A fuzzy discrete event system approach to determining optimal HIV/AIDS treatment regimens.

Treatment decision-making is complex and involves many factors. A systematic decision-making and optimization technology capable of handling variations and uncertainties of patient characteristics and physician's subjectivity is currently unavailable. We recently developed a novel general-purpose fuzzy discrete event systems theory for optimal decision-making. We now apply it to develop an innovative system for medical treatment, specifically for the first round of highly active antiretroviral therapy of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients involving three historically widely used regimens. The objective is to develop such a system whose regimen choice for any given patient will exactly match expert AIDS physician's selection to produce the (anticipated) optimal treatment outcome. Our regimen selection system consists of a treatment objectives classifier, fuzzy finite state machine models for treatment regimens, and a genetic-algorithm-based optimizer. The optimizer enables the system to either emulate an individual doctor's decision-making or generate a regimen that simultaneously satisfies diverse treatment preferences of multiple physicians to the maximum extent. We used the optimizer to automatically learn the values of 26 parameters of the models. The learning was based on the consensus of AIDS specialists A and B on this project, whose exact agreement was only 35%. The performance of the resulting models was first assessed. We then carried out a retrospective study of the entire system using all the qualifying patients treated in our institution's AIDS Clinical Center in 2001. A total of 35 patients were treated by 13 specialists using the regimens (four and eight patients were treated by specialists A and B, respectively). We compared the actually prescribed regimens with those selected by the system using the same available information. The overall exact agreement was 82.9% (29 out of 35), with the exact agreement with specialists A and B both at 100%. The exact agreement for the remaining 11 physicians not involved in the system training was 73.9% (17 out of 23), an impressive result given the fact that expert opinion can be quite divergent for treatment decisions of such complexity. Our specialists also carefully examined the six mismatched cases and deemed that the system actually chose a more appropriate regimen for four of them. In the other two cases, either would be reasonable choices. Our approach has the capabilities of generalizing, learning, and representing knowledge even in the face of weak consensus, and being readily upgradeable to new medical knowledge. These are practically important features to medical applications in general, and HIV/AIDS treatment in particular, as national HIV/AIDS treatment guidelines are modified several times per year.     

Using new technologies for stimulating interpersonal communication on HIV and AIDS

Part of the current academic discourse on primary HIV and AIDS interventions, is focussed on the importance of interpersonal communication. Interpersonal communication is believed to mediate campaign effects through the creation of social learning environments. Therefore, many HIV and AIDS strategies (e.g. entertainment education programmes) use mass media channels for conveying messages on the one hand and spurring interpersonal communication among target groups on the other hand. However, it seems hard to find solid evidence that mass media campaigns are able to stimulate interpersonal communication. Simultaneously, there is a rising interest in the use of new technologies for HIV and AIDS prevention. As a result of their unique characteristics, such as interactivity and anonymity, they could be more appropriate than traditional channels to stimulate interpersonal communication. To gain insights in the challenges and opportunities of new technologies for primary HIV/AIDS prevention, this article presents the findings of a case study carried out at the University of the Western Cape. This study aimed at developing, implementing and evaluating an anonymous online discussion platform for students to share experiences and discuss sensitive subjects. The discussion forum was used in three ways: compulsory (through curriculum integration), semi-voluntarily and voluntarily. An extensive evaluation provided strong evidence that the online discussion forum was only successful when formally integrated into the curriculum. The most important opportunity of the formally integrated online forum relates to the creation of a social learning environment. The anonymous character of the online platform allayed fear for stigma and discrimination and removed cultural barriers concerning the inappropriateness of discussing HIV/AIDS related issues. As a result, the platform created a space in which students discussed freely, considered old and new ideas, acquired knowledge, and learned to esteem varying views on the subjects of discussion. Although no assertions can be made on the effects of these outcomes on sustainable changes in attitudes or behaviour, these findings indicate that participating in an anonymous online platform can instigate students to reflect on HIV/AIDS in a different way.     

