In 1940, the tidal Delaware River was "one of the most grossly polluted areas in the United States." During the 1950s, water quality was so poor along the river at Philadelphia that zero oxygen levels prevented migration of American shad leading to near extirpation of the species. Since then, water quality in the Delaware Basin has improved with implementation of the 1961 Delaware River Basin Compact and 1970s Federal Clean Water Act Amendments. At 15 gages along the Delaware River and major tributaries between 1980 and 2005, water quality for dissolved oxygen, phosphorus, nitrogen, and sediment improved at 39%, remained constant at 51%, and degraded at 10% of the stations. Since 1980, improved water-quality stations outnumbered degraded stations by a 4 to 1 margin. Water quality remains good in the nontidal river above Trenton and, while improved, remains fair to poor for phosphorus and nitrogen in the tidal estuary near Philadelphia and in the Lehigh and Schuylkill tributaries. Water quality is good in heavily forested watersheds (>50%) and poor in highly cultivated watersheds. Water quality recovery in the Delaware Basin is coincident with implementation of environmental laws enacted in the 1960s and 1970s and is congruent with return of striped bass, shad, blue crab, and bald eagle populations.
HIV-1 disrupts the host epigenetic landscape with consequences for disease pathogenesis, viral persistence, and HIV-associated comorbidities. Here, we examined how soon after infection HIV-associated epigenetic changes may occur in blood and whether early initiation of antiretroviral therapy (ART) impacts epigenetic modifications. We profiled longitudinal genome-wide DNA methylation in monocytes and CD4+ T lymphocytes from 22 participants in the RV254/SEARCH010 acute HIV infection (AHI) cohort that diagnoses infection within weeks after estimated exposure and immediately initiates ART. We identified monocytes harbored 22,697 differentially methylated CpGs associated with AHI compared to 294 in CD4+ T lymphocytes. ART minimally restored less than 1% of these changes in monocytes and had no effect upon T cells. Monocyte DNA methylation patterns associated with viral load, CD4 count, CD4/CD8 ratio, and longitudinal clinical phenotypes. Our findings suggest HIV-1 rapidly embeds an epigenetic memory not mitigated by ART and support determining epigenetic signatures in precision HIV medicine. Trial Registration: NCT00782808.
Background: Frailty is an important clinical concern for the aging population of people living with HIV (PLWH). The objective of this study was to identify the combination of risk features that distinguish frail from nonfrail individuals. Setting: Machine learning analysis of highly dimensional risk features was performed on a clinical cohort of PLWH. Methods: Participants included 105 older (average age = 55.6) PLWH, with at least a 3-month history of combination antiretroviral therapy (median CD4 = 546). Predictors included demographics, HIV clinical markers, comorbid health conditions, cognition, and neuroimaging (ie, volumetrics, resting-state functional connectivity, and cerebral blood flow). Gradient-boosted multivariate regressions were implemented to establish linear and interactive classification models. Model performance was determined by sensitivity/specificity (F1 score) with 5-fold cross validation. Results: The linear gradient-boosted multivariate regression classifier included lower current CD4 count, lower psychomotor performance, and multiple neuroimaging indices (volumes, network connectivity, and blood flow) in visual and motor brain systems (F1 score = 71%; precision = 84%; and sensitivity = 66%). The interactive model identified novel synergies between neuroimaging features, female sex, symptoms of depression, and current CD4 count. Conclusions: Data-driven algorithms built from highly dimensional clinical and brain imaging features implicate disruption to the visuomotor system in older PLWH designated as frail individuals. Interactions between lower CD4 count, female sex, depressive symptoms, and neuroimaging features suggest potentiation of risk mechanisms. Longitudinal data-driven studies are needed to guide clinical strategies capable of preventing the development of frailty as PLWH reach advanced age.
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