30921 research outputs found
Sort by
Integrating oxylipins into the 'omics' research framework
Oxylipins are a class of lipids encompassing the oxygenated metabolites of polyunsaturated fatty acids (PUFAs). As current biochemical analytical techniques have enabled the high-throughput quantification of whole profiles of oxylipins from biological samples, the interpretation of this data has posed a challenge to researchers. The studies presented here will consist of three different contexts in which oxylipin analysis was improved by integrating data layers from other omics analyses, clinical data, or oxylipins in other tissues. Specifically, multi-omics analysis of the hearts of rats orally exposed to the cardiotoxic food contaminant 2-monochloropropane-1,3-diol (2-MCPD) identified upregulation of immune response pathways and downregulation of energy metabolism and cardiac function. The inflammatory nature of 2-MCPD-induced cardiotoxicity included the suppression of anti-inflammatory docosahexaenoic acid (DHA)-derived oxylipins. The integration of the oxylipin data with transcriptomic data elucidated the suppression of DHA oxylipins by identifying dysregulation of secreted phospholipase A2, which has substrate preference for DHA. In another analysis rats were exposed to 2-MCPD with and without adequate dietary α-linolenic acid (ALA), the essential dietary n-3 PUFA. This study demonstrated that dietary ALA modulated oxylipins, enhancing n-3 PUFA-derived oxylipins in the heart, liver, kidney, and serum, while 2-MCPD exposure elevated pro-inflammatory arachidonic acid-derived oxylipins in heart and possibly liver. Adequate ALA revealed 2-MCPD exposure reduced cardiac DHA oxylipins, not apparent in the ALA-deficient diet. Integration of the oxylipin profiles across tissues identified 3-hydroxy-octadecatrienoic acid-γ (13-HOTrE-γ) as the top contributor to the distinct oxylipin profiles induced by 2-MCPD exposure, thus highlighting 13-HOTrE-γ’s association with 2-MCPD exposure across tissues. The final study analyzed valvular and plasma oxylipins from patients with severe calcific aortic valve stenosis (AVS). Valvular oxylipins were found to be broadly increased with AVS severity. The integration of the oxylipin data with clinical data, which included AVS risk factors, made for a more robust model by controlling for these factors, and enabled the identification of specific associations of arachidonic acid derived prostanoids with AVS severity markers. These studies contribute to the molecular understanding of lipid metabolism pathways altered by toxic exposure, diet, and disease, as well as providing a framework for integration of oxylipins into the omics framework.February 202
Home-based prehabilitation for frail cardiac surgery patients (HOME FREE) - a quasi-experimental feasibility study
Introduction: Frailty is a syndrome characterized by loss of muscle mass, strength, and difficulty completing activities of daily living. It’s presence in patients undergoing major surgical procedure is associated with prolonged postoperative recovery, resulting in functional decline and increased rates of morbidity and mortality.
Methods: A prospective, quasi-experimental study was conducted on pre-frail and frail patients undergoing cardiac surgery at St. Boniface Hospital. Patient’s with an estimated wait time of ≥ 3 weeks for their surgical procedure and who scored ≤ 60 on the short form 36 physical functioning scale were approached to participate in a 100% virtually delivered preoperative home-based exercise intervention. Participants were assessed and prescribed standardized exercises over Zoom and monitored via weekly Zoom conferencing with a physiotherapist (4 sessions over 3 weeks). The program focused on balance and strengthening exercises 3 x/week at a moderate intensity. The primary outcome was the feasibility and practicality of the intervention, defined as a consent rate of ≥ 30% of eligible patients as well as an adherence rate of ≥ 65% to the prescribed exercise program. Secondary outcomes evaluated safety and exploratory efficacy of the home-based program.
Results: Among 209 screened patients, only 27 met the eligibility criteria. Nine of the 27 consented to participate, 2 were lost due to early surgical dates and 1 dropped out. Visit data of 6 participants were analyzed and their adherence to exercise was > 75%, with proper exercise technique demonstrated 88% of the time. No safety events occurred and clinically meaningful change in the SPPB score was demonstrated with an effect size of d = -0.99. Gait speed also improved clinically and statistically with a p = 0.026, and effect size of d = -1.57.
