Detection of brown dwarf-like objects in the core of NGC3603

We use near-infrared data obtained with the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope to identify objects having the colors of brown dwarfs (BDs) in the field of the massive galactic cluster NGC 3603. These are identified through use of a combination of narrow and medium band filters spanning the J and H bands, and which are particularly sensitive to the presence of the 1.3-1.5{\mu}m H2O molecular band - unique to BDs. We provide a calibration of the relationship between effective temperature and color for both field stars and for BDs. This photometric method provides effective temperatures for BDs to an accuracy of {\pm}350K relative to spectroscopic techniques. This accuracy is shown to be not significantly affected by either stellar surface gravity or uncertainties in the interstellar extinction. We identify nine objects having effective temperature between 1700 and 2200 K, typical of BDs, observed J-band magnitudes in the range 19.5-21.5, and that are strongly clustered towards the luminous core of NGC 3603. However, if these are located at the distance of the cluster, they are far too luminous to be normal BDs. We argue that it is unlikely that these objects are either artifacts of our dataset, normal field BDs/M-type giants or extra-galactic contaminants and, therefore, might represent a new class of stars having the effective temperatures of BDs but with luminosities of more massive stars. We explore the interesting scenario in which these objects would be normal stars that have recently tidally ingested a Hot Jupiter, the remnants of which are providing a short-lived extended photosphere to the central star. In this case, we would expect them to show the signature of fast rotation.Comment: 26 Pages, 8 Figures, Accepted for publication on Ap

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

*This research was funded, in part, by the Russell Sage and Rockefeller Foundations. We wish to

earlier drafts of this paper and Jorge Menèndez for his research assistance. We especially wish to thank James Heckman for providing us with a version of the statistical software used in some of the empirical analyses conducted for this paper and Steve Cameron and George Yates for their assistance This paper examines the impacts of work experience acquired while youth were in high school (and college) on young men’s wage rates during the 1980s and 1990s. Previous studies have found evidence of sizeable and persistent rates of return to working while enrolled in school, especially high school, on subsequent wage growth. Such findings may represent causal effects of having acquired work experience while still enrolled in school, but they may also be the result of failure to fully account for individual differences in young adults ’ capacities to acquire such skills and be productive in the work force later in life. We re-examine the robustness of previous attempts to control for unobserved heterogeneity and selectivity. We explore more general methods for dealing with dynamic forms of selection by explicitly modeling the educational and work choices of young men from age 13 through their late twenties. Using data on young men from the 1979 National Longitudinal Survey of Youth, (NLSY79), we find that th

Targeting eukaryotic translation in mesothelioma cells with an eIF4E-specific antisense oligonucleotide.

BACKGROUND: Aberrant cap-dependent translation is implicated in tumorigenesis in multiple tumor types including mesothelioma. In this study, disabling the eIF4F complex by targeting eIF4E with eIF4E-specific antisense oligonucleotide (4EASO) is assessed as a therapy for mesothelioma. METHODS: Mesothelioma cells were transfected with 4EASO, designed to target eIF4E mRNA, or mismatch-ASO control. Cell survival was measured in mesothelioma treated with 4EASO alone or combined with either gemcitabine or pemetrexed. Levels of eIF4E, ODC, Bcl-2 and β-actin were assessed following treatment. Binding to a synthetic cap-analogue was used to study the strength of eIF4F complex activation following treatment. RESULTS: eIF4E level and the formation of eIF4F cap-complex decreased in response to 4EASO, but not mismatch control ASO, resulting in cleavage of PARP indicating apoptosis. 4EASO treatment resulted in dose dependent decrease in eIF4E levels, which corresponded to cytotoxicity of mesothelioma cells. 4EASO resulted in decreased levels of eIF4E in non-malignant LP9 cells, but this did not correspond to increased cytotoxicity. Proteins thought to be regulated by cap-dependent translation, Bcl-2 and ODC, were decreased upon treatment with 4EASO. Combination therapy of 4EASO with pemetrexed or gemcitabine further reduced cell number. CONCLUSION: 4EASO is a novel drug that causes apoptosis and selectively reduces eIF4E levels, eIF4F complex formation, and proliferation of mesothelioma cells. eIF4E knockdown results in decreased expression of anti-apoptotic and pro-growth proteins and enhances chemosensitivity

4EASO transfection suppresses mesothelioma proliferation.

<p>Normal mesothelial cells (LP9) and mesothelioma cell lines H2373, H2461 and H2596 were treated with the indicated concentration of mmASO (open columns) and 4EASO (filled columns), and viable cells were counted. Normal LP9 cells were most resistant to 4EASO treatment, while growth of mesothelioma cell lines was reduced extensively. <i>Columns</i>, the mean of three independent determinations of cell number normalized to untreated cells, <i>bars</i>, s.d.</p

eIF4E expression is reduced by 4EASO treatment in mesothelioma.

<p>Cultured normal mesothelial and mesothelioma cells were transfected with mmASO or 4EASO and eIF4E and β-actin protein expression was evaluated by immunoblot analysis from lysates harvested after 72 hours. The mmASO does not alter eIF4E levels in mesothelial cells or mesothelioma cells. The band intensity levels for eIF4E following 4EASO treatment was normalized to untreated cells for each cell line and was determined using ImageJ. β-actin level does not change upon treatment and serves as a loading control.</p