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Biochar for Urban Forestry Applications: Improving Tree Establishment in Urban Soils
Get PDFThe majority of the global population lives in urban areas and trends indicate urbanization will continue to increase into the future. Urban soil and forest health is a concern as communities struggle to support vegetation in the face of climate change, drought, soil disturbance, compaction, erosion, nutrient imbalances, and environmental toxins. Biochar is a novel climate-positive high-carbon soil amendment created through pyrolysis of organic material. Recent research has demonstrated biochar benefits for agriculture, but it remains understudied for urban applications. Biochar use varies with feedstock and processing, but availability is rising in Canada and across the world as researchers study its production methods and qualities for different applications. When correctly matched to soil conditions, biochar amendments increase plant survival and growth in difficult conditions via improvements to soil chemistry, structure, and plant nutrition.
My thesis investigates biochar applications to improve establishment of trees and shrubs in urban forests. Through a series of greenhouse and multi-year field trials of wood biochar as a soil amendment in fine-textured high-pH urban soils in Toronto, Canada, I found that 20 t/ha doses of wood biochar in a range of particle sizes 1) induced positive growth, nutrient, and survival effects on a range of temperate woody plants with notable responses from N-fixing and pioneer species, 2) increased soil C and reduced soil bulk density, without significant effect on soil moisture, 3) when combined with microbial or N-fixing companion plant biofertilizers, led to significant gains in plant growth and nutrient uptake compared to biochars alone. This research is the first to test biochars in combination with bacterial, inert yeast, and N-fixing companion plant biofertilizers on woody species, and includes the largest urban forestry field trial to date in terms of scale and species diversity. The results show biochar holds promise to improve urban soil conditions and woody plant growth, particularly in combination with biofertilizers. Future research should test biochars with co-amendments across a range of additional species and nursery production, street tree, soft surface, and green roof urban plantings.Ph.D
Quantum Algorithms for Chemistry and Differential Equations
Get PDFQuantum computers were first proposed to perform simulation -- in particular, quantum simulation. The premise is that such computers can simulate quantum dynamics exponentially faster than a classical computer. Some of the early proposals of practical applications of quantum computers come from quantum chemistry. Algorithms for more general systems, described by ordinary and partial differential equations, emerged later on. This thesis grounds on an extensive amount of prior research and proposes a set of improvements as well as new algorithms or algorithmic tools, focusing on applications from quantum chemistry and differential equations.First, we propose a technique relating to finding ground-states for electronic systems via the variational quantum eigensolver. The presented method enables solving the problem on early quantum hardware by a partitioning of the computational problem into smaller problems, using only classical resources to perform the partitioning. Next, the thesis considers simulation problems from chemistry in a more general sense. Following the idea that dynamical simulation of many chemical systems is efficient, whereas preparing ground-states is a `hard' problem, our computational framework leverages simulation routines to prepare molecular states as an input to a computation, relying only on `hard' input states for small problem instances. The preparation relies on dynamical scattering of initial fragments supported by a trap potential, allowing to estimate the success probability for certain bonds. A weak measurement scheme enables preparation of molecular states.
Furthermore, this dissertation investigates quantum algorithms for differential equations. More specifically, the the Carleman linearization approach is considered to solve nonlinear differential equations. This entails bounding the Carleman truncation error, re-scaling of the solution to avoid an exponentially vanishing success probability, and discussing higher-order discretization. Moreover, this thesis introduced a penalty-based method to enforce constraints on the solution of differential equations, with inspiration from complex absorbing potentials and the quantum Zeno effect. We bound the approximation errors and embed the penalty method into an efficient quantum algorithm, with computational overhead only logarithmic in the penalty's strength. Efficiency is enabled by an interaction-picture approach with fast-forwardable constraint projections.Ph.D
The Experiences of Women Senior Housing Officers in Canadian Universities
Get PDFThe purpose of this study was to ascertain how participants had attained their positions and made meaning of their career progression. Using a narrative inquiry research design and qualitative methodology I explored the experiences of 12 women senior housing officers (SHOs) at 12 Canadian universities, in three provinces (i.e., Ontario, Manitoba, and British Columbia). For the analysis of the findings I used a radical feminist theoretical framework to better understand the experiences of participants (MacKay, 2015; Millett, 1969; Rowland & Klein, 1990). Conducting two sets of interviews with participants and a document analysis on their resumes, LinkedIn profiles, and position descriptions, I used a thematic analysis approach and identified four core themes. The core themes were giving back to community, on-going learning, demonstrating self-confidence, and gender bias. My findings provided insights on the influences and experiences that led participants to become a SHO and retain the position.
