Hydrogen negative ion beams of 507 keV, 1 A and 486 keV, 2.8 A have been successfully produced in the JT-60U negative ion source with a three-stage accelerator by overcoming a poor voltage holding of the accelerator with large-size grids of ∼2 m2. This is the first result of H− beam acceleration up to 500 keV at a high current of over 1 A. In order to improve the voltage holding capability, the breakdown voltages of the large-size grids and small-size electrodes with uniform and locally strong electric fields were examined by changing the gap length. It was found that the voltage holding of the large-size grids was below half of that of the small-size electrodes with a uniform electric field which was used in the design of the accelerator. This degradation was found to be caused by the local electric field concentrations in addition to the size. Based on the results of the voltage holding tests and beam optics calculations, the gap lengths of the large-size grids were tuned to have a capability to sustain 600 kV. As a result, the gap tuning realized stable voltage holding during beam accelerations without significant degradations of the beam optics and stripping loss. These results indicated that stable 500 keV beam accelerations required for JT-60SA are feasible and this gap tuning is also applicable for the design of ITER accelerator.
Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colonystimulating factor 1 receptor. This phase I, nonrandomized, open-label multiple-dose study evaluated pexidartinib safety and efficacy in Asian patients with symptomatic, advanced solid tumors. Materials and Methods Patients received pexidartinib: cohort 1, 600 mg/d; cohort 2, 1000 mg/d for 2 weeks, then 800 mg/d. Primary objectives assessed pexidartinib safety and tolerability, and determined the recommended phase 2 dose; secondary objectives evaluated efficacy and pharmacokinetic profile. Results All 11 patients (6 males, 5 females; median age 64, range 23-82; cohort 1 n = 3; cohort 2 n = 8) experienced at least one treatment-emergent adverse event; 5 experienced at least one grade ≥ 3 adverse event, most commonly (18%) for each of the following: increased aspartate aminotransferase, blood alkaline phosphatase, gamma-glutamyl transferase, and anemia. Recommended phase 2 dose was 1000 mg/d for 2 weeks and 800 mg/d thereafter. Pexidartinib exposure, area under the plasma concentration-time curve from zero to 8 h (AUC 0-8h ), and maximum observed plasma concentration (C max ) increased on days 1 and 15 with increasing pexidartinib doses, and time at C max (T max ) was consistent throughout all doses. Pexidartinib exposure and plasma levels of adiponectin and colony-stimulating factor 1 increased following multiple daily pexidartinib administrations. One patient (13%) with tenosynovial giant cell tumor showed objective tumor response. Conclusions This was the first study to evaluate pexidartinib in Asian patients with advanced solid tumors. Pexidartinib was safe and tolerable in this population at the recommended phase 2 dose previously determined for Western patients (funded by Daiichi Sankyo; clinicaltrials.gov number, NCT02734433).
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