McMaster University

Background For many diseases, early diagnosis and treatment are more cost-effective, reduce community spread of infectious diseases and result in better patient outcomes. However, healthcare-seeking and diagnoses for several diseases are unnecessarily delayed. For example, in 2022, 3 million and 5.6 million people living with tuberculosis (TB) and HIV, respectively, were undiagnosed. Many patients never access appropriate testing, remain undiagnosed after testing or drop out shortly after treatment initiation. This underscores challenges in accessing healthcare for many individuals. Understanding healthcare-seeking obstacles can expose bottlenecks in healthcare delivery and promote equity of access. We aimed to synthesise methodologies used to portray healthcare-seeking trajectories and provide a conceptual framework for patient journey analyses. Design/methods We conducted a literature search using keywords related to “patient/care healthcare-seeking/journey/pathway analysis” AND “TB” OR “infectious/pulmonary diseases” in PubMed, CINAHL, Web of Science and Global Health (OVID). From a preliminary scoping search and expert consultation, we developed a conceptual framework and honed the key data points necessary to understand patients’ healthcare-seeking journeys, which then served as our inclusion criteria for the subsequent expanded review. Retained papers included at least three of these data points. Results Our conceptual framework included five data points and seven related indicators that contribute to understanding patients’ experiences during healthcare-seeking. We retained 66 studies that met our eligibility criteria. Most studies (56.3%) were in Central and Southeast Asia, explored TB healthcare-seeking experiences (76.6%), were quantitative (67.2%), used in-depth, semistructured or structured questionnaires for data collection (73.4%). Healthcare-seeking journeys were explored, measured and portrayed in different ways, with no consistency in included information. Conclusions We synthesised various methodologies in exploring patient healthcare-seeking journeys and found crucial data points necessary to understand challenges patients encounter when interacting with health systems and offer insights to researchers and healthcare practitioners. Our framework proposes a standardised approach to patient journey research.

We establish the spacetime Penrose inequality in spherical symmetry in spacetime dimensions n + 1 ≥ 3 with charge and cosmological constant from the initial data perspective. We also show that this result extends to the Gauss-Bonnet theory of gravity.

INTRODUCTION Oxidative stress (OS) is implicated in dementia. While elevated peripheral OS biomarkers were observed in vascular mild cognitive impairment (vMCI), the role of central antioxidants remains unclear. We assessed levels of the major brain antioxidant glutathione (GSH) in vMCI compared to cognitively normal coronary artery disease (CAD) controls (CN). METHODS In vivo tissue‐corrected GSH in the anterior cingulate cortex (ACC) and occipital cortex (OC) were quantified in persons with vMCI and CN using MEscher–GArwood Point RESolved magnetic resonance Spectroscopy. RESULTS Among participants (vMCI, n = 22, age [mean ± SD] = 67.4 ± 7.3; CN, n = 21, age = 66.7 ± 7.8), ACC‐GSH (i.u. ± SD) was higher in vMCI (4.42 ± 0.59) versus CN (3.72 ± 1.01) (Z = −2.5, p = .01), even after controlling for age and sex (B [SE] = 0.74 [0.26], p = .007). Increased ACC‐GSH correlated with poorer executive function (EF) (B [SE] = −0.31 [0.14], p = .04). OC‐GSH showed no effect. DISCUSSION Higher ACC‐GSH in vMCI may reflect a compensatory response to OS. ACC‐GSH was negatively correlated with EF, suggesting a linkage between regional brain antioxidants and disease‐relevant cognitive domains. Highlights Brain GSH was measured in vascular MCI and matched controls using MEGA‐PRESS. In contrast to GSH deficits in AD, anterior cingulate GSH was elevated in vMCI. Brain GSH was correlated with disease‐relevant cognitive domains in vMCI. The GSH antioxidant system may be etiologically implicated in vMCI.

