The Gaia-ESO Survey : The analysis of high-resolution UVES spectra of FGK-type stars

Date of Acceptance: 01/09/2014Context. The ongoing Gaia-ESO Public Spectroscopic Survey is using FLAMES at the VLT to obtain high-quality medium-resolution Giraffe spectra for about 105 stars and high-resolution UVES spectra for about 5000 stars. With UVES, the Survey has already observed 1447 FGK-type stars. Aims. These UVES spectra are analyzed in parallel by several state-of-the-art methodologies. Our aim is to present how these analyses were implemented, to discuss their results, and to describe how a final recommended parameter scale is defined. We also discuss the precision (method-to-method dispersion) and accuracy (biases with respect to the reference values) of the final parameters. These results are part of the Gaia-ESO second internal release and will be part of its first public release of advanced data products. Methods. The final parameter scale is tied to the scale defined by the Gaia benchmark stars, a set of stars with fundamental atmospheric parameters. In addition, a set of open and globular clusters is used to evaluate the physical soundness of the results. Each of the implemented methodologies is judged against the benchmark stars to define weights in three different regions of the parameter space. The final recommended results are the weighted medians of those from the individual methods. Results. The recommended results successfully reproduce the atmospheric parameters of the benchmark stars and the expected Teff-log g relation of the calibrating clusters. Atmospheric parameters and abundances have been determined for 1301 FGK-type stars observed with UVES. The median of the method-to-method dispersion of the atmospheric parameters is 55 K for Teff, 0.13 dex for log g and 0.07 dex for [Fe/H]. Systematic biases are estimated to be between 50-100 K for Teff, 0.10-0.25 dex for log g and 0.05-0.10 dex for [Fe/H]. Abundances for 24 elements were derived: C, N, O, Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ba, Nd, and Eu. The typical method-to-method dispersion of the abundances varies between 0.10 and 0.20 dex. Conclusions. The Gaia-ESO sample of high-resolution spectra of FGK-type stars will be among the largest of its kind analyzed in a homogeneous way. The extensive list of elemental abundances derived in these stars will enable significant advances in the areas of stellar evolution and Milky Way formation and evolution.Peer reviewe

RNAi screen for NRF2 inducers identifies targets that rescue primary lung epithelial cells from cigarette smoke induced radical stress

Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent condition characterized by inflammation and progressive obstruction of the airways. At present, there is no treatment that suppresses the chronic inflammation of the disease, and COPD patients often succumb to the condition. Excessive oxidative stress caused by smoke inhalation is a major driving force of the disease. The transcription factor NRF2 is a critical player in the battle against oxidative stress and its function is impaired in COPD. Increasing NRF2 activity may therefore be a viable therapeutic option for COPD treatment. We show that down regulation of KEAP1, a NRF2 inhibitor, protects primary human lung epithelial cells from cigarette-smoke-extract (CSE) induced cell death in an established in vitro model of radical stress. To identify new potential drug targets with a similar effect, we performed a siRNA screen of the 'druggable' genome using a NRF2 transcriptional reporter cell line. This screen identified multiple genes that when down regulated increased NRF2 transcriptional activity and provided a survival benefit in the in vitro model. Our results suggest that inhibiting components of the ubiquitin-proteasome system will have the strongest effects on NRF2 transcriptional activity by increasing NRF2 levels. We also find that down regulation of the small GTPase Rab28 or the Estrogen Receptor ESRRA provide a survival benefit. Rab28 knockdown increased NRF2 protein levels, indicating that Rab28 may regulate NRF2 proteolysis. Conversely ESRRA down regulation increased NRF2 transcriptional activity without affecting NRF2 levels, suggesting a proteasome-independent mechanism

A CRISPR screen identifies a pathway required for paraquat-induced cell death

Paraquat, a herbicide linked to Parkinson's disease, generates reactive oxygen species (ROS), which causes cell death. Because the source of paraquat-induced ROS production remains unknown, we conducted a CRISPR-based positive-selection screen to identify metabolic genes essential for paraquat-induced cell death. Our screen uncovered three genes, POR (cytochrome P450 oxidoreductase), ATP7A (copper transporter), and SLC45A4 (sucrose transporter), required for paraquat-induced cell death. Furthermore, our results revealed POR as the source of paraquat-induced ROS production. Thus, our study highlights the use of functional genomic screens for uncovering redox biology

Quality and reporting of clinical guidelines for breast cancer treatment: A systematic review

