Non-sputum methods are urgently needed to improve tuberculosis diagnosis and treatment monitoring in children. This study evaluated the ability of a serum assay quantifying a species-specific peptide ...of the Mycobacterium tuberculosis CFP-10 virulence factor via nanotechnology and matrix-assisted laser desorption ionization time-of-flight mass spectrometry to diagnose tuberculosis in HIV-infected and HIV-uninfected infants.
Serum CFP-10 peptide signal was blinded evaluated in cryopreserved sera of 519 BCG-immunized, HIV-exposed infants (284 HIV-infected, 235 HIV-uninfected) from a multi-center randomized placebo-controlled isoniazid prophylaxis trial conducted in southern Africa between 2004 and 2008, who were followed up to 192 weeks for Mtb infection and TB. Children were classified as confirmed, unconfirmed, or unlikely tuberculosis cases using 2015 NIH diagnostic criteria for pediatric TB.
In HIV-infected infants, CFP-10 signal had 100% sensitivity for confirmed TB (5/5, 95% CI, 47.8-100) and 83.7% sensitivity for unconfirmed TB (36/43, 95% CI 69.3-93.2), with 93.1% specificity (203/218, 95% CI 88.9-96.1). In HIV-uninfected infants, CFP-10 signal detected the single confirmed TB case and 75.0% of unconfirmed TB cases (15/20; 95% CI 50.9-91.3), with 96.2% specificity (177/184, 95% CI, 92.3-98.5). Serum CFP-10 achieved 77% diagnostic sensitivity for confirmed and unconfirmed TB (13/17, 95% CI, 50-93%) at ≤ 24 weeks pre-diagnosis, and both CFP-10-positivity and concentration declined following anti-TB therapy initiation.
Serum CFP-10 signal exhibited high diagnostic sensitivity and specificity for tuberculosis in HIV-infected and HIV-uninfected infants and potential utility for early TB detection and monitoring of anti-TB treatment responses.
Bacterial survival is fraught with antagonism, including that deriving from viruses and competing bacterial cells. It is now appreciated that bacteria mount complex antiviral responses; however, ...whether a coordinated defense against bacterial threats is undertaken is not well understood. Previously, we showed that
possess a danger-sensing pathway that is a critical fitness determinant during competition against other bacteria. Here, we conducted genome-wide screens in
that reveal three conserved and widespread interbacterial antagonism resistance clusters (
). We find that although
are coordinately activated by the Gac/Rsm danger-sensing system, they function independently and provide idiosyncratic defense capabilities, distinguishing them from general stress response pathways. Our findings demonstrate that Arc3 family proteins provide specific protection against phospholipase toxins by preventing the accumulation of lysophospholipids in a manner distinct from previously characterized membrane repair systems. These findings liken the response of
to bacterial threats to that of eukaryotic innate immunity, wherein threat detection leads to the activation of specialized defense systems.
We report the discovery of a sextuply eclipsing sextuple star system from TESS data, TIC 168789840, also known as TYC 7037-89-1, the first known sextuple system consisting of three eclipsing ...binaries. The target was observed in Sectors 4 and 5 during Cycle 1, with light curves extracted from TESS Full Frame Image data. It was also previously observed by the WASP survey and ASAS-SN. The system consists of three gravitationally bound eclipsing binaries in a hierarchical structure of an inner quadruple system with an outer binary subsystem. Follow up
observations from several different observatories were conducted as a means of determining additional parameters. The system was resolved by speckle interferometry with a 0 42 separation between the inner quadruple and outer binary, inferring an estimated outer period of ∼2 kyr. It was determined that the fainter of the two resolved components is an 8.217 day eclipsing binary, which orbits the inner quadruple that contains two eclipsing binaries with periods of 1.570 days and 1.306 days. Markov Chain Monte Carlo (MCMC) analysis of the stellar parameters has shown that the three binaries of TIC 168789840 are “triplets,” as each binary is quite similar to the others in terms of mass, radius, and Teff. As a consequence of its rare composition, structure, and orientation, this object can provide important new insight into the formation, dynamics, and evolution of multiple star systems. Future observations could reveal if the intermediate and outer orbital planes are all aligned with the planes of the three inner eclipsing binaries.
Within schistosomiasis control, assessing environmental risk of currently non-treated demographic groups e.g. pre-school-aged children (PSAC) and their mothers is important. We conducted a pilot ...micro-epidemiological assessment at the crater lake of Barombi Kotto, Cameroon with GPS tracking and infection data from 12 PSAC-mother pairs (n = 24) overlaid against environmental sampling inclusive of snail, parasite and water-use information. Several high-risk locations or ‘hotspots’ with elevated water contact, increased intermediate snail host densities and detectable schistosome environmental DNA (eDNA) were identified. Exposure between PSAC and mother pairs was temporally and spatially associated, suggesting interventions which can benefit both groups simultaneously might be feasible. When attempting to interrupt parasite transmission in future, overlaid maps of snail, parasite and water contact data can guide fine-scale spatial targeting of environmental interventions.
