https://www.selleckchem.com/products/cc-115.html Design optimization for cementless hip prosthesis signifies one of the key topics of research to improve its performances. However, majority of the studies have not considered the presence of uncertainties while it has been shown that a deterministic optimization leads to an unreliable design. In this paper, a multi-objective reliability-based design optimization (MORBDO) procedure is proposed for cementless hip prosthesis design. The proposed methodology consists in combining the finite element simulation (FES), surrogating techniques and optimization procedure. The constructed meta-models are validated and compared using different measures such as error predictions and cross-validation (CV). The results show that the constrained non-dominated sorting genetic algorithm (C-NSGA-II) coupled with the hybrid method (HM) was capable to generate well-distributed reliable Pareto solutions.Purpose Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC. Patients and methods Eligible patients included those with oral cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to IVB HNSCC (according to American Joint Committee on Cancer, 7th edition, staging system) eligible for cisplatin-based, standard-dose (70 Gy) chemoradiotherapy. Pembrolizumab was administered concurrently with and after chemoradiotherapy with weekly cisplatin. Safety was the primary end point and was determined by incidence of chemoradiotherapy adverse events (AEs) and immune-related AEs vestigation of this approach.Pu