Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice

Peer reviewedPublisher PD

Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.

BackgroundNovel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045.Patients and methodsAdult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.ResultsA total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.ConclusionsLong-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.Trial registrationClinicalTrials.gov: NCT02256436

The penetration of FUV radiation into molecular clouds

The solution of the FUV radiative transfer equation can be complicated if the most relevant radiative processes such as dust scattering and gas line absorption are included, and have realistic (non-uniform) properties. We have extended the spherical harmonics method to solve for the FUV radiation field in illuminated clouds taking into account gas absorption and coherent, nonconservative and anisotropic scattering by dust grains. Our formalism allows us to consistently include: (i) varying dust populations and (ii) gas lines in the FUV radiative transfer. The FUV penetration depth rises for increasing dust albedo and anisotropy of the scattered radiation (e.g. when grains grow towards cloud interiors). Illustrative models of illuminated clouds where only the dust populations are varied confirm earlier predictions for the FUV penetration in diffuse clouds (A_V1) we show that the FUV radiation field inside the cloud can differ by orders of magnitude depending on the grain properties. We show that the photochemical and thermal gradients can be very different depending on grain growth. Therefore, the assumption of uniform dust properties and averaged extinction curves can be a crude approximation to determine the resulting scattering properties, prevailing chemistry and atomic/molecular abundances in ISM clouds or protoplanetary disks.Comment: Accepted for publication in Astronomy & Astrophysics. Section 2. Astrophysical processes. Version 2: minor language corrections added. Figs. 2, 4 and 8 bitmapped to lower resolutio

Shifts of criteria or neural timing? The assumptions underlying timing perception studies

In timing perception studies, the timing of one event is usually manipulated relative to another, and participants are asked to judge if the two events were synchronous, or to judge which of the two events occurred first. Responses are analyzed to determine a measure of central tendency, which is taken as an estimate of the timing at which the two events are perceptually synchronous. When these estimates do not coincide with physical synchrony, it is often assumed that the sensory signals are asynchronous, as though the transfer of information concerning one input has been accelerated or decelerated relative to the other. Here we show that, while this is a viable interpretation, it is equally plausible that such effects are driven by shifts in the criteria used to differentiate simultaneous from asynchronous inputs. Our analyses expose important ambiguities concerning the interpretation of simultaneity judgement data, which have hitherto been underappreciated

Upper limits on bolometric luminosities of ten type Ia supernova progenitors from Chandra observations

We present an analysis of Chandra observations of the position of ten nearby (< 25 Mpc) type Ia supernovae, taken before the explosions. No sources corresponding to progenitors were found in any of the observations. We calculated upper limits on the bolometric luminosities of the progenitors assuming black-body X-ray spectra with temperatures of 30-150 eV. This is inspired by the fact that luminous super-soft X-ray sources have been suggested as the direct progenitors of type Ia supernovae. The upper limits of two supernovae in our sample are comparable to the luminosities of the brightest observed super-soft sources, ruling out such sources as the progenitors of these supernovae. In contrast to Liu et al (2012) we find that for SN2011fe we can rule out Eddington luminosity systems for black body temperatures as low as 40 eV. Our findings are consistent with statistical studies comparing the observed type Ia supernova rate to the number of super-soft sources or the integrated X-ray luminosity in external galaxies. This suggest that either the progenitors of type Ia supernovae are not accreting, nuclear burning white dwarfs, or that they do not look like the classical super-soft sources, e.g. because they are obscured.Comment: Accepted, MNRAS. 10 pages, 11 figures, 3 table

Evidence for ultra-fast outflows in radio-quiet AGNs: III - location and energetics

Using the results of a previous X-ray photo-ionization modelling of blue-shifted Fe K absorption lines on a sample of 42 local radio-quiet AGNs observed with XMM-Newton, in this letter we estimate the location and energetics of the associated ultra-fast outflows (UFOs). Due to significant uncertainties, we are essentially able to place only lower/upper limits. On average, their location is in the interval ~0.0003-0.03pc (~10^2-10^4 r_s) from the central black hole, consistent with what is expected for accretion disk winds/outflows. The mass outflow rates are constrained between ~0.01-1 M_{\odot} yr^{-1}, corresponding to >5-10% of the accretion rates. The average lower-upper limits on the mechanical power are log\dot{E}_K~42.6-44.6 erg s^{-1}. However, the minimum possible value of the ratio between the mechanical power and bolometric luminosity is constrained to be comparable or higher than the minimum required by simulations of feedback induced by winds/outflows. Therefore, this work demonstrates that UFOs are indeed capable to provide a significant contribution to the AGN cosmological feedback, in agreement with theoretical expectations and the recent observation of interactions between AGN outflows and the interstellar medium in several Seyferts galaxies.Comment: 5 pages, 3 figures, accepted for publication in MNRA

Measurement of end-expiratory lung volume in intubated children without interruption of mechanical ventilation

Purpose: Monitoring end-expiratory lung volume (EELV) is a valuable tool to optimize respiratory settings that could be of particular importance in mechanically ventilated pediatric patients. We evaluated the feasibility and precision of an intensive care unit (ICU) ventilator with an in-built nitrogen washout/wash

Obscuration of Supersoft X-ray Sources by Circumbinary Material - A Way to Hide Type Ia Supernova Progenitors?

