
fuel
gas chromatography mass spectroscopy
hydrocarbon
Polycyclic Aromatic Hydrocarbons (PAHs)
soot
Advisor: Thomson, Murray J.
Correction of Cerebrovascular CFTR Expression and Systemic Adrenergic Receptor Blockade Normalize Cerebrovascular Resistance and Mitigate Cardiovascular Dysfunction Following Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) is a deadly stroke subtype that kills or causes permanent disability in most of its victims. Nimodipine therapy is currently the standard of care for SAH patients. Although nimodipine provides neuroprotective benefits to SAH patients, the resulting rates of morbidity and mortality are still alarmingly high. SAH standard of care has not significantly changed in three decades, highlighting the urgent need to develop better therapeutic strategies. Importantly, SAH also inflicts damage to peripheral tissues, likely due to the surge in circulating catecholamine levels that accompanies SAH. Notably, cardiac dysfunction is a common side effect and detrimental increases in blood pressure are frequently observed in SAH patients. We propose that SAH standard of care can be refined with the addition of two elements: (i) specific targeting of cerebrovascular processes that are altered by SAH and (ii) systemic protection of the cardiovascular system from collateral damage that would otherwise exacerbate the primary cerebral pathology.In an experimental murine model of SAH, we found that lumacaftor, a reagent that increases expression of the cystic fibrosis transmembrane conductance regulator (CFTR), prevents the SAH-induced augmentation of cerebrovascular myogenic responsiveness and the subsequent neuronal injury. In contrast, the current standard of care nimodipine fails to normalize cerebrovascular reactivity and neuronal injury in our SAH model. Importantly, CFTR is not expressed in the peripheral vasculature; lumacaftor therefore exerts high specificity for the cerebral microcirculation and targets only the pathological elevation of cerebrovascular myogenic responsiveness in SAH. Additionally, we investigated the effects of our SAH model on peripheral cardiovascular function. We found evidence of impaired cardiac function and elevated myogenic responsiveness in peripheral arteries; this latter effect is associated with increased total peripheral resistance, a main determinant of blood pressure. Anti-adrenergic therapy with the clinically-available β-blocker bisoprolol and α-blocker terazosin effectively prevents the cardiac dysfunction and restores peripheral artery myogenic responsiveness, respectively. In summary, this investigation provides detailed mechanistic insight into a novel therapeutic approach towards correcting cerebral microvascular dysfunction following SAH and a complementary therapeutic approach towards alleviating peripheral cardiovascular dysfunction that is suited to improve clinical outcome in SAH patients.

Keywords: catecholamine
cerebral blood flow
mechanosensor
myogenic response
resistance artery
subarachnoid hemorrhage
Advisor: Bolz, Steffen-Sebastian