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Biological Ageing of the Heart and Brain in Cardiovascular Disease
No full textDeteriorations in heart and brain health have been linked to age-like changes in healthy and non-healthy individuals. Recently, the so-called age gap biomarkers have been proposed to quantify age-like changes in specific organs. These biomarkers are calculated using a machine learning model trained with data from healthy subjects for which the predicted biological age is assumed equal to the chronological age. In unseen subjects, the age gap is calculated as the difference between the predicted biological and chronological age. Thus, age gaps provide a quantitative measurement of deviations from healthy ageing. Previously, a bidirectional relationship was found between the heart and brain, with improvements in cardiovascular health correlated with improved neurological health and vice versa. Therefore, this thesis aims to explore how cardiovascular diseases manifest in the heart and brain by utilizing respective age gap biomarkers. This work aims to provide a more holistic understanding of cardiovascular disease manifestation throughout the body, which may create new opportunities for disease management. This was accomplished through two aims using data from over 34,000 UK Biobank participants: (1) develop a brain age prediction model using T1-weighted brain MRIs and investigate how the brain age gap (BAG) differs among individuals with cardiovascular diseases; (2) implement a heart age prediction model using cardiac MRI derived features and analyze how the heart age gap (HAG) relates to the BAG in individuals with cardiovascular diseases. Regarding the first objective, cardiovascular diseases were found to exhibit trends in the BAG similar to those of neurological diseases, providing evidence for the impact of cardiovascular diseases on neurological health. Regarding the second objective, it was found that various cardiovascular disease groups exhibited significant differences when comparing the HAG and BAG to healthy subjects. In the examination of the correlation between HAG and BAG for each individual, it was found that the two were weakly correlated with each other, exemplifying heterogeneity in biological ageing throughout patients with cardiovascular diseases. Overall, this thesis provides support for the combination of the heart and brain age gap to provide useful insight into how cardiovascular diseases manifest in the heart and brain
Modeling, Designing, and Evaluating Lens Visualizations for 3D and Immersive Analytics
No full textLens visualization has been a prominent research area in the visualization community, fueled by the continuous need to mitigate visual clutter and occlusion resulting from the increasingly large datasets. Interactive lenses for 3D data, particularly, challenge visualization designers to conceive design strategies that facilitates the analysis of dense, multifaceted data with spatial referents. Given their relevance, the overarching research goal of this dissertation is to investigate how visualization lenses may support 3D data exploration and analysis—across both conventional and immersive environments. To this end, we begin with (1) modeling lenses by conducting a systematic review of existing lenses operating within spatial contexts. From this survey, we derive a design space that captures core design dimensions and choices involved in constructing spatially-embedded visualization lenses. Building upon this theoretical foundation, we proceed with (2) designing lenses, through the design, development, and evaluation of four immersive lenses tailored to support distinct forms of 3D data analysis: i) a deformable quadric lens for heterogeneous feature analysis, ii) a dual-imagery lens for multivariate, multi-geometry analysis, iii) a view-dependent lens for reservoir uncertainty analysis, and iv) a shape-conformal lens for spatiotemporal urban data analysis. Afterwards, we probe (3) evaluating lenses by complementing our prior theoretical and practical endeavors with empirical evidence from a controlled study comparing the efficacy of four lens-based designs in supporting time-varying urban data analysis. Throughout the course of our research agenda, we document domain-specific lessons learned and translate them into generalizable design guidelines intended to inform the broader visualization community. Finally, this dissertation concludes by suggesting future research directions for advancing visualization lenses in 3D data exploration and analysis—across both traditional and immersive environments. In the long term, we hope that this dissertation serve valuable reference points for visualization researchers and practitioners operating at either a theoretical, design, or empirical level
Experience Design: A Human-Centered Approach to Campus Planning
