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A briefing paper on the state of the art of accessibility research focusing on disabled people, including research on attitudinal accessibility and attitudinal barriers
No full textFunding: This research was funded by the Social Sciences and Humanities Research Council of Canada (SSHRC) Insight grant, 435-2024-0750; Computational Urban Accessibility: Understanding, Mapping, and Scoring Barriers in the Built Environment.Disabled people face many accessibility problems in their lived reality as evident by the United Nations Convention on the Rights of Persons with Disabilities (CRPD). Many societal developments and discussions can influence accessibility and be influenced by accessibility. The objective of this briefing paper for the members of the Social Sciences and Humanities Research Council of Canada (SSHRC) Insight grant, 435-2024-0750; Computational Urban Accessibility: Understanding, Mapping, and Scoring Barriers in the Built Environment was to better understand the academic coverage of accessibility-related to disabled people, with a particular focus on attitudinal accessibility and attitudinal barriers. We performed a scoping review of abstracts from Scopus, Web of Science, and the 70 databases accessible through EBSCO-HOST using manifest coding and thematic content analysis approaches to fulfill the objective. Our analysis generated various insights: for instance, of the 526,556 abstracts that contained the term “accessibility” only 6.9% also included the disability terms we used. For some other accessibility related terms, the % was even lower. The term “attitudinal accessibility” was only found in 48 full texts, of which 16 had content related to disabled people. Healthcare was the main topic mentioned under attitudinal barriers. Words and phrases such as health, healthcare, “public health”, rehabilitation and “health services” were mentioned substantially, others such as intersectionality, health promotion, “social determinants of health”, health equity, science and technology governance terms and others reflecting various social discussions were rarely mentioned. International normative legal documents were rarely mentioned or not at all. Our findings highlight significant opportunities to engage more deeply with multifaceted accessibility issues affecting disabled people, including the use of occupational rights-based, ability judgment-based, intersectionality-based and spatial rights-based concepts as analytical tools. Such efforts are essential for advancing social inclusion, health and wellbeing and equity of disabled people.Social Sciences and Humanities Research Council of Canada (SSHRC)Social Sciences and Humanities Research Council (SSHRC
Efficacy and safety of corticosteroids for stroke and traumatic brain injury: a systematic review and meta-analysis
No full textAbstract Background Corticosteroids are frequently used in practice to treat patients with neurological disorders. However, its effect for stroke and traumatic brain injury (TBI) remains controversial. This study aimed to systematically review and evaluate efficacy and safety of corticosteroids for the treatment of stroke and TBI. Methods We searched Ovid-Medline and Ovid-Embase databases for randomised controlled trials (RCTs) and cohort studies evaluating the efficacy and safety of corticosteroids in patients with ischaemic stroke, intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH) or TBI. The treatment intervention was corticosteroid, and the control was placebo or routine care. Outcome measures were death, functional outcomes and adverse events. We calculated odds ratio (OR) and 95% confidence interval (CI) for the effect size, pooled the results using random-effects modelling, and assessed heterogeneity by I2 statistic. Results We identified 47 studies (41 RCTs and 6 cohort studies). Nine studies enrolled patients with ischaemic stroke (n = 2806), 6 studies for ICH (n = 1229), 1 study recruited both ischaemic stroke (n = 13) and ICH (n = 27), 10 studies for SAH (n = 1318) and 21 studies for TBI (n = 12,414). Dexamethasone was the most used corticosteroid (28 studies). Corticosteroids reduced risk of death at 3 months after ischaemic stroke (n = 1791; 31% vs. 26%, OR 0.77, 95% CI 0.62–0.95; df = 1, I2 = 0%) and after ICH (1 study; n = 850; 44% vs. 27%, OR 0.48, 95% CI 0.35–0.64), had no effect on death at 1 month after SAH (1 study; n = 140; 22% vs. 32%, OR 1.73, 95% CI 0.81–3.68), and increased risk of death at 6 months after TBI (n = 10,755; 23% vs. 27%, OR 1.20, 95% CI 1.10–1.32; df = 6, I2 = 0%). The pooled analyses found no significant effect of corticosteroids on functional outcome after ischaemic stroke, ICH, SAH or TBI, respectively. Conclusion Corticosteroids reduced the risk of death and in selected patients with stroke, such as those with large artery occlusion after thrombectomy, but increased the risk of death after TBI, had no effect on functional outcomes. Further trials are needed to identify individual stroke patients who may benefit from corticosteroids. Systematic review registration International Prospective Register of Systematic Reviews (CRD42023474473)
Application of hyphenated analytical techniques to separate mercurials and to probe the bioinorganic chemistry of gold nanoparticles in blood plasma
No full textThe increasing emission of mercury (Hg) into the global environment necessitates a deeper understanding of its bioinorganic chemistry in mammals and the development of robust analytical methods to quantify inorganic mercury (Hg²⁺) and methylmercury (MeHg⁺) in environmental samples. This thesis addresses these challenges by exploring advanced separation and detection techniques. In the first project, anion-exchange high-performance liquid chromatography (AEXHPLC) coupled with flame atomic absorption spectrometry (FAAS) was employed to investigate the retention behavior of Hg²⁺ and MeHg⁺ across a pH range of 5.0–8.0, using a mobile phase containing 10 mM L-cysteine in 100 mM phosphate buffer. The addition of methanol (5–20%) to the mobile phase revealed that while the Hg²⁺ retention remained largely unaffected, the retention of MeHg⁺ was significantly reduced. A 15% methanol-containing mobile phase was identified as optimal to enable a rapid baseline separation of Hg²⁺ and MeHg⁺ in under 400 s. The method's robustness was validated using inductively coupled plasma atomic emission spectrometry (ICPAES), which allowed achieving a detection limit of 1.5 ppm for Hg²⁺ and 2.9 ppm for MeHg⁺. The developed method was successfully applied for wastewater spiked with both mercurials. In the second project, the interactions of gold nanoparticles (AuNPs) with plasma proteins were investigated to address challenges in targeted drug delivery. Size-exclusion chromatography (SEC) and transmission electron microscopy (TEM) revealed the formation of large (>670 kDa) AuNP-plasma protein aggregates, which would restrict effective drug delivery. To mitigate this, AuNPs were surface-modified with dithiols, including dithiothreitol (DTT), meso-2,3-dimercaptosuccinic acid (DMSA), and 2,3-dimercapto-1-propanesulfinic acid (DMPS). DMSAand DMPS-modified AuNPs demonstrated a superior reduction of the protein corona formation compared to DTT-modified AuNPs, suggesting their potential to enable their targeted delivery to the intended tissues. Excess dithiols, left over after the coating step, were found to mobilize iron from plasma metalloproteins, underscoring the need for their removal before any clinical application of dithiols-modified AuNPs. Together, these results advance the fields of environmental mercury analysis and nanomedicine by developing innovative separation techniques and surface modification strategies, to address critical challenges in environmental monitoring and targeted drug delivery
Investigations into the Physiological Role of MTARC1
No full textMetabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), previously known as Non-Alcoholic Fatty Liver Disease (NAFLD), is the most common type of chronic liver disease, affecting an estimated 20–30% of North American adults (Miao et al., 2024). By 2040, it is projected that MASLD will impact nearly 50% of the global population due to the rising rates of diabetes, dyslipidemia, and obesity, making it a significant health care concern (Miao et al., 2024). MASLD progresses through various stages, beginning with excessive lipid accumulation in the liver (steatosis), followed by inflammation, fibrosis, and ultimately, cirrhosis. Unfortunately, effective therapeutic options remain limited. In March 2024, the FDA approved one of the first treatments for this disease: Rezdiffra (Resmetirom). Given the complexity of MASLD, a single therapeutic approach is unlikely to be sufficient, highlighting the need for further research to identify new treatment strategies. A genome-wide association study (GWAS) identified a protective variant in mitochondrial amidoxime reducing component 1 (MTARC1), which appears to reduce the risk of MASLD. Individuals carrying the T165A variant (a mutation of threonine 165 to alanine) exhibited lower hepatic lipid levels, decreased liver enzyme levels and reduced incidence of MASLD (Emidin et al., 2020). These findings suggest that MTARC1 may be a promising target for MASLD therapy. To explore the biological functions of MTARC1, we employed proteomic, metabolomic, and imaging approaches to investigate its role in lipid metabolism. We hypothesize that MTARC1 regulates lipid homeostasis through anabolic pathways that enhance lipid production while reducing lipid breakdown. Our findings indicate that MTARC1 influences the pentose phosphate pathway, an anaplerotic pathway, leading to increased production of deoxynucleotide triphosphates (dNTPs) and nicotinamide adenine dinucleotide phosphate (NADPH). Both these metabolites contribute to protection against oxidative stress, enhance lipid synthesis, and may protect against inflammation. This suggests that MTARC1 may play a critical role in metabolic and inflammatory pathways associated with MASLD, potentially making it a viable therapeutic target for the disease
The Association Between Female Sex-Specific Events and Blood Pressure Across the Lifespan