Background The LoDoCo2 (Low‐Dose Colchicine 2) trial showed that colchicine reduced the risk for cardiovascular events in patients with chronic coronary syndrome. Current guidelines recommend colchicine use in selected high‐risk patients. The aim of this secondary analysis was to explore the relative and absolute benefits of colchicine according to baseline risk. Methods The LoDoCo2 trial randomized 5522 patients to colchicine 0.5 mg or placebo. The primary end point was a composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia‐driven coronary revascularization. First, a LoDoCo2 risk score was developed by Cox regression to identify high‐risk features for the primary end point. Second, the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention was applied to explore robustness of findings. Results In the LoDoCo2 risk score, high‐risk features were age ≥75, diabetes, and current smoker. In high‐risk (≥1 high‐risk feature), compared with low‐risk (0 high‐risk features) patients, colchicine was associated with consistent relative (high risk: hazard ratio [HR], 0.72 [95% CI, 0.56–0.94] versus low risk: HR, 0.67 [95% CI, 0.52–0.88]; P for interaction=0.73) and absolute benefits (high risk: HR, −1.33 [95% CI, −2.38 to −0.27] versus low risk: HR, −0.93 [95% CI −1.57 to −0.30] events per 100 person‐years). Using the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention, consistent relative and absolute benefits were found in high‐, intermediate‐, and low‐risk patients. Conclusions In patients with chronic coronary syndrome, the relative and absolute benefits of colchicine were consistent in those at high, intermediate, and low risk for cardiovascular events. These findings support the use of colchicine across the spectrum of baseline risk. Registration URL: https://www.anzctr.org.au ; Unique identifier: 12614000093684.

Objectives Non-suicidal self-injury (NSSI) is a common behaviour in youth with mental disorder and in the general population. While NSSI is an important predictor of suicide attempts, not all youth with NSSI experience this outcome. The objective of this study is to report on the overlap between NSSI and suicidal ideation or attempt among Canadian youth self-reporting these behaviours in the general population to define a group of youth who engage in NSSI alone. This group of youth may represent a unique clinical phenotype. Methods We used data from 14–17 year olds ( N = 2,576) from the 2014 Ontario Child Health Study, a province-wide, cross-sectional, epidemiologic study of child health and mental disorder. Based on their responses to questions about past year experiences of suicidal thoughts and behaviours including NSSI, 6 mutually exclusive groups were created reflecting their differing profiles of suicidal thoughts and behaviours. These groups were compared to each other on socio-demographic and symptom characteristics. Results A total of 9.2% of youth reported NSSI, and half of these youth endorsed NSSI alone (without suicidal ideation or attempts). Both groups had significantly more females. Compared to other groups of youth endorsing suicidal thoughts and behaviours, the NSSI alone group had lower symptoms of mental disorder in all domains except for social anxiety symptoms. They also had the lowest perceived need for help of all groups. Conclusions About half of youth who self-harm do so without suicidal intent, and some for as long as 1 year during adolescence. Further prospective study of youth with NSSI alone is needed, to determine symptom stability as well as incident more risky suicidal behaviour before recommendations regarding the appropriateness of minimal medical or psychological intervention for youth who engage in this behaviour can be considered. There also are important sex differences in NSSI that deserve additional prospective study.

In modern society, with the accelerating pace of urbanization and the increasing frequency of global travel, densely populated areas have become hotspots for the outbreak of infectious diseases. These areas, such as large-scale urban centers and crowded public transportation hubs, facilitate the rapid spread of pathogens. The patients affected by infectious diseases span a wide spectrum of different groups, including the elderly with weakened immune systems, children whose immune systems are still developing, and individuals with pre-existing chronic health conditions. The impact of infectious diseases on patients varies significantly. Depending on a patient's underlying health condition, the course of the disease can range from a mild, self-limiting illness to a severe, life-threatening condition. For example, in the case of influenza, some healthy individuals may experience only mild symptoms like a runny nose and mild fever, while the elderly or those with respiratory diseases may develop severe pneumonia, which can be fatal. In the context of the ongoing global health challenges, such as the COVID - 19 pandemic, there is an urgent need to explore innovative methods for predicting the risk of patients infected by infectious diseases. To demonstrate whether machine learning techniques can be effectively used for this purpose, this study employs neural networks to develop a model specifically designed to predict the risk of death among COVID-19 patients. Through rigorous testing and validation, the model has been proven to have a high degree of accuracy in predicting these risks. This indicates that the method proposed in this study can be applied to identify which patients have a more urgent need for medical resources, thus providing valuable reference for healthcare providers to optimize the allocation of healthcare resources.

