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Supporting northern Indigenous elders’ right to self-determination in healthcare: Stanley Mission elders’ experiences
Full text linkThrough a wâhkôhtowin research paradigm that upholds relationality and responsibility, this research used a case study approach to explore the perspectives of First Nation and Métis elders from Stanley Mission on their experiences with their health and healthcare services on and off reserve. A literature review identified hospital barriers and gaps in access and services, and this information was used to guide conversational interviews. I discussed the findings from the elders’ interviews in context with literature findings and information from the Saskatchewan Health Authority (SHA) website. Overall, this proposed research highlights the experiences of Stanley Mission elders and what does and does not work for them regarding their healthcare.
This major and minor themes of the research centred around the Cree worldview of wâhkôhtowin, a term emphasizing notions of being related. It largely reflected findings that suggested that most of the positive care and experiences in healthcare were attributed to good access to healthcare and support from family and community. Having healthcare available in the community and provided by community members is considered imperative for elders in the north. Community health workers and health professionals see through a community-based care lens that contributes to the wrap-around wholistic healthcare service provided by the Elders Haven, a reserve-based elder care facility in Stanley Mission, SK. Although the healthcare workers and health professionals at the Haven provide outstanding healthcare to elders, this research suggests the Haven will also benefit from having more sustainable, long-term financial, and infrastructural resources.
Facilities like the Elders Haven are vital for First Nation and Métis elders because of the various barriers they face when accessing hospitals. The elders' lived experiences and barriers to hospital services suggests that the health policies and jurisdictions of the federal and provincial governments, and hospitals themselves, need to better integrate to support the needs of Indigenous Peoples. Elders want and need to be able to stay close to home to receive continuing care. If elders cannot stay close to home for the care they need, they need to be made to feel welcome and safe in hospitals and other health care facilities
A Justification of Wanuskewin Heritage Park's Merit as a United Nations Educational, Scientific and Cultural Organization (UNESCO) World Heritage Site
Full text linkThe aim of this thesis is to define and defend the justification of Wanuskewin Heritage Park’s eligibility and merits as a United Nations Educational Scientific and Cultural Organization (UNESCO) World Heritage Site. The research process included collecting existing information and data; identifying appropriate publications and resources for review; discussing and receiving input from leaders and staff at Wanuskewin Heritage Park, Elders and knowledge keepers, and subject matter experts; analysing existing information and data; synthesizing ideas and concepts, particularly as they related to the World Heritage criteria and process; and producing this final thesis. Coursework, fieldwork, literature review, case study reviews, archival studies and interviews with stakeholders and Elders resulted in clear recommendations. Analysis was completed of Canadian and global World Heritage Sites against Wanuskewin’s proposed case for inscription.
The research indicates that Wanuskewin has a strong case for designation under UNESCO World Heritage criterion III: To bear a unique or at least exceptional testimony to a cultural tradition or to a civilization which is living or which has disappeared with a primary focus on the archaeological record as the foundation for nomination. The archaeological records at Wanuskewin are a complete and intact record of human settlement and interaction with their environment. While none of the heritage resources represent the best global example of their type, there is no other location in the world where the assemblage of these resources exist together. Archaeological and heritage resources at Wanuskewin include bison jumps, tipi rings, multi-component habitation sites, a Medicine Wheel and the findings of four petroglyphs. The diversity of resources and the diversity of human populations who visited the site offer a strong foundation for nomination
Microgrid Planning in Distribution Networks Through Optimal Allocation and Sizing of Distributed Generation and Microgrid Formation
No full textThe abstract of this item is unavailable due to an embargo
Changes in qMRI relaxation times and 3D pose of meniscus with load and flexion at 3T
Full text linkKnee osteoarthritis (OA) is a degenerative joint disease that afflicts about 13% of the Canadian population. Unfortunately, there is no cure available for this progressive disease and affected individuals have to deal with the symptoms for the rest of their lives. Therefore, the best available course of action is to try preventing OA and diagnose the disease at early stages to prevent the progress; however, unfortunately, it is a clinical challenge to detect OA before gross-morphological alterations appear. OA is usually associated with injuries to the meniscus which is a tissue with a key role in load bearing and stability of the knee joint. Meniscal injuries are more common during knee flexion, however, research studying the behaviour of the meniscus under load and during flexion has been limited due to the challenges in non-invasive assessments of the meniscus. One of the most suitable techniques to study this tissue non-invasively is the quantitative magnetic resonance imaging technique (qMRI) since it provides images with superior soft tissue resolution as well as numerical values that represent the tissue’s health. Two of the most common qMRI techniques are T2 and T2* relaxation times which correlate with meniscal biochemical composition and structure. Thus, they are expected to be sensitive to the changes in the meniscal structure associated with knee loading and flexion. This project is exploratory research to determine if meniscus T2 and T2* relaxation times change in response to load and flexion.
