VictorJuiz/thesis huggingface dataset:
Economic Evaluation of a Point of Care Pharmacogenetic Test (CYP2C19) from an Ontario Perspective

Abstract Background: Appropriate pharmacotherapy for patients with acute coronary syndrome depends on the functional capacity of their CYP2C19*2 allele. Patients with a fully functional allele could be treated with clopidogrel while prasugrel or ticagrelor could be prescribed to patients with a loss of function allele. Pharmacogenetic (PGx) testing could optimize pharmacotherapy (i.e. fewer adverse event rates with PGx option, where results are available in 1 hour) Purpose: To quantify net social benefit of implementing a PGx test in Ontario hospitals. Methods: A systematic review identified the evidence from full economic evaluations related to the CYP2C19*2 PGx test. An exploratory review highlighted the structure of published discrete choice experiments (DCEs) related to pharmaceutical therapeutics. Components used to quantify net social benefit were: patient preference expressed as willingness to pay, budget impact (BIA) analysis (aggregate Ontario hospitals, and Ontario Drug Formulary) and impact on productivity. Principles and good practice guidance as presented by the International Society for Pharmacoeconomic and Outcome Research Task force were adhered to for the BIA. A web survey tool that included a DCE was developed to assess preferences for attributes (levels) of a PGx test (i.e. mode of sample collection (cheek swab, blood, or finger prick), and turnaround time for results (1 hour, 3 days and 1 week). Cost was added to quantify the WTP of each attribute. To ascertain starting point bias with respect to the cost attribute, respondents were presented with one of two sets of costs (Version 1: $0, $1, and $5 or Version 2: $0, $2 and $10). Conditional logit regression was used to analyze data. Results: Regression coefficients were statistically significant for turnaround times as well as for cost regardless of the sample on which they were calculated. WTP for 1 hour versus a 3 day turnaround time was $2.91 (Confidence intervals (CI $1.90, $4.07) in additional annual premiums. WTP values were higher for 1 hour versus 1 week turnaround times. The results suggest that a net social benefit of over $9 million. Conclusions: Respondents showed a preference for 1 hour turnaround time for test results but no statistically significant preference in how samples were extracted. Given the financial constraints, hospital administrator decision to fund the PGx test would need to balance the additional $3.5 million expenditure to cover the PGx option with the potential benefit of 981 fewer adverse events.

Keywords: Budget impact analysis
Cost benefit analysis
Discrete choice experiment
Pharmacogenetics
Advisor: Papadimitropoulos, Emanual
Grootendorst, Paul
Efficient Light Coupling Techniques for Integrated Photonics

Given the fact that efficient and compact light emitters on a silicon (Si) platform yet do not exist, in most cases, light is still coupled to photonic chips from an external source (i.e. off-chip lasers) through single mode optical fibers (SMF). In this thesis, my investigations are focused on the problem of efficient light coupling to nano-photonic devices of different types. I propose and demonstrate a few compact on-chip solutions to efficiently couple light to specific modes of conventional photonic devices. The size mismatch between an optical fiber mode and the on-chip nano-photonic/plasmonic mode of a photonic circuitry is the major contributing factor to an inefficient fiber-to-chip coupling. Additionally, due to the inherent birefringence of the on-chip waveguides (i.e. silicon-on-insulator waveguides) the coupling efficiencies are also polarization dependent. In this thesis, I propose and demonstrate a compact bilayer inverse taper edge-coupler with enhanced fiber-to-chip coupling efficiencies for both TE and TM polarizations of commercial Si photonic circuitry. The current commercial practice of CMOS-photonics integration is limited to separate fabrication of the respective devices and connecting them by chip-to-chip interconnect systems. In this thesis, I propose and demonstrate a broadside beam routing mechanism in the telecom wavelength using a high index dielectric (i.e. Si) micro-prism structure. I extended the design to an elastic PDMS (Polydimethylsiloxane) platform to achieve beam scanning capability in both telecom and visible wavelength ranges diversifying its applications. I have further extended my work to the field of plasmonics and have designed a compact and highly efficient surface plasmon polariton (SPP) mode excitation scheme at the telecom wavelength regime using a gable shaped Si-tip with an optimized geometry. Fabrication of the Si-tip is compatible with standard Si processes. I have demonstrated the effectivity of the proposed scheme via a proof-of-principal experiment showing the high efficiency excitation of the SPP mode at an Au/SiO2 interface. Furthermore, I present a detailed design of an SPP excitation device capable of efficiently exciting an SPP mode at an Au/air interface, facilitating an easy access to the excited SPP mode from the outside environment, making it more suitable for plasmonic sensing applications.

