Chandra Study of Young Stellar Objects in the NGC 1333 Star-forming Cloud

NGC 1333, a highly active star formation region within the Perseus molecular cloud complex, has been observed with the ACIS-I detector on board the Chandra X-ray Observatory. In our image with a sensitivity limit of ~ 1e28 erg/s, we detect 127 X-ray sources, of which, 95 are known cluster members. The X-ray luminosity function of the discovered YSO population spans a range of 1e28-3.2e31 erg/s in the 0.5-8 keV band. Comparison with K-band source counts indicates that we detect all of the known cluster members with K < 12, and about half of members with K > 12. We detect seven X-ray emitting YSOs which drive optically visible jets as well as one deeply embedded object that has not been detected in near-IR observations. The presence or absence of an outflows does not appear to produce any difference in X-ray properties of YSOs. We also find no systematic differences in X-ray luminosity distributions between two complete subsamples of CTTs and WTTs. That suggests that there is no difference in the astrophysical mechanism of WTT and CTT X-ray emission production. Additional results include: the X-ray emission from two late-B stars which illuminate the reflection nebula originates from unresolved late-type companions; two T Tauri stars are discovered as previously unknown components of visual binaries; and the X-ray counterpart of SVS 16 has the column density much lower than that expected from near-IR photometry and thus its X-ray luminosity is not anomalously high, as has been previously suggested.Comment: 53 pages, 14 figures, 3 tables. To appear in the Astrophysical Journal; scheduled for 2002, ApJ, 575 (August 10th). High quality copy available at ftp://ftp.astro.psu.edu/pub/gkosta/ngc1333

From sulphur to perfume: spa and SPA at Monchique, Algarve

In the thermal village of Monchique, Algarve, different streams of water-related knowledge and practices coexisted for centuries. Those waters were traditionally known as águas santas (holy waters) and believed to have redemptive healing powers. In the seventeenth century, the Catholic church took control of the place, refashioned the bathing rituals, developed infrastructures and provided assistance to the patients, granting free treatment to the poor. In the nineteenth century, the state replaced the church and imposed that treatments should be provided by professionals trained in the scientific principles of medical hydrology. Secular and scientific as they were, clinical logbooks still allowed for the account of patients that embodied miracle-like redemptive cures ‘at the third bath’. People went to Monchique both for its magic and its medicine, bringing in the body ailments achieved in their lives of hard labour. They also went there for a socialising break while healing. From mendicants to rich landowners, coming mostly from the Algarve and neighbouring Alentejo, they crowded the place in summertime. In the twentieth century, as in other places in continental Europe, the spa evolved into a highly medicalised place that qualified for medical expenses reimbursements, which implied the eclipsing – at least from representation – of its leisure component. In the twenty-first century, a new trend of consumer-centred, market-based, post-water balneology with an emphasis on wellness and leisure reinvented the spa as place for lush and diversified consumption. This article argues that the seemingly contradictory systems (markets and medicine) coexist much in the same way that magic, religion and medicine coexisted in the old water sites. The new SPAs, rather than putting an end to the old spas, have enabled them to survive by reinventing thermal sites as places of attraction and leisure

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Stellar Spectroscopy in the Near-infrared with a Laser Frequency Comb

The discovery and characterization of exoplanets around nearby stars is driven by profound scientific questions about the uniqueness of Earth and our Solar System, and the conditions under which life could exist elsewhere in our Galaxy. Doppler spectroscopy, or the radial velocity (RV) technique, has been used extensively to identify hundreds of exoplanets, but with notable challenges in detecting terrestrial mass planets orbiting within habitable zones. We describe infrared RV spectroscopy at the 10 m Hobby-Eberly telescope that leverages a 30 GHz electro-optic laser frequency comb with nanophotonic supercontinuum to calibrate the Habitable Zone Planet Finder spectrograph. Demonstrated instrument precision <10 cm/s and stellar RVs approaching 1 m/s open the path to discovery and confirmation of habitable zone planets around M-dwarfs, the most ubiquitous type of stars in our Galaxy

Florbetapir F 18 amyloid PET and 36-month cognitive decline:a prospective multicenter study

This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ−), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ− subjects on the ADAS-Cog over 36 months (5.66±1.47 vs −0.71±1.09, P=0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P<0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P<0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ− subjects do

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

SCYX-7158, an Orally-Active Benzoxaborole for the Treatment of Stage 2 Human African Trypanosomiasis

Human African trypanosomiasis (HAT) is caused by infection with the parasite Trypanosoma brucei and is an important public health problem in sub-Saharan Africa. New, safe, and effective drugs are urgently needed to treat HAT, particularly stage 2 disease where the parasite infects the brain. Existing therapies for HAT have poor safety profiles, difficult treatment regimens, limited effectiveness, and a high cost of goods. Through an integrated drug discovery project, we have discovered and optimized a novel class of boron-containing small molecules, benzoxaboroles, to deliver SCYX-7158, an orally active preclinical drug candidate. SCYX-7158 cured mice infected with T. brucei, both in the blood and in the brain. Extensive pharmacokinetic characterization of SCYX-7158 in rodents and non-human primates supports the potential of this drug candidate for progression to IND-enabling studies in advance of clinical trials for stage 2 HAT

Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors

Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior

A sub-Neptune sized planet transiting the M2.5-dwarf G 9-40: Validation with the Habitable-zone Planet Finder

We validate the discovery of a 2 Earth radii sub-Neptune-size planet around the nearby high proper motion M2.5-dwarf G 9-40 (EPIC 212048748), using high-precision near-infrared (NIR) radial velocity (RV) observations with the Habitable-zone Planet Finder (HPF), precision diffuser-assisted ground-based photometry with a custom narrow-band photometric filter, and adaptive optics imaging. At a distance of $d=27.9\mathrm{pc}$, G 9-40b is the second closest transiting planet discovered by K2 to date. The planet's large transit depth ($\sim$3500ppm), combined with the proximity and brightness of the host star at NIR wavelengths (J=10, K=9.2) makes G 9-40b one of the most favorable sub-Neptune-sized planet orbiting an M-dwarf for transmission spectroscopy with JWST, ARIEL, and the upcoming Extremely Large Telescopes. The star is relatively inactive with a rotation period of $\sim$29 days determined from the K2 photometry. To estimate spectroscopic stellar parameters, we describe our implementation of an empirical spectral matching algorithm using the high-resolution NIR HPF spectra. Using this algorithm, we obtain an effective temperature of $T_{\mathrm{eff}}=3404\pm73$K, and metallicity of $\mathrm{[Fe/H]}=-0.08\pm0.13$. Our RVs, when coupled with the orbital parameters derived from the transit photometry, exclude planet masses above $11.7 M_\oplus$ with 99.7% confidence assuming a circular orbit. From its radius, we predict a mass of $M=5.0^{+3.8}_{-1.9} M_\oplus$ and an RV semi-amplitude of $K=4.1^{+3.1}_{-1.6}\mathrm{m\:s^{-1}}$, making its mass measurable with current RV facilities. We urge further RV follow-up observations to precisely measure its mass, to enable precise transmission spectroscopic measurements in the future.Comment: Accepted for publication in AJ, 22 pages, 15 figure