Findings illustrate that participants make-meaning of their career advancement through reflections on their own motivations for attaining and staying in the role, engaging in ongoing learning opportunities, developing strategies around working through times when they lacked self-confidence, demonstrating self-confidence when not yet fully feeling self-confident, engaging in ongoing learning, and through their persistence during incidents of gender bias and inequality. Findings also highlight that participants experienced incidents of gender bias and inequality through interactions within the context of a patriarchal university environment.
This research contributes to Canadian student affairs scholarship related to women in SHO positions, and the findings are intended as considerations for future women aspiring to be SHOs on the challenges ahead and strategies to overcome the challenges. Finally, insight gained from this research raises the consciousness of women SHOs voices, which I hope senior university administrators will note in an effort to create a more inclusive workplace.Ph.D
Studies of Microsatellite Instability Signatures in Replication Repair Deficient Malignant and Germline Tissues
Get PDFDNA replication errors are resolved by the mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, or PMS2) although pathogenic variants in MMR genes result in mismatch repair deficiency (MMRD). MMRD arises through primary causes (somatic or germline variants), or secondary causes (treatment-induced). Monoallelic germline variants in MMR genes causes Lynch Syndrome in adults who develop primarily gastrointestinal cancers. Biallelic germline MMR variants cause constitutional mismatch repair deficiency (CMMRD) in children who develop predominantly central nervous system malignancies. MMRD induces extreme genomic instability causing cancers characterized by hypermutation, microsatellite instability (MSI), and resistance to chemoradiation. The unique biology of MMRD tumors and high likelihood of cancer development means accurate diagnosis is crucial. MMRD diagnosis has relied on several methods which are insufficient in non-colorectal and childhood cancers. Fortunately, signatures of MSI provide highly specific diagnosis.Leveraging millions of microsatellites across the genome, this thesis resulted in creation of the functional assay LOw-pass Genomic Instability Characterization (LOGIC) for robust MMRD diagnosis in tumors. LOGIC additionally achieved diagnosis of CMMRD using germline tissues and MSI analysis revealed biological insights into MMRD mutagenesis. MSI correlated with specific MMR variants, tissues, and age at initial cancer diagnosis, enabling tailored screening protocols for the future.
The capacity to reliably diagnose MMRD enabled determination of its prevalence in primary gliomas, which represent the leading cause of cancer-related mortality in children. A population-based screen of gliomas in children, adolescents, and young adults (CAYA, 0-40 years) from Toronto, St Jude Children’s Research Hospital, and the Children’s Brain Tumor Network revealed a significant prevalence in high-grade gliomas. MMRD was enriched in IDH- and H3-WT high-grade gliomas but was absent in gliomas with pediatric-type alterations, fusions, or copy number variants. Almost all MMRD gliomas were driven by primary causes, namely germline alterations in MMR genes causing Lynch Syndrome, redefining the cancer spectrum in Lynch Syndrome. Immunotherapy in a cohort from the International Replication Repair Deficiency Consortium revealed significantly improved overall survival in MMRD CAYA gliomas. We suggest increased MMRD screening in specific glioma subtypes, germline testing for patients and family members, and further studies of immunotherapies in CAYA.Ph.D
Limits of control and robustness in biochemical reaction networks
Get PDFUnderstanding quantitative principles of biological control through gene regulatory networks is a key goal of systems biology and is necessary for engineering cellular systems. In this dissertation, I present theoretical limits on control and robustness in biochemical reaction networks.
