We present the spectral analysis of Chandra/High Energy Transmission Grating Spectrometer (HETGS) and NuSTAR observations of the quasar PDS 456 from 2015, and XMM-Newton and NuSTAR archival data from ...2013 to 2014, together with Chandra/HETGS data from 2003. We analyzed these three different epochs in a consistent way, looking for absorption features corresponding to highly ionized blueshifted absorption lines from H-like and He-like ions of iron (and nickel), as well as of other elements (O, Ne, Si, and S) in the soft band. We confirm the presence of a persistent ultra-fast outflow (UFO) with a velocity of vout = −0.24 to −0.29 c, that has previously been detected. We also report the detection of an additional faster component of the UFO with a relativistic velocity of vout = −0.48 c. We implemented photoionization modeling, using XSTAR analytic model warmabs, to characterize the physical properties of the different kinematic components of the UFO and of the partially covering absorber detected in PDS 456. These two relativistic components of the UFO observed in the three epochs analyzed in this paper are powerful enough to impact the host galaxy of PDS 456 through feedback from active galactic nuclei.
The CATNON trial investigated the addition of concurrent, adjuvant, and both current and adjuvant temozolomide to radiotherapy in adults with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas. ...The benefit of concurrent temozolomide chemotherapy and relevance of mutations in the IDH1 and IDH2 genes remain unclear.
This randomised, open-label, phase 3 study done in 137 institutions across Australia, Europe, and North America included patients aged 18 years or older with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas and a WHO performance status of 0–2. Patients were randomly assigned (1:1:1:1) centrally using a minimisation technique to radiotherapy alone (59·4 Gy in 33 fractions; three-dimensional conformal radiotherapy or intensity-modulated radiotherapy), radiotherapy with concurrent oral temozolomide (75 mg/m2 per day), radiotherapy with adjuvant oral temozolomide (12 4-week cycles of 150–200 mg/m2 temozolomide given on days 1–5), or radiotherapy with both concurrent and adjuvant temozolomide. Patients were stratified by institution, WHO performance status score, age, 1p loss of heterozygosity, the presence of oligodendroglial elements on microscopy, and MGMT promoter methylation status. The primary endpoint was overall survival adjusted by stratification factors at randomisation in the intention-to-treat population. A second interim analysis requested by the independent data monitoring committee was planned when two-thirds of total required events were observed to test superiority or futility of concurrent temozolomide. This study is registered with ClinicalTrials.gov, NCT00626990.
Between Dec 4, 2007, and Sept 11, 2015, 751 patients were randomly assigned (189 to radiotherapy alone, 188 to radiotherapy with concurrent temozolomide, 186 to radiotherapy and adjuvant temozolomide, and 188 to radiotherapy with concurrent and adjuvant temozolomide). Median follow-up was 55·7 months (IQR 41·0–77·3). The second interim analysis declared futility of concurrent temozolomide (median overall survival was 66·9 months 95% CI 45·7–82·3 with concurrent temozolomide vs 60·4 months 45·7–71·5 without concurrent temozolomide; hazard ratio HR 0·97 99·1% CI 0·73–1·28, p=0·76). By contrast, adjuvant temozolomide improved overall survival compared with no adjuvant temozolomide (median overall survival 82·3 months 95% CI 67·2–116·6 vs 46·9 months 37·9–56·9; HR 0·64 95% CI 0·52–0·79, p<0·0001). The most frequent grade 3 and 4 toxicities were haematological, occurring in no patients in the radiotherapy only group, 16 (9%) of 185 patients in the concurrent temozolomide group, and 55 (15%) of 368 patients in both groups with adjuvant temozolomide. No treatment-related deaths were reported.
Adjuvant temozolomide chemotherapy, but not concurrent temozolomide chemotherapy, was associated with a survival benefit in patients with 1p/19q non-co-deleted anaplastic glioma. Clinical benefit was dependent on IDH1 and IDH2 mutational status.
Merck Sharpe & Dohme.
The hard state of X-ray binaries (XRBs) is characterized by a power-law spectrum in the X-ray band and a flat/inverted radio/IR spectrum associated with occasionally imaged compact jets. It has ...generally been thought that the hard X-rays result from Compton upscattering of thermal accretion disk photons by a hot, coronal plasma whose properties are inferred via spectral fitting. Interestingly, these properties - especially those from certain magnetized corona models - are very similar to the derived plasma conditions at the jet footpoints. Here we explore the question of whether the "corona" and "jet base" are in fact related, starting by testing the strongest premise that they are synonymous. In such models, the radio through the soft X-rays are dominated by synchrotron emission, while the hard X-rays are dominated by inverse Compton at the jet base - with both disk and synchrotron photons acting as seed photons. The conditions at the jet base fix the conditions along the rest of the jet, thus creating a direct link between the X-ray and radio emission. We also add to this model a simple iron line and convolve the spectrum with neutral reflection. After forward-folding the predicted spectra through the detector response functions, we compare the results to simultaneous radio/X-ray data obtained from the hard states of the Galactic XRBs GX 339-4 and Cygnus X-1. Results from simple Compton corona model fits are also presented for comparison. We demonstrate that the jet model fits are statistically as good as the single-component corona model X-ray fits, yet are also able to address the simultaneous radio data.
