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With use of EGFR tyrosine-kinase inhibitor monotherapy for patients with activating EGFR mutation-positive non-small-cell lung cancer (NSCLC), median progression-free survival has been extended to about 12 months. Nevertheless, new strategies are needed to further extend progression-free survival and overall survival with acceptable toxicity and tolerability for this population. We aimed to compare the efficacy and safety of the combination of erlotinib and bevacizumab compared with erlotinib alone in patients with non-squamous NSCLC with activating EGFR mutation-positive disease. In this open-label, randomised, multicentre, phase 2 study, patients from 30 centres across Japan with stage IIIB/IV or recurrent non-squamous NSCLC with activating EGFR mutations, Eastern Cooperative Oncology Group performance status 0 or 1, and no previous chemotherapy for advanced disease received erlotinib 150 mg/day plus bevacizumab 15 mg/kg every 3 weeks or erlotinib 150 mg/day monotherapy as a first-line therapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, as determined by an independent review committee. Randomisation was done with a dynamic allocation method, and the analysis used a modified intention-to-treat approach, including all patients who received at least one dose of study treatment and had tumour assessment at least once after randomisation. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-111390. Between Feb 21, 2011, and March 5, 2012, 154 patients were enrolled. 77 were randomly assigned to receive erlotinib and bevacizumab and 77 to erlotinib alone, of whom 75 patients in the erlotinib plus bevacizumab group and 77 in the erlotinib alone group were included in the efficacy analyses. Median progression-free survival was 16·0 months (95% CI 13·9–18·1) with erlotinib plus bevacizumab and 9·7 months (5·7–11·1) with erlotinib alone (hazard ratio 0·54, 95% CI 0·36–0·79; log-rank test p=0·0015). The most common grade 3 or worse adverse events were rash (19 [25%] patients in the erlotinib plus bevacizumab group vs 15 [19%] patients in the erlotinib alone group), hypertension (45 [60%] vs eight [10%]), and proteinuria (six [8%] vs none). Serious adverse events occurred at a similar frequency in both groups (18 [24%] patients in the erlotinib plus bevacizumab group and 19 [25%] patients in the erlotinib alone group). Erlotinib plus bevacizumab combination could be a new first-line regimen in EGFR mutation-positive NSCLC. Further investigation of the regimen is warranted. Chugai Pharmaceutical Co Ltd.

Models of the active site in [NiFe]hydrogenase enzymes have proven challenging to prepare. We isolated a paramagnetic dinuclear nickel-ruthenium complex with a bridging hydrido ligand from the heterolytic cleavage of H2 by a dinuclear NiRu aqua complex in water under ambient conditions (20 degrees C and 1 atmosphere pressure). The structure of the hexacoordinate Ni(mu-H)Ru complex was unequivocally determined by neutron diffraction analysis, and it comes closest to an effective analog for the core structure of the proposed active form of the enzyme.

Ruthenium (Ru) via atomic layer deposition (ALD) has emerged as a promising alternative to copper‐interconnects. For the first time, a small yet simple molecular structure Ru precursor, [Ru(trimethylenemethane (TMM))(p‐cymene)], with excellent thermal stability up to 400 °C is introduced that enables a high‐temperature ALD‐Ru process with a high growth per cycle of ≈1.28 Å cycle−1 and a short incubation period (≈8 cycles) on TiN, facilitating uniform, dense film growth. The process achieves low impurity levels and resistivities as low as 10.6 µΩ cm at 350 °C without postannealing, approaching bulk Ru values (7.4 µΩ cm). Additionally, no Ru nucleation is observed on SiO2 even after 1000 cycles, indicating excellent substrate selectivity. Computational analyses confirm the substrate‐selective adsorption behavior of the precursor, favoring TMM‐terminated configurations on Ru and RuO2, while nucleation on SiO2 can be delayed. Fragmentation energy calculations further support the precursor's thermal robustness through strong Ru─ligand bonding. Advanced crystallography/microstructure analysis using electron backscatter diffraction reveals that the enhanced grain growth and the formation of low‐energy coincidence site lattice boundaries are critical for minimizing resistivity, which is supported by combined Fuchs–Sondheimer–Mayadas–Shatzkes modeling. These findings position the new Ru precursor as a robust candidate for durable, scalable ALD‐Ru processes in advanced interconnect technology. A thermally robust (≈400 °C), critically small‐size‐simple ligand structure ruthenium (Ru) precursor enables exceptional growth per cycle (≈1.28 Å cycle−1), short incubation (≈8 cycles), ultralow resistivity (8.65 µΩ cm) and outstanding substrate selectivity via atomic layer deposition (ALD) process at high temperatures, overcoming prior Ru‐ALD limitations, offering a scalable, impurity free pathway for next generation interconnects beyond copper.

