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Predictors of intraparenchymal hemorrhage progression and markers of injury severity on magnetic resonance imaging following acute cervical spinal cord injury
No full textBackground: Prior to the release of the 2024 management guidelines for spinal cord injury (SCI), previous guidelines suggested augmenting the systemic mean arterial pressure (MAP) to a target of 85-90mmHg for the first 7 days after injury. Although this may improve blood flow to the injured cord and reduce ischemia, it could cause an inadvertent increase in intraparenchymal hemorrhage (IPH). This study aims to assess the impact of MAP augmentation and venous thromboembolism (VTE) prophylaxis on IPH progression after acute human SCI. Methods: In SCI patients, Norepinephrine alone or in conjunction with Vasopressin was used to keep MAP between 85-90 mmHg. Magnetic Resonance Imaging (MRI) was done on admission (within 24 hours post-SCI) and on days 2, 4, 7, and 14 post-injury. Hemorrhage was quantified on T2-weighted MRI scans. Hemorrhage progression (Delta IPH or ΔIPH) was determined by calculating the difference between the hemorrhage volume on the baseline MRI and at other time points. The cumulative MAP exposure is the Time-Weighted Average MAP (TWA-MAP), which was calculated by dividing the area under the curve of the MAP measurements by the total hours of exposure. Regression (simple and multivariate) and linear mixed effect model analysis were used to explore the relationship between Delta IPH and TWA-MAP and the factors influencing hemorrhage progression after SCI. Results: Data from 13 patients were analyzed. While IPH progressively increased on days 2 and 4, it decreased from day 7. TWA-MAP was significantly associated with Delta IPH p=<0.0001 during the first two days following SCI. The baseline IPH was the most significant predictor of hemorrhage progression from the time of injury to days 2 and 4 post-trauma. From days 2 to 4 post-trauma, TWA-MAP was the most important predictor of hemorrhage progression. The time to initiation of VTE and Norepinephrine dose did not affect hemorrhage progression. Conclusions: There is a positive correlation between MAP exposure and hemorrhage progression after SCI, more evident with severe IPH at baseline. Hence, harmful bleeding within the spinal cord may be a contributing factor to the difficulty of establishing the effectiveness of maintaining MAP above 85 mmHg for neurological recovery.Medicine, Faculty ofGraduat
The pulmonary metastasis assay (PUMA) : a tool to study novel therapies for ovarian cancer
No full textClear Cell Ovarian Cancer (CCOC) is a chemoresistant subtype of ovarian cancer, accounting for ~10% of epithelial ovarian carcinomas (EOC) in North America and up to 30% in Japan. Unlike in the more common high-grade serous ovarian cancers, hematogenous spread and extraperitoneal metastasis are prevalent in CCOC but have been understudied due to a lack of suitable models.
High expression of Cystathionine Gamma-Lyase (CTH) and mutations in AT-Rich Interactive Domain-Containing Protein 1A (ARID1A) are common in CCOC. CTH, a key enzyme in the transsulfuration pathway, is a marker for CCOC. Inactivating CTH reduces CCOC’s metastatic potential and improves chemotherapy responsiveness. Loss of ARID1A occurs in ~65% of CCOC cases, inducing ROS accumulation and reliance on oxidative phosphorylation (OXPHOS) for energy. EO3001, a synthetic drug, selectively transports extracellular Cu (II) to mitochondria, inducing ROS and triggering cuproptosis. ARID1A-deficient cells show increased sensitivity to EO3001.
To investigate the effectiveness of EO3001 and CTH inhibitors in CCOC, we used the Pulmonary Metastasis Assay (PuMA). This model enables metastases to be seeded via tail vein injections and studied either immediately or after full establishment, providing a more complex microenvironment than traditional 2D/3D models.
We generated isogenic CCOC cell lines (-/+ CTH loss & -/+ ARID1A loss) using CRISPR-Cas9. EO3001 was obtained through collaboration, while a CTH inhibitor library was screened by our collaborators; 3 candidates showed promising effects and were further tested. We evaluated EO3001's therapeutic impact on tumorigenic potential and cell growth in vitro and ex vivo. Both early- and late-harvest PuMA were optimized to assess CTH inhibitors and EO3001.
In both assays, all 3 CTH inhibitors showed significant inhibitory effects on CCOC, offering a novel therapeutic strategy not only for CCOC but also other cancers expressing CTH. Differences in EO3001 response were noted between CCOC -/+ ARID1A cell lines, with hypoxia reducing EO3001's effects, likely due to changes in glycolysis and OXPHOS. Exploiting OXPHOS dependence in ARID1A-deficient CCOC, EO3001 could be a promising therapeutic approach.
