VictorJuiz/thesis huggingface dataset:
PET Theranostics for Molecular Imaging and Radioimmunotherapy of Pancreatic Cancer
Keywords: cellular dosimetry
EGFR
pancreatic cancer
panitumumab
radioimmunotherapy

Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of pancreatic cancer tumours. Panitumumab is an antibody that targets EGFR and can be radiolabeled for molecular imaging and radioimmunotherapy (RIT). This thesis aimed to develop a “theranostic” agent that could be used for both imaging and treatment of pancreatic tumours. The first study demonstrated the ability of 64Cu-panitumumab F(ab′)2 fragments to visualize patient-derived orthotopic pancreatic cancer xenograft mouse models with PET/CT imaging and showed the superiority of panitumumab F(abʹ)2 over IgG or Fab fragments. Next, studies were performed involving metal-chelating polymers (MCPs) to allow antibodies to carry up to 20-fold more chelation sites compared to antibodies directly derivatized with chelators for 64Cu-radiolabeling, thereby amplifying radiation delivered per antibody. This work demonstrated that the presence of pendant PEG chains on MCPs resulted in longer blood circulation times compared to MCPs without pendant PEG chains. The next study demonstrated that 64Cu-panitumumab F(ab′)2 was useful in RIT when combined with radiosensitizing agents in pancreatic cancer xenograft mouse models. Tumour regression was not achieved so the final investigation compared 64Cu and 177Lu-panitumumab F(abʹ)2, which have similar β-emission energies but 177Lu has double the abundance of β-emissions compared to 64Cu. 64Cu-RIT and 177Lu-RIT were compared to external γ-irradiation to determine their relative biological effectiveness (RBE) in four pancreatic cancer cell lines, with different EGFR overexpression and proliferation rates. This work demonstrated that the degree of EGFR overexpression did not predict responsiveness of cells to RIT with 64Cu- or 177Lu-RIT. Also, fast growing cells responded very well to 64Cu-RIT while slow growing cells responded extremely poorly, while proliferation rate did not correlate with response to 177Lu-RIT. In conclusion, 64Cu-panitumumab F(ab′)2 fragments can be useful in PET imaging of pancreatic cancer tumours and that 177Lu-panitumumab F(ab′)2 fragments are more appropriate for RIT.
Algorithmic Trading with Latent Models and Mean-Field Games
Keywords: Algorithmic Trading
Game Theory
Mathematical Finance
Mean-Field Games
Probability
Stochastic Control

This thesis explores how agents should optimally trade in electronic markets when they account for latent factors and the optimal actions of other traders. It investigates the problem from the perspective of large-scale stochastic games with incomplete information and populations composed of heterogeneous agents, to which it provides closed form and model-agnostic solutions. The thesis contains two main parts. In the first part, we study the single agent optimal control problem when an agent has incomplete market information. Using the dynamic programming principle and filtration projection techniques we obtain closed-form formulae for the optimal trading strategy for a wide class of latent Markov models. We generalize this problem to an economy where the agent simultaneously trades multiple assets and tracks a stochastic benchmark. Using a novel method based on infinite-dimensional convex analysis we solve the agent’s optimization problem by representing it as the solution to a system of forward-backward stochastic differential equations. This allows both the extension to very general models for asset prices and implicitly provides the existence and uniqueness of solutions to the optimal control problem. In addition, we consider the practical implementation of these latent models and provide algorithms for the estimation of model parameters using expectation-maximization algorithm. In the second part, we consider the case of large populations of heterogeneous agents competing amongst one another on an exchange. We model these as stochastic games with partial and asymmetric information driven by latent semi-martingale price processes. By taking the limit as the population size tends to infinity, we obtain a mean-field game for which we can solve the Nash equilibrium in closed form by generalizing the convex analysis methods developed earlier. We further extend these models to incorporate disagreement amongst agents, represented by their beliefs on the probability measure driving asset prices. Although solutions to the extended model cannot be computed explicitly, we provide a least-square Monte-Carlo based algorithm to approximate the Nash equilibrium. In both cases, we show that the optimal solutions we obtain satisfy an ε-Nash equilibrium property in finite population games.
St Antonin of Florence on Justice in Buying and Selling: Introduction, Critical Edition, and Translation
Keywords: Antonino
Antoninus
canon law
justice
preaching
theology

