A First-in-Human Study of Novel Cereblon Modulator Avadomide (CC-122) in Advanced Malignancies.

Purpose Avadomide is a novel, small-molecule therapeutic agent that modulates cereblon E3 ligase activity and exhibits potent antitumor and immunomodulatory activities. This first-in-human phase I study (NCT01421524) evaluated the safety and clinical activity of avadomide in patients with advanced solid tumors, non-Hodgkin lymphoma (NHL), and multiple myeloma.Patients and methods Thirty-four patients were treated with avadomide in 7 dose-escalation cohorts using a 3 + 3 design (0.5-3.5 mg, 28-day continuous dosing cycles). The primary objectives were to determine the dose-limiting toxicity (DLT), nontolerated dose (NTD), maximum tolerated dose (MTD), recommended phase II dose, and pharmacokinetics of avadomide. The secondary objective was to determine preliminary avadomide efficacy. Exploratory objectives included evaluation of pharmacodynamic effects of avadomide.Results DLTs were reported in 2 patients, and grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 14 patients (41%). The most common TEAEs (≥15%) were fatigue, neutropenia, and diarrhea. The NTD and MTD were 3.5 and 3.0 mg, respectively. Of 5 patients with NHL, 1 achieved a complete response, and 2 had partial responses. Although no objective responses were observed in patients with solid tumors, 5 of 6 patients with brain cancer experienced nonprogression of ≥6 months. A dose-dependent relationship between Aiolos degradation in peripheral B and T cells occurred within 5 hours of the first dose of avadomide administered, starting at 0.5 mg.Conclusions Avadomide monotherapy demonstrated acceptable safety and favorable pharmacokinetics in patients with solid tumors, NHL, and multiple myeloma. In addition, 3 objective responses were observed in NHL

Key 19^{19}Ne states identified affecting γ\gamma-ray emission from 18^{18}F in novae

Detection of nuclear-decay $\gamma$ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense $\gamma$-ray flux is thought to be annihilation radiation from the $\beta^+$ decay of $^{18}$F, which is destroyed prior to decay by the $^{18}$F($p$,$\alpha$)$^{15}$O reaction. Estimates of $^{18}$F production had been uncertain, however, because key near-threshold levels in the compound nucleus, $^{19}$Ne, had yet to be identified. This Letter reports the first measurement of the $^{19}$F($^{3}$He,$t\gamma$)$^{19}$Ne reaction, in which the placement of two long-sought 3/2$^+$ levels is suggested via triton-$\gamma$-$\gamma$ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of $1.5-17$ at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.Comment: 6 pages, 4 figure

New γ\gamma-ray Transitions Observed in 19^{19}Ne with Implications for the 15^{15}O(α\alpha,γ\gamma)19^{19}Ne Reaction Rate

The $^{15}$O($\alpha$,$\gamma$)$^{19}$Ne reaction is responsible for breakout from the hot CNO cycle in Type I x-ray bursts. Understanding the properties of resonances between $E_x = 4$ and 5 MeV in $^{19}$Ne is crucial in the calculation of this reaction rate. The spins and parities of these states are well known, with the exception of the 4.14- and 4.20-MeV states, which have adopted spin-parities of 9/2$^-$ and 7/2$^-$, respectively. Gamma-ray transitions from these states were studied using triton-$\gamma$-$\gamma$ coincidences from the $^{19}$F($^{3}$He,$t\gamma$)$^{19}$Ne reaction measured with GODDESS (Gammasphere ORRUBA Dual Detectors for Experimental Structure Studies) at Argonne National Laboratory. The observed transitions from the 4.14- and 4.20-MeV states provide strong evidence that the $J^\pi$ values are actually 7/2$^-$ and 9/2$^-$, respectively. These assignments are consistent with the values in the $^{19}$F mirror nucleus and in contrast to previously accepted assignments

