MPS - Decision Support System for Multiobjective Project Scheduling

The report presents a decision support system (DSS) for multiobjective project scheduling under multiple-category resource constraints. It handles quite a general class of nonpreemptive scheduling problems with renewable, nonrenewable and doubly-constrained resources, multiple performing modes of activities, precedence constraints in the form of an activity network and multiple project performance criteria of time and cost type. The DSS has been implemented on a microcomputer compatible with IBM PC, and called MPS. It is based on three kinds of heuristics: parallel priority rules, simulated annealing and branch-and-bound. The last algorithm can even yield exact solutions when sufficient processing time is available. Some parts of the MPS are interactive, in particular, the search for a best compromise schedule. Graphical facilities enable a thorough evaluation of feasible schedules. The report starts with a methodological guide presenting the problem formulation and the three heuristics. Then, the general scheme of the MPS is given together with an executive guide. An expanding menu and all its options are described and illustrated with a simple example. The last part presents a real problem solving consisting in scheduling 40 farm activities

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Combining Monte-Carlo and hyper-heuristic methods for the multi-mode resource-constrained multi-project scheduling problem

Multi-mode resource and precedence-constrained project scheduling is a well-known challenging real-world optimisation problem. An important variant of the problem requires scheduling of activities for multiple projects considering availability of local and global resources while respecting a range of constraints. A critical aspect of the benchmarks addressed in this paper is that the primary objective is to minimise the sum of the project completion times, with the usual makespan minimisation as a secondary objective. We observe that this leads to an expected different overall structure of good solutions and discuss the effects this has on the algorithm design. This paper presents a carefully-designed hybrid of Monte-Carlo tree search, novel neighbourhood moves, memetic algorithms, and hyper-heuristic methods. The implementation is also engineered to increase the speed with which iterations are performed, and to exploit the computing power of multicore machines. Empirical evaluation shows that the resulting information-sharing multi-component algorithm significantly outperforms other solvers on a set of “hidden” instances, i.e. instances not available at the algorithm design phase

Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes