Winona

https://digitalcommons.library.umaine.edu/mmb-me/1319/thumbnail.jp

Simultaneous optimisation of structural topology and material grading using level set method

Peer reviewedPublisher PD

Stress-based shape and topology optimization with the level set method

This paper proposes a level set method to solve minimum stress and stress-constrained shape and topology optimization problems. The method solves a sub-optimization problem every iteration to obtain optimal boundary velocities. A p-norm stress functional is used to aggregate stresses in a single constraint. The shape sensitivity function is derived and a computational procedure based on a least squares interpolation approach is devised in order to compute sensitivities at the boundaries. Adaptive constraint scaling is used to enforce exact control of stress limits. Numerical results show that the method is able to solve the problem e�ciently for single and multiple load cases obtaining solutions with smooth boundaries

A phase I study of nolatrexed dihydrochloride in children with advanced cancer. A United Kingdom Children's Cancer Study Group Investigation

A phase I study of nolatrexed, administered as a continuous 5 day intravenous infusion every 28 days, has been undertaken for children with advanced malignancy. 16 patients were treated at 3 dose levels; 420, 640 and 768 mg/m2 24 h−1. 8 patients were evaluable for toxicity. In the 6 patients treated at 768 mg/m2 24 h−1, dose-limiting oral mucositis and myelosuppression were observed. Plasma nolatrexed concentrations and systemic exposure, measured in 14 patients, were dose related, with mean AUC values of 36 mg−1 ml−1 min−1, 50 mg ml−1 min−1 and 80 mg ml−1 min−1at the 3 dose levels studied. Whereas no toxicity was encountered if the nolatrexed AUC was <45 mg ml−1 min−1, Grade 3 or 4 toxicity was observed with AUC values of >60 mg ml−1 min−1. Elevated plasma deoxyuridine levels, measured as a surrogate marker of thymidylate synthase inhibition, were seen at all of the dose levels studied. One patient with a spinal primitive neuroectodermal tumour had stable disease for 11 cycles of therapy, and in two patients with acute lymphoblastic leukaemia a short-lived 50% reduction in peripheral lymphoblast counts was observed. Nolatrexed can be safely administered to children with cancer, and there is evidence of therapeutic activity as well as antiproliferative toxicity. Phase II studies of nolatrexed in children at the maximum tolerated dose of 640 mg/m2 24 h−1are warranted. © 2001 Cancer Research Campaign http://www.bjcancer.co