Limited sampling strategies for estimation of cyclosporine exposure in pediatric hematopoietic stem cell transplant recipients : methodological improvement and introduction of sampling time deviation analysis.

Le suivi thérapeutique est recommandé pour l’ajustement de la dose des agents immunosuppresseurs. La pertinence de l’utilisation de la surface sous la courbe (SSC) comme biomarqueur dans l’exercice du suivi thérapeutique de la cyclosporine (CsA) dans la transplantation des cellules souches hématopoïétiques est soutenue par un nombre croissant d’études. Cependant, pour des raisons intrinsèques à la méthode de calcul de la SSC, son utilisation en milieu clinique n’est pas pratique. Les stratégies d’échantillonnage limitées, basées sur des approches de régression (R-LSS) ou des approches Bayésiennes (B-LSS), représentent des alternatives pratiques pour une estimation satisfaisante de la SSC. Cependant, pour une application efficace de ces méthodologies, leur conception doit accommoder la réalité clinique, notamment en requérant un nombre minimal de concentrations échelonnées sur une courte durée d’échantillonnage. De plus, une attention particulière devrait être accordée à assurer leur développement et validation adéquates. Il est aussi important de mentionner que l’irrégularité dans le temps de la collecte des échantillons sanguins peut avoir un impact non-négligeable sur la performance prédictive des R-LSS. Or, à ce jour, cet impact n’a fait l’objet d’aucune étude. Cette thèse de doctorat se penche sur ces problématiques afin de permettre une estimation précise et pratique de la SSC. Ces études ont été effectuées dans le cadre de l’utilisation de la CsA chez des patients pédiatriques ayant subi une greffe de cellules souches hématopoïétiques. D’abord, des approches de régression multiple ainsi que d’analyse pharmacocinétique de population (Pop-PK) ont été utilisées de façon constructive afin de développer et de valider adéquatement des LSS. Ensuite, plusieurs modèles Pop-PK ont été évalués, tout en gardant à l’esprit leur utilisation prévue dans le contexte de l’estimation de la SSC. Aussi, la performance des B-LSS ciblant différentes versions de SSC a également été étudiée. Enfin, l’impact des écarts entre les temps d’échantillonnage sanguins réels et les temps nominaux planifiés, sur la performance de prédiction des R-LSS a été quantifié en utilisant une approche de simulation qui considère des scénarios diversifiés et réalistes représentant des erreurs potentielles dans la cédule des échantillons sanguins. Ainsi, cette étude a d’abord conduit au développement de R-LSS et B-LSS ayant une performance clinique satisfaisante, et qui sont pratiques puisqu’elles impliquent 4 points d’échantillonnage ou moins obtenus dans les 4 heures post-dose. Une fois l’analyse Pop-PK effectuée, un modèle structural à deux compartiments avec un temps de délai a été retenu. Cependant, le modèle final - notamment avec covariables - n’a pas amélioré la performance des B-LSS comparativement aux modèles structuraux (sans covariables). En outre, nous avons démontré que les B-LSS exhibent une meilleure performance pour la SSC dérivée des concentrations simulées qui excluent les erreurs résiduelles, que nous avons nommée « underlying AUC », comparée à la SSC observée qui est directement calculée à partir des concentrations mesurées. Enfin, nos résultats ont prouvé que l’irrégularité des temps de la collecte des échantillons sanguins a un impact important sur la performance prédictive des R-LSS; cet impact est en fonction du nombre des échantillons requis, mais encore davantage en fonction de la durée du processus d’échantillonnage impliqué. Nous avons aussi mis en évidence que les erreurs d’échantillonnage commises aux moments où la concentration change rapidement sont celles qui affectent le plus le pouvoir prédictif des R-LSS. Plus intéressant, nous avons mis en exergue que même si différentes R-LSS peuvent avoir des performances similaires lorsque basées sur des temps nominaux, leurs tolérances aux erreurs des temps d’échantillonnage peuvent largement différer. En fait, une considération adéquate de l'impact de ces erreurs peut conduire à une sélection et une utilisation plus fiables des R-LSS. Par une investigation approfondie de différents aspects sous-jacents aux stratégies d’échantillonnages limités, cette thèse a pu fournir des améliorations méthodologiques notables, et proposer de nouvelles voies pour assurer leur utilisation de façon fiable et informée, tout en favorisant leur adéquation à la pratique clinique.