Objective: Targeted alpha-particle therapy (TAT) is a promising approach for treating metastatic cancers, utilizing alpha-emitting radionuclides conjugated to tumor-targeting molecules. Actinium-225 (²²⁵Ac) has emerged as a clinically relevant candidate due to its decay chain, which produces four successive alpha emissions, effectively damaging cancer cells. However, the nuclear recoil effect can lead to off-target redistribution of decay daughters, complicating dosimetry and increasing potential toxicity. This study aims to address these challenges by developing a direct alpha spectroscopy method for in vitro investigations of ²²⁵Ac radiopharmaceuticals. Approach: We developed the Bio-Sample Alpha Detector (BAD), a silicon-based detector designed to operate under ambient conditions, enabling direct alpha spectroscopy of cell samples. AR42J rat pancreatic tumor cells, which express somatostatin receptor 2 (SSTR2), were incubated with [²²⁵Ac]Ac-crown-TATE, [²²⁵Ac]Ac-PSMA-617, and [²²⁵Ac]Ac³⁺. The BAD setup allowed radiolabeled cell samples to be positioned within 100 µm of the detector for alpha spectra acquisition with statistical uncertainties of less than 1% in count rates. Geant4 Monte Carlo simulations were employed to validate the experimental results. Main Results: Distinct spectral differences between radiolabeled cells and reference samples confirmed the uptake of [²²⁵Ac]Ac-crown-TATE by AR42J cells. Detection of ²¹³Po, a decay daughter of ²²⁵Ac, indicated partial retention and release of decay products from cells, providing insight into intracellular retention and radionuclide redistribution. Geant4 simulations confirmed the alignment of experimental data with theoretical predictions. Significance: This study introduces a novel method for directly measuring the behaviour of ²²⁵Ac and its decay daughters in biological samples using alpha spectroscopy. The BAD setup provides a valuable tool for investigating radionuclide retention, redistribution, and microdosimetry in radiopharmaceutical research.

Endurance and resistance exercise lead to distinct functional adaptations: the former increases aerobic capacity and the latter increases muscle mass. However, the signalling pathways that drive these adaptations are not well understood. Here we identify phosphorylation events that are differentially regulated by endurance and resistance exercise. Using a model of unilateral exercise in male participants and deep phosphoproteomic analyses, we find that a prolonged activation of a signalling pathway involving MKK3b/6, p38, MK2 and mTORC1 occurs specifically in response to resistance exercise. Follow-up studies in both male and female participants reveal that the resistance-exercise-induced activation of MKK3b is highly correlated with the induction of protein synthesis (R = 0.87). Additionally, we show that in mice, genetic activation of MKK3b is sufficient to induce signalling through p38, MK2 and mTORC1, along with an increase in protein synthesis and muscle fibre size. Overall, we identify core components of a signalling pathway that drives the growth-promoting effects of resistance exercise.