Keywords: Coupling
Edge Coupler
Inverse Taper
Mode Conversion
Surface Plasmon Polariton
Tip Excitatiom
Advisor: Mojahedi, Mo
Aitchison, J. Stewart
Regenerating Political Animals

Regenerating Political Animals situates the Declaration of the Rights of Man and of the Citizen (1789) and the French Revolution in the theological natural science and political theory of the eighteenth century. Beginning with a “counter-revolutionary” account of the philosophy of this period—which situated the “return to nature” and assertion of natural right in atheistic and materialist philosophy—this thesis argues that the more influential and dominant account of “nature” in this period was one which asserted the uniqueness of the human being through the “spirituality of his soul,” and his capacity to perfect and regenerate himself through regenerating his moral and political conditions. Rooted in the natural theology of Georges-Louis LeClerc Comte de Buffon and Charles Bonnet, the “perfectible” human being also served as the Archimedean point of Jean-Jacques Rousseau’s philosophy. These three thinkers are the focal points of the thesis, which culminates in the argument that what was born in Revolutionary France was a “new man” —l’homme régénéré—and a new conception of human nature that still courses through our contemporary conception of human rights, and of the human being. Rights are still grounded in a natural theology that has faith that a future possible world will better accord with nature; and we, as regenerative political animals, are the self-regenerative agents of the transformation of the world.

Keywords: Buffon
French Revolution
Natural Science
Palingenesis
Regeneration
Rousseau
Advisor: Kohn, Margaret
Race, Empire and Inherited Histories: Readings of Kafka, Schnitzler and Heyse

My dissertation examines the discourses of empire during the shift from aesthetic to biopolitical ways of reading race, which influenced nineteenth and twentieth century German language writings. Seemingly disparate novellas from Paul Heyse and Arthur Schnitzler and a short story from Franz Kafka serve to illustrate how race was locally defined through the narrative of inherited histories in the German and Austro-Hungarian Empires. â Inherited historiesâ is a term which privileges heredity, race and kinship networks as sites to study empire during a period when national and linguistic terms of defining bodies were different. In collocation, the first historical exploration of German and Austrian family business networks in colonial Ceylon and an autobiography from John George Hagenbeck show how views on race were globally ordered through colonialism but also blurred in order to accommodate trade. Additional materials such as postcards, photographs and stagings of ethnographic exhibits further inform the unstable constructions of race in the through kinship networks and heredity. There are three key contributions this dissertation makes to race, sexuality and colonial studies. The first section shows how the German and Austro-Hungarian Empire did not require formal colonies, comparable to the British or French regimes, to own businesses in colonial Ceylon. Transimperial family business connections were preferred for sharing resources, infrastructure, and labour as Ceylonese-German impresario Hagenbeck recounts in his writings. When he assembled, managed and travelled with his South Asian ethnographic exhibitions to various European cities, Hagenbeck took great care to play the role of white German citizen, hiding his racialized identity and revealing how race defined global mobility. The second section discusses what kinds of racial and sexual anxieties began to surface as ethnographic exhibitions moved through the German and Austro-Hungarian Empires. The presence of a racialized child in Vienna provokes fears about European and African sexuality whereas the plight of an unwed mother and son residing in Munich uncovers black family genealogies in European cities going back to the global slave trade. Comparing literary texts in both empires exposes contradictions in racial discourse and a need for nuance readings of racial vocabulary and transnational history. The third section demonstrates how the German Empire utilized alcohol, a lucrative consumer commodity, as a way to influence the behavior of labourers at home and in the colonies. Returning to the site of Hagenbeckâ s South Asian ethnographic exhibitions illustrates how performers, made drunk and put on exhibit, shaped perceptions of racialized people.

