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The Preterm Infant Gut Microbiome and Probiotics Influence Growth Rates and Synaptic Development in Gnotobiotic Mice
No full textPreterm birth increases the risk of neurodevelopmental disorders, potentially linked to impaired growth and neuroinflammation. Emerging evidence suggests that gut microbiome maturation, especially colonization by bifidobacteria, influences neurodevelopment via the gut-brain axis. However, mechanistic insights are limited by the lack of representative animal models. We investigated the impact of preterm infant-derived microbiomes on early growth and neurodevelopment by transferring fecal microbes (FMT) to germ-free C57Bl/6J mice. In one experiment, germ-free dams were colonized with fecal slurries from preterm infants with either high (>60%) or low (0%) bifidobacterial abundance (n = 5 per group). Pups were weighed on postnatal days (P)3, P5, P10, and P21. At P21, brains were collected for hippocampal immunofluorescence, and fecal microbiota sequencing was performed at both P10 and P21. In a second experiment, slurries from late preterm (+ high-bifido) or extreme preterm (+ low-bifido) infants were combined with maternal separation stress and FloraBABY probiotic treatment. Pups were weighed daily from P7 to P21; fecal microbiome sequencing was performed at P21. Across experiments, mice showed only partial colonization of donor microbiota, notably lacking bifidobacteria. In Experiment 1, high-bifido recipients exhibited reduced microbial richness at P21 (p < 0.05) and a shift in beta diversity (p < 0.001). In the context of neurodevelopment, they also had heavier brains and increased hippocampal Synapsin I (Syn1) expression (p < 0.001). In Experiment 2, mice receiving extreme preterm and probiotic treatment exhibited reduced weight gain (p < 0.05) and a shift in beta diversity (p < 0.001). Probiotic treatment also decreased alpha diversity (p < 0.05). Early-life microbiome composition was associated with prematurity-influenced growth and neurodevelopment in neonatal mice. Microbiome differences related to prematurity affected brain weight, synaptic markers, and body growth. However, the lack of bifidobacterial colonization in mice posed a key limitation of using mice to model the effects of human-specific microbiota. Probiotic treatment also unexpectedly reduced diversity and weight gain, underscoring the complexity and host-species dependence of early-life microbiome composition and responses to interventions
An Ultra-Wideband-Based Indoor Ranging and Positioning System with Wireless Synchronized Beacons Networks for Asynchronized Receivers
No full textThis thesis designs and studies an Ultra-Wideband (UWB)-based radio frequency (RF) infrastructure aimed at accurate ranging and positioning in GNSS-denied environments such as tunnels and other indoor facilities. This study evaluates the performance and reliability of UWB ranging technology in multipath-rich environments with Line-of-Sight (LOS) path clear, LOS path weak, and LOS path blocked conditions between two modules. The thesis proposes a novel Leading and Secondary beacons – Time Difference of Arrival (LS-TDOA) method for beacon-based positioning systems to eliminate synchronization requirements between beacons and receivers while mitigating clock errors to achieve a good balance in the trade-off between device compatibility, deployment convenience, and positioning accuracy. The thesis details the proposed LS-TDOA algorithm, system-level design, UWB technology selection, wireless channel analysis, and hardware implementation. The thesis provides a comparative analysis of the LS-TDOA with Two-Way Ranging (TWR) and traditional Time Difference of Arrival (TDOA) methods and highlights its efficiency. Simulation and experimental results confirm the feasibility and accuracy of the LS-TDOA approach. Finally, the thesis provides some future work suggestions focusing on scalability and performance in complex environments
Analog Phase Synchronization for Optical Aperture Synthesis using Digital Source Modulation
No full textRadio and microwave frequencies are widely used for astronomy and satellite communications globally. Increasing the size of antennas can increase data throughput, signal strength, and resolution. Aperture synthesis antenna arrays are often used in astronomy instead of larger antennas due to their design feasibility, versatility, and smaller required size per telescope. Optical-infrared (terahertz frequency) telescopes are also used for astronomy research to observe different types of astronomical phenomena; however, aperture synthesis techniques in the terahertz range are difficult to implement due to the required precision for phase-delay matching and the need for sensitive interferometric equipment. Optical beamforming and interferometry using digital source modulation (OBI-DSM) is currently being experimented with by the National Research Council (NRC) Herzberg Astronomy & Astrophysics photonics aperture synthesis exoplanet resolver (PHASER) project with the intent of demonstrating how beams from widely separated optical-infrared telescopes can be combined. Conversion from the optical domain to the analog domain is accomplished using an avalanche photo diode (APD), which is then applied to a digital system that attempts to coherently phase adjust the optical signal phase using a thermo-optic phase shifter. This research project proposes to avoid a secondary domain shift by designing an analog channel-locking loop (CLL) control system which attempts to reduce the optical path length errors of the optical signal primarily caused by atmospheric turbulence with nano-meter phase control accuracy. A phase-locked loop (PLL) is used to generate a reference signal, which is used by the CLL to phase-lock all channels coherently. A CLL is designed and experimented with in simulation software to confirm the functionality of the selected components and to optimize the loop bandwidth to reduce noise entering the system. This leads to the optimization and design of a four-channel CLL PCB through which the theoretical analysis is verified. The purpose of this project was to develop an instrumented test circuit CLL which can be used for further noise analysis and testing
