Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/03.

PURPOSE Rituximab maintenance therapy has been shown to improve progression-free survival in patients with follicular lymphoma; however, the optimal duration of maintenance treatment remains unknown. PATIENTS AND METHODS Two hundred seventy patients with untreated, relapsed, stable, or chemotherapy-resistant follicular lymphoma were treated with four doses of rituximab monotherapy in weekly intervals (375 mg/m(2)). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of 5 years or until disease progression or unacceptable toxicity). The primary end point was event-free survival (EFS). Progression-free survival, overall survival (OS), and toxicity were secondary end points. Comparisons between the two arms were performed using the log-rank test for survival end points. RESULTS One hundred sixty-five patients were randomly assigned to the short-term (n = 82) or long-term (n = 83) maintenance arms. Because of the low event rate, the final analysis was performed after 95 events had occurred, which was before the targeted event number of 99 had been reached. At a median follow-up period of 6.4 years, the median EFS was 3.4 years (95% CI, 2.1 to 5.3) in the short-term arm and 5.3 years (95% CI, 3.5 to not available) in the long-term arm (P = .14). Patients in the long-term arm experienced more adverse effects than did those in the short-term arm, with 76% v 50% of patients with at least one adverse event (P < .001), five versus one patient with grade 3 and 4 infections, and three versus zero patients discontinuing treatment because of unacceptable toxicity, respectively. There was no difference in OS between the two groups. CONCLUSION Long-term rituximab maintenance therapy does not improve EFS, which was the primary end point of this trial, or OS, and was associated with increased toxicity.

HEALTH MAINTENANCE ORGANIZATION ENVIRONMENT: AN EMPIRICAL STUDY OF THE RELATIONSHIP OF EXTERNAL CONTEXT AND PERFORMANCE

The research project is an extension of a series of administrative science and health care research projects evaluating the influence of external context, organizational strategy, and organizational structure upon organizational success or performance. The research will rely on the assumption that there is not one single best approach to the management of organizations (the contingency theory). As organizational effectiveness is dependent on an appropriate mix of factors, organizations may be equally effective based on differing combinations of factors. The external context of the organization is expected to influence internal organizational strategy and structure and in turn the internal measures affect performance (discriminant theory). The research considers the relationship of external context and organization performance.^ The unit of study for the research will be the health maintenance organization (HMO); an organization the accepts in exchange for a fixed, advance capitation payment, contractual responsibility to assure the delivery of a stated range of health sevices to a voluntary enrolled population. With the current Federal resurgence of interest in the Health Maintenance Organization (HMO) as a major component in the health care system, attention must be directed at maximizing development of HMOs from the limited resources available. Increased skills are needed in both Federal and private evaluation of HMO feasibility in order to prevent resource investment and in projects that will fail while concurrently identifying potentially successful projects that will not be considered using current standards.^ The research considers 192 factors measuring contextual milieu (social, educational, economic, legal, demographic, health and technological factors). Through intercorrelation and principle components data reduction techniques this was reduced to 12 variables. Two measures of HMO performance were identified, they are (1) HMO status (operational or defunct), and (2) a principle components factor score considering eight measures of performance. The relationship between HMO context and performance was analysed using correlation and stepwise multiple regression methods. In each case it has been concluded that the external contextual variables are not predictive of success or failure of study Health Maintenance Organizations. This suggests that performance of an HMO may rely on internal organizational factors. These findings have policy implications as contextual measures are used as a major determinant in HMO feasibility analysis, and as a factor in the allocation of limited Federal funds. ^

Optimal Multiresolution 3D Level-Set Method for Liver Segmentation incorporating Local Curvature Constraints

Advanced liver surgery requires a precise pre-operative planning, where liver segmentation and remnant liver volume are key elements to avoid post-operative liver failure. In that context, level-set algorithms have achieved better results than others, especially with altered liver parenchyma or in cases with previous surgery. In order to improve functional liver parenchyma volume measurements, in this work we propose two strategies to enhance previous level-set algorithms: an optimal multi-resolution strategy with fine details correction and adaptive curvature, as well as an additional semiautomatic step imposing local curvature constraints. Results show more accurate segmentations, especially in elongated structures, detecting internal lesions and avoiding leakages to close structures

