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Background: In the phase III double-blind European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 trial, pembrolizumab improved recurrence free and distant metastasis-free survival in patients with stage III cutaneous melanoma with complete resection of lymph nodes. In the pembrolizumab group, the incidence of grade I-V and of grade III-V immune-related adverse events (irAEs) was 37% and 7%, respectively. Methods: Patients were randomised to receive intravenous (i.v.) pembrolizumab 200 mg (N = 514) or placebo (N = 505) every 3 weeks, up to 1 year. On recurrence, patients could enter part 2 of the study: pembrolizumab 200 mg i.v. every 3 weeks up to 2 years, for crossover (those who received placebo) or rechallenge (those who had recurrence >6 months after completing 1-year adjuvant pembrolizumab therapy). For these patients, we present the safety profile and efficacy outcomes. Results: At the clinical cut-off (16-Oct-2020), in the placebo group, 298 patients had a disease recurrence, in which 155 (52%) crossed over ('crossover'). In the pembrolizumab group, 297 patients completed the 1-year treatment period; 47 had a recurrence >6 months later, in which 20 (43%) entered the rechallenge part 2 ('rechallenge'). In the crossover group, the median progression-free survival (PFS) was 8.5 months (95% confidence interval [CI] 5.7-15.2) and the 3-year PFS rate was 32% (95% CI 25-40%). Among 80 patients with stage IV evaluable disease, 31 (39%) had an objective response: 14 (18%) patients with complete response (CR) and 17 (21%) patients with partial response. The 2-year PFS rate from response was 69% (95% CI 48-83%). In the rechallenge group, the median PFS was 4.1 months (95% CI 2.6-NE). Among 9 patients with stage IV evaluable disease, 1 had an objective response (CR). Among the 175 patients, 51 (29%) had a grade I-IV irAE and 11 (6%) had a grade III-IV irAE. Conclusions: Pembrolizumab treatment after crossover yielded an overall 3-year PFS ra

Thesis: Nav. E., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2015., Thesis: S.M. in Engineering and Management, Massachusetts Institute of Technology, Engineering Systems Division, 2015., Cataloged from PDF version of thesis., Includes bibliographical references (pages 85-86)., Hydrodynamic analysis of two models of the Offshore Floating Nuclear Plant [91 was conducted. The OFNP-300 and the OFNP-1100 were both exposed to computer simulated sea states in the computer program OrcaFlex: first to sets of monochromatic waves, each consisting of a single frequency and waveheight, and then to Bretschneider and JONSWAP spectra simulating 100-year storms in, respectively, the Gulf of Mexico and the North Sea. Hydrodynamic coefficients for these simulations were obtained using a separate computer program, WAMIT. Both models exhibited satisfactory performance in both heave and pitch. An alternative design of the OFNP-300 was developed and similarly analyzed in attempt to further improve hydrodynamic performance. A catenary mooring system was designed and analyzed for both plant models. The number of chains and the length of each were selected to ensure the mooring systems would withstand, with sufficient margins of safety, the maximum tension produced in a 100-year storm. This analysis was conducted both with all the designed mooring lines intact, and with the worst-case line broken. A lifecycle cost analysis of various mooring systems was conducted in order to minimize the cost of the mooring system while maintaining adequate performance., by Matthew Brian Strother., Nav. E., S.M. in Engineering and Management