Impact of lowering fine particulate matter from major emission sources on mortality in Canada: A nationwide causal analysis.

Emissions of fine particulate matter (PM2.5) from human activities have been linked to substantial disease burdens, but evidence regarding how reducing PM2.5 at its sources would improve public health is sparse. We followed a population-based cohort of 2.7 million adults across Canada from 2007 through 2016. For each participant, we estimated annual mean concentrations of PM2.5 and the fractional contributions to PM2.5 from the five leading anthropogenic sources at their residential address using satellite observations in combination with a global atmospheric chemistry transport model. For each source, we estimated the causal effects of six hypothetical interventions on 10-y nonaccidental mortality risk using the parametric g-formula, a structural causal model. We conducted stratified analyses by age, sex, and income. This cohort would have experienced tangible health gains had contributions to PM2.5 from any of the five sources been reduced. Compared with no intervention, a 10% annual reduction in PM2.5 contributions from transportation and power generation, Canada's largest and fifth-largest anthropogenic sources, would have prevented approximately 175 (95%CI: 123-226) and 90 (95%CI: 63-117) deaths per million by 2016, respectively. A more intensive 50% reduction per year in PM2.5 contributions from the two sources would have averted 360 and 185 deaths per million, respectively, by 2016. The potential health benefits were greater among men, older adults, and low-income earners. In Canada, where PM2.5 levels are among the lowest worldwide, reducing PM2.5 contributions from anthropogenic sources by as little as 10% annually would yield meaningful health gains.

The impacts of extreme heat events on non-accidental, cardiovascular, and respiratory mortality: An analysis of 12 Canadian cities from 2000 to 2020.

Background: Extreme heat has significant impacts on mortality. In Canada, past research has analyzed the degree to which non-accidental mortality increases during single extreme heat events; however, few studies have considered multiple causes of death and the impacts of extreme heat events on mortality over longer time periods. Data and methods: Daily death counts attributable to non-accidental, cardiovascular, and respiratory causes were retrieved for the 12 most populous cities in Canada from 2000 to 2020. Generalized additive models were applied to quantify daily mortality risks for people aged younger than 65 years and for those aged 65 years and older in each city and for each cause of death. Model results were used to calculate the change in mortality risks and the number of excess deaths attributable to extreme heat during extreme heat events. Results: Elevated mortality risks were observed during extreme heat events in most cities for non-accidental and respiratory causes. The impacts of extreme heat on non-accidental mortality were typically greater for people aged 65 and older than for those aged younger than 65. Significantly higher non-accidental mortality risks were observed during extreme heat events for people aged 65 and older in Montréal, the city of Québec, Surrey, and Toronto. For cardiovascular and respiratory causes, people aged 65 and older had significantly higher mortality risks during extreme heat events in Montréal, and both Montréal and Toronto, respectively. In the 12 cities, approximately 670 excess non-accidental deaths, 115 excess cardiovascular deaths, and 115 excess respiratory deaths were attributable to extreme heat events during the study period. Mortality risks during extreme heat events were generally higher in cities with larger proportions of renter households and fewer extreme heat events. Interpretation: This study estimates the longer-term impacts of extreme heat events on three mortality outcomes in a set of large Canadian cities. As climate change causes more frequent and intense extreme heat events, and as policy makers aim to reduce the health impacts of heat, it is important to understand how and where extreme heat affects health.

The prevalence of household air conditioning in Canada.

Background: Household air conditioning is one of the most effective approaches for reducing the health impacts of heat exposure; however, few studies have measured the prevalence of household air conditioning in Canada. Data and methods: Data were obtained from the 2017 Canadian Community Health Survey and the 2017 Households and the Environment Survey. Statistics Canada linked the survey respondents and created survey weights. Four heat-vulnerable populations were defined: older adults, older adults living alone, older adults with at least one health condition associated with reduced thermoregulation and older adults living alone and with a health condition associated with reduced thermoregulation. Weighted ratios and logistic regression models were used to analyze person-level air conditioning rates for national, regional and heat-vulnerable populations. Results: Approximately 61% of the national population had household air conditioning. Regional rates ranged between 32% in British Columbia and 85% in Ontario. People living alone and people who did not own a home were significantly less likely to have air conditioning in Canada and in most regions. One heat vulnerable group, older adults living alone, had significantly lower air conditioning rates compared with the national and Ontario averages, at 56% and 81%, respectively. Interpretation: This study is the first to quantify air conditioning prevalence in Canada at the person-level. The results of this study may inform heat-health policies and climate change adaptation strategies that aim to identify populations with high risks of heat-related mortality or morbidity and low access to household air conditioning.

Microanatomy of the cervical and anorectal squamocolumnar junctions: a proposed model for anatomical differences in HPV-related cancer risk.

