VictorJuiz/thesis huggingface dataset:
The Spectrum, Impact, and Management of Cardiovascular Disease in Ontario Women with Early Stage Breast Cancer
Keywords: breast cancer
cardiovascular disease
clinical epidemiology
competing risks

Background: There are limited data about the epidemiology of cardiovascular disease after early stage breast cancer. Methods: We conducted four cohort studies utilizing data from Ontario women diagnosed with early stage breast cancer between 1998 and 2015. The first study describes causes of death after breast cancer, with a focus on patient strata where death from cardiovascular causes may exceed that from breast cancer. The second study examines hospital presentations for different categories of cardiovascular disease, and their temporal relationship to heart failure, comparing early stage breast cancer cases to age-matched women without cancer. The third study develops a score for predicting cardiovascular risk after early stage breast cancer. The final study examines 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitor (also known as statins) use after early stage breast cancer as a marker of cardiovascular preventative therapy, with comparison to cancer-free women of similar cardiovascular risk. Results: Breast cancer was the most common cause of death. Among patients with prior cardiovascular disease, the risks of death from breast cancer and cardiovascular disease were equivalent for the first five years, after which death from cardiovascular causes was more frequent. For women aged ≥66 years who survived ≥5 years after diagnosis, cardiovascular disease exceeded breast cancer as the leading cause of death at ten years post-diagnosis. The 10-year cumulative incidence of cardiovascular hospitalization was 11.7% after early stage breast cancer and 10.6% in controls. The ratio of cardiovascular disease rates between the cohorts increased with time. 76% of cardiovascular hospitalizations were for diagnoses other than heart failure. 36% of first heart failure presentations were preceded by hospital presentation with another cardiovascular disease. We developed a score to predict the risk of death or hospitalization from cardiovascular disease. Model calibration and discrimination were good. The c-index in the validation cohort was 81.3% at 5 years. Finally, we observed that women with early stage breast cancer were less likely to dispense statins compared to cancer-free women, though the differences were small. Relevance: These data provide useful insights into the importance of cardiovascular disease and how its management can be improved in women with early stage breast cancer.
Learning in the 'Land of Ashes': 'Poland' through the windows of a bus on the Toronto March of the Living
Keywords: Holocaust
Israel
Jewish education
March of the Living
Pilgrimage
Poland

This dissertation seeks to determine how learning in situ in Poland during the March of the Living (a trip which takes young Jews to Poland and Israel) shapes the curricular experience of Holocaust education. It examines the trip’s purpose of constructing Jewish self and communal identities through the history, and what impact that may have on the participants’ understanding of history, their Jewish identity and the Polish-Jewish relationship. This qualitative research study revolves around three questions: What pre-existing beliefs and attitudes regarding Poland do students bring into the trip? How do pedagogical choices employed in Poland change the narrative of the Holocaust from static to active? And, how does this act of experiential Holocaust education shape the participants’ beliefs, actions, and relationships with the Jewish community over time? It determines that many participants have a tendency to ‘inherit’ negative memory and myth about Poland from previous participants and family members, and the March’s creation of a ‘Poland’ that exists entirely as a Jewish construct certainly reinforces those pre-trip attitudes. Once there, the conflict between experiential and formal education that the program tries to negotiate results in the prioritization of emotional understandings of history over intellectual ones. The common use of ‘embodiment’ within the trip encourages students to “enter history” on the side of Nazi victims, and in the absence of Nazis, local Poles surrounding the students become placeholders for the perpetrators and bystanders as a counterpoint to the students’ embodied ‘victim.’ The highly emotional, identity-building pedagogy on the trip feeds into various types of ‘modeled’ types of Jewishness presented to students throughout the trip, and the most pervasive form students exit with is one that is both under threat and empowered (represented by Holocaust and Israel respectively). This research indicates that the March attempts to bridge both educational and identity-building agendas, but is at present unable to successfully negotiate that tension, resulting in students lacking considerable knowledge about the Holocaust. Their Jewish identity building measures also seem to work to change attitudes, but not behaviours. This would indicate mixed levels of success for the March of the Living’s key goals.
An Examination of the Culture of Health education and Education for Health in Timor-Leste
Keywords: Community health education
Timor-Leste

