VictorJuiz/thesis huggingface dataset:
Quantum and Classical Optics of Dispersive and Absorptive Structured Media

This thesis presents a Hamiltonian formulation of the electromagnetic fields in structured (inhomogeneous) media of arbitrary dimensionality, with arbitrary material dispersion and absorption consistent with causality. The method is based on an identification of the photonic component of the polariton modes of the system. Although the medium degrees of freedom are introduced in an oscillator model, only the macroscopic response of the medium appears in the derived eigenvalue equation for the polaritons. For both the discrete transparent-regime spectrum and the continuous absorptive-regime spectrum, standard codes for photonic modes in nonabsorptive systems can easily be leveraged to calculate polariton modes. Two applications of the theory are presented: pulse propagation and spontaneous parametric down-conversion (SPDC). In the propagation study, the dynamics of the nonfluctuating part of a classical-like pulse are expressed in terms of a Schrödinger equation for a polariton effective field. The complex propagation parameters of that equation can be obtained from the same generalized dispersion surfaces typically used while neglecting absorption, without incurring additional computational complexity. As an example I characterize optical pulse propagation in an Au/MgF 2 metallodielectric stack, using the empirical response function, and elucidate the various roles of Bragg scattering, interband absorption and field expulsion. Further, I derive the Beer coefficient in causal structured media. The SPDC calculation is rigorous, captures the full 3D physics, and properly incorporates linear dispersion. I obtain an expression for the down-converted state, quantify pair-production properties, and characterize the scaling behavior of the SPDC energy. Dispersion affects the normalization of the polariton modes, and calculations of the down-conversion efficiency that neglect this can be off by 100% or more for common media regardless of geometry if the pump is near the band edge. Furthermore, I derive a 3D three-wave group velocity walkoff factor; due to the interplay of a topological property with a symmetry property, I show that even if down-conversion is into a narrow forward cone, neglect of the transverse walkoff can lead to an overestimate of the SPDC energy by orders of magnitude.

Keywords: Hamiltonian
dispersive
absorptive
dielectric
propagation
spontaneous
parametric
down-conversion
downconversion
metallodielectric
structured media
metamaterial
Advisor: Sipe, John E.
Emergence of Unconventional Phases in Quantum Spin Systems

In this thesis, we investigate strongly correlated phenomena in quantum spin systems. In the first part of this work, we study geometrically frustrated antiferromagnets (AFMs). Generalizing the SU(2) Heisenberg Hamiltonian to Sp(N) symmetry, we obtain, in the large-N limit, the mean-field phase diagrams for the planar pyrochlore and cubic AFMs. We then use gauge theories to consider fluctuation effects about their respective mean-field configurations. We find, in addition to conventional Neel states, a plethora of novel magnetically disordered phases: two kinds of spin liquids, Z2 in 2+1D and U(1)in 3+1D, and several valence bond solids such as two and three-dimensional plaquette and columnar singlet states. We use the same approach to study the diamond lattice AFM which possesses extended classical ground state degeneracy. We demonstrate that quantum and entropic fluctuations lift this degeneracy in different ways. In the second part of the thesis, we study ultracold spinor atoms confined in optical lattices. We first demonstrate the feasibility of experimental realization of rotor models using ultracold spin-one Bose atoms in a spin-dependent and disordered optical lattice. We show that the ground state of such disordered rotor models with quadrupolar interactions can exhibit biaxial nematic ordering in the disorder-averaged sense, and suggest an imaging experiment to detect the biaxial nematicity in such systems. Finally, using variational wavefunction methods, we study the Mott phases and superfluid-insulator transition of spin-three bosons in an optical lattice with an anisotropic two dimensional optical trap. We chart out the phase diagrams for Mott states with n = 1 and n = 2 atoms per lattice site. We show that the long-range dipolar interaction stabilizes a state characterized by antiferromagnetic chains made of ferromagnetically aligned spins. We also obtain the mean-field phase boundary for the superfluid-insulator transition, and show that inside the superfluid phase and near the superfluid-insulator phase boundary, the system undergoes a first order antiferromagnetic-ferromagnetic spin ordering transition.