This dissertation presents an extensive introduction to the Summa of St Antonin (Antoninus, Antonino) of Florence and his teaching on justice in buying and selling. It also presents, for the first time, critical editions and English translations of three chapters of his Summa: 2.1.16 (On fraud), 3.8.1 (On merchants and artisans), and 3.8.2 (On the various kinds of contracts). St Antonin was a Dominican friar and archbishop of Florence from 1446 to 1459, and composed one of the most comprehensive medieval manuals of moral theology, his Summa. In his preaching and writing, Antonin sought to teach the merchants and artisans of Florence about the proper conduct of trade and exhorted them to practice virtue and moderation in the pursuit of profit. The first part of this dissertation is an introduction with four chapters. Chapter One provides a brief literature review on St Antonin and a biography. Chapter Two is a study of his Summa: its conception, textual witnesses, and process of composition. This chapter demonstrates that the manuscripts traditionally considered to be the originals are indeed the author’s autographs, and offers the most extensive analysis of these manuscripts yet produced. Chapter Three expounds the development of scholastic teaching on justice in buying and selling in the thirteenth-century faculties of canon law and theology. Chapter Four explains Antonin’s teaching: its social context in renaissance Florence; its content, sources, and method; and its purpose, namely, helping the clergy in their pastoral duties of preaching, hearing confessions, and resolving moral dilemmas. A postscript comments on Antonin’s place in the history of moral theology. The second part of the dissertation, the appendices, is the critical edition and English translation, preceded by an explanation of the edition and followed by tables illustrating the recensions of each chapter, as well as a description of Antonin’s handwriting.
Late Gadolinium Hyperintensity (LGH) of Colorectal Liver Metastases (CRLM) on Magnetic Resonance Imaging (MRI)
Keywords: colorectal cancer
fibrosis
gadolinium
liver
magnetic resonance imaging
neoplasm metastases

Late gadolinium hyperintensity (LGH) of solid focal liver lesions on MRI with extracellular contrast agents is typically considered a “benign” finding seen most commonly with hemangiomas, but has also been observed with colorectal liver metastases (CRLM). In the first part of this thesis, we determined the prevalence of LGH in CRLM on MRI with extracellular contrast agents. In a retrospective cohort of 134 patients with 232 pathology-confirmed CRLMs, the prevalence of LGH in CLRMs was 47.8% (95% CI: 39.7%-56.0%). Some CRLMs demonstrate tumour fibrosis, which is associated with long-term survival. LGH with extracellular contrast agents in CRLMs may be due to leakage of contrast and progressive accumulation in the extracellular space of fibrotic tumours. In the second part of this thesis, we determined whether LGH is associated with tumour fibrosis and overall survival in patients with CRLM using extracellular contrast agents. In a retrospective cohort of 121 surgical patients who received preoperative MRI with extracellular contrast agents after chemotherapy, LGH was associated with tumour fibrosis (R=0.43, p
Three-Dimensional Musculoaponeurotic Architecture of the Human Lower Limb and its Functional Implications
Keywords: Anatomy
Architecture
Biomechanics
Human
Modelling
Skeletal muscle

