VictorJuiz/thesis huggingface dataset:
Use of Troponin Testing after Non-cardiac Surgery

Myocardial injury after noncardiac surgery (MINS), which is most often asymptomatic, is associated with increased mortality and morbidity. In 2017, the Canadian Cardiovascular Society (CCS) published guidelines recommending broad post-operative troponin surveillance in high-risk patients having major non-cardiac surgery. The objectives of this thesis were to: (1) evaluate the proportion of patients having major non-cardiac surgery in Ontario that would meet guideline recommendations for routine post-operative troponin testing; (2) determine the patient-, surgical-, and hospital-factors associated with post-operative troponin testing; and (3) evaluate whether high-intensity troponin testing practices at the hospital-level were associated with fewer adverse outcomes after major non-cardiac surgery. In Chapter 2, I identified 257,704 patients who underwent non-cardiac surgery in Ontario. Applying the CCS guidelines to this cohort, 71.2% of elective surgery patients and 81.0% of urgent surgery patients would have met recommendations for post-operative troponin screening, while only 10.8% and 27.1% of guideline recommended patients received post-operative troponin testing, respectively. In Chapter 3, I identified 176,454 patients undergoing orthopedic, colorectal, or vascular surgery in Ontario. Hierarchical logistic regression modeling was used to assess the association of patient-, surgery-, and hospital-factors with postoperative troponin testing. I found that troponin testing varied substantially across hospitals for selected major non-cardiac surgery procedures even after accounting for differences in patient-level cardiac risk factors. In Chapter 4, I identified 18,467 patients undergoing common vascular surgical procedures (carotid endarterectomies and abdominal aortic aneurysm repairs). Cox proportional hazards modeling was used to assess the association of hospital-specific testing intensity with 30-day and 1-year major adverse cardiovascular outcomes (MACE). Compared to patients at low-testing intensity hospitals, patients at high-testing intensity hospitals experienced a lower hazard of MACE over 30-days and 1-year. Overall, I established that CCS guidelines recommend routine troponin testing for most patients having major non-cardiac surgery. Prior to the publication of the CCS perioperative guidelines, the overall testing rate was low, and there was substantial hospital-level variation in the use of routine troponin testing. Finally, in a cohort of vascular surgery patients, I found that patients who had procedures at high-testing intensity hospitals experienced fewer adverse outcomes, thus supporting recommendations to increase testing to detect MINS in the future.

Keywords: Guideline
MINS
Myocardial injury after noncardiac surgery
noncardiac surgery
Revised cardiac risk index
Troponin
Advisor: Ko, Dennis T
Probing Atom On-site Interactions in an Optical Lattice

In this thesis, we observe and characterize both s-wave and p-wave interactions of fermionic 40K atoms in deep optical lattices. The p-wave interactions especially draw our attention, as they have a well understood connection to topological properties. The discovery of p-wave interactions in ultracold-atom systems is promising, as the systems are tunable and controllable, but the experimental efforts have been severely limited by the short lifetime of atoms due to the three-body loss mechanism. The deep lattice potential applied in our study ensures near-zero tunneling, such that we are able to directly measure the on-site interaction energies of isolated pairs of atoms, and this isolation especially helps to suppress three-body losses for p-wave interacting pairs.For s-wave interactions between two lowest spin states in the ground hyperfine manifold, the binding energies of the s-wave molecular dimers have been studied pre- viously. However, in our study, we also measure the repulsive interaction energies via the radio-frequency (RF) spectroscopy. The obtained energy eigenspectrum for the atom pairs can be well explained by the theory based on two atoms in a harmonic trap interacting via a pseudopotential. Another experimental technique to measure the s-wave interaction energies is developed as well using Raman excitation. By cou- pling both spin and motional degrees of freedom, we obtain an energy spectrum that agrees well to the one using RF spectroscopy. To study p-wave interactions between two identical atoms in a spin triplet state, we prepare an initial non-interacting triplet state with a motional excitation via Raman excitation, and then directly measure the p-wave interaction energies by RF coupling the initial state to the final interacting one. The resulting universal energy spectra obtained at various conditions are well characterized by an exact solution for two harmonically confined atoms interacting via a p-wave pseudopotential with anharmonic corrections. We also measure the Rabi oscillations of the p-wave interacting pairs, and take the first steps towards the coher- ent control of the oscillations. Finally, we set up an experiment to test the lifetime of the p-wave interacting pairs, and find that losses are limited by the intrinsic lifetime of the molecular dimer. The lifetimes are measured to be much longer than observed for free-space dimers, and are predicted well by calculating the short-range fraction of the wavefunctions. Another theory based on an ab initio interaction potential is applied as well, which gives similar results to the pseudopotential theory, and again proves their validity.

