Pharmacogenetics of Warfarin: Development of a Dosing Algorithm for Brazilian Patients

A dosing algorithm including genetic (VKORC1 and CYP2C9 genotypes) and nongenetic factors (age, weight, therapeutic indication, and cotreatment with amiodarone or simvastatin) explained 51% of the variance in stable weekly warfarin doses in 390 patients attending an anticoagulant clinic in a Brazilian public hospital. The VKORC1 3673G>A genotype was the most important predictor of warfarin dose, with a partial R(2) value of 23.9%. Replacing the VKORC1 3673G>A genotype with VKORC1 diplotype did not increase the algorithm`s predictive power. We suggest that three other single-nucleotide polymorphisms (SNPs) (5808T>G, 6853G>C, and 9041G>A) that are in strong linkage disequilibrium (LD) with 3673G>A would be equally good predictors of the warfarin dose requirement. The algorithm`s predictive power was similar across the self-identified ""race/color"" subsets. ""Race/color"" was not associated with stable warfarin dose in the multiple regression model, although the required warfarin dose was significantly lower (P = 0.006) in white (29 +/- 13 mg/week, n = 196) than in black patients (35 +/- 15 mg/week, n = 76).

Evidence for diffusional coupling in electrochemical thin layers: implications for surface coverage calibration via electrochemical infrared spectroscopy

The time dependence of the concentration of CO2 in an electrochemical thin layer cavity is studied with Fourier transform infrared spectroscopy (FTIR) in order to evaluate the extent to which the thin layer cavity is diffusionally decoupled from the surrounding bulk electrolyte. For the model system of CO on Pt(111) in 0.1 M HClO4, it is found that the concentration of CO2, formed by electro-oxidation of CO, equilibrates rapidly with the surrounding bulk electrolyte. This rapid equilibration indicates that there is diffusion out of the thin layer, even on the short time scales of typical infrared experiments (1-3 min). However, since the measured CO2 absorbance intensity as a function of time is reproducible to within 10%, a new time-dependent method for surface coverage calibration using solution-phase species is proposed.

Signal Processing and patternrecognition algorithm for monitoringParkinson’s disease.

This masters thesis describes the development of signal processing and patternrecognition in monitoring Parkison’s disease. It involves the development of a signalprocess algorithm and passing it into a pattern recogniton algorithm also. Thesealgorithms are used to determine , predict and make a conclusion on the study ofparkison’s disease. We get to understand the nature of how the parkinson’s disease isin humans.

Solving the Vehicle Routing Problem with Genetic ALgorithm and Simulated Annealing

This Thesis Work will concentrate on a very interesting problem, the Vehicle Routing Problem (VRP). In this problem, customers or cities have to be visited and packages have to be transported to each of them, starting from a basis point on the map. The goal is to solve the transportation problem, to be able to deliver the packages-on time for the customers,-enough package for each Customer,-using the available resources- and – of course - to be so effective as it is possible.Although this problem seems to be very easy to solve with a small number of cities or customers, it is not. In this problem the algorithm have to face with several constraints, for example opening hours, package delivery times, truck capacities, etc. This makes this problem a so called Multi Constraint Optimization Problem (MCOP). What’s more, this problem is intractable with current amount of computational power which is available for most of us. As the number of customers grow, the calculations to be done grows exponential fast, because all constraints have to be solved for each customers and it should not be forgotten that the goal is to find a solution, what is best enough, before the time for the calculation is up. This problem is introduced in the first chapter: form its basics, the Traveling Salesman Problem, using some theoretical and mathematical background it is shown, why is it so hard to optimize this problem, and although it is so hard, and there is no best algorithm known for huge number of customers, why is it a worth to deal with it. Just think about a huge transportation company with ten thousands of trucks, millions of customers: how much money could be saved if we would know the optimal path for all our packages.Although there is no best algorithm is known for this kind of optimization problems, we are trying to give an acceptable solution for it in the second and third chapter, where two algorithms are described: the Genetic Algorithm and the Simulated Annealing. Both of them are based on obtaining the processes of nature and material science. These algorithms will hardly ever be able to find the best solution for the problem, but they are able to give a very good solution in special cases within acceptable calculation time.In these chapters (2nd and 3rd) the Genetic Algorithm and Simulated Annealing is described in details, from their basis in the “real world” through their terminology and finally the basic implementation of them. The work will put a stress on the limits of these algorithms, their advantages and disadvantages, and also the comparison of them to each other.Finally, after all of these theories are shown, a simulation will be executed on an artificial environment of the VRP, with both Simulated Annealing and Genetic Algorithm. They will both solve the same problem in the same environment and are going to be compared to each other. The environment and the implementation are also described here, so as the test results obtained.Finally the possible improvements of these algorithms are discussed, and the work will try to answer the “big” question, “Which algorithm is better?”, if this question even exists.

A Genetic Algorithm for Solar Boat

Genetic algorithm has been widely used in different areas of optimization problems. Ithas been combined with renewable energy domain, photovoltaic system, in this thesis.To participate and win the solar boat race, a control program is needed and C++ hasbeen chosen for programming. To implement the program, the mathematic model hasbeen built. Besides, the approaches to calculate the boundaries related to conditionhave been explained. Afterward, the processing of the prediction and real time controlfunction are offered. The program has been simulated and the results proved thatgenetic algorithm is helpful to get the good results but it does not improve the resultstoo much since the particularity of the solar driven boat project such as the limitationof energy production

Branch and Bound Algorithm for Multiprocessor Scheduling

The multiprocessor task graph scheduling problem has been extensively studied asacademic optimization problem which occurs in optimizing the execution time of parallelalgorithm with parallel computer. The problem is already being known as one of the NPhardproblems. There are many good approaches made with many optimizing algorithmto find out the optimum solution for this problem with less computational time. One ofthem is branch and bound algorithm.In this paper, we propose a branch and bound algorithm for the multiprocessor schedulingproblem. We investigate the algorithm by comparing two different lower bounds withtheir computational costs and the size of the pruned tree.Several experiments are made with small set of problems and results are compared indifferent sections.

