Microstructure and mechanical properties of AA6056 friction stir welded plate

The microstructure and mechanical properties of a friction stir welded AA6056-T6 aluminum alloy plate were investigated by using polarized optical and transmission electron microscopy techniques. The microstructure revealed different grain morphologies in the thermomechanically affected zones, in proximity of the weld nugget; as the advancing side had fairly elongated, bent grains, whilst the broader retreating side had elongated grains whose width is narrower compared to the advancing side. On both sides, the thermo-mechanical affected zones showed a process of grain subdivision due to shear strain and temperature increase on approaching the nugget zone. Along with overaged precipitates in both thermomechanically affected zones, ß? and ß' particles were detected only within the retreating side. Tensile tests showed yield and ultimate strength slightly lower across the weld compared to the parent material; this difference resulted in a reduction in ductility of the weld region

A randomized open-label phase III trial evaluating the addition of denosumab to standard first-line treatment in advanced NSCLC : the European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR trial

Introduction Receptor activator of NF-kB ligand stimulates NF-kB–dependent cell signaling and acts as the primary signal for bone resorption. Retrospective analysis of a large trial comparing denosumab versus zoledronic acid in bone metastatic solid tumors suggested significant overall survival (OS) advantage for patients with lung cancer with denosumab (p = 0.01). The randomized open-label phase III SPLENDOUR trial was designed to evaluate whether the addition of denosumab to standard first-line platinum-based doublet chemotherapy improved OS in advanced NSCLC. Methods Patients with stage IV NSCLC were randomized in a 1:1 ratio to either chemotherapy with or without denosumab (120 mg every 3–4 wks), stratified by the presence of bone metastases (at diagnosis), Eastern Cooperative Oncology Group performance status, histology, and region. To detect an OS increase from 9 to 11.25 months (hazard ratio [HR] = 0.80), 847 OS events were required. The trial closed prematurely owing to decreasing accrual rate. Results A total of 514 patients were randomized, with 509 receiving one or more doses of the assigned treatment (chemotherapy: 252, chemotherapy-denosumab: 257). The median age was 66.1 years, 71% were men, and 59% were former smokers. Bone metastases were identified in 275 patients (53%). Median OS (95% confidence interval [CI]) was 8.7 (7.6–11.0) months in the control arm versus 8.2 (7.5–10.4) months in the chemotherapy-denosumab arm (HR = 0.96; 95% CI: 0.78–1.19; one-sided p = 0.36). For patients with bone metastasis, HR was 1.02 (95% CI: 0.77–1.35), whereas for those without, HR was 0.90 (95% CI: 0.66–1.23). Adverse events grade 3 or greater were observed in 40.9%, 5.2%, 8.7% versus 45.5%, 10.9%, 10.5% of patients. Conditional power for OS benefit was less than or equal to 10%. Conclusions Denosumab was well-tolerated without unexpected safety concerns. There was no OS improvement for denosumab when added to chemotherapy in the intention-to-treat population and the subgroups with and without bone metastases. Our data do not provide evidence of a clinical benefit for denosumab in patients with NSCLC without bone metastases