Keywords: Biopolitics
Colonialism
Gender Studies
German Cultural History
Race
South Asia
Advisor: Goetschel, Will
A Developmental Cascade Model of Neurocognitive Functioning: Risk, Resilience, and Implications for Children's Mental Health

Theory of Mind (ToM) and executive functioning (EF) are two neurocognitive abilities that develop rapidly over the preschool period. ToM and EF are highly interrelated, both behaviourally and neurologically, and are predictive of a host of psychosocial outcomes across the lifespan. This dissertation delineates a developmental cascade model of ToM and EF in which key social-cognitive skills in the second year of life are examined as precursors to ToM and EF through their impact on children's nascent language skills. Further, both cumulative social disadvantage and biomedical risk are investigated as risk factors that increase vulnerability to cognitive morbidity over the early years. Finally, it is suggested that these social and biomedical risks are non-deterministic, and that positive postnatal socialization experiences with caregivers may protect children against their deleterious influence. The implications for prevention and intervention will be discussed with the overarching suggestion that early programming may help to mitigate the negative cascading effects of poor early adaptation on later psychosocial health and development.

Keywords: biomedical risk
cumulative risk
Developmental cascade
Executive function
protective influences
Theory of mind
Advisor: Jenkins, Jennifer M
The Utility of Measuring Disability, Functioning and Other Factors when Assessing Mental Health in both the General Population and a Patient Population that Seeks Treatment at a Psychiatric Emergency Department

The social, economic and health burdens of mental and behavioural disorders are large, and although treatment rates for such disorders are low, the use of emergency departments for mental and behavioural disorders is high. Accordingly, this thesis compares the use of disability, functioning, non-specific psychological distress and diagnosis to characterize mental and behavioural disorders. Furthermore, this thesis examines if predisposing and levels of mental illness factors are correlated to baseline and subsequent emergency department visits. The general population surveys of the 2011, 2012 and 2013 Centre for Addiction and Mental Health (CAMH) Monitors were used as a general population sample of Ontario adults. Data from patients were obtained by time-based sampling from August 2011 to February 2012 in the emergency department of CAMH (a psychiatric hospital that provides services to adults); the CAMH emergency department database was used to track subsequent emergency department visits. Disability and functioning were measured using the World Health Organization Disability Assessment Schedule, and non-specific psychological distress was measured using the General Health Questionnaire. Data from the CAMH Monitors indicated that although disability, functioning and non-specific psychological distress are correlated (except for people with somatic illnesses), all such measures are needed to accurately describe mental health. Among patients in the psychiatric emergency department, differences in disability and functioning were not significant across diagnoses; however, a substantial heterogeneity in disability and functioning was observed within diagnoses. Furthermore, using data from patients in the psychiatric emergency department, we observed that the number of previous visits, the WHODAS scores, and employment status were predictors of psychiatric emergency department recidivism. Based on the results of this study, it is clear that measures of disability, functioning and non-specific psychological distress may be needed to adequately describe the mental health of the general population. Furthermore, in psychiatric as well as in general hospital emergency departments, data on disability and functioning and on the number of previous visits if collected in addition to diagnosis data for patients with mental and behavioural disorders could lead to more effective triaging of these patients, alignment with the appropriate intensity of resources, and prediction of recidivism.

