Associations between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts

Importance: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. Objective: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. Design, Setting, and Participants: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. Exposures: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. Main Outcomes and Measures: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. Results: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. Conclusions and Relevance: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Why arguments against infanticide remain convincing - a reply to Joona Räsänen

In ‘Pro-life arguments against infanticide and why they are not convincing’ Joona Räsänen argues that Christopher Kaczor’s objections to Giubilini and Minerva’s position on infanticide are not persuasive. We argue that Räsänen’s criticism is largely misplaced, and that he has not engaged with Kaczor’s strongest arguments against infanticide. We reply to each of Räsänen’s criticisms, drawing on the full range of Kaczor’s arguments, as well as adding some of our own

Runoff and erosion from a rapidly eroding pinyon-juniper hillslope

The dramatic acceleration of erosion associated with the expansion of pinyon-juniper woodlands over the past 100 years has been a widely recognized but poorly understood phenomenon. A more complete understanding will come only through long-term observations of erosion and related factors. To this end, we are conducting a study of a small (1-ha) catchment in a rapidly eroding pinyon-juniper woodland. Since July 1993, we have been collecting data on runoff, erosion, and weather conditions in the catchment, as well as on the topography, soils, and vegetation. Our preliminary results suggest that (1) the catchment is currently in a cycle of accelerated erosion that began concomitant with a shift from ponderosa pine forest to pinyon-juniper woodland that was initiated by a prolonged drought; (2) the intercanopy soils cannot be sustained at the current erosion rates and will be mostly stripped away in about a century; (3) large summer thunderstorms are the most important agents of erosion (4) erosion increases dramatically as the scale increases; (5) runoff makes up <10% of the water budget

Invasion of shrublands by exotic grasses: ecohydrological consequences in cold versus warm deserts

Across the globe, native savannas and woodlands are undergoing conversion to exotic grasslands. Here we summarize the current state of knowledge concerning the ecohydrological consequences of this conversion for the cold deserts (Great Basin, Colorado Plateau) and the warm deserts (Mojave, Sonoran, Chihuahuan) of North America. Our analysis is based on a synthesis of relevant literature, complemented by simulation modelling with a one-dimensional, soil water redistribution model (HYDRUS-1D) and a hillslope runoff and erosion model (MAHLERAN). When shrublands are invaded by grasses, many changes take place: rooting depths, canopy cover, species heterogeneity, water use, and fire regimes are radically altered. These changes then have the potential to alter key ecohydrological processes. With respect to the processes of runoff and erosion, we find that grass invasion influences cold and warm deserts in different ways. In cold deserts, runoff and erosion will increase following invasion; in particular, erosion on steep slopes (>15%) will be greatly accelerated following burning. In addition, evapotranspiration (ET) will be lower and soil water recharge will be higher—which after several decades could affect groundwater levels. For warm deserts, grass invasion may actually reduce runoff and erosion (except for periods immediately following fire), and is likely to have little effect on either ET fluxes or soil water. Significant gaps in our knowledge do remain, primarily because there have been no comprehensive studies measuring all components of the water and energy budgets at multiple scales. How these changes may affect regional energy budgets, and thus weather patterns, is not yet well understood