Prenatal Exposure to Tetrachloroethylene-Contaminated Drinking Water and the Risk of Congenital Anomalies: A Retrospective Cohort Study

BACKGROUND: Prior animal and human studies of prenatal exposure to solvents including tetrachloroethylene (PCE) have shown increases in the risk of certain congenital anomalies among exposed offspring. OBJECTIVES: This retrospective cohort study examined whether PCE contamination of public drinking water supplies in Massachusetts influenced the occurrence of congenital anomalies among children whose mothers were exposed around the time of conception. METHODS: The study included 1,658 children whose mothers were exposed to PCE-contaminated drinking water and a comparable group of 2,999 children of unexposed mothers. Mothers completed a self-administered questionnaire to gather information on all of their prior births, including the presence of anomalies, residential histories and confounding variables. PCE exposure was estimated using EPANET water distribution system modeling software that incorporated a fate and transport model. RESULTS: Children whose mothers had high exposure levels around the time of conception had an increased risk of congenital anomalies. The adjusted odds ratio of all anomalies combined among children with prenatal exposure in the uppermost quartile was 1.5 (95% CI: 0.9, 2.5). No meaningful increases in the risk were seen for lower exposure levels. Increases were also observed in the risk of neural tube defects (OR: 3.5, 95% CI: 0.8, 14.0) and oral clefts (OR 3.2, 95% CI: 0.7, 15.0) among offspring with any prenatal exposure. CONCLUSION: The results of this study suggest that the risk of certain congenital anomalies is increased among the offspring of women who were exposed to PCE-contaminated drinking water around the time of conception. Because these results are limited by the small number of children with congenital anomalies that were based on maternal reports, a follow-up investigation should be conducted with a larger number of affected children who are identified by independent records.National Institute of Environmental Health (5 P42 ES007381); National Institutes of Healt

Global Properties of Neutral Hydrogen in Compact Groups

Compact groups of galaxies provide a unique environment to study the evolution of galaxies amid frequent gravitational encounters. These nearby groups have conditions similar to those in the earlier universe when galaxies were assembled and give us the opportunity to witness hierarchical formation in progress. To understand how the compact group environment affects galaxy evolution, we examine the gas and dust in these groups. We present new single-dish GBT neutral hydrogen (HI) observations of 30 compact groups and define a new way to quantify the group HI content as the HI-to-stellar mass ratio of the group as a whole. We compare the HI content with mid-IR indicators of star formation and optical [g-r] color to search for correlations between group gas content and star formation activity of individual group members. Quiescent galaxies tend to live in HI-poor groups, and galaxies with active star formation are more commonly found in HI-rich groups. Intriguingly, we also find "rogue" galaxies whose star formation does not correlate with group HI content. In particular, we identify three galaxies (NGC 2968 in RSCG 34, KUG 1131+202A in RSCG 42, and NGC 4613 in RSCG 64) whose mid-IR activity is discrepant with the HI. We speculate that this mismatch between mid-IR activity and HI content is a consequence of strong interactions in this environment that can strip HI from galaxies and abruptly affect star-formation. Ultimately, characterizing how and on what timescales the gas is processed in compact groups will help us understand the interstellar medium in complex, dense environments similar to the earlier Universe.Comment: Accepted to A

A dinucleotide deletion in the ankyrin promoter alters gene expression, transcription initiation and TFIID complex formation in hereditary spherocytosis

Ankyrin defects are the most common cause of hereditary spherocytosis (HS). In some HS patients, mutations in the ankyrin promoter have been hypothesized to lead to decreased ankyrin mRNA synthesis. The ankyrin erythroid promoter is a member of the most common class of mammalian promoters which lack conserved TATA, initiator or other promoter cis elements and have high G+C content, functional Sp1 binding sites and multiple transcription initiation sites. We identified a novel ankyrin gene promoter mutation, a TG deletion adjacent to a transcription initiation site, in a patient with ankyrin-linked HS and analyzed its effects on ankyrin expression. In vitro, the mutant promoter directed decreased levels of gene expression, altered transcription initiation site utilization and exhibited defective binding of TATA-binding protein (TBP) and TFIID complex formation. In a transgenic mouse model, the mutant ankyrin promoter led to abnormalities in gene expression, including decreased expression of a reporter gene and altered transcription initiation site utilization. These data indicate that the mutation alters ankyrin gene transcription and contributes to the HS phenotype by decreasing ankyrin gene synthesis via disruption of TFIID complex interactions with the ankyrin core promoter. These studies support the model that in promoters that lack conserved cis elements, the TFIID complex directs preinitiation complex formation at specific sites in core promoter DNA and provide the first evidence that disruption of TBP binding and TFIID complex formation in this type of promoter leads to alterations in start site utilization, decreased gene expression and a disease phenotype in viv

Using Residential History and Groundwater Modeling to Examine Drinking Water Exposure and Breast Cancer