The musculoaponeurotic architecture of the human lower limb has not been previously investigated in three-dimension (3D) at the fiber bundle (FB) level. As musculoaponeurotic architecture is a primary determinant of muscle function, the lack of architectural data has limited our understanding of functional characteristics of lower limb musculature and the development of high-fidelity simulation and biomechanical models. The overall objective of this thesis is to capture the 3D musculoaponeurotic architecture of all of the lower limb muscles, and to use this data to elucidate functional capabilities of muscle groups, individual muscles, and/or intramuscular partitions. In the first study, 48,000 FBs and all of the tendinous/aponeurotic components of 59 lower limb muscles were digitized and modelled, as in situ, to construct an architecturally comprehensive 3D lower limb muscle model. A detailed architectural analysis of three lower limb muscles demonstrated that each had unique spatial arrangement and morphology of the musculoaponeurotic elements resulting in functionally relevant intramuscular partitioning. The second study captured the 3D musculoaponeurotic architecture of vastus medialis obliquus (VMO) and longus (VML) in 12 specimens. The comparison of architectural parameters of VMO and VML indicated that the two partitions have distinct functional characteristics. The more vertical line of action (LoA), greater excursion and force-generating capability of VML suggested that it contributes primarily to knee extension, whereas, VMO’s more horizontal LoA, suggested a role in medial patellar stabilization. The third study investigated and quantified the 3D musculoaponeurotic architecture of the great toe muscles, in 10 specimens, at the FB/aponeurosis level. Functional differences were elucidated through the comparison of the architectural parameters of the medial and lateral great toe muscles and their intramuscular partitions. The medial musculature was found to have similar force generating capability as the lateral musculature, suggesting that medial and lateral forces are balanced. In conclusion, the 3 studies captured high-resolution 3D architectural data, which enabled detailed morphologic and architectural analysis of the lower limb musculature not possible to date. This volumetric data can be used for the development of finite element models capable of higher fidelity lower limb muscle simulation than presently available.
Intimate Partner Violence in South Asian University Students
Keywords: Dating violence
Disclosure
Feminist
Intimate Partner Violence
South Asian
University

Intimate Partner Violence (IPV) is a substantial problem affecting women of all social, economic, and cultural backgrounds. Although women worldwide are affected by IPV, research suggests that belief systems justifying violence against women or adherence to traditional gender roles may place some women at particularly high risk. Moreover, although women are exposed to IPV at high rates, many choose not to disclose to formal support (e.g., law enforcement) or informal supports (friends, family) due to numerous barriers. Experiences of disclosure are essential to understand since the response received after IPV disclosure is important to psychological functioning. The current study adopted an intersectional framework to examine the experience of IPV from the perspective of young, female South Asian students. Based on a mixed methods approach, the overall results indicated that women were frequently affected by psychological/emotional forms of IPV and that some of these forms of IPV were particularly meaningful within the South Asian culture. Similar to women of the majority culture, more than half of participants disclosed to informal supports while very few disclosed formally. A substantial barrier to disclosure were cultural norms about dating. Finally, while psychological health was qualitatively related to the experience of IPV, statistical analyses did not support a relationship between the response received after disclosure and psychological health.
Immune Mechanisms in Arterial Homeostasis and Disease
Keywords: Aorta
Atherosclerosis
Macrophage
Plasma Cell

Immune cells contribute to numerous homeostatic and pathological tissue processes making them an attractive target for therapeutic intervention. Large arteries exemplify this paradigm as they naturally harbor immune cells within the arterial wall, accumulating during chronic inflammatory diseases such as atherosclerosis. Despite our advances in our understanding of these processes, the regulatory networks, ancestry and mechanisms that maintain and propagate arterial immune responses remain unknown. This dissertation aims to elucidate these concepts during homeostasis and during atherosclerosis. The first chapter investigates the molecular signature of tissue resident arterial macrophages, their developmental pathways, and key mechanism that ensure their homeostasis. We show through gene expression profiling and multiple fate mapping approaches that adventitial macrophages represent a unique macrophage population with both primitive and definitive hematopoietic origins. These cells are maintained by self-renewal instead of circulating monocytes in both the steady state and acute inflammation. The second chapter focuses on the role of master transcription factor c-Myb in the development of atherosclerotic disease. Through the use of animals that are hypomorphic for c-Myb or have cell specific c-Myb depletion we show that c-Myb exacerbates atherosclerosis. This occurs directly through its effects on B cell development, regulating survival of B cell progenitors, harmful B2 cells and IgM-producing antibody secreting cells at multiple tissues sites. Collectively this work adds to the current field of arterial biology and provides a further impetus to investigate the mechanisms that regulate the artery in the steady state and inflammation.
Physiology of the Swallow and the Impact of Thickened Liquids in Post-radiation Head and Neck Cancer Patients
Keywords: Dysphagia
Head and Neck
Oncology
Radiation Therapy
Swallowing
Texture Modification