The progenitors of supernovae (SNe) type Ia are usually assumed to be either a single white dwarf (WD) accreting from a non-degenerate companion (the SD channel) or the result of two merging WDs (DD channel). However, no consensus currently exists as to which progenitor scenario is the correct one, or whether the observed SN Ia rate is produced by a combination of both channels. Unlike a DD progenitor a SD progenitor is expected to emit supersoft X-rays for a prolonged period of time (~1 Myr) as a result of the burning of accreted matter on the surface of the WD. An argument against the SD channel as a significant producer of SNe type Ia has been the lack of observed supersoft X-ray sources (SSS) and the lower-than-expected integrated soft X-ray flux from elliptical galaxies. We wish to determine if it is possible to obscure the supersoft X-ray emission from a nuclear burning white dwarf in an accreting single degenerate binary system. In case of obscured systems we wish to determine their general observational characteristics. We examine the emergent X-ray emission from a canonical SSS system surrounded by a spherically symmetric configuration of material, assuming a black body spectrum with T_BB=50 eV and L=10^38 erg/s. The circumbinary material is assumed to be of solar chemical abundances, and we leave the mechanism behind the mass loss into the circumbinary region unspecified. If steadily accreting, nuclear burning WDs are canonical SSS our analysis suggests that they can be obscured by relatively modest circumbinary mass loss rates. This may explain the discrepancy of SSS compared to the SN Ia rate inferred from observations if the SD progenitor scenario contributes significantly to the SN Ia rate. Recycled emissions from obscured systems may be visible in other wavebands than X-rays. It may also explain the lack of observed SSS in symbiotic binary systems.Comment: 10 pages, 4 figures, accepted A&

The imprint of a symbiotic binary progenitor on the properties of Kepler's supernova remnant

We present a model for the Type Ia supernova remnant (SNR) of SN 1604, also known as Kepler's SNR. We find that its main features can be explained by a progenitor model of a symbiotic binary consisting of a white dwarf and an AGB donor star with an initial mass of 4-5 M_sun. The slow, nitrogen rich wind emanating from the donor star has partially been accreted by the white dwarf, but has also created a circumstellar bubble. Based on observational evidence, we assume that the system moves with a velocity of 250 km/s. Due to the systemic motion the interaction between the wind and the interstellar medium has resulted in the formation of a bow shock, which can explain the presence of a one-sided, nitrogen rich shell. We present two-dimensional hydrodynamical simulations of both the shell formation and the SNR evolution. The SNR simulations show good agreement with the observed kinematic and morphological properties of Kepler's SNR. Specifically, the model reproduces the observed expansion parameters (m=V/(R/t)) of m=0.35 in the north and m=0.6 in the south of Kepler's SNR. We discuss the variations among our hydrodynamical simulations in light of the observations, and show that part of the blast wave may have traversed through the one-sided shell completely. The simulations suggest a distance to Kepler's SNR of 6 kpc, or otherwise require that SN 1604 was a sub-energetic Type Ia explosion. Finally, we discuss the possible implications of our model for Type Ia supernovae and their remnants in general.Comment: 13 pages, 9 figures. Submitted to A&

Discovery of 90 Type Ia supernovae among 700,000 Sloan spectra: the Type-Ia supernova rate versus galaxy mass and star-formation rate at redshift ~0.1

Using a method to discover and classify supernovae (SNe) in galaxy spectra, we find 90 Type Ia SNe (SNe Ia) and 10 Type II SNe among the ~700,000 galaxy spectra in the Sloan Digital Sky Survey Data Release 7 that have VESPA-derived star-formation histories (SFHs). We use the SN Ia sample to measure SN Ia rates per unit stellar mass. We confirm, at the median redshift of the sample, z = 0.1, the inverse dependence on galaxy mass of the SN Ia rate per unit mass, previously reported by Li et al. (2011b) for a local sample. We further confirm, following Kistler et al. (2011), that this relation can be explained by the combination of galaxy "downsizing" and a power-law delay-time distribution (DTD; the distribution of times that elapse between a hypothetical burst of star formation and the subsequent SN Ia explosions) with an index of -1, inherent to the double-degenerate progenitor scenario. We use the method of Maoz et al. (2011) to recover the DTD by comparing the number of SNe Ia hosted by each galaxy in our sample with the VESPA-derived SFH of the stellar population within the spectral aperture. In this galaxy sample, which is dominated by old and massive galaxies, we recover a "delayed" component to the DTD of 4.5 +/- 0.6 (statistical) +0.3 -0.5 (systematic) X 10^-14 SNe Msun^-1 yr^-1 for delays in the range > 2.4 Gyr. The mass-normalized SN Ia rate, averaged over all masses and redshifts in our galaxy sample, is R(Ia,M,z=0.1) = 0.10 +/- 0.01 (statistical) +/- 0.01 (systematic) SNuM, and the volumetric rate is R(Ia,V,z=0.1) = 0.247 +0.029 -0.026 (statistical) +0.016 -0.031 (systematic) X 10^-4 SNe yr^-1 Mpc^-3. This rate is consistent with the rates and rate evolution from other recent SN Ia surveys, which together also indicate a ~t^-1 DTD.Comment: MNRAS accepted. 20 pages, 12 figures, 5 tables. Revised following referee report. A full version of figure 8 can be found at http://www.astro.tau.ac.il/~orgraur/Graur_SDSS_SNe_full.pd