No full textExperience Design: A Human-Centered Approach to Campus Planning Many small private universities are currently experiencing declining, flat, or slow undergraduate enrollment rates affecting financial stability and resulting in the risk of closure if solutions are not discovered and implemented. Instead of relying on traditional campus planning methods to solve these challenges, this doctoral thesis introduces Experience Design Master Planning. As a genesis level long-range planning tool, this novel approach focuses on the intangible experiences encountered on university campuses. XD|MP is an interactive approach to campus planning that intentionally maps design elements foregrounding the development of an enriched campus experience. This work builds on my twenty-five years of experience as an architect and planner working with a variety of universities and a diversified portfolio of master planning and design projects. Through an exploration of precedents and case studies, experience design principles are applied to the university setting. The proposed tool is developed and tested using the practice-based Design Science Research (DSR) methodology utilizing semi-structured interviews with curated key informants to guide and evaluate the creative project. DSR provides an opportunity to explore the question of how architects and planners can influence university enrollment through planning and design of the physical environment. The XD|MP toolkit is a flexible, adaptable, and practical solution that works through a systematic framework to create awareness and value to constituents. The contribution of this research enables a more holistic design approach toward human-centered campus planning inspiring universities to create more meaningful and memorable experiences for potential and current students, as well as faculty, administration, and staff. Experience Design Master Planning (XD|MP) positions the architect and planner to influence university enrollment through its ability to connect the intangible human experience to the tangible physical environment. Keywords: campus planning, experience design, experience design master planning, human-centered design, intangible, master planning, sense of belonging, sense of community, sense of connectedness, sense of distinction, sense of place, sense of purpose, XD|M
Total Suspended Solids Impact on the Stress Response and Swimming Performance of Fish
No full textTotal suspended solids (TSS) levels are subject to daily fluctuations in major waterways like the Bow River that flows through the City of Calgary. TSS can negatively impact the aquatic environment by increasing water temperatures, decreasing dissolved oxygen contents, decreasing foraging abilities, and causing behavioural changes in fish. These behavioural changes include foraging, aggression, and increased gill flaring in fish. Behavioural changes are associated with stressful events and have been well studied previously with TSS. This project aims to build on previous studies by measuring sublethal indicators of stress, including hormonal and metabolic endpoints such as cortisol, glucose, glycogen, and lactate in response to TSS exposure in several species of fish. We hypothesized that TSS exposure will elicit a hormonal and metabolic stress response indicative of metabolic adjustments to cope with the stressor. To test this hypothesis, we exposed 5 different fish species, including rainbow trout (Oncorhynchus mykiss), brook trout (Salvelinus fontinalis), cutthroat trout (Oncorhynchus clarkii), longnose dace (Rhinichthys cataractae), and fathead minnows (Pimephales promelas) to 0, 50, 100, 500, and 1000 mg/L of TSS for 96 h. The fishes in this study did not show any significant effects on the hormonal or metabolic stress response. To further assess if the fitness of the fish were impaired by TSS exposure, salmonids (rainbow trout, brook trout) and cyprinids (fathead minnows, longnose dace) were subjected to a 3-min air stressor post-TSS exposure to determine their stress performance. The salmonids and cyprinids elicited a stress response to the acute stressor; however, there were alterations in the cortisol and glucose response to the stressor in the cyprinid fish but not salmonids, suggesting species-specific stress responsiveness to TSS exposure in fishes. We also tested how TSS exposure impacted the swimming performance of rainbow trout by exposing them to 0 or 100 mg/L of TSS for 7-d, then measuring cortisol, metabolites, and global metabolites with and without swimming. A subset of the fish exposed to TSS were allowed to recover for 3-weeks in clean water and the same endpoints were analyzed except for the global metabolites. We found that TSS significantly effected many metabolic endpoints in conjunction with swimming, and the fish’s metabolic scope was significantly reduced by TSS exposure. However, trout were able to recover from many of these effects after 3 weeks in clean water. Our results suggest that the TSS exposure affects the stress performance of fishes, including altered tissue metabolic capacity and swimming performance in rainbow trout. Overall, TSS exposure has the potential to reduce the fitness of fish to cope with other environmental challenges, including predator avoidance and climate warming, but this may be dependent on the concentration and duration of exposure
Electrotactile Tongue Interface for Human-Computer Interaction and Robot Teleoperation