Keywords: physics
theoretical condensed matter
frustrated magnets
spin liquids
valence bond solids
cold atoms
biaxial nematicity
Mott insulators
superfluid
order by disorder
quantum fluctuations
Advisor: Kim, Yong Baek
Gravitational Lensing and the Maximum Number of Images

Gravitational lensing, initially a phenomenon used as a solid confirmation of General Relativity, has defined itself in the past decade as a standard astrophysical tool. The ability of a lensing system to produce multiple images of a luminous source is one of the aspects of gravitational lensing that is exploited both theoretically and observationally to improve our understanding of the Universe. In this thesis, within the field of multiple imaging we explore the case of maximal lensing, that is, the configurations and conditions under which a set of deflecting masses can produce the maximum number of images of a distant luminous source, as well as a study of the value for this maximum number itself. We study the case of a symmetric distribution of n-1 point-mass lenses at the vertices of a regular polygon of n-1 sides. By the addition of a perturbation in the form of an n-th mass at the center of the polygon it is proven that, as long as the mass is small enough, the system is a maximal lensing configuration that produces 5(n-1) images. Using the explicit value for the upper bound on the central mass that leads to maximal lensing, we illustrate how this result can be used to find and constrain the mass of planets or brown dwarfs in multiple star systems. For the case of more realistic mass distributions, we prove that when a point-mass is replaced with a distributed lens that does not overlap with existing images or lensing objects, an additional image is formed within the distributed mass while positions and numbers of existing images are left unchanged. This is then used to conclude that the maximum number of images that n isolated distributed lenses can produce is 6(n-1)+1. In order to explore the likelihood of observational verification, we analyze the stability properties of the symmetric maximal lensing configurations. Finally, for the cases of n=4, 5, and 6 point-mass lenses, we study asymmetric maximal lensing configurations and compare their stability properties against the symmetric case.

Keywords: Gravitational Lensing
Multiple Images
Microlensing
Advisor: Dyer, Charles C.
The Role of Drinking Water as a Source of Transmission of Antimicrobial Resistant Escherichia coli

Antimicrobial resistance is a serious threat to the treatment of infectious diseases and a leading public health concern of the 21st century. Antimicrobial resistant E. coli has been detected in many places including domestic livestock, humans, food items, surface water, and drinking water. Although the use of antibiotics is a major contributor to the emergence of resistance, the ingestion of water contaminated with antimicrobial resistant bacteria may contribute to the prevalence of antimicrobial resistance in humans. Purpose: The objectives of the research were to determine the prevalence of human faecal carriage of antimicrobial resistant E. coli in people residing in southern Ontario who used private water sources and to determine whether the use of water contaminated with antimicrobial resistant E. coli was associated with human carriage of same. Method: The study population consisted of people living in Ontario households that submitted water samples from private water sources for bacteriological testing between May 2005 and September 2006. Respondents completed a questionnaire and submitted a self-collected rectal swab. Results: Antimicrobial resistant E. coli were detected in the swabs of 41% of the 699 respondents, with 28% resistant to ampicillin, 25% to tetracycline, and 24% to sulfisoxazole, and 29% that were multi-drug resistant. Subjects from households using untreated water contaminated with antimicrobial resistant E. coli were 40% more likely to carry antimicrobial resistant E. coli in their gastrointestinal system than people from households using uncontaminated water, even after adjusting for the effect of other variables. Implications: The association between the consumption of water contaminated with antimicrobial resistant E. coli and human carriage of resistant E. coli highlights the ongoing risks associated with water contamination and antimicrobial resistance in Ontario. The high rates of resistant E. coli in healthy non-institutional persons provides further rationale for public health programs to reduce antibiotic use in medicine and agriculture.

Keywords: epidemiology
public health science
Advisor: McGeer, Allison
The Relationship Between Temperature and 911 Medical Dispatch Data for Heat-Related Illness in Toronto, 2002-2005: An Application of Syndromic Surveillance

Heat-related illness (HRI) is of growing public health importance, particularly with climate change and an anticipated increased frequency of heat waves. A syndromic surveillance system for HRI could provide new information on the population impact of excessive heat and thus be of value for public health planning. This study describes the association between 911 medical dispatch calls for HRI and temperature in Toronto, Ontario during the summers of 2002-2005. A combination of methodological approaches was used to understand both the temporal trend and spatial pattern in the relationship between 911 medical dispatch data and temperature. A case definition for HRI was developed using clinical and empirical assessments. Generalized Additive Models (GAM) and Zero inflated Poisson regression (ZIP) were used to determine the association between 911 calls and mean and maximum temperature. The validity of the HRI case definition was investigated by making comparisons with emergency department visits for HRI. Descriptive, aberration detection, and cross-correlation methods were applied to explore the timing and volume of HRI calls in relation to these visits, and the declaration of heat alerts. Finally, the existence of neighbourhood level spatial variation in 911 calls for HRI was analyzed using geospatial methods. This is the first study to demonstrate an association between daily 911 medical dispatch calls specifically for HRI and temperature. On average, 911 calls for HRI increased up to a maximum of 36% (p<.0001) (median 29%) for each 1°C increase in temperature. The temporal trend of 911 calls for HRI was similar to emergency department visits for HRI and heat alerts, improving confidence in the validity of this data source. Heterogeneity in the spatial pattern of calls across neighbourhoods was also apparent, with recreational areas near the waterfront demonstrating the highest percentage increase in calls. Monitoring 911 medical dispatch data for HRI could assist public health units carrying out both temporal and geospatial surveillance, particularly in areas where synoptic based mortality prediction algorithms are not being utilized. This previously untapped data source should be further explored for its applications in understanding the relationship between heat and human health and more appropriately targeting public health interventions.

