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Item type: Item , Access status: Open Access , Association between neurofilament light chain concentrations and outcomes in patients with moderate to severe traumatic brain injury: a systematic review and meta-analysis(BMC, 2026-05-04) Bouras, Marwan; Pageau, Mathieu; Gagnon, Marc-Aurèle; Costerousse, Olivier; Demers, Karolane; Grenier-Gagnon, Anouk; Isaac, Chartelin J.; Torkomyan, Tomas H.; Lauzier, François; Zarychanski, Ryan; Francoeur, Charles L.; Gerges, Peter; Abiala, Godwill; Moore, Lynne; Englis, Shane W.; Turgeon, Alexis F.Background: Moderate to severe traumatic brain injury (TBI) is associated with high rates of mortality and long-term disability. Accurate biomarkers are needed to predict longterm neurological outcomes and guide decision-making early after TBI. Neurofilament light chain (NfL), a structural protein of neurons, has emerged as a promising candidate, but its association with outcomes in this population remains uncertain. Methods: We conducted a systematic review and meta-analysis to assess the association between blood or cerebrospinal fluid NfL concentrations and outcomes in adults with moderate to severe TBI. We searched MEDLINE, Embase, Cochrane CENTRAL and Web of Science from inception to October 2025. Eligible studies included cohort studies or randomized controlled trials reporting NfL levels measured during the acute phase and reporting at least one outcome of interest. Our primary outcome was long-term neurological function, defined as the latest available Glasgow Outcome Scale (GOS) or Glasgow Outcome Scale–Extended (GOS-E) score, dichotomized into unfavorable (GOS ≤ 3 or GOS-E ≤ 4) and favorable (GOS > 3 or GOS-E > 4). Mortality, at any time point, was a secondary outcome. Risk of bias was assessed using an adapted scale from the QUADAS-2 tool, and certainty of evidence was evaluated using GRADE criteria. Results: Fourteen studies (2,905 participants) were included, with ten (n = 1,648) contributing to the meta-analysis for our primary outcome. Higher NfL concentrations were associated with unfavorable neurological outcomes, with moderately higher levels in patients with poor outcomes compared with those with favorable outcomes (SMD 0.45, 95% CI 0.33–0.56; I² = 12%). Six studies (n = 483) assessed mortality; higher NfL concentrations were associated with increased mortality (SMD 0.71, 95% CI 0.04–1.39; I² = 82%), with a more consistent association when NfL was measured within 24 h after injury (I² = 0%). The certainty of evidence was graded as very low for both outcomes, reflecting risk of bias and, for mortality, additional inconsistency and imprecision. Conclusions: Higher NfL concentrations were associated with unfavorable neurological outcomes after moderate-to-severe TBI. The association with mortality was more uncertain and should be interpreted with caution given the substantial heterogeneity across studies. Its incremental prognostic value beyond known predictors remains uncertain. Trial registration: PROSPERO CRD42022332110, 22 May 2022.Item type: Item , Access status: Open Access , Impact of risk mitigation measures on oral fluoroquinolone prescribing: a multi-site population-based Canadian cohort study(BMC, 2026-03-25) Lix, Lisa; Dahl, Matthew; St-Jean, Audray; Golandouz, Hassan M.; Ling, Vicki; Janzen, Donica; Ronksley, Paul E.; Scory, Tayler D.; Dutton, Daniel J.; Manning, Devin; Carney, Greg; Perras, Christine; Ernst, PierreBackground: Use of fluoroquinolones (FQs), broad-spectrum antibiotics, has been linked to adverse health outcomes and resulted in safety warnings by regulatory agencies worldwide. We tested the effect of Canadian risk mitigation measures (RMMs) introduced in January 2017 on FQ prescription rates. Methods: We conducted a retrospective multi-site cohort study using administrative data from six Canadian provinces. The cohort included adults (18 + years) with outpatient prescriptions for four oral systemic FQs (ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin) between 2008 and 2022. Overall FQ prescription rates and percentage of FQ prescriptions for three antibiotic indications (acute bacterial sinusitis [ABS], acute exacerbation of chronic obstructive pulmonary disease [AECOPD], urinary tract infection [UTI]) were assessed before and after RMMs were introduced. Segmented generalized linear models were applied to monthly prescription rates and percentages for: (1) pre-RMM (January 2008-December 2016; reference), (2) post-RMM pre-COVID (January 2017-Feburary 2020), and (3) post-RMM within-COVID (March 2020-December 2022) segments. We estimated province-specific relative rates (RR) for the post-RMM segments and slope coefficients for pre- and post-RMM segments and their 95% confidence intervals (CIs) and pooled them using random-effects models. Results: Crude annual FQ prescription rates decreased from 107.5 to 45.0 per 1,000 population over the study period; in the pre-RMM segment, age- and sex-adjusted rates