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      • Mono and multi-objective optimization techniques applied to a large range of industrial test casesusing Metamodel assisted Evolutionary Algorithms

        Lionel FOURMENT,Richard DUCLOUX,Stephane MARIE,Mohsen EJDAY,Dominique MONNEREAU,Thomas MASSE,Pierre MONTMITONNET 한국소성가공학회 2010 기타자료 Vol.2010 No.6

        The use of material processing numerical simulation allows a strategy of trial and error to improve virtual processes without incurring material costs or interrupting production and therefore save a lot of money, but it requires user time to analyze the results, adjust the operating conditions and restart the simulation. Automatic optimization is the perfect complement to simulation. Evolutionary Algorithm coupled with metamodelling makes it possible to obtain industrially relevant results on a very large range of applications within a few tens of simulations and without any specific automatic optimization technique knowledge. Ten industrial partners have been selected to cover the different area of the mechanical forging industry and provide different examples of the forming simulation tools. It aims to demonstrate that it is possible to obtain industrially relevant results on a very large range of applications within a few tens of simulations and without any specific automatic optimization technique knowledge. The large computational time is handled by a metamodel approach. It allows interpolating the objective function on the entire parameter space by only knowing the exact function values at a reduced number of “master points”. Two algorithms are used: an evolution strategy combined with a Kriging metamodel and a genetic algorithm combined with a Meshless Finite Difference Method. The later approach is extended to multi-objective optimization. The set of solutions, which corresponds to the best possible compromises between the different objectives, is then computed in the same way. The population based approach allows using the parallel capabilities of the utilized computer with a high efficiency. An optimization module, fully embedded within the Forge2009 IHM, makes possible to cover all the defined examples, and the use of new multi-core hardware to compute several simulations at the same time reduces the needed time dramatically. The presented examples demonstrate the method versatility. They include billet shape optimization of a common rail, the cogging of a bar and a wire drawing problem.

      • Efficacy and Safety of Tenofovir DF (TDF) in Chronic Hepatitis B Patients (CHB) with Lamivudine Resistance (LAM-R): 5-year Results

        ( Florence Wong ),( Scott Fung ),( Hie-won Hann ),( Magdy Elkhashab ),( Thomas Berg ),( Milotka J. Fabri ),( Andrzej Horban ),( Mijomir Pelemis ),( Ioan Sporea ),( John F. Flaherty ),( Benedetta Masse 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

        Aims: In CHB patients with LAM-R, TDF has shown efficacy comparableto FTC/TDF and no detectable TDF resistance at 2 years. The final5 year efficacy and safety results from this trial are presented.Methods: CHB patients on LAM with HBV DNA >3 log10 IU/mL andwith documented LAM-R were randomized (1:1) to TDF or FTC/TDFand followed for 5 years.Results: Two hundred eighty patients were randomized; 232 (83%)completed 5 years of treatment. At baseline, mean age was 47 years,most were male (75%) and non-Asian (66%); 53% were HBeAgnegative. Mean HBV DNA was 5.7 log10 IU/mL and 42% had ALT≤ULN at baseline. At Year 5, virologic, serologic, and biochemicalresponses were similar among groups, and remained stable. Ninepatients (4-TDF, 5-FTC/TDF) discontinued due to an adverse event,including increased serum creatinine in 1 patient. For both groupscombined, confirmed renal safety endpoints over 5 years were: CrCL<50 mL/min in 19 (6.8%) patients (12 requiring dose modification),increases in serum creatinine of ≥0.3 and ≥0.5 mg/dL from baselinein 21 (7.5%) and 2 (0.7%) patients, respectively, and serum phosphorus<2 mg/dL in 3 (1.1%) patients. Mean declines in BMD (g/cm2)from baseline for hip and spine BMD, respectively, were 1.7% and1.5% at Year 2, and 2.5%, and 1% at Year 5. Seven patientsexperienced fracture (all except 1 were trauma-related). No TDF resistancewas detected through 5 years by population sequencing.Conclusions: In LAM R patients with CHB treated for 5 years withTDF, a high rate of HBV DNA suppression was achieved and maintainedwith no detectable TDF resistance. There is no apparent ad advantageof combination FTC/TDF in this population. Renal eventsassociated with TDF occurred in up to 7.5% of patients, and averagelosses in bone mineral density of 1 2.5% were observed.

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