Overcoming GNSS Limitations: Real-Time Locomotive Localization Algorithms in Tunnel-Like Railway Stations
No full textPositive Train Control (PTC) relies on precise locomotive location data to continuously monitor speed and track conditions, thereby reducing the risk of accidents. However, global navigation satellite system (GNSS)-based localization becomes challenging or even impossible in tunnel-like train stations, due to the obstruction of the line-of-sight (LOS) path between satellites and the locomotive receiver. This thesis employs an ul-trawideband (UWB) time difference of arrival (TDOA)-based local positioning system (LPS) within tunnel environments to replicate the localization performance typically achievable under open-sky conditions. A two-stage TDOA-based algorithm is proposed to achieve sub-meter-level positioning accuracy for loco-motives operating in a tunnel with four UWB beacons deployed. The first stage minimizes the errors caused by environmental non-line-of-sight (NLOS) conditions in epoch TDOA measurements. This approach is shown to be independent of the ground truth position, unlike most existing works. The second stage pro-cesses these refined TDOA measurements using a nonlinear least squares (NLLS) algorithm, incorporating Huber loss and grid search initialization to estimate the locomotive’s raw position estimate. Then, the po-sition estimates pass through the map-matching algorithm, which integrates tunnel and track layout data to determine the locomotive’s actual track. The accuracy of the two-stage positioning algorithm depends on the right placement of the beacons, regardless of the NLOS conditions. In that regard, the beacon posi-tions are first determined by an optimization process that runs a block-coordinate-wise minimization (BCM) algorithm to minimize the root-mean-square error (RMSE) across many sample points in the train track region, where locomotives are likely to be located. Additionally, to achieve any desired positioning accuracy (RMSE), a modified BCM algorithm that determines the minimum number of beacons to deploy and their optimal positions is also proposed in this thesis. Simulated TDOA measurements using four UWB beacons demonstrate sub-meter accuracy under various NLOS conditions, meeting the requirements of PTC systems. More importantly, the two-stage positioning algorithm achieves an average runtime of 0.8 seconds, which is well below the required one-minute PTC initialization requirement. The positioning algorithms developed in this thesis account for non-homogeneous environments where signal propagation conditions may vary from one location to another. Therefore, this thesis applies not only to locomotive position estimation but also to other indoor positioning challenges
Health status and care utilization among Afghan refugees recently resettled in Calgary, Canada between 2011–2020
No full textAbstract Background The United States and Canada have resettled over 120,000 Afghan refugees since August 2021, but sociodemographic and health status data remains sparse with investigations often limited to refugee entrance exams, standardized health screenings, or acute health settings. Methods This retrospective community-engaged cross-sectional study investigated Afghan patients who received care between January 1, 2011 and December 31, 2020 at an interdisciplinary specialized refugee clinic in Calgary, Canada that provides care to newly arrived refugees. Two reviewers independently extracted and manually verified sociodemographic factors, medical diagnoses, and clinic utilization variables from patients’ electronic medical records, then coded patient diagnoses into ICD-10 codes and chapter groups. Diagnosis frequencies were calculated and stratified by age group and sex. We corroborated these findings with Afghan refugee co-investigators. Findings Among 402 Afghan refugee patients, 228 were adults (mean age 34.2 [SD 13] years), and 174 were children (mean age 7.5 [SD 5.4] years). We identified 1535 total individual diagnoses and classified them into 382 unique ICD-10 codes. Patients had a median 2 diagnoses each [IQR 0–6], 4 clinic visits across primary, specialty and multidisciplinary care annually, and an 11% appointment no-show rate. Among adults, the most frequent diagnoses were abdominal pain (26.3%, 60/228), mechanical back pain (20.2%, 46/228), and H. pylori infection (19.3%, 44/228). Among children, the most frequent diagnoses were upper respiratory tract infection (12.1%, 21/174), Giardia (10.3%, 18/174), and short stature (7.5%, 13/174). Conclusions Recently resettled Afghan refugees in Canada were relatively young, experienced diverse health characteristics, and had multi-specialty care engagement in their first two years after arrival. These findings may guide specialized healthcare provision to this inadequately characterized but growing population of refugee arrivals in North America and elsewhere
Brodalumab for Plaque Psoriasis in the Canadian Real-World Setting: A Retrospective Cohort Analysis of up to 4 Years