For this project, six human cadaver knee specimens and five healthy participants were imaged using a 3T MRI scanner to obtain T2 and T2* images. Cadavers were scanned unloaded and under an axial load of 0.5 to 0.75 body weight stimulating prolonged standing. To consider the effect of the time-dependent viscoelastic nature of the meniscus, scans were performed after 110 minutes of loading. Healthy participants were scanned with knees in unloaded-fully extended and loaded-flexed of 0.25 body weight and a 30° flexion angle. The Wilcoxon-singed rank test was used to compare the mean value and texture features of the T2 and T2* relaxation time maps of the meniscus between the unloaded and loaded conditions and between the extended and flexed positions. In addition, the morphological images were used to assess the translation of the meniscus during knee flexion and under axial load.
Results of this study showed significant changes in meniscal T2 and T2* mean values and some of the texture features in response to load and knee flexion. A significant reduction was found in mean T2 and T2* relaxation times from the unloaded and loaded conditions in cadavers. Also, significant changes were observed in texture features of T2 and T2* relaxation time maps between unloaded and loaded meniscus indicating a decrease in the overall heterogeneity of meniscal maps in response to load. A significant increase in mean T2 value and overall heterogeneity of the meniscal maps were found in response to loaded flexion in healthy participants. In addition, from the morphological images, a posterior translation of the meniscus was observed during knee flexion while this movement was negligible under axial loads.
These results indicate that T2 and T2* relaxation times are sensitive to changes in the meniscus with load. Further work needs to be done to determine how the changes in relaxation times can be used to detect diseases such as OA at early stages before the observation of degenerative morphological changes
NEURAL MARKERS OF SELF-OTHER DIFFERENTIATION DURING DYNAMIC JOINT ACTION
Full text linkJoint actions, in which two or more people coordinate their actions with each other to achieve a common goal, are ubiquitous in daily life. Examples range from moving furniture with a friend to musical ensemble performance. Despite the ubiquity of joint actions, researchers know relatively little about the underlying neural processes that operate during real-world, dynamic joint action. Furthermore, recent research emphasizes the importance of using one’s own sensorimotor system to represent and simulate others’ contributions to the joint action to facilitate coordination. However, the notion that people represent their own and others’ contributions to a joint action using the same neural resources raises the question of how people nevertheless maintain a distinction between each person’s individual contributions. This dissertation will focus on delineating neural markers of self-other differentiation during dynamic joint action. In four experiments, I employ a joint sequence production paradigm in which pairs of participants take turns producing tones to match a metronome pace. I use electroencephalography (EEG) to examine the time course of neural activity associated with each person’s actions (i.e., taps) and sensory consequences (i.e., tones) as the sequence unfolds. In Chapters 2 and 3 (Experiments 1 and 2), I investigate whether there is a perceptual differentiation in the processing of sensory consequences that result from one’s own vs. others’ actions by measuring auditory event-related potentials (ERPs) elicited by self- and partner-produced tones. Together, the findings from Experiments 1 and 2 indicate that self-specific attenuation of the auditory P2 provides a neural marker of self-other differentiation at a perceptual level. The findings from Experiment 2 also show that orienting processes associated with the coordination requirements of a joint action enhance P2 amplitude for partner-produced tones, suggesting that people direct their attention to their partner’s tone onsets to better coordinate with them. In Chapter 3 (Experiment 3 and 4), I investigate whether there is a differentiation in the motor activity that is associated with each person’s actions by conducting novel analyses of the data previously reported in Experiments 1 and 2 to examine motor-related cortical oscillations during self- and partner-produced taps. Together, the findings from Experiments 3 and 4 indicate that motor-related suppression provides a neural marker of self-other differentiation at a motor level. The findings from Experiment 3 and 4 also show that the coordination requirements of a joint action affect the degree of motor-related suppression for a partner’s actions, suggesting that people simulate their partners action timing to better coordinate with them. Overall, this research suggests that distinct neural activity for one’s own contributions to a joint action is dynamically coupled with periods of neural activity that reflect the integration of a partner’s actions based on the coordination demands of the joint action. Together, the experiments presented in this dissertation provide important and direct implications for theoretical accounts of joint action, as they further our understanding of how people maintain a distinction between their own and their partners’ contributions to a joint action, while also dynamically integrating information about the timing of their partners’ actions and sensory consequences to better coordinate with them. More broadly, these experiments contribute to our understanding of disorders associated with self-other processing deficits, such as schizophrenia, and provide valuable insight into the development of effective paradigms for motor training and rehabilitation