Content Delivery System for Optimal VoD Streaming

The demand of video contents has rapidly increased in the past years as a result of the wide deployment of IPTV and the variety of services offered by the network operators. One of the services that has especially become attractive to the customers is real-time video on demand (VoD) because it offers an immediate streaming of a large variety of video contents. The price that the operators have to pay for this convenience is the increased traffic in the networks, which are becoming more congested due to the higher demand for VoD contents and the increased quality of the videos. As a solution, in this paper we propose a hierarchical network system for VoD content delivery in managed networks, which implements redistribution algorithm and a redirection strategy for optimal content distribution within the network core and optimal streaming to the clients. The system monitors the state of the network and the behavior of the users to estimate the demand for the content items and to take the right decision on the appropriate number of replicas and their best positions in the network. The system's objectives are to distribute replicas of the content items in the network in a way that the most demanded contents will have replicas closer to the clients so that it will optimize the network utilization and will improve the users' experience. It also balances the load between the servers concentrating the traffic to the edges of the network.

Optimal and Long-Term Dynamic Transport Policy Design: Seeking Maximum Social Welfare through a Pricing Scheme.

This article presents an alternative approach to the decision-making process in transport strategy design. The study explores the possibility of integrating forecasting, assessment and optimization procedures in support of a decision-making process designed to reach the best achievable scenario through mobility policies. Long-term evaluation, as required by a dynamic system such as a city, is provided by a strategic Land-Use and Transport Interaction (LUTI) model. The social welfare achieved by implementing mobility LUTI model policies is measured through a cost-benefit analysis and maximized through an optimization process throughout the evaluation period. The method is tested by optimizing a pricing policy scheme in Madrid on a cordon toll in a context requiring system efficiency, social equity and environmental quality. The optimized scheme yields an appreciable increase in social surplus through a relatively low rate compared to other similar pricing toll schemes. The results highlight the different considerations regarding mobility impacts on the case study area, as well as the major contributors to social welfare surplus. This leads the authors to reconsider the cost-analysis approach, as defined in the study, as the best option for formulating sustainability measures.

