Population analysis of the pharmacokinetics of tiagabine in patients with epilepsy

PURPOSE: In two open-label long-term safety studies, we determined tiagabine (TGB) pharmacokinetics in patients with epilepsy. METHODS: In all, 2,147 plasma samples from 511 patients who participated in the studies were available. The total daily dose ranged from 2 mg administered once daily to 80 mg administered in four doses. A one-compartment model with first-order absorption and elimination was used to fit the TGB plasma concentration-time data, with a population pharmacokinetic approach. RESULTS: The patients' average (+/-SD) weight and age were 73.8+/-20.7 kg and 32.1+/-12.3 years. The most significantly factor affecting TGB pharmacokinetics was concomitant administration of other antiepileptic drugs (AEDs). The central clearance value in patients receiving AEDs known to induce hepatic drug metabolism was 21.4 L/h, a value 67% higher than the central clearance estimate obtained for the patients receiving AEDs not known to affect hepatic drug metabolism (12.8 L/h). There was no evidence of any dose or time effect, indicating that TGB pharmacokinetics are linear. TGB pharmacokinetics were not different in white, black, or Hispanic patients, although our ability to explore racial effects was limited since 90% of the patients were white. No other demographic variables (including age and smoking) or any clinical chemistry measurements (including bilirubin, SGOT, and SGPT) were important in explaining the variability in the clearance estimates. CONCLUSIONS: TGB pharmacokinetics are linear, influenced by enzyme-inducing AEDs, and largely unaffected by other demographic variables.     

CACHE RP : A novel dynamic cache size tuning model working with relative object popularity for fast web information retrieval

The CACHE_RPframework leverages the relative object popularity as the sole parameter for dynamic cache size tuning. In the process it consistently maintains the prescribed cache hit ratio on the fly by deriving the popularity ratio from the current statistics. As a result the accuracy of the statistical CACHE_RPoperation is independent of changes in the Internet traffic pattern that may switch suddenly. The contribution by the novel CACHE_RPframework is that by adaptively maintaining the given hit ratio it effectively reduces the end-to-end information retrieval roundtrip time (RTT) and frees more bandwidth for sharing. This bandwidth would otherwise be consumed in transferring large amounts of data from remote data sources to the proxy server before it is given to the client or requestor.     

Knowledge acquisition of conjunctive rules using multilayered neural networks

A major bottleneck in developing knowledge-based systems is the acquisition of knowledge. Machine learning is an area concerned with the automation of this process of knowledge acquisition. Neural networks generally represent their knowledge at the lower level, while knowledge-based systems use higher-level knowledge representations. the method we propose here provides a technique that automatically allows us to extract conjunctive rules from the lower-level representation used by neural networks, the strength of neural networks in dealing with noise has enabled us to produce correct rules in a noisy domain. Thus we propose a method that uses neural networks as the basis for the automation of knowledge acquisition and can be applied to noisy, realworld domains. © 1993 John Wiley & Sons, Inc.     

Influence of rare earth metals on the nucleation and solidification behavior of iron and 1045 steel

Two series of experiments have been conducted to determine the influence of rare earth additions on the nucleation and crystallization behavior of pure iron and 1045 steel. In the first series, additions of rare earth suicide or cerium dioxide powder to two-Kg 1045 steel ingots indicated that rare earth suicide can refine the as-cast structure of such ingots. However, if the holding time after rare earth silicide addition is over two minutes, the grain refinement decreases. With cerium dioxide additions, a relatively large columnar zone was obtained. In the second series, the effects of cerium metal or cerium dioxide powder additions on the degree of undercooling obtainable in pure iron and 1045 steel were examined by the lévitation melting method. Surface tension measurements of the levitated droplets were carried out at the same time to investigate the possible effects of surface tension variations on the nucleation and crystallization behavior of the metals. The experimental data show that rare earth inclusions can greatly reduce the degree of undercooling of iron and steel, and that a small amount of dissolved cerium can further reduce the degree of undercooling of levitated droplets. The structure and reaction products obtained with Fe-Ce levitated droplets were examined with both optical and scanning electron microscopy as well as X-ray diffraction analysis. The experimental results clearly indicated that cerium solute redistribution during solidification is the dominant factor in refining the as-cast structure. A nucleation and solidification model for the Fe-Ce levitated droplets has been developed, which can successfully explain the experimental results. on research leave from Beijing University of Iron and Steel Technology     

Using single-layered neural networks for the extraction of conjunctive rules and hierarchical classifications

Machine Learning is an area concerned with the automation of the process of knowledge acquisition. Neural networks generally represent their knowledge at the lower level, while knowledge based systems use higher level knowledge representations. The method we propose here, provides a technique which automatically allows us to extract production rules from the lower level representation used by a single-layered neural networks trained by Hebb's rule. Even though a single-layered neural network can not model complex, nonlinear domains, their strength in dealing with noise has enabled us to produce correct rules in a noisy domain.     

