Specific treatment of advanced Schistosomiasis liver disease in man: favourable results

One hundred eighty-four patients with hepatosplenic schistosomiasis mansoni from the northeast of Brazil were studied. All were treated with a single dose of Oxamniquine or Praziquantel, and were observed over 6 to 12 months. Special attention was given to the evolution of severe hepatopathy. Favourable results were obtained, particularly with the compensated hepatosplenic form. Hepatic function showed great improvement. Hepatomegaly and splenomegaly were significantly reduced in size, to a greater or lesser extent, in the great majority of patients. The implications of the results obtained are considered below.

Soll man in der klinischen Praxis Frailty abschätzen?

Frailty, ein geriatrisches Syndrom mit altersbedingter Gebrechlichkeit assoziiert, heisst Verlust physiologischer Reserven verschiedener Organe. Die Folge ist eine erhöhte Verletzlichkeit durch Stress. Eine allseits anerkannte Definition fehlt, und die Abschätzung erfolgt hauptsächlich aufgrund zweier Modelle: des Phänotyps nach Fried und des Index nach Rockwood. Frailty bringt ein deutlich erhöhtes Risiko für funktionelle Hilfebedürftigkeit, Hospitalisation oder Einweisung in eine Institution für Langzeitpflege sowie Tod mit sich. Der Spontanverlauf ist progressiv, kann aber auch reversibel sein, und daher könnte Prävention grundsätzlich in Frage kommen. Unsere Kenntnisse sind derzeit aber immer noch zu lückenhaft, als dass wir gezielt gegen Frailty angehen könnten. Klinische Forschung über Frailty wird erst seit kurzem betrieben. Die Empfehlung, den Frailtygrad durch Leistungsmessung (wie Ganggeschwindigkeit, Griffkraft etc.) zu evaluieren, stützt sich auf die Beobachtung eines Zusammenhangs mit einer späteren ungünstigen Entwicklung, und nicht darauf, dass wir wirksam eingreifen könnten. Klinische und epidemiologische Studien über Frailty sind wichtig. Da die Babyboomer nun älter werden, ist die Gefahr einer Epidemie funktioneller Hilfebedürftigkeit Mitte des Jahrhunderts absehbar, und somit stellt das Problem der Frailty eine grosse Herausforderung dar.

Benchmarking therapeutic drug monitoring software: A review of available computer tools

Therapeutic drug monitoring (TDM) aims to optimize treatments by individualizing dosage regimens based on the measurement of blood concentrations. Dosage individualization to maintain concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculations currently represent the gold standard TDM approach but require computation assistance. In recent decades computer programs have been developed to assist clinicians in this assignment. The aim of this survey was to assess and compare computer tools designed to support TDM clinical activities. The literature and the Internet were searched to identify software. All programs were tested on personal computers. Each program was scored against a standardized grid covering pharmacokinetic relevance, user friendliness, computing aspects, interfacing and storage. A weighting factor was applied to each criterion of the grid to account for its relative importance. To assess the robustness of the software, six representative clinical vignettes were processed through each of them. Altogether, 12 software tools were identified, tested and ranked, representing a comprehensive review of the available software. Numbers of drugs handled by the software vary widely (from two to 180), and eight programs offer users the possibility of adding new drug models based on population pharmacokinetic analyses. Bayesian computation to predict dosage adaptation from blood concentration (a posteriori adjustment) is performed by ten tools, while nine are also able to propose a priori dosage regimens, based only on individual patient covariates such as age, sex and bodyweight. Among those applying Bayesian calculation, MM-USC*PACK© uses the non-parametric approach. The top two programs emerging from this benchmark were MwPharm© and TCIWorks. Most other programs evaluated had good potential while being less sophisticated or less user friendly. Programs vary in complexity and might not fit all healthcare settings. Each software tool must therefore be regarded with respect to the individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Computer-assisted TDM is gaining growing interest and should further improve, especially in terms of information system interfacing, user friendliness, data storage capability and report generation.

Towards an emotion-driven interactive music system: ridging the gaps between affect, physiology and sound generation

Report for the scientific sojourn at the Stanford University from January until June 2007. Music is well known for affecting human emotional states, yet the relationship between specific musical parameters and emotional responses is still not clear. With the advent of new human-computer interaction (HCI) technologies, it is now possible to derive emotion-related information from physiological data and use it as an input to interactive music systems. Providing such implicit musical HCI will be highly relevant for a number of applications including music therapy, diagnosis, nteractive gaming, and physiologically-based musical instruments. A key question in such physiology-based compositions is how sound synthesis parameters can be mapped to emotional states of valence and arousal. We used both verbal and heart rate responses to evaluate the affective power of five musical parameters. Our results show that a significant correlation exists between heart rate and the subjective evaluation of well-defined musical parameters. Brightness and loudness showed to be arousing parameters on subjective scale while harmonicity and even partial attenuation factor resulted in heart rate changes typically associated to valence. This demonstrates that a rational approach to designing emotion-driven music systems for our public installations and music therapy applications is possible.

Lack of evidence of the interaction of the Aß peptide with the Wnt signaling cascade in Drosophila models of Alzheimer's disease.

Background Alzheimer's disease (AD) is the leading form of dementia worldwide. The Aß-peptide is believed to be the major pathogenic compound of the disease. Since several years it is hypothesized that Aß impacts the Wnt signaling cascade and therefore activation of this signaling pathway is proposed to rescue the neurotoxic effect of Aß. Findings Expression of the human Aß42 in the Drosophila nervous system leads to a drastically shortened life span. We found that the action of Aß42 specifically in the glutamatergic motoneurons is responsible for the reduced survival. However, we find that the morphology of the glutamatergic larval neuromuscular junctions, which are widely used as the model for mammalian central nervous system synapses, is not affected by Aß42 expression. We furthermore demonstrate that genetic activation of the Wnt signal transduction pathway in the nervous system is not able to rescue the shortened life span or a rough eye phenotype in Drosophila. Conclusions Our data confirm that the life span is a useful readout of Aß42 induced neurotoxicity in Drosophila; the neuromuscular junction seems however not to be an appropriate model to study AD in flies. Additionally, our results challenge the hypothesis that Wnt signaling might be implicated in Aß42 toxicity and might serve as a drug target against AD.

Le code-switching comme ressource stratégique pour la gestion de l'interaction multilingue : coordination et leadership dans un groupe de travail

In this article, we analyze a multilingual interaction in a students' working group and hypothesize a correlation between management of languages in interaction and leadership. We consider Codeswitching as one of the most relevant observables in multilingual interaction and attempt to analyze how it is used by speakers. After a brief presentation of three theoretical and analytical conceptions of Code-switching in interaction (Auer, Mondada & Myers Scotton), we define Code-switching as an interactional, strategical, multilingual resource exploited by speakers to achieve various interactionaland non interactional goals. We then show in two CA-like analysis how multilingual strategical resources occur in the interactional practices of the analyzed working group, and how they are exploited by speakers in order to organize interaction, work, tasks, and to construct one's leadership.We also consider the metadiscourses of the students about their own practices and multilingualism in general, in order to confront them to their actual multilingual practices. We draw the hypothesis that discrepancies observed between metadiscourses and practices can be explained through the development of (meta)discourses showing a unilingual conception in describing multilingual practices.

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The use of the Internet now has a specific purpose: to find information. Unfortunately, the amount of data available on the Internet is growing exponentially, creating what can be considered a nearly infinite and ever-evolving network with no discernable structure. This rapid growth has raised the question of how to find the most relevant information. Many different techniques have been introduced to address the information overload, including search engines, Semantic Web, and recommender systems, among others. Recommender systems are computer-based techniques that are used to reduce information overload and recommend products likely to interest a user when given some information about the user's profile. This technique is mainly used in e-Commerce to suggest items that fit a customer's purchasing tendencies. The use of recommender systems for e-Government is a research topic that is intended to improve the interaction among public administrations, citizens, and the private sector through reducing information overload on e-Government services. More specifically, e-Democracy aims to increase citizens' participation in democratic processes through the use of information and communication technologies. In this chapter, an architecture of a recommender system that uses fuzzy clustering methods for e-Elections is introduced. In addition, a comparison with the smartvote system, a Web-based Voting Assistance Application (VAA) used to aid voters in finding the party or candidate that is most in line with their preferences, is presented.

