Extramural US Federal Research Grants For Health Outcomes Associated With Climate Change Inadequate, Too Narrow In Focus.

Climate change causes and exacerbates disease, creates and worsens health disparities, disrupts health care delivery, and imposes a significant disease burden in the US and globally. Critical knowledge gaps hinder an evidence-based response and are perpetuated by scarce federal research funds. We identified and described extramural US federal research funding (that is, grants provided to organizations and institutions outside of federal agencies) that both addressed health outcomes associated with climate change and was awarded between 2010 and 2020. During this eleven-year period, 102 grants met our criteria, totaling approximately $58.7 million, or approximately $5.3 million per year (2020 adjusted US dollars). Federal investments in climate change and health research during this period failed to address the breadth of climate-sensitive exposures, health outcomes, and impacts on vulnerable populations. Moving forward, in addition to increasing investment in climate and health research across all known hazards, critical attention should be placed on vulnerable populations and health equity. To achieve this, increased federal research coordination and cooperation are needed, as well as a mechanism to track this funding.

Seasonal Temperature Variability and Mortality in the Medicare Population.

BACKGROUND: Seasonal temperature variability remains understudied and may be modified by climate change. Most temperature-mortality studies examine short-term exposures using time-series data. These studies are limited by regional adaptation, short-term mortality displacement, and an inability to observe longer-term relationships in temperature and mortality. Seasonal temperature and cohort analyses allow the long-term effects of regional climatic change on mortality to be analyzed. OBJECTIVES: We aimed to carry out one of the first investigations of seasonal temperature variability and mortality across the contiguous United States. We also investigated factors that modify this association. Using adapted quasi-experimental methods, we hoped to account for unobserved confounding and to investigate regional adaptation and acclimatization at the ZIP code level. METHODS: We examined the mean and standard deviation (SD) of daily temperature in the warm (April-September) and cold (October-March) season in the Medicare cohort from 2000 to 2016. This cohort comprised 622,427,230 y of person-time in all adults over the age of 65 y from 2000 to 2016. We used daily mean temperature obtained from gridMET to develop yearly seasonal temperature variables for each ZIP code. We used an adapted difference-in-difference approach model with a three-tiered clustering approach and meta-analysis to observe the relationship between temperature variability and mortality within ZIP codes. Effect modification was assessed with stratified analyses by race and population density. RESULTS: For every 1°C increase in the SD of warm and cold season temperature, the mortality rate increased by 1.54% [95% confidence interval (CI): 0.73%, 2.15%] and 0.69% (95% CI: 0.22%, 1.15%) respectively. We did not see significant effects for seasonal mean temperatures. Participants who were classified by Medicare into an "other" race group had smaller effects than those classified as White for Cold and Cold SD and areas with lower population density had larger effects for Warm SD. DISCUSSION: Warm and cold season temperature variability were significantly associated with increased mortality rates in U.S. individuals over the age of 65 y, even after controlling for seasonal temperature averages. Warm and cold season mean temperatures showed null effects on mortality. Cold SD had a larger effect size for those who were in the racial subgroup other, whereas Warm SD was more harmful for those living in lower population density areas. This study adds to the growing calls for urgent climate mitigation and environmental health adaptation and resiliency. https://doi.org/10.1289/EHP11588.

MLL::AF9 degradation induces rapid changes in transcriptional elongation and subsequent loss of an active chromatin landscape.

MLL rearrangements produce fusion oncoproteins that drive leukemia development, but the direct effects of MLL-fusion inactivation remain poorly defined. We designed models with degradable MLL::AF9 where treatment with small molecules induces rapid degradation. We leveraged the kinetics of this system to identify a core subset of MLL::AF9 target genes where MLL::AF9 degradation induces changes in transcriptional elongation within 15 minutes. MLL::AF9 degradation subsequently causes loss of a transcriptionally active chromatin landscape. We used this insight to assess the effectiveness of small molecules that target members of the MLL::AF9 multiprotein complex, specifically DOT1L and MENIN. Combined DOT1L/MENIN inhibition resembles MLL::AF9 degradation, whereas single-agent treatment has more modest effects on MLL::AF9 occupancy and gene expression. Our data show that MLL::AF9 degradation leads to decreases in transcriptional elongation prior to changes in chromatin landscape at select loci and that combined inhibition of chromatin complexes releases the MLL::AF9 oncoprotein from chromatin globally.