Excitación y control de IGBTs de un inversor trifásico sinusoidal

El origen del proyecto se encuentra en la mejora de un inversor trifásico sinusoidal comercial sobre la base del estudio de las técnicas de excitación óptimas para los IGBTs que lo componen en su etapa de potencia. En las primeras fases de planteamiento del proyecto se propone una idea mucho más ambiciosa, la realización de un nuevo convertidor de emergencia, destinado al sector ferroviario, para dar servicio de climatización. Este convertidor está formado por la asociación en cascada de un bloque DC/DC elevador y un bloque inversor DC/AC trifásico controlado mediante PWM con modulación sinusoidal. Se pretendía así dar solución a las siguientes problemáticas detectadas en los convertidores comercializados hasta el momento: un bloque elevador excesivamente sobredimensionado, subsistemas de control independientes para los dos bloques que configuran el convertidor, adicionalmente, la tarjeta driver se rediseña con cada cambio de especificaciones por parte de un nuevo cliente y finalmente, las comunicaciones tanto de diagnosis como de mantenimiento necesitaban una importante actualización. Inicialmente, se ha realizado un estudio teórico de los bloques elevador e inversor para poder realizar el diseño y dimensionamiento de sus componentes tanto semiconductores como electromagnéticos. Una vez completada la parte de potencia, se estudia el control que se realiza mediante medidas directas y simulación tanto de la estrategia de control del elevador como del inversor. Así se obtiene una información completa de la funcionalidad de las tarjetas existentes. Se desea realizar el diseño de una única tarjeta controladora y una única tarjeta de drivers para ambos bloques. Por problemas ajenos, en el transcurso de este proyecto se cancela su realización comercial, con lo que se decide al menos crear la placa de control y poder gobernar un convertidor ya existente, sustituyendo la tarjeta de control del bloque elevador. Para poder fabricar la placa de control se divide en dos tarjetas que irán conectadas en modo sándwich. En una tarjeta está el microcontrolador y en otra está todo el interface necesario para operar con el sistema: entradas y salidas digitales, entradas y salidas analógicas, comunicación CAN, y un pequeño DC/DC comercial que proporciona alimentación al prototipo. Se realiza un pequeño programa funcional para poder manejar el convertidor, el cual con una tensión de 110V DC, proporciona a la salida una tensión de 380V AC. Como ya se ha expuesto, debido a la cancelación del proyecto industrial no se profundiza más en su mejora y se decide proponerlo para su evaluación en su fase actual. ABSTRACT. The beginning of the project is found in the improvement of a commercial sine wave three phase inverter which is based in a study about optimal excitation techniques to IGBTs which compose in the power stage. In the early phases of project it is proposed a much more ambitious idea, the fact of a new emergency converter, proposed for the rail sector to work in an air condition unit. This converter is formed by an association of a block cascaded DC/DC booster and a block DC/AC inverter three-phase controlled by a sine wave modulation PWM. The purposed was to give a solution to following problems detected in commercial converters nowadays: an excessively oversized block boost, independent control subsystems for two blocks that configure the converter. In addition, driver board is redesigned with each specifications change demand it a new customer, and finally, the communications, diagnostic and maintenance that needed a important upgrade. Initially, it has been performed a theoretical study of boost and the inverter blocks to be able to perform the component’s design and the size (semiconductor and electromagnetic fields). Once finished power study, it is analysed the control performed using direct measures and simulation of boost control strategy and inverter. With this it is obtained complete information about existing cards functionality. The project is looking for the design of just one controller card and one drivers´ card for both blocks. By unrelated problems, during the course of this project a commercial realization. So at least its decided to create control board to be able to existing converter, replacing boost block’s control board. To be able to manufacture control board it is divided in two cards connected in sandwiching mode. In a card is microcontroller and in another is all needed interface to operate with the system: digital inputs and outputs, analogical inputs and outputs, CAN communication, and a small DC / DC business that provide power supply to the prototype. It is performed a small functional program to handle the converter, which with an input voltage 110V DC provides an output voltage 380V AC. As already has been exposed, due to industrial project cancellation it is decided no to continue with all improvements and directly to evaluate it in the current phase.

Membrane Systems Working with the PFactor: Best Strategy to Solve Complex Problems.

A membrane system is a massive parallel system, which is inspired by the living cells when processing information. As a part of unconventional computing, membrane systems are proven to be effective in solving complex problems. A new factor is introduced. This factor can decide whether a technique is worthwhile being used or not. The use of this factor provides the best chances for selecting the strategy for the rules application phase. Referring to the “best” is in reference to the one that reduces execution time within the membrane system. A pre-analysis of the membrane system determines the P-factor, which in return advises the optimal strategy to use. In particular, this paper compares the use of two strategies based on the P-factor and provides results upon the application of them. The paper concludes that the P-factor is an effective indicator for choosing the right strategy to implement the rules application phase in membrane systems.

What if criminals optimize their choice? Optimal strategies to defend public goods

We investigate optimal strategies to defend valuable goods against the attacks of a thief. Given the value of the goods and the probability of success for the thief, we look for the strategy that assures the largest benefit to each player irrespective of the strategy of his opponent. Two complementary approaches are used: agent-based modeling and game theory. It is shown that the compromise between the value of the goods and the probability of success defines the mixed Nash equilibrium of the game, that is compared with the results of the agent-based simulations and discussed in terms of the system parameters.