Open- and closed-loop multiobjective optimal strategies for HIV therapy using NSGA-II

In this paper, multiobjective open- and closed-loop optimal treatment strategies for HIV/AIDS are presented. It is assumed that highly active antiretroviral therapy is available for treatment of HIV infection. Amount of drug usage and the quality of treatment are defined as two objectives of a biobjective optimization problem, and Nondominated Sorting Genetic Algorithm II is used to solve this problem. Open- and closed-loop control strategies are used to produce optimal control inputs, and the Pareto frontiers obtained from these two strategies are compared. Pareto frontier, resulted from the optimization process, suggests a set of treatment strategies, which all are optimal from a perspective, and can be used in different medical and economic conditions. Robustness of closed-loop system in the presence of measurement noises is analyzed, assuming various levels of noise.     

Chemokine receptors--the next therapeutic target for HIV?

To date, the available therapies for the treatment of HIV infection are targeted against proteins encoded by the virus itself. Thus, combination drug therapies for HIV with reverse transciptase and protease inhibitors have resulted in spectacular reductions of viraemia, often leading to a remarkable improvement in symptoms and recovery from disease in infected people. There is still however, a great need for improved therapies since many patients are unable to take these drugs, either for reasons of intolerance, strain resistance, complexity of regimen or prohibitive cost. Multiple therapies aimed at different events in the HIV life cycle will ensure switching of treatments to combat resistant viruses, and also allow treatment flexibility if patients are unable to tolerate particular therapies. One event that could provide a key to reducing or even eliminating viral infection would be to prevent the virus from entering the host cell. Intense efforts are now underway to produce drugs that target chemokine receptors, one of the essential components for HIV cell entry. HIV needs two receptors on the host cell surface for efficient attachment and infection. The first is CD4 and the second, identified in 1996, is a member of the family of chemokine receptors, members of the G-protein coupled 7TM superfamily, which are involved in the trafficking of leukocytes in immune surveillance and inflammation. Many small, orally bioavailable molecules that block various 7TM receptors are used to treat a panoply of diseases including ulcers, allergies, migraines, and schizophrenia. These molecules are the cornerstone of the pharmaceutical industry's contribution to the fight against so many diseases. Small molecule inhibitors of the HIV-coreceptors are now entering the first stages of clinical trials as new therapeutics for the fight against AIDS.     

Increases in Calls to the CDC National STD and AIDS Hotline Following AIDS-Related Episodes in a Soap Opera

In the United States, minority women are at risk of HIV infection and comprise a disproportionate share of daytime soap opera viewers. In August 2001, a soap opera subplot delivered HIV prevention messages to viewers and displayed the National STD and AIDS Hotline's toll-free number (800–342–2437) after 2 episodes. On both days, the number of attempted calls to the Hotline in the 1-hour time slots during and just after the 30-minute broadcasts rose dramatically. These increases in information-seeking behavior are consistent with predictions based on social cognitive theory, the health belief model, and various models of information processing. The increases also provide support for the Education-Entertainment approach and underscore the importance of a productive partnership between public health and the entertainment industry.     

Scaring the Already Scared: Some Problems With HIV/AIDS Fear Appeals in Namibia

Fear appeals are often used in public health campaigns in Africa to prevent further spread of HIV/AIDS. Based on the extended parallel processing model framework (K. Witte, 1991), this research assessed the impact of such messages in a high-fear situation. A 2 (high threat, low threat) × 2 (high efficacy, no efficacy) experiment with a no-message offset control and efficacy-only conditions tested several predictions. Participants demonstrated high preexisting fear about HIV/AIDS. As a likely consequence, statistical equivalence tests indicated that messages' threat levels had little impact on perceptions of fear or on outcome measures such as attitudes, intentions, or behaviors. It is concluded that the use of fear appeals to persuade audience with high levels of preexisting fear is ill-advised and ineffective.     