I confirm a previously conjectured trade-off between noise control and perfect adaptation of cellular averages through sequestration-based integral control. However, I show that this "trade-off'" is singular in that it only applies to systems in the idealized limit of perfect adaptation: leaky integral feedback which achieves arbitrarily small parameter sensitivity for the controlled average can achieve significant noise suppression. I additionally propose a topological variation of sequestration-based integral control which may exhibit improved noise control in both the idealized perfect and near-perfect adaptation regimes. Across both controller variations, I predict that noise control is limited by the effective control burden, quantified through molecular turnover fluxes.
Sequestration-based integral control relies on tight coupling of degradation fluxes between two control species, i.e. where two subunits assemble into a complex. Yet, such tight coupling through efficient assembly has been proposed to lead to diverging fluctuations in a broad class of molecular assembly processes. Here I use statistical moment invariants to constrain subunit fluctuations within incompletely specified reaction networks. I show that an efficiency-fluctuation trade-off in which subunit fluctuations diverge in the perfect efficiency limit constrains much broader classes of assembly processes than previously considered. In particular, I show that a previously reported molecular noise filter is a singular limit of the broader class of systems considered and in biologically relevant regimes cannot filter fluctuations as efficiency approaches 100%. In contrast, I show that biomolecular integral controllers belong to a broader class of systems which incorporate distinct subunit synthesis rates with feedback to avoid diverging fluctuations in the high efficiency limit.
Lastly, I present a spatial extension of sequestration-based integral control for regulation of morphogen gradients. I show that the integral control structure now applies to the spatial integral of the regulated signal but that this does not lead to tight control of the gradient shape. Interestingly, inhibition of Nodal morphogens involved in vertebrate mesendoderm patterning takes place through a sequestration reaction. Thus, inspired by recent experiments on robustness in zebrafish development, I revise the spatial integral control system to model additional details of Nodal signalling regulation underlying mesendodermal patterning. I show the revised model predicts improved control of signalling gradients. I then use the revised model to predict the perturbation response of Nodal signalling gradients in embryos of wild-type as well as several feedback-compromised zebrafish lines. I then discuss these predictions in the context of experiments planned by our collaborators to further explore the origin of robustness in mesendodermal patterning.
The results of this dissertation make experimentally testable predictions of quantitative trade-offs limiting control in single-cells and multicellular tissues, and suggest design principles for designing robust biomolecular control systems for synthetic biology applications.Ph.D
Cost and Clinical Effectiveness of High-Intensity Focused Ultrasound versus Open Radical Prostatectomy, Robot-Assisted Radical Prostatectomy, or External Beam Radiation Therapy in Men with Localized Low and Intermediate Risk Prostate Cancer: A Cost-Utility Analysis
Get PDFProstate cancer (PCa) is the fifth leading cause of cancer death among Canadian men. Open radical prostatectomy (ORP), robot-assisted radical prostatectomy (RARP), and external beam radiation therapy (RT) are main lines of primary treatment for localized low and intermediate risk PCa. ORP is a major surgery in which a single large incision is made to access the pelvis and to completely remove the prostate, while RARP is a minimally invasive surgery in which several small incisions are made to access the abdomen and completely remove the prostate using a robotic device. In RT, a machine delivers focused beams of radiation from outside the body on the prostate gland to treat PCa. Focal therapies like high intensity focused ultrasound (HIFU) are emerging, less invasive treatment strategies with potential advantages as organ preservation, short recovery time, and few adverse events. There is limited published literature comparing HIFU with the standard of care (ORP, RARP, and RT) for primary treatment of localized low and intermediate-risk PCa and none of the previously published studies assessed the cost-effectiveness of primary HIFU from the Canadian healthcare payer’s perspective or provided insight into clinical subgroups of patients. We conducted an economic evaluation (cost-utility analysis) to compare the cost-utility of HIFU vs the standard of care as primary