Human papilloma virus (HPV) infection causes cancers and their precursors (high-grade squamous intraepithelial lesions) near cervical and anal squamocolumnar junctions. Recently described cervical squamocolumnar junction cells are putative residual embryonic cells near the cervical transformation zone. These cells appear multipotential and share an identical immunophenotype (strongly CK7-positive) with over 90% of high-grade squamous intraepithelial lesions and cervical carcinomas. However, because the number of new cervical cancers discovered yearly world wide is 17-fold that of anal cancer, we posed the hypothesis that this difference in cancer risk reflects differences in the transition zones at the two sites. The microanatomy of the normal anal transformation zone (n=37) and topography and immunophenotype of anal squamous neoplasms (n=97) were studied. A discrete anal transition zone was composed of multilayered CK7-positive/p63-negative superficial columnar cells and an uninterrupted layer of CK7-negative/p63-positive basal cells. The CK7-negative/p63-positive basal cells were continuous with-and identical in appearance to-the basal cells of the mature squamous epithelium. This was in contrast to the cervical squamocolumnar junction, which harbored a single-layered CK7-positive/p63-negative squamocolumnar junction cell population. Of the 97 anal intraepithelial neoplasia/squamous cell carcinomas evaluated, only 27% (26/97) appeared to originate near the anal transition zone and only 23% (22/97) were CK7-positive. This study thus reveals two fundamental differences between the anus and the cervix: (1) the anal transition zone does not harbor a single monolayer of residual undifferentiated embryonic cells and (2) the dominant tumor immunophenotype is in keeping with an origin in metaplastic (CK7-negative) squamous rather than squamocolumnar junction (CK7-positive) epithelium. The implication is that, at birth, the embryonic cells in the anal transition zone have already begun to differentiate, presenting a metaplasia that-similar to vaginal and vulvar epithelium-is less prone to HPV-directed carcinogenesis. This in turn underscores the link between cancer risk and a very small and discrete population of vulnerable squamocolumnar junction cells in the cervix.

Identifying food deserts and swamps based on relative healthy food access: a spatio-temporal Bayesian approach.

BACKGROUND: Obesity and other adverse health outcomes are influenced by individual- and neighbourhood-scale risk factors, including the food environment. At the small-area scale, past research has analysed spatial patterns of food environments for one time period, overlooking how food environments change over time. Further, past research has infrequently analysed relative healthy food access (RHFA), a measure that is more representative of food purchasing and consumption behaviours than absolute outlet density. METHODS: This research applies a Bayesian hierarchical model to analyse the spatio-temporal patterns of RHFA in the Region of Waterloo, Canada, from 2011 to 2014 at the small-area level. RHFA is calculated as the proportion of healthy food outlets (healthy outlets/healthy + unhealthy outlets) within 4-km from each small-area. This model measures spatial autocorrelation of RHFA, temporal trend of RHFA for the study region, and spatio-temporal trends of RHFA for small-areas. RESULTS: For the study region, a significant decreasing trend in RHFA is observed (-0.024), suggesting that food swamps have become more prevalent during the study period. For small-areas, significant decreasing temporal trends in RHFA were observed for all small-areas. Specific small-areas located in south Waterloo, north Kitchener, and southeast Cambridge exhibited the steepest decreasing spatio-temporal trends and are classified as spatio-temporal food swamps. CONCLUSIONS: This research demonstrates a Bayesian spatio-temporal modelling approach to analyse RHFA at the small-area scale. Results suggest that food swamps are more prevalent than food deserts in the Region of Waterloo. Analysing spatio-temporal trends of RHFA improves understanding of local food environment, highlighting specific small-areas where policies should be targeted to increase RHFA and reduce risk factors of adverse health outcomes such as obesity.

Inequality in the Distribution of Air Pollution Attributable Mortality Within Canadian Cities.

Recent studies have identified inequality in the distribution of air pollution attributable health impacts, but to our knowledge this has not been examined in Canadian cities. We evaluated the extent and sources of inequality in air pollution attributable mortality at the census tract (CT) level in seven of Canada's largest cities. We first regressed fine particulate matter (PM2.5) and nitrogen dioxide (NO2) attributable mortality against the neighborhood (CT) level prevalence of age 65 and older, low income, low educational attainment, and identification as an Indigenous (First Nations, Métis, Inuit) or Black person, accounting for spatial autocorrelation. We next examined the distribution of baseline mortality rates, PM2.5 and NO2 concentrations, and attributable mortality by neighborhood (CT) level prevalence of these characteristics, calculating the concentration index, Atkinson index, and Gini coefficient. Finally, we conducted a counterfactual analysis of the impact of reducing baseline mortality rates and air pollution concentrations on inequality in air pollution attributable mortality. Regression results indicated that CTs with a higher prevalence of low income and Indigenous identity had significantly higher air pollution attributable mortality. Concentration index, Atkinson index, and Gini coefficient values revealed different degrees of inequality among the cities. Counterfactual analysis indicated that inequality in air pollution attributable mortality tended to be driven more by baseline mortality inequalities than exposure inequalities. Reducing inequality in air pollution attributable mortality requires reducing disparities in both baseline mortality and air pollution exposure.