There is an increasing prevalence of head and neck cancers (HNC) in Canada and the United States, with approximately 52,000 new cases every year, and approximately 9,500 deaths annually due to the disease in the United States alone. In Canada, there are approximately 220 new diagnoses of oropharyngeal cancer and an estimated 120 deaths resulting from this cancer type per annum. Patients with oropharynx cancers commonly are undergo radiation treatment for their disease, which has good results in terms of tumor control. While survival is improving, patients are left suffering from radiation-induced toxicities. Dysphagia (swallowing impairment) is one of the side effects that can become a long-term, pervasive issue. Individuals with dysphagia are at risk for aspiration (food/liquid entering into the airway). Aspiration is estimated to occur in 30-69% of HNC patients after radiation treatment (range of 1-12 months) and is often silent (i.e. with no overt symptoms). Thickened liquids are commonly used to reduce aspiration in the neurogenic dysphagia population but there is a gap in our knowledge with regards to the impact that viscosity and texture modification have on swallowing in the head and neck cancer population. The studies in this dissertation will examine the potential of thickened liquids to reduce aspiration in patients who present with unsafe swallowing onthin liquids after the completion of radiation treatment (post-3-6 months) for cancers focal to the oropharynx.
The Economic Evaluation of Early Intervention with Anti-TNF-α Treatments in Pediatric Crohn’s Disease
Keywords: anti-TNF-α
cost-effectiveness analysis
Crohn’s disease
economic evaluation
infliximab
pediatric

BACKGROUND: Crohn’s disease is a chronic disorder in which sections of the gastrointestinal tract become inflamed and ulcerated through an abnormal immune response. Costly anti-TNF-α treatments are indicated only after other treatments have not worked. However, anti-TNF-α treatments have been proposed as first line therapy due to their effectiveness. OBJECTIVE: The primary objective was to assess the incremental cost-effectiveness of early intervention with anti-TNF-α treatment vs. conventional step-up strategy at improving the number of steroid-free remission weeks gained from public healthcare payer and societal perspectives. METHODS: A two-dimensional probabilistic microsimulation Markov model with seven health states was constructed for children with moderate to severe Crohn’s disease. Newly-diagnosed children with Crohn’s disease aged 4-17 years who received anti-TNF-α treatment and other concomitant treatments, such as steroids and immunomodulators, within the first three months of diagnosis were compared to children with newly-diagnosed Crohn’s disease who received standard care of steroids and/or immunomodulators with the possibility of anti-TNF-α treatment only after three months of diagnosis. The outcome measure was weeks in steroid-free remission. The time horizon was three years. A scenario analysis examined variation in costs of anti-TNF-α treatment. A North American multi-centre, observational study of children with Crohn’s disease provided input into clinical outcomes and health care resource use. To reduce selection bias, propensity score analysis was used. RESULT: From a public healthcare payer perspective, early intervention with anti-TNF-α treatment was more costly with an incremental cost of $31,112 (95% CI: 2,939, 91,715) and more effective with 11.3 more weeks in steroid-free remission (95% CI: 10.6, 11.6) compared to standard care, resulting in an incremental cost per steroid-free remission week gained of $2,756. From a societal perspective, the incremental cost per steroid-free remission week gained for early anti-TNF-α treatment was $2,968. CONCLUSION: While unknown, if a willingness-to-pay threshold was assumed to be $2,500 per week in steroid-free remission, early intervention with anti-TNF-α would not be cost-effective. However, there is considerable uncertainty in the incremental cost-effectiveness ratio and many patients escalate to anti-TNF-α eventually. Therefore, restrictive policies on anti-TNF-α treatment access for pediatric Crohn’s patients may want to be re-visited by decision makers.
Negotiating Fathers’ Care: Canadian Fathers’ Leave-taking as Conformity and Change
Keywords: Caregiving
Division of Labour
Family
Fathers
Gendered Dynamics
Parental Leave