Keywords: Epidemiology
Advisor: Cole, Donald
Reporting Adverse Drug Reactions Associated with Herbal Products: Consumer, Health Food Store Personnel and Pharmacist Perspectives

Natural health products (NHPs) are sold over-the-counter and are often perceived to be safe, despite potential risks. The current Canadian reporting system collects information on suspected adverse drug reactions (ADRs) and suffers from severe under-reporting. As retailers, pharmacists and health food store personnel may be in a position to facilitate collection of herbal ADR reports because of their accessibility to consumers. Objective: To investigate retailer and consumer responses to herbal ADRs. Methods: In-depth interviews were conducted with retailers and consumers across Toronto until theoretical saturation was achieved (n=36). Participants were purposefully selected to ensure diverse backgrounds and experiences. Interviews were transcribed and coded for key emerging themes. Results: Consumers tended to self-prescribe NHPs and were only likely to discuss their NHP use with people they trusted – usually health food store personnel, family and friends. Many consumers did not have good relationships with their conventional health providers, which inhibited discussions about NHP-related ADRs. When consumers did disclose suspected ADRs to retailers, the retailers generally did not report these NHP-related ADRs to Health Canada. Most pharmacists found workplace challenges insurmountable, although pharmacist approaches to herbal ADRs tended to vary depending on their professional disposition. Pharmacists who saw themselves as knowledge generators were more likely to report. Health food store personnel offered generous product return policies and actively returned NHPs suspected of causing an ADR to the manufacturer. However, they had no knowledge of the Canadian ADR reporting system and thus did not submit any reports. Conclusion: Consumers tended to disclose suspected NHP-related ADRs only rarely and to retailers with whom they had developed previous good relationships. This highlights the importance of improving patient-practitioner (or retailer) communication. Pharmacists generally did not report ADRs due to workplace challenges, unless they had a very strong professional disposition. These results have important implications with respect to pharmacy education. Health food store return policies resulted in suspected ADR reports to the manufacturers. Manufacturers are mandated to report ADRs to Health Canada, so this finding may have important implications within industry for the future of ADR reporting systems involving herbal products and public health.

Advisor: Boon, Heather
Mechanisms of Drug-induced Oxidative Stress in the Hepatocyte Inflammation Model

Drug induced idiosyncratic agranulocytosis has been attributed to oxidation by hypochlorite formed by bone marrow myeloperoxidase (MPO). Idiosyncratic liver toxicity could also involve drug oxidative activation by cytochrome P450 (in hepatocytes) or MPO (in Kupffer cells or infiltrating neutrophil/macrophages). Such drug reactive metabolites could cause cytotoxicity or release “danger signals” that attract immune cells which release H2O2 resulting from nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) activation. In vivo animal studies have shown that low level tissue inflammation markedly increased drug-induced tissue toxicity which was prevented by immune cell inhibitors and increased by cell activators. It is suggested that idiosyncratic drugs are much more toxic, taken during symptomless inflammation periods. Furthermore, it is hypothesized that hepatocytes are much more susceptible to some idiosyncratic drugs if they are exposed to hydrogen peroxide (H2O2)/myeloperoxidase or cytokines released by inflammatory cells. A hepatocyte inflammation model, in which hepatocytes were exposed to a non-toxic H2O2 generating system and peroxidase, was found to be much more vulnerable to four idiosyncratic drugs e.g., troglitazone, isoniazid, hydralazine and amodiaquine. The molecular cytotoxic mechanisms for this marked increase in cytotoxicity were investigated as follows: 1) A P450/H2O2-catalyzed pathway not involving oxidative stress e.g., hydralazine and isoniazid; 2) A P450/H2O2-catalyzed oxidative stress-mediated cytotoxic pathway e.g., hydrazine (an isoniazid metabolite) and hydralazine; and 3) A peroxidase/H2O2-catalyzed oxidative stress-mediated cytotoxic pathway e.g,, hydralazine, amodiaquine and troglitazone. Before cytotoxicity ensued, GSH oxidation, protein carbonyl formation and often lipid peroxidation occurred followed by a decrease in mitochondrial membrane potential indicating that oxidative stress was the molecular mechanism of cytotoxicity. In summary, a H2O2-enhanced hepatocyte system in the presence and absence of peroxidase may prove useful for a more robust screening of drugs for assessing the enhanced drug toxicity risk associated with taking drugs during periods of inflammation.

