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Optimal cerebrovascular reactivity thresholds for the determination of individualized intracranial pressure thresholds in traumatic brain injury: a CAHR-TBI cohort study
Get PDFIt has been demonstrated that patient-specific intracranial pressure (ICP) thresholds are possible to derive using the function intersectionality between ICP and cerebrovascular reactivity (CVR). Such individualized ICP (iICP) thresholds represent a potential personalized medicine approach to neurocritical care management. However, it is currently unknown how various CVR thresholds compare in regard to deriving iICP. Here we attempt to identify the CVR thresholds that are best suited for iICP derivation. Leveraging 365 patient data sets from the CAnadian High-Resolution TBI (CAHR-TBI) Research Collaborative, iICP was derived using three ICP-based CVR indices: the pressure reactivity index (PRx); the pulse amplitude index (PAx); and the RAC index, and thresholds ranging from − 1 to + 1, in 0.05 increments. Patients were dichotomized based on 6-month outcome scores into Alive vs. Dead and Favorable vs. Unfavorable outcome. 2 × 2 tables were created for each threshold, grouping patients by outcome and whether their mean ICP was greater or less than their calculated iICP. Chi-squares were calculated for each table and subsequently plotted. The thresholds that produced the largest Chi-square values were identified as those able to derive the iICP with the greatest ability to predict outcomes. Next, Spearman rank correlation testing was used to evaluate associations between iICP, for each threshold, and measures of cerebral physiologic insult burden. With consideration of yield data, ability to predict outcome, and association with cerebral physiologic insult burden, a threshold of + 0.05 was identified for PRx. No optimal threshold could be identified for PAx or RAC
Prion replication in organotypic brain slice cultures is distinct from in vivo inoculation and is species dependent
Get PDFAbstract Cultured brain slices rapidly replicate murine prions, exhibit prion pathology, and are amenable towards drug discovery, but have not been infected with human prions. As deer mice (Peromyscus maniculatus) are susceptible to human prions in vivo, here we investigated deer mouse organotypic brain slice cultures as a potential model of human prion disease. Deer mouse brain slices supported replication of rodent-adapted strains of scrapie and Creutzfeldt-Jakob disease (CJD), but they resisted infection with primary human prion inoculum. To better understand this discrepancy, we quantified prion replication rates, characterized cellular and molecular changes, and estimated inoculum clearance within wildtype CD1 and deer mouse brain slice cultures. Prion replication rates varied by species, strain, and brain region, independently of PrP sequence homology. Scrapie-infected CD1 cerebellar slice cultures exhibited the fastest prion replication rate, closely matching in vivo bioassay kinetics and showing neuronal and synaptic degeneration at similar timepoints. However, deer mouse slice cultures replicated deer mouse-adapted sCJD MM1 prions less efficiently than in vivo inoculation. These findings clarify both the utility and constraints of brain slice cultures in modeling prion disease and imply that the slice culture molecular environment may be suboptimal for human prion replication
Genome mining of Leptographium wingfieldii, an invasive species in Canadian forests, and related taxa in the order Ophiostomatales for the characterization of secondary metabolites and ribozymes
Get PDFLeptographium wingfieldii is an invasive fungal species in Canadian forests which was originally isolated in Europe (France and Greece). Leptographium wingfieldii and other fungi in the order Ophiostomatales (Ascomycota) are vectored by arthropods, and they can be either pathogenic to tree species or cause blue stain on sapwood in conifer (and hardwood) species. These fungi are ecologically and economically significant due to their impact on forest ecosystems and lumber industry. Whole genome sequences were obtained from Leptographium wingfieldii and related fungi (including Leptographium procerum, Leptographium terebrantis, Grosmannia aureum, Ophiostoma minus, and Ophiostoma piliferum). The mitochondrial genomes of these fungi were assembled and found to contain autocatalytic group I and group II introns, intron-encoded homing endonucleases along with intron-encoded reverse transcriptase enzymes that have applications in genome editing. These elements contribute toward the genetic diversity observed among the mitochondrial genomes studied. The study provided information to generate a mitochondrial intron