Abstract
The pharmaceutical industry operates in a very competitive and regulated market The increased pressure of pharmacies to order fewer products and to receive them more frequently is overcharging the pharmaceutical's distribution network Furthermore, the tight margins and the continuous growth of generic drugs consumption are pressing wholesalers to optimize their supply chains. In order to survive, wholesalers are rethinking their strategies to increase competitiveness. This paper proposes an optimization-simulation approach to address the wholesalers network redesign problem, trading off the operational costs and customer service level. Firstly, at a strategic-tactical level, the supply chain network redesign decisions are optimized via a mixed integer programming model. Here, the number, location, function and capacity of the warehouses, the allocation of customers to the warehouses and the capacity and function of the distribution channels are defined. Secondly, at an operation level, the solution found is evaluated by means of a discrete event simulation model to assess the impact of the redesign in the wholesaler's daily activities. Computational results on a pharmaceutical wholesaler case-study are discussed and the benefits of this solution approach exposed.

Abstract
Mathematical formulations for production planning are increasing complexity, in order to improve their realism. In short-term planning, the desirable level of detail is particularly high. Exact solvers fail to generate good quality solutions for those complex models on medium- and large-sized instances within feasible time. Motivated by a real-world case study in the pulp and paper industry, this paper provides an efficient solution method to tackle the short-term production planning and scheduling in an integrated mill. Decisions on the paper machine setup pattern and on the production rate of the pulp digester (which is constrained to a maximum variation) complicate the problem. The approach is built on top of a mixed integer programming (MIP) formulation derived from the multi-stage general lotsizing and scheduling problem. It combines a Variable Neighbourhood Search procedure which manages the setup-related variables, a specific heuristic to determine the digester's production speeds and an exact method to optimize the production and flow movement decisions. Different strategies are explored to speed-up the solution procedure and alternative variants of the algorithm are tested on instances based on real data from the case study. The algorithm is benchmarked against exact procedures.

Abstract
Many combinatorial optimization problems (COPs) encountered in real-world logistics, transportation, production, healthcare, financial, telecommunication, and computing applications are NP-hard in nature. These real-life COPs are frequently characterized by their large-scale sizes and the need for obtaining high-quality solutions in short computing times, thus requiring the use of metaheuristic algorithms. Meta-heuristics benefit from different random-search and parallelization paradigms, but they frequently assume that the problem inputs, the underlying objective function, and the set of optimization constraints are deterministic. However, uncertainty is all around us, which often makes deterministic models oversimplified versions of real-life systems. After completing an extensive review of related work, this paper describes a general methodology that allows for extending metaheuristics through simulation to solve stochastic COPs. 'Simheuristics' allow modelers for dealing with real-life uncertainty in a natural way by integrating simulation (in any of its variants) into a metaheuristic-driven framework. These optimization-driven algorithms rely on the fact that efficient metaheuristics already exist for the deterministic version of the corresponding COP. Simheuristics also facilitate the introduction of risk and/or reliability analysis criteria during the assessment of alternative high-quality solutions to stochastic COPs. Several examples of applications in different fields illustrate the potential of the proposed methodology. (c) 2015 The Authors. Published by Elsevier Ltd.

Abstract
Disturbance Management is a major issue in process industries like the pulp and paper (P&P) industry. In this paper, a case study in an integrated P&P mill is examined. Production plans for the whole mill need not only to be optimized concerning company's indicators, but also to be robust so that disturbances can be avoided. We present a simulation-optimization approach that generates plans, correctly weighting their quality (regarding various indicators) and robustness. A discrete-event simulation model replicates the dynamics of implementation and adaptation of production plans in practice. The simulation model gives then feedback to optimization, in order to enhance the analytical model, which is thus able to generate robust plans. © IFAC.

Abstract
Credit-card fraud leads to billions of dollars in losses for online merchants. With the development of machine learning algorithms, researchers have been finding increasingly sophisticated ways to detect fraud, but practical implementations are rarely reported. We describe the development and deployment of a fraud detection system in a large e-tail merchant. The paper explores the combination of manual and automatic classification, gives insights into the complete development process and compares different machine learning methods. The paper can thus help researchers and practitioners to design and implement data mining based systems for fraud detection or similar problems. This project has contributed not only with an automatic system, but also with insights to the fraud analysts for improving their manual revision process, which resulted in an overall superior performance.

Abstract
This work addresses the well-known capacitated lot sizing problem (CLSP) which is proven to be an NP-hard optimization problem. Simple period-by-period heuristics are popular solution approaches due to the extremely low computational effort and their suitability for rolling planning horizons. The aim of this work is to apply genetic programming (GP) to automatically generate specialized heuristics specific to the instance class. Experiments show that we are able to obtain better solutions when using GP evolved lot sizing rules compared to state-of-the-art constructive heuristics.