Multi-institutional, prospective, randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high-risk melanoma patients: A subgroup analysis

Background: Checkpoint inhibitors (CPI) in combination with cell-based vaccines may produce synergistic antitumor immunity. The primary analysis of the randomized and blinded phase IIb trial in resected stage III/IV melanoma demonstrated TLPLDC is safe and improved 24-month disease-free survival (DFS) in the per treatment (PT) analysis. Here, we examine efficacy within pre-specified and exploratory subgroups. Methods: Stage III/IV patients rendered disease-free by surgery were randomized 2:1 to TLPLDC vaccine versus placebo. The pre-specified PT analysis included only patients completing the primary vaccine/placebo series at 6 months. Kaplan–Meier analysis was used to compare 24-month DFS among subgroups. Results: There were no clinicopathologic differences between subgroups except stage IV patients were more likely to receive CPI. In stage IV patients, 24-month DFS was 43% for vaccine versus 0% for placebo (p = 0.098) in the ITT analysis and 73% versus 0% (p = 0.002) in the PT analysis. There was no significant difference in 24-month DFS when stratified by use of immunotherapy or CPI. For patients with resected recurrent disease, 24-month DFS was 88.9% versus 33.3% (p = 0.013) in the PT analysis. All benefit from vaccination was in the PT analysis; no benefit was found in patients receiving up to three doses. Conclusion: The TLPLDC vaccine improved DFS in patients completing the primary vaccine series, particularly in the resected stage IV patients. The efficacy of the TLPLDC vaccine will be confirmed in a phase III study evaluating adjuvant TLPLDC + CPI versus Placebo + CPI in resected stage IV melanoma patients. © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Dust, Ice, and Gas In Time (DIGIT) Herschel program first results: A full PACS-SED scan of the gas line emission in protostar DK Chamaeleontis

Aims. We aim to study the composition and energetics of the circumstellar material of DK Cha, an intermediate-mass star in transition from an embedded configuration to a star plus disk stage, during this pivotal stage of its evolution. Methods. Using the range scan mode of PACS on the Herschel Space Observatory, we obtained a spectrum of DK Cha from 55 to 210 mu m as part of the DIGIT key program. Results. Almost 50 molecular and atomic lines were detected, many more than the 7 lines detected in ISO-LWS. Nearly the entire ladder of CO from J = 14-13 to 38-37 (E-u/k = 4080 K), water from levels as excited as J(K-1K+1) = 7(07) (E-u/k = 843 K), and OH lines up to E-u/k = 290 K were detected. Conclusions. The continuum emission in our PACS SED scan matches the flux expected by a model consisting of a star, a surrounding disk of 0.03 M-circle dot, and an envelope of a similar mass, supporting the suggestion that the object is emerging from its main accretion stage. Molecular, atomic, and ionic emission lines in the far-infrared reveal the outflow's influence on the envelope. The inferred hot gas may be photon-heated, but some emission may be caused by C-shocks in the walls of the outflow cavity

First results of the Herschel key program "Dust, Ice and Gas In Time" (DIGIT): Dust and gas spectroscopy of HD 100546

Context. We present far-infrared spectroscopic observations, taken with the Photodetector Array Camera and Spectrometer (PACS) on the Herschel Space Observatory, of the protoplanetary disk around the pre-main-sequence star HD 100546. These observations are the first within the DIGIT Herschel key program, which aims to follow the evolution of dust, ice, and gas from young stellar objects still embedded in their parental molecular cloud core, through the final pre-main-sequence phases when the circumstellar disks are dissipated. Aims. Our aim is to improve the constraints on temperature and chemical composition of the crystalline olivines in the disk of HD 100546 and to give an inventory of the gas lines present in its far-infrared spectrum. Methods. The 69 μm feature is analyzed in terms of position and shape to derive the dust temperature and composition. Furthermore, we detected 32 emission lines from five gaseous species and measured their line fluxes. Results. The 69 μm emission comes either from dust grains with ~70 K at radii larger than 50 AU, as suggested by blackbody fitting, or it arises from ~200 K dust at ~13 AU, close to the midplane, as supported by radiative transfer models. We also conclude that the forsterite crystals have few defects and contain at most a few percent iron by mass. Forbidden line emission from [C ii] at 157 μm and [O i] at 63 and 145 μm, most likely due to photodissociation by stellar photons, is detected. Furthermore, five H2O and several OH lines are detected. We also found high-J rotational transition lines of CO, with rotational temperatures of ~300 K for the transitions up to J = 22-21 and T ~ 800 K for higher transitions

Observation of Gravitational Waves from the Coalescence of a 2.5−4.5 M⊙2.5-4.5~M_\odot Compact Object and a Neutron Star

International audienceWe report the observation of a coalescing compact binary with component masses $2.5-4.5~M_\odot$ and $1.2-2.0~M_\odot$ (all measurements quoted at the 90% credible level). The gravitational-wave signal GW230529_181500 was observed during the fourth observing run of the LIGO-Virgo-KAGRA detector network on 2023 May 29 by the LIGO Livingston Observatory. The primary component of the source has a mass less than $5~M_\odot$ at 99% credibility. We cannot definitively determine from gravitational-wave data alone whether either component of the source is a neutron star or a black hole. However, given existing estimates of the maximum neutron star mass, we find the most probable interpretation of the source to be the coalescence of a neutron star with a black hole that has a mass between the most massive neutron stars and the least massive black holes observed in the Galaxy. We estimate a merger rate density of $55^{+127}_{-47}~\text{Gpc}^{-3}\,\text{yr}^{-1}$ for compact binary coalescences with properties similar to the source of GW230529_181500; assuming that the source is a neutron star-black hole merger, GW230529_181500-like sources constitute about 60% of the total merger rate inferred for neutron star-black hole coalescences. The discovery of this system implies an increase in the expected rate of neutron star-black hole mergers with electromagnetic counterparts and provides further evidence for compact objects existing within the purported lower mass gap

Observation of Gravitational Waves from the Coalescence of a 2.5−4.5 M⊙2.5-4.5~M_\odot Compact Object and a Neutron Star

International audienceWe report the observation of a coalescing compact binary with component masses $2.5-4.5~M_\odot$ and $1.2-2.0~M_\odot$ (all measurements quoted at the 90% credible level). The gravitational-wave signal GW230529_181500 was observed during the fourth observing run of the LIGO-Virgo-KAGRA detector network on 2023 May 29 by the LIGO Livingston Observatory. The primary component of the source has a mass less than $5~M_\odot$ at 99% credibility. We cannot definitively determine from gravitational-wave data alone whether either component of the source is a neutron star or a black hole. However, given existing estimates of the maximum neutron star mass, we find the most probable interpretation of the source to be the coalescence of a neutron star with a black hole that has a mass between the most massive neutron stars and the least massive black holes observed in the Galaxy. We estimate a merger rate density of $55^{+127}_{-47}~\text{Gpc}^{-3}\,\text{yr}^{-1}$ for compact binary coalescences with properties similar to the source of GW230529_181500; assuming that the source is a neutron star-black hole merger, GW230529_181500-like sources constitute about 60% of the total merger rate inferred for neutron star-black hole coalescences. The discovery of this system implies an increase in the expected rate of neutron star-black hole mergers with electromagnetic counterparts and provides further evidence for compact objects existing within the purported lower mass gap