landscape, identified complex intron arrangements, and demonstrated the correlation of mitogenome expansion with the number of introns. The whole genome sequence data were also analyzed with regards to the presence of nuclear genome encoded biosynthetic gene clusters (BGCs). This effort identified the presence of 205 BGCs categorized into PKS I, PKS III, NRPS, RiPPS, Terpenes, and hybrid types and these could be sources for potential antimicrobials and industrially important chemical compounds. The study provides a platform for downstream biochemical characterization and heterologous expression of the identified genetic elements, facilitating their functional annotation and explore their potential for industrial applications.October 202
“There’s just such a mismatch”: a qualitative exploration of health systems and organizational-level barriers to accessing cancer services among people experiencing structural marginalization
Get PDFAbstract Background Within the context of cancer care, access to timely, high-quality care is closely correlated with better health outcomes and quality of life. Yet in Canada, research continues to show that inequities in access to cancer care persist across the cancer continuum, particularly among people experiencing structural marginalization. Although some Canadian research has explored barriers accessing cancer care, little research has explicitly focused on barriers arising from organizational and health systems contexts. Our objective was to explore barriers to accessing cancer services within the health system and organizations delivering cancer services across the cancer continuum for people experiencing structural marginalization. Methods This study drew on critical ethnographic methods, employing a participatory, integrated knowledge translation approach. Data collection included interviews with health and social service providers (n = 24) and key informants (n = 7), interviews and focus groups with individuals with lived experience of significant health and social inequities (n = 29), and 40 h of observations with service providers working in clinical oncology settings. Guided by social justice, critical and intersectional theoretical perspectives, data analysis followed an interpretive descriptive approach. Results Four interrelated themes were developed through our analysis, with the overarching thread of a ‘mismatch evident throughout: (1) the design of cancer services does not always account for social contexts and structural determinants of health; (2) discourses of operational efficiency are competing with equity-oriented care; (3) the physical spaces of cancer care matter; and (4) experiences of stigma and discrimination are incompatible with accessing cancer care. Our findings suggest that the ways in which cancer services across the continuum are designed, including the types of services available, how care activities are structured, what activities take priority, and how services are experienced, create barriers that particularly impact people experiencing structural marginalization. Conclusions Our findings highlight the mismatches between how cancer services are currently designed and delivered, and the specific needs of people experiencing health and social inequities. These findings also point to organizations delivering cancer services as potential sites for transformation toward more equitable access to cancer care. Equity-oriented healthcare may offer a framework for service design and delivery to improve access to cancer care and experiences of care
Rational analysis of empirically designed bridge decks using PUNCHED
Get PDFReinforced concrete bridge deck slabs make up a significant portion of bridges worldwide and are designed to efficiently withstand traffic loads. The empirical design method, specified in the Canadian Highway Bridge Design Code (CHBDC), uses the inherent arching action in these slabs to provide strength and durability. The PUNCH program was developed to analyze externally restrained steel-free bridge deck slabs, but it cannot analyze directly deck slabs with embedded reinforcement.
This research focuses on modifying the PUNCH program to enable the analysis of internally reinforced deck slabs by introducing the concept of equivalent diameter for embedded reinforcement. The study investigates how the axial stiffness of steel-concrete composites changes under varying loads and integrates these findings into the modified program, PUNCHED. The enhanced program accounts for equivalent diameters to accurately model reinforced concrete deck slabs under different loading conditions. Validation using experimental data from multiple studies confirms that PUNCHED reliably predicts both load-deflection behavior and ultimate failure loads.