UAS See-and-Avoid Strategy using a Fuzzy Logic Controller Optimized by Cross-Entropy in Scaling Factors and Membership Functions

This work aims to develop a novel Cross-Entropy (CE) optimization-based fuzzy controller for Unmanned Aerial Monocular Vision-IMU System (UAMVIS) to solve the seeand- avoid problem using its accurate autonomous localization information. The function of this fuzzy controller is regulating the heading of this system to avoid the obstacle, e.g. wall. In the Matlab Simulink-based training stages, the Scaling Factor (SF) is adjusted according to the specified task firstly, and then the Membership Function (MF) is tuned based on the optimized Scaling Factor to further improve the collison avoidance performance. After obtained the optimal SF and MF, 64% of rules has been reduced (from 125 rules to 45 rules), and a large number of real flight tests with a quadcopter have been done. The experimental results show that this approach precisely navigates the system to avoid the obstacle. To our best knowledge, this is the first work to present the optimized fuzzy controller for UAMVIS using Cross-Entropy method in Scaling Factors and Membership Functions optimization.

Optimal and Long-Term Dynamic Transport Policy Design: Seeking Maximum Social Welfare through a Pricing Scheme

This article presents an alternative approach to the decision-making process in transport strategy design. The study explores the possibility of integrating forecasting, assessment and optimization procedures in support of a decision-making process designed to reach the best achievable scenario through mobility policies. Long-term evaluation, as required by a dynamic system such as a city, is provided by a strategic Land-Use and Transport Interaction (LUTI) model. The social welfare achieved by implementing mobility LUTI model policies is measured through a cost-benefit analysis and maximized through an optimization process throughout the evaluation period. The method is tested by optimizing a pricing policy scheme in Madrid on a cordon toll in a context requiring system efficiency, social equity and environmental quality. The optimized scheme yields an appreciable increase in social surplus through a relatively low rate compared to other similar pricing toll schemes. The results highlight the different considerations regarding mobility impacts on the case study area, as well as the major contributors to social welfare surplus. This leads the authors to reconsider the cost-analysis approach, as defined in the study, as the best option for formulating sustainability measures.

Electricity price forecasting accounting for renewable energies: optimal combined forecasts

Electricity price forecasting is an interesting problem for all the agents involved in electricity market operation. For instance, every profit maximisation strategy is based on the computation of accurate one-day-ahead forecasts, which is why electricity price forecasting has been a growing field of research in recent years. In addition, the increasing concern about environmental issues has led to a high penetration of renewable energies, particularly wind. In some European countries such as Spain, Germany and Denmark, renewable energy is having a deep impact on the local power markets. In this paper, we propose an optimal model from the perspective of forecasting accuracy, and it consists of a combination of several univariate and multivariate time series methods that account for the amount of energy produced with clean energies, particularly wind and hydro, which are the most relevant renewable energy sources in the Iberian Market. This market is used to illustrate the proposed methodology, as it is one of those markets in which wind power production is more relevant in terms of its percentage of the total demand, but of course our method can be applied to any other liberalised power market. As far as our contribution is concerned, first, the methodology proposed by García-Martos et al(2007 and 2012) is generalised twofold: we allow the incorporation of wind power production and hydro reservoirs, and we do not impose the restriction of using the same model for 24h. A computational experiment and a Design of Experiments (DOE) are performed for this purpose. Then, for those hours in which there are two or more models without statistically significant differences in terms of their forecasting accuracy, a combination of forecasts is proposed by weighting the best models(according to the DOE) and minimising the Mean Absolute Percentage Error (MAPE). The MAPE is the most popular accuracy metric for comparing electricity price forecasting models. We construct the combi nation of forecasts by solving several nonlinear optimisation problems that allow computation of the optimal weights for building the combination of forecasts. The results are obtained by a large computational experiment that entails calculating out-of-sample forecasts for every hour in every day in the period from January 2007 to Decem ber 2009. In addition, to reinforce the value of our methodology, we compare our results with those that appear in recent published works in the field. This comparison shows the superiority of our methodology in terms of forecasting accuracy.