SOFTLIB — a documentation management system

This paper describes a software sysem (SOFTLIB) that has been developed to assist in the management of software documentation generated during systems development projects. It provides facilities to manage large numbers of documents, to file documents when they are complete and to issue them to system developers and maintainers. It also includes an information retrieval facility that allows programming staff to find documents, to examine their contents before issue and to assess the state of the software project documentation. SOFTLIB is explicitly intended to help manage the documentation generated during software development — it is not designed for use by end-users of that software or for managing end-user documentation. The novel characteristic of this system is the approach that is taken to the consistency and completeness of documentation. The documentation associated with a software system is organized in such a way that it may be detected if document sets are complete (that is, if all documentation which should be provided for a software component is available) and if document sets are likely to be inconsistent. This means that if a document has been changed without a comparable change being made to other associated documents, this is detectable by the librarian system. In addition, a subsidiary aim of our work was to investigate the utility of menu systems to complex software tools by building a user interface to SOFTLIB. We conclude that menu systems are far from ideal in such situations because of the range of possible options which must be handled by the system.     

Trust ontologies for e‐service environments

In this article, we introduce trust ontologies. An ontology represents a set of concepts that are commonly shared and agreed to by all parties in a particular domain. Here, we introduce generic and specific trust ontologies. These ontologies include the following: an agent trust ontology and trustworthiness; agents include sellers, service providers, Web sites, brokers, shops, suppliers, buyers, or reviewers. A services trust ontology and trustworthiness assists in measuring the quality of service that agents provide in the service‐oriented environment such as sales, orders, track and trace, warehousing, logistics, education, governance, advertising, entertainment, trading, online databases, virtual community services, security, information services, opinions, and e‐reviews. A goods or products trust ontology and trustworthiness is useful for measuring the quality of products such as commercial products, information products, entertainment products, or second‐hand products. We present a trust ontology that is suitable for all types of agents that exist in the service‐oriented environment. As agent trust is measured through the quality of goods and services, we introduce two additional distinct concepts of service trust ontology and product trust ontology. © 2007 Wiley Periodicals, Inc. Int J Int Syst 22: 519–545, 2007.     

Investigation into the use of large-scale total-energy systems in mild and warm climates

The concept of total energy has been known and used for several years. Large-scale applications of such systems, however, have occurred only in countries with severe winter climates where space heating provides the major low-grade heat load. This paper presents an investigation into the viability of total-energy systems in mild and warm climatic conditions. Under such conditions, to be viable, the main load for the total-energy system must come from industry. An investigation into the types of industries and their low-grade requirements was therefore carried out. It was found that industrial heating loads are such that approximately 35% of the heat energy requirements of a typical industrial mix can be supplied by low-grade heat below 230 ° C. When supplemented by conventional and domestic requirements, it is shown that total-energy plants fuelled by coal with an electrical capacity of about 300 MW are economically viable in mild Mediterranean climates. The paper presents a detailed analysis of capital and operating costs for such a plant over a twenty five-year period. It also presents a sensitivity study of the capital cost of such systems to rate of growth of electrical load and of owning costs to changes in the prices of fuel.     

Age-related changes in children's use of external representations.

This study explored children's use of external representations. Experiment 1 focused on representations of self. Self-recognition was assessed by a mark test as a function of age (3 vs. 4 years), delay (5 s vs. 3 min), and media (photographs vs. drawings). Four-year-olds outperformed 3-year-olds; children performed better with photographs than drawings; and there was no effect of delay. In Experiment 2, 3- and 4-year-olds used a delayed video image to locate a sticker on themselves (self task) or a stuffed animal (other task). The 2 tasks were positively correlated with age and vocabulary partialed out. Experiment 3 used a search task to assess whether children have particular difficulty using external representations that conflict with their expectations: 3- and 4-year-olds were informed of an object's location verbally or through video; on half of the trials, this information conflicted with children's initial belief. Three-year-olds performed worse than 4-year-olds on conflict trials, indicating that assessments of self and other understanding may reflect children's ability to reason about conflicting external representations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)