The gait index (GI), a valuable metric to assess human gait, incorporates clinically relevant parameters such as walking speed, knee angle, stride length, and stance-to-swing phase ratio. This index offers insights into an individual's gait pattern, aiding in the identification of subtle gait abnormalities and enabling continuous monitoring of gait changes over time. Building upon this foundation, the present study investigated the influence of specific gait parameters and demographic factors on the gait index, alongside their interaction effects. Analyzing data from 120 healthy individuals using beta regression models, we uncovered significant predictors and interaction effects shaping the Index. Our comparative assessment between Variable Dispersion Beta Regression (VDBR) and Fixed Dispersion Beta Regression (FDBR) models revealed VDBR's superiority over FPBR in capturing gait data heterogeneity. Our analysis revealed that while aging was correlated with decreased GI, gender and BMI exhibited limited individual impact. However, gait-specific predictors such as knee angle, stride length, walking speed, and stance-to-swing phase ratio significantly contributed to GI variability. Additionally, significant interaction effects were identified between knee angle and height normalized stride length, age and knee angle, and age and walking speed, highlighting the complex interplay between demographic and gait-related factors. These findings underscore the multifaceted nature of gait dynamics and offer valuable insights for clinicians, aiding in precise gait pattern assessment and informing the development of gait-related clinical practice, preventive care strategies, and rehabilitation programs. Overall, our research contributes to enhancing mobility and functionality in individuals with gait degradation by identifying significant predictors and interaction effects.

The CARD system (Comfort Ask Relax Distract) is a protocol for vaccine delivery that includes interventions that facilitate vaccine recipient coping and improve the vaccination experience. CARD was compared to control (usual care) in a pragmatic hybrid effectiveness-implementation cluster randomized trial. Of 25 participating community pharmacies, 12 were randomized to CARD and 13 to control for all vaccines administered between November 2023 and January 2024. Implementation strategies planned to support CARD integration included an educational webinar, customized implementation recommendations, change equipment, online chat group, and audit and feedback. Educational outreach was added to improve intervention fidelity. This paper reports on implementation outcomes of the trial. Provider surveys and focus groups revealed acceptability and feasibility of CARD and implementation strategies. Vaccinators in CARD pharmacies (vs. control) reported higher satisfaction with vaccine recipient interactions and that overall, CARD was time neutral. They also reported higher utilization of some CARD-recommended injection techniques. Administrative data verified utilization of the CARD coping checklist, which solicits vaccine recipient coping preferences, in 96% of vaccine recipients that participated. Post-vaccination feedback surveys were available for 90% of vaccine recipients that participated. Implementation results were aligned with trial effectiveness outcomes, and support routine use of CARD in community pharmacies. Trial registration : NCT06098703

In the late 1930s, children in three Malawian villages were subjected to a peculiar test for vitamin A deficiency devised by Dr. Benjamin Platt, director of the Nyasaland Nutrition Survey and a leading colonial nutrition scientist. Platt constructed a makeshift adaptometer, appropriate for field conditions, that could be placed over a subject’s head to measure retinal adaptation to light. He built this contraption from simple materials, including a five-pound tea-box and sticking plaster. This article takes the curious commingling of commodity objects and scientific materials (where a discarded tea-box finds new life as an experimental technology) as an entry point for examining how scientific practices are woven from semiotic and material threads, demonstrating how heterogeneous social and material elements overlap and influence one another. The article first analyses how Platt’s tea-box adaptometer – and the discourses and ambitions framing the Survey – imagined a new kind of nutrition research hinged to the space of the field rather than the laboratory. It then proceeds to consider how the tea-box, an incipient manifestation of ‘appropriate technology’, points us towards the more tacit ways that tea wove itself into the fabric of the Survey and colonial society, as a gustatory discourse steeped in racial anxieties. Attending to the ‘stuff’ of scientific work cued me to broader imperial circuits and interests that shaped colonial nutrition research.