Finding the Best Gene Candidate(s) as a Potential Therapeutic Target for N-MYC Overexpressing Neuroendocrine Prostate Cancer (NEPC)
Full text linkNeuroendocrine prostate cancer (NEPC) is the most aggressive form of prostate tumorigenesis. Recent studies have shown that one of the key genes that regulate the development of NEPC cells is the N-MYC oncogene, along with the loss of tumor suppressors such as TP53 and RB1 (Lee et al., 2016). Resistance to current treatments results in the transformation of prostate cancer (PC) cells into Castration-resistant prostate cancer (CRPC), which at later stages trans-differentiates into neuroendocrine prostate cancer (NEPC). NEPC is resistant to hormonal therapy as cancer cells lack androgen receptors (AR) at this level, which results in rapid death (Huang et al., 2019). Due to the molecular structure of the N-MYC protein, N-MYC cannot be directly targeted as it lacks a binding pocket. Thus, finding a target gene on which N-MYC expression is dependent will result in introducing a novel therapy. My master’s thesis aims to apply the concept of synthetic dosage lethality to identify target genes that become essential when N-MYC is overexpressed. Synthetic dosage lethality (SDL) denotes a genetic interaction whereby underexpression of gene A combined with overexpression of gene B results in the killing of the cell (Megchelenbrink et al., 2015). This approach requires the overexpression of one gene, such as N-MYC, with the loss of function of a second gene to cause lethality in cells. Accordingly, genes that exhibit SDL with N-MYC should result in lethality in N-MYC+ prostate cancer cells. The Vizeacoumar lab performed genome-wide shRNA and CRISPR screening to identify genes that become essential in N-MYC overexpressing cells. My work will specifically focus on validating three candidate genes (WNT1, SOX17, and FOXN1) identified from the genome-wide screen. Moreover, to suggest a more effective strategy to treat NEPC, we applied a combination of gene knockout and drug therapy. Three drugs, Chidamide, Belinostat, and Fludarabine, were tested to check cell viability and find the best drug for treatment
Exploring the Behavioural Effects of Compound-21 Using Novel Object Recognition and Object in Place Tests in Long Evans Rats
Full text linkDesigner Receptors Exclusively Activated by Designer Drugs (DREADDs) have gained popularity as a tool to investigate the neural substrates of behaviour in rodents. When used with spontaneous behavioural tests of memory in rodents, DREADDs allow for a unique opportunity to advance our understanding of how specific neuronal populations contribute to cognition. While data on the use of DREADDs to study memory with spontaneous tasks in rats is somewhat limited, there is evidence to suggest that the canonical DREADD agonist, clozapine-N-oxide (CNO), exhibits off target effects on recognition memory assessed with the Novel Object Recognition (NOR) test. While newer DREADD agonists are available, an understanding of how these novel compounds impact rat behaviour unspecific to DREADD activation is lacking. Therefore, I sought to test whether the DREADD agonist, Compound 21 (C21), affected recognition memory assessed by NOR or, associative memory assessed by the Object-in-Place (OiP) test. I also investigated whether DREADD-mediated inhibition of parvalbumin (PV+) gamma-amino butyric acid (GABA)ergic interneurons of the medial prefrontal cortex (mPFC) would impair associative memory as measured by OiP. I showed that C21 did not affect either sex in NOR, or females in OiP. Male rats failed to exhibit robust discrimination in OiP following either control or C21 treatment; however, total object exploration times of male rats were not altered by C21. Lastly, PV-Cre rats transfected with an inhibitory DREADD in the mPFC and treated with C21 showed normal exploration of objects in OiP. Poor discrimination in OiP and low vector co-expression of DREADD with mPFC parvalbumin-containing interneurons precluded conclusions about potential impacts of inhibiting these cells on associative memory. While C21 did not impair discrimination of objects in females tested in OiP, further work is needed to replicate this finding in males
The Holy Ones: Stories