Regional productivity variation and the impact of public capital stock: an analysis with spatial interaction, with reference to Spain

In this paper we examine whether variations in the level of public capital across Spain‟s Provinces affected productivity levels over the period 1996-2005. The analysis is motivated by contemporary urban economics theory, involving a production function for the competitive sector of the economy („industry‟) which includes the level of composite services derived from „service‟ firms under monopolistic competition. The outcome is potentially increasing returns to scale resulting from pecuniary externalities deriving from internal increasing returns in the monopolistic competition sector. We extend the production function by also making (log) labour efficiency a function of (log) total public capital stock and (log) human capital stock, leading to a simple and empirically tractable reduced form linking productivity level to density of employment, human capital and public capital stock. The model is further extended to include technological externalities or spillovers across provinces. Using panel data methodology, we find significant elasticities for total capital stock and for human capital stock, and a significant impact for employment density. The finding that the effect of public capital is significantly different from zero, indicating that it has a direct effect even after controlling for employment density, is contrary to some of the earlier research findings which leave the question of the impact of public capital unresolved.

CD28/CTLA4-B7 interaction is dispensable for T cell stimulation by mouse mammary tumor virus superantigen but not for B cell differentiation and virus dissemination.

B cells are the primary targets of infection for mouse mammary tumor virus (MMTV). However, for productive retroviral infection, T cell stimulation through the virally-encoded superantigen (SAG) is necessary. It activates B cells and leads to cell division and differentiation. To characterize the role of B cell differentiation for the MMTV life cycle, we studied the course of infection in transgenic mice deficient for CD28/CTLA4-B7 interactions (mCTLA4-H gamma 1 transgenic mice). B cell infection occurred in CTLA4-H gamma 1 transgenic mice as integrated proviral DNA could be detected in draining lymph node cells early after infection by polymerase chain reaction analysis. In mice expressing I-E, B cells were able to present the viral SAG efficiently to V beta 6+ T cells. These cells expanded specifically and were triggered to express the activation marker CD69. Further stages of progression of infection appeared to be defective. Kinetics experiments indicated that T and B cell stimulation stopped more rapidly than in control mice. B cells acquired an activated CD69+ phenotype, were induced to produce IgM but only partially switched to IgG secretion. Finally, the dissemination of infected cells to other lymph nodes and spleen was reduced and the peripheral deletion of V beta 6+ T cells was minimal. In contrast, in mice lacking I-E, T cell stimulation was also impaired and B cell activation undetectable. These data implicate B7-dependent cellular interactions for superantigenic T cell stimulation by low-affinity TCR ligands and suggest a role of B cell differentiation in viral dissemination and peripheral T cell deletion.

Pharmacokinetic drug interaction potential of risperidone with cytochrome p450 isozymes as assessed by the dextromethorphan, the caffeine, and the mephenytoin test.

Two published case reports showed that addition of risperidone (1 and 2 mg/d) to a clozapine treatment resulted in a strong increase of clozapine plasma levels. As clozapine is metabolized by cytochrome P450 isozymes, a study was initiated to assess the in vivo interaction potential of risperidone on various cytochrome P450 isozymes. Eight patients were phenotyped with dextromethorphan (CYP2D6), mephenytoin (CYP2C19), and caffeine (CYP1A2) before and after the introduction of risperidone. Before risperidone, all eight patients were phenotyped as being extensive metabolizers of CYP2D6 and CYP2C19. Risperidone at dosages between 2 and 6 mg/d does not appear to significantly inhibit CYP1A2 and CYP2C19 in vivo (median plasma paraxanthine/caffeine ratios before and after risperidone: 0.65, 0.69; p = 0.89; median urinary (S)/(R) mephenytoin ratios before and after risperidone:0.11, 0.12; p = 0.75). Although dextromethorphan metabolic ratio is significantly increased by risperidone (median urinary dextromethorphan/dextrorphan ratios before and after risperidone: 0.010, 0.018; p = 0.042), risperidone can be considered a weak in vivo CYP2D6 inhibitor, as this increase is modest and none of the eight patients was changed from an extensive to a poor metabolizer. The reported increase of clozapine concentrations by risperidone can therefore not be explained by an inhibition of CYP1A2, CYP2D6, CYP2C19 or by any combination of the three.

The Child is father of the man: implications for the demographic transition

We propose a new theory of the demographic transition based on the evidence that body development during childhood is an important predictor of adult life expectancy. This theory is embodied in an OLG framework where fertility, longevity and education all result from individual decisions. The model displays different regimes, allowing the economy to move slowly from an initial Malthusian regime towards the Modern era. The dynamics reproduces the key features of the demographic transition, including the permanent increase in life expectancy, resulting from improvements in body development, the hump in both population growth and fertility, and a late increase in secondary educational attainments.