Conclusion: Feasibility was demonstrated with a consent rate of 33% and an adherence to the exercise protocol of > 75%. Participants safely completed the virtually delivered prehabilitation program and effect sizes were determined to inform future trials. Researchers should test the efficacy of virtually delivered preoperative home-based exercise programming for patients who will undergo cardiac surgery. Eligibility criteria should be expanded to optimize participation in prehabilitation.October 202
Role and promise of health policy and systems research in integrating rehabilitation into the health systems
Abstract Despite recognized need and reasonable demand, health systems and rehabilitation communities keep working in silos, independently with minimal recognition to the issues of those who require rehabilitation services. Consolidated effort by health systems and rehabilitation parties, recognizing the value, power and promise of each other, is a need of the hour to address this growing issue of public health importance. In this paper, the importance and the need for integration of rehabilitation into health system is emphasized. The efforts being made to integrate rehabilitation into health systems and the potential challenges in integration of these efforts were discussed. Finally, the strategies and benefits of integrating rehabilitation in health systems worldwide is proposed. Health policy and systems research (HPSR) brings a number of assets that may assist in addressing the obstacles discussed above to universal coverage of rehabilitation. It seeks to understand and improve how societies organize themselves to achieve collective health goals; considers links between health systems and social determinants of health; and how different actors interact in policy and implementation processes. This multidisciplinary lens is essential for evidence and learning that might overcome the obstacles to the provision of rehabilitation services, including integration into health systems. Health systems around the world can no longer afford to ignore rehabilitation needs of their populations and the World Health Assembly (WHA) resolution marked a global call to this effect. Therefore, national governments and global health community must invest in setting a priority research agenda and promote the integration of rehabilitation into health systems. The context-specific, need-based and policy-relevant knowledge about this must be made available globally, especially in low- and middle-income countries. This could help integrate and implement rehabilitation in health systems of countries worldwide and also help achieve the targets of Rehabilitation 2030, universal health coverage and Sustainable Development Goals
Healing the emergency department: exploring the role of an Indigenous patient advocate
Background: Although the Emergency Department (ED) acts as an entry point into the acute healthcare system, it is often a source of anxiety and uncertainty for Indigenous patients. Racism and discriminatory practices in the ED, resulting in Brian Sinclair’s untimely death at Winnipeg’s Health Sciences Centre in 2008, and Joyce Echaquan’s viral plea for help before she died in a Quebec hospital in 2020, show the need for increased patient advocacy. The literature surrounding the use and role of a patient advocate in the ED is limited. However, the few hospitals that have utilized a designated ED patient advocate have reported higher patient satisfaction. With this in mind, this study examines the potential for an Indigenous patient advocate patients in the ED.
Objectives: The objectives of this thesis were to examine (1) why culturally unsafe care continues to persist for Indigenous Peoples in ED environments and (2) the feasibility of a newly imagined Indigenous patient advocate role in the ED.
Methods: In this qualitative study, eight semi-structured interviews were conducted with Indigenous and non-Indigenous healthcare professionals who have worked or currently work in advocating for Indigenous patients to ensure greater cultural safety generally and in the ED of a major tertiary care hospital in Winnipeg, Manitoba (Canada). Interviews were audio-recorded, transcribed verbatim, and thematically analyzed.
Results: Results indicate that high-pressure situations, specifically in the ED, are where racist incidents are likely to transpire. Participants identified the dangers the Indigenous patient advocate might encounter in the health care system and recommended how to improve the Indigenous patient experience.
Conclusion: The findings reveal that cultural safety training and system wide policy changes are required to heal the ED, namely creating an environment where an anti-Indigenous racism agenda is reflected in all emergency medicine workings and system operations.The University of Manitoba
The Prairie Indigenous Knowledge Exchange Network
The Manitoba Métis Federation.October 202
The genetic architecture of youth anxiety: a study protocol
Background
Anxiety disorders are the most common psychiatric problems among Canadian youth and typically have an onset in childhood or adolescence. They are characterized by high rates of relapse and chronicity, often resulting in substantial impairment across the lifespan. Genetic factors play an important role in the vulnerability toward anxiety disorders. However, genetic contribution to anxiety in youth is not well understood and can change across developmental stages. Large-scale genetic studies of youth are needed with detailed assessments of symptoms of anxiety disorders and their major comorbidities to inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care.
