http://repub.eur.nl/res/aut/5448/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/16419/ 2009-04-23T00:00:00Z Background: This Phase 1/2a study evaluated the safety, immunogenicity, and efficacy of an experimental malaria vaccine comprised of the recombinant Plasmodium falciparum protein apical membrane antigen-1 (AMA-1) representing the 3D7 allele formulated with either the AS01B or AS02A Adjuvant Systems. Methodology/Principal Findings: After a preliminary safety evaluation of low dose AMA-1/AS01B (10 μg/0.5 mL) in 5 adults, 30 malaria-naïve adults were randomly allocated to receive full dose (50 μg/0.5 mL) of AMA-1/AS01B (n = 15) or AMA-1/AS02A (n = 15), followed by a malaria challenge. All vaccinations were administered intramuscularly on a 0-, 1-, 2-month schedule. All volunteers experienced transient injection site erythema, swelling and pain. Two weeks post-third vaccination, anti-AMA-1 Geometric Mean Antibody Concentrations (GMCs) with 95% Confidence Intervals (CIs) were high: low dose AMA-1/AS01B 196 μg/mL (103-371 μg/mL), full dose AMA-1/AS01B 279 μg/mL (210-369 μg/ mL) and full dose AMA-1/AS02A 216 μg/mL (169-276 μg/mL) with no significant difference among the 3 groups. The three vaccine formulations elicited equivalent functional antibody responses, as measured by growth inhibition assay (GIA), against homologous but not against heterologous (FVO) parasites as well as demonstrable interferon-gamma (IFN-γ) responses. To assess efficacy, volunteers were challenged with P. falciparum-infected mosquitoes, and all became parasitemic, with no significant difference in the prepatent period by either light microscopy or quantitative polymerase chain reaction (qPCR). However, a small but significant reduction of parasitemia in the AMA-1/AS02A group was seen with a statistical model employing qPCR measurements. Significance: All three vaccine formulations were found to be safe and highly immunogenic. These immune responses did not translate into significant vaccine efficacy in malaria-naïve adults employing a primary sporozoite challenge model, but encouragingly, estimation of parasite growth rates from qPCR data may suggest a partial biological effect of the vaccine. Further evaluation of the immunogenicity and efficacy of the AMA-1/AS02A formulation is ongoing in a malaria-experienced pediatric population in Mali. http://repub.eur.nl/res/pub/1126/ 2004-01-19T00:00:00Z This article provides empirical tests of the hypothesis of ‘optimal cognitive distance’, proposed by Nooteboom (1999, 2000), in two distinct empirical settings. Variety of cognition, needed for learning, has two dimensions: the number of agents with different cognition, and differences in cognition between them (cognitive distance). The hypothesis is that in interfirm relationships optimal learning entails a trade-off between the advantage of increased cognitive distance for a higher novelty value of a partner’s knowledge, and the disadvantage of less mutual understanding. If the value of learning is the mathematical product of novelty value and understandability, it has an inverse-U shaped relation with cognitive distance, with an optimum level that yields maximal value of learning. With auxiliary hypotheses, the hypothesis is tested on interfirm agreements between pharmaceutical companies and biotech companies, as well as on interfirm agreements in ICT industries. http://repub.eur.nl/res/pub/12500/ 1997-01-01T00:00:00Z http://repub.eur.nl/res/pub/12502/ 1997-01-01T00:00:00Z Over the past decade, case-based reasoning (CBR) has emerged as a major research area within the artificial intelligence research field due to both its widespread usage by humans and its appeal as a methodology for building intelligent systems. Conventional CBR systems have been largely designed as automated problem-solvers for producing a solution to a given problem by adapting the solution to a similar, previously solved problem. Such systems have had limited success in real-world applications. More recently, there has been a search for new paradigms and directions for increasing the utility of CBR systems for decision support. This paper focuses on the synergism between the research areas of CBR and decision support systems (DSSs). A conceptual framework for DSSs is presented and used to develop a taxonomy of three different types of CBR systems: 1) conventional, 2) decision-aiding, and 3) stimulative. The major characteristics of each type of CBR system are explained with a particular focus on decision-aiding and stimulative CBR systems. The research implications of the evolution in the design of CBR systems from automation toward decision-aiding and stimulation are also explored.