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Introduction The prevalence of non-diabetic hyperglycemia (NDH) and type 2 diabetes mellitus (T2DM) is increasing. While T2DM is recognised to be associated with multimorbidity and early mortality, people with NDH are frequently thought to be devoid of such complications, potentially exposing individuals with NDH to suboptimal care. We therefore used the Discover London Secure Data Environment (SDE) dataset to appreciate the relationship of NDH/T2DM with multimorbidity, healthcare usage, and clinical outcomes.Research design and methods The dataset was retrospectively analysed between January 1, 2015 and December 31, 2020 to understand the relationship between NDH/T2DM and multimorbidity primary/secondary healthcare usage and clinical outcomes. This was compared with a cohort of individuals with thyroid disease but no NDH/T2DM.Results The dataset identified 152,384 and 124,190 adults with NDH and T2DM compared with 11,626 individuals with thyroid disease (control group). Individuals with NDH and individuals with T2DM had a high burden of disease, with only 13.1% of individuals with either NDH or T2DM not found to be suffering from at least one of the disease states of interest. The three most common comorbidities experienced by individuals with NDH were hypertension (41.4%), hypercholesterolemia (37.5%), and obesity (29.8%) compared with retinopathy (68.7%), hypertension (59.4%), and obesity (45.8%) in individuals with T2DM. Comparatively, the most common comorbidities in the control group were depression (30.8%), hypercholesterolemia (24.4%), and hypertension (17.1%). 28 (control group), 12 (NDH), and 16 (T2DM) primary care contacts per individual per year were identified, with 27,881, 282,371, and 314,880 inpatient admissions for the control, NDH, and T2DM cohorts, respectively. Prescription of drugs used to treat T2DM in individuals with NDH and T2DM was 27,772 (18.2%) and 109,361 (88.1%), respectively, accounting for approximately one in five individuals with NDH developing T2DM.Conclusion Both NDH and T2DM were associated with significant multimorbidity alongside primary and secondary care utilisation. Given the morbidity highlighted with NDH, we highlight the need for earlier detection of NDH, recognition of multimorbidity associated with both NDH and T2DM, as well as the need for the further implementation of interventions to prevent progression to T2DM/multimorbidity.

Introduction Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable. To apply and adapt implementation science for healthy cities, we have launched our mixed-methods research programme, CapaCITY/É. We aim to understand how, why and for whom sustainable transportation interventions are successful and when they are not.Methods and analysis Across nine Canadian municipalities and the State of Victoria (Australia), our research will focus on two types of sustainable transportation interventions: all ages and abilities bicycle networks and motor vehicle speed management interventions. We will (1) document the implementation process and outcomes of both types of sustainable transportation interventions; (2) examine equity, health and mobility impacts of these interventions; (3) advance implementation science by developing a novel sustainable transportation implementation science framework and (4) develop tools for scaling up and scaling out sustainable transportation interventions. Training activities will develop interdisciplinary scholars and practitioners able to work at the nexus of academia and sustainable cities.Ethics and dissemination This study received approval from the Simon Fraser University Office of Ethics Research (H22-03469). A Knowledge Mobilization Hub will coordinate dissemination of findings via a website; presentations to academic, community organisations and practitioner audiences; and through peer-reviewed articles.

Vaccinating patients receiving dialysis may prevent morbidity and mortality in this vulnerable population. The National Forum of End-Stage Renal Disease Networks (the Forum) published a revised vaccination toolkit in 2021 to update evidence and recommendations on vaccination for patients receiving dialysis. Significant changes in the last 10 years include more data supporting the use of a high-dose influenza vaccine, the introduction of the Heplisav-B vaccine for hepatitis B, and changes in pneumococcal vaccines, including the approval of the PCV15 and PCV20 to replace the PCV13 and PPSV23 vaccines. Additional key items include the introduction of vaccines against severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19), and a new vaccine to prevent respiratory syncytial virus disease. Historically, influenza and pneumococcal vaccinations were routinely administered by dialysis facilities, and because of possible risks of hematogenous spread of hepatitis B, dialysis providers often have detailed hepatitis B vaccine protocols. In March 2021, COVID-19 vaccines were made available for dialysis facilities to administer, although with the end of the public health emergency, vaccine policies by dialysis facilities against COVID-19 remains uncertain. The respiratory syncytial virus vaccine was authorized in 2023, and how dialysis facilities will approach this vaccine also remains uncertain. This review summarizes the Forum’s vaccination toolkit and discusses the role of the dialysis facility in vaccinating patients to reduce the risk of severe infections.

Parkinson’s disease (PD) is a chronic and progressive age-related neurodegenerative disease affecting up to 3% of the global population over 65 years of age. Currently, the underlying physiological aetiology of PD is unknown. However, the diagnosed disorder shares many common non-motor symptoms associated with ageing-related neurodegenerative disease progression, such as neuroinflammation, microglial activation, neuronal mitochondrial impairment, and chronic autonomic nervous system dysfunction. Clinical PD has been linked to many interrelated biological and molecular processes, such as escalating proinflammatory immune responses, mitochondrial impairment, lower adenosine triphosphate (ATP) availability, increasing release of neurotoxic reactive oxygen species (ROS), impaired blood brain barrier integrity, chronic activation of microglia, and damage to dopaminergic neurons consistently associated with motor and cognitive decline. Prodromal PD has also been associated with orthostatic hypotension and many other age-related impairments, such as sleep disruption, impaired gut microbiome, and constipation. Thus, this review aimed to present evidence linking mitochondrial dysfunction, including elevated oxidative stress, ROS, and impaired cellular energy production, with the overactivation and escalation of a microglial-mediated proinflammatory immune response as naturally occurring and damaging interlinked bidirectional and self-perpetuating cycles that share common pathological processes in ageing and PD. We propose that both chronic inflammation, microglial activation, and neuronal mitochondrial impairment should be considered as concurrently influencing each other along a continuum rather than as separate and isolated linear metabolic events that affect specific aspects of neural processing and brain function.

Radial velocity (RV) measurements of transiting multiplanet systems allow us to understand the densities and compositions of planets unlike those in the solar system. Kepler-102, which consists of five tightly packed transiting planets, is a particularly interesting system since it includes a super-Earth (Kepler-102d) and a sub-Neptune-sized planet (Kepler-102e) for which masses can be measured using RVs. Previous work found a high density for Kepler-102d, suggesting a composition similar to that of Mercury, while Kepler-102e was found to have a density typical of sub-Neptune size planets; however, Kepler-102 is an active star, which can interfere with RV mass measurements. To better measure the mass of these two planets, we obtained 111 new RVs using Keck/HIRES and Telescopio Nazionale Galileo/HARPS-N and modeled Kepler-102's activity using quasiperiodic Gaussian process regression. For Kepler-102d, we report a mass upper limit M _d < 5.3 M _⊕ (95% confidence), a best-fit mass M _d = 2.5 ± 1.4 M _⊕ , and a density ρ _d = 5.6 ± 3.2 g cm ^−3 , which is consistent with a rocky composition similar in density to the Earth. For Kepler-102e we report a mass M _e = 4.7 ± 1.7 M _⊕ and a density ρ _e = 1.8 ± 0.7 g cm ^−3 . These measurements suggest that Kepler-102e has a rocky core with a thick gaseous envelope comprising 2%–4% of the planet mass and 16%–50% of its radius. Our study is yet another demonstration that accounting for stellar activity in stars with clear rotation signals can yield more accurate planet masses, enabling a more realistic interpretation of planet interiors.

Abstract Background Pedestrian related deaths have recently been on the rise in Canada. The effect of changing posted speeds on the frequency and severity of pedestrian motor vehicle collisions (PMVC) is not well studied using controlled quasi-experimental designs. The objective of this study was to examine the effect of lowering speed limits from 40 km/h to 30 km/h on PMVC on local roads in Toronto, Canada. Methods A 30 km/h speed limit on local roads in Toronto was implemented between January 2015 and December 2016. Streets that remained at a 40 km/h speed limit throughout the study period were selected as comparators. A quasi-experimental, pre-post study with a comparator group was used to evaluate the effect of the intervention on PMVC rates before and after the speed limit change using repeated measures Poisson regression. PMVC data were obtained from police reports for a minimum of two years pre- and post-intervention (2013 to 2018). Results Speed limit reductions from 40 km/h to 30 km/h were associated with a 28% decrease in the PMVC incidence rate in the City of Toronto (IRR = 0.72, 95% CI: 0.58–0.89). A non-significant 7% decrease in PMVC incidence rates were observed on comparator streets that remained at 40 km/h speed limits (IRR = 0.93, 95% CI: 0.70–1.25). Speed limit reduction also influenced injury severity, with a significant 67% decrease in major and fatal injuries in the post intervention period on streets with speed limit reductions (IRR = 0.33, 95% CI: 0.13–0.85) compared with a 31% not statistically significant decrease in major and fatal injuries on comparator streets (IRR = 0.69, 95% CI: 0.37–1.31). The interaction term for group and pre-post comparisons was not statistically significant (p = 0.14) indicating that there was no evidence to suggest a pre-post difference in IRRs between the intervention and comparator streets. Conclusions Declines in the rate of PMVC were observed on roads with posted speed limit reductions from 40 km/h to 30 km/h, although this effect was not statistically greater than reductions on comparator streets.