These findings highlight the PuMA assay’s potential for testing novel treatments for metastatic CCOC.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat
SARS-CoV-2 Infection and the Risk of New Chronic Conditions : Insights from a Longitudinal Population-Based Study
No full textBackground: The post-acute impact of SARS-CoV-2 infections on chronic conditions remains poorly understood, particularly in general populations. Objectives: Our
primary aim was to assess the association between SARS-CoV-2 infections and new diagnoses of chronic conditions. Our two secondary aims were to explore geographic variations
in this association and to assess the association between SARS-CoV-2 infections and the
exacerbation of pre-existing conditions. Methods: This longitudinal study used data from
8086 participants of the Specchio-COVID-19 cohort in the canton of Geneva, Switzerland
(2021–2023). Mixed-effects logistic regressions and geographically weighted regressions adjusted for sociodemographic, socioeconomic, and healthcare access covariates were used to
analyze self-reported SARS-CoV-2 infections, new diagnoses of chronic conditions, and the
exacerbation of pre-existing ones. Results: Participants reporting a SARS-CoV-2 infection
were more likely to be diagnosed with a new chronic condition compared to those who
did not report an infection (adjusted odds ratio [aOR] = 2.15, 95% CI 1.43–3.23, adjusted
p-value = 0.002). Notable geographic variations were identified in the association between
SARS-CoV-2 infections and new diagnoses. While a positive association was initially observed between SARS-CoV-2 infections and exacerbation of pre-existing chronic conditions,
this association did not remain significant after adjusting p-values for multiple comparisons.
Conclusions: These findings contribute to understanding COVID-19’s post-acute impact
on chronic conditions, highlighting the need for targeted health management approaches
and calling for tailored public health strategies to address the pandemic’s long-term effects.Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofReviewedFacultyResearche
Cree Food Knowledge and Being Well
No full textThis paper explores the crucial role of Cree elders’ knowledge in revitalizing Indigenous food sovereignty, focusing on food as a cornerstone of Cree identity, spirituality, and wellbeing. Based on a study of Cree elders in Manitoba in 2020, this paper highlights the depth of Cree food knowledge, intertwined with spiritual practices, language, and land ethics. Using an Indigenous research paradigm, ten Cree elders were interviewed and shared their experiences of traditional communal practices, the detrimental impacts of colonialism on food systems, and the spiritual connections between food, land, and community. The elders emphasized the need for education and the preservation of Cree languages, which encode critical knowledge for sustaining food practices. Through their stories, elders illustrated how food sovereignty is not merely about physical sustenance but involves maintaining sacred relationships and responsibilities to the land and all its inhabitants. This research underscores the importance of Cree knowledge in reclaiming and sustaining Indigenous food systems, essential for the health and resilience of Cree communities.Land and Food Systems, Faculty ofNon UBCReviewedFacult
The feature thriller film Killer Ending breaking the rules of the traditional movie of the week
No full textAs a successful commercial television movie director and screenwriter, I set out to challenge the conventions of thriller movies made for television. Traditionally dismissed by critics as formulaic and lacking artistic merit, these "movies of the week" often neglect depth in storytelling. This paper serves as a supporting document for my thesis film, Killer Ending, offering an in-depth exploration of its creation, themes, and impact. By prioritizing complex characters, including a sympathetic antagonist, and exploring themes such as mental health and motherhood, this project sought to elevate the genre. The film’s narrative and visual aesthetics were designed to rival those of feature films, creating a psychological thriller with nuanced character motivations and a female-driven perspective. The process revealed the challenges and triumphs of pushing artistic boundaries within a commercial framework, ultimately earning critical recognition and furthering the discourse on gender representation in televised thrillers.Arts, Faculty ofGraduat
Convergence and conflagration : wildfires and shifting landscapes in the Cache la Poudre Canyon, Colorado
No full textHigh severity wildfire and post-fire flooding can dramatically alter landscapes and disrupt people’s
lives, sometimes in complex ways not readily visible to the broader public or to the naked eye. Wildfires in the western U.S., and elsewhere in the world, are becoming more destructive for communities and ecological systems. In response to the changes in how wildfires are affecting our communities and environments over roughly the last two decades, this research explores how people are reorienting to transformed lives and landscapes and coping with loss as a result of wildfire. Drawing on over two years of situated, ethnographic fieldwork in a wildfire-impacted landscape, I ask: how do people understand their own lives and experiences within the different timescales and lifecycles of human and more than human ecologies in the formation of wildfire? What capacity do we have to make sense of affective and ecological transformations wrought
by wildfire and post-fire flooding? How do institutional and policy responses to wildfires shape people’s relations with different forms of governance and the environment? How do such responses affect the capacity of people to make decisions about their lives and futures? I explore these questions through an anthropological exploration in the landscapes of the upper Poudre Canyon in northern Colorado.
My research highlights three main arguments. First, in mountain watersheds, we can anticipate social consequences resulting from wildfire by examining the ecological disturbance cascade it initiates. Second, state-sponsored efforts to cultivate best practices for living with wildfire risk should be more geographically and socially expansive, to acknowledge that contending with wildfire and its associated hazards of smoke and flooding is a society-wide challenge. Third, people experience a recalibration of relationship to place from engaging in processes of sensemaking in response to extreme wildfires and resultant landscape changes. This dissertation contributes to a more than human anthropology by attending to the qualities of fire and
flood as they exist in a processual and relational material world through sustained ethnographic engagement with people and place.Arts, Faculty ofAnthropology, Department ofGraduat
Trace-element geochemistry, isotopic and geochronological results from the Ridge Zone at the Burgundy Cu-Au Alkalic Porphyry Prospect, Golden Triangle, Northwestern British Columbia, Canada
No full textCritical raw materials (CRM) are key in the transition to green economies. Therefore, emphasis has been placed on the research of geologic deposits hosting economically significant amounts of CRM, such as alkalic porphyry deposits. As such, elucidating the characteristics of known alkalic porphyry deposits will aid in prospecting for this potentially CRM-rich deposit type.
