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The short report aims to examine differences in self-rated general health across racialized post-secondary students at a university in Ontario, Canada. Binary logistic regression analysis was used to examine poor health as an outcome among racialized students as whole, as well as across Asian, South Asian, Afro-Caribbean and Middle Eastern student groups in comparison to white Caucasian post-secondary students. After adjusting for several covariates, racialized students as a whole had 2.43 times the odds of reporting poor general health compared to white Caucasian students. Asian (OR = 2.77; CI = 1.84-4.18; p < 0.05) and South Asian (OR = 2.52; CI = 1.56-4.08; p < 0.05) students were significantly more likely to report poor health compared to white Caucasian students. The findings call for further attention to the health needs of racialized post-secondary students living in Canada and creating campuses where diverse student populations feel safe and systemically included. [ABSTRACT FROM AUTHOR]

Background: Human milk is a potential source of lead exposure. Yet lactational transfer of lead from maternal blood into breast milk and its contribution to infant lead burden remains poorly understood. Objectives: We explored the dose-response relationships between maternal blood, plasma, and breast milk to better understand lactational transfer of lead from blood and plasma into milk and, ultimately, to the breastfeeding infant. Methods: We measured lead in 81 maternal blood, plasma, and breast milk samples at 1 month postpartum and in 60 infant blood samples at 3 months of age. Milk-to-plasma (M/P) lead ratios were calculated. Multivariate linear, piecewise, and generalized additive models were used to examine dose-response relationships between blood, plasma, and milk lead levels. Results: Maternal lead levels (mean ± SD) were as follows: blood: 7.7 ± 4.0 μg/dL; plasma: 0.1 ± 0.1 μg/L; milk: 0.8 ± 0.7 μg/L. The average M/P lead ratio was 7.7 (range, 0.6–39.8) with 97% of the ratios being > 1. The dose–response relationship between plasma lead and M/P ratio was nonlinear (empirical distribution function = 6.5, p = 0.0006) with the M/P ratio decreasing by 16.6 and 0.6 per 0.1 μg/L of plasma lead, respectively, below and above 0.1 μg/L plasma lead. Infant blood lead level (3.4 ± 2.2 μg/dL) increased by 1.8 μg/dL per 1 μg/L milk lead (p < 0.0001, R2 = 0.3). Conclusions: The M/P ratio for lead in humans is substantially higher than previously reported, and transfer of lead from plasma to milk may be higher at lower levels of plasma lead. Breast milk is an important determinant of lead burden among breastfeeding infants. [ABSTRACT FROM AUTHOR]

Simple Summary: Precision medicine is needed for muscle-invasive bladder cancer to improve survival rates due to high rates of tumour recurrence and poor patient outcomes. Hypoxia and an immunosuppressive tumour microenvironment are both independent poor prognostic factors that are targetable by hypoxia-modification and immune checkpoint inhibitors (ICIs), respectively. CD8 T cell counts are showing promise as a predictive biomarker for a durable response to ICIs. However, there is currently no biomarker to stratify patients to either hypoxia-targeting or immune-targeting therapies. Using data from a phase III trial where patients were randomised to radiotherapy +/− hypoxia-modifying therapy, we demonstrate that low CD8 T cell counts predict benefit from hypoxia-modifying therapy and associate with high hypoxia. These results inform the design of a clinical trial using CD8 T cell count as a biomarker for stratification to receive either radiotherapy with hypoxia-modifying therapy (low CD8 counts) or standard-of-care alone or with an ICI (high CD8 counts). Background: As hypoxia can drive an immunosuppressive tumour microenvironment and inhibit CD8+ T cells, we investigated if patients with low tumour CD8+ T