Advisor: Thywissen, Joseph H
Selection and Evolutionary Constraint in Ipomoea hederacea

Understanding how adaptive evolution proceeds in populations experiencing different environments is the basis of much of evolutionary biology. Genetic variation is required for evolutionary change by natural selection to occur, and that genetic variation is oftentimes correlated among traits. Selection acts on the entirety of an organism’s phenotype and is thusalso best considered in a multivariate context. The interaction between selection and the organization of genetic variation together produces the evolutionary trajectory of a population. In my doctoral work, I have explored the influence of genetic correlations between traits on the response of populations to selection in populations across a geographic range, using the Ivyleaf Morning Glory (Ipomoea hederacea). I demonstrate the constancy of these genetic correlations among populations in the face of the destabilizing force of genetic drift. I investigate how genetic correlations and strong natural selection have shaped divergence among populations across space. Additionally, I consider what these evolutionary patterns suggest about the maintenance of range limits and potential for future northward expansion of Ipomoea hederacea. I find overall stability of the genetic relationships among quantitative traits, and strong selection which acts counter to the majority of the genetic variation. The observed divergence among populations has occurred despite the constraining influence of their quantitative genetic architecture. Future adaptive evolution beyond the range margin will largely depend on the source population, as minor difference in the structure and quantity of genetic variation may have critical impact of population persistence. Further, I demonstrate the potential for using machine learning to predict fitness using gene expression data from a field experiment with I. hederacea. I find that photosynthesis-related genes, and genes related to stress response are major contributors to fitness differences.

Keywords: G-matrix
Genetic correlations
Natural selection
Quantitative genetics
Advisor: Stinchcombe, John R
Finding Oneself in the World

Thinking about oneself as the subject of a perspective on the world leaves unanswered fundamental questions about one’s identity as an object in the world: about which thing one is, what kind of thing one is, and about whether one exists as an object at all. I put forward a new way of thinking about these questions by outlining the subject-as-object problem, a problem for any attempt to adopt a third-person perspective on oneself qua subject. I argue that the source of the problem lies in the relationship between a basic precondition for inquiry – that something be present – and a framework that enables us to conceive of ourselves as inquirers in an objective world – the framework of objectivity. Once the problem is recognized, we can explain why it is possible to raise questions about one’s identity in response to any account of oneself and one’s relation to the world. Furthermore, having the problem in view enables us to more deeply engage with a range of philosophical issues that concern, in one way or another, the relationship between the subject’s perspective and the objective circumstances under which this perspective discloses a part of the world.

Keywords: First-person perspective
Inquiry
Objectivity
Presence
Subject of experience
Third-person perspective
Advisor: Rattan, Gurpreet
Concerto for Alto Saxophone and Orchestra

Concerto for Alto Saxophone and Orchestra is a three-movement, eighteen-minute-long musical composition for orchestra and saxophone soloist. The orchestra’s size, aligned with contemporary standard, consists of two flutes (Flute 2 doubling piccolo), two oboes (Oboe 2 doubling English horn), two clarinets in A, two bassoons, four horns in F, two trumpets in C, two tenor trombones, one bass trombone, one tuba, timpani, one percussionist, and strings. The work’s three movements are unified by a progressive degradation of linear material. The opening movement consists of musical materials that follow Classical conventions of melody-writing, emphasizing stepwise motion within a diatonic framework and notably utilizing a modified dorian mode referred to in jazz as the dorian bebop scale. In the second movement, the interval of a seventh – the intervallic inversion of a step – asserts itself as a defining feature of melodic and harmonic devices, before the entire framework collapses in the final movement, in which the scalar materials of the previous movements are reduced to three- or four-note motifs. Following the conventional construction of a concerto, the soloist is frequently the focal point of the ensemble. Great care was taken during the composition process to provide the soloist with material that is impressive both musically and as a feat of saxophone performance. In particular, the extreme upper altissimo register of the saxophone is used extensively throughout all three movements of the piece – the saxophonist must utilize more than three-and-one-half octaves, as opposed to the instrument’s typical range of two-and-one-half octaves. The soloist is frequently tasked with playing soft, delicate material in the altissimo register, in contrast to the register’s more typical usage for forceful, resonant passages. The finale movement is a monstrous tour de force for both soloist and ensemble, as both are forced to reckon with registral extremes and rapid meter changes.

