VictorJuiz/thesis huggingface dataset:
Preventing Osteoporotic Fractures in Men Living with HIV: Model Calibration and Economic Evaluation Studies

I aimed to provide Ontario’s public healthcare payers with an economic evaluation of fracture prevention strategies for HIV-positive men who take antiretroviral therapy (ART). When developing microsimulations models for this purpose, calibration is critical and computationally expensive. Studies that explore efficient calibration methods for microsimulation models are limited. As such, I sought to determine whether simulated annealing or Nelder-Mead is the best-performing parameter search algorithm to calibrate a microsimulation model in project one; determine whether a discrete-event simulation model of fractures leads to more efficient calibrations than a patient-level, discrete-time simulation model in project two; and, estimate the cost-effectiveness of osteoporosis screening and treatment strategies in ART-treated men over a lifetime horizon in project three. For projects one and two, I constructed a Markov microsimulation model that tracked bone loss and incident fractures. All calibrations were based on 4 calibration targets, 12 calibration inputs, a binomial log-likelihood goodness-of fit measure, and first-order searches in a simulated sample of 1000. I assessed calibration performance according to differences in the goodness-of-fit and the time to identifying a good parameter set. In project one, both algorithms produced good sets that had similar fit, but simulated annealing identified the sets two times faster than Nelder-Mead. In project two, both model structures generated similarly accurate good sets, while the discrete-event simulation generated these three times as quickly as the discrete-time simulation. In project three, I evaluated 13 strategies for initiating osteoporosis treatment based on Fracture Risk Assessment Tool (FRAX) scores, with and without bone mineral density (BMD). The base-case included 50-year-old, HIV-positive men who took ART for ≥3 years and did not have a history of fractures or osteoporosis treatment. I incorporated the calibrated results from projects 1 and 2 in project 3’s probabilistic analysis. I discounted outcomes annually by 1.5%. At a willingness-to-pay threshold of $50,000/QALY, it is most cost-effective to assess FRAX without BMD, offer treatment if FRAX is ≥10%, and re-screen annually. Collectively, these studies suggest using simulated annealing and discrete-event simulation as efficient calibration methods; as well as that the payer should not pay for BMD screening in older HIV-positive men.

Keywords: Health economics
Medical decision modelling
Model calibration
Advisor: Bayoumi, Ahmed M
Sustainable Energy Use in Dar es Salaam: Current Trends, Future Scenarios, and Policy Options

In 2019, Africa accounted for only 5% of global energy demand and 3.7% of energy-related carbon dioxide emissions. However, Africa’s rapid urbanization will contribute to rising energy use and emissions, both regionally and globally. Using the case of Dar es Salaam, Tanzania, this thesis offers new insights relevant to the discourse on Africa’s evolving energy landscape. The thesis: (1) Estimates possible changes in Dar es Salaam’s residential energy use and greenhouse gas (GHG) emissions between 2015 and 2050, (2) Identifies key household and transport-related drivers of energy use and GHG emissions, (3) Assesses variations in energy use at the sub-city (ward) level, i.e., between settlements of differing socio-economic profiles and spatial location in the city, and (4) Examines institutional and societal factors that may constrain low-carbon development in Dar es Salaam. Three studies are presented to address the four aforementioned thesis aims. The first study – Modelling Future Patterns of Urbanization, Residential Energy Use and Greenhouse Gas Emissions in Dar es Salaam with the Shared Socio-Economic Pathways – employs a scenario-framework to scope different urban growth and GHG emissions pathways in Dar es Salaam. The work demonstrates an approach for projecting GHG emissions in an Africa city context that may be data constrained. The second study – Does Location Matter? Investigating the Spatial and Socio-Economic Drivers of Residential Energy Use in Dar es Salaam – shows the differences and clustering of energy use that exist at the ward level, and employs statistical methods to correlate energy use with different socio-economic and spatial characteristics of wards. The final study – Assessing Institutional and Societal Barriers to Low-Carbon Development in Dar es Salaam – asserts that processes to implement low-carbon measures (e.g., electrification and public transport projects) would need to engage multiple stakeholders in a collaborative process to leverage the power and mandate of different institutions. Together, these studies seek to inform energy and urban planning policies in Dar es Salaam that (1) enhance synergies between GHG mitigation investments, (2) support implementation strategies that consciously account for local energy use realities and infrastructure access needs, and (3) acknowledge linkages between sustainability, climate change, and socio-economic development strategies.

