Oxygen isotopic composition of our solar system is believed to have resulted from mixing of two isotopically distinct nebular reservoirs, 16 O-rich and 17,18 O-rich relative to Earth. The nature and composition of the 17,18 O-rich reservoir are poorly constrained. We report an in situ discovery of a chemically and isotopically unique material distributed ubiquitously in fine-grained matrix of a primitive carbonaceous chondrite Acfer 094. This material formed by oxidation of Fe,Ni-metal and sulfides by water either in the solar nebula or on a planetesimal. Oxygen isotopic composition of this material indicates that the water was highly enriched in 17 O and 18 O (δ 17,18 O SMOW = +180‰ per mil), providing the first evidence for an extremely 17,18 O-rich reservoir in the early solar system.

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BackgroundLenvatinib has been approved by regulatory agencies in Japan, the United States, and the European Union for treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). Thyroid cancer, however, is a clinically diverse disease that includes anaplastic thyroid cancer (ATC), the subtype associated with the highest lethality. Effective therapy for ATC is an unmet need.Patients and methodsThis phase 2, single-arm, open-label study in patients with thyroid cancer, including ATC, RR-DTC, and medullary thyroid cancer was conducted from 3 September 2012 to 9 July 2015. Patients received lenvatinib 24 mg daily until disease progression or development of unacceptable toxicity. The primary endpoint was safety, and the secondary endpoint was efficacy, as assessed by progression-free survival (PFS), overall survival (OS), and objective response rate.ResultsAt data cutoff, 17 patients with ATC were enrolled. All experienced ≥1 treatment-emergent adverse event (TEAE). The most frequent TEAEs were decreased appetite (82%), hypertension (82%), fatigue (59%), nausea (59%), and proteinuria (59%). Of note, only one patient required lenvatinib withdrawal because of a TEAE, and this TEAE was considered unrelated to lenvatinib. The median PFS was 7.4 months [95% confidence interval (CI): 1.7–12.9], the median OS was 10.6 months (95% CI: 3.8–19.8), and the objective response rate was 24%.ConclusionIn this study, lenvatinib demonstrated manageable toxicities with dose adjustments and clinical activity in patients with ATC. This clinical activity of lenvatinib warrants further investigation in ATC.NCT01728623.

The minerals (Mg,Fe)SiO3-ilmenite and -perovskite were identified in the shock-induced veins in the Tenham chondritic meteorite. Both phases are inferred to have transformed from pyroxene at high pressures and temperatures by shock metamorphism. Columnar-shaped ilmenite grains, one of two types of morphologies, have a topotaxial relationship with neighboring pyroxene grains, indicating shear transformation. Granular-shaped perovskite grains showed a diffraction pattern consistent with orthorhombic perovskite, but these grains were not stable under the electron beam irradiation and became amorphous. The higher iron concentration in both phases compared with those experimentally reported may suggest their metastable transition from enstatite because of shock compression.

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Lenvatinib significantly prolonged progression‐free survival (PFS) versus placebo in patients with radioiodine‐refractory differentiated thyroid cancer (RR‐DTC) in the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. This subanalysis evaluated the efficacy and safety of lenvatinib in Japanese patients who participated in SELECT. Outcomes for Japanese patients (lenvatinib, n = 30; placebo, n = 10) were assessed in relationship to the SELECT population (lenvatinib, n = 261; placebo, n = 131). The primary endpoint was PFS; secondary endpoints included overall survival, overall response rate, and safety. Lenvatinib PFS benefit was shown in Japanese patients (median PFS: lenvatinib, 16.5 months; placebo, 3.7 months), although significance was not reached, presumably due to sample size (hazard ratio, 0.39; 95% confidence interval, 0.10–1.57; P = 0.067). Overall response rates were 63.3% and 0% for lenvatinib and placebo, respectively. No significant difference was found in overall survival. The lenvatinib safety profile was similar between the Japanese and overall SELECT population, except for higher incidences of hypertension (any grade: Japanese, 87%; overall, 68%; grade ≥3: Japanese, 80%; overall, 42%), palmar–plantar erythrodysesthesia syndrome (any grade: Japanese, 70%; overall, 32%; grade ≥3: Japanese, 3%; overall, 3%), and proteinuria (any grade: Japanese, 63%; overall, 31%; grade ≥3: Japanese, 20%; overall, 10%). Japanese patients had more dose reductions (Japanese, 90%; overall, 67.8%), but fewer discontinuations due to adverse events (Japanese, 3.3%; overall, 14.2%). There was no difference in lenvatinib exposure between the Japanese and overall SELECT populations after adjusting for body weight. In Japanese patients with radioiodine‐refractory differentiated thyroid cancer, lenvatinib showed similar clinical outcomes to the overall SELECT population. Some differences in adverse event frequencies and dose modifications were observed. Clinical trial registration no.: NCT01321554.

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