This study examines public health culture in Timor-Leste, subsequent to independence in 2002. After having been a colony of Portugal for 450 years and under Indonesian occupation for almost 25 years, Timor-Leste has established a new health system and began promoting health education in the country. This thesis is a qualitative case study in which prominent local people and international workers in Timor-Leste were interviewed, and existing information from both international and local organizations was investigated, along with relevant research from the literature review. The information was compared with neighbouring countries’ health education programs and similar studies. Moreover, this study explores the benefits and disadvantages between one district near the capital and another district at the east end of the country. The government organized the flagship program, Servisu Integradu da Saúde Communitária (SISCa) (Integrated Community Health Services) titled, “From, With and To the Community,” as a bottom-up program in 2008, for participation by the citizens. The government is successfully shifting from only hospital health care to community health care. In addition, the model of curable health care was changed successfully to one of preventative health care. The government will need to continue development of the country’s health plan by implanting more fully health education in the schools and communities, and by organizing infrastructures, such as the clean water system and the sewage system in the whole country, to modify the sanitation and hygiene problems.
Thinking Beyond the Secular-Pious Divide: A Relational Study Within and In-Between Secular Feminists and Pious Feminists in Turkey
Keywords: Political Theory
Turkish Politics
Women's Studies

My dissertation examines the relationship between secular feminists and pious feminists in Turkey from a relationship-centered, transformation-oriented, multi-discursive approach. Despite the growing research on either one group or the other, the current literature that brings together the two sides of the debate and explores the interpersonal relationships between the two women’s groups is at best minimal. This lack of relational focus not only reinforces the secular-pious binary in Turkey and reduces the complex and dynamic relationship between the two women’s groups into a relentless, seemingly irresolvable political opposition, but also, it limits further opportunities for possible future collaboration. My study is an effort to relationally rethink and deconstruct this common assumption. Based on my data from open-ended, one-on-one interviews, group interviews, and participant observation in Turkey in between 2011 and 2013, I analyze secular feminist and pious feminist narratives and identify alternative concepts to rethink the relationship between the two groups beyond the secular-pious divide. In the intersection of applied theory and empirical ethnographic research, I provide detailed discussions of secular feminist friendship (Chapter 3), pious feminist autonomy (Chapter 4), and the overall dynamics of disagreement and collaboration between the two groups (Chapter 5). In this manner, rather than predominantly relying on the assumptions of the secular/pious and analyzing how it predetermines feminist relationships, my analysis contributes to the previous debates by analyzing feminist relationships and how they iteratively challenge the assumptions of the secular/pious. While documenting both group’s perceptions of selfhood and otherhood, I also document how these perceptions change when my participants think about their Other in relation to themselves. I pursue this task by posing two inter-related questions: How can secular feminists and pious feminists in Turkey transcend their political fixities and transform their relationship in a more plural and collaborative manner? How can secular feminists and pious feminists in Turkey act upon their shared feminist interests instead of political disagreements, and in this way collaborate on the same women’s civil society project as equal partners and by mutual consent?
Automating High Content Screening with Deep Learning
Keywords: Deep learning
High content screening
Machine learning
Microscopy
Phenomics
Saccharomyces cerevisiae

High-content screening (HCS) combines automated microscopy with high throughput technologies for assaying genetic or environmental perturbations. HCS systems have enabled experiments designed to infer relationships between genetic mutations, compound libraries, and cellular phenotypes. Despite the benefits of image-based screens, analyzing large amounts of microscopy data remains a challenging bottleneck. Complex patterns, such as sub-cellular protein localizations, are difficult to quantify and several research groups have resorted to scoring these phenotypes manually by eye. Other researchers have developed customized computational analysis pipelines that need to be re-engineered for every screen. In this thesis, I apply supervised deep learning to HCS datasets as a computational approach that can be used to analyze a wide range of microscopy screens. First, I show that the classification performance of a deep convolutional neural network (CNN) outperforms a previously published computational pipeline for assessing the subcellular localization of fluorescently tagged proteins in genome wide yeast screens. I further show that this CNN can be used and updated on other protein localization datasets, including one generated by a different lab and on different imaging equipment. The CNN was used to identify ~300 proteins that change in localization in response to mating pheromone exposure. I trained a similar CNN to assign single cells in HCS images to 1 of 6 cell cycle stage categories, enabling in-silico synchronization of single cells. I combined the outputs from these two CNNs with data from RNA sequencing and ribosome profiling experiments to generate a comprehensive database of protein dynamics throughout the cell cycle. Additionally, I developed a novel CNN architecture to train models on HCS images without requiring cell segmentation or annotations for individual cells. This architecture only requires a list of phenotypes evident in a handful of images for training and can then predict which phenotypes are visible in other images and can indicate which cells in the images exhibit them. This model takes a major step toward automating the analysis of HCS images as minimal input is required to use it for analyzing different screens.
Combined Cell and Gene Therapy Towards the Treatment of Age-related Macular Degeneration and Diabetic Retinopathy
Keywords: Age-related Macular Degeneration
Cell Therapy
Diabetic Retinopathy
Gene Therapy
Neovascularization
Stem Cell