Background: High-quality, well-reported clinical practice guidelines (CPGs) and consensus statements (CSs) underpinned by systematic reviews are needed. We appraised the quality and reporting of CPGs and CSs for breast cancer (BC) treatment. Methods: Following protocol registration (Prospero no: CRD42020164801), CPGs and CSs on BC treatment were identified, without language restrictions, through a systematic search of bibliographic databases (MEDLINE, EMBASE, Web of Science, Scopus, CDSR) and online sources (12 guideline databases and 51 professional society websites) from January 2017 to June 2020. Data were extracted in duplicate assessing overall quality using AGREE II (% of maximum score) and reporting compliance using RIGHT (% of total 35 items); reviewer agreement was 98% and 96% respectively. Results: There were 59 relevant guidance documents (43 CPGs, 16 CSs), of which 20 used systematic reviews for evidence synthesis. The median overall quality was 54.0% (IQR 35.9e74.3) and the median overall reporting compliance was 60.9% (IQR 44.5e84.4). The correlation between quality and reporting was 0.9. Compared to CSs, CPGs had better quality (55.4% vs 44.2%; p ¼ 0.032) and reporting (67.18% vs 44.5%; p ¼ 0.005). Compared to subjective methods of evidence analysis, guidance documents that used systematic reviews had better quality (76.3% vs 51.4%; p ¼ 0.001) and reporting (87.1% vs 59.4%; p ¼ 0.001). Conclusion: The quality and reporting of CPGs and CSs in BC treatment were moderately strong. Systematic reviews should be used to improve the quality and reporting of CPGs and CSs.Beatriz Galindo (senor modality) Program by the Ministry of Science, Innovation, and Universities of the Spanish Governmen

The High-Altitude Water Cherenkov (HAWC) Observatory in M\'exico: The Primary Detector

The High-Altitude Water Cherenkov (HAWC) observatory is a second-generation continuously operated, wide field-of-view, TeV gamma-ray observatory. The HAWC observatory and its analysis techniques build on experience of the Milagro experiment in using ground-based water Cherenkov detectors for gamma-ray astronomy. HAWC is located on the Sierra Negra volcano in M\'exico at an elevation of 4100 meters above sea level. The completed HAWC observatory principal detector (HAWC) consists of 300 closely spaced water Cherenkov detectors, each equipped with four photomultiplier tubes to provide timing and charge information to reconstruct the extensive air shower energy and arrival direction. The HAWC observatory has been optimized to observe transient and steady emission from sources of gamma rays within an energy range from several hundred GeV to several hundred TeV. However, most of the air showers detected are initiated by cosmic rays, allowing studies of cosmic rays also to be performed. This paper describes the characteristics of the HAWC main array and its hardware.Comment: Accepted for publications in Nuclear Inst. and Methods in Physics Research, A (2023) 168253 ( https://www.sciencedirect.com/science/article/abs/pii/S0168900223002437 ); 39 pages, 14 Figure

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Medicinal and ethnoveterinary remedies of hunters in Trinidad

BACKGROUND: Ethnomedicines are used by hunters for themselves and their hunting dogs in Trinidad. Plants are used for snakebites, scorpion stings, for injuries and mange of dogs and to facilitate hunting success. RESULTS: Plants used include Piper hispidum, Pithecelobium unguis-cati, Bauhinia excisa, Bauhinia cumanensis, Cecropia peltata, Aframomum melegueta, Aristolochia rugosa, Aristolochia trilobata, Jatropha curcas, Jatropha gossypifolia, Nicotiana tabacum, Vernonia scorpioides, Petiveria alliacea, Renealmia alpinia, Justicia secunda, Phyllanthus urinaria,Phyllanthus niruri,Momordica charantia, Xiphidium caeruleum, Ottonia ovata, Lepianthes peltata, Capsicum frutescens, Costus scaber, Dendropanax arboreus, Siparuma guianensis, Syngonium podophyllum, Monstera dubia, Solanum species, Eclipta prostrata, Spiranthes acaulis, Croton gossypifolius, Barleria lupulina, Cola nitida, Acrocomia ierensis (tentative ID). CONCLUSION: Plant use is based on odour, and plant morphological characteristics and is embedded in a complex cultural context based on indigenous Amerindian beliefs. It is suggested that the medicinal plants exerted a physiological action on the hunter or his dog. Some of the plants mentioned contain chemicals that may explain the ethnomedicinal and ethnoveterinary use. For instance some of the plants influence the immune system or are effective against internal and external parasites. Plant baths may contribute to the health and well being of the hunting dogs

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)