No full textGlobally, cardiovascular disease is the leading cause of death in women and hypertension is the most common modifiable risk factor for cardiovascular mortality. Highlighting the importance of blood pressure control, the World Health Organization had set a global target of a 25% relative reduction in uncontrolled hypertension by 2025. Furthermore, in Canada, the prevalence of hypertension has remained relatively steady between 2007 and 2017. However, the rates of awareness, treatment and control have worsened, especially among Canadian women, highlighting the urgent need to identify and understand how events across the female lifespan may contribute to hypertension in this population. Overall, the studies are united by an aim to examine the association between female sex-specific events (e.g., pregnancy, menopausal hormone therapy use, hysterectomy) and blood pressure. In our first study, we examine the association between parity and gravidity & hypertension and blood pressure through a systematic review and meta-analysis. We determined that parous individuals may be at an elevated odds of hypertension when compared to parous individuals. Furthermore, when stratified by parity number, greater parity number may be associated with greater odds of hypertension. Our second study estimated the association between the duration of menopausal hormone therapy use and cardiovascular health in healthy postmenopausal individuals through an exploratory cross-sectional study. We found that duration of menopausal hormone therapy may not be associated with blood pressure or arterial stiffness in our study cohort. The final study evaluated the association between hysterectomy and hypertension through a retrospective case-cohort study based out of Alberta, Canada. Through this study, we found that hysterectomy was significantly associated with a greater risk of incident hypertension, when compared to age-matched individuals who did not undergo hysterectomy or oophorectomy. Overall, the results from these studies enhance our understanding of how various events across the female lifecycle may contribute to blood pressure and ultimately cardiovascular risk. Furthermore, the findings from this thesis have the potential to inform future clinical care, allow for increased intervention, and allow for informed decision-making between individuals and their health care providers
The impact of oxygen levels on reactive astrogliosis
No full textThere is recent evidence that astrocytes play an essential role in the pathogenesis of multiple sclerosis (MS) and other neuroinflammatory conditions. MS is characterized by inflammation in the central nervous system (CNS), which results in demyelination and injury of axons. Astrocytes contribute to both the progression of MS by promoting inflammation and neurodegeneration through cytokine release and impaired remyelination. Despite these pro-inflammatory mechanisms, astrocytes also exert protective effects by inhibiting de-myelination and supporting neuronal regeneration. Cell cultures, a common technique used to study astrocytes, require growth conditions that mimic the environment from which the cells were extracted. However, in conventional cell culture, cells are often exposed to oxygen levels almost four times higher (21%) than what they encounter in the brain (3-6%). Furthermore, previous studies have indicated that astrocytes are sensitive to changes in oxygen levels. Therefore, using a tri-gas incubator, in which oxygen concentrations can be controlled, I investigated how astrocytes behave and respond to hypoxic insults when cultured at physiologically relevant oxygen concentrations. I found that culturing astrocytes at physiological, as opposed to atmospheric, oxygen levels changed their morphology, decreased their proliferation rate, reduced their ability to repopulate a scratched area, and decreased major histocompatibility class I expression. My results indicate that culturing astrocytes at a physiologically relevant oxygen concentration and exposing them to hypoxic insults decreased their reactivity, pro-inflammatory profile, and neuroprotective capabilities, but increased their glycolytic activity. These findings highlight the importance of taking oxygen concentrations into account when studying reactive astrogliosis. Moreover, considering that hypoxia is associated with MS disease progression, these findings also set the stage for further studies into the effect of hypoxia on astrocyte functions in neurological disorders like MS
Public Policy Analysis: Social Prescribing and Improving Older Adults' Access to Healthy Food