No full textAbstract Introduction Psoriasis, a chronic inflammatory skin disease, affects approximately one million Canadians, with plaque psoriasis (PsO) being the most common subtype. While brodalumab has shown efficacy and safety in phase III clinical trials, Canadian real-world evidence remains limited. This retrospective cohort study aims to report on the real-world outcomes of Canadian patients with PsO who initiated treatment with brodalumab within the 4-year period following its approval by Health Canada. Methods Data from patients with PsO initiating brodalumab treatment in the Canadian patient support program between July 1, 2018 and June 30, 2022 were analyzed. The primary objective evaluated the proportion of patients achieving a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) at selected time windows. Secondary and exploratory objectives included assessing the 90% reduction in PASI score (PASI 90), changes from baseline in mean PASI, body surface area (BSA), and Dermatology Life Quality Index (DLQI) scores, as well as treatment persistence. Results A total of 2482 patients (58.5% male; mean age 51.0 years) were included, with over half being biologic-naïve (56.9%). In a subset of patients with baseline and at least one follow-up data, 66.1% and 53.2% achieved PASI 90 and PASI 100, respectively, within the first 3 months. These rates were sustained, with 68.1% and 52.2% achieving PASI 90 and PASI 100, respectively, beyond 24 months. Significant improvements from baseline were observed for PASI, BSA, and DLQI scores, and these improvements were maintained over time. Among all patients, the 1-year persistence rate was 73.4%. Conclusions This study provides valuable insights into the profile of patients treated with brodalumab in Canada. While the rapid and sustained skin clearance, as well as improvements in PASI, BSA, and DLQI scores, support the therapeutic benefits of brodalumab beyond clinical trials, further research on long-term effectiveness and safety is warranted
Extracellular vesicles derived from menstrual blood-derived mesenchymal stem cells suppress inflammatory atherosclerosis by inhibiting NF-κB signaling
No full textAbstract Background Numerous studies have highlighted the beneficial effects of mesenchymal stem cells (MSCs) in various inflammatory disorders. However, the regulatory role of MSCs in inflammatory atherosclerosis and the molecular mechanisms underlying their anti-inflammatory properties have largely remained elusive. Methods Differential ultracentrifugation was performed to isolate extracellular vesicles (EVs) released by menstrual blood-derived mesenchymal stem cells (MenSCs). An ApoE knockout atherosclerotic animal model was employed to investigate the regulatory effect of MenSC-EVs on inflammatory atherosclerosis. miRNA microarray screening analyses were conducted to identify potential effectors in MenSC-EVs that play a key role in the suppression of atherosclerosis mediated by the EVs. Results We demonstrated the remarkable potential of MenSC-EVs in alleviating atherosclerosis through the NF-κB signaling pathway. miR-574-5p serves as a crucial effector molecule transported by MenSC-EVs, suppressing endothelial inflammation and promoting nitric oxide production. This regulation contributes to the attenuation of atherosclerosis by regulating the abundance of c-Rel. The miR-574-5p/c-Rel axis shows significant clinical relevance to atherosclerosis. Conclusions This study reveals that the engineering of EVs derived from MenSCs holds significant promise as a strategic clinical approach for addressing inflammatory atherosclerosis.Highlights • MenSC-derived EVs possess an intrinsic ability to suppress inflammatory atherosclerosis. • miR-574 knockout clearly promotes atherosclerotic plaque formation. • The MenSC-EVs lacking miR-574-5p exhibit a diminished therapeutic effect on inflammatory atherosclerosis. • miR-574-5p negatively regulates NF-κB signaling through the posttranscriptional degradation of c-Rel
A qualitative investigation of the feasibility and acceptability of lower risk gambling guidelines
No full textAbstract Effective and comprehensive harm reduction strategies to mitigate gambling-related harms are needed worldwide. The development of such strategies is however resource intensive. Using existing models in multiple contexts would thus be advisable. This study is part of a larger project investigating the feasibility and acceptability of the Canadian Lower Risk Gambling Guidelines (LRGG) within a Finnish cultural context. The Canadian guidelines recommend not gambling more than 1% of one’s household income, not gambling more than 4 days per month, and to avoid regularly gambling at more than 2 types of gambling products. 13 Focus group interviews were conducted (N = 37, 23 women, 14 men) across five subpopulations: individuals gambling at no-risk/low-risk levels, individuals with past experiences of problematic gambling, concerned significant others of those with gambling problems, professional gamblers, and social workers and health care professionals. The analysis utilised a deductive approach. While the subpopulations differed in their assessment of the LRGG in some regards, we were able to synthesise three concrete suggestions to adjust the Canadian LRGGs into the Finnish context. Participants proposed rephrasing the guidelines as follows: (1) Limit gambling to a fixed percentage of monthly personal income after taxes and other fixed expenses, (2) Restrict the number and duration of weekly gambling sessions, (3) Avoid regular participation in the most harmful forms of gambling, such as online casino games. Overall, the LRGG were considered as useful also in the Finnish context. However, our results suggest that some culturally specific rewording may be advisable. The main challenge in the implementation of the LRGG is that respondents across groups considered the guidelines to be aimed at someone else. Implementation therefore requires clear communication that these guidelines are for all individuals who gamble, not only those experiencing problems
