Using a simulation model for knowledge elicitation and knowledge management

The work reported in this paper is part of a project simulating maintenance operations in an automotive engine production facility. The decisions made by the people in charge of these operations form a crucial element of this simulation. Eliciting this knowledge is problematic. One approach is to use the simulation model as part of the knowledge elicitation process. This paper reports on the experience so far with using a simulation model to support knowledge management in this way. Issues are discussed regarding the data available, the use of the model, and the elicitation process itself. © 2004 Elsevier B.V. All rights reserved

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche

Untargeted Metabolome- and Transcriptome-Wide Association Study Suggests Causal Genes Modulating Metabolite Concentrations in Urine.

Gene products can affect the concentrations of small molecules (aka "metabolites"), and conversely, some metabolites can modulate the concentrations of gene transcripts. While many specific instances of this interplay have been revealed, a global approach to systematically uncover human gene-metabolite interactions is still lacking. We performed a metabolome- and transcriptome-wide association study to identify genes influencing the human metabolome using untargeted metabolome features, extracted from <sup>1</sup> H nuclear magnetic resonance spectroscopy (NMR) of urine samples, and gene expression levels, quantified from RNA-Seq of lymphoblastoid cell lines (LCL) from 555 healthy individuals. We identified 20 study-wide significant associations corresponding to 15 genes, of which 5 associations (with 2 genes) were confirmed with follow-up NMR data. Using metabomatching, we identified the metabolites corresponding to metabolome features associated with the genes, namely, N-acetylated compounds with ALMS1 and trimethylamine (TMA) with HPS1. Finally, Mendelian randomization analysis supported a potential causal link between the expression of genes in both the ALMS1- and HPS1-loci and their associated metabolite concentrations. In the case of HPS1, we additionally observed that TMA concentration likely exhibits a reverse causal effect on HPS1 expression levels, indicating a negative feedback loop. Our study highlights how the integration of metabolomics, gene expression, and genetic data can pinpoint causal genes modulating metabolite concentrations

Prevalence of Tremor and Parkinson\u27s Disease

To determine the prevalence of essential tremor (ET) and Parkinson\u27s disease (PD) in a retirement community, all residents of Carefree, Arizona, aged over 65 years were contacted. All participants completed validated questionnaires for PD and ET, and were examined using the Unified Parkinson\u27s Disease Rating Scale. Of 356 individuals evaluated, 155 (43.5%) had tremor; 73 (20.5%) had ET; 26 (7.3%) had PD; and 56 (15.7%) had postural tremor (PT). Thus, a large percentage of individuals were found to have tremor, in the plurality of whom it could be classified as ET. The number of individuals with Parkinson\u27s disease exceeded our expectations

Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization

Postvaccination meningoencephalitis occurred without clear relation to serum anti-Abeta42 antibody titers. Potential mechanisms such as T-cell and microglial activation may be responsible and are under consideration to develop a safer anti-Abeta immunotherapy for AD

Simulation based knowledge elicitation : effect of visual representation and model parameters

Since much knowledge is tacit, eliciting knowledge is a common bottleneck during the development of knowledge-based systems. Visual interactive simulation (VIS) has been proposed as a means for eliciting experts’ decision-making by getting them to interact with a visual simulation of the real system in which they work. In order to explore the effectiveness and efficiency of VIS based knowledge elicitation, an experiment has been carried out with decision-makers in a Ford Motor Company engine assembly plant. The model properties under investigation were the level of visual representation (2-dimensional, 2½-dimensional and 3-dimensional) and the model parameter settings (unadjusted and adjusted to represent more uncommon and extreme situations). The conclusion from the experiment is that using a 2-dimensional representation with adjusted parameter settings provides the better simulation-based means for eliciting knowledge, at least for the case modelled