No full textWhile federal and provincial social security programs exist that provide general economic assistance, and social and welfare services exist for addressing emergent need for food, healthy food access remains suboptimal, affecting the physical and mental health of affected populations, and older adults are especially vulnerable. This policy analysis used a modified version of Patton's Rational Problem-Solving Process: problem identification, determining evaluation criteria, identifying and assessing policy options, selecting the preferred policy, and implementing, monitoring. The policy problem used is: Too many older adults cannot afford enough healthy food to follow the nutritional advice of their healthcare providers. Six policy options were identified in a previously conducted environmental scan that systematically scanned and identified literature on programs to reduce the cost of, and improve access to, healthy foods. These policy options were evaluated using decision criteria adapted from the National Collaborating Centre for Healthy Public Policy, effectiveness, unintended effects, equity, cost, feasibility, and acceptability. Stakeholders with expertise in health service and delivery, food insecurity and social prescribing were consulted. The top policy options identified were voucher prescriptions and income support with reimbursement. Following a fulsome analysis and stakeholder feedback, the highest scoring and recommended option was income support with reimbursement
Creating Salt Tolerant Canola (Brassica napus) Germplasm through overexpression of SOS1 (Salt Overly Sensitive 1), a Na+/H+ Plasma Membrane Antiporter
No full textSoil salinization poses a significant abiotic stress that impacts optimal growth of economically important crops globally. Climate change-associated weather patterns have increased the occurrence of drought which consequently favors the buildup of salt within the soil rendering agricultural lands uncultivable. Canola (Brassica napus) is an oilseed glycophytic crop of high economic value to Canadians as it generates a revenue of nearly $30B/year but is unable to withstand salinized soils. However, Kochia (Bassia scoparia) is a halophytic broadleaf weed that grows abundantly on salinized soils across the Canadian prairies. Previous studies conducted in Arabidopsis thaliana have shown that SOS1 (Salt Overly Sensitive 1) to be the key component of the SOS pathway that significantly improves salt tolerance when overexpressed. SOS pathway is highly conserved in most plants and is responsible for combating salt stress within cells. It consists of 3 genes: SOS1, 2, and 3. SOS1 is a plasma membrane localized Sodium/Hydrogen (Na+/H+) antiporter, SOS2 is a Serine/Threonine kinase, and SOS3 is a calcium binding protein. In both canola and Kochia, SOS1 expression is upregulated by salt treatments and given that the protein identity between kochia and canola SOS1 is low (65%), SOS1 versions from both these species were utilized for transgenic testing. This study assessed whether overexpression of canola or Kochia SOS1 (BnSOS1) can confer salt tolerance in fission yeast (Schizosaccharomyces pombe), Arabidopsis, and canola. Although no substantial improvement in salt tolerance was observed in yeast strains and Arabidopsis, overexpression of SOS1 in canola showed a significant improvement in the ability of transgenic plants to germinate and maintain yield in the presence of 200 mM and 300 mM of NaCl relative to unmodified Brassica napus cv.1. Adoption of this new germplasm could allow for marginal, saline lands to be utilized for agriculture
Assessing Surface Water Dynamics of Young Boreal Wetlands with Satellite Based Remote Sensing
No full textWetland landscapes are important ecological environments that provide many valuable ecological and socio-economic functions including water management and filtration, habitat provision for many plants and ani-mals, sources for tourism and recreation, and sources for peat and timber for industrial applications. Wet-lands are also under threat from factors such as climate change, industrial activity and development, and urban development. Many wetland restoration projects are underway to reclaim and restore damaged land-scapes to their previous state, but methods to evaluate the success of these reclamation activities need to be developed. Additionally, there is the need to compare and contrast these reclaimed landscapes with natural wetlands. In this thesis we present a comprehensive framework for evaluating and measuring water and vegetation dynamics in young wetlands using satellite based remote sensing. We use a combination of optical and radar imagery, and we approximate imagery obscured by clouds or shadows where appro-priate to build a complete picture of the landscape. We developed software tools to perform classification, visualize the results, and approximate missing data. We focused our measurement on open water areas, semi-aquatic emergent vegetation, and upland vegetation in areas surrounding the wetlands. We create easy to understand summary statistical images that can be used to measure the rate of occurrence of different phenomena or the variability of the phenomena. We also compare and contrast our approach with existing, established techniques for monitoring and measurement of Boreal wetlands. We show how our approach is able to improve on the results generated from these existing techniques. In some cases we are able to detect and measure wetlands that other techniques miss, while in other cases we are able to provide additional temporal context that other techniques might be missing