Health Effects Institute

We present a novel Adverse Outcome Pathway (AOP) network for environmental chemical-induced cardiotoxicity using a bottom-up, data-driven AOP development approach. Mechanistic endpoints were systematically extracted from 339 in vitro and in vivo studies, yielding 1,759 Key Event (KE) entries and 4,938 Key Event Relationship (KER) entries, including information on experimental methods, essentiality evidence (intervention experiments demonstrating upstream-downstream dependence), and study metadata. After quality filtering (high risk of bias, confounding cytotoxicity in vitro, excessive toxicity or animal well-being concerns in vivo, and low-frequency observations), 112 unique KEs and 829 unique KERs supported by at least three independent observations were retained for network construction. Network analysis identified oxidative stress and mitochondrial dysfunction as dominant hub processes linking diverse upstream perturbations to downstream cardiomyocyte injury, inflammation, cardiac remodelling (fibrosis and hypertrophy), decreased cardiac contractility, and reduced left ventricular function. Incorporating exposure duration at the KER level enabled time-resolved pathway interpretation and demonstrated that KE timing is relationship-dependent, revealing temporal patterns not apparent when analysing KEs in isolation. This evidence-weighted, time-resolved AOP network can support endpoint prioritisation and exposure-window selection for non-animal method (NAM) test batteries and mechanistically informed cardiotoxicity assessment.

Dental and veterinary technicians performing dental work are predominately female. The goal of this study was to determine whether exposure to high-frequency vibration, similar to that generated by dental tools, contributes to changes in sensory and vascular function. The tails of female rats were exposed to vibration at 1250 Hz (constant acceleration of 49 m/s 2 ) for 4 hours per day, for 10 days. The effects on sensory nerve function, and vascular function were measured. Vibration increased sensitivity to applied pressure but not to transcutaneous electrical stimulation. It also resulted in changes in blood flow. Changes in vascular and sensorineural function detected in this study are consistent with the idea that high-frequency vibration is injurious to soft tissues.

The difference in differences design is widely used to assess treatment effects in natural experiments or other situations where random assignment cannot, or is not, used (see, e.g., Angrist & Pischke, 2009). The researcher must make important decisions about which comparisons to make, the measurements to make, and perhaps the number of individuals whose data is included in each timepoint. Also, interpretation of any statistical results, particularly null results, is improved by understanding the sensitivity of the design. This paper describes methods for computing the statistical power for tests of treatment effects in the difference in differences design. We describe alternative approaches to the analysis of the design, show which are equivalent, and provide expressions for computing statistical power and determining minimum detectable effect sizes. We then discuss how these methods could be generalized to unbalanced designs, designs with covariates, and designs more than two timepoints including difference in difference in differences designs.

The purpose of this article is to present practice-based evidence of the transition to competitive integrated employment using person-driven planning. Not a program, the use of active person-driven planning pivots on teaching and practicing self-advocacy and self-determination. Different from person-centered approaches, person-driven planning amplifies the voices of individuals with disabilities and assists their parents, families, and support team members to advocate for them. In person-driven planning, the use of culturally appropriate and engaging formats is emphasized that from the person’s perspective are reachable, accessible, and personalized. With person-driven education and counseling, the person and their family are directly impacted through having informed choices, support for decision-making, and a person-driven plan (PDP) to link to other individualized plans such as developing Individualized Education Programs (IEPs) and Individualized Plans for Employment (IPEs). Legal precedents, descriptions, and discussion are offered with the overall goal of reinforcing a shift in language and practices. Highlighted in this article are exemplary person-driven planning experiences that actualize the legislative precedents and represent the shifts in language and practices needed to support human rights. The results dispel myths regarding process, predictability, and time with suggestions to overcome the limitations of traditional readiness, capacity, and/or other value-based assessments as well as the restrictions of individualized approaches. Operations are shared for moving from person-centered to person-driven planning for maximizing relational autonomy, building working alliances, using resources collaboratively, and demonstrating the risks are outweighed by the benefits to everyone.

China is one of the largest producers and consumers of coal in the world. The National Action Plan on Air Pollution Prevention and Control in China (2013–2017) particularly aimed to reduce emissions from coal combustion. Here, we show whether the acute health effects of PM2.5 changed from 2013 to 2018 and factors that might account for any observed changes in the Beijing–Tianjin–Hebei (BTH) and the surrounding areas where there were major reductions in PM2.5 concentrations. We used a two-stage analysis strategy, with a quasi-Poisson regression model and a random effects meta-analysis, to assess the effects of PM2.5 on mortality in the 47 counties of BTH. We found that the mean daily PM2.5 levels and the SO42− component ratio dramatically decreased in the study period, which was likely related to the control of coal emissions. Subsequently, the acute effects of PM2.5 were significantly decreased for total and circulatory mortality. A 10 μg/m3 increase in PM2.5 concentrations was associated with a 0.16% (95% CI: 0.08, 0.24%) and 0.02% (95% CI: −0.09, 0.13%) increase in mortality from 2013 to 2015 and from 2016 to 2018, respectively. The changes in air pollution sources or PM2.5 components appeared to have played a core role in reducing the health effects. The air pollution control measures implemented recently targeting coal emissions taken in China may have resulted in significant health benefits.