Abstract Background Active transportation, such as walking and biking, is a healthy way for children to explore their environment and develop independence. However, children can be injured while walking and biking. Many cities make changes to the built environment (e.g., traffic calming features, separated bike lanes) to keep people safe. There is some research on how effective these changes are in preventing adult pedestrians and bicyclists from getting hurt, but very little research has been done to show how safe various environments are for children and youth. Our research program will study how features of the built environment affect whether children travel (e.g., to school) using active modes, and whether certain features increase or decrease their likelihood of injury. Methods First, we will use a cross-sectional study design to estimate associations between objectively measured built environment and objectively measured active transportation to school among child elementary students. We will examine the associations between objectively measured built environment and child and youth pedestrian-motor vehicle collisions (MVCs) and bicyclist-MVCs. We will also use these data to determine the space-time distribution of pedestrian-MVCs and bicyclist-MVCs. Second, we will use a case-crossover design to compare the built environment characteristics of the site where child and youth bicyclists sustain emergency department reported injuries and two randomly selected sites (control sites) along the bicyclist’s route before the injury occurred. Third, to identify implementation strategies for built environment change at the municipal level to encourage active transportation we will conduct: 1) an environmental scan, 2) key informant interviews, 3) focus groups, and 4) a national survey to identify facilitators and barriers for implementing built environment change in municipalities. Finally, we will develop a built environment implementation toolkit to promote active transportation and prevent child pedestrian and bicyclist injuries. Discussion This program of research will identify the built environment associated with active transportation safety and form an evidence base from which municipalities can draw information to support change. Our team’s national scope will be invaluable in providing information regarding the variability in built environment characteristics and is vital to producing evidence-based recommendations that will increase safe active transportation.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide claiming almost 17. 9 million deaths annually. A primary cause is atherosclerosis within the coronary arteries, which restricts blood flow to the heart muscle resulting in myocardial infarction (MI) and cardiac cell death. Despite substantial progress in the management of coronary heart disease (CHD), there is still a significant number of patients developing chronic heart failure post-MI. Recent research has been focused on promoting neovascularisation post-MI with the ultimate goal being to reduce the extent of injury and improve function in the failing myocardium. Cardiac cell transplantation studies in pre-clinical models have shown improvement in cardiac function; nonetheless, poor retention of the cells has indicated a paracrine mechanism for the observed improvement. Cell communication in a paracrine manner is controlled by various mechanisms, including extracellular vesicles (EVs). EVs have emerged as novel regulators of intercellular communication, by transferring molecules able to influence molecular pathways in the recipient cell. Several studies have demonstrated the ability of EVs to stimulate angiogenesis by transferring microRNA (miRNA, miR) molecules to endothelial cells (ECs). In this review, we describe the process of neovascularisation and current developments in modulating neovascularisation in the heart using miRNAs and EV-bound miRNAs. Furthermore, we critically evaluate methods used in cell culture, EV isolation and administration.

Background: Transnational funders provide up to 80% of funds for medical devices in resource-limited settings, yet sustained access to medical devices remains unachievable. The primary goal of this study was to identify what factors hinder access to medical devices through the perspectives of frontline public hospital staff in Ghana involved in the implementation of transnational funding initiatives. Methods: A case study was developed that involved an analysis of semi-structured interviews of 57 frontline technical, clinical and administrative public health care staff at 23 sites in Ghana between March and April 2017; a review of the national guidelines for donations; and images of abandoned medical devices. Results: Six key themes emerged, demonstrating how policy, collaboration, quality, lifetime operating costs, attitudes of health care workers and representational leadership influence access to medical devices. An in-depth assessment of these themes has led to the development of an enterprise-wide comprehensive acquisition and management framework for medical devices in the context of transnational funding initiatives. Conclusion: The findings in this study underscore the importance of incorporating frontline health care staff in developing solutions that are targeted at improving delivery of care. Sustained access to medical devices may be achieved in Ghana through the adoption of a rigorous and comprehensive approach to acquisition, management and technical leadership. Funders and public health policy makers may use the study’s findings to inform policy reform and to ensure that the efforts of transnational funders truly help to facilitate sustainable access to medical devices in Ghana.