Keywords: Africa
Cities
Energy Transitions
Greenhouse Gas Emissions
Infrastructure Sustainability
Urban Planning
Advisor: MacLean, Heather L.
Material Regimes of Bodily (Re)Formation: Person Shaping and Display in Urban Tuscan Homes for Abandoned Children, ca. 1570-1650

This dissertation examines material, embodied, disciplinary regimes of person shaping in Tuscan, civic-religious institutions circa 1570-1650. In particular, I analyze how three homes for abandoned children, Florence’s Innocenti and Santa Maria e San Niccolò del Ceppo and Prato’s Misericordia e Dolce, aimed to use food, textiles, wax, educational materials, and deportmental discipline to shape abandoned children uprightly, body and soul, according to contemporary, intersecting prescriptions about Catholic reform and patriarchal discipline. This person-shaping endeavour had both practical/economic and spiritual/rhetorical purposes. On the one hand, all three of the institutions took in socio-economically precarious dependents, but none offered free charity. Abandoned children were put to work to keep the institutions running, overwhelmingly in manual tasks. This shared occupation—manual labour—profoundly influenced material provisions, which both reflected and reinscribed abandoned children’s socio-economic place as labourers onto their bodies. On the other hand, provisions and rules governing conduct also reflected the institutions’ shared aim of raising devout and virtuous Catholics. In both cases, homes for abandoned children framed their material provisions and deportmental discipline as acts of bodily and spiritual care. Further, they displayed the outcomes of this charity and person shaping on—or perhaps more accurately, as—the carefully shaped bodies of their dependents. In other words, they used highly curated displays of abandoned children to publicize the apparent efficacy of their patriarchal, civic-religious charity and, by extension, the virtue of the institutions themselves, the cities in which they operated, and the grand dukes that ruled them. This study, then, brings together a number of threads: histories of institutionalization and child-raising, of Catholic reform and patriarchal authority, of the body, soul, and senses, of workfare and materials, of age, gender, and status. By applying the lenses of materiality, the body, and the senses to institutionalization, it shows how late sixteenth- through mid-seventeenth century reforms and patriarchal discipline were felt, embodied, and displayed by some of early modern Tuscany’s most vulnerable residents—institutionalized, abandoned children.

Advisor: Terpstra, Nicholas
The Association between Immigration Status and Stroke Incidence, Care and Outcomes

Immigrants to high-income countries have a lower cardiovascular disease incidence and mortality compared to host populations, a phenomenon termed the healthy immigrant effect. However, differences in stroke incidence, care and outcomes between immigrants and host populations have not been well-characterized. We studied the incidence, acute care, and short-term and long-term outcomes of stroke in immigrants compared to long-term residents in Ontario, Canada. People born outside of Canada who immigrated after 1985 were considered immigrants. Compared to long-term residents, immigrants had stroke at a younger age and had a lower adjusted hazard of stroke (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.66-0.68). Compared to long-term residents, immigrants were less likely to seek care for transient ischemic attacks, and among patients with ischemic stroke, immigrants received equal or better acute stroke care, had higher disability on discharge (adjusted risk ratio 1.18, 95% CI 1.13-1.22), and marginally lower long-term (15 years) mortality (adjusted HR 0.94, 95% CI 0.88-1.00). These associations varied with age at the time of stroke, stroke subtype, ethnicity, country of origin, and immigration class, highlighting heterogeneity in the observed healthy immigrant effect. While the lower incidence of stroke and the lower mortality following stroke in immigrants compared to long-term residents may suggest a healthy immigrant effect, the younger age at the time of stroke and the higher disability on discharge in immigrants compared to long-term residents highlights a higher risk of premature and disabling stroke in immigrants. Further research should evaluate the reasons for the observed differences, which could then inform the design of effective interventions to improve stroke outcomes for both immigrants and long-term residents.

Keywords: care
ethnicity
immigration
incidence
outcomes
stroke
Advisor: Kapral, Moira K.
Population Genomics of Herbicide Resistance Contemporary Agricultural Adaptation in Amaranthus tuberculatus

The evolution of resistance in response to herbicides is a striking example of repeated, human-induced evolution. While much is known about the effects of particular point mutations that confer resistance, the extent to which they arise repeatedly de novo, draw from standing variation, or spread across populations through gene flow is unclear (Chapter 4). Beyond these simple mutations, complex genetic bases such as gene amplification (Chapter 2) and polygenic architectures (Chapter 3) also contribute to resistance in weed populations, but their population genomics have yet to be characterized. In this thesis, I quantify the repeatability of resistance evolution across these genomic architectures by characterizing adaptive origins and causes and consequences for heterogeneity in the spread of resistance across the range of Amaranthus tuberculatus. A. tuberculatus is native to North America, with an annual life history and wind-pollinated dioecious sexual system. While historically found in riparian habitats, A. tuberculatus has successfully colonized agricultural landscapes and recently become problematic to manage in these ruderal settings due to widespread resistance to multiple modes of herbicides. In Chapter 5, I go on to test hypotheses about the timescale of adaptation to agricultural environments in A. tuberculatus, with phenotypic and genomic data from paired natural-agricultural collections grown in a common garden. I find that nearly all possible mechanisms contribute to the evolution of herbicide resistance and agricultural adaptation in A. tuberculatus, drawing from standing variation, repeated de novo mutations, and widespread gene flow among populations—highlighting the role of both slow gradual change and rapid genetic turnover during plant evolution to contemporary landscapes. Overall, my thesis contributes to our understanding of the extent and magnitude of evolutionary parallelism in the wild, population-level factors that influence the rate of evolution, and the timescale of adaptation to extreme selection and to human-mediated environmental transitions.