Abnormal and leaky blood vessel growth (neovascularization, NV), caused by an up-regulation of VEGF, is the common cause for vascular leakage, vessel dilatation, tortuosity, haemorrhage, cell death and ultimately blindness in age-related macular degeneration and diabetic retinopathy. Current anti-VEGF treatments (e.g. Avastin) can improve visual function but only temporarily and therefore patients require monthly eye injections. In addition, the anti-VEGF therapies cause side effects such as stroke, gastrointestinal perforations and bleeding. To address these problems, we have generated a novel bi-functional VEGF trap (VEGF Sticky-trap) that is able to trap VEGF as well as bind ("stick") to the extracellular matrix (ECM). This consequently allows inhibition of neovascularization only at the site of administration without causing systemic side effects as we have demonstrated in a retinopathy mouse model (OIR). To avoid the invasiveness of current therapies we have generated retinal pigment epithelium cells that express VEGF Sticky-trap in an inducible manner. We have shown that VEGF Sticky-trap expressed by these cells in-vitro is able to bind to ECM and trap soluble VEGF only upon doxycycline induction. In addition, we have demonstrated that these cells incorporate into the subretinal space long-term (up to 10 month), express VEGF Sticky-trap that a) remains bound to eye ECM and b) inhibits laser-induced chorodial NV. Here we have shown that the combination of cell and novel anti-VEGF gene therapy can inhibit neovascularization in a controlled and long-term manner; potentially improve vision, while avoiding the risk of side effects.
What are the best treatments for proliferative lupus nephritis?
Keywords: Bayesian analysis
causal inference
clinical trials
immunosuppressive treatment
lupus nephritis
metaanalysis

Background. Trial evidence, in adults, examining the relative effectiveness of immunosuppressive agents in the treatment of proliferative lupus nephritis (PLN) has been controversial. Trial evidence is sparse, particularly lacking long-term data, because trials are very difficult to do in this disease (due to its rarity and heterogeneous manifestations). There is no trial data to inform pediatric treatment. Observational treatment studies are limited by indication bias. A class of causal models, marginal structural models (MSMs), has been recommended in the literature to estimate treatment effectiveness using observational data, while correcting for indication bias. In order to determine the most effective immunosuppressive therapy for this disease, we designed and conducted this project. Methods. Systematic reviews and Bayesian network meta-analyses of trial evidence were performed. A MSM was used for an unbiased estimate of treatment effectiveness for childhood-onset PLN (cPLN). Results. Mycophenolate mofetil (MMF), in addition to prednisone, is the most effective therapy in the treatment of PLN, both in the short-term and long-term use, based on current evidence. Our pediatric findings were consistent with adult evidence and suggestive of MMF's superiority over other agents. Tacrolimus seemed better than MMF for adults in inducing renal remission at 6 months, but it has been insufficiently examined in other geographical regions than Asia. The probability of inducing renal remission for the best therapy was about 50% or lower at 6 months. Interestingly, the probability of preventing renal death at 2--3 years for azathioprine used at the current dose was second only to MMF. The 6% improvement in renal function, on average over a period of about 4 years in cPLN, induced by MMF versus other immunosuppressive agents (while correcting for indication bias) was statistically significant (p = 0.02). Conclusions. Whereas the evidence may not be sufficient to be definitive, MMF appears to be the best treatment for PLN. More studies are needed. Future clinical trials need to use a standardized conduct protocol and have a longer study duration. Future observational treatment studies should consider using MSM, especially for children and youth for rare diseases where clinical trials are infeasible.
The Struggle for WHOIS Privacy: Understanding the Standoff Between ICANN and the World's Data Protection Authorities
Keywords: data protection
Domain name system
ICANN
Internet governance
Multi-stakeholderism
privacy