Methods
The Genetic Architecture of Youth Anxiety (GAYA) study is a Pan-Canadian effort of clinical and genetic experts with specific recruitment sites in Calgary, Halifax, Hamilton, Toronto, and Vancouver. Youth aged 10–19 (n = 13,000) will be recruited from both clinical and community settings and will provide saliva samples, complete online questionnaires on demographics, symptoms of mental health concerns, and behavioural inhibition, and complete neurocognitive tasks. A subset of youth will be offered access to a self-managed Internet-based cognitive behavioral therapy resource. Analyses will focus on the identification of novel genetic risk loci for anxiety disorders in youth and assess how much of the genetic risk for anxiety disorders is unique or shared across the life span.
Discussion
Results will substantially inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. Given that the GAYA study will be the biggest genomic study of anxiety disorders in youth in Canada, this project will further foster collaborations nationally and across the world
Design and implementation of low mass short backfire antennas using additive manufacturing
This thesis presents research into the design of low-mass short backfire (SBF) antennas with enhanced performance.
In the first section of this thesis, modern techniques that can be utilized to decrease the mass of the aluminum SBF antenna were introduced. Two different antenna designs were developed using additive manufacturing and perforation techniques. The first design was created by manufacturing the antenna using additive manufacturing techniques, resulting in a significant reduction in mass. Simulations were conducted on this design to analyze the impact of additive manufacturing on the antenna’s performance. The results indicated that the gain was significantly affected by high levels of surface roughness introduced during the manufacturing process. The second low-mass antenna design, the perforated 3D-printed SBF antenna, combines additive manufacturing and perforation techniques. Parametric studies were conducted on this antenna to determine the optimal size, shape, and arrangement of perforations to achieve the best mass reduction and gain results. Simulation studies found that the antenna with a 3x37 circular array of perforations on its rim, each with a radius of 4.5 mm, performed the best. The simulated results were validated by fabricating and measuring the antennas. The mass of the 3D-printed and perforated 3D-printed SBF antennas were approximately 70% and 80% lighter than the aluminum antenna, respectively, while maintaining minimal loss in gain.
The second part of this thesis discusses the enhancement of gain and bandwidth in the SBF antenna. This was done by flaring the rim to increase the aperture size of the antenna. Simulation studies were conducted to examine the impact of rim flaring and rim height on antenna performance. The results of these studies indicate that this technique significantly improved both the gain and bandwidth of the antenna while having minimal effect on the cross-polarization ratio. To further enhance the bandwidth, an iris was introduced to the waveguide feed aperture to obtain better impedance matching. The antenna was then manufactured and tested to confirm the accuracy of the simulations. The measured and simulated results were in excellent agreement.Research Manitoba #5645 IPOC GRANT
Natural Resources Canada (NRCan) (grant number OSRC-04)May 202
Satellite-tagged Eastern Beaufort Sea beluga whales (Delphinapterus leucas): from autecology to a model organism used to test broad ecological principles
Understanding the mechanisms behind animal movement decisions is fundamental in identifying what makes a movement strategy successful and in predicting how an individual will respond to environmental change. The unprecedented physical changes occurring on Earth can have profound consequences for animal movements, which have evolved to be finely tuned to environmental cues or rely on specific conditions at certain sites. This is especially true in the Arctic, where elevated water temperatures and reduced sea ice pose stressors to cryophilic species, which have movement strategies tied to the extreme but predictable seasonality of the environment.
In this thesis, I use satellite tag data from male beluga whales of the Eastern Beaufort Sea (EBS) population to develop a comprehensive understanding of their movements and the relationship between these movements and the environment, from small-scale decisions related to foraging to large-scale seasonal redistribution. I also consider the functional traits of belugas to frame my research in the broader field of movement ecology such that the findings can be applied to other marine predators. Much of this thesis centres around beluga dive behaviour, where I characterised and inferred likely functions behind individual dives over an annual cycle, used this to infer seasonal changes in behaviour, and answer further questions about the environmental drivers of movement, activity cycles, foraging ecology, and question our understanding of migration in highly mobile marine predators.