Keywords: De novo adaptation
Gene Flow
Plant Evolution
Rapid Adaptation
Standing variation
Advisor: Wright, Stephen I
Stinchcombe, John R
Backside-integrated III-V-on-Silicon Lasers and Modulators

III-V-on-silicon (III-V-on-Si) bonding has emerged as a viable way to integrate lasers with Si photonic circuits at the wafer-scale. However, hybrid III-V-on-Si integration is often plagued by high thermal impedance and difficulty in co-integration with other materials. In this thesis, we design and demonstrate the first active devices on a new Back-Side-on-Buried-Oxide (BSoBOX integration process, in which the III-V material is introduced from the back of the silicon-on-insulator (SOI) wafer to address the common problems of III-V-on-Si integration. While designing and characterizing devices on the BSoBOX platform, the merits and limitations of the platform are also evaluated. First, we develop an optimization technique for producing short, broadband transitions between the SOI waveguides and the hybrid III-V-on-Si waveguides. The eigenmode-expansion based optimization process manipulates the lengths of short sub-tapers to produce a transition that maintains adiabaticity in the shortest length possible. Compared to an 80 µm long linear taper, with a power transfer efficiency of ∼85% at 1310 nm, the optimized design has a length of 80 µm and an efficiency ≥99.5% across the O-band. Next, two types of lasers are evaluated. We demonstrate distributed feedback lasers with threshold currents as low as 32 mA and 20 mW of waveguide-coupled power from a single end of the device. The side mode suppression ratio (SMSR) is around 50 dB within the range of 20 °C-60 °C and operation up to 80 °C is observed. We also demonstrate the first III-V-on-Si discrete-mode lasers, with the best device exhibiting 17 mW of waveguide-coupled power, a Lorentzian linewidth of 18 kHz and a SMSR ≥60 dB. The performance of these devices is comparable to the state-of-the-art III-V-on-Si lasers, despite this being the first iteration of the BSoBOX platform. Lastly, the first high-speed InP-on-Si modulators are designed and characterized on a frontside integrated platform that can be later converted to BSoBOX integration. The DC efficiency is 1.3 V·cm, roughly twice as high as lateral PN junction designs, while maintaining a comparable bandwidth of 30 GHz. Simulations show the BSoBOX designs will lead to a ∼4x improvement in efficiency and roughly 50% improvement in bandwidth compared to the current work.

Keywords: Hybrid lasers
Integrated optics
Modulators
Photonics
Advisor: Poon, Joyce
Menezo, Sylvie
Novel Strategies for the Prolonged Preservation of Donor Lungs Prior to Transplantation

The gold standard of lung preservation involves cold flushing the organ with a specialized solution, which is subsequently followed by storage in an ice cooler at a resting temperature of approximately 4°C. Developed over 30 years ago, this method continues to be used without significant advances due to its logistical simplicity. Although the primary goal of this approach is to shutdown cellular activity, several deleterious processes may ensue, ultimately compromising the length of time the organ can be kept in this state. According to international large registry reports, average clinical preservation times are only 5-6h. We hypothesized that through the implementation of novel strategies aimed to optimize the current cold storage protocol, prolonged preservation periods could be obtained. We first evaluated the effects of supplementing a novel extracellular oxygen within the standard preservation solution. Although the lungs are stored inflated with oxygen, some regions of the lung may be poorly inflated, leading to a risk of cellular damage over extended periods of time. By storing the lungs with an extracellular oxygen carrier supplemented solution during a prolonged preservation period, we show that cellular oxygen levels can be better maintained, and that post-transplant graft function is enhanced. We then go on to evaluate the role of temperature during prolonged cold storage periods. Previous literature has suggested 10°C to be the optimal lung storage temperature, however, little is known about the mechanism by which it is functionally superior. With the use of a simple thermoelectric cooler, we demonstrate prolonged storage at 10°C to be superior to current methods and identify mitochondrial protection to be a key determinant of this strategy. As a proof-of-concept, we further go on to demonstrate 10°C storage as a feasible approach to allow for clinical semi-elective transplantation. Lastly, we aimed to evaluate the potential of normothermic ex vivo lung perfusion (EVLP) to allow for multi-day preservation. Although initially developed as a tool for organ assessment, EVLP presents itself as an opportunity to interrupt the continuous manifestation of cold damage. By subjecting lungs to an intermittent EVLP protocol, we achieved successful 3-day lung preservation with excellent post-transplant outcomes.