ObjectivesThe optimal size of the health workforce for children’s surgical care around the world remains poorly defined. The goal of this study was to characterise the surgical workforce for children across Brazil, and to identify associations between the surgical workforce and measures of childhood health.DesignThis study is an ecological, cross-sectional analysis using data from the Brazil public health system (Sistema Único de Saúde).Settings and participantsWe collected data on the surgical workforce (paediatric surgeons, general surgeons, anaesthesiologists and nursing staff), perioperative mortality rate (POMR) and under-5 mortality rate (U5MR) across Brazil for 2015.Primary and secondary outcome measuresWe performed descriptive analyses, and identified associations between the workforce and U5MR using geospatial analysis (Getis-Ord-Gi analysis, spatial cluster analysis and linear regression models).FindingsThere were 39 926 general surgeons, 856 paediatric surgeons, 13 243 anaesthesiologists and 103 793 nurses across Brazil in 2015. The U5MR ranged from 11 to 26 deaths/1000 live births and the POMR ranged from 0.11–0.17 deaths/100 000 children across the country. The surgical workforce is inequitably distributed across the country, with the wealthier South and Southeast regions having a higher workforce density as well as lower U5MR than the poorer North and Northeast regions. Using linear regression, we found an inverse relationship between the surgical workforce density and U5MR. An U5MR of 15 deaths/1000 births across Brazil is associated with a workforce level of 5 paediatric surgeons, 200 surgeons, 100 anaesthesiologists or 700 nurses/100 000 children.ConclusionsWe found wide disparities in the surgical workforce and childhood mortality across Brazil, with both directly related to socioeconomic status. Areas of increased surgical workforce are associated with lower U5MR. Strategic investment in the surgical workforce may be required to attain optimal health outcomes for children in Brazil, particularly in rural regions.

Somatization may contribute to persistent symptoms after mild traumatic brain injury (mTBI). In two independently-recruited study samples, we characterized the extent to which symptoms atypical of mTBI but typical for patients suffering from somatization (e.g., gastrointestinal upset, musculoskeletal, and cardiorespiratory complaints) were present in adult patients with prolonged recovery following mTBI. The first sample was cross-sectional and consisted of mTBI patients recruited from the community who reported ongoing symptoms attributable to a previous mTBI (n = 16) along with a healthy control group (n = 15). The second sample consisted of patients with mTBI prospectively recruited from a Level 1 trauma center who had either good recovery (GOSE = 8; n = 32) or poor recovery (GOSE < 8; n = 29). In all participants, we evaluated atypical somatic symptoms using the Patient Health Questionnaire-15 and typical post-concussion symptoms with the Rivermead Post-Concussion Symptom Questionnaire. Participants with poor recovery from mTBI had significantly higher “atypical” somatic symptoms as compared to the healthy control group in Sample 1 (b = 4.308, p < 0.001) and to mTBI patients with good recovery in Sample 2 (b = 3.169, p < 0.001). As would be expected, participants with poor outcome in Sample 2 had a higher burden of typical rather than atypical symptoms [t(28) = 4.750, p < 0.001, d = 0.88]. However, participants with poor recovery still reported atypical somatic symptoms that were significantly higher (1.4 standard deviations, on average) than those with good recovery. Our results suggest that although “typical” post-concussion symptoms predominate after mTBI, a broad range of somatic symptoms also frequently accompanies mTBI, and that somatization may represent an important, modifiable factor in mTBI recovery.

