Robust airline scheduling with controllable cruise times and chance constraints

[No abstract available

Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis b virus ınfection

Background Long-term tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB) is associated with sustained viral suppression and regression of fibrosis and cirrhosis at year 5 (240 weeks) and no TDF resistance through 6 years (288 weeks). Aim We assessed the efficacy, safety, and resistance of TDF for up to 7 years (336 weeks) in HBeAg-positive and HBeAg-negative CHB patients. Methods Patients who completed 1 year (48 weeks) of randomized treatment with TDF or adefovir dipivoxil were eligible to receive open-label TDF for a total duration of 8 years (384 weeks). Results Of 641 patients initially randomized, 585 (91.3 %) entered the open-label phase; 437/585 (74.7 %) remained on study at year 7. For patients on treatment at year 7, 99.3 % maintained viral suppression (HBV DNA = 0.5 mg/dL above baseline. No significant change in bone mineral density was observed from year 4 to year 7 (week 192 to week 336). Conclusions Long-term TDF treatment was associated with sustained virologic, biochemical, and serologic responses, without resistance. TDF treatment was well tolerated, with a low incidence of renal and bone events. These data confirm the safety and efficacy of long-term TDF for CHB.Gilead Science

Long-term clinical outcomes in cirrhotic chronic hepatitis B patients treated with tenofovir disoproxil fumarate for up to 5 years

Background: Phase 3 clinical studies have shown that long-term treatment with tenofovir disoproxil fumarate (TDF) can suppress hepatitis B viral load and promote significant fibrosis regression and cirrhosis reversal in a majority of treated chronic hepatitis B (CHB) patients. This retrospective analysis investigated the impact of baseline cirrhosis status on virologic, serologic, and histologic outcomes in patients treated with TDF. Methods: Patients enrolled in studies GS-US-174-0102 and GS-US-174-0103 who had baseline liver biopsy–diagnosed cirrhosis and entered the open-label phase of the studies were included in the virologic and serologic analyses. Patients (both HBeAg positive and negative) with paired liver biopsies at baseline and 5 years (N = 348) were included in a histologic analysis. Results: After 5 years on study, comparing patients with and without baseline cirrhosis, respectively: 99.2 and 98.0 % achieved virologic response (hepatitis B viral load < 69 IU/ml) (p = 0.686); 79.7 and 81.9 % had normal serum levels of alanine aminotransferase (p = 0.586); 4.0 and 1.2 % developed hepatocellular carcinoma (p = 0.044). In HBeAg-positive patients with and without baseline cirrhosis, HBsAg loss occurred in 14.4 and 8.3 % of patients, respectively (p = 0.188). One HBeAg-negative patient had HBsAg loss. Conclusions: This represents the largest analyses to date of CHB patients with sequential liver biopsies demonstrating that treatment with TDF for up to 5 years is associated with favorable virologic, serologic, and histologic outcomes, regardless of baseline cirrhosis status. Notably, histologic improvement was observed in the majority of cirrhotic and noncirrhotic patients

Optimal allocation and processing time decisions on non-identical parallel CNC machines: epsilon-constraint approach

When the processing times of jobs are controllable, selected processing times affect both the manufacturing cost and the scheduling performance. A well known example for such a case that this paper specifically deals with is the turning operation on a CNC machine. Manufacturing cost of a turning operation is a nonlinear convex function of its processing time. In this paper, we deal with making optimal machine-job assignments and processing time decisions so as to minimize total manufacturing cost while the makespan being upper bounded by a known value, denoted as E-constraint approach for a bicriteria problem. We then give optimality properties for the resulting single criterion problem. We provide alternative methods to compute cost lower bounds for partial schedules, which are used in developing an exact (branch and bound) algorithm. For the cases where the exact algorithm is not efficient in terms of computation time, we present a recovering beam search algorithm equipped with an improvement search procedure. In order to find improving search directions, the improvement search algorithm uses the proposed cost bounding properties. Computational results show that our lower bounding methods in branch and bound algorithm achieve a significant reduction in the search tree size that we need to traverse. Also, our recovering beam search and improvement search heuristics achieve solutions within 1% of the optimum on the average while they spent much less computational effort than the exact algorithm

Scheduling parallel CNC machines with time/cost trade-off considerations

www.elsevier.com/locate/cor When the processing times of jobs are controllable, selected processing times affect both the manufacturing cost and the scheduling performance.A well-known example for such a case that this paper specifically deals with is the turning operation on a CNC machine. Manufacturing cost of a turning operation is a nonlinear convex function of its processing time. We also know that scheduling decisions are quite sensitive to the processing times. Therefore, this paper considers minimizing total manufacturing cost (F1) and total completion time (F2) objectives simultaneously on identical parallel CNC turning machines. Since decreasing processing time of a job increases its manufacturing cost, we cannot minimize both objectives at the same time, so the problem is to generate non-dominated solutions. We consider the problem of minimizing F1 subject to a given F2 level and give an effective formulation for the problem. For this problem, we prove some optimality properties which facilitated designing an efficient heuristic algorithm to generate approximate non-dominated solutions. Computational results show that proposed algorithm performs almost equal with the GAMS/MINOS commercial solver although it spends much less computation time

Machining conditions-based preventive maintenance

In this study we propose an operating conditions-based preventive maintenance (PM) approach for computer numerical control (CNC) turning machines. A CNC machine wears according to how much it is used and the conditions under which it is used. Higher power or production rates result in more wear and higher failure rates. This relationship between the operating conditions and maintenance requirements is usually overlooked in the literature. On CNC turning machines we can control the machining conditions such as cutting speed and feed rate, which in turn affect the PM requirements of the CNC machine. We provide a new model to link the PM decisions to the machining conditions selection decisions, so that these two decision-making problems can be solved together by considering their impact on each other. We establish that our proposed geometric programming model captures the related cost terms along with the technological restrictions of CNC machines. The proposed preventive maintenance index function can be used to provide an intelligent CNC machine degradation assessment. Keywords: Preventive maintenance; Condition-based maintenance; CNC machines; Machining conditions selection; Geometric programming 1

Aircraft recovery model with flight time controllability

[No abstract available