82 research outputs found

    Prenatal exposure to per-and polyfluoroalkyl substances, umbilical cord blood DNA methylation, and cardio-metabolic indicators in newborns: The healthy start study

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    BACKGROUND: Per-and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype. OBJECTIVES: We estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators. METHODS: Among 583 mother–infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate (FDR) <0:05 and differentially methylated regions (DMRs) were identified using comb-p (Šidák-adjusted p <0:05). We estimated associations between methylation at candidate DMPs and DMR sites and the following outcomes: newborn weight, adiposity, and cord blood glucose, insulin, lipids, and leptin. RESULTS: Maternal serum PFAS concentrations were below the median for females in the U.S. general population. Moderate to high pairwise correla-tions were observed between PFAS concentrations (q =0:28 − 0:76). Methylation at one DMP (cg18587484), annotated to the gene TJAP1, was associated with perfluorooctanoate (PFOA) at FDR < 0:05. Comb-p detected between 4 and 15 DMRs for each PFAS. Associated genes, some common across multiple PFAS, were implicated in growth (RPTOR), lipid homeostasis (PON1, PON3, CIDEB, NR1H2), inflammation and immune activity (RASL11B, RNF39), among other functions. There was suggestive evidence that two PFAS-associated loci (cg09093485, cg09637273) were associated with cord blood triglycerides and birth weight, respectively (FDR < 0:1). DISCUSSION: DNA methylation in umbilical cord blood was associated with maternal serum PFAS concentrations during pregnancy, suggesting potential associations with offspring growth, metabolism, and immune function. Future research should explore whether DNA methylation changes mediate associations between prenatal PFAS exposures and child health outcomes. https://doi.org/10.1289/EHP6888

    Absolute Proper Motions to B~22.5: IV. Faint, Low Velocity White Dwarfs and the White Dwarf Population Density Law

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    The reduced proper motion diagram (RPMD) for a complete sample of faint stars with high accuracy proper motions in the North Galactic Pole field SA57 is investigated. Eight stars with very large reduced proper motions are identified as faint white dwarf candidates. We discriminate these white dwarf candidates from the several times more numerous QSOs based on proper motion and variability. We discuss the implausibility that these stars could be any kind of survey contaminant. If {\it bona fide} white dwarfs, the eight candidates found here represent a portion of the white dwarf population hitherto uninvestigated by previous surveys by virtue of the faint magnitudes and low proper motions. The newly discovered stars suggest a disk white dwarf scaleheight larger than the values of 250-350 pc typically assumed in assessments of the local white dwarf density. Both a <V/V_{max}> and a more complex maximum likelihood analysis of the spatial distribution of our likely thin disk white dwarfs yield scaleheights of 400-600 pc while at the same time give a reasonable match to the local white dwarf volume density found in other surveys. Our results could have interesting implications for white dwarfs as potential MACHO objects. We can place some direct constraints (albeit weak ones) on the contribution of halo white dwarfs to the dark matter of the Galaxy. Moreover, the elevated scale height that we measure for the thin disk could alter the interpretation of microlensing results to the extent of making white dwarfs untenable as the dominant MACHO contributor. (Abridged)Comment: 38 pages, 5 figures, to appear in April Ap

    The effect of bisphosphonate treatment on osteoclast precursor cells in postmenopausal osteoporosis: The TRIO study

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    Bisphosphonates are used to treat bone disease characterised by increased bone resorption by inhibiting the activity of mature osteoclasts, resulting in decreased bone turnover. Bisphosphonates may also reduce the population of osteoclast precursor cells. Our aims were to investigate the effect of bisphosphonates on i) osteoclast precursor cells and ii) circulating cytokine and cytokine receptor in postmenopausal women with osteoporosis compared with healthy premenopausal women. Participants were 62 postmenopausal women (mean age 66) from a 48-week parallel group trial of bisphosphonates. They received ibandronate 150 mg/month (n = 22), alendronate 70 mg/week (n = 19) or risedronate 35 mg/week (n = 21). Fasting blood was collected at baseline, weeks 1 and 48. At baseline, blood was also collected from 25 healthy premenopausal women (mean age 37) to constitute a control group. Peripheral blood mononuclear cells were extracted and stained for CD14, M-CSFR, CD11b and TNFRII receptors. Flow cytometry was used to identify cells expressing CD14 + and M-CSFR + or CD11b + or TNFRII +. RANKL and OPG were measured to evaluate potential mediation of the bisphosphonate effect. After 48 weeks of treatment, there was a decrease in the percentage of cells expressing M-CSFR and CD11b receptors by 53% and 49% respectively (p < 0.01). Cells expressing M-CSFR and CD11b were decreased with ibandronate and risedronate after 48 weeks to the lower part of the premenopausal reference interval. These effects were not significantly different between each of the treatment groups. There was no significant effect on RANKL and OPG throughout the study period. Bisphosphonates inhibit bone resorption in the short-term by direct action on mature osteoclasts. There is also a later effect mediated in part by a reduction in the population of circulating osteoclast precursors

    Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design

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    The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories

    Gendered narratives of child sexual abuse in fiction film

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    Feminism without men: feminist media studies in a post-feminist age

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    Courting consumers and legitimating exploitation: the representation of commercial sex in television documentaries

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    The explosion of sexually explicit imagery in popular culture in recent years has been widely noted. On television, this has led to the birth of a new genre, a pornography-documentary hybrid. This article examines the kind of stories about sex that have emerged in this new generic space at the beginning of the twenty-first century and makes the case for retaining a central focus on gender as a relational matrix in feminist responses to both television and pornography. The article begins by sketching the classic feminist positions on pornography and considering how recent shifts in pornography research have limited the nature of feminist enquiry in a way that is broadly consistent with the normalising of pornography in mainstream culture. This provides the context for an analysis of docuporn that examines the stories the genre tells about commercial sex, arguing that, in the absence of an on-screen "John", these programmes court the viewer as a present and future consumer, negating the gendered inequalities and exploitation that make commercial sex, in its currently dominant forms, possible

    Media and violence: gendering the debates

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    Attractions and distractions: mums, babies and 'early' cinemagoing

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    This article reports on a small-scale audience study of women attending dedicated parent-and-baby screenings at one Glasgow cinema as a means of engaging with questions about exhibition context and cinema audiences that have been somewhat marginalised in contemporary accounts of film viewing. It uses Tom Gunning’s account of early cinema's 'attractions' as a way of framing the various pleasures on offer for women in these screenings, including the ways in which they think about their babies' engagements with the experience. The interviews reveal the extent to which, whilst the film choice is by no means incidental to the 'Watch With Baby' experience, the women's accounts of the films are embedded in a very embodied account of cinemagoing in which the organisation of the space and the relationship of bodies within it is central. This does not – as canonical film theory suggests – depend upon the negation of the apparatus, but rather displays a fascination with its possibilities as they might be perceived by the infant au
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