Keywords: Disability
Emergency medicine
Functioning
Mental Health
Psychological distress
Advisor: Rehm, J端rgen T
First Winter

Thesis (orchestral composition) Duration: 9 minutes Instrumentation: 2 flutes (2nd doubling piccolo), 2 oboes, 2 clarinets, 2 bassoons, 4 horns, 2 trumpets, 3 trombones, tuba, timpani, 2 percussion, harp, strings ABSTRACT The concept of this single-movement, 9-minute, tone poem is essentially the dichotomy of ‘nature’ and ‘humankind’, placed in the context of the age when the very first humans set foot on an untouched Canadian landscape, more than 12,000 years ago. The music does not seek to be programmatic, culturally or historically-specific in any way. Nor is the dichotomy of nature and humankind presented as an adversarial one. Rather, the music aims to explore the various emotions that any human being might feel upon first discovering a new landscape, and eventually when having to mesh with this landscape. These might well include feelings of mystery, awe, trepidation, and excitement, to name a few. There are three main sections to this piece. The first (until b.41) primarily aims to evoke an untouched natural, wintery landscape. The proto-melody, that begins at b.41 and develops quickly, signals the first motivations of humankind. The 4-chord chorale at b.141 heralds the final section, which signals the first dawn of spring, and a general sense of optimism. There are a select few deliberate examples of tone-painting: bars 29-32 depict a tree branch collapsing under the weight of accumulating snow, and bars 102-121 are inspired by birds in flight. At the very end, there remains the dichotomy of nature’s constancy and humankind’s footprint. This particular piece marks a stark departure from my usual compositional style, which is typically explicit in its explorations of the boundaries between cultures, and between composition and improvisation. The purpose of this thesis has been to set aside my usual preoccupations with rhythm and melody to explore instead a more textural world of shifting colours and emotions, where rhythmic material is organic as opposed to constructed, and melodic material is - at most - fragmented.

Keywords: Orchestra
Symphonic Poem
Tone Poem
Advisor: Hatzis, Christos
Strategies for Investigating Intrathymic Human T-Cell Development Using Humanized Mouse Models

T-cells play a critical role in mediating antigen-specific and long-term adaptive immunity against viral and bacterial pathogens. The thymus provides a highly specialized microenvironment for the generation of T-cells. T-cell immunodeficiency, or T-lymphopenia, can result from perturbations to the thymic microenvironment due to aging or irradiation required for cancer treatment, or from infections that directly target T-cells. Previous work by our group supports the co-transplant of in vitro-generated T-cell progenitors (proT-cells) for accelerating long-term hematopoietic stem cell (HSC)-derived T-cell reconstitution during periods of T-lymphopenia after HSC transplantation. However, an understanding of the mechanisms underlying proT mediated effects within the thymus, as well as systems for the generation of clinically scalable numbers of proT-cells, remain to be fully elucidated. I revealed a potential mechanism by which receptor activator of NF-ÎşB (RANKL)-expressing proT-cells reorganize the stromal cell compartment within the thymus of NOD/SCID/Îłcnull (NSG), creating chemokine-rich niches that likely favor the recruitment of HSC-derived progenitors. Given that proT-cells have important implications for T-cell regeneration during periods of lymphopenia, I established a scalable differentiation system, which enabled >250-fold expansion of hematopoietic stem/progenitor cells (HSPCs), for generation of increased quantities of proT-cells from a single HSPC donor. Both CD34+CD7+ and CD34-CD7+ proT-cells were generated using this strategy and while both subsets had thymus-engrafting capabilities, CD34+CD7+ cells exhibited higher thymic reconstitution. Building on the ability to manipulate HSPCs ex vivo, I also gene-modified HSPCs to express a secreted HIV entry inhibitor, soluble CD4 (sCD4). When tested in vivo, NSG hosts supported multi-lineage differentiation of human gene-modified HSPCs. Upon infection with HIV, I observed that humanized mice capable of secreting sCD4 demonstrated a reduction in viral load over time compared to control humanized mice. Taken together, this work demonstrates how large quantities of in vitro-generated proT-cells can be generated from ex vivo manipulated HSPCs for intrathymic repair and immunotherapeutic application.