cells benefitted from hypoxia-modifying therapy. Methods: BCON was a phase III trial that randomised patients with muscle-invasive bladder cancer (MIBC) to radiotherapy alone or with hypoxia-modifying carbogen plus nicotinamide (CON). Tissue microarrays of diagnostic biopsies from 116 BCON patients were stained using multiplex immunohistochemistry (IHC) with the markers CD8, CD4, FOXP3, CD68 and PD-L1, plus DAPI. Hypoxia was assessed using CA9 IHC (n = 111). Linked transcriptomic data (n = 80) identified molecular subtype. Relationships with overall survival (OS) were investigated using Cox proportional hazard models. Results: High (upper quartile) vs. low CD8 T cell counts associated with a better OS across the whole cohort at 16 years (n = 116; HR 0.47, 95% CI 0.28–0.78, p = 0.003) and also in the radiotherapy alone group (n = 61; HR 0.39, 95% CI 0.19–0.76, p = 0.005). Patients with low CD8+ T cells benefited from CON (n = 87; HR 0.63, 95% CI 0.4–1.0, p = 0.05), but those with high CD8 T cells did not (n = 27; p = 0.95). CA9 positive tumours had fewer CD8+ T cells (p = 0.03). Prognostic significance of low CD8+ T cells in the whole cohort remained after adjusting for clinicopathologic variables. Basal vs. luminal subtype had more CD8+ cells (p = 0.02) but was not prognostic (n = 80; p = 0.26). Exploratory analyses with other immune markers did not improve on findings obtained with CD8 counts. Conclusions: MIBC with low CD8+ T cell counts may benefit from hypoxia-modifying treatment. [ABSTRACT FROM AUTHOR]

Purpose: Many muscle-invasive bladder cancers are hypoxic, which limits the efficacy of radiation therapy. Hypoxia modification using carbogen and nicotinamide has been tested in a phase 3 trial, Bladder Carbogen Nicotinamide. We present mature follow-up data with biomarker predictions of outcomes.Methods and Materials: Bladder Carbogen Nicotinamide is a prospective, phase 3, multicenter, randomized, 2-arm, nonblinded clinical trial. Participants were randomized to receive radical radiation therapy (RT; control arm) alone or with the addition of carbogen (98% O2; 2% CO2) and nicotinamide (CON). Patients with muscle-invasive or high-grade non-muscle invasive bladder cancer were included. Tumor tissue was collected at entry and was analyzed for tumor necrosis, hypoxia (24-gene signature), and basal and luminal tumor molecular subtypes. Overall survival (OS) and disease-free survival and relationships with biomarker status outcomes are analyzed using multivariable Cox regression and log-rank analysis.Results: We analyzed 333 patients with a median follow-up of 10.3 years. The 10-year OS rates were 30% (95% confidence interval [CI], 0.23-0.39) in RT + CON patients and 24% (95% CI, 0.18-0.33) in the RT-alone patients (hazard ratio [HR], 0.80; 95% CI, 0.61-1.04; P = .08). The greatest benefit from CON was seen in patients with tumor necrosis (n = 79; 5-year OS, 53% vs. 33% in patients without tumor necrosis; HR, 0.59; 95% CI, 0.36-0.99; P = .04). Cases with a high hypoxia gene score (n = 75) had a 5-year OS rate of 51%, compared to 34% for a low score (HR, 0.64; 95% CI, 0.38-1.08; P = .09); those with the basal molecular subtype (n = 70) had a 5-year OS rate of 58%, compared to 38% for those with the luminal subtype (HR, 0.58; 95% CI, 0.32-1.06; P = .08).Conclusions: Although the improvement in long-term OS in the whole population is not statistically significant, patients selected by necrosis and high hypoxia gene score benefitted from hypoxia modification. [ABSTRACT FROM AUTHOR]

