Development of novel testing strategies to detect adverse human health effects is of interest to replace in vivo-based drug and chemical safety testing. The aim of the present study was to investigate whether physiologically based kinetic (PBK) modeling-facilitated conversion of in vitro toxicity data is an adequate approach to predict in vivo cardiotoxicity in humans. To enable evaluation of predictions made, methadone was selected as the model compound, being a compound for which data on both kinetics and cardiotoxicity in humans are available. A PBK model for methadone in humans was developed and evaluated against available kinetic data presenting an adequate match. Use of the developed PBK model to convert concentration–response curves for the effect of methadone on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in the so-called multi electrode array (MEA) assay resulted in predictions for in vivo dose–response curves for methadone-induced cardiotoxicity that matched the available in vivo data. The results also revealed differences in protein plasma binding of methadone to be a potential factor underlying variation between individuals with respect to sensitivity towards the cardiotoxic effects of methadone. The present study provides a proof-of-principle of using PBK modeling-based reverse dosimetry of in vitro data for the prediction of cardiotoxicity in humans, providing a novel testing strategy in cardiac safety studies.
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The 2014 EU Directive on Maritime Spatial Planning (MSP) lays down obligations for the EU Member States to establish a maritime planning process, resulting in a maritime spatial plan by 2020. Consultation should be carried out with local, national and transnational stakeholders. Stakeholder engagement in MSP is complex because of the great number and diversity of maritime stakeholders and the unfamiliarity of some of these stakeholders with MSP and its potential impact. To facilitate stakeholder engagement in MSP, the 'MSP Challenge' table top strategy game was designed and played as part of several stakeholder events in different European countries. The authors study the efficacy of the game for stakeholder engagement. Background and evaluation data of nineteen game sessions with a total of 310 stakeholders with different backgrounds were collected through post-game surveys. Furthermore, the efficacy of the game for stakeholder engagement processes, organised by competent MSP authorities in Scotland and Belgium, is studied in more detail. The results show that the board game, overall, has been a very efficient and effective way of familiarising a great diversity of stakeholders with MSP and to create meaningful interaction and learning among stakeholders in formal planning processes. However, the case studies also show that contextual factors-the level of familiarity with MSP and participants' perception to sustainability-influences the efficacy of the game.
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Micro Ring Resonators (MRRs) have become the workhorse in photonics, both for data/telecomas well as bio-chemical sensing applications. In this contribution the use of MRRs as sensors for food-safety applications will be discussed.
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