Optimised dose titration for Duodopatreatment based on simulation experiments– implementation in a decision supportsystem

The aim of this work was to design a set of rules for levodopa infusion dose adjustment in Parkinson’s disease based on a simulation experiments. Using this simulator, optimal infusions dose in different conditions were calculated. There are seven conditions (-3 to +3)appearing in a rating scale for Parkinson’s disease patients. By finding mean of the differences between conditions and optimal dose, two sets of rules were designed. The set of rules was optimized by several testing. Usefulness for optimizing the titration procedure of new infusion patients based on rule-based reasoning was investigated. Results show that both of the number of the steps and the errors for finding optimal dose was shorten by new rules. At last, the dose predicted with new rules well on each single occasion of majority of patients in simulation experiments.

Heuristic optimization of the p-median problem and population re-distribution

This thesis contributes to the heuristic optimization of the p-median problem and Swedish population redistribution.   The p-median model is the most representative model in the location analysis. When facilities are located to a population geographically distributed in Q demand points, the p-median model systematically considers all the demand points such that each demand point will have an effect on the decision of the location. However, a series of questions arise. How do we measure the distances? Does the number of facilities to be located have a strong impact on the result? What scale of the network is suitable? How good is our solution? We have scrutinized a lot of issues like those. The reason why we are interested in those questions is that there are a lot of uncertainties in the solutions. We cannot guarantee our solution is good enough for making decisions. The technique of heuristic optimization is formulated in the thesis.   Swedish population redistribution is examined by a spatio-temporal covariance model. A descriptive analysis is not always enough to describe the moving effects from the neighbouring population. A correlation or a covariance analysis is more explicit to show the tendencies. Similarly, the optimization technique of the parameter estimation is required and is executed in the frame of statistical modeling. 

Short Communication: A compelling argument for the gravity p-median model

The p-median model is used to locate P facilities to serve a geographically distributed population. Conventionally, it is assumed that the population always travels to the nearest facility. Drezner and Drezner (2006, 2007) provide three arguments on why this assumption might be incorrect, and they introduce the extended the gravity p-median model to relax the assumption. We favour the gravity p-median model, but we note that in an applied setting, Drezner and Drezner’s arguments are incomplete. In this communication, we point at the existence of a fourth compelling argument for the gravity p-median model.

An empirical test of the gravity p-median model

A customer is presumed to gravitate to a facility by the distance to it and the attractiveness of it. However regarding the location of the facility, the presumption is that the customer opts for the shortest route to the nearest facility.This paradox was recently solved by the introduction of the gravity p-median model. The model is yet to be implemented and tested empirically. We implemented the model in an empirical problem of locating locksmiths, vehicle inspections, and retail stores ofv ehicle spare-parts, and we compared the solutions with those of the p-median model. We found the gravity p-median model to be of limited use for the problem of locating facilities as it either gives solutions similar to the p-median model, or it gives unstable solutions due to a non-concave objective function.

Distance measure and the p-median problem in rural areas

The p-median model is used to locate P facilities to serve a geographically distributed population. Conventionally, it is assumed that the population patronize the nearest facility and that the distance between the resident and the facility may be measured by the Euclidean distance. Carling, Han, and Håkansson (2012) compared two network distances with the Euclidean in a rural region witha sparse, heterogeneous network and a non-symmetric distribution of thepopulation. For a coarse network and P small, they found, in contrast to the literature, the Euclidean distance to be problematic. In this paper we extend their work by use of a refined network and study systematically the case when P is of varying size (2-100 facilities). We find that the network distance give as gooda solution as the travel-time network. The Euclidean distance gives solutions some 2-7 per cent worse than the network distances, and the solutions deteriorate with increasing P. Our conclusions extend to intra-urban location problems.

Network density and the p-median solution

The p-medianmodel is commonly used to find optimal locations of facilities for geographically distributed demands. So far, there are few studies that have considered the importance of the road network in the model. However, Han, Håkansson, and Rebreyend (2013) examined the solutions of the p-median model with densities of the road network varying from 500 to 70,000 nodes. They found as the density went beyond some 10,000 nodes, solutions have no further improvements but gradually worsen. The aim of this study is to check their findings by using an alternative heuristic being vertex substitution, as a complement to their using simulated annealing. We reject the findings in Han et al (2013). The solutions do not further improve as the nodes exceed 10,000, but neither do the solutions deteriorate.

A computational comparison of different algorithms for very large p-median problems

In this paper, we propose a new method for solving large scale p-median problem instances based on real data. We compare different approaches in terms of runtime, memory footprint and quality of solutions obtained. In order to test the different methods on real data, we introduce a new benchmark for the p-median problem based on real Swedish data. Because of the size of the problem addressed, up to 1938 candidate nodes, a number of algorithms, both exact and heuristic, are considered. We also propose an improved hybrid version of a genetic algorithm called impGA. Experiments show that impGA behaves as well as other methods for the standard set of medium-size problems taken from Beasley’s benchmark, but produces comparatively good results in terms of quality, runtime and memory footprint on our specific benchmark based on real Swedish data.

Chloroquine is grossly under dosed in young children with malaria : implications for drug resistance

Background: Plasmodium falciparum malaria is treated with 25 mg/kg of chloroquine (CQ) irrespective of age. Theoretically, CQ should be dosed according to body surface area (BSA). The effect of dosing CQ according to BSA has not been determined but doubling the dose per kg doubled the efficacy of CQ in children aged <15 years infected with P. falciparum carrying CQ resistance causing genes typical for Africa. The study aim was to determine the effect of age on CQ concentrations. Methods and Findings: Day 7 whole blood CQ concentrations were determined in 150 and 302 children treated with 25 and 50 mg/kg, respectively, in previously conducted clinical trials. CQ concentrations normalised for the dose taken in mg/kg of CQ decreased with decreasing age (p<0.001). CQ concentrations normalised for dose taken in mg/m(2) were unaffected by age. The median CQ concentration in children aged <2 years taking 50 mg/kg and in children aged 10-14 years taking 25 mg/kg were 825 (95% confidence interval [CI] 662-988) and 758 (95% CI 640-876) nmol/l, respectively (p = 0.67). The median CQ concentration in children aged 10-14 taking 50 mg/kg and children aged 0-2 taking 25 mg/kg were 1521 and 549 nmol/l. Adverse events were not age/concentration dependent. Conclusions: CQ is under-dosed in children and should ideally be dosed according to BSA. Children aged <2 years need approximately double the dose per kg to attain CQ concentrations found in children aged 10-14 years. Clinical trials assessing the efficacy of CQ in Africa are typically performed in children aged <5 years. Thus the efficacy of CQ is typically assessed in children in whom CQ is under dosed. Approximately 3 fold higher drug concentrations can probably be safely given to the youngest children. As CQ resistance is concentration dependent an alternative dosing of CQ may overcome resistance in Africa.

Testing the gravity p-median model empirically

Regarding the location of a facility, the presumption in the widely used p-median model is that the customer opts for the shortest route to the nearest facility. However, this assumption is problematic on free markets since the customer is presumed to gravitate to a facility by the distance to and the attractiveness of it. The recently introduced gravity p-median model offers an extension to the p-median model that account for this. The model is therefore potentially interesting, although it has not yet been implemented and tested empirically. In this paper, we have implemented the model in an empirical problem of locating vehicle inspections, locksmiths, and retail stores of vehicle spare-parts for the purpose of investigating its superiority to the p-median model. We found, however, the gravity p-median model to be of limited use for the problem of locating facilities as it either gives solutions similar to the p-median model, or it gives unstable solutions due to a non-concave objective function.