BACKGROUND: Air pollution-attributable disease burdens reported at global, country, state, or county levels mask potential smaller-scale geographic heterogeneity driven by variation in pollution levels and disease rates. Capturing within-city variation in air pollution health impacts is now possible with high-resolution pollutant concentrations. OBJECTIVES: We quantified neighborhood-level variation in air pollution health risks, comparing results from highly spatially resolved pollutant and disease rate data sets available for the Bay Area, California. METHODS: We estimated mortality and morbidity attributable to nitrogen dioxide (NO2), black carbon (BC), and fine particulate matter [PM =2.5 µm in aerodynamic diameter (PM2.5)] using epidemiologically derived health impact functions. We compared geographic distributions of pollution-attributable risk estimates using concentrations from a) mobile monitoring of NO2 and BC; and b) models predicting annual NO2, BC and PM2.5 concentrations from land-use variables and satellite observations. We also compared results using county vs. census block group (CBG) disease rates. RESULTS: Estimated pollution-attributable deaths per 100,000 people at the 100-m grid-cell level ranged across the Bay Area by a factor of 38, 4, and 5 for NO2 [mean = 30 (95% CI: 9, 50)], BC [mean = 2 (95% CI: 1, 2)], and PM2.5, [mean = 49 (95% CI: 33, 64)]. Applying concentrations from mobile monitoring and land-use regression (LUR) models in Oakland neighborhoods yielded similar spatial patterns of estimated grid-cell–level NO2-attributable mortality rates. Mobile monitoring concentrations captured more heterogeneity [mobile monitoring mean = 64 (95% CI: 19, 107) deaths per 100,000 people; LUR mean = 101 (95% CI: 30, 167)]. Using CBG-level disease rates instead of county-level disease rates resulted in 15% larger attributable mortality rates for both NO2 and PM2.5, with more spatial heterogeneity at the grid-cell–level [NO2 CBG mean = 41 deaths per 100,000 people (95% CI: 12, 68); NO2 county mean = 38 (95% CI: 11, 64); PM2.5 CBG mean = 59 (95% CI: 40, 77); and PM2.5 county mean = 55 (95% CI: 37, 71)]. DISCUSSION: Air pollutant-attributable health burdens varied substantially between neighborhoods, driven by spatial variation in pollutant concentrations and disease rates. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is growing evidence that exposure to ultrafine particles (UFP; particles smaller than 100 nm) may play an underexplored role in the etiology of several illnesses, including cardiovascular disease (CVD). OBJECTIVES: We aimed o investigate the relationship between long-term exposure to ambient UFP and incident cardiovascular and cerebrovascular disease (CVA). As a secondary objective, we sought to compare effect estimates for UFP with those derived for other air pollutants, including estimates from two-pollutant models. METHODS: Using a prospective cohort of 33,831 Dutch residents, we studied the association between long-term exposure to UFP (predicted via land use regression) and incident disease using Cox proportional hazard models. Hazard ratios (HR) for UFP were compared to HRs for more routinely monitored air pollutants, including particulate matter with aerodynamic diameter =10 lm (PM10), PM with aerodynamic diameter =2:5 (PM2:5), and NO2. RESULTS: Long-term UFP exposure was associated with an increased risk for all incident CVD [HR=1:18 per 10,000 particles=cm3; 95% confidence interval (CI): 1.03, 1.34], myocardial infarction (MI) (HR=1:34; 95% CI: 1.00, 1.79), and heart failure (HR=1:76; 95% CI: 1.17, 2.66). Positive associations were also estimated for NO2 (HR for heart failure=1:22; 95% CI: 1.01, 1.48 per 20 lg=m3) and coarse PM (PMcoarse; HR for all CVD=1:21; 95% CI: 1.01, 1.45 per 10 lg=m3). CVD was not positively associated with PM2:5 (HR for all CVD=0:95; 95% CI: 0.75, 1.28 per 5 lg=m3). HRs for UFP and CVAs were positive, but not significant. In two-pollutant models (UFP+NO2 and UFP+PMcoarse), positive associations tended to remain for UFP, while HRs for PMcoarse and NO2 generally attenuated towards the null. CONCLUSIONS: These findings strengthen the evidence that UFP exposure plays an important role in cardiovascular health and that risks of ambient air pollution may have been underestimated based on conventional air pollution metrics. [ABSTRACT FROM AUTHOR]