Keywords: Inflammation, Oxidative Stress, Hepatocytes
Advisor: O'Brien, Peter J.
Application of Pharmacokinetic Theory to Examine Roles of Transporters and Enzymes in Intestinal and Hepatic Drug Disposition

The interplay of transporters and enzymes and their transporter-enzyme was examined in Caco-2 cell monolayer and recirculating perfused rat liver preprations via both theoretical and experimental approaches. First, a Caco-2 catenary model that consisted of the apical, cellular, basolateral compartments and encompasses influx, efflux transporters and enzymes was shown to be superior to the single barrier approach for data interpretation on transporter- and enzyme- mediated processes. The kinetics of baicalein, a flavonoid that undergoes glucuronidation and sulfation, were found to be described better by the catenary model for the complex kinetics of substrate inhibition in metabolism. Second, estradiol-17beta-D-glucuronide (E217G), a protypic substrate of Oatp1a1, 1a4, and 1b2 and Mrp2 that underwent futile cycling with its 3-sulfate metabolite (E23S17G) via estrogen sulfotransferase (Sult1e1) and arylsulfatase C, was examined in the perfused rat liver preparation. Solutions of the AUC and clearances were solved to relate the intrinsic clearances of transporters and enzymes to understand how these affected the apparent clearances in the presence of futile cycling. Transporters and enzymes were perturbed experimentally by the intraportal injection of CC531 colon carcinoma cells for tumor induction in Wag/Rij rat livers. The protein expression of Oatp1a1 and Oatp1b2 were reduced to half whereas Sult1e1 was increased by 40% with tumor development versus the sham-operated control. These data were well predicted by the physiologically-based liver model, showing the impact of increased sulfation intrinsic clearance but not the decreased influx clearance. The TR- (Mrp2 mutant) rat model was used to examine how the absence of Mrp2 for biliary secretion of both E217G and E23S17G affected futile cycling. Absence of Mrp2 was found to result in a pseudo steady-state and reduction of the total, excretion, and metabolic clearances in the liver. The work shed new insight on the interplay between enzymes and transporters and how kinetic processes mediated by enzymes or efflux transporters affected futile cycling.

Keywords: pharmacokinetics
transporter
enzyme
drug disposition
PBPK modeling
drug first-pass removal
Caco-2
liver perfusion
Advisor: Pang, K. Sandy
Methods to Predict Individualized Combined Benefit/Harm Patient Profiles for Warfarin

Warfarin has well-proven benefit (stroke prevention) but an associated increase in harm (major bleeding) in patients with atrial fibrillation (AF). Current clinical prediction rules (CPRs) are limited in that stroke CPRs predict only the probabilities of “stroke” and “no stroke” and bleeding CPRs predict only “bleed” and “no bleed” despite the fact that outcomes actually include combinations of these four groups. The study objective was to evaluate methods to create a CPR that calculates individual patient probabilities of warfarin’s four combined benefit/harm outcome groups: i) no stroke/no bleed; ii) no stroke/bleed; iii) stroke/no bleed; iv) stroke/bleed. Methods: Patient-level data were analyzed from a randomized controlled trial database (n=9,155) and an observational anticoagulant clinic database (n=5,475) from start of trial or time of AF diagnosis respectively (baseline), until end of follow-up. Patients were stratified into the four groups based on their outcomes during follow-up. Due to high mortality in both datasets, death was included as an outcome. Decision tree modeling and polytomous logistic regression (PLR) were conducted to identify baseline patient factors predicting each outcome group. Results: Based on a literature review of recent high quality RCTs, benefit and harm are reported separately and not at a more individualized level than subgroup analysis. In this individualized combined benefit/harm analysis, both PLR and decision tree modeling identified predictors of no stroke/no bleed, no stroke/bleed, stroke/no bleed and death without a prior stroke or bleed. PLR results predicted probabilities of combined benefit/harm outcomes for every patient but required detailed computation. However, results could potentially be converted into automated form for ease of use. Decision trees provided a visual algorithm approach to risk assessment but did not i) predict the probability of warfarin’s combined benefit/harm outcomes based on all predictors simultaneously, ii) predict the probability of these outcomes for every patient or iii) provide statistical parameters of predictive value (odds ratios). Conclusions: The PLR technique could be used to predict patient probabilities of combined benefit/harm outcomes with warfarin. The study results require validation, preferably prospectively, in other cohorts. If validated, this approach should be tested to determine if it aids patient decision-making.

Keywords: warfarin
risk assessment
methods
Advisor: Holbrook, Anne