Despite some changes to the ways contemporary families are handling the allocation of paid and unpaid work, the path of least resistance still tends be maternal caregiving with mothers more likely than fathers to cut back on their employment or drop out of the workforce entirely. Because men typically maintain, and may even strengthen, their ties to the labour market at the transition to parenthood, offering them paid parental leave is thought to provide an important opportunity for fathers to develop the skills and sense of responsibility that are characteristic of mothers’ parenting, ultimately reducing gender inequality in families. Although leave schemes that specifically target fathers are praised for their high usage rates, there has been little research into the quality of men’s time at home. This dissertation addresses this gap in the literature by probing the time-bounded and gender-laden circumstances of early parenthood to consider the ways in which fathers’ early involvement might set the stage for their greater participation in domestic life. I do so by examining how Canadian fathers come to use, experience, and act in response to their time on parental leave. The men in this study waxed enthusiastically about the parenting skills and emotional bonds they developed while on leave. Many were so moved by the experience that they came to incorporate the values and practices of care into their identities. Yet at the same time, the allocation of leave time and couple’s subsequent divisions of housework and domestic responsibility remained gendered. Couples had to engage with gendered cultural expectations that took men’s employment for granted but allowed them greater leeway than women when it came to meeting parenting standards. Nevertheless, I argue that the transformative potential of fathers’ leave-taking should not be dismissed – even small changes to couples’ gendered roles and fathers’ identities are important in undoing gender inequality.
Coupling Between Flame Stabilization and Hydrodynamic Instability in Swirl Combustion
Keywords: hydrodynamic instability
lift-off
PIV
PLIF
PVC
swirl flame

The coupling between hydrodynamic instability and flame lift-off in premixed swirl combustion was investigated in a gas turbine model combustor using multi-kHz repetitionrate OH* chemiluminescence (CL), OH planar laser induced fluorescence (PLIF), and stereoscopic particle image velocimetry (S-PIV). Over 60 different combinations of fuel composition, equivalence ratio, and reactant preheat temperature were studied, allowing systematic variation of the reactant-to-product density ratio, laminar flame speed, and Lewis number. Depending on the test conditions, the flame could either be stably attached to the nozzle, stably lifted, or intermittently transitioning between attached and lifted states. Transition between stabilization states was linked with the transition between convective and absolute instability at the flame base; formation of an m = 1 (m denotes the azimuthal wavenumber) globally unstable wave was associated with the lifted flame, manifested by a helical precessing vortex core (PVC). A detailed physical mechanism, involving density stratification, local extinction, strain rate, and PVC formation, was proposed to elucidate swirl flame lift-off. The minimum bulk velocity at which the flame was stably lifted was linearly correlated with the laminar flame extinction strain rate, while none of the other commonly reported key parameters governing hydrodynamic instability was able to collapse the data alone. Hence, lift-off was associated with a relatively constant Damk¨ohler number based on the bulk fluid strain rate and extinction strain rate. The roles of local strain and extinction on the transition process were further explained by the test conditions with intermittent lift-off/reattachment. The probability of the flame being in the lifted state was roughly linearly correlated with the degree of local extinction at the flame base while the flame was still attached. Moreover, this probability also was linearly related to the ratio of fluid-dynamic strain rate to extinction strain rate, but not the fluid-dynamic strain rate itself. In addition, using visibility graph, transition from the attached to the lifted regime was found to be associated with the transition from a scale-free to a regular network via intermittency. Intermittency was further quantified using spatially extended networks. It was shown that prediction of hydrodynamic instability limits might be possible using certain network measures.