UAS See-and-Avoid Strategy using a Fuzzy Logic Controller Optimized by Cross-Entropy in Scaling Factors and Membership Functions.

This work aims to develop a novel Cross-Entropy (CE) optimization-based fuzzy controller for Unmanned Aerial Monocular Vision-IMU System (UAMVIS) to solve the seeand-avoid problem using its accurate autonomous localization information. The function of this fuzzy controller is regulating the heading of this system to avoid the obstacle, e.g. wall. In the Matlab Simulink-based training stages, the Scaling Factor (SF) is adjusted according to the specified task firstly, and then the Membership Function (MF) is tuned based on the optimized Scaling Factor to further improve the collison avoidance performance. After obtained the optimal SF and MF, 64% of rules has been reduced (from 125 rules to 45 rules), and a large number of real flight tests with a quadcopter have been done. The experimental results show that this approach precisely navigates the system to avoid the obstacle. To our best knowledge, this is the first work to present the optimized fuzzy controller for UAMVIS using Cross-Entropy method in Scaling Factors and Membership Functions optimization.

Unit Commitment and Electricity Prices Forecasting for Market Strategy Preparation in Interconnected Systems

In this paper we present a solution for building a better strategy to take part in external electricity markets. For an optimal strategy development, both the internal system costs as well as the future values of the series of electricity prices in external markets need to be known. But in practice, the real problems that must be faced are that both future electricity prices and costs are unknown. Thus, the first ones must be modeled and forecasted and the costs must be calculated. Our methodology for building an optimal strategy consists of three steps: The first step is modeling and forecasting market prices in external systems. The second step is the cost calculation on internal system taking into account the expected prices in the first step. The third step is based on the results of the previous steps, and consists of preparing the bids for external markets. The main goal is to reduce consumers' costs unlike many others that are oriented to increase GenCo's profits.

Integrated plant monitoring to improve plant operation strategy and results

The more and more demanding conditions in the power generation sector requires to apply all the available technologies to optimize processes and reduce costs. An integrated asset management strategy, combining technical analysis and operation and maintenance management can help to improve plant performance, flexibility and reliability. In order to deploy such a model it is necessary to combine plant data and specific equipment condition information, with different systems devoted to analyze performance and equipment condition, and take advantage of the results to support operation and maintenance decisions. This model that has been dealt in certain detail for electricity transmission and distribution networks, is not yet broadly extended in the power generation sector, as proposed in this study for the case of a combined power plant. Its application would turn in direct benefit for the operation and maintenance and for the interaction to the energy market

c-Abl is required for development and optimal cell proliferation in the context of p53 deficiency

The c-Abl tyrosine kinase and the p53 tumor suppressor protein interact functionally and biochemically in cellular genotoxic stress response pathways and are implicated as downstream mediators of ATM (ataxia-telangiectasia mutated). This fact led us to study genetic interactions in vivo between c-Abl and p53 by examining the phenotype of mice and cells deficient in both proteins. c-Abl-null mice show high neonatal mortality and decreased B lymphocytes, whereas p53-null mice are prone to tumor development. Surprisingly, mice doubly deficient in both c-Abl and p53 are not viable, suggesting that c-Abl and p53 together contribute to an essential function required for normal development. Fibroblasts lacking both c-Abl and p53 were similar to fibroblasts deficient in p53 alone, showing loss of the G1/S cell-cycle checkpoint and similar clonogenic survival after ionizing radiation. Fibroblasts deficient in both c-Abl and p53 show reduced growth in culture, as manifested by reduction in the rate of proliferation, saturation density, and colony formation, compared with fibroblasts lacking p53 alone. This defect could be restored by reconstitution of c-Abl expression. Taken together, these results indicate that the ATM phenotype cannot be explained solely by loss of c-Abl and p53 and that c-Abl contributes to enhanced proliferation of p53-deficient cells. Inhibition of c-Abl function may be a therapeutic strategy to target p53-deficient cells selectively.