The Burgundy prospect is a silica-undersaturated Cu-Au alkalic porphyry prospect located on the Enduro Metals’ Newmont Lake property in the Golden Triangle of British Columbia. In situ LA-ICP-MS trace-element mapping and sulfur isotope analyses of pyrite and chalcopyrite, along with in situ LA-ICP-MS Rb-Sr geochronology of biotite, provide a better understanding of the mineral paragenesis of mineralization at this poorly characterized prospect. Map results demonstrate that grain boundaries and fractures are enriched in trace-elements, indicating that Au, Ag, and CRM concentrations were upgraded by overprinting hydrothermal fluids. Sulfur isotope analyses of pyrite yield depleted rims (i.e., -6.2 ± 2.8‰; n = 62) and slightly more enriched cores (i.e., -4.2 ± 2.0‰; n = 34). Chalcopyrite grains yield marginally more enriched δ³⁴S values than pyrite (i.e., -3.9 ± 2.8‰; n = 169/172), but with no systematic rim and core zonation. Overall, the negative δ³⁴S values are indicative of sulfide mineralization from oxidized fluids. Results from Rb-Sr geochronology of biotite interpreted to be cogenetic with pyrite and chalcopyrite yield isochron dates ranging between 220.1 ± 1.2 and 196.6 ± 4.6 Ma. The youngest dates (197.8 ± 1.0 Ma and 196.6 ± 4.6 Ma) are interpreted to reflect late fluid alteration due to the chloritization of biotite in these samples. The remaining dates (220.1 ± 1.2 and 204.9 ± 1.2) are considered to record the timing of mineralization for the Burgundy prospect.
The results from this study indicate that mineralization in the Burgundy prospect occurred during infiltration of late, oxidized low-temperature hydrothermal-magmatic fluids between 220 to 205 Ma. The timing and sulfur isotope results are broadly similar to those of the nearby Galore Creek deposit and highlight the potential for discovering other alkalic porphyries in the Golden Triangle.Science, Irving K. Barber Faculty of (Okanagan)Earth, Environmental and Geographic Sciences, Department of (Okanagan)Graduat
Side-channel security in networks : from the internet to interconnects
No full textIn today's interconnected world, the protection of data during transmission is crucial to maintaining privacy and security. While encryption effectively secures the contents of transmitted data, it fails to conceal associated metadata, such as packet sizes and timings, which can be exploited in network side-channel attacks. These attacks have been widely studied in Internet and data centre networks but are under-explored in interconnects.
We first present NetShaper, a modular and scalable system designed to mitigate network side-channel attacks in Internet networks. NetShaper provides the user with the facility to customise their own trade-offs between the side-channel mitigation guarantees, bandwidth overhead, and latency overhead. Secondly, we present new attack vectors in the PCIe interconnect that do not necessitate saturating the PCIe link. These findings contribute to the broader goal of designing more resilient and secure communication mechanisms.Science, Faculty ofComputer Science, Department ofGraduat
Towards the elucidation of the PPZ gene cluster in fungal insect pathogen Metarhizium majus
No full textThe full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.Science, Faculty ofChemistry, Department ofGraduat
Hensel’s lemma for the norm principle for type Dₙ groups
No full textClassical norm principles examine the behavior of quadratic forms and central simple algebras under the extensions of the base field. Merkurjev reformulated them as a property of algebraic groups, and Gille reformulated them as a property of torsors under algebraic groups using Galois cohomology. After recalling the classical norm principles, we will show that Merkurjev’s formulation of the norm principle for reductive linear algebraic groups is equivalent to Gille’s formulation for torsors under semisimple groups. We will then prove that it is sufficient to show the norm principle for simply connected groups. Among classical groups, the only case for which the norm principle is open, are groups of type Dₙ. Absolutely simple, simply connected, classical groups of type Dₙ are spinor groups of central simple algebras with orthogonal involution. We will reduce the norm principle for the spinor groups to the case that the field extension has degree 2. We then focus on the spinor groups of skew-hermitian forms defined over quaternion algebras and will reduce the question in this case to the case that the skew-hermitian form is anisotropic. Let K be a complete discretely valued field with residue field k with char(k) ≠ 2. Suppose that the norm principle holds for spinor groups Spin(h) for every nonsingular skew-hermitian form h defined over every quaternion algebra with canonical involution defined over finite separable extensions of k. Then we will show that it holds for spinor groups Spin(H) for every nonsingular skew-hermitian form H defined over every quaternion algebra with canonical involution defined over K.Science, Faculty ofMathematics, Department ofGraduat