Full text linkThe Holy Ones is a collection of five short stories and two novellas exploring relationships and solitude through a fabulist prism. In keeping with the tenants of fabulism, most of these stories take the primary world as their starting point and imbue it with one magical, mystical, or absurd quirk. While these stories are somewhat strange, they attempt to find relevance and resonance in the banality of their characters’ desires: a wizard wishes to rent the perfect apartment, a group of boys want to ask their crushes to the school dance, a Mennonite girl wants to climb a sycamore tree, and so on. The Holy Ones, like many fabulist collections, combines the mystical with the banal in an attempt to defamiliarize common emotions and experiences—like a fear of commitment, adolescent love, a search of a higher power, and so on—and perhaps, at least momentarily, return these emotions and experiences to their original state of strangeness
BACTERIAL AMYLOID CURLI INFLUENCES AGGREGATION OF AMYLOID BETA PEPTIDES ASSOCIATED WITH ALZHEIMER ́S DISEASE
Full text linkAmyloid proteins are associated with various disorders such as Alzheimer's, Parkinson's,
prion diseases, and type 2 diabetes. Each of these illnesses involves a specific amyloid protein or
peptide that misfolds and forms fibrils. Apart from pathological amyloids, there are amyloids that
are considered functional amyloids. Functional amyloids are produced by different organisms, and
in contrast to pathological amyloids, they serve various biological functions. For my MSc. project
I focus on the pathological amyloid-β (Aβ) associated with Alzheimer's disease and the functional
amyloid curli. Curli is produced by the foodborne pathogen Salmonella and the commensal
bacteria Escherichia coli. Curli is classified as a functional amyloid because it provides a structural
role in the biofilm extracellular matrix. CsgA and CsgB are the curli structural components. When
CsgA and CsgB reach the cell surface, they change from an unstructured state as secreted proteins
to -rich structures that assemble into amyloid fibrils at the cell surface. Despite being encoded by
distinct protein sequences, curli fibrils share a common 3D structure with Aβ. The mechanism of
how Aβ peptides convert from soluble functional proteins into insoluble amyloid fibrils is not fully
understood. Given that both proteins are naturally amyloidogenic and share a similar structural
fold, the subject of my M.Sc. research is to investigate if Salmonella curli can cross-react with A
peptides. The effects of curli on aggregation and aggregate cytotoxicity of Aβ(1-42) and A(1-40)
peptides were investigated by a combination of biophysical (Western blot analysis and kinetic
studies with thioflavin T fluorescence) and cellular assays (cell viability in male and female human
fibroblasts). I demonstrate that curli can physically interact with both A peptides in vitro. The
biophysical data shows that curli promotes Aβ(1-42) fibrillization and accelerate the overall
aggregation of Aβ(1-40) (i.e., oligomers + fibrils). The data with cultured cells shows that Aβ(1-
42)/curli aggregates are less cytotoxic that Aβ(1-42) aggregates. Our results support mounting
evidence that oligomers—as opposed to mature fibrils— are probably the more toxic species of
the peptides. Although we cannot correlate our results to the complex pathology of AD yet, our
findings contribute to evidence that exogenous (sometimes bacterial) amyloids may influence and
cross-react with host amyloids. Moreover, the interactions shown in my work may provide new
insights into the molecular mechanisms of interactions between bacterial amyloids and human
amyloids
WHALES, BIRDS, REEDS, AND BOOK-WORMS: WHAT OLD ENGLISH RIDDLES SAY ABOUT ANGLO-SAXON ATTITUDES TOWARDS WRITING AND READING
Full text linkRiddling culture existed in multiple forms in early medieval England: Latin enigmata, visual art inscribed with riddles or riddle-like texts, the Old English Exeter Book Riddles, and, presumably, oral transmission. Several Old English riddles that have been preserved in writing self-consciously invite their solvers to think about the nature of the written word as the Anglo-Saxons crafting these riddles attempted to navigate this newly introduced form of language. Many of these riddles, such as the Franks Casket Riddle and Exeter Book Riddles 26 and 60, describe written language by exploring the past lives of the very materials used to create it. These riddles present the power of written language by borrowing from the life forces of the material supports for writing. However, they also emphasize the communal nature of reading by connecting speech with writing. Finally, Riddle 47 calls attention to the limitations of the written word. The common solution to this riddle is a book-worm; however, I contend this by comparing Riddle 47 with its Latin counterpart, the Franks Casket Riddle, and Exeter Book Riddles 26 and 60. I argue that Riddle 47 is actually about the written word, and is meant to call writing’s power into question by demonstrating its fragility and its ability to be misinterpreted through carelessness. Ultimately, these four riddles reflect Anglo-Saxon attitudes towards language and interrogate the possible cultural changes that come along with literacy