Keywords: Ex vivo lung perfusion
Extended Preservation
Lung Preservation
Lung Transplantation
Oxygen
Temperature
Advisor: Cypel, Marcelo
Altered Landscapes: The Process of Conquest in the Eleventh-century Norman Chronicles of the Mezzogiorno and Sicily

This dissertation examines the first generation of Latin chronicles patronized by the Norman conquerors of southern Italy and Sicily in the eleventh century: Amatus of Montecassino’s Ystoire de li Normant, William of Apulia’s Gesta Roberti Wiscardi, and, Geoffrey Malaterra’s De Gestis Rogerii Comitis et Roberti Guiscardi Ducis. These chronicles constitute meaningful assertions regarding the nature and actuality of Norman lordship in the region at a time of great precarity for the Siculo-Norman imperial project: the succession of the second generation of Norman lords. Indeed, I argue that these early texts must be examined in their pre-kingdom context, as the heavy work of conquest is often clearest in spaces of imperial precarity and anxiety. In addition, this dissertation is grounded in an understanding of the world-creating function of historical texts. It contends that each chronicle’s curated historical world reveals the ways in which the eternally-incomplete process of conquest continuously remade the collective identities, affinities and alterities, that gave shape to the socio-political, historical, emotional, and geographical landscapes of Norman Italy and Sicily. It first explores the internal logic of each history (and its respective historical world) individually, focusing on the specific preoccupations and aims of each historian, in order to explore their implications for current historians’ understanding of medieval conquest. These three distinct and interconnected worlds are then brought into conversation with each other in order to examine the logic of the Norman conquest more broadly. In particular, this dissertation contends that the process of conquest embodied in these histories was grounded in the twinned forces of alienation and appropriation as the chronicles worked to naturalize the bodies, emotions and lineage of the foreign conquerors within the landscape while simultaneously alienating their local subjects from it. In doing so, the chronicles obscured the rupture inherent in conquest behind the mask of continuity provided by these acts of naturalization.

Keywords: historiography
imperialism
landscape
literature
Mediterranean
multiculturalism
Advisor: Cochelin, Isabelle
Conklin Akbari, Suzanne
Mapping the Conformational Landscape Spatial Organization of G Protein-coupled Receptors using Single-molecule Fluorescence

G protein-coupled receptors (GPCRs) are the largest class of transmembrane proteins, making them an important target for therapeutics. Several aspects of GPCR signalling pathways, however, still remains elusive. In this thesis, two key aspects are addressed: the role ligands play in shaping the conformational landscape of GPCRs, and the oligomeric size of GPCRs during different stages of signalling. Here, a combination of ensemble and single-molecule fluorescence techniques were used to investigate the above, whereby the A2A adenosine receptor (A2AR), and the M2 muscarinic receptor (M2R) were used as model systems. Using single-molecule Förster Resonance Energy Transfer (smFRET), it was shown that A2AR exhibits a high degree of basal activity, and that the relative populations of inactive and active states is modulated upon binding of ligand. Furthermore, photoinduced electron transfer, monitored via Fluorescence Correlation Spectroscopy (PET-FCS), showed that ligands also effect the dynamics within and between several conformational states of A2AR. This work provides a quantitative approach to study how ligands modulate the conformational landscape of GPCRs. The oligomeric size of detergent-purified M2R and its attendant G protein (Gi1) were determined using single-molecule Photobleaching (smPB) analysis via a total internal reflection fluorescence (TIRF) microscope. The smPB analysis revealed that both M2R and Gi1 were oligomeric in nature prior to coupling, predominantly consisting of tetramers for M2R and hexamers for Gi1, regardless of ligand. In the coupled state (RG), it was found that a tetrameric M2R couples to tetrameric Gi1, whereby the binding of nucleotide (guanosine triphosphate) causes the disassembly of the RG complex, and a reduction in the oligomeric size of Gi1 from tetramers to dimers. The binding of an inverse antagonist also results in disassembly of the RG complex, and a reduction in the oligomeric size of M2R from tetramers to monomers or dimers. The work suggests that active M2R is tetrameric and solely capable of binding to tetrameric forms of Gi1, whereas the active form of Gi1 is dimeric and only activatable when coupled to M2R.

Keywords: Fluorescence
FRET
GPCRs
membrane proteins
protein dynamics
Single-molecule
Advisor: Gradinaru, Claudiu C