Forests significantly influence regional and global water cycles through transpiration, which is affected by meteorological variables, soil water availability, and stand and site characteristics. Variable retention harvesting (VRH) is a forest management practice in which varying densities of trees, such as 55% and 33%, are retained after thinning or harvesting. These trees can be grouped together or evenly distributed. VRH aims to enhance forest growth, improve biodiversity, preserve ecosystem functions, and generate economic revenue from harvested timber. Application of VRH treatment in forest ecosystems can potentially impact the response of forest transpiration to environmental controls. This study analyzed the impacts of four different VRH treatments on sap flow velocity (SV) in an 83‐year‐old red pine (Pinus resinosa Ait.) plantation forest in the Great Lakes region in Canada. These VRH treatments included 55% aggregated (55A), 55% dispersed (55D), 33% aggregated (33A), and 33% dispersed (33D) basal area retention, and an unharvested control (CN) plot, 1 ha each. Analysis of counterclockwise hysteresis loops between SV and meteorological variables showed larger hysteresis areas between SV and photosynthetically active radiation (PAR) than vapor pressure deficit (VPD) and air temperature (Tair), particularly in clear sky and warm temperatures in the summer. It demonstrated that PAR was the primary control on SV across VRH treatments, followed by VPD and Tair. Larger hysteresis loop areas and higher SV values were observed in the CN and 55D treatments, with lower values found in the 55A, 33D, and 33A plots. This suggests that maintaining dispersed retention of 55% basal area (55D) is the optimal forest management practice that can be utilized to enhance transpiration and forest growth. These findings will assist forest managers and other stakeholders to adopt sustainable forest management practices, thereby enhancing forest growth, water use efficiency, and resilience to climate change. Additionally, these practices will contribute to nature‐based climate solutions.

Objective The purpose of this review is to assess the effects of JIIM on growth and pubertal development. Methods A systematic review was conducted by searching EMBASE, MEDLINE, PubMed®, PsycINFO, Cochrane, and Web of Science to identify studies published in English from inception to December 2024. Data were extracted regarding puberty- and development-related outcomes. Meta-analyses were conducted for outcomes measured consistently across studies, using the R package metafor (Version 3.4-0). Results Of 5,838 identified unique records, 24 were included. Inter-rater reliability for abstract and full-text screening was Κ=0.93 and Κ=1.0, respectively. Eighteen articles discussed growth (14/18 demonstrated decreased height or growth failure). Meta-analysis of 7 studies noted the overall prevalence of growth failure is 17.9%, 95% C.I. [10.7-25.0]. Five articles reported delays of secondary sex characteristics or puberty. Five articles discussed age of menarche onset; 4 reported delays and one did not. Conclusion JIIM can cause several deleterious effects on development including growth failure. The impact of hormonal changes or delayed puberty has been less well studied. Endocrine abnormalities should be actively screened for and treated. Additional research is needed to assess long-term impacts.

Background Health inequities disproportionately impact equity-deserving groups, which include individuals marginalized due to race, ethnicity, Indigenous identity, sex and gender, socioeconomic status, and other social determinants of health. This qualitative study aimed to explore Canadian chiropractors’ experiences and perceptions in delivering care to equity-deserving groups and identify individual and institutional factors that may influence care delivery. Methods We utilized interpretive description for data development, sampling, collection, and analysis. Participants were recruited as part of a larger mixed-methods research study, where we conducted a cross-sectional survey assessing Canadian chiropractors' diversity and cultural competency. We used maximum variation sampling to recruit chiropractors who indicated their interest in participating in the qualitative study. Results Fourteen participants (N = 7, female) were included in this study, ranging from 28–64 years of age. We identified three major themes: 1) Perceived role of institutions to advance cultural competency , describing the approaches and strategies of professional associations and educational institutions in making changes concerning diversity, equity, and inclusion (DEI), 2) Fostering a culturally responsive clinical practice, describing factors that impact the delivery of care to equity-deserving groups (e.g. ensuring clinicians’ cultural awareness and sensitivity, promoting culturally competent behaviours, and understanding patients’ cultural values), and 3) Understanding the contextual determinants in accessing care (e.g., socioeconomic status, lack of accessibility, patient advocacy). Conclusion The results suggest that culturally congruent care involves top-down and bottom-up approaches that integrate DEI practices at institutional and clinician levels. Specifically, the incorporation of DEI training within curricula, the development of policies that foster diversity, the engagement of equity-deserving groups to understand unique cultural needs, and tailoring treatments to each patient rather than a one-size-fits-all approach.