离轴三反大视场空间相机像移速度场模型

大视场空间相机在轨成像期间,由于地球自转、卫星姿态机动和颤振等因素导致焦面像速场呈非线性各向异性分布。为此提出了一种新的基于刚体运动学的像移速度场建模方法,考虑离轴角参数,推导了离轴三反大视场空间相机的像速场解析式。以某大视场空间相机为例,分析了侧摆成像时同速与异速像移速度匹配模式对相机成像质量的影响。分析结果表明:以传函下降5%为约束,侧摆15成像时,当积分级数大于10级时应采用异速匹配模式,积分级数为32级时,异速匹配相比于同速匹配使焦面动态MTF从0.340 8提高到0.970 2。当积分级数确定为16级时,侧摆角在12.3以内时可采用同速匹配模式。在轨成像结果证明了像移速度场模型的准确性,可为大视场空间相机像移补偿提供可靠依据。     

CCR5 and HIV infection

Chemokines and chemokine receptors play a crucial role in the trafficking of leukocyte populations across the body, and are involved in the development of a large variety of human diseases. CCR5 is the main coreceptor used by macrophage (M)-tropic strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2, which are responsible for viral transmission. CCR5 therefore plays an essential role in HIV pathogenesis. A number of inflammatory CC-chemokines, including MIP-1 alpha, MIP-1 beta, RANTES, MCP-2, and HCC-1[9-74] act as CCR5 agonists, while MCP-3 is a natural antagonist of the receptor. CCR5 is mainly expressed in memory T-cells, macrophages, and immature dendritic cells, and is upregulated by proinflammatory cytokines. It is coupled to the Gi class of heterotrimeric G-proteins, and inhibits cAMP production, stimulates Ca2+ release, and activates PI3-kinase and MAP kinases, as well as other tyrosine kinase cascades. A mutant allele of CCR5, CCR5 delta 32 is frequent in populations of European origin, and encodes a nonfunctional truncated protein that is not transported to the cell surface. Homozygotes for the delta 32 allele exhibit a strong, although incomplete, resistance to HIV infection, whereas heterozygotes display delayed progression to acquired immunodeficiency syndrome (AIDS). Many other alleles, affecting the primary structure of CCR5 or its promoter have been described, some of which lead to nonfunctional receptors or otherwise influence AIDS progression. CCR5 is considered as a drug target in the field of HIV, but also in a growing number of inflammatory diseases. Modified chemokines, monoclonal antibodies and small chemical antagonists, as well as a number of gene therapy approaches have been developed in this frame.     

Dynamic HIV/AIDS parameter estimation with application to a vaccine readiness study in southern Africa

This paper proposes a procedure of parameter estimation for all parameters of the three-dimensional HIV model. The least square based procedure uses standard optimization routines to allow parameter extraction for individual patients. It is shown how additional information from outside a measurement dataset can be included in the estimation routine to increase the reliability and accuracy of parameter estimates. A dataset from 44 patients of Southern Africa is analyzed to find the set point and the time until set point for these patients together with an estimate of the model parameters with confidence intervals for the cohort. The procedure is also applied to a long-term dataset of the HIV/AIDS progression to find possible variations in parameters.     

成本管理发展趋势

成本管理是生产力发展的产物,随着经济的发展而逐渐深化。文章从成本管理发展的三个历史阶段分别阐述成本管理的发展特点和规律,以及我国的成本管理发展现状。通过传统成本管理与作业成本管理的对比分析,指出当前成本管理的主要形式和未来成本管理将随着信息化的发展可能形成的主流模式。     

An energy-based three-dimensional segmentation approach for the quantitative interpretation of electron tomograms.

Electron tomography allows for the determination of the three-dimensional structures of cells and tissues at resolutions significantly higher than that which is possible with optical microscopy. Electron tomograms contain, in principle, vast amounts of information on the locations and architectures of large numbers of subcellular assemblies and organelles. The development of reliable quantitative approaches for the analysis of features in tomograms is an important problem, and a challenging prospect due to the low signal-to-noise ratios that are inherent to biological electron microscopic images. This is, in part, a consequence of the tremendous complexity of biological specimens. We report on a new method for the automated segmentation of HIV particles and selected cellular compartments in electron tomograms recorded from fixed, plastic-embedded sections derived from HIV-infected human macrophages. Individual features in the tomogram are segmented using a novel robust algorithm that finds their boundaries as global minimal surfaces in a metric space defined by image features. The optimization is carried out in a transformed spherical domain with the center an interior point of the particle of interest, providing a proper setting for the fast and accurate minimization of the segmentation energy. This method provides tools for the semi-automated detection and statistical evaluation of HIV particles at different stages of assembly in the cells and presents opportunities for correlation with biochemical markers of HIV infection. The segmentation algorithm developed here forms the basis of the automated analysis of electron tomograms and will be especially useful given the rapid increases in the rate of data acquisition. It could also enable studies of much larger data sets, such as those which might be obtained from the tomographic analysis of HIV-infected cells from studies of large populations.     