University Scheduling using Genetic Algorithm

The automated timetabling and scheduling is one of the hardest problem areas. This isbecause of constraints and satisfying those constraints to get the feasible and optimizedschedule, and it is already proved as an NP Complete (1) [1]. The basic idea behind this studyis to investigate the performance of Genetic Algorithm on general scheduling problem underpredefined constraints and check the validity of results, and then having comparative analysiswith other available approaches like Tabu search, simulated annealing, direct and indirectheuristics [2] and expert system. It is observed that Genetic Algorithm is good solutiontechnique for solving such problems and later analysis will prove this argument. The programis written in C++ and analysis is done by using variation in various parameters.

University Timetabling using Genetic Algorithm

The field of automated timetabling and scheduling meeting all the requirementsthat we call constraints is always difficult task and already proved as NPComplete. The idea behind my research is to implement Genetic Algorithm ongeneral scheduling problem under predefined constraints and check the validityof results, and then I will explain the possible usage of other approaches likeexpert systems, direct heuristics, network flows, simulated annealing and someother approaches. It is observed that Genetic Algorithm is good solutiontechnique for solving such problems. The program written in C++ and analysisis done with using various tools explained in details later.

First-principle data-driven models for assessment of motor disorders in Parkinson’s disease

Parkinson’s disease (PD) is an increasing neurological disorder in an aging society. The motor and non-motor symptoms of PD advance with the disease progression and occur in varying frequency and duration. In order to affirm the full extent of a patient’s condition, repeated assessments are necessary to adjust medical prescription. In clinical studies, symptoms are assessed using the unified Parkinson’s disease rating scale (UPDRS). On one hand, the subjective rating using UPDRS relies on clinical expertise. On the other hand, it requires the physical presence of patients in clinics which implies high logistical costs. Another limitation of clinical assessment is that the observation in hospital may not accurately represent a patient’s situation at home. For such reasons, the practical frequency of tracking PD symptoms may under-represent the true time scale of PD fluctuations and may result in an overall inaccurate assessment. Current technologies for at-home PD treatment are based on data-driven approaches for which the interpretation and reproduction of results are problematic.  The overall objective of this thesis is to develop and evaluate unobtrusive computer methods for enabling remote monitoring of patients with PD. It investigates first-principle data-driven model based novel signal and image processing techniques for extraction of clinically useful information from audio recordings of speech (in texts read aloud) and video recordings of gait and finger-tapping motor examinations. The aim is to map between PD symptoms severities estimated using novel computer methods and the clinical ratings based on UPDRS part-III (motor examination). A web-based test battery system consisting of self-assessment of symptoms and motor function tests was previously constructed for a touch screen mobile device. A comprehensive speech framework has been developed for this device to analyze text-dependent running speech by: (1) extracting novel signal features that are able to represent PD deficits in each individual component of the speech system, (2) mapping between clinical ratings and feature estimates of speech symptom severity, and (3) classifying between UPDRS part-III severity levels using speech features and statistical machine learning tools. A novel speech processing method called cepstral separation difference showed stronger ability to classify between speech symptom severities as compared to existing features of PD speech. In the case of finger tapping, the recorded videos of rapid finger tapping examination were processed using a novel computer-vision (CV) algorithm that extracts symptom information from video-based tapping signals using motion analysis of the index-finger which incorporates a face detection module for signal calibration. This algorithm was able to discriminate between UPDRS part III severity levels of finger tapping with high classification rates. Further analysis was performed on novel CV based gait features constructed using a standard human model to discriminate between a healthy gait and a Parkinsonian gait. The findings of this study suggest that the symptom severity levels in PD can be discriminated with high accuracies by involving a combination of first-principle (features) and data-driven (classification) approaches. The processing of audio and video recordings on one hand allows remote monitoring of speech, gait and finger-tapping examinations by the clinical staff. On the other hand, the first-principles approach eases the understanding of symptom estimates for clinicians. We have demonstrated that the selected features of speech, gait and finger tapping were able to discriminate between symptom severity levels, as well as, between healthy controls and PD patients with high classification rates. The findings support suitability of these methods to be used as decision support tools in the context of PD assessment.

Data based Calibration System for Radar used by Vehicle Activated Signs

The accurate measurement of a vehicle’s velocity is an essential feature in adaptive vehicle activated sign systems. Since the velocities of the vehicles are acquired from a continuous wave Doppler radar, the data collection becomes challenging. Data accuracy is sensitive to the calibration of the radar on the road. However, clear methodologies for in-field calibration have not been carefully established. The signs are often installed by subjective judgment which results in measurement errors. This paper develops a calibration method based on mining the data collected and matching individual vehicles travelling between two radars. The data was cleaned and prepared in two ways: cleaning and reconstructing. The results showed that the proposed correction factor derived from the cleaned data corresponded well with the experimental factor done on site. In addition, this proposed factor showed superior performance to the one derived from the reconstructed data.