Keywords: Gene Therapy
Hematopoietic Stem Cell
Human Immunodeficiency Virus
Immunodeficient Mouse Models
T-Cell Development
T-Cell Progenitors
Advisor: Zúñiga-Pflücker, Juan Carlos
A Pragmatic, Existentialist Approach to the Scientific Realism Debate

The debate between scientific realists and anti-realist empiricists is often treated as a question about whose position is true, or rationally preferable per se. This debate is widely considered to have been argued to a stalemate. I suggest we accept this stalemate and instead investigate when and whether scientific realism or anti-realist empiricism is more useful, and thereby rationally preferable, for certain individuals. I develop a methodological framework for doing this, then put it to use by investigating the practical benefits for working scientists of adopting one view over the other. This investigation is historical rather than philosophical, and therefore empirical rather than theoretical, focused around a case study of the way philosophical commitments influenced the scientific practice of late 19th c. electrodynamics researchers in positive and negative ways.

Keywords: History of Electrodynamics
Meta-Epistemology
Pragmatism
Scientific Realism
van Fraassen
Voluntarism
Advisor: Brown, James R
Influencing Behaviour to Improve Diabetes Self-Management: The Design and Evaluation of Mobile Health Applications

The global increase in the prevalence of diabetes along with the cost associated with complications is challenging traditional approaches to healthcare delivery. While the pervasiveness of mobile phones has resulted in a consumer-driven market for diabetes-focused mobile health applications (apps), the majority of these apps are not evidence-based or rigorously evaluated. The main objectives of this research were to design, develop and evaluate, a consumer-focused, behavioural app for the self-management of diabetes. Following a knowledge translation framework, existing evidence around behaviour change theory, diabetes self-management, and mHealth was reviewed, and informed the conceptualization of the app features. The app was developed following user-centered design principles, where iterative feedback was obtained from patients throughout the process. The resulting intervention, bant2, was a consumer-focused app for the self-management of type 2 diabetes, focused on the contextualization of blood glucose readings with personalized lifestyle behaviours. While a 12-month randomized controlled trial (RCT) was designed to evaluate the impact of bant2 on clinical outcomes, findings from recent studies led to reconsider both the intervention the evaluation approach. The bant RCT (n=96) and

Keywords: Behaviour Change
Chronic Disease
Diabetes
Evaluation
Mobile Applications
Technology
Advisor: Cafazzo, Joseph A
Operations Management of Crowdsourcing and Crowd Behavior

This thesis studies problems in operations management about how to manage crowd behavior. In the first chapter, we investigate the crowdsourcing contest. In a crowdsourcing contest, innovation is outsourced by a firm to an open crowd that compete in generating innovative solutions. Since the projects typically consist of multiple attributes, we consider two alternative mechanisms. One is a simultaneous contest, where the best solution is chosen from the aggregate solutions simultaneously submitted by all contestants. The other is multiple sequential sub-contests, with each dedicated to one attribute and the contestants asked to build upon the best work in progress from previous sub-contests. The comparison of the expected \emph{best} performances in the two contests depends on the project's characteristics. In the second chapter, we study the revenue sharing policy in the subscription platform. Subscription providers such as Spotify, Netflix and OneGo (an all-you-can-fly subscription service provider) crowdsource products/services from many vendors and bundle them for the price of one. The collected subscription fees for the bundle then are allocated according to the realized contributions by each crowdsourced product. However, this allocation scheme may create incentive incompatibility for vendors, given their options of not joining the bundle. We examine the incentive compatibility of different parties under various bundling strategies. In the third chapter, we study the customer behavior with an online reservation system. Online reservation system allows customers to join a queue and virtually wait for service before arriving on site. For example, some platforms have been designed to collect the information of restaurants and show the real-time congestion levels (e.g., Nowait). We consider a model in which customers must travel from their location to the service area and incur a travelling cost. When customers intend to book service online, they are informed about their positions in the queue at the time of booking, so that they make their decision whether to join the queue taking into account both their travelling time and expected waiting time. With those customer behaviors, the optimal policy of a firm heavily relies on the conditions of the travelling and benefit of the service.

Keywords: Bundling theory
Crowdsourcing contest
Queueing theory
Strategic behavior
Subscription service
Tournament theory
Advisor: Hu, Ming