The findings demonstrate that the modified PUNCHED program provides a dependable tool for engineers to evaluate the performance of reinforced concrete deck slabs. By bridging the gap between empirical design and analytical modeling, this research contributes to more precise and effective analysis of bridge deck slabs.The project was funded by Research Manitoba
Identifier: Innovation Proof-of-Concept Grant
Project title: Developing software based on the empirical evidence to rationalise design provisions of the Canadian
Highway Bridge Design Code (CHBDC) of reinforced concrete deck slab
project number 5275
CharleenOctober 202
Alcid communication at sea: vocal repertoire and individual chick signatures
Get PDFSeabirds are highly vocal at breeding colonies, and although they spend most of their life at sea, our understanding of their vocal behaviour away from breeding colonies is limited. Seabird vocalisations are uniquely adapted to communicate both within dense breeding colonies and at sea, but vocalisations likely serve distinct functions and experience different environmental conditions that influence propagation within these distinct contexts. Here, we investigated the vocal behaviour in alcid seabirds (Family Alcidae) on the northeastern coast of Newfoundland, Canada. In Chapter 2, we identified and quantitatively described vocalisations emitted by common murres (Uria aalge) while foraging at sea and qualitatively compared these calls to colony-based repertoires. Four call types were described (‘eng’, ‘arg’, ‘crow’, ‘eur’) and call type assignments were validated using supervised multivariate analyses (random forest) and observer agreement. Three of these call types visually resembled call types previously described at murre colonies with one exhibiting high temporal variation that appeared to grade between different call types. The fourth call type was novel and may only be emitted at sea. Finally, we postulated functions of these four call types at sea based on the behavioural and social contexts in which they were emitted. In Chapter 3, we investigated the presence and ontogeny of individual-specific signatures in razorbill (Alca torda) chick vocalisations used in parent-chick communication at sea. We quantitatively described the individual signatures encoded within ‘departure’ calls of six razorbill chicks during early (3-5 days old) and late (15-19 days old) nestling stages. Calls were reliably assigned to individuals in both stages with similar classification success (early: 66.7%, late: 69.4%), but classification varied considerably among chicks. Temporal attributes had the strongest potential of individual coding (PIC > 1) and the potential to encode identity increased across nestling development, suggesting their importance in signalling identity during fledging and at sea. These findings provide insight into alcid ecology at sea by highlighting the diversity of acoustic signals used by seabirds in this understudied environment and increasing understanding of the acoustic adaptations to specific ecological pressures experienced away from breeding colonies.October 202
Canopy-dependent environmental factors impact on nitrogen fixation in Shepherdia canadensis in the boreal forest and tundra
Get PDFActinorhizal shrubs, plants that symbiotically associate with nitrogen-fixing bacteria and do not depend on soil nitrogen, can increase productivity and facilitate successional changes. High-latitude environments are characterized by harsh abiotic climatic conditions that limit nitrogen availability to plants. However, actinorhizal shrubs are less prevalent at higher latitudes, even though those environments are generally nitrogen-limited. Reduced year-round temperatures, water availability, and light availability are all thought to limit nitrogen fixation due to its energetic costs, making nitrogen fixation unfavourable at higher latitudes. Shepherdia canadensis (buffalo berry) is an actinorhizal shrub that is found in higher-latitude environments across Canada. We wanted to determine, within the northern edge of the boreal forest and tundra, how much nitrogen fixation is occurring in buffalo berry, and how it varies across naturally occurring habitat and canopy-dependent environmental factors. The natural abundance stable isotope technique was used to quantify nitrogen fixation, while canopy-dependent variables were measured using hemispherical image analysis. We found that buffalo berry shrubs were getting a majority of their nitrogen content through nitrogen fixation (55.32% - 94.74%) and that on average, fixation occurred at a higher rate in the forest (74.67%) compared to the tundra (68.00%). Notably, foliar δ13C values varied with canopy openness. Specifically, shrubs in more open areas and the tundra had higher δ13C values, which were interpreted to be a result of stomatal closure in response to reduced water availability. Nitrogen fixation was found to be sensitive to water availability, decreasing with canopy openness (17.99% – 99.79%). This limitation could reduce the productivity of nitrogen-fixing plants in response to warmer climate conditions
Life performance
Get PDFThis thesis attempts to show the inextricable relationship between art and life by combining individual life experiences and reflections, different periods from my art practice, and its contextualization within the history of art. The first chapter will be set in the context of my art practice prior to my MFA program at the University of Manitoba. From painting to jewellery to performance, these seemingly huge leaps are actually traceable, and these changes correspond to certain periods in art history. In this process, I took my life as a source of inspiration for my art practice and materialized it until I found a way to dematerialize it.
The second chapter will introduce my artistic practice during my MFA program at the University of Manitoba, which can be broadly divided into language, image and sound. I will cite different works in each section and discuss theoretical reflections related to them.