Little is known about kindergarten students' active school transportation (AST) and stroller/wagon use as sedentary travel devices. The primary objective of this cross-sectional study was to determine the prevalence of kindergarten children arriving to school by active and sedentary modes, including strollers, in Toronto elementary schools and compare to students in kindergarten to grade 6 (K–6). The secondary objective was to examine factors associated with AST in kindergarten and K–6 students. School travel mode was counted using direct observations at elementary schools in the City of Toronto in 2015. Two samples were observed: 1) Kindergarten sample: a random sample of schools with separate kindergarten entrances (n = 26 schools, 1069 children); 2) Kindergarten to grade 6 sample: observations were conducted at arrival locations at 50% of eligible elementary schools for students of all ages (n = 88 schools, 17,224 children). Proportions arriving by different travel modes were compared using Chi-square analysis. Negative binomial regression was conducted to examine the association between school characteristics and AST. AST was lower in the kindergarten compared to the K–6 sample (60% versus 74%, χ2 = 91.37, p

This paper examines the relationship between reported collisions involving pedestrians and interaction rates based on field observation of street crossing behavior at selected urban intersections in Quebec, Canada (n=60). Data from a naturalistic observational study of pedestrian street crossing behavior was used to calculate interaction rates (n= 4286 observations) per intersection. Collisions (2003-2012, n=358 pedestrian collisions) were mapped and pooled at the same intersections to evaluate the relationship between the two. We found a positive and significant correlation between collisions (all-years) and interaction rates (Spearman’s coefficient between 0.329 and 0.340). This seems to be particularly the case on larger arterial roads.

Skin bacterial communities can protect amphibians from a fungal pathogen; however, little is known about how these communities are maintained. We used a neutral model of community ecology to identify bacteria that are maintained on salamanders by selection or by dispersal from a bacterial reservoir (soil) and ecological drift. We found that 75% (9/12) of bacteria that were consistent with positive selection, < 1% of bacteria that were consistent with random dispersal and none of the bacteria that were consistent under negative selection had a 97% or greater match to antifungal isolates. Additionally we performed an experiment where salamanders were either provided or denied a bacterial reservoir and estimated immigration and loss (emigration and local extinction) rates of bacteria on salamanders in both treatments. Loss was strongly related to bacterial richness, suggesting competition is important for structuring the community. Bacteria closely related to antifungal isolates were more likely to persist on salamanders with or without a bacterial reservoir, suggesting they had a competitive advantage. Furthermore, over-represented and under-represented OTUs had similar persistence on salamanders when a bacterial reservoir was present. However, under-represented OTUs were less likely to persist in the absence of a bacterial reservoir, suggesting that the over-represented and under-represented bacteria are selected for or against on salamanders through time. Our findings from the neutral model, migration and persistence analyses show that bacteria that exhibit a high similarity to antifungal isolates persist on salamanders, which likely protect hosts against pathogens and improve fitness. This research is one of the first to apply ecological theory to investigate assembly of host associated-bacterial communities, which can provide insights for probiotic bioaugmentation as a conservation strategy against disease.

Amphibians possess beneficial skin bacteria that protect against the disease chytridiomycosis by producing secondary metabolites that inhibit the pathogen Batrachochytrium dendrobatidis (Bd). Metabolite production may be a mechanism of competition between bacterial species that results in host protection as a by-product. We expect that some co-cultures of bacterial species or strains will result in greater Bd inhibition than mono-cultures. To test this, we cultured four bacterial isolates (Bacillus sp., Janthinobacterium sp., Pseudomonas sp. and Chitinophaga arvensicola) from red-backed salamanders (Plethodon cinereus) and cultured isolates both alone and together to collect their cell-free supernatants (CFS). We challenged Bd with CFSs from four bacterial species in varying combinations. This resulted in three experimental treatments: 1) CFSs of single isolates; 2) combined CFSs of two isolates; and 3) CFSs from co-cultures. Pair-wise combinations of four bacterial isolates CFSs were assayed against Bd and revealed additive Bd inhibition in 42.2% of trials, synergistic inhibition in 42.2% and no effect in 16.6% of trials. When bacteria isolates were grown in co-cultures, complete Bd inhibition was generally observed, and synergistic inhibition occurred in four out of six trials. A metabolite profile of the most potent co-culture, Bacillus sp. and Chitinophaga arvensicola, was determined with LC-MS and compared with the profiles of each isolate in mono-culture. Emergent metabolites appearing in the co-culture were inhibitory to Bd, and the most potent inhibitor was identified as tryptophol. Thus mono-cultures of bacteria cultured from red-backed salamanders interacted synergistically and additively to inhibit Bd, and such bacteria produced emergent metabolites when cultured together, with even greater pathogen inhibition. Knowledge of how bacterial species interact to inhibit Bd can be used to select probiotics to provide amphibians with protection against Bd.