Urban greenness has been shown to confer many health benefits including reduced risks of chronic disease, depression, anxiety, and, in a limited number of studies, loneliness. In this first Canadian study on this topic, we investigated associations between residential surrounding greenness and loneliness and social isolation among older adults. This cross-sectional analysis of the Canadian Longitudinal Study on Aging included 26,811 urban participants between 45 and 86 years of age. The Normalized Difference Vegetation Index (NDVI), a measure of greenness, was assigned to participants' residential addresses using a buffer distance of 500 m. We evaluated associations between the NDVI and (i) self-reported loneliness using the Center for Epidemiological Studies Depression Scale, (ii) whether participants reported "feeling lonely living in the local area", and (iii) social isolation. Logistic regression models were used to characterize associations between greenness and loneliness/social isolation while adjusting for individual socio-economic and health behaviours. Overall, 10.8% of participants perceived being lonely, while 6.5% reported "feeling lonely in their local area". Furthermore, 16.2% of participants were characterized as being socially isolated. In adjusted models, we observed no statistically significant difference (odds ratio (OR) = 0.99; 95% confidence interval (CI) 0.93-1.04) in self-reported loneliness in relation to an interquartile range (IQR) increase of NDVI (0.06). However, for the same change in greenness, there was a 15% (OR = 0.85; 95% CI 0.72-0.99) reduced risk for participants who strongly agreed with "feeling lonely living in the local area". For social isolation, for an IQR increase in the NDVI, we observed a 7% (OR = 0.93; 95% CI 0.88-0.97) reduction in prevalence. Our findings suggest that urban greenness plays a role in reducing loneliness and social isolation among Canadian urbanites.

Hundreds of thousands of documented and undocumented orphaned oil and gas wells exist in the United States (U.S.). These wells have the potential to contaminate water supplies, degrade ecosystems, and emit methane and other air pollutants. Thus, orphaned wells present risks to climate stability and to environmental and human health, which can be reduced by plugging. To quantify environmental risks and opportunities of well plugging at the national level, we analyze data on 81 857 documented orphaned wells across the U.S. We find that 4.6 million people live within 1 km of a documented orphaned well. 35% of the documented orphaned wells are located within 1 km of a domestic groundwater well, yet only 8% of the wells have groundwater quality data within a 1 km radius. Methane emissions from the documented orphaned wells represent approximately 3%–6% of total U.S. methane emissions from abandoned oil and gas wells, but this estimate is based on measurements at 0.03% of U.S. abandoned wells. 91% of the documented orphaned wells overlie formations favorable for geologic storage of carbon dioxide and hydrogen, meaning that orphaned well plugging can reduce leakage risks from future storage projects. Finally, we estimate plugging costs for documented orphaned wells to exceed the $4.7 billion federal funding by 30%–80%, emphasizing the importance of prioritizing federal spending on wells with large remediation benefits. Overall, environmental monitoring data are not extensive enough to quantify risks, especially those related to air and water quality and human health. Plugging orphaned wells can provide opportunities for geologic storage of carbon dioxide and hydrogen and geothermal energy development, thereby facilitating efforts to transition to net-zero energy systems. Our analysis on environmental risks and opportunities of orphaned wells provides a framework that can be used to manage the millions of documented and undocumented orphaned wells in the U.S. and abroad.

Air pollution is one of the leading risk factors for poor health in Africa, resulting in millions of premature deaths and economic losses. Of particular interest is exposure to fine particulate matter (PM2.5) which is the driver for a majority of deaths across the continent. However, PM monitoring, and by extension, ground-level data on PM2.5 is very limited; this limits our understanding of the widespread societal and health impacts linked to PM pollution. The robustness of low-cost PM sensors and their ability to report in situ data in tropical environments via internet-based platforms as well as relative affordability has created the opportunity to employ low-cost sensors (LCS) for air quality monitoring but calibration methodologies and the usefulness of the high-temporal resolution data for source identification remain a challenge. Increasingly, local governments in African countries are also turning to low-cost sensors to monitor air quality. In this study, two Airnote PM monitors were colocated with reference-grade Teledyne PM mass monitor T640 for ~4 weeks at the University of Ghana, Accra to establish their performance using a simplified data correction methodology - multiple linear regression (MLR) model. A split ratio of 80% and 20% was used to train and test the populated Airnote PM2.5 data respectively based on measurements from Teledyne T640 with temperature and relative humidity values from the Airnote monitor. Sectoral and calendar analysis with wind component data were used to triangulate the sources of PM2.5. We observed a high consistency between the two Airnote monitors. Hourly and 24-hour average PM2.5 values ranged from 25 to 95 μg/m3, and 29 to 54 μg/m3 respectively, and in most cases, were significantly higher than the WHO Air Quality Guideline. MLR using Pearson’s correlation analysis improved the out-of-the-box quality of low-cost Airnote PM2.5 data; the R2 improved from 0.69 to 0.84 and the mean absolute error from 11.75 to 4.20 μg/m3 respectively. Also, the MLR correction model was found to improve the Airnote PM2.5 data quality for higher relative humidity (between 50 and 90%) but not lower. PM2.5 pollution was local and from N, NE and SW winds for the raw, corrected and Teledyne PM mass monitor T640 measurements. Together, these results indicate that with appropriate corrections, low-cost PM sensors can generate the much needed data for air pollution research and mitigation in areas with limited air quality monitoring and data.