Reliability Growth Apportionment

A method is presented for apportioning reliability growth to the subsystems that make up a system in order to achieve the required reliability at least cost. Reliability growth apportionment is handled as an s-expected cost minimization problem subject to the constraint of meeting a system reliability requirement. The problem is formulated in terms of Duane's reliability growth model, and is solved using geometric programming. The method can be useful in the early stages of system design to determine subsystem reliability growth that will allow a system reliability requirement to be met, and in the latter stages of system design when reliability has fallen short of the required goal and improvements are necessary.     

A taxonomy of interaction models for Internet and ATM quality of service architectures

In communication systems there are two worlds at the moment: Internet and ATM. Both possess Quality of Service (QoS) architectures which shall allow them to integrate services of data and telecommunications formerly performed by separate infrastructures. We believe that none of them will be able to oust the other. That means both will exist for at least the middle-term future. Therefore, an interaction between both appears to be necessary, especially in the field of distributed multimedia applications where both worlds meet first. In order to perform gracefully, distributed multimedia applications require a certain QoS provision, in particular from the communication system. Thus, for such applications the existence of heterogeneous IP/ATM networks makes the interaction between Internet and ATM QoS architectures an important issue. In this article a taxonomy of interaction models for the Internet and ATM QoS architectures is developed. We do not let our view be restricted by existing approaches for the interaction between ATM and Internet. Instead we will derive more unconventional models by regarding the possible communication patterns based on different topological variants for heterogeneous IP/ATM networks. The investigation is driven by applications' communication requirements. This is accomplished by examining possibly interacting applications and their communication patterns. The interaction models are contrasted and compared to each other and their assumptions and implications are shown. The derived taxonomy of models allows us to classify proposed approaches for the interaction of Internet and ATM QoS architectures. Thereby we are able to identify the basic assumptions of these approaches and their corresponding restrictions.     

The Safer Sex Communication of Transgender Adults: Processes and Problems

As HIV continues to devastate marginalized communities, organizations have prioritized the development of evidence‐based HIV prevention programs. Although the transgender community is disproportionately affected by HIV/AIDS, no effective HIV prevention interventions have been identified for this group. The few published interventions focus on communication skills and community‐building efforts, necessitating greater understanding of the sexual communication experiences of a broad segment of the trans‐community. To explore the transgender experience with safer sex communication, 41 transgender adults were interviewed. Participants described safer sex communication as a complicated endeavor, involving privacy management, uncertainty reduction, and discussion of various approaches to sexual safety. Understanding the process of (and associated problems with) safer sex communication for transgender adults suggests implications for theory, research, and practice.     

Support vector machine incremental learning triggered by wrongly predicted samples

According to the classic Karush-Kuhn-Tucker (KKT) theorem, at every step of incremental support vector machine (SVM) learning, the newly adding sample which violates the KKT conditions will be a new support vector (SV) and migrate the old samples between SV set and non-support vector (NSV) set, and at the same time the learning model should be updated based on the SVs. However, it is not exactly clear at this moment that which of the old samples would change between SVs and NSVs. Additionally, the learning model will be unnecessarily updated, which will not greatly increase its accuracy but decrease the training speed. Therefore, how to choose the new SVs from old sets during the incremental stages and when to process incremental steps will greatly influence the accuracy and efficiency of incremental SVM learning. In this work, a new algorithm is proposed to select candidate SVs and use the wrongly predicted sample to trigger the incremental processing simultaneously. Experimental results show that the proposed algorithm can achieve good performance with high efficiency, high speed and good accuracy.     