Nonparametric estimation of the leverage effect: a trade-off between robustness and efficiency

We consider two new approaches to nonparametric estimation of the leverage effect. The first approach uses stock prices alone. The second approach uses the data on stock prices as well as a certain volatility instrument, such as the CBOE volatility index (VIX) or the Black-Scholes implied volatility. The theoretical justification for the instrument-based estimator relies on a certain invariance property, which can be exploited when high frequency data is available. The price-only estimator is more robust since it is valid under weaker assumptions. However, in the presence of a valid volatility instrument, the price-only estimator is inefficient as the instrument-based estimator has a faster rate of convergence. We consider two empirical applications, in which we study the relationship between the leverage effect and the debt-to-equity ratio, credit risk, and illiquidity.

Parameter Estimation in Minification Processes

In this article it is proved that the stationary Markov sequences generated by minification models are ergodic and uniformly mixing. These results are used to establish the optimal properties of estimators for the parameters in the model. The problem of estimating the parameters in the exponential minification model is discussed in detail.

Estimation for the semipareto processes

This paper proposes different estimators for the parameters of SemiPareto and Pareto autoregressive minification processes The asymptotic properties of the estimators are established by showing that the SemiPareto process is α-mixing. Asymptotic variances of different moment and maximum likelihood estimators are compared.

Nonparametric Estimation of the Average Availability

The average availability of a repairable system is the expected proportion of time that the system is operating in the interval [0, t]. The present article discusses the nonparametric estimation of the average availability when (i) the data on 'n' complete cycles of system operation are available, (ii) the data are subject to right censorship, and (iii) the process is observed upto a specified time 'T'. In each case, a nonparametric confidence interval for the average availability is also constructed. Simulations are conducted to assess the performance of the estimators.

Energy Management in Wireless Sensor Networks: A Crosslayer,Channel Adaptive Approach Towards Performance Optimization

The proliferation of wireless sensor networks in a large spectrum of applications had been spurered by the rapid advances in MEMS(micro-electro mechanical systems )based sensor technology coupled with low power,Low cost digital signal processors and radio frequency circuits.A sensor network is composed of thousands of low cost and portable devices bearing large sensing computing and wireless communication capabilities. This large collection of tiny sensors can form a robust data computing and communication distributed system for automated information gathering and distributed sensing.The main attractive feature is that such a sensor network can be deployed in remote areas.Since the sensor node is battery powered,all the sensor nodes should collaborate together to form a fault tolerant network so as toprovide an efficient utilization of precious network resources like wireless channel,memory and battery capacity.The most crucial constraint is the energy consumption which has become the prime challenge for the design of long lived sensor nodes.

Investment analysis of chemical projects and development of standerdised mathematical co-relation for cost estimation of pressure vessels in chemical industry

The present study is intended to provide a new scientific approach to the solution of the worlds cost engineering problems encountered in the chemical industries in our nation. The problem is that of cost estimation of equipments especially of pressure vessels when setting up chemical industries .The present study attempts to develop a model for such cost estimation. This in turn is hoped would go a long way to solve this and related problems in forecasting the cost of setting up chemical plants.

Nonparametric Estimation of Survivor Function in Bivariate Competing Risk Models’

So far, in the bivariate set up, the analysis of lifetime (failure time) data with multiple causes of failure is done by treating each cause of failure separately. with failures from other causes considered as independent censoring. This approach is unrealistic in many situations. For example, in the analysis of mortality data on married couples one would be interested to compare the hazards for the same cause of death as well as to check whether death due to one cause is more important for the partners’ risk of death from other causes. In reliability analysis. one often has systems with more than one component and many systems. subsystems and components have more than one cause of failure. Design of high-reliability systems generally requires that the individual system components have extremely high reliability even after long periods of time. Knowledge of the failure behaviour of a component can lead to savings in its cost of production and maintenance and. in some cases, to the preservation of human life. For the purpose of improving reliability. it is necessary to identify the cause of failure down to the component level. By treating each cause of failure separately with failures from other causes considered as independent censoring, the analysis of lifetime data would be incomplete. Motivated by this. we introduce a new approach for the analysis of bivariate competing risk data using the bivariate vector hazard rate of Johnson and Kotz (1975).