decreased an average of 0.30 per 1,000 population per month (95% CI: 0.19–0.41); province-specific estimates of decrease ranged from 0.16 to 0.48. The pooled RR for the post-RMM pre-COVID segment was 0.50 (95% CI: 0.43–0.59); the post-RMM within-COVID segment pooled RR was similar (RR = 0.38; 95% CI: 0.29–0.50). The decline in percentage of FQ prescriptions post-RMM pre-COVID was largest for UTI (pooled RR = 0.32, 95% CI: 0.25–0.41), followed by ABS (RR = 0.41, 95% CI: 0.34–0.51) and AECOPD (RR = 0.51, 95% CI: 0.37–0.69), although there was variation across provinces. Conclusions: Canadian RMMs for FQ use were associated with a decrease in prescription rates overall and for three indications, although rates had begun to decline before RMMs were introduced and the magnitude of decrease varied across provinces. Safety warnings tailored to specific indications and regional practices may be needed to address variation in FQ prescribing. Trial registration: HMA-EMA catalogue of real-world data studies (Study ID: 108,049).Item type: Item , Access status: Open Access , Are current practices best practices? Examining how forensic psychologists assess individuals with limited English proficiency(2026-06-05) Aminot, Katérine; Chung-Fat-Yim, Ashley (Psychology); Sobkow, Kasmira (Clinical Health Psychology); Nijdam-Jones, AliciaBackground: Psycho-legal evaluations can inform life-changing outcomes for defendants. Therefore, psychologists must consider potential impacts of cultural and linguistic diversity to avoid misidentifying the psychological needs of individuals with limited English proficiency (LEP). Studies indicate that multilingual clinicians report having higher cultural knowledge and awareness and that cultural training and cultural humility improve psychological practice; however, it is unclear whether clinical forensic psychologists engage in best practices when evaluating individuals with LEP. Objective: This study examined psychologists’ current practices for evaluating individuals with LEP in legal contexts with two primary objectives to explore: 1)forensic psychologists’ current approaches and engagement in best practices when assessing individuals with LEP and how clinician characteristics (years of experience, levels of multilingualism, cultural humility, and nationality) correlate with best practice engagement, and 2) forensic psychologists’ current training for assessing individuals with LEP and whether training differences exist based on career stage and nationality. Method: This exploratory study surveyed 88 Canadian (n = 18) and American (n = 70) forensic psychologists. Descriptive statistics were used to analyze demographics and current practices and training, and multiple linear regressions were used to examine effects of participants’ characteristics on best practice engagement and training. Results: Most participants reported using structured assessment measures and clinician-rated measures with evaluees with LEP; however, participants reported that there were no appropriately translated or normed measures available in 43.59% of evaluations. Over three-quarters of the sample indicated using an interpreter within the past 12 months, but 73.91% reported encountering challenges in working with interpreters. Best practice engagement was positively correlated with multilingualism and cultural humility, but not years of experience. Additionally, years of experience did not predict level of training received in this area. Less than half of participants reported being able to complete evaluations with LEP individuals independently and 41.18% reported not having enough training or resources to complete these evaluations. Significance: Accurate and linguistically responsive psychological assessments for individuals with LEP are integral to the proper administration of justice. Results from this study indicate a need for more validated psychological assessment measures and increased training in conducting evaluations with individuals with LEP.Item type: Item , Access status: Open Access , Development of risk prediction model for chronic pain after knee replacement surgery: protocol for an individual patient data meta-analysis(BMC, 2026-03-19) Sadeghirad, Behnam; Khalili, Malahat; Busse, Jason W.; Abdelkader, Wael; Foroutan, Farid; Mbuagbaw, Lawrence; Gilron, Ian; Khan, James; Madden, Kim; Tushinski, Daniel; Bohm, Eric; Gademan, Maaike G. J.; Poolman, Rudolf W.; Adili, Anthony; Perruccio, Anthony V.; Rampersaud, Y. R.; Righolt, Christiaan; Shanthanna, Harsha; Khaled, Maram; Gabbott, Ben; Marcucci, Maura; Zalzal, Paul; Griffin, Xavier; Schemitsch, Emil; Iorio, AlfonsoBackground: Chronic post-surgical pain (CPSP) impacts approximately one in four patients following total knee arthroplasty (TKA) and is associated with reduced function and quality of life. We will conduct a systematic review of prospective studies to identify eligible data and establish an international repository of individual patient data (IPD) on prognostic factors for