BACKGROUND. Spatial analyses of case-control data have suggested a possible link between breast cancer and groundwater plumes in upper Cape Cod, Massachusetts. OBJECTIVE. We integrated residential histories, public water distribution systems, and groundwater modeling within geographic information systems (GIS) to examine the association between exposure to drinking water that has been contaminated by wastewater effluent and breast cancer. METHODS. Exposure was assessed from 1947 to 1993 for 638 breast cancer cases who were diagnosed from 1983 to 1993 and 842 controls; we took into account residential mobility and drinking water source. To estimate the historical impact of effluent on drinking water wells, we modified a modular three-dimensional finite-difference groundwater model (MODFLOW) from the U.S. Geological Survey. The analyses included latency and exposure duration. RESULTS. Wastewater effluent impacted the drinking water wells of study participants as early as 1966. For > 0-5 years of exposure (versus no exposure), associations were generally null. Adjusted odds ratios (AORs) for > 10 years of exposure were slightly increased, assuming latency periods of 0 or 10 years [AOR = 1.3; 95% confidence interval (CI), 0.9-1.9 and AOR = 1.6; 95% CI, 0.8-3.2, respectively]. Statistically significant associations were estimated for ever-exposed versus never-exposed women when a 20-year latency period was assumed (AOR = 1.9; 95% CI, 1.0-3.4). A sensitivity analysis that classified exposures assuming lower well-pumping rates showed similar results. CONCLUSION. We investigated the hypothesis generated by earlier spatial analyses that exposure to drinking water contaminated by wastewater effluent may be associated with breast cancer. Using a detailed exposure assessment, we found an association with breast cancer that increased with longer latency and greater exposure duration.National Cancer Institute (5R03CA119703-02); National Institute of Environmental Health Sciences (5P42 ES007381

In Defence of Modest Doxasticism About Delusions

Here I reply to the main points raised by the commentators on the arguments put forward in my Delusions and Other Irrational Beliefs (OUP, 2009). My response is aimed at defending a modest doxastic account of clinical delusions, and is articulated in three sections. First, I consider the view that delusions are in-between perceptual and doxastic states, defended by Jacob Hohwy and Vivek Rajan, and the view that delusions are failed attempts at believing or not-quite-beliefs, proposed by Eric Schwitzgebel and Maura Tumulty. Then, I address the relationship between the doxastic account of delusions and the role, nature, and prospects of folk psychology, which is discussed by Dominic Murphy, Keith Frankish, and Maura Tumulty in their contributions. In the final remarks, I turn to the continuity thesis and suggest that, although there are important differences between clinical delusions and non-pathological beliefs, these differences cannot be characterised satisfactorily in epistemic terms. \u

Spectral Energy Distributions and Multiwavelength Selection of Type 1 Quasars

We present an analysis of the mid-infrared (MIR) and optical properties of type 1 (broad-line) quasars detected by the Spitzer Space Telescope. The MIR color-redshift relation is characterized to z ~ 3, with predictions to z = 7. We demonstrate how combining MIR and optical colors can yield even more efficient selection of active galactic nuclei (AGNs) than MIR or optical colors alone. Composite spectral energy distributions (SEDs) are constructed for 259 quasars with both Sloan Digital Sky Survey and Spitzer photometry, supplemented by near-IR, GALEX, VLA, and ROSAT data, where available. We discuss how the spectral diversity of quasars influences the determination of bolometric luminosities and accretion rates; assuming the mean SED can lead to errors as large as 50% for individual quasars when inferring a bolometric luminosity from an optical luminosity. Finally, we show that careful consideration of the shape of the mean quasar SED and its redshift dependence leads to a lower estimate of the fraction of reddened/obscured AGNs missed by optical surveys as compared to estimates derived from a single mean MIR to optical flux ratio

Project-Based Learning in Introductory Statistics: Comparing Course Experiences and Predicting Positive Outcomes for Students from Diverse Educational Settings

In order to evaluate the acceptability and potential impact of the Passion-Driven Statistics curriculum, this article describes background characteristics, and course experiences and outcomes of students enrolled in the multidisciplinary, introductory, project-based course in liberal arts colleges, large state universities, regional college/universities, and community colleges. We found that the course could be successfully delivered across these diverse educational settings. After controlling for educational setting and pre-survey responses to individual outcome measures, consistent predictors of positive course outcomes included student’s initial interest in conducting research, their higher likelihood of enrolling in a statistics course if it were not required, finding the project-based course less challenging, and finding the research project more rewarding than other students. Regional college/university, and community college students reported working significantly harder in the course and finding the course more challenging than students taking the course at liberal arts colleges or state universities. Students from liberal arts colleges generally reported more positive course experiences than students from other educational settings. However, when compared to students from both liberal arts colleges and large state universities, those from regional colleges/universities reported being more likely to have learned more in the project-based course than in other college courses they had taken. Taken together, the project-based course was successfully delivered across diverse post-secondary educational settings and provides a promising model for getting students hooked on the power and excitement of applied statistics