treatment for localized low and intermediate risk PCa in Ontario. To conduct the cost-utility analysis, we estimated the parameters of a Markov cohort state-transition model. To run the model, we collected the transition probabilities, the direct costs, and the utility values for HIFU and the standard of care, and calculated the number of life years gained, the quality adjusted life years (QALYs) gained, the cost per QALY gained for HIFU and the standard of care, and the incremental cost-utility ratio (ICUR) for HIFU vs the standard of care. In addition, we conducted a one-way deterministic analysis that evaluated the sensitivity of the model results to variations of the parameters, a probabilistic sensitivity analysis which assessed the probability of cost-effectiveness for HIFU vs the standard of care at the willingness to pay (WTP) threshold, and a value of Information (VOI) analysis to calculate the expected value of perfect information (EVPI) and the expected value of partial perfect Information (EVPPI). Initially, we conducted a systematic review of all relevant published case-control, cohort, and randomised controlled studies that evaluated cancer related and functional outcomes of HIFU and the standard of care from inception through August 31, 2021 to collect the transition probabilities. The cancer related and functional outcomes were stratified into subgroups according to patient’s anthropometric, socio-demographic, and medical characteristics. Meta-analysis was performed with Microsoft Excel® Data Analysis Toolpak version 16.77 using maximum likelihood estimation and reported as a point estimate (ˆp) and Cochrane Tools using a random effects model with Mantel Haenszel (M-H) estimator for Tau2 statistic and reported as odds ratio (OR). Fourteen studies were included in the review for a total number of 34,927 participants. Among the 8 studies of HIFU as the primary treatment of localized low and intermediate risk PCa, 4 studies reported 5-year failure free survival (FFS) rates ranging from 67.8% to 97.8%, 3 studies reported 5-year biochemical disease-free survival ranging from 58% to 85.4%, 5 studies reported 1-year urinary incontinence (UI) rates ranging from 0% to 6%, and 4 studies reported 1-year erectile dysfunction (ED) rates ranging from 11.4% to 38.7%. Furthermore, our search revealed 5-year FFS benefit favoring ORP compared to RT (OR = 3.56, 95% CI = 2.50 - 5.08), 1 year UI rate favoring ORP compared to RARP (OR = 0.54, 95% CI = 0.10 - 2.89), and 1-year ED rate favoring ORP compared to RARP (OR = 0.46, 95% CI = 0.12 - 1.73). The direct costs of 20 patients with localized low or intermediate risk PCa who received whole-gland HIFU at a privately-owned clinic in Ontario were collected and compared with the direct costs of the standard of care in primary treatment of localized low and intermediate risk PCa. Our one-way deterministic analysis revealed that the main parameters that influenced the ICUR for HIFU vs RARP included the stable disease health state utilities for both groups, the clinic and amortization costs of HIFU, and the hospital, consumables, amortization, and maintenance costs of RARP, respectively. When we varied the annual transition probability of stable disease health state progressing towards metastasis after delivering HIFU from 0.01 to 0.05, the total QALYs generated with HIFU were 14.85 QALYs, and after a lifetime horizon, the ICUR of HIFU compared to RARP increased to 50,000/QALY. The probabilistic sensitivity analysis showed that, for HIFU vs RARP, a total of 9,444 ICURs out of the 10,000 ICURs resulting from the Monte Carlo simulations are situated below the WTP threshold, which means that the cost-effectiveness probability of HIFU compared to RARP is 94.44% when we trade-off between the lower cost of RARP and the higher effectiveness of HIFU and confirms our base case analysis result that showed HIFU to be highly cost-effective when compared to RARP. Our VOI analysis showed an EVPI over all simulations of 0.04 net benefit (NB) when all parameters were varied, a population EVPI for low and intermediate risk PCa in Ontario of 3,120.48 and 7,253.54 NB which is equivalent to 362,677,000 when assuming a WTP threshold of $50,000/QALY, respectively, an EVPPI over all simulations of 0.02 NB when the utilities subset of parameters was varied, an EVPPI over all simulations of 0.00 NB when the cost subset of parameters was varied, and concluded a very high value associated with further research on the cost-utility of HIFU vs RARP with special emphasis on the utility parameters. We concluded that the data collected in our mixed quantitative and qualitative research study can be utilized by patients in Ontario to engage in the shared decision-making process and mapped by policy makers to the current treatment landscape of localized low and intermediate risk PCa to identify policy gaps, evaluate HIFU’s eligibility for public funding and reimbursement, and leverage a data-driven policy that considers the allocation of HIFU within the existing treatment algorithm.Ph.D
