College Opportunity at Risk: An Assessment of the States — State Risk Assessments

A public compact for postsecondary education in the 21st century must have at its core a commitment to educational opportunity. The demands of the knowledge economy and modern democracy require that most Americans have the opportunity to develop critical thinking, problem solving, communication, and technological knowledge and skills

Genetic Modification of the Association between Peripubertal Dioxin Exposure and Pubertal Onset in a Cohort of Russian Boys

Background: Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins. Objectives: We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset. Methods: In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene–environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys’ serum at age 8–9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations. Results: After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-α (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene–environment tests or only to those with marginal genetic associations. Conclusions: Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-α genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings

The First Quiescent Galaxies in TNG300

We identify the first quiescent galaxies in TNG300, the largest volume of the IllustrisTNG cosmological simulation suite, and explore their quenching processes and time evolution to z=0. We find that the first quiescent galaxies with stellar masses M_* > 3 x 10^{10} M_sun and specific star formation rates sSFR < 10^{-11} yr^{-1} emerge at z~4.2 in TNG300. Suppression of star formation in these galaxies begins with a thermal mode of AGN feedback at z~6, and a kinetic feedback mode acts in each galaxy by z~4.7 to complete the quenching process, which occurs on a time-scale of ~0.35 Gyr. Surprisingly, we find that the majority of these galaxies are not the main progenitors of their z=0 descendants; instead, four of the five galaxies fall into more massive galaxies in subsequent mergers at a range of redshifts 2.5 < z < 0.2. By z=0, these descendants are the centres of galaxy clusters with average stellar masses of 8 x 10^{11} M_sun. We make predictions for the first quenched galaxies to be located by the James Webb Space Telescope (JWST).Comment: 6 pages, 4 figure

Work, Parenting and Gender: The care-work negotiations of three couple relationships in the UK

Changes globally mean that there are now record numbers of mothers in paid employment and a reported prevalence of involved fathering. This poses challenges to mothers and fathers as they negotiate care-work practices within their relationships. Focusing on interviews with three heterosexual couples (taken from a wider UK qualitative project on working parents), the paper considers care-work negotiations of three couples, against a backdrop of debates about intensive mothering and involved fathering. It aims to consider different configurations of work and care within three different couple relationships. We found that power within the relationships was negotiated along differential axis of gender and working status (full or part time paid work) . We present qualitatively rich insights into these negotiations. Framed by a critical discursive psychological approach, we call on other researchers to think critically about dominant discourses and practices of working, caring and parenting, pointedly how couples situated around the world operationalise these discourses in talking about themselves as worker and carers

Associations of Serum 25-Hydroxyvitamin D, Parathyroid Hormone and Calcium with Cardiovascular Risk Factors: Analysis of 3 NHANES Cycles (2001–2006)

Increasing evidence suggests a role for mineral metabolism in cardiovascular disease risk. 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), and calcium may be directly associated with cardiovascular risk factors or mediated by each other.We combined data for adult participants in three cycles of the National Health and Nutrition Examination Survey (2001-2, 2003-4, 2005-6), a representative sample of the civilian, non-institutionalized US population (N = 3,958). Using this data we examined joint associations of 25(OH)D, PTH and calcium with a range of cardiovascular risk factors. 25(OH)D was inversely associated with fasting insulin (mean difference in insulin per 1 standard deviation 25(OH)D: -0.053 (95%CI: -0.091, -0.015)), glucose (-0.046 95%CI: -0.081, -0.012) and systolic blood pressure (SBP) (-0.032 95%CI: -0.062, -0.001), and positively associated with high density lipoprotein cholesterol HDL-c (0.088 95%CI: 0.044, 0.148), after adjustment for ethnicity, smoking, socio-economic status and waist circumference. PTH was positively associated with diastolic blood pressure (0.110, 95%CI: 0.055, 0.164) in confounder adjusted models, but was not associated with other cardiovascular risk factors. Albumin adjusted calcium was associated with triglycerides (0.102 95%CI: 0.063, 0.141), postload glucose (0.078, 95%CI: 0.025, 0.130), fasting insulin (0.074, 95%CI: 0.044, 0.104), HbA1c (0.070, 95%CI: 0.036, 0.105), SBP (0.064, 95%CI: 0.028, 0.100), fasting glucose (0.055, 95%CI: 0.018, 0.092) and low density lipoprotein cholesterol (0.052, 95%CI: 0.014, 0.091). With mutual adjustment for each other, these associations remained essentially unchanged.Lower levels of 25(OH)D and higher levels of calcium and PTH appear to be associated with different cardiovascular risk factors and may therefore affect cardiovascular disease risk through different mechanisms

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

Anti-stromal treatment together with chemotherapy targets multiple signalling pathways in pancreatic adenocarcinoma.

Stromal targeting for pancreatic ductal adenocarcinoma (PDAC) is rapidly becoming an attractive option, due to the lack of efficacy of standard chemotherapy and increased knowledge about PDAC stroma. We postulated that the addition of stromal therapy may enhance the anti-tumour efficacy of chemotherapy. Gemcitabine and all-trans retinoic acid (ATRA) were combined in a clinically applicable regimen, to target cancer cells and pancreatic stellate cells (PSCs) respectively, in 3D organotypic culture models and genetically engineered mice (LSL-Kras(G12D) (/+) ;LSL-Trp53(R172H) (/+) ;Pdx-1-Cre: KPC mice) representing the spectrum of PDAC. In two distinct sets of organotypic models as well as KPC mice, we demonstrate a reduction in cancer cell proliferation and invasion together with enhanced cancer cell apoptosis when ATRA is combined with gemcitabine, compared to vehicle or either agent alone. Simultaneously, PSC activity (as measured by deposition of extracellular matrix proteins such as collagen and fibronectin) and PSC invasive ability were both diminished in response to combination therapy. These effects were mediated through a range of signalling cascades (Wnt, hedgehog, retinoid, and FGF) in cancer as well as stellate cells, affecting epithelial cellular functions such as epithelial-mesenchymal transition, cellular polarity, and lumen formation. At the tissue level, this resulted in enhanced tumour necrosis, increased vascularity, and diminished hypoxia. Consequently, there was an overall reduction in tumour size. The enhanced effect of stromal co-targeting (ATRA) alongside chemotherapy (gemcitabine) appears to be mediated by dampening multiple signalling cascades in the tumour-stroma cross-talk, rather than ablating stroma or targeting a single pathway. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.This work was supported by project grants from the Knowledge Transfer Network (Engineering and Physical Sciences Research Committee) and Pancreatic Cancer Research Fund (UK) to HMK. CF was supported by an EMBO long term fellowship and by a Marie Curie Intra8European Fellowship within the 7th European Community Framework Programme. TB and FR were supported by Cancer Research UK (grant C14303/A17197). Other grant funding includes project grants from Pancreatic Cancer Research Fund, Cancer Research UK and Barts Charity.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/path.472