Study of coupled thermal electric behavior of compliant micro-spring interconnects for next generation probing applications

Advances in integrated circuit fabrication have given rise to a need for an innovative, inexpensive, yet reliable probing technology with ultra-fine pitch capability. Flexible micro-spring structures that can exceed the probing needs of the next-generation microelectronic devices have been developed. Highly compliant cantilevered springs have been fabricated at pitches as small as 6/spl mu/m. These micro-springs are designed to accommodate topological variation in probing surfaces while flexing within the elastic regime. Coupled thermal-electric numerical models have been developed to understand the thermal contours and current density developed across these springs. Based on the models and experiments, it is seen that the electrical resistance of the probe spring under study will be less than 1 /spl Omega/. Also, it is seen that the maximum temperature due to Joule heating is localized near the tip of the probe and can be about 93/spl deg/C above the ambient temperature, when temperature dependent bulk material properties are used. Optimization of the spring geometry to reduce this maximum temperature is outlined. In addition, the role of scale effects on the thermal conductivity of the spring material is studied. Based on the work, it can be said that it is possible to design micro-contact springs for probing applications such that the electrical resistance and the temperature increase during probing will be within acceptable limits.     

Global ocean tide models on the eve of TOPEX/Poseidon

Global ocean tide models that can provide tide corrections to TOPEX/Poseidon altimeter data are described. Emphasis is given to the Schwiderski and Cartwright-Ray models, as these are the most comprehensive, highest resolution models, but other models that will soon appear are mentioned. Differences between models for M₂ often exceed 10 cm over vast stretches of the ocean. Comparisons to 80 selected pelagic and island gauge measurements indicate the Schwiderski model is more accurate for the major solar tides, the Cartwright-Ray for the major lunar tides. The adequacy of available tide models for studying basin-scale motions is probably marginal at best, although rapid advancement is expected over the next several years     

A Bayes Reliability Growth Model for A Development Testing Program

The problem of estimating the reliability of a system during development is considered. The development process has several stages at each stage binomial test data are obtained by testing a number of such systems on a success/fail basis. Marginal posterior distributions are derived under the assumption that the development process constrains the reliabilities to be nondecreasing and that the prior distribution for reliability at each stage is uniform. Simulation models are designed to facilitate testing for the validity and computation of the Bayesian model with ordered reliabilities as well as to compare results with other reliability growth models.     

Parametric methods in the analysis of survival data

Parametric methods have been used extensively to analyze survival data. The parametric distribution that has been most widely used in fitting survival data is the exponential. However, the exponential survival distribution does not generally provide a satisfactory fit to survival data. One reason is that the hazard rate in survival studies is not usually constant with respect to time. In roughly the last decade, other survival distributions have been used to fit to survival data. They include the Weibull, gamma, lognormal and extreme value distributions. These distributions allow more flexibility than the exponential because their associated hazard rates are not constant with respect to time.Methods are presented for estimating the parameters of the survival distributions mentioned above in the cases for which the data are uncensored and censored. Furthermore, survival may be correlated with some other variable or variables such as age, weight, or a diagnostic characteristic such as white blood count. To account for the relationship between survival and the variables related to survival, survival models have been developed which take into consideration these concomitant variables. Methodology is also presented for estimating parameters of survival models that include concomitant variables.Finally, methods are discussed concerning growth in survival. For example, a clinical trial may be conducted in stages; each stage representing a treatment regimen that is an improvement over previous stage treatments. Reliability growth models are discussed in order to assess survival at all stages of the clinical trial that have been conducted and predict survival probabilities at future stages.     

Crosstalk Prediction of Single- and Double-Walled Carbon-Nanotube (SWCNT/DWCNT) Bundle Interconnects

The crosstalk effects in single- and double-walled carbon-nanotube (SWCNT and DWCNT) bundle-interconnect architectures are investigated in this paper. Some modified equivalent-circuit models are proposed for both SWCNT and DWCNT bundles, where capacitive couplings between adjacent bundles are incorporated. These circuit models are further used to predict the performance of SWCNT and DWCNT bundle interconnects in comparison with the Cu wire counterpart at all interconnect levels for advanced future technology generations. It is found that, compared with the SWCNT bundle, the DWCNT bundle interconnect can lead to a reduction of crosstalk-induced time delay, which will be more significant with increasing bundle length, while the peak voltage of the crosstalk-induced glitch in SWCNT and DWCNT bundle interconnects is in the same order as that of Cu wires. Due to the improvement in time delay, it is numerically confirmed that the DWCNT bundle interconnect will be more suitable for the next generation of interconnect technology as compared with the SWCNT bundle counterpart.