Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Radial velocity confirmation of K2-100b: A young, highly irradiated, and low-density transiting hot Neptune

We present a detailed analysis of HARPS-N radial velocity observations of K2-100, a young and active star in the Praesepe cluster, which hosts a transiting planet with a period of 1.7 d. We model the activity-induced radial velocity variations of the host star with a multidimensional Gaussian Process framework and detect a planetary signal of 10.6 \ub1 3.0 m s−1, which matches the transit ephemeris, and translates to a planet mass of 21.8 \ub1 6.2 M. We perform a suite of validation tests to confirm that our detected signal is genuine. This is the first mass measurement for a transiting planet in a young open cluster. The relatively low density of the planet, 2.04+−006661 g cm−3, implies that K2-100b retains a significant volatile envelope. We estimate that the planet is losing its atmosphere at a rate of 1011–1012 g s−1 due to the high level of radiation it receives from its host star

A dense mini-Neptune orbiting the bright young star HD 18599

© 2022 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stac2845Very little is known about the young planet population because the detection of small planets orbiting young stars is obscured by the effects of stellar activity and fast rotation which mask planets within radial velocity and transit data sets. The few planets that have been discovered in young clusters generally orbit stars too faint for any detailed follow-up analysis. Here we present the characterization of a new mini-Neptune planet orbiting the bright (V=9) and nearby K2 dwarf star, HD 18599. The planet candidate was originally detected in TESS light curves from Sectors 2, 3, 29, and 30, with an orbital period of 4.138~days. We then used HARPS and FEROS radial velocities, to find the companion mass to be 25.5$\pm$4.6~M$_\oplus$. When we combine this with the measured radius from TESS, of 2.70$\pm$0.05~R$_\oplus$, we find a high planetary density of 7.1$\pm$1.4~g cm$^{-3}$. The planet exists on the edge of the Neptune Desert and is the first young planet (300 Myr) of its type to inhabit this region. Structure models argue for a bulk composition to consist of 23% H$_2$O and 77% Rock and Iron. Future follow-up with large ground- and space-based telescopes can enable us to begin to understand in detail the characteristics of young Neptunes in the galaxy.Peer reviewe

The mass determination of TOI-519 b: a close-in giant planet transiting a metal-rich mid-M dwarf

We report the mass determination of TOI-519 b, a transiting substellar object around a mid-M dwarf. We carried out radial velocity measurements using Subaru / InfraRed Doppler (IRD), revealing that TOI-519 b is a planet with a mass of $0.463^{+0.082}_{-0.088}~M_{\rm Jup}$. We also find that the host star is metal rich ($\rm [Fe/H] = 0.27 \pm 0.09$ dex) and has the lowest effective temperature ($T_{\rm eff}=3322 \pm 49$ K) among all stars hosting known close-in giant planets based on the IRD spectra and mid-resolution infrared spectra obtained with NASA Infrared Telescope Facility / SpeX. The core mass of TOI-519 b inferred from a thermal evolution model ranges from $0$ to $\sim30~M_\oplus$, which can be explained by both the core accretion and disk instability models as the formation origins of this planet. However, TOI-519 is in line with the emerging trend that M dwarfs with close-in giant planets tend to have high metallicity, which may indicate that they formed in the core accretion model. The system is also consistent with the potential trend that close-in giant planets around M dwarfs tend to be less massive than those around FGK dwarfs.Comment: 10 pages, 5 figures. Accepted for publication in PAS

TOI-2119: A transiting brown dwarf orbiting an active M-dwarf from NASA’s TESS mission

We report the discovery of TOI-2119b, a transiting brown dwarf (BD) that orbits and is completely eclipsed by an active M-dwarf star. Using light curve data from the Transiting Exoplanet Survey Satellite mission and follow-up high-resolution Doppler spectroscopic observations, we find the BD has a radius of $R_b = 1.08 \pm 0.03{\rm R_J}$, a mass of $M_b = 64.4 \pm 2.3{\rm M_J}$, an orbital period of $P = 7.200865 \pm 0.00002$ days, and an eccentricity of $e=0.337\pm 0.002$. The host star has a mass of $M_\star = 0.53 \pm 0.02{\rm M_\odot}$, a radius of $R_\star= 0.50 \pm 0.01{\rm R_\odot}$, an effective temperature of $T_{\rm eff} = 3621 \pm 48$K, and a metallicity of $\rm [Fe/H]=+0.06\pm 0.08$. TOI-2119b joins an emerging population of transiting BDs around M-dwarf host stars, with TOI-2119 being the ninth such system. These M-dwarf--brown dwarf systems typically occupy mass ratios near $q = M_b/M_\star \approx 0.1-0.2$, which separates them from the typical mass ratios for systems with transiting substellar objects and giant exoplanets that orbit more massive stars. The nature of the secondary eclipse of the BD by the star enables us to estimate the effective temperature of the substellar object to be $2030\pm 84$K, which is consistent with predictions by substellar evolutionary models.Comment: 14 pages, 13 figures, 4 tables, accepted in MNRA

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure