In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly ...reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months.
For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval CI, 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported.
In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT02435849 .).
Drifting asteroid fragments around WD 1145+017 Rappaport, S; Gary, B L; Kaye, T ...
Monthly notices of the Royal Astronomical Society,
06/2016, Letnik:
458, Številka:
4
Journal Article
Recenzirano
We have obtained extensive photometric observations of the polluted white dwarf WD 1145+017 which has been reported to be transited by at least one, and perhaps several, large asteroids with dust ...emission. Observation sessions on 37 nights spanning 2015 November to 2016 January with small to modest size telescopes have detected 237 significant dips in flux. Periodograms reveal a significant periodicity of 4.5004 h consistent with the dominant ('A') period detected with K2. The folded light curve shows an hour-long depression in flux with a mean depth of nearly 10 per cent. This depression is, in turn, comprised of a series of shorter and sometimes deeper dips which would be unresolvable with K2. We also find numerous dips in flux at other orbital phases. Nearly all of the dips associated with this activity appear to drift systematically in phase with respect to the 'A' period by about 2.5 min d super( -1) with a dispersion of ~0.5 min d super( -1), corresponding to a mean drift period of 4.4928 h. We are able to track ~15 discrete drifting features. The 'B'-'F' periods found with K2 are not detected, but we would not necessarily have expected to see them. We explain the drifting motion as due to smaller fragmented bodies that break off from the asteroid and go into a slightly smaller orbit. In this interpretation, we can use the drift rate to determine the mass of the asteroid, which we find to be ...10 super( 23) g, or about 1/10th the mass of Ceres. (ProQuest: ... denotes formulae/symbols omitted.)
Drifting asteroid fragments around WD 1145+017 Rappaport, S.; Gary, B. L.; Kaye, T. ...
Monthly Notices of the Royal Astronomical Society,
06/2016, Letnik:
458, Številka:
4
Journal Article
WD 1145+017 was observed from 2015 November to 2016 July, for the purpose of characterizing transit behaviour of the white dwarf by dust clouds thought to be produced by fragments of an asteroid in ...close orbit with the star. Fortuitously, most of these observations were carried out during a time when the overall 'dip' activity was dramatically enhanced over that during its discovery with Kepler K2. By the end of our reported observations, the dip activity had declined to a level close to its K2 discovery state. Three notable events were observed. In 2016 January, a large number of dust clouds appeared that had an orbital period of 4.4912 h, and this event also marked the end of a three-month interval dominated by the K2 'A' period. The second event was a 2016 April 21 appearance of four dip features with drift lines in a waterfall (date versus phase) diagram that diverged from their origin date, at a location away from the 'A' asteroid, and which lasted for two weeks. The third event was the sudden appearance of a dip feature with a period of 4.6064 h, which is essentially the same as the K2 'B' period. The evolution of dip shape, depth, and total fade amount provide constraints on dust production and loss mechanisms. Collisions can account for the sudden appearance of dust clouds, and the sudden increase in dust amount, but another mechanism for continual dust production is also required.
Abstract
WD 1145+017 was observed from 2016 November through 2017 June for the purpose of further characterizing the transit behaviour of the dusty debris clouds orbiting this white dwarf. The ...optical observations were carried out with a small ground-based telescope run by an amateur astronomer, and covered 53 different nights over the 8-month interval. We have found that the optical activity has increased to the highest level observed since its discovery with Kepler K2, with approximately 17 per cent of the optical flux extinguished per orbit. The source exhibits some transits with depths of up to 55 per cent and durations as long as 2 h. The dominant period of the orbiting dust clouds during 2016–2017 is 4.49126 h. We present ‘waterfall’ images for the entire 2016–2017 and 2015–2016 observing seasons. In addition, the white dwarf was observed with the Chandra X-ray Observatory for 10-ks on each of four different occasions, separated by about a month each. The upper limit on the average X-ray flux from WD 1145+017 is ≃ 5 × 10−15 erg cm−2 s−1 (unabsorbed over the range 0.1–100 keV), which translates to an upper limit on the X-ray luminosity, Lx, of ≃ 2 × 1028 erg s−1. If $L_{\rm x} \simeq G M_{\rm wd} \dot{M}_{\rm acc}/R_{\rm wd}$, where Mwd and Rwd are the mass and radius of the white dwarf, and $\dot{M}_{\rm acc}$ is the accretion rate, then $\dot{M}_{\rm acc} \lesssim 2 \times 10^{11}$ g s−1. This is just consistent with the value of $\dot{M}$ that is inferred from the level of dust activity.
ABSTRACT
In this work we report the discovery and analysis of three new triply eclipsing triple star systems found with the TESS mission during its observations of the northern skies: TICs 193993801, ...388459317, and 52041148. We utilized the TESS precision photometry of the binary eclipses and third-body eclipsing events, ground-based archival and follow-up photometric data, eclipse timing variations, archival spectral energy distributions, as well as theoretical evolution tracks in a joint photodynamical analysis to deduce the system masses and orbital parameters of both the inner and outer orbits. In one case (TIC 193993801) we also obtained radial velocity measurements of all three stars. This enabled us to ‘calibrate’ our analysis approach with and without ‘truth’ (i.e. RV) data. We find that the masses are good to 1–3 per cent accuracy with RV data and 3–10 per cent without the use of RV data. In all three systems we were able to find the outer orbital period before doing any detailed analysis by searching for a longer-term periodicity in the ASAS-SN archival photometry data – just a few thousand ASAS-SN points enabled us to find the outer periods of 49.28 d, 89.86 d, and 177.0 d, respectively. From our full photodynamical analysis we find that all three systems are coplanar to within 1°−3°. The outer eccentricities of the three systems are 0.003, 0.10, and 0.62, respectively (i.e. spanning a factor of 200). The masses of the three stars {Aa, Ab, and B} in the three systems are: {1.31, 1.19, 1.34}, {1.82, 1.73, 2.19}, and {1.62, 1.48, 2.74} M⊙, respectively.
ABSTRACT
We have discovered a doubly eclipsing, bound, quadruple star system in the field of K2 Campaign 7. EPIC 219217635 is a stellar image with Kp = 12.7 that contains an eclipsing binary (EB) ...with PA = 3.59470 d and a second EB with PB = 0.61825 d. We have obtained follow-up radial velocity (RV) spectroscopy observations, adaptive optics imaging, and ground-based photometric observations. From our analysis of all the observations, we derive good estimates for a number of the system parameters. We conclude that (1) both binaries are bound in a quadruple star system; (2) a linear trend to the RV curve of binary A is found over a 2-yr interval, corresponding to an acceleration, $\dot{\gamma }= 0.0024 \pm 0.0007$ cm s−2; (3) small irregular variations are seen in the eclipse timing variations (ETVs) detected over the same interval; (4) the orbital separation of the quadruple system is probably in the range of 8–25 au; and (5) the orbital planes of the two binaries must be inclined with respect to each other by at least 25°. In addition, we find that binary B is evolved, and the cooler and currently less massive star has transferred much of its envelope to the currently more massive star. We have also demonstrated that the system is sufficiently bright that the eclipses can be followed using small ground-based telescopes, and that this system may be profitably studied over the next decade when the outer orbit of the quadruple is expected to manifest itself in the ETV and/or RV curves.
Amorphous solid dispersion (ASD) is a widely employed formulation technique for drugs with poor aqueous solubility. Polymers are integral components of ASDs, but mechanisms by which polymers lead to ...the generation and maintenance of supersaturated solutions, which enhance oral absorption in vivo, are poorly understood. Herein, a diverse group of newly synthesized cellulose derivatives was evaluated for their ability to inhibit crystallization of enzalutamide, a poorly soluble compound used to treat prostate cancer. ASDs were prepared from selected polymers, specifically a somewhat hydrophobic polymer that was extremely effective at inhibiting drug crystallization, and a less effective, but more hydrophilic, crystallization inhibitor, that might afford better release. Drug membrane transport rate was evaluated in vitro and compared to in vivo performance, following oral dosing in rats. Good correlation was noted between the in vitro diffusion cell studies and the in vivo data. The ASD formulated with the less effective crystallization inhibitor outperformed the ASD prepared with the highly effective crystallization inhibitor in terms of the amount and rate of drug absorbed in vivo. This study provides valuable insight into key factors impacting oral absorption from enabling ASD formulations, and how best to evaluate such formulations using in vitro approaches.
We report the discovery of a massive planet (image ; total mass = image), large planet in a transiting, eccentric orbit around a 10th magnitude F5 V star in the constellation Camelopardalis. We ...designate the planet XO-3b and the star XO-3, also known as GSC 03727-01064. The orbital period of XO-3b is image days. XO-3 lacks a trigonometric parallax; we estimate its distance to be image pc. The radius of XO-3 is image, its mass is image, its image km s super(-1), and its metallicity is image. This system is unusual for a number of reasons. XO-3b is one of the most massive planets discovered around any star for which the orbital period is less than 10 days. The mass is near the deuterium-burning limit of 13 image, which is a proposed boundary between planets and brown dwarfs. Although Burrows et al. propose that formation in a disk or formation in the interstellar medium in a manner similar to stars is a more logical way to differentiate planets and brown dwarfs, our current observations are not adequate to address this distinction. XO-3b is also unusual in that its eccentricity is large given its relatively short orbital period. Both the planetary radius and the inclination are functions of the spectroscopically determined stellar radius. Analysis of the transit light curve of XO-3b suggests that the spectroscopically derived parameters may be overestimated. Though relatively noisy, the light curves favor a smaller radius in order to better match the steepness of the ingress and egress. The light curve fits imply a planetary radius of image, which would correspond to a mass of image. A precise trigonometric parallax measurement or a very accurate light curve is needed to resolve the uncertainty in the planetary mass and radius.
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