Summary
Areas with elevated water contact for pre-school-aged children (PSAC) and their mothers were found to have high intermediate snail host densities and detectable schistosome environmental DNA (eDNA). Display omitted
Abstract
We present a strongly interacting quadruple system associated with the K2 target EPIC 220204960. The K2 target itself is a Kp = 12.7-mag star at Teff ≃ 6100 K, which we designate as ‘B-N’ ...(blue northerly image). The host of the quadruple system, however, is a Kp ≃ 17-mag star with a composite M-star spectrum, which we designate as ‘R-S’ (red southerly image). With a 3.2-arcsec separation and similar radial velocities and photometric distances, ‘B-N’ is likely physically associated with ‘R-S’, making this a quintuple system, but that is incidental to our main claim of a strongly interacting quadruple system in ‘R-S’. The two binaries in ‘R-S’ have orbital periods of 13.27 and 14.41 d, respectively, and each has an inclination angle of ≳89°. From our analysis of radial-velocity (RV) measurements, and of the photometric light curve, we conclude that all four stars are very similar with masses close to 0.4 M⊙. Both of the binaries exhibit significant eclipse-timing variations where those of the primary and secondary eclipses ‘diverge’ by 0.05 d over the course of the 80-d observations. Via a systematic set of numerical simulations of quadruple systems consisting of two interacting binaries, we conclude that the outer orbital period is very likely to be between 300 and 500 d. If sufficient time is devoted to RV studies of this faint target, the outer orbit should be measurable within a year.
Aims. We have identified nearly a hundred close triply eclipsing hierarchical triple star systems from data taken with the space telescope TESS. These systems are noteworthy in that we can ...potentially determine their dynamical and astrophysical parameters with a high precision. In the present paper, we report the comprehensive study of seven new compact triply eclipsing triple star systems taken from this larger sample: TICs 133771812, 176713425, 185615681, 287756035, 321978218, 323486857, and 650024463. Methods. Most of the data for this study come from TESS observations, but two of them have Gaia measurements of their outer orbits, and we obtained supplemental radial velocity (RV) measurements for three of the systems. The eclipse timing variation curves extracted from the TESS data, the photometric light curves, the RV points, and the spectral energy distribution (SED) are combined in a complex photodynamical analysis to yield the stellar and orbital parameters of all seven systems. Results. Four of the systems are quite compact with outer periods in the range of 41–56 days. All of the systems are substantially flat, with mutual inclination angles of ≲2°. Including the systems reported in this work, we have now studied in considerable detail some 30 triply eclipsing triples with TESS, and are accumulating a meaningful census of these systems.
ABSTRACT
We report detection of quasi-periodic (1.5-d) dimming of HD 240779, the solar-mass primary in a 5 arcsec visual binary (also TIC 284730577), by the Transiting Exoplanet Survey Satellite. ...This dimming, as has been shown for other ‘dipper’ stars, is likely due to occultation by circumstellar dust. The barycentric space motion, lithium abundance, rotation, and chromospheric emission of the stars in this system point to an age of ≈125 Myr, and possible membership in the AB Doradus moving group. As such it occupies an important but poorly explored intermediate regime of stars with transient dimming between young stellar objects in star-forming regions and main-sequence stars, and between UX Orionis-type Ae/Be stars and M-type ‘dippers’. HD 240779, but not its companion BD+10 714B, has Wide-field Infrared Survey Explorer (WISE)-detected excess infrared emission at 12 and 22 μm indicative of circumstellar dust. We propose that infrared emission is produced by collisions of planetesimals during clearing of a residual disc at the end of rocky planet formation, and that quasi-periodic dimming is produced by the rapid disintegration of a ≳100 km planetesimal near the silicate evaporation radius. Further studies of this and similar systems will illuminate a poorly understood final phase of rocky planet formation like that which produced the inner Solar system.
Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene are responsible for a familial form of amyotrophic lateral sclerosis. In humans and experimental models, death of motor neurons is preceded by ...formation of cytoplasmic aggregates containing mutant SOD-1 protein. In our previous studies, heat shock protein 70 (HSP70) prolonged viability of cultured motor neurons expressing mutant human SOD-1 and reduced formation of aggregates. In this paper, we report that mutant SOD-1 proteins have altered solubility in cells relative to wild-type SOD-1 and can form a direct association with HSP70 and other stress proteins. Whereas wild-type human and endogenous mouse SOD-1 were detergent-soluble, a portion of mutant SOD-1 was detergent-insoluble in protein extracts of NIH3T3 transfected with SOD-1 gene constructs, spinal cord cultures established from G93A SOD-1 transgenic mouse embryos, and lumbar spinal cord from adult G93A transgenic mice. A direct association of HSP70, HSP40, and alphaB-crystallin with mutant SOD-1 (G93A or G41S), but not wild-type or endogenous mouse SOD-1, was demonstrated by coimmunoprecipitation. Mutant SOD-1.HSP70 complexes were predominantly in the detergent-insoluble fraction. However, only a small percentage of total cellular mutant SOD-1 was detergent-insoluble, suggesting that mutation-induced alteration of protein conformation may not in itself be sufficient for direct interaction with heat shock proteins.
The World Health Organization recommends isoniazid preventive therapy (IPT) for people living with HIV (PLHIV) to prevent tuberculosis (TB), including pregnant women. Recent trial results suggest ...increased adverse pregnancy outcomes associated with IPT during pregnancy. Data are limited regarding programmatic IPT use in pregnant PLHIV.
We assessed previous programmatic IPT during pregnancy among HIV-infected mothers on enrollment to an infant TB prevention trial in Kenya. Pregnancy IPT use was assessed by the estimated conception date assuming 38 weeks of gestation. Correlates of initiation and completion were analyzed by relative risk regression, using generalized linear models with log link and Poisson family adjusted for IPT initiation year.
Between August 15, 2016, to June 6, 2018, 300 HIV-infected women enrolled at 6 weeks postpartum. Two hundred twenty-four (74.7%) women reported previous IPT, of whom 155/224 (69.2%) had any pregnancy IPT use. Forty-five (29.0%) initiated preconception extending into early pregnancy, 41 (26.5%) initiated and completed during pregnancy, and 69 (44.5%) initiated in pregnancy and extended into early postpartum. The median gestational age at IPT pregnancy initiation was 15.1 weeks (interquartile range 8.3-28.4). Pregnancy/early postpartum IPT initiation was associated with new pregnancy HIV diagnosis adjusted relative risk 1.9 95% confidence interval (CI): 1.6 to 2.2, P < 0.001. Six-month IPT completion rates were high 147/160 (91.9%) among women with sufficient time to complete before trial enrollment and similar among preconception or during pregnancy initiators adjusted relative risk 0.93 (95% confidence interval: 0.83 to 1.04, P = 0.19).
Programmatic IPT use was high in pregnant PLHIV, with frequent periconception and early pregnancy initiation. Programmatic surveillance could provide further insights on pregnancy IPT implementation and maternal and infant safety outcomes.
Abstract
Background
The purpose of this study was to estimate prevalence of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients admitted to obstetric ...inpatient units throughout the United States as detected by universal screening. We sought to describe the relationship between obstetric inpatient asymptomatic infection rates and publicly available surrounding community infection rates.
Methods
A cross-sectional study in which medical centers reported rates of positive SARS-CoV-2 testing in asymptomatic pregnant and immediate postpartum patients over a 1–3-month time span in 2020. Publicly reported SARS-CoV-2 case rates from the relevant county and state for each center were collected from the COVID Act Now dashboard and the COVID Tracking Project for correlation analysis.
Results
Data were collected from 9 health centers, encompassing 18 hospitals. Participating health centers were located in Alabama, California, Illinois, Louisiana, New Jersey, North Carolina, Pennsylvania, Rhode Island, Utah, and Washington State. Each hospital had an active policy for universal SARS-CoV-2 testing on obstetric inpatient units. A total of 10 147 SARS-CoV-2 tests were administered, of which 124 were positive (1.2%). Positivity rates varied by site, ranging from 0–3.2%. While SARS-CoV-2 infection rates were lower in asymptomatic obstetric inpatient groups than the surrounding communities, there was a positive correlation between positivity rates in obstetric inpatient units and their surrounding county (P=.003, r=.782) and state (P=.007, r=.708).
Conclusions
Given the correlation between community and obstetric inpatient rates, the necessity of SARS-CoV-2–related healthcare resource utilization in obstetric inpatient units may be best informed by surrounding community infection rates.
There was a significant positive correlation between SARS-CoV-2 positivity rates in obstetric inpatient units and their surrounding county and state. Healthcare resource utilization related to SARS-CoV-2 testing in obstetric inpatient units may be best informed by surrounding community infection rates.
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