Dilepton Production in High Luminosity Multi-GeV Electron Scattering

We consider the production of a 300GeV dilepton in very intense 4GeV electron scattering off of a lead target. The production cross-section and angular distribution of the resulting muons are calculated. There occur several such events per year, and their detection is rendered feasible by measurement of $e^+\mu^-\mu^-$ angular correlations.Comment: 9 pages latex, 5 figures not included (captions only

γ spectroscopy of states in Cl 32 relevant for the S 31 (p,γ) Cl 32 reaction rate

Background: The S31(p,γ)Cl32 reaction becomes important for sulfur production in novae if the P31(p,α)Si28 reaction rate is somewhat greater than currently accepted. The rate of the S31(p,γ)Cl32 reaction is uncertain, primarily due to the properties of resonances at Ec.m.=156 and 549 keV. Purpose: We precisely determined the excitation energies of states in Cl32 through high-resolution γ spectroscopy including the two states most important for the S31(p,γ)Cl32 reaction at nova temperatures. Method: Excited states in Cl32 were populated using the B10(Mg24,2n)Cl32 reaction with a Mg24 beam from the ATLAS facility at Argonne National Laboratory. The reaction channel of interest was selected using recoils in the Fragment Mass Analyzer, and precise level energies were determined by detecting γ rays with Gammasphere. Results: We observed γ rays from the decay of six excited states in Cl32. The excitation energies for two unbound levels at Ex=1738.1 (6) keV and 2130.5 (10) keV were determined and found to be in agreement with a previous high-precision measurement of the S32(He3,t)Cl32 reaction [1]. Conclusions: An updated S31(p,γ)Cl32 reaction rate is presented. With the excitation energies of important levels firmly established, the dominant uncertainty in the reaction rate at nova temperatures is due to the strength of the resonance corresponding to the 2131-keV state in Cl32

Measurement of \u3csup\u3e17\u3c/sup\u3eF + p reactions with ANASEN

Reactions involving radioactive nuclei play an important role in stellar explosions, but those reactions involving short-lived nuclei have only limited experimental information available due to currently limited beam intensities. Several facilities are aiming to provide greater access to these unstable isotopes at higher beam intensities, but more efficient and selective techniques and devices are needed to properly study these important reactions. The Array for Nuclear Astrophysics Studies with Exotic Nuclei (ANASEN), a charged particle detector designed by Louisiana State University (LSU) and Florida State University (FSU), was created for this purpose. ANASEN is used to study the reactions important in the αp- and rp- processes with proton-rich exotic nuclei, providing essentially complete solid angle coverage through an array of 40 silicon-strip detectors backed with CsI scintillators, covering an area of roughly 1300 cm2. ANASEN also includes an active gas target/detector in a position-sensitive annular gas proportional counter, which allows direct measurement of (α,p) reactions in inverse kinematics. The first in-beam measurements with a partial implementation of ANASEN were performed at the RESOLUT radioactive beam facility of FSU during the summer of 2011. They included stable beam experiments and measurements of the 17F(p,p) 17F and 17F(p,α)14O reactions which are important to understanding the structure of 18Ne and the 14O(α,p)17F reaction rate. The performance of ANASEN and initial results from the 17F studies will be presented. © Published under licence by IOP Publishing Ltd

Improving Fission-product Decay Data for Reactor Applications: Part I -- Decay Heat

Effort has been expended to assess the relative merits of undertaking further decay-data measurements of the main fission-product contributors to the decay heat of neutron-irradiated fissile fuel and related actinides by means of Total Absorption Gamma-ray Spectroscopy (TAGS/TAS) and Discrete Gamma-ray Spectroscopy (DGS). This review has been carried out following similar work performed under the auspices of OECD/WPEC-Subgroup 25 (2005-2007) and the International Atomic Energy Agency (2010, 2014), and various highly relevant TAGS measurements completed as a consequence of such assessments. We present our recommendations for new decay-data evaluations, along with possible requirements for total absorption and discrete high-resolution gamma-ray spectroscopy studies that cover approximately 120 fission products and various isomeric states.Comment: Submitted to European Physical Journal