Tacrolimus (TAC), a calcineurin inhibitor, and everolimus (EVL), an mTOR inhibitor, have been used as immunosuppressive (ISS) drugs in post-kidney transplantation therapy. The objective of this study was to compare the efficacy of EVL vs TAC in the ISS maintenance triple therapy. Ninety-seven kidney transplant patients, who received triple maintenance therapy with TAC, mycophenolate mofetil (MMF), and methyl prednisone (PRED), were evaluated. After four months of post-kidney transplant therapy, 30 patients enrolled in a randomized controlled clinical trial, in which 16 patients received TAC+MMF+PRED (cohort 1), and 14 patients switched to EVL+MMF+PRED (cohort 2). The patients were followed-up for 36 months. Two patients from cohort 1 lost their grafts after one year due to non-adherence. Two patients from cohort 2 had intolerance to mTOR inhibitors and were switched back to TAC from EVL. One case (6.25%) in cohort 1 and three cases (21.43%) in cohort 2 of acute T-cell-mediated rejection was observed. Antibody-mediated acute rejection (ABMAR) was observed in four patients (25.0%) in cohort 1, and antibody-mediated chronic rejection (ABMCR) was observed in two patients (12.50%). One patient from cohort 2 lost the graft after 15 months due to polyomavirus infection. The graft survival rate was 87.50% in cohort 1 and 92.86% in cohort 2. This clinical trial showed that the EVL+MMF+PRED triple maintenance therapy was efficacious compared with TAC during 32 months of follow-up. However, further studies are needed to confirm the efficacy of this regimen for long-term graft survival.

RESUMO. Dois importantes problemas de otimização combinatória ocorrem no planejamento da produção em indústrias papeleiras: o problema de dimensionamento de lotes e o problema de corte de estoque multiperíodo. O problema de dimensionamento de lotes deve determinar a quantidade de bobinas jumbos de diferentes tipos de papel (gramaturas) a serem produzidos em cada máquina, ao longo de um horizonte de planejamento finito. Estes jumbos são então cortados para atender a demanda de itens para cada período. Neste trabalho, tratamos da integração desses dois problemas, procurando minimizar custos com produção e estoque dos jumbos, como também a perda de papel durante o processo de corte. Duas modelagens matemáticas para o problema integrado foram consideradas, e os modelos foram resolvidos heuristicamente usando um pacote de otimização. Procurando obter limitantes inferiores para o problema, foram resolvidas versões relaxadas dos modelos. Finalmente, experimentos computacionais são apresentados e discutidos.

ABSTRACT. Two important optimization problems occur in the planning and production scheduling inpaper industries: the lot sizing problem and the cutting stock problem. The lot sizing problem must determine the quantity of jumbos of different types of paper to be produced in each machine over a finite planning horizon. These jumbos are then cut in order to meet the demand of items for each period. In this paper, we deal with the integration of these two problems, aiming to minimize costs of production and inventory of jumbos, as well as the trim loss of paper generated during the cutting process. Two mathematical models for the integrated problem are considered, and these models are solved both heuristically and using an optimization package. Attempting to get lower bounds for the problem, relaxed versions of the models also have been solved. Finally, computational experiments are presented and discussed.

Este trabalho aborda o problema de dimensionamento de lotes em um ambiente com várias plantas. Cada item pode ser produzido em qualquer planta e é possível atender a demanda de uma determinada planta com produção proveniente de uma (ou várias outras) planta(s), para tanto, incorre-se um custo de transferência. O objetivo deste trabalho consiste em desenvolver formulações fortes para o problema. São investigadas reformulações que baseiam-se no problema do caminho mínimo e localização de facilidades. Por fim, alguns resultados computacionais são apresentados comparando todas as formulações propostas.

This paper considers the multi-plant lot sizing problem. Each item can be produced in any plant and it is possible to meet the demand of a particular plant with production from one (or several) other plants, in this case, incurs a transfer cost. The objective is todevelop strong formulations for this problem. Reformulations that based on the shortest path problem and facility location problem are investigated. Finally, some computational results are presented comparing all the proposed formulations.

Este trabalho aborda o problema de dimensionamento de lotes monoestágio em um ambiente com máquinas paralelas distintas. Cada item pode ser produzido em qualquer máquina e incorre em um tempo de preparação antes de começar a produção. O objetivo do trabalho consiste em obter limitantes inferiores de boa qualidade para este problema. Para tanto, é desenvolvido um método de solução baseado numa reformulação do problema e na relaxação Lagrangiana de um conjunto de restrições. Alguns resultados computacionais são apresentados comparando o método proposto com um trabalho da literatura e com um pacote computacional.

This paper addresses the single stage lot-sizing problem in parallel machines. Each item can be produced on any machine, and incurs a setup time before to start the production. The objective of this paper is to obtain lower bounds of good quality for this problem. A solution method is developed based on a reformulation of the problem and the Lagrangian relaxation of a set of constraints. Some computational results are presented comparing the proposed method with a method from the literature and with a computational package.