No full textBy exploiting the tongue’s exceptional density of nerve endings and low-threshold electrical response, electrotactile tongue displays provide a precise, low-power sensory-substitution pathway for teleoperated robotic systems. This approach addresses the persistent lack of effective haptic sensation in Robot Assisted Surgery (RAS) which recognized as a critical limitation. In this thesis, we introduce TactTongue, a modular electrotactile tongue-display toolkit with a simplified high-level user interface for rapid prototyping of electrotactile tongue stimulation (ETS). Building on previous works that informed the design of a flexible electrotactile tongue display, we investigate: (1) the efficacy of ETS for delivering force feedback during teleoperated manipulation tasks; (2) the design requirements and user-interface (UI) design to support rapid prototyping; (3) the potential for tongue-gesture input and applications; and (4) how tongue-based feedback can be compared to kinesthetic haptics during robot-assisted needle-insertion task. First, we evaluated ETS in an egg-lifting teleoperation task under visual-only and tongue-stimulation conditions, demonstrating potential or higher control accuracy with tongue feedback compared to vision alone. Building on these results, we refined the hardware and UI into a compact, modular TactTongue toolkit that lowers entry barriers for both researchers and practitioners. Moreover, we show a diverse set of application demonstrators—from accessibility aids with touch input and medical‐surgery overlays to extended‐reality, taste and texture rendering—highlighting the platform’s versatility beyond the force feedback. Drawing on insights from these early studies, in ongoing work, we explore integration of electrotactile tongue stimulation with kinesthetic haptic device to enhance force perception during robot assisted needle insertion in soft tissue. These findings validate TactTongue’s design, establish UI guidelines for rapid prototyping of tongue-based interfaces, and suggest a promising multimodal feedback paradigm for preciser RAS
Behavioural and neurological correlates of cognitive map training in children
No full textSpatial cognition is important for everyday functioning, from simple tasks such as moving around a house to more complex undertakings like navigating unfamiliar cities. Research has shown that children between the ages of 10 and 13 undergo critical developmental shifts in their ability to form and utilize cognitive maps (i.e., mental representations of large-scale environments). Although lower-order spatial skills (for example, mental rotation) have been well-studied, less is known about how higher-order navigation and cognitive mapping might be enhanced both behaviourally and neurologically in children through targeted training. To address this gap, the present dissertation integrates three major aims. The first aim maps the landscape of electroencephalography (EEG) studies on human navigation, synthesizing the research on complex, large-scale wayfinding investigated by EEG. This methodological overview (Chapter 2) illustrates the potential of EEG to capture real-time neural correlates of spatial navigation. The second aim examines whether specialized cognitive map training elicits measurable neural changes in children aged 10 to 13. Using a two-week intervention (~7.5 hours total) in a virtual “town” environment, the thesis shows shifts in children’s resting-state EEG (particularly in frontal frequency bands) compared to a control group engaged in a non-navigational video game (Chapter 3). These findings suggest that short-term, game-based spatial training can result in changes to EEG activity in late childhood. The third aim probes the behavioural changes associated with this training, with an emphasis on possible sex differences (Chapter 4). While girls in the experimental group showed significant improvements to cognitive mapping ability following training, an unexpected performance increase in the male control group highlights the nuanced and context-dependent nature of sex differences during spatial interventions. Collectively, these studies provide preliminary evidence that higher-order spatial cognition in children is not only malleable but also linked to real neurophysiological changes. They further underscore how video game-inspired training designs can function as accessible, engaging, and effective platforms for enhancing navigational skills. Given the small sample and exploratory analyses, results should be viewed as preliminary and hypothesis‑generatin
Evaluating Force-based Haptics for Immersive Tangible Interactions with Surface Visualizations
No full textHaptic feedback provides an essential sensory stimulus crucial for interaction and analyzing three-dimensional spatio-temporal phenomena on surface visualizations. Given its ability to provide enhanced spatial perception and scene maneuverability, virtual reality (VR) catalyzes haptic interactions on surface visualizations. Various interaction modes, encompassing both mid-air and on-surface interactions, with or without the application of assisting force stimuli, have been explored using haptic force feedback devices. In this thesis, we evaluate the use of on-surface and assisted on-surface haptic modes of interaction compared to a no-haptic interaction mode. A force-based haptic stylus is used for all three modalities; the on-surface mode uses collision based forces, whereas the assisted on-surface mode is accompanied by an additional snapping force. We conducted a within-subjects user study involving fundamental interaction tasks performed on surface visualizations. Keeping a consistent visual design across all three modes, our study incorporates tasks that require the localization of the highest, lowest, and random points on surfaces; and tasks that focus on brushing curves on surfaces with varying complexity and occlusion levels. Our findings show that participants took almost the same time to brush curves using all the interaction modes. They could draw smoother curves using the on-surface interaction modes compared to the no-haptic mode. However, the assisted on-surface mode provided better accuracy than the on-surface mode. The on-surface mode was slower in point localization, but the accuracy depended on the visual cues and occlusions associated with the tasks. Finally, we discuss participant feedback on using haptic force feedback as a tangible input modality and share takeaways to aid the design of haptics-based tangible interactions for surface visualizations
