Publications

The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences of 170 pediatric high-grade gliomas and find that truncating mutations in PPM1D that increase the stability of its phosphatase are clonal driver events in 11% of Diffuse Midline Gliomas (DMGs) and are enriched in primary pontine tumors. Through the development of DMG mouse models, we show that PPM1D mutations potentiate gliomagenesis and that PPM1D phosphatase activity is required for in vivo oncogenesis. Finally, we apply integrative phosphoproteomic and functional genomics assays and find that oncogenic effects of PPM1D truncation converge on regulators of cell cycle, DNA damage response, and p53 pathways, revealing therapeutic vulnerabilities including MDM2 inhibition.

Wildfires have destroyed multiple residential communities in California in recent years. After fires in 2017 and 2018, high concentrations of benzene and other volatile organic compounds (VOCs) were found in public drinking water systems in fire-affected areas. The sources of the contamination and appropriate remediation have been urgent matters for investigation. This study characterizes target and non-target VOCs and semi volatile organic compounds (SVOCs) in water from a highly contaminated service line after the 2018 Camp Fire (Paradise, CA). Ninety-five organic compounds were identified or tentatively identified in the service line. Laboratory combustion experiments with drinking water pipes made of polyvinyl chloride (PVC), cross-linked polyethylene (PEX) and high-density polyethylene (HDPE) and a review of the literature were used to evaluate potential sources of the detected chemicals. Among the service line contaminants were thirty-two compounds associated with PVC pyrolysis and twenty-eight organic compounds also associated with the pyrolysis of polyethylene. The service line sample also contained fifty-five compounds associated with uncontrolled burning of biomass and waste materials. The findings support hypotheses that wildfires can contaminate drinking water systems both by thermal damage to plastic pipes and intrusion of smoke. Residual chlorine disinfectant in the water system modifies the contaminant distribution observed.

BACKGROUND

HIV and other medical complications of drug use, including overdose, are rising among people who inject drugs in the United States (US). Risk of complications and mortality increase with injection behaviors such as syringe sharing, rushing injections, and injecting in isolated places. Studies suggest safe consumption sites (SCS) reduce high-risk injection behaviors by offering sterile syringes and a safe, supervised space to consume drugs, although this has yet to be evaluated in the US.

SETTING

An unsanctioned SCS in an undisclosed US location.

METHODS

From 2018 to 2019, we recruited people who inject drugs using targeted sampling methods (N = 494) and conducted interviews at baseline, 6-, and 12-months. We sought to determine associations of past-month SCS use with past-month receptive syringe sharing, rushed injections, and injections in isolated places. We analyzed data using inverse probability of treatment weighted Poisson regression models. Generalized estimating equations accounted for repeated measures.

RESULTS

Fifty-two (11%) participants had past-month SCS use. Participants with past-month SCS use had decreased rates of receptive syringe sharing (Incident rate ratio [IRR] 0.17, 95% CI: 0.03 to 1.02) and injecting in an isolated location (IRR 0.77, 95% CI: 0.54 to 1.27) compared with those without past-month SCS use, although results were not statistically conclusive. Rate of rushed injections was only slightly lower (IRR 0.94, 95% CI: 0.70 to 1.30).

CONCLUSION

SCS may show benefit in reducing high-risk injection practices, and legal sanctioning of an SCS may offer further advantages. SCS implementation should be considered to help reduce the spread of HIV, overdose mortality, and prevent other medical complications of injection drug use.

Emerging evidence links structural sexism and structural discrimination against lesbian, gay, and bisexual (LGB) populations to poor health outcomes, but studies have yet to examine the combined effects of these mutually reinforcing systems of inequality. Therefore, we developed a composite measure of structural heteropatriarchy-which includes state-level LGB policies, family planning policies, and indicators of structural sexism (e.g., women's political and economic position relative to men)-and examined its relationship to birth outcomes using data from Waves I to V of the National Longitudinal Study of Adolescent to Adult Health. Multivariate regression analyses demonstrated that higher levels of heteropatriarchy were associated with an increased risk of preterm birth and decreased birth weight, net of important covariates. There was no association between clinical low birth weight and heteropatriarchy, or interactions between heteropatriarchy and individuals' race, ethnicity or sexual identity, suggesting a negative effect of heteropatriarchy on birth outcomes for all pregnant people. This study demonstrates the importance of considering gender and sexuality as mutually reinforcing systems of oppression that impact population health. Future research should examine the impact of heteropatriarchy on additional health outcomes and in conjunction with other structural inequalities such as racism and transgender oppression.