Speech sample estimation from composite zerocrossings and encoding via adaptive switching of transforms

This thesis investigates the potential use of zerocrossing information for speech sample estimation. It provides 21 new method tn) estimate speech samples using composite zerocrossings. A simple linear interpolation technique is developed for this purpose. By using this method the A/D converter can be avoided in a speech coder. The newly proposed zerocrossing sampling theory is supported with results of computer simulations using real speech data. The thesis also presents two methods for voiced/ unvoiced classification. One of these methods is based on a distance measure which is a function of short time zerocrossing rate and short time energy of the signal. The other one is based on the attractor dimension and entropy of the signal. Among these two methods the first one is simple and reguires only very few computations compared to the other. This method is used imtea later chapter to design an enhanced Adaptive Transform Coder. The later part of the thesis addresses a few problems in Adaptive Transform Coding and presents an improved ATC. Transform coefficient with maximum amplitude is considered as ‘side information’. This. enables more accurate tfiiz assignment enui step—size computation. A new bit reassignment scheme is also introduced in this work. Finally, sum ATC which applies switching between luiscrete Cosine Transform and Discrete Walsh-Hadamard Transform for voiced and unvoiced speech segments respectively is presented. Simulation results are provided to show the improved performance of the coder

Estimation of temperature effects on fission barriers

An accurate mass formula at finite temperature has been used to obtain a more precise estimation of temperature effects on fission barriers calculated within the liquid drop model.

Channel Adaptive MAC Protocol with Traffic-Aware Distributed Power Management in Wireless Sensor Networks-Some Performance Issues

In Wireless Sensor Networks (WSN), neglecting the effects of varying channel quality can lead to an unnecessary wastage of precious battery resources and in turn can result in the rapid depletion of sensor energy and the partitioning of the network. Fairness is a critical issue when accessing a shared wireless channel and fair scheduling must be employed to provide the proper flow of information in a WSN. In this paper, we develop a channel adaptive MAC protocol with a traffic-aware dynamic power management algorithm for efficient packet scheduling and queuing in a sensor network, with time varying characteristics of the wireless channel also taken into consideration. The proposed protocol calculates a combined weight value based on the channel state and link quality. Then transmission is allowed only for those nodes with weights greater than a minimum quality threshold and nodes attempting to access the wireless medium with a low weight will be allowed to transmit only when their weight becomes high. This results in many poor quality nodes being deprived of transmission for a considerable amount of time. To avoid the buffer overflow and to achieve fairness for the poor quality nodes, we design a Load prediction algorithm. We also design a traffic aware dynamic power management scheme to minimize the energy consumption by continuously turning off the radio interface of all the unnecessary nodes that are not included in the routing path. By Simulation results, we show that our proposed protocol achieves a higher throughput and fairness besides reducing the delay

Estimation of Effective Impervious Surface Area of Cochin using Satellite Images

Urbanization refers to the process in which an increasing proportion of a population lives in cities and suburbs. Urbanization fuels the alteration of the Land use/Land cover pattern of the region including increase in built-up area, leading to imperviousness of the ground surface. With increasing urbanization and population pressures; the impervious areas in the cities are increasing fast. An impervious surface refers to an anthropogenic ally modified surface that prevents water from infiltrating into the soil. Surface imperviousness mapping is important for the studies related to water cycling, water quality, soil erosion, flood water drainage, non-point source pollution, urban heat island effect and urban hydrology. The present study estimates the Total Impervious Area (TIA) of the city of Kochi using high resolution satellite image (LISS IV, 5m. resolution). Additionally the study maps the Effective Impervious Area (EIA) by coupling the capabilities of GIS and Remote Sensing. Land use/Land cover map of the study area was prepared from the LISS IV image acquired for the year 2012. The classes were merged to prepare a map showing pervious and impervious area. Supervised Maximum Likelihood Classification (Supervised MLC),which is a simple but accurate method for image classification, is used in calculating TIA and an overall classification accuracy of 86.33% was obtained. Water bodies are 100% pervious, whereas urban built up area are 100% impervious. Further based on percentage of imperviousness, the Total Impervious Area is categorized into various classes

Reliable and Damage-Free Estimation of Resistivity of ZnO Thin Films for Photovoltaic Applications Using Photoluminescence Technique

This work projects photoluminescence (PL) as an alternative technique to estimate the order of resistivity of zinc oxide (ZnO) thin films. ZnO thin films, deposited using chemical spray pyrolysis (CSP) by varying the deposition parameters like solvent, spray rate, pH of precursor, and so forth, have been used for this study. Variation in the deposition conditions has tremendous impact on the luminescence properties as well as resistivity. Two emissions could be recorded for all samples—the near band edge emission (NBE) at 380 nm and the deep level emission (DLE) at ∼500 nm which are competing in nature. It is observed that the ratio of intensities of DLE to NBE ( DLE/ NBE) can be reduced by controlling oxygen incorporation in the sample. - measurements indicate that restricting oxygen incorporation reduces resistivity considerably. Variation of DLE/ NBE and resistivity for samples prepared under different deposition conditions is similar in nature. DLE/ NBE was always less than resistivity by an order for all samples.Thus from PL measurements alone, the order of resistivity of the samples can be estimated.