chronic pain after TKA. This repository will be then used to develop and validate a prediction model for CPSP following TKA. Methods: We will identify eligible studies through a search of MEDLINE, CINAHL, EMBASE, and Cochrane CENTRAL from January 2005 to August 2025. We will include prospective studies that: (1) enrolled adults undergoing elective TKA, (2) assessed perioperative risk factors for CPSP, and (3) measured knee pain longitudinally at least 3 months post-surgery. Pairs of reviewers will independently screen titles and abstracts of retrieved citations and review the full texts of potentially eligible studies. We will reach out to principal investigators or authors of eligible studies to notify them of our initiative and request to receive their IPD into a secured repository, based on a data sharing agreement. We will use a one-stage approach for IPD meta-analysis of factors associated with CPSP following TKA, and development of a risk prediction model. Discussion: We will use anonymized de-identified data for our IPD meta-analysis. This protocol was reviewed and approved by the Hamilton Integrated Research Ethics Board (HiREB). We will develop an online calculator to support our risk assessment model for research and clinical use. This IPD meta-analysis will facilitate the development of a robust prognostic model to guide clinical decisions or enrolment in interventional studies, with the ultimate goal of identifying pathways to effective CPSP prevention strategies after TKA. Trial registration: CRD42024591329.Item type: Item , Access status: Open Access , Lessons learned: challenges in recruiting and engaging people with heavy cannabis use for online interventions in Canada(BMC, 2026-04-16) Rysen, Karli K.; Mackenzie, Corey S.; Carusone, Julian M.; Schaub, Michael P.; Wenger, Andreas; Wallbridge, Harold; Edgerton, Jason D.; Kruk, Richard; Keough, Matthew T.Background: People who seek treatment often disengage between completing screening and starting treatment. Among those who begin treatment, many have low completion of program content and are lost to follow up. Currently, little is known about predictive factors of treatment initiation and engagement. The aims of this secondary analysis of the Canadian CANreduce program were to discuss the practicality of a randomized controlled trial for online heavy cannabis use treatment and to examine predictors of treatment initiation and engagement in the Canadian CANreduce program. Method: The CANreduce intervention was pre-registered on clinicaltrials.gov for traceability (ID: NCT04965012). Statistical models were organized into three conceptual predictor groupings using baseline data: individual cannabis-specific factors, mental health and other substance use factors, and treatment belief factors. Binary logistic regressions examined which factors predicted treatment initiation in the CANreduce treatment program and multiple regression analyses examined which factors predicted percentage of the CANreduce program modules completed among participants who initiated treatment. Results: Despite following the core elements of published treatment retention protocols, challenges in recruitment were evident. Of 928 people who created a profile on the website and began screeners, 86.3% (n = 801) completed screeners. Of the 801 who completed screeners, 31.3% (n = 251) were eligible for the program. Of those eligible and assigned to active treatment, 54.3% (n = 51) assigned to the therapist condition and 45.7% (n = 43) assigned to the research assistant condition initiated treatment. Treatment initiation predictors included higher cannabis use problems score, lower family history density, increased alcohol use frequency, and more positive attitudes towards treatment. Treatment engagement (percentage of program completed) predictors included increased social motives for cannabis use and more positive attitudes towards treatment. Discussion: This secondary analysis shifts the focus from treatment efficacy to pre-treatment attrition and early engagement in an online cannabis intervention. Substantial recruitment and initiation challenges were observed, highlighting vulnerabilities in the treatment-seeking pathway before content is accessed. By identifying predictors of treatment initiation and module completion, this study offers practical “lessons learned” to inform recruitment and engagement strategies in future online cannabis trials.Item type: Item , Access status: Open Access , Examining individual differences in imagery- and simulation-based processes and their links to mental health(2026-07-09) McCheyne, Reegan; Johnson, Ed (Psychology); Greening, Steven (Psychology); Holens, Pam (Clinical Health Psychology); Felmingham, Kim (University of Melbourne); Jakobson, LornaThis dissertation explored how individual differences in the personality variables alexithymia and sensory processing sensitivity (SPS) relate to three specific cognitive-affective mechanisms that involve imagery- and simulation-based