Urban-rural variation in the association between social support availability and cognitive function in middle-aged and older adults: Results from the baseline Tracking Cohort of the Canadian Longitudinal Study on Aging.

The purpose of this study was to investigate if and how the associations between social support availability (SSA) and cognitive function varied across urban, rural, and geographical regions in Canada. Data from a population-level sample of community-dwelling adults aged 45-85 years were obtained from the baseline Tracking Cohort of the Canadian Longitudinal Study on Aging. The associations between SSA and two domains of cognitive function, memory and executive function, were analyzed using multilevel regression models. SSA was positively and significantly associated with both executive function and memory. We found SSA had stronger positive associations with executive function among participants living in rural areas compared to urban areas in all geographical regions; however, geographical variation in the associations between SSA and memory were not supported by model results. Understanding how the associations between cognitive function and modifiable risk factors, including SSA, vary across geographical contexts is important for developing policies and programs to support healthy aging.

A Replication of DiMaggio et al. (2020) in Phoenix, AZ.

This research replicates in Phoenix, Arizona a study originally conducted by DiMaggio et al. (2020) that investigated the associations between positive COVID-19 tests and demographic, socioeconomic, and racial characteristics in New York City at the ZIP Code Tabulation Area level. We extend that work through a conceptual replication that introduces covariates appropriate to Phoenix, AZ. Our direct replication, which focuses on that city's first wave of COVID-19 (May 31, 2020 to August 1, 2020), demonstrates that the framework used by DiMaggio et al. can be transferred across cities, but also identifies specification decisions that need careful consideration. Our conceptual replication identifies the proportion of Hispanic residents, rather than that of Black/African American residents, to be a key predictor of positive COVID-19 testing. This finding sheds light on the dynamics of race during the pandemic.

Examining the Association between Community-Level Marginalization and Emergency Room Wait Time in Ontario, Canada.

OBJECTIVE: This study examines the association between community-level marginalization and emergency room (ER) wait time in Ontario. METHODS: Data sources included ER wait time data and Ontario Marginalization Index scores. Linear regression models were used to quantify the association. RESULTS: A positive association between total marginalization and overall, high-acuity and low-acuity ER wait time was found. Considering specific marginalization dimensions, we found positive associations between residential instability and ER wait time and negative associations between dependency and ER wait time. CONCLUSIONS: Reductions in community-level marginalization may impact ER wait time. Future studies using individual-level data are necessary.

Directed Evolution of Heterologous tRNAs Leads to Reduced Dependence on Post-transcriptional Modifications.

Heterologous tRNA:aminoacyl tRNA synthetase pairs are often employed for noncanonical amino acid incorporation in the quest for an expanded genetic code. In this work, we investigated one possible mechanism by which directed evolution can improve orthogonal behavior for a suite of Methanocaldococcus jannaschii ( Mj) tRNATyr-derived amber suppressor tRNAs. Northern blotting demonstrated that reduced expression of heterologous tRNA variants correlated with improved orthogonality. We suspected that reduced expression likely minimized nonorthogonal interactions with host cell machinery. Despite the known abundance of post-transcriptional modifications in tRNAs across all domains of life, few studies have investigated how host enzymes may affect behavior of heterologous tRNAs. Therefore, we measured tRNA orthogonality using a fluorescent reporter assay in several modification-deficient strains, demonstrating that heterologous tRNAs with high expression are strongly affected by some native E. coli RNA-modifying enzymes, whereas low abundance evolved heterologous tRNAs are less affected by these same enzymes. We employed mass spectrometry to map ms2i6A37 and Ψ39 in the anticodon arm of two high abundance tRNAs (Nap1 and tRNAOptCUA), which provides (to our knowledge) the first direct evidence that MiaA and TruA post-transcriptionally modify evolved heterologous amber suppressor tRNAs. Changes in total tRNA modification profiles were observed by mass spectrometry in cells hosting these and other evolved suppressor tRNAs, suggesting that the demonstrated interactions with host enzymes might disturb native tRNA modification networks. Together, these results suggest that heterologous tRNAs engineered for specialized amber suppression can evolve highly efficient suppression capacity within the native post-transcriptional modification landscape of host RNA processing machinery.