An overriding theme revealed by these analyses is the complexity and diversity of the movements and dive behaviour exhibited by EBS belugas. This population forages nearly continuously over the annual cycle, including in their winter habitat and during so-called migrations, but they use a range of strategies depending on environmental conditions. They exhibit traits during long-distance movements characteristic of migration and nomadism, but conform wholly to the classical views of neither. We identified that EBS belugas occupy and forage over a range of sea ice conditions, from open water to areas approaching 100% ice cover, and even with a small sample size we found individual variability in the routes taken and dive behaviour. The flexibility in strategies at the individual level and the diversity of traits at the population level may provide resilience for EBS belugas in the face of environmental change.ArcticNet
Fisheries and Oceans Canada
V.E. Barber Memorial FellowshipOctober 202
Electrochemical Detection of Platinum-Based Chemoresistance and Correlation with MEK1 Activity in Living Cancer Cells
Drug resistance is responsible for most chemotherapy failures, making it an urgent issue in modern oncology. In ovarian cancer, resistance to platinum-based chemotherapeutics, such as carboplatin, is common. However, its underlying mechanisms remain poorly understood. A mitogen-activated protein kinase kinase, MEK1, may play a role in the development of this resistance mechanism. This project aims to understand this mechanism by using western blots to measure MEK1 activity in patient-obtained living ovarian cancer cells, comparing between carboplatin-susceptible and carboplatin-resistant cells. Moreover, early detection of chemoresistance can improve treatment outcomes. However, current detection methods are inefficient and time-consuming. To address this, the project also proposes an unconventional approach to identifying chemoresistance. This involves the use of scanning electrochemical microscopy for the rapid and accurate quantification of glutathione, a prominent antioxidant that may serve as a biomarker for platinum-based resistance mechanisms, in both cell lines. The findings suggest a correlation between lower MEK1 activity and increased glutathione levels in the resistant cells. This research may contribute to the development of an efficient and reliable method for detecting chemoresistance, with the potential of significantly improving cancer treatment outcomes
Physician perspectives on gender-affirming care for trans youth
Background: Many trans people who seek medical transition, particularly youth, struggle to access care in a timely manner. Frequently, specialized clinics tend serve the majority of the trans population and the capacity of these clinics ends up being overburdened by demand. Yet, the provision of gender-affirming medical care is not beyond the skillset of general practitioners and if more took up prescribing it, access could be improved.
Objectives: This study sought to understand physician perspectives on gender-affirming care for trans youth in the hopes that insights into how to encourage more practitioners to take up providing care could be gleaned. The study had two central research questions. 1) What are Canadian physicians’ perceptions, education, and knowledge base surrounding gender-affirming care for youth under the age of 18? 2)How does this differ between knowledgeable physicians who have experience with gender-affirming care and inexperienced physicians who do not?
Methodology: An anti-oppressive queer theoretical lens was applied to this study. Individual, semi-structured, in-depth, interviews were conducted with 13 physicians who had a range of experiences providing care for trans patients. The interviews were transcribed and coded for similar themes which constructed the results.
Results: Participants discussed a wide range of topics related to gender-affirming care for trans patients, both specific to youth and more general to trans healthcare broadly. Many participants argued, some with direct firsthand experience, that gender-affirming care does not need to be specialized care and can be prescribed, easily, by primary care providers. Many physicians receive little, or no education related to gender-affirming care in medical school. Despite this lack of education several participants became knowledgeable and willing to provide care to trans patients. Knowledgeable physicians frequently shared similar motivations, and accessed similar resources, in order to become willing and able to provide care.
Discussion: This study proposes recommendations for improving access to gender-affirming care for trans youth, and trans patients broadly. Improving and implementing education regarding gender-affirming care in medical schools and expanding resources for currently practicing physicians who take on trans patients. As well as framing gender-affirming care to exist within primary care practice.Research Manitoba
Manitoba Training Program for Health Services ResearchFebruary 202
Urban green spaces, Lahore, Pakistan
This practicum focuses on improving the ecological conditions of Lahore. The city which was once known for its open spaces and was called the city of gardens. This city of gardens is now becoming a city of concrete. The city is losing its previous identity. An overpopulated urban city like Lahore cannot survive rapid and unsustainable development. This exerts pressure on existing natural resources, leading to water problems, decline in green spaces, pollution, and changes in the city’s temperatures. The green spaces are being paved to make room for roads and land-use buildings. Urban green spaces are an essential element of development planning, providing multiple benefits to society. This practicum studies the towns of Lahore in terms of population densities and the accessibility/availability of green spaces to the people who live in the towns. With help of photographs the quality of existing green spaces is also studied to understand what is lacking in the existing green spaces. New potential green spaces within the densely populated towns are identified. More detailed designs are created for two sites, each with different opportunities and challenges.October 202