Understanding the motion properties of cells or particles is important in microfluidic imaging applications. Motion-related analysis has proven to be a valuable tool for phenotyping particulates in biological samples. However, relying solely on trajectory features from individual cells may not always be sufficient to describe their overall motion patterns. This highlights the need for a more effective solution focusing on rotational components in movement. In this study, we developed a generalized motion pattern representation framework using deep variational embeddings to characterize biological samples with different morphology. First, we build a simplified optical setup with sufficient throughput to record sequential frames of cells containing orientational changes. Then, a self-supervised learning pipeline was developed to embed its motion pattern into a latent space. The latent variables are visualized as the generalized motion pattern to represent a sequence of consecutive frames. Finally, segment key frames of individual cells’ motion to divide a motion trajectory into consecutive sub-trajectories. Each sub-trajectory has a predefined specific meaning to be collected for downstream motion-related analysis. Our framework has been verified with two cell types with common shapes: plate-like erythrocytes and rod-like yeasts. The results demonstrate that the motion pattern representation is distinct and interpretable for these two samples. Utilized in a motion segmentation application, the represented motion achieved over 90% accuracy with unsupervised clustering, which has significantly enhanced relevant motion analysis. These promising findings underscore the practical value of our developed framework in extracting informative motion patterns for phenotyping.

Background Lifestyle or behavioural changes can help to address the burden associated with chronic diseases. However, they take time and use of multiple techniques or strategies tailored to a person’s needs. The primary objective of this study was to assess the feasibility of the Healthy Lifestyles Program (HLP), a novel 12-month complex intervention based in cognitive behavioural therapy and theories of behaviour change, delivered in a community-based setting in Hamilton, Canada. The secondary objective of the study was to explore implementation factors of the HLP. Methods This pilot pragmatic randomised controlled trial used quantitative and qualitative evaluation methods. Participants were randomly allocated to either intervention group (n = 15) or comparator group (n = 15). The intervention group attended weekly group education sessions and met with the program intervention team monthly to create and review personalized health goals and action plans. The comparator group met with a trained research assistant every three months to develop health goals and action plans. We assessed program feasibility by measuring recruitment, participation and retention rates, missing data, and attendance. Implementation was assessed in accordance with the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. Participant-directed and clinical outcome measures were analyzed for between and within group changes using Generalized Estimating Equations (GEE). Thematic analysis was conducted for qualitative data. Results Retention rate was 60% (9/15) for the intervention group and 47% (7/15) for the comparator group. Less than 1% of participant-directed and clinical outcomes were missing for those that completed the study. Participants attended an average of 29 of 43 educational sessions and 100% of one-to-one sessions. The program intervention team valued the holistic approach to care, increased time and interaction with participants, professional collaboration, and the ability to provide counselling and health support. Location accessibility was an important factor facilitating implementation. Reducing the number of psycho-social education sessions and having access to a gym could improve retention and program delivery for a larger trial. Conclusion This study demonstrated the feasibility of the HLP with minor modifications recommended for a larger trial and for the intervention.

Arterial calcification is prevalent in peripheral artery disease (PAD), especially among patients with advanced age, diabetes, or renal disease. Peripheral arterial calcium score (PACS) is an emerging tool to quantify calcification in peripheral arteries and predict outcomes such as amputation and mortality. This systematic review evaluates PACS methodologies and its association with these adverse outcomes. In a comprehensive search of Embase, MEDLINE, and PubMed from January 1991 to January 2025, 1092 studies were retrieved, of which 17 met the inclusion criteria. Computed tomography and X-ray imaging were the main imaging modalities used to detect calcification through a variety of PACS. A higher PACS was linked to increased risk of amputation and/or mortality. PACS holds potential for predicting outcomes in PAD, particularly amputation and mortality. Standardization of PACS methods is needed to enhance its clinical utility and integration into practice.