processes: motor simulation, mentalizing, and future thinking. It also addressed the question of whether accounting for these personality variables might help to explain previously reported links between these three mechanisms and symptoms of anxiety and depression. In Study 1, I assessed individuals’ use of spatial embodiment vs. motoric simulation when completing a hand laterality judgment task and whether this differed depending on endorsement of personality variables. Results of Study 1 (N = 134) supported the conclusion that people generally use spatial embodiment when processing back views of hands and motoric simulation when processing palm views; however, SPS was related to the tendency to apply motoric simulation more broadly. Alexithymia and SPS accounted for unique variance in depression and anxiety when controlling for performance variables and participant sex. In Study 2, I assessed bias in how information about another’s changing emotion is represented in working memory. Results of Study 2 (N = 145) offered preliminary support for the idea that individuals who score high (vs. low) on orienting sensitivity (a feature of SPS) display a stronger tendency to anticipate a negative shift in another’s affective state when viewing a fading expression of joy. As in Study 1, alexithymia and SPS were stronger predictors of the severity of anxiety and depression symptoms than task performance. In Study 3, I assessed how personality and mental health variables related to variables such as the vividness of cued imagery regarding future events and the tendency to experience intrusive thoughts and images and to view negative events as being likely to occur. Results of Study 3 (N = 167) suggested that facets of alexithymia and/or SPS accounted for unique variance in future thinking which, in turn, predicted the severity of symptoms of anxiety and depression. Implications for clinical practice and future directions were discussed.Item type: Item , Access status: Open Access , Antibody Validation as a tool to study “Synaptic Adhesion Proteins”(2026-03) Ameena, Nabiha; Stacey, Joy (Biological Sciences); Siddiqui, Tabrez; Balci, FuatHistorically there has been an absence of reliable and validated antibodies against synaptic adhesion proteins, particularly neurexins and neuroligins. This has led to the failure of the vital experiments that study the function of these synaptic proteins, leading to wastage of time and expensive resources. My project validated antibodies against neurexins and neuroligins through the process of immunoprecipitation, which pulls the protein of interest, followed by the process of western blot to visualize the results. The results indicated that the antibodies against β isoforms across the three neurexins performed better. Similarly, antibodies against Nlgn 2 and Nlgn 3 showed consistent bands congruent with the molecular weight of neuroligin. This project also investigated the role of Nrxn1γ, an isoform of neurexin1, in maintaining the excitatory-inhibitory balance between synapses that is required for optimal synaptic function. Collectively, these findings not only establish a dependable set of antibodies for probing neurexin and neuroligin biology but also underscore Nrxn1γ as a meaningful contributor to inhibitory synapse maintenance, strengthening both the technical and conceptual foundations for future synaptic research.Item type: Item , Access status: Open Access , First Nations culture in schools(2026-06-29) Francois, Cherie; Tamtik, Merli (Educational Administration, Foundations and Psychology); Delgado, Lucy (Educational Administration, Foundations and Psychology); Deer, FrankFirst Nations education is a relatively new area of educational concern in primary and secondary schools. If taken out of the context of Eurocentric public education and situated within a traditional First Nation’s structural conceptual framework, one can see its advancement and potential future trajectory. Eurocentric formal education, as it currently exists, is rooted in Eurocentric mainstream standards and is geared toward Eurocentric mainstream culture, greatly overlooking the uniqueness and essential elements of First Nations heritage and traditions that instill pride and esteem in its students. First Nations activism and resultant changes in policy have enhanced education; however, immersion in and development within Eurocentric mainstream contexts complicates the differentiation between Eurocentric and First Nations perspectives and their impact upon school administration and programming. Furthermore, the trauma suffered from government-enforced assimilation practices still firmly reside within the consciousness of First Nations peoples, including First Nations teachers who tend to recycle Eurocentric customs and unconsciously reinforce Eurocentric educational foundations that are damaging to FN students. This study examines both Eurocentric and First Nations cultures in relation to education, aiming to understand and map