The third chapter will focus on my graduate exhibition at the School of Art Gallery, which involves the topics of technology, humans and space. I consider the exhibition as a work of art in its own right, rather than a vessel for other works.October 202
Evaluating temporal trends in behavior and demographics to understand the lack of recovery of an endangered whale population
Get PDFBeluga whales (Delphinapterus leucas) are critical components of the Arctic marine ecosystem, and they face numerous threats from environmental changes and human activities. Understanding their population dynamics, habitat use, and social structure is crucial for their conservation. The research outlined here investigates the endangered Cumberland Sound beluga whale population using various techniques including drone surveys, aerial surveys, and satellite telemetry. The thesis begins with an overview of beluga whale ecology, behavior, and the threats they face, and explores how many of these aspects vary between populations. Satellite telemetry was used to explore behavioral trends, revealing stable migration timing over several years. Dive behavior analyses suggest a change in prey preference from Arctic cod (Boreogadus saida) to capelin (Mallotus villosus), which may have negative consequences for the population over time as the distribution and abundance of capelin can be less predictable. Drone technology was used to create a photographic identification catalog for the beluga whale population, allowing for detailed monitoring of individual whales, minimizing disturbance, and providing insights into age structure and social dynamics. From 2017 to 2019, drone surveys identified 93 individual whales, revealing many uniquely marked adults and consistent resightings, and the existence of stable social groups over multiple years. Aerial surveys in 2014 and 2017 provided extensive coverage of the beluga whale population and showed a potential contraction in geographical range and a lower proportion of juveniles compared to other populations. The integration of drone and aerial surveys in this study resulted in comprehensive data on demographic trends, crucial for understanding population health. This thesis also examined the long-term impacts of satellite tagging. Two whales were photographed with tag remnants and scars, suggesting although tagging did not result in long-term health issues in these cases, the remnants of tagging may remain long after intended. In summary, this thesis provides a detailed examination of the Cumberland Sound beluga whale population, demonstrating the importance of varied research methods for effective monitoring. Given interpopulation differences in beluga whale ecology, these insights are crucial for developing targeted conservation strategies and ensuring the long-term resilience of the population against environmental and anthropogenic pressures.The World Wildlife Fund, Canada Arctic Species Conservation Fund, G-0520-004-00-D
The Nunavut Wildlife Management Board, Nunavut Wildlife Research Trust project, 3-19-08
The Oakes-Riewe Aboriginal-Environmental Studies Research Award, 46216May 202
Smart wound dressings for accelerated scar-free wound healing
Get PDFWound healing is a complex process comprising four main stages: hemostasis, inflammation, proliferation, and remodeling. Disruptions at any stage can lead to delayed healing, chronic wounds, or excessive scar formation. This project leverages nanotechnology to develop strategies that modulate different phases of wound healing, promoting tissue regeneration. Nanotechnology enables the manipulation of the wound healing trajectory through various chemical and physical cues to accelerate healing while minimizing scar formation. This study focuses on two key approaches: (1) infection prevention to reduce inflammation-related healing delays and (2) responsive delivery of an anti-scar drug within the critical window of scar formation.
For infection prevention, a theranostic biosensor was developed. The biosensor integrates a hemicyanine dye that undergoes a color change upon detecting bacterial lipase, allowing early and visible identification of bacterial presence. Additionally, it incorporates responsive nanoparticles that release antibacterial agents selectively in environments with elevated reactive oxygen species (ROS), ensuring targeted bacterial elimination.
For anti-scar drug delivery, solid lipid nanoparticles (SLNs) were engineered for targeted drug release during the early stages of scar formation. Since premature or delayed drug delivery can interfere with normal healing, a biomarker overexpressed specifically during scar formation was identified. SLNs were functionalized with a ligand targeting this marker. To prevent premature drug release, a cage-like protein coating was applied to the SLNs, enhancing stability until the optimal release window.
These strategies enabled early bacterial detection at low concentrations, selective bacterial elimination in ROS-rich environments, and precise delivery of anti-scar drugs to cells overexpressing connective tissue growth factor (CTGF), a biomarker specific to scar formation. By modulating different wound healing stages, this study aims to accelerate healing while minimizing scarring. However, further in vivo studies are essential to validate the clinical potential of these approaches.MITACS Grant (IT30856)
Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (RGPIN-2019-06094),
Canada Foundation for Innovation (award number: 23679)
University of Manitoba GETS programOctober 202