Examining the Influence of Sex and Inflammation on Brain Health and Cognition in a Multiethnic Canadian Cohort
Get PDFInflammation may play a key role in women’s increased risk of Alzheimer’s disease (AD). However, few studies have examined the impact of sex on relationships between inflammation, brain health, and cognitive outcomes in mid-to-late life. To address this gap, cross-sectional data were analyzed from N=132 cognitively unimpaired older adults (mean age 66.7; 73%F), primarily of South Asian, Chinese, or non-Hispanic White descent. Findings demonstrated higher levels of inflammation as measured by plasma C-reactive protein (CRP) in females compared to males overall (d =0.52; p=0.008). Furthermore, females had lower gray matter volume (ß=0.35, p<0.001), lower white matter microstructural integrity (ß=0.52, p=0.02), and higher free water (ß=-0.29, p=0.07) at greater levels of inflammation compared to males. These findings highlight a female-specific brain vulnerability to inflammation that may contribute to sex differences in AD risk, emphasizing the need for early preventative interventions targeting inflammatory processes.M.A
Clinical, Molecular, and Management Perspectives on Replication Repair Deficiency Syndromes
Get PDFFaithful replication of the human genome is essential for maintaining genomic stability, a process upheld by DNA polymerase and the mismatch (MMR) system. Defects in these mechanisms lead to replication repair deficiency (RRD), a major driver of hypermutant cancers in humans. These malignancies exhibit distinct genomic characteristics, are often resistant to conventional chemotherapies, yet demonstrate susceptibility to immune-based therapies. Constitutional mismatch repair deficiency (CMMRD) is an aggressive pediatric cancer predisposition syndrome caused by biallelic pathogenic variants in the MMR genes (MLH1, MSH2, MSH6, PMS2). Patients with CMMRD are susceptible to multisystem cancers, primarily brain, gastrointestinal and hematopoietic malignancies, alongside diverse non-malignant manifestations that resemble other genetic disorders such as neurofibromatosis type 1. A majority of patients succumb to malignant brain tumors prior to reaching young adulthood.
Despite its severity, CMMRD remains underrecognized and current knowledge on it is largely derived from small cohort studies and literature reviews. The absence of a well-defined clinical phenotype, comprehensive spectrum and genomic profile of CMMRD cancers, genotype-phenotype correlations, and evidence-based management strategies contributes to diagnostic delays and poor outcomes. This thesis aims to address these gaps by providing the most comprehensive analysis of the clinical and biological landscape of CMMRD to date, leveraging data from the International Replication Repair Deficiency Consortium (IRRDC) and its global collaborators.
Chapter 1 highlights significant findings on replication repair deficiency, diagnostic and management strategies, current challenges as well as recent and emerging approaches. Chapter 2 presents the largest international cohort of CMMRD patients, defining key clinical and biological pathognomonic features, characterizing the mutational landscape of CMMRD-driven cancers, uncovering novel genotype-phenotype associations, and its implication for current management strategies. Chapter 3 systematically evaluates the effectiveness of surveillance guidelines on early detection of malignancies and low-grade tumors, and its impact on overall survival in CMMRD patients. This provides critical evidence to optimize future surveillance strategies for these patients. Chapter 4 focuses on the significance of this work, potential limitations, and future directions.
Collectively, this doctoral thesis advances understanding of CMMRD pathophysiology, the mutagenic processes underlying these cancers, and lays the foundation for precision-guided approaches in diagnosis, surveillance and treatment of affected individuals.Ph.D
Fortifying the Front Lines: Incorporating the Buddhadharma of Suffering and Compassion into the Provision of Spiritual Care to Front-Line Hospital Staff
Get PDFThis thesis explores how spiritual care providers of any faith tradition can employ the Buddhadharma—the teachings of the Buddha—to support front-line hospital staff who experience profound emotional, spiritual, and moral suffering in their work. Set within the context of a Catholic Level I Trauma Centre in Toronto during and after the COVID-19 pandemic, the research examines how spiritual care providers can address the crises of meaning, moral injury, and psychological distress that healthcare workers face daily.