The role of temozolomide chemotherapy in newly diagnosed 1p/19q non-co-deleted anaplastic gliomas, which are associated with lower sensitivity to chemotherapy and worse prognosis than 1p/19q ...co-deleted tumours, is unclear. We assessed the use of radiotherapy with concurrent and adjuvant temozolomide in adults with non-co-deleted anaplastic gliomas.
This was a phase 3, randomised, open-label study with a 2 × 2 factorial design. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with WHO performance status scores of 0–2. The randomisation schedule was generated with the electronic EORTC web-based ORTA system. Patients were assigned in equal numbers (1:1:1:1), using the minimisation technique, to receive radiotherapy (59·4 Gy in 33 fractions of 1·8 Gy) alone or with adjuvant temozolomide (12 4-week cycles of 150–200 mg/m2 temozolomide given on days 1–5); or to receive radiotherapy with concurrent temozolomide 75 mg/m2 per day, with or without adjuvant temozolomide. The primary endpoint was overall survival adjusted for performance status score, age, 1p loss of heterozygosity, presence of oligodendroglial elements, and MGMT promoter methylation status, analysed by intention to treat. We did a planned interim analysis after 219 (41%) deaths had occurred to test the null hypothesis of no efficacy (threshold for rejection p<0·0084). This trial is registered with ClinicalTrials.gov, number NCT00626990.
At the time of the interim analysis, 745 (99%) of the planned 748 patients had been enrolled. The hazard ratio for overall survival with use of adjuvant temozolomide was 0·65 (99·145% CI 0·45–0·93). Overall survival at 5 years was 55·9% (95% CI 47·2–63·8) with and 44·1% (36·3–51·6) without adjuvant temozolomide. Grade 3–4 adverse events were seen in 8–12% of 549 patients assigned temozolomide, and were mainly haematological and reversible.
Adjuvant temozolomide chemotherapy was associated with a significant survival benefit in patients with newly diagnosed non-co-deleted anaplastic glioma. Further analysis of the role of concurrent temozolomide treatment and molecular factors is needed.
Schering Plough and MSD.
Abstract
4U 1957+11 is a black hole candidate system that has been in a soft X-ray spectral state since its discovery. We present analyses of recent joint NICER and NuSTAR spectra, which are ...extremely well described by a highly inclined disk accreting into a near maximally spinning black hole. Owing to the broad X-ray coverage of NuSTAR, the fitted spin and inclination are strongly constrained for our hypothesized disk models. The faintest spectra are observed out to 20 keV, even though their hard tail components are almost absent when described with a simple corona. The hard tail increases with luminosity, but shows clear two-track behavior with one track having appreciably stronger tails. The disk spectrum color-correction factor is anticorrelated with the strength of the hard tail (e.g., as measured by the Compton
y
parameter). Although the spin and inclination parameters are strongly constrained for our chosen model, the mass and distance are degenerate parameters. We use our spectral fits, along with a theoretical prior on color-correction, an observational prior on likely fractional Eddington luminosity, and an observational prior on distance obtained from Gaia studies, to present mass and distance contours for this system. The most likely parameters, given our presumed disk model, suggest a 4.6
M
⊙
black hole at 7.8 kpc observed at luminosities ranging from ≈1.7% to 9% of Eddington. This would place 4U 1957+11 as one of the few actively accreting sources within the
mass gap
of ≈2–5
M
⊙
where there are few known massive neutron stars or low-mass black holes. Higher mass and distance, however, remain viable.
We present the analysis of seven Chandra High Energy Transmission Grating Spectrometer and six simultaneous RXTE Proportional Counter Array observations of the persistent neutron star (NS) low-mass ...X-ray binary GX 13+1 on its normal and horizontal branches. Across nearly 10 years, GX 13+1 is consistently found to be accreting at 50%-70% Eddington, and all observations exhibit multiple narrow, blueshifted absorption features, the signature of a disk wind, despite the association of normal and horizontal branches with jet activity. A single absorber with standard abundances cannot account for all seven major disk wind features, indicating multiple absorption zones may be present. Two or three absorbers can produce all of the absorption features at their observed broadened widths and reveal that multiple kinematic components produce the accretion disk wind signature. Assuming the most ionized absorber reflects the physical conditions closest to the NS, we estimate a wind launching radius of 7 × 1010 cm, for an electron density of 1012 cm−3. This is consistent with the Compton radius and also with a thermally driven wind. Because of the source's high Eddington fraction, radiation pressure likely facilitates the wind launching.