them on the medicine wheel, specifically the First Nations Education Medicine Wheel, to distinguish between them, observe progress, and identify boundaries that enable First Nations to meet the needs of their students more efficiently. The study analyzes provincial education policy frameworks through a self-developed lens of First Nations culture from my Peguis Ojibwe childhood, Cree from my travels in my northern career experiences and various traditional spiritual experiences in an effort to reflect upon their effectiveness in addressing the needs of First Nations students and teachers.Item type: Item , Access status: Open Access , The activity and kinetic mechanisms of histone lysine methyltransferases involved in cancer(2026-07-15) Ige, Oluwafolahanmi (Olufola); Davie, Jim (Biochemistry and Medical Genetics); Qi, Dake (Pharmacy); Ed, Krol (University of Saskatchewan); Lakowski, TedEpigenetic regulation of gene expression is mediated in part by chromatin-modifying enzymes that catalyze post-translational modifications on histones. Among these, histone lysine methyltransferases (KMTs) play a central role in gene regulation and are frequently implicated in disease aetiology. Despite their recognized importance, the catalytic mechanisms, substrate specificity, and kinetic activities of most histone methyltransferases remain poorly understood. In this thesis, a novel method was developed to rapidly purify recombinant histones in less than one day, providing substrates for biochemical investigation of KMTs. Using these substrates, as well as nucleosomes and modified nucleosomes, the histone methyltransferases SET7/9 (KMT7 or SETD7) and DOT1L (KMT4) were systematically characterized through substrate profiling and bi-substrate kinetic analyses. Substrate profiling was performed to define enzyme-specific residue selectivity and methylation patterns, followed by initial-rate kinetics, substrate-variation experiments, and product inhibition studies to resolve catalytic mechanisms. The methods used include mass spectrometry, proteomics and other biochemical techniques. The kinetic analyses demonstrate that SET7/9 and DOT1L exhibit distinct substrate preferences and sequential reaction mechanisms. These results establish that histone lysine methylation is controlled by intrinsic kinetic and substrate-recognition systems. This thesis provides an insight into KMT activity and mechanism and offers insights for drug discovery programs.Item type: Item , Access status: Open Access , Discovery of Antibacterial Compounds from Medicinal Plant Endophytes(2026-04) Kwiatkowski, Nadia; Kumar, Ayush (Medical Microbiology and Infectious Diseases); Lee, Jae-Hyeok (Biological Sciences); Whyard, Steve; Hausner, GeorgAntimicrobial resistance is an escalating global health threat that necessitates the discovery of new bioactive compounds. Fungal endophytes, which live asymptomatically within plant tissues, are increasingly recognized as promising sources of novel secondary metabolites with antimicrobial activity. In this study, fungal endophytes were isolated from seven medicinal plant species and screened for antibacterial activity against clinically relevant bacterial pathogens. A total of 264 morphologically distinct fungal endophytes were isolated from surface-sterilized root and leaf tissues. Initial antibacterial screening identified 58 isolates (22%) capable of inhibiting the sensitive Acinetobacter baumannii strain AB258. Antibacterial isolates were disproportionately derived from root tissues (74.1%), suggesting that roots represent a particularly rich source of bioactive endophytes. Of these active isolates, 24 demonstrated broader-spectrum activity against additional bacterial strains. Fifteen isolates producing the strongest inhibition zones were selected for crude extract preparation and secondary screening using disc diffusion assays against a bacterial panel including methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Acinetobacter spp. Several extracts exhibited multi-strain inhibitory activity, with isolates DL16, GB29, and GB2 producing the largest zones of inhibition. Three candidate isolates (GB2, LV6, and DL16) were prioritized for chemical investigation. Thin-layer chromatography revealed distinct metabolite profiles, with GB2 displaying the greatest compound separation. Consequently, GB2 was selected for further purification using flash chromatography, yielding three pure fractions. Minimum inhibitory concentration (MIC) assays of these fractions revealed relatively high MIC values (128–256 μg mL⁻¹) across tested strains, indicating limited antibacterial potency of individual compounds but suggesting potential synergistic interactions among metabolites. Overall, this study highlights the diversity of fungal endophytes associated with medicinal plants and demonstrates their potential as sources of antibacterial metabolites. These findings support continued exploration of plant-associated fungi for novel antimicrobial compound discovery.