BRAF mutation testing algorithm for vemurafenib treatment in melanoma: recommendations from an expert panel.

The incidence of melanoma has increased rapidly over the past 30 years, and the disease is now the sixth most common cancer among men and women in the U.K. Many patients are diagnosed with or develop metastatic disease, and survival is substantially reduced in these patients. Mutations in the BRAF gene have been identified as key drivers of melanoma cells and are found in around 50% of cutaneous melanomas. Vemurafenib (Zelboraf(®) ; Roche Molecular Systems Inc., Pleasanton, CA, U.S.A.) is the first licensed inhibitor of mutated BRAF, and offers a new first-line option for patients with unresectable or metastatic melanoma who harbour BRAF mutations. Vemurafenib was developed in conjunction with a companion diagnostic, the cobas(®) 4800 BRAF V600 Mutation Test. The purpose of this paper is to make evidence-based recommendations to facilitate the implementation of BRAF mutation testing and targeted therapy in patients with metastatic melanoma in the U.K. The recommendations are the result of a meeting of an expert panel and have been reviewed by melanoma specialists and representatives of the National Cancer Research Network Clinical Study Group on behalf of the wider melanoma community. This article is intended to be a starting point for practical advice and recommendations, which will no doubt be updated as we gain further experience in personalizing therapy for patients with melanoma.

Optimal day-ahead scheduling of integrated urban energy systems

An optimal day-ahead scheduling method (ODSM) for the integrated urban energy system (IUES) is introduced, which considers the reconfigurable capability of an electric distribution network. The hourly topology of a distribution network, a natural gas network, the energy centers including the combined heat and power (CHP) units, different energy conversion devices and demand responsive loads (DRLs), are optimized to minimize the day-ahead operation cost of the IUES. The hourly reconfigurable capability of the electric distribution network utilizing remotely controlled switches (RCSs) is explored and discussed. The operational constraints from the unbalanced three-phase electric distribution network, the natural gas network, and the energy centers are considered. The interactions between the electric distribution network and the natural gas network take place through conversion of energy among different energy vectors in the energy centers. An energy conversion analysis model for the energy center was developed based on the energy hub model. A hybrid optimization method based on genetic algorithm (GA) and a nonlinear interior point method (IPM) is utilized to solve the ODSM model. Numerical studies demonstrate that the proposed ODSM is able to provide the IUES with an effective and economical day-ahead scheduling scheme and reduce the operational cost of the IUES.