The study employs a hermeneutical phenomenology methodology to capture the lived experiences of ten front-line staff members through semi-structured interviews and validated psychological and spiritual surveys. Participants described a deep and often silent suffering, stemming from moral injury, lack of institutional and emotional support, and the ethical complexity of patient care, during and after the COVID-19 pandemic. The data reveal common threads, including institutional neglect, emotional exhaustion, and a longing for meaning and recognition.
This suffering is interpreted through both Western philosophical frameworks (such as Simone Weil and Dorothee Söelle’s reflections on affliction) and Buddhist concepts, particularly the Four Noble Truths and the Brahmavihārās—the Four Immeasurables. The research shows that chaplaincy interpreted through a Buddhist lens, with its focus on mindfulness, compassion, and the transformation of suffering, offers a powerful and non-theistic framework for spiritual care that resonates with both religious and secular caregivers.
In response to participant feedback, the second phase of the study involved the creation of three asynchronous educational video modules on Buddhist perspectives on suffering, mindfulness, and self-compassion. These modules were designed to provide staff with practical and accessible tools for personal reflection and emotional resilience.
The findings suggest that a chaplaincy practice that employs this Buddhist perspective offers valuable resources for supporting staff well-being in acute care settings, especially in moments of crisis. The study concludes with recommendations for institutional investment in chaplaincy services that include spiritual care for staff, the integration of meaning-centered approaches, and the need for systemic acknowledgment of healthcare workers’ moral and emotional burdens.Doctor of Ministry (DMin
National Memories of Ethnic Cleansing in Jelenia Góra and Drohobych: Conflicting Nationalization Processes in Poland and Ukraine
Get PDFThis dissertation is a comparative analysis of two regional towns in East Central Europe: Jelenia Góra, Poland, and Drohobych, Ukraine. The study covers material between the nineteenth and twenty-first centuries. Beginning with the rise of late nineteenth-century nationality movements, the dissertation provides a detailed picture of genocide, ethnic cleansing, and post-World War II nationalization projects. It concludes with contemporary Russian aggression against Ukraine. Before 1945, Jelenia Góra was German Hirschberg. The town lies in a valley of the ‘Giant Mountains’ – (Riesengebirge in German, Karkonosze in Polish), southwest of Wrocław. Drohobych (Polish Drohobycz) belonged to the Second Polish Republic between 1919 and 1939. Drohobych lies in the Carpathian foothills, 80 kilometres southwest of Lviv. In the immediate postwar years, Hirschberg’s entire German population was deported and replaced by incoming Poles. In Polonized Jelenia Góra, diverse groups of forcibly resettled and Polonized ‘pioneers’ endured decades of stagnant social and cultural decay.
Between 1944 and the mid-1950s, a mixed population of Poles attended mandatory ‘Polonization’ courses. Practical policies of forced de-Germanization were adopted throughout Lower Silesia. The Polish state disseminated an ethno-nationalist myth claiming that centuries of Germanic rule in the region were a historic aberration. After years of oppressive German and Soviet occupation, and the full-scale genocide of the town’s Jewish community during the Holocaust, in September 1944, Drohobych was incorporated into Soviet Ukraine.
This dissertation considers the long-term impact of shared collective trauma and memories of wartime violence, and the political upheaval caused by war, ethnic cleansing, and forced population displacement. It also focuses on contested identities and territorial claims, and the isolation of Polish, Ukrainian, and German wartime animosities. The research and analysis place Jelenia Góra and Drohobych at the centre of borderland, war, postwar relation studies and the treatment of ‘dissonant heritage.’
The thesis draws on archival and museum collections in Poland, Ukraine, Germany, and Israel. The research, and the conclusions based on it, are complemented by memoirs, historical documentation, psychological theories of violence and trauma, political analysis, contemporary news reports, and photography and analysis of monuments and ‘memory landscapes.’Ph.D