This dissertation examines the struggle over privacy rights in WHOIS, the public directory of registrants of Internet domain names. ICANN, the Internet Corporation for Assigned Names and Numbers, is the non-profit corporation established by the U.S. government to run the Domain Name System and the Internet Assigned Numbers Authority, functions essential for Internet operations. Through contractual obligation, ICANN requires registrars to collect and publish personal data in the WHOIS directory, contravening many national data protection laws. My research first asked how ICANN managed to avoid the demands of authorities mandated to enforce data protection laws. Analyzing extensive documentary records maintained by ICANN, I demonstrate that the organization refused to effectively accommodate privacy concerns in their policies. I found that, since its inception, ICANN rebuffed repeated complaints by data protection authorities that WHOIS requirements violate national laws and continue to avoid privacy compliance. I provide evidence of a clash of values in the emerging commercial Internet. Business enterprises with strong intellectual property interests, supported by the U.S. government, initiated the focus on an open WHOIS policy to ensure they could identify suspected copyright and trademark violators. Law enforcement agencies represented at ICANN’s Governmental Advisory Committee also demanded open access to registrant data. A growing information services industry depended on the sale of this data to domain businesses and cybercrime fighters in both the public and private sectors. In combination, these stakeholders have prevented privacy advocates from gaining a foothold. Data Protection Authorities have also declined to exercise their powers, and they have remained outsiders and unsuccessful interveners in ICANN’s multi-stakeholder process. The dissertation then explores the implications of this failure of privacy law from the perspectives of Internet privacy scholarship and accountability issues in multi-stakeholder governance. Establishing WHOIS as a wide-open information resource not only erodes legitimate expectations of privacy in telecommunications directories, it undermines our ability to negotiate personal space and speech on the Internet. This research contributes to understanding challenges to Internet privacy, law enforcement access to personal data, and the prospects for developing international Internet governance regimes that promote the public interest while protecting the rights of individuals.
A Study of Four Single-Witness English Texts from the 14th and 15th Centuries in Manuscript, Early Print, and Modern Editions
Keywords: Editing
Editorial theory
Manuscript and Book history

This dissertation examines four single-witness manuscripts, written in English, dating from between the last quarter of the fourteenth century and the third quarter of the fifteenth: London, British Library MS Cotton Nero A.x, which contains the Pearl poems; Cambridge, Cambridge University Library MS Ll.iv.14, containing the fragmentary poem Richard the Redeless; London, British Library MS Additional 41666, which holds the fragmentary poem Mum and the Sothsegger; and London, British Library Additional MS 61823, which contains The Book of Margery Kempe. Each chapter traces the editorial and scholarly history of a single-witness medieval literary text from its first manuscript inscription through its various later forms, including manuscript marginalia, early printed versions, as well as modern editions from the mid-nineteenth century through to the present day. What unites each of these studies is a central interest in the relationship between the single manuscript version of each text and the various other versions of the text that have emerged since its medieval composition. I interrogate the decisions made by individual agents as they read, transcribed, edited, and critiqued these texts across time, and in the way that these decisions reflect contemporary scholarly, social, and political concerns. I am interested in the intractability of certain kinds of editorial decisions, even long after the assumptions that preceded them have changed or disappeared, and in the way that certain decisions—many of them built on editorial principles of authority and textual stability—become cemented in the editorial tradition of the texts, sometimes against manuscript evidence or to the exclusion of other, equally possible readings. Throughout, I hope to enact a kind of criticism that is mobilized by curiosity: curiosity about why editors and critics made the choices that they did, and curiosity about what else might be possible if we could get out from under the weight of already-inscribed interpretations. I am interested in seeing what happens when the editorial tradition of these texts is cracked open: when texts whose form has seemed to be settled can be unsettled again, even temporarily, in order to generate new ways of seeing them.
Biological Differences or Social Constructions? The Entanglement of Sex and Gender in Health and Physical Education
Keywords: Adolescents
Gender
Health and Physical Education
Nutrition
Physical Activity
Sex

Increasing concern over the wellness of young people has placed an increased emphasis on health and physical education as part of the schooling process for young men and women (13–18 years). An increasing number of policies have been implemented in schools in a consorted effort to address student wellbeing. This dissertation explores the discourses that shape the experiences of young men and women in secondary school. Specifically, I explore biological assumptions and social behaviours of young people which influence their eating behaviours and physical activities. Using a biopedagogical theoretical perspective combined with a sex and gender framework, this analysis engages with the complex relationships between biological understandings and resulting social behaviours with the intention of determining whether or not one is a predictor or resistor of the other. Data collection occurred in three phases (interviews with participants in policy implementation and dissemination, focus groups with secondary students, and policy analysis) and was conducted in a public school board in the Greater Toronto Area. I demonstrate that young people’s own understandings of about natural biological differences between young men and women are reinforced and (re)produced in social behaviours. Dominant discourses and constructions about sex and gender create binary categories and give rise to behaviours which impede the experiences and expressions of some young men and women. This research demonstrates the need to understand sex and gender as a continuum instead of binary categories. This would broaden the expressions of eating behaviours and physical activities for both young men and women.