Background This observational study investigated the safety and effectiveness of continuous erythropoietin receptor activator in patients with renal anemia in Japan. Methods Patients were enrolled between August 2011 and November 2015 and followed for up to 1 year. Outcomes were analyzed according to disease stage (not receiving dialysis, on hemodialysis, on peritoneal dialysis). Results Three thousand six hundred eighty-four patients were enrolled (1678 not receiving dialysis, 1605 on hemodialysis, 392 on peritoneal dialysis, and 9 other). Study treatment was well tolerated with no new safety concerns; adverse drug reactions were reported in 3.06%, 4.19%, and 4.46% of patients. Study treatment improved or maintained hemoglobin levels in 54.05–77.27% of patients, including erythropoiesis stimulating agent-naïve responders (hemoglobin ≥10.0 g/dL and hemoglobin increase ≥ 1.0 g/dL until week 24) and erythropoiesis-stimulating agent-switched responders (hemoglobin 10.0–12.0 g/dL at week 48). Conclusions This study shows the safety and effectiveness of long-term continuous erythropoietin receptor activator for renal anemia.

Models of the active site in [NiFe]hydrogenase enzymes have proven challenging to prepare. We isolated a paramagnetic dinuclear nickel-ruthenium complex with a bridging hydrido ligand from the heterolytic cleavage of H 2 by a dinuclear NiRu aqua complex in water under ambient conditions (20°C and 1 atmosphere pressure). The structure of the hexacoordinate Ni(μ-H)Ru complex was unequivocally determined by neutron diffraction analysis, and it comes closest to an effective analog for the core structure of the proposed active form of the enzyme.

With use of EGFR tyrosine-kinase inhibitor monotherapy for patients with activatingEGFRmutation-positive non-small-cell lung cancer (NSCLC), median progression-free survival has been extended to about 12 months. Nevertheless, new strategies are needed to further extend progression-free survival and overall survival with acceptable toxicity and tolerability for this population. We aimed to compare the efficacy and safety of the combination of erlotinib and bevacizumab compared with erlotinib alone in patients with non-squamous NSCLC with activatingEGFRmutation-positive disease. Methods In this open-label, randomised, multicentre, phase 2 study, patients from 30 centres across Japan with stage IIIB/IV or recurrent non-squamous NSCLC with activatingEGFRmutations, Eastern Cooperative Oncology Group performance status 0 or 1, and no previous chemotherapy for advanced disease received erlotinib 150 mg/day plus bevacizumab 15 mg/kg every 3 weeks or erlotinib 150 mg/day monotherapy as a first-line therapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, as determined by an independent review committee. Randomisation was done with a dynamic allocation method, and the analysis used a modified intention-to-treat approach, including all patients who received at least one dose of study treatment and had tumour assessment at least once after randomisation. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-111390. Findings Between Feb 21, 2011, and March 5, 2012, 154 patients were enrolled. 77 were randomly assigned to receive erlotinib and bevacizumab and 77 to erlotinib alone, of whom 75 patients in the erlotinib plus bevacizumab group and 77 in the erlotinib alone group were included in the efficacy analyses. Median progression-free survival was 16·0 months (95% CI 13·9-18·1) with erlotinib plus bevacizumab and 9·7 months (5·7-11·1) with erlotinib alone (hazard ratio 0·54, 95% CI 0·36-0·79; log-rank test p=0·0015). The most common grade 3 or worse adverse events were rash (19 [25%] patients in the erlotinib plus bevacizumab groupvs15 [19%] patients in the erlotinib alone group), hypertension (45 [60%]vseight [10%]), and proteinuria (six [8%]vsnone). Serious adverse events occurred at a similar frequency in both groups (18 [24%] patients in the erlotinib plus bevacizumab group and 19 [25%] patients in the erlotinib alone group). Interpretation Erlotinib plus bevacizumab combination could be a new first-line regimen inEGFRmutation-positive NSCLC. Further investigation of the regimen is warranted. Funding Chugai Pharmaceutical Co Ltd.

Models of the active site in [NiFe]hydrogenase enzymes have proven challenging to prepare. We isolated a paramagnetic dinuclear nickel-ruthenium complex with a bridging hydrido ligand from the heterolytic cleavage of H₂ by a dinuclear NiRu aqua complex in water under ambient conditions (20°C and 1 atmosphere pressure). The structure of the hexacoordinate Ni(μ-H)Ru complex was unequivocally determined by neutron diffraction analysis, and it comes closest to an effective analog for the core structure of the proposed active form of the enzyme.

Models of the active site in [NiFe]hydrogenase enzymes have proven challenging to prepare. We isolated a paramagnetic dinuclear nickel-ruthenium complex with a bridging hydrido ligand from the heterolytic cleavage of H sub(2) by a dinuclear NiRu aqua complex in water under ambient conditions (20C and 1 atmosphere pressure). The structure of the hexacoordinate Ni(k-H)Ru complex was unequivocally determined by neutron diffraction analysis, and it comes closest to an effective analog for the core structure of the proposed active form of the enzyme.