Although the term "vaccine hesitancy" has achieved great prominence, the extent to which US parents have reluctance, doubts, or indecision when it comes to vaccines recommended for children and how ...such hesitancy is manifest are unclear. A narrative review approach that placed emphasis on recent data and published work is used to surface evidence and insights into the current state of US parent vaccine hesitancy. The assessment finds evidence that ∼6% to 25% of parents may be vaccine hesitant, that hesitancy is higher for influenza and HPV vaccines, and there are indications that addressing parent hesitancy has become more challenging.
Combination chemotherapy is commonly used to treat advanced breast cancer. However, treatment success is often limited due to systemic toxicity. To improve therapeutic efficacy, polymer drug ...conjugates carrying synergistic pairs of chemotherapy drugs can be used to reduce drug administration dose. Here, we systematically evaluated the effect of temporal scheduling of doxorubicin (DOX) and gemcitabine (GEM) on drug synergy. Hyaluronic acid (HA) drug conjugates with distinct linkers conjugating both DOX and GEM were synthesized to control relative release kinetics of each drug. We show that polymer conjugates that release GEM faster than DOX are more effective at killing triple negative breast cancer cells in vitro. We further show that the optimal dual drug conjugate more effectively inhibits the growth of an aggressive, orthotopic 4T1 tumor model in vivo than free DOX and GEM and the single drug HA conjugates. The dual drug HA conjugate can inhibit 4T1 tumor growth in vivo during treatment through both intravenous and non-local subcutaneous injections. These results emphasize the importance of understanding the effect release rates have on the efficacy of synergistic drug carriers and motivate the use of HA as a delivery platform for multiple cancer types.
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An accreting millisecond X-ray pulsar, IGR J17591−2342 was discovered in 2018 August in scans of the Galactic bulge and center by the International Gamma-Ray Astrophysics Laboratory X-ray and ...gamma-ray observatory. It exhibited an unusual outburst profile with multiple peaks in the X-ray, as observed by several X-ray satellites over 3 months. Here we present observations of this source performed in the X-ray/gamma-ray and near-infrared domains and focus on a simultaneous observation performed with the Chandra High Energy Transmission Gratings Spectrometer (HETGS) and the Neutron Star Interior Composition Explorer (NICER). The HETGS provides high-resolution spectra of the Si edge region that yield clues as to the source's distance and reveal evidence (at 99.999% significance) of an outflow with a velocity of 2800 km s−1. We demonstrate good agreement between the NICER and HETGS continua, provided that one properly accounts for the differing manners in which these instruments view the dust-scattering halo in the source's foreground. Unusually, we find a possible set of Ca lines in the HETGS spectra (with significances ranging from 97.0% to 99.7%). We hypothesize that IGR J17591−2342 is a neutron star low-mass X-ray binary at the distance of the Galactic bulge or beyond that may have formed from the collapse of a white dwarf system in a rare, calcium-rich Type Ib supernova explosion.
The Chandra Source Catalog Evans, Ian N; Primini, Francis A; Glotfelty, Kenny J ...
The Astrophysical journal. Supplement series,
07/2010, Letnik:
189, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The Chandra Source Catalog (CSC) is a general purpose virtual X-ray astrophysics facility that provides access to a carefully selected set of generally useful quantities for individual X-ray sources, ...and is designed to satisfy the needs of a broad-based group of scientists, including those who may be less familiar with astronomical data analysis in the X-ray regime. The first release of the CSC includes information about 94,676 distinct X-ray sources detected in a subset of public Advanced CCD Imaging Spectrometer imaging observations from roughly the first eight years of the Chandra mission. This release of the catalog includes point and compact sources with observed spatial extents {approx}<30''. The catalog (1) provides access to the best estimates of the X-ray source properties for detected sources, with good scientific fidelity, and directly supports scientific analysis using the individual source data; (2) facilitates analysis of a wide range of statistical properties for classes of X-ray sources; and (3) provides efficient access to calibrated observational data and ancillary data products for individual X-ray sources, so that users can perform detailed further analysis using existing tools. The catalog includes real X-ray sources detected with flux estimates that are at least 3 times their estimated 1{sigma} uncertainties in at least one energy band, while maintaining the number of spurious sources at a level of {approx}<1 false source per field for a 100 ks observation. For each detected source, the CSC provides commonly tabulated quantities, including source position, extent, multi-band fluxes, hardness ratios, and variability statistics, derived from the observations in which the source is detected. In addition to these traditional catalog elements, for each X-ray source the CSC includes an extensive set of file-based data products that can be manipulated interactively, including source images, event lists, light curves, and spectra from each observation in which a source is detected.
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