Advisor: Kulesha, Gary
Associations Between Genetic Variation and Cigarette Smoking and Alcohol Drinking during Youth: Longitudinal Investigations

We evaluated genetic-based associations with early smoking and drinking behaviours among European-ancestry youth in a longitudinal cohort design. In Study 1, we examined associations between genetic variation in TAS2R38, which encodes a bitter taste receptor, and early smoking behaviours. Individuals with the PAV/PAV or PAV/AVI diplotypes (i.e., PAV diplotypes) are considered bitter tasters, whereas AVI/AVI (i.e., AVI diplotype) are non-tasters. Cox proportional hazards models estimated associations between TAS2R38 diplotype and time to early smoking outcomes in adolescent incident smokers (i.e., those who initiated smoking during study follow-up). While similar diplotype-based rates to first whole cigarette were found, those with the PAV diplotypes attained monthly smoking and converted to tobacco dependence (measured using three indicators ICD-10, mFTQ, and HONC) faster than those with the AVI diplotype. When these participants reached young adulthood (age 24), those with PAV diplotypes had higher mean cotinine + 3’hydroxycotinine, a biomarker of nicotine intake.In Study 2, we examined associations between genetic variation in fatty acid amide hydrolase (FAAH) and early drinking behaviours, and whether similar associations were observed with early smoking milestones. As part of the endocannabinoid system, which is implicated in psychiatric disorders and drug dependence, FAAH metabolizes endocannabinoids such as anandamide. Individuals with A-group genotypes (C/A or A/A) of a FAAH missense variant (rs324420; C>A) have slower enzymatic activity than those in the C-group (C/C genotype). We first replicated findings from two studies in adults, where those in the A-group had higher odds of past-year binge drinking at ages 20 and 30. Next, Cox proportional hazards models were used to estimate associations during adolescence, where those in the A-group had faster time to drinking initiation and daily drinking. Although the genotype associations extended to faster rates to smoking initiation, associations with early smoking milestones were inconsistent. Thus, the ability to taste bitter compounds increases the risk for early smoking behaviours, while slow FAAH activity increases risk for drug use initiation and harmful drinking behaviours. Our findings underscore the importance of examining genetic associations in acquisition and early drug use behaviours and contribute to our understanding of inter-individual differences in substance use in adolescence.

Advisor: Tyndale, Rachel F.
Improvements to Digital Microfluidic Technologies: Towards Automated Point-of-Care Diagnostics

Digital microfluidics (DMF) is a liquid handing technique that allows precise manipulation of discrete droplets of liquids by electrostatic forces. Individual droplets can be dispensed, mixed, merged, and separated in DMF, allowing automation of liquid handling steps that are required in complex multi-step operations. This automation capability makes DMF an attractive candidate for developing point-of-care (POC) systems with minimal user involvement and training. However, the biofluids that are commonly handled by POC systems can negatively impact droplet movement in DMF through non-specific adsorption (NSA) to the device surfaces; thus, there are substantial challenges that must be overcome before this dream can be realized. This thesis describes my work investigating Pluronic®/Tetronic® surfactants in combatting NSA in DMF to enable automated sample processing in POC systems. Chapter 2 describes a systematic study of the anti-fouling performance and mechanism of a series of Pluronic® and Tetronic® surfactant additives. Chapter 3 describes the development of a novel microscopic technique, supercritical angle fluorescence microscopy, for monitoring surface adsorption on a Teflon-AF film and determining the anti-fouling mechanism of surfactant additives. Chapter 4 describes the hardware and methodological improvements that enable viral nucleic acid extraction and amplification in DMF for detecting infection for Zika virus in a field trial in Recife, Brazil. Chapter 5 describes work-in-progress towards the application of DMF with surfactant additives for a new type of portable SARS-CoV-2 nucleic acid-based diagnostic technique. In summary, this thesis addressed the challenges of NSA in DMF and describes how to push the boundaries of what is possible for DMF in automating liquid handling in POC systems.

Keywords: biofouling
COVID19
digital microfluidics
disease diagnosis
nucleic acid amplification assay
supercritical angle fluorescence spectroscopy
Advisor: Wheeler, Aaron R
Reconstructing Past Sea Ice Cover with Coralline Red Algae

Arctic sea ice plays a pivotal role in climate regulation. Its decline in recent decades has contributed to Arctic Amplification, the fast rate of Arctic warming in comparison to other regions. Models that aim to predict future climate are continuously under development as they still underestimate warming, and particularly sea ice loss and variability. These models must be refined with long-term, spatially diverse, and highly resolved data, to be as accurate as possible. However, instrumental data records are short-term and spatially constrained. The use and continued development of environmental proxies such as sediment and ice cores help lengthen data records (Chapter 1). Likewise, the coralline red algae species Clathromorphum compactum is a sea ice cover proxy in development. Several multi-century algal timeseries of past sea ice variability have been generated using this proxy, however, uncertainties remain about: 1) whether sea ice cover can be reconstructed at all C. compactum collection sites, and 2) whether methodological standardization ensure data replicability between intra-site specimens and validate C. compactum-based chronologies. In this thesis, I first tested whether growth increments, Mg/Ca averages, or combined anomalies were best suited to capture sea ice variability during the ~40-year satellite record at 11 subarctic and arctic sites (Chapter 2). Results showed that growth increment-based chronologies from exposed sites, far from runoff sources, experiencing long lasting sea ice cover (>6-7 months) best captured sea ice variability. However, intra-site replicability was low and insignificant at most sites in this multi-site study. This prompted a study on the application of dendrochronological crossdating methods to improve intra-site replicability of algal chronologies (Chapter 3). The findings suggested that the previously utilized methods incorporated subjective interpretation and that crossdating improved intra- and inter-specimen replicability, setting a new standardized methodology for age model determination and validation. Validated algal chronologies were then used to study the relationship between sea ice and large-scale atmospheric patterns and showed a significant sea ice response to the Arctic Oscillation and other atmospheric patterns (Chapter 4). This thesis has examined the advantages and limitations of the algal sea ice proxy and should methodologically guide future research with C. compactum-based proxies.