Electrical vestibular stimulation to improve balance in older adults: a pilot randomized controlled trial
No full textAbstract Background Falls are the leading cause of injury-related hospitalizations among older adults, often linked to vestibular dysfunction. While vestibular rehabilitation therapy is a standard intervention, designed to compensate for vestibular impairment with proprioceptive and visual cues, potential cumulative effects of noisy Electrical Vestibular Stimulation (nEVS) on balance improvement in older adults are not well understood. Objective This study evaluated the efficacy of cumulative nEVS dosing in improving static balance, its potential mechanisms, and clinical significance. Methods A single-blind, pilot randomized controlled trial enrolled 40 older adults (mean age: 77.7 ± 11.8 years). Participants were randomly assigned to a Stimulation group (nEVS intervention) or Sham group. The nEVS regimen included low-amplitude wideband stimulation (± 0.35 mA, 0.001–300 Hz) for 20 min, three times weekly for six weeks. Balance performance was assessed immediately before and after nEVS using a head-mounted sensor to measure physiological vibration acceleration (‘Phybrata’) power as a measure of postural stability in four conditions: Floor Eyes Open, Floor Eyes Closed, Foam Eyes Open, and Foam Eyes Closed. Follow-ups occurred at 3 months and 6 months post-intervention. Results The Stimulation group exhibited significant and sustained reductions in Phybrata power with improvements observed as early as Session 3 and persisting through 6 months in Foam EC. Additionally, the Sham group demonstrated smaller reductions in Phybrata power, potentially reflecting a learning effect. Conclusion nEVS may be a safe and effective intervention for improving balance in older adults. Its benefits in addressing age-related deficits in balance and sensory integration highlight its potential for fall prevention and rehabilitation. This study was retrospectively registered as a clinical trial on February 25, 2025 (NCT06846047)
Enhancing the Use of Building Information Modelling (BIM) to Better Enable Life Cycle Assessment (LCA) in Sustainable Architectural Practice
No full textThis dissertation examines the intersection of environmental sustainability and architectural practice through the lens of Building Information Modelling (BIM), the environmental impact potential (EIP) of building materials, and embodied carbon accounting using Life Cycle Assessment (LCA) methodology. The research focuses on evaluating the Quality Control (QC) of industry-prepared BIM models within the Canadian Architecture, Engineering, and Construction (AEC) industry, aiming to establish a practical framework for assessing model readiness in conducting BIM-based LCA. By investigating the roles of architects and sustainability consultants in early-stage design decision-making and leveraging BIM tools to facilitate LCA, the study aims to advance sustainable architectural workflows and foreground embodied carbon considerations during the design phase. A comprehensive review of current literature was undertaken to explore best practices, standards, governmental mandates, and commonly adopted tools by architectural and engineering professionals. Particular attention is given to the interoperability between BIM software (Autodesk Revit®) and LCA applications (Tally™), examining their integration to support embodied carbon accounting. The research underscores the importance of embedding sustainability into architectural design by refining QC procedures and establishing a “Systematic Evaluation Workflow” (SEW) to examine the readiness of Revit® models before conducting LCA using Tally™ to reduce environmental impact and support informed decision-making. The primary objective is to gather empirical data from architectural firms, LCA consultants, and industry-generated BIM models to identify existing gaps and provide actionable strategies for enabling BIM-based LCA. The study leverages current practices to enhance sustainable design thinking and extend early-stage decision-making frameworks within architectural workflows, thereby minimizing distractions during implementation. The methodology combines qualitative and quantitative approaches, including stakeholder interviews, model and content analysis, to assess the prevailing conditions of embodied carbon optimization among professionals in Alberta, Canada, and across North America. In addition, case studies are employed to explore the practical implementation of LCA simulations and evaluate BIM model compliance with current requirements set by Authorities Having Jurisdiction (AHJs). The findings yield key recommendations to bridge knowledge and practice gaps, enhance communication protocols, and introduce a structured QC framework (SEW) at the project’s inception, representing the dissertation’s main contribution. Results indicate that the building consulting sector possesses the capacity to adopt BIM-based LCA with minimal disruption to existing operations, demonstrating that embodied carbon assessments are not only feasible but can be seamlessly integrated into standard practice. Through these contributions, the dissertation supports the advancement of sustainable architectural practice and the cultivation of environmental stewardship within the AEC industry