Active chromatin marks and up-regulation of FOXC1 in uterine epithelial cells demarcate the onset of reproductive decline in aging females
No full textAdvanced maternal age increases the risk of pregnancy complications due, in part, to changes in the uterine environment. Here, we show that uterine aging in mice is associated with a progressive increase in transcriptional variation, accompanied by a notable accumulation of activating histone marks at multiple genomic loci. Importantly, the transcriptional signatures of uterine aging differ substantially from senescence markers associated with organismal aging. We demonstrate that maternal age-induced effects largely originate in the epithelial compartment and entail a dramatic up-regulation of the pioneer transcription factor FOXC1, combined with a hyper-enrichment for H3K27ac and H3K4me3 across the locus. FOXC1 over-expression in human endometrial epithelial cells causes profound transcriptomic shifts and increased proliferation, recapitulating the aging phenotype. Using endometrial epithelial organoids of young and aged mice, we find that aging hallmarks including Foxc1 up-regulation and epithelial H3K27ac hyper-enrichment are conserved in vitro. Recapitulating the epithelial hyperplasia phenotype seen in vivo, endometrial epithelial organoids from aged mice are larger and mis-express key factors, such as SOX9, critical for uterine gland maturity and function. Collectively, our data highlight the susceptibility of uterine epithelial cells to early-onset aging, demarcated by an increase in activating epigenetic marks that converge on the mis-regulation of FOXC1.FUNDING STATEMENT
This work was supported by Canadian Institutes of Health Research (CIHR) project grant PJT-174982 to M.H. and W.D., by BBSRC-NC3R ageing project grant BB/S002995/1 to H.C. and M.H., by a Tier I Canada Research Chair in Developmental Genetics and Epigenetics (CRC-2018-00240) to M.H., by the UK Biotechnology and Biological Sciences Research Council grant BBS/E/B/000C0423 to G.D.K., by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant RGPIN-2021-02417 to M.H., and by funds of the Alberta Children’s Hospital Research Institute grant ACHF22-0911 to M.H. and W.D.Canadian Institutes of Health Research (CIHR)Natural Sciences and Engineering Research Council (NSERC)Othe
The Role of the Gold Coast Brigade in the East African Campaign of the Second World War-(1940-1941)
No full textOriginating in the late 19th century as a small colonial force, the Gold Coast Regiment (GCR) initially focused on internal security and protecting the colony against external aggression. Following its operations in the First World War, the GCR was expanded, reorganized and retooled in the late 1930s. When the Second World War began in September 1939, the GCR was upgraded to a brigade and deployed as part of the West African Expedition Force to East Africa in 1940. In collaboration with other British Imperial forces, the Gold Coast Brigade played a significant role in defeating Italian troops, thus thwarting Benito Mussolini’s expansionist designs and securing Britain’s key sea lines of communication (SLOC) via the Red Sea and the Suez Canal. This study uses primary sources from the UK National Archives at Kew and the Imperial War Museum to examine the Gold Coast Brigade’s role in Allied campaigns in East Africa, focusing on the brigade’s initial engagements in Kenya’s northern frontier districts and the El Wak raid, the Juba River crossing, the battle of Wadera and operations in the southern Ethiopian highlands
Exploring the Unique and Shared Proteolytic Properties of Calpain-1 and Calpain-2
No full textCalpain-1 (µ-calpain) and calpain-2 (m-calpain) are ubiquitous Ca²⁺-dependent cysteine proteases with overlapping and divergent roles in human cells that remain incompletely defined. This research leverages a genetic knockout model in HCT116 colon-carcinoma cells, coupled with proteomics and immunofluorescence microscopy, to chart the substrate landscapes of each isoform and relate proteolysis to subcellular distribution. Wild-type, CAPN1-/- and CAPN2-/- lines were incubated with a calcium ionophore to permit acute calpain activation; wholeproteome and N-terminal peptide fractions were analysed by liquid chromatography and tandem mass spectrometry (LC-MS/MS), and spatial distributions were visualised by immunofluorescence confocal microscopy. Quantitative N-terminomics and proteomics revealed 69 calpain-1 substrates, 41 calpain-2 substrates, with 23 shared cleavage substrates, representing proteins implicated in signalling, cytoskeletal and metabolic proteins previously unlinked to calpain biology. Visualisation of calpain distribution within colon cancer cells by immunofluorescence microscopy identified spatial differences between calpain-1 and calpain-2. Our results demonstrate the capacity for our techniques to be applied to studying protease distribution and reveal novel unique characteristics of calpain-1 and -2. These insights refine the longstanding view of calpains as interchangeable effectors, demonstrating instead that each isoform occupies a distinct biochemical and spatial niche in colorectal cancer cells. The work establishes a curated substrate catalogue, iv identifies cleavage-site motifs for future prediction algorithms, and lays experimental groundwork for isoform-selective therapeutic targeting