Keywords: Arctic
Coralline red algae
Crossdating
Mg/Ca
Paleoclimate
Sea ice
Advisor: Halfar, Jochen
The Canadian Punitive Paradox: The Evolution of Conservative Political Marketing Practices and the Late Onset of Penal Populism in Canadian Federal Politics

At the height of the punitive turn that occurred among Western liberal democracies, Canadian federal politics stands out as exceptional for choosing not to embrace a ‘tough-on-crime’ agenda. Instead, penal populism emerged as a salient political marketing tool in Canadian federal politics much later — at a time when many of the failures associated with its outcomes were coming to light elsewhere. The latent emergence of penal populism in Canadian federal politics was atypical as it often surfaced as a hollow performative tool that consisted of expressive rhetoric over substantive outcomes. This dissertation argues that the political marketing strategies that governed political campaigns were critical in the decision to adopt or reject penal populism as a campaign tool. By situating the presence or absence of penal populism within the context of shifting campaign strategies, this study deepens our understanding of Canadian punitive exceptionalism and shows that the Canadian version of penal populism was heavily influenced by advancements in political marketing strategies. This study also advances our understanding of the narratives used to shape a ‘tough-on-crime’ image and the extent to which it existed between electorally successful conservative campaigns. Through an analysis of the emotional rhetoric used to promote punitive sentencing policy, specifically mandatory minimum and maximum sentences, this dissertation exposes the manner in which emotionality is used to enhance the appeal of these political offerings.

Keywords: Emotionality
Penal populism
Political Marketing
Sentencing Policy
Advisor: Maurutto, Paula
A Thermosensitive Liposome Formulation of Vinorelbine for the Treatment of Recurrent Rhabdomyosarcoma

Approximately one third of rhabdomyosarcoma (RMS) patients experience disease recurrence and subsequently face a dismal prognosis. In most cases, the disease recurrence involves or is confined to the primary disease site, highlighting the need for effective treatment approaches that can improve local control. Chemotherapy continues to play an important role in treating residual disease and preventing local recurrence but is often associated with severe adverse effects. Common strategies to improve efficacy and toxicity profiles of chemotherapy, including liposomal encapsulation, heavily rely on passive tumor targeting via the enhanced permeability and retention (EPR) effect. Due to the recognized heterogeneity associated with the EPR effect in humans, other approaches for achieving tumor targeted drug delivery are needed. This thesis aims (1) to develop a thermosensitive-liposome formulation of vinorelbine (ThermoVRL) to provide EPR-independent drug delivery targeted to the tumor, (2) to evaluate the therapeutic efficacy of ThermoVRL in combination with localized mild hyperthermia (HT) compared to treatment with a non-thermosensitive liposomal formulation of vinorelbine (NTSL-VRL) in murine models of RMS and to identify the underlying pharmacokinetics and biodistribution, and (3) to determine the therapeutic efficacy of ThermoVRL and HT in an immunocompetent model of RMS and to explore if the addition of immunotherapy (i.e., immune checkpoint inhibition therapy (ICI)) to this treatment approach can enhance systemic anti-tumor effects. In summary, this work successfully developed a ThermoVRL formulation. Treatment with ThermoVRL and HT afforded superior therapeutic efficacy relative to treatment with free drug in a mouse xenograft model of RMS. Importantly, pharmacokinetic and biodistribution assessments of vinorelbine revealed an increase in tumor specific drug delivery when administered as ThermoVRL compared to administration as NTSL-VRL. Studies employing a bilateral RMS tumor model in immunocompetent mice revealed that anti-tumor effects following treatment with ThermoVRL and HT remain largely localized to the primary tumor site. However, the addition of ICI significantly enhanced the systemic treatment effects of ThermoVRL in combination with HT. The results of these studies demonstrate that this delivery approach can confer targetability to an untargeted drug molecule and open the door to treatment combinations with ICI to enhance the systemic treatment capabilities of thermosensitive liposomes.

Keywords: Drug Delivery
Mild Hyperthermia
Rhabdomyosarcoma
Thermosensitive Liposome
Vinorelbine
Advisor: Allen, Christine
Heerklotz, Heiko