New approach methodologies predicting human cardiotoxicity are of interest to support or even replace in vivo-based drug safety testing. The present study presents an in vitro–in silico approach to predict the effect of inter-individual and inter-ethnic kinetic variations in the cardiotoxicity of R- and S-methadone in the Caucasian and the Chinese population. In vitro cardiotoxicity data, and metabolic data obtained from two approaches, using either individual human liver microsomes or recombinant cytochrome P450 enzymes (rCYPs), were integrated with physiologically based kinetic (PBK) models and Monte Carlo simulations to predict inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. Chemical specific adjustment factors were defined and used to derive dose–response curves for the sensitive individuals. Our simulations indicated that Chinese are more sensitive towards methadone-induced cardiotoxicity with Margin of Safety values being generally two-fold lower than those for Caucasians for both methadone enantiomers. Individual PBK models using microsomes and PBK models using rCYPs combined with Monte Carlo simulations predicted similar inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. The present study illustrates how inter-individual and inter-ethnic variations in cardiotoxicity can be predicted by combining in vitro toxicity and metabolic data, PBK modelling and Monte Carlo simulations. The novel methodology can be used to enhance cardiac safety evaluations and risk assessment of chemicals.
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The authors describe why and how different types of simulations can be used to understand and support the challenges of utility deregulation. They present an overview of liberalization and deregulation efforts in three utility markets - electricity, natural gas, and drinking water - and describe the main challenges and opportunities for regulators and business managers. A general classification of seven different types of simulation is presented, including market simulations, policy simulations, dynamic business simulations, capability simulations, day-in-a-life simulations, performance simulations, and gaming simulations. The authors reflect on the role of these simulations for utility deregulation and give examples.
from the paper: "This paper presents a research endeavouring to model site work in a 4D BIM model. Next simulations are performed with this model in 5 scenarios including specific interventions in work organisation, notably changing positons of facilities for site workers. A case study has been done in a construction project in the Netherlands. The research has showed the possibility to model time use of site workers in 4D BIM. Next the research has showed potential to perform and calculate specific interventions in the model, and prospect realistic changes in productive time use as a result."
Nederland kent ongeveer 220.000 bedrijfsongevallen per jaar (met 60 mensen die overlijden). Vandaar dat elke werkgever verplicht is om bedrijfshulpverlening (BHV) te organiseren, waaronder BHV-trainingen. Desondanks brengt slechts een-derde van alle bedrijven de arbeidsrisico’s in kaart via een Risico-Inventarisatie & Evaluatie (RI&E) en blijft het aandeel werknemers met een arbeidsongeval hoog. Daarom wordt er continu geïnnoveerd om BHV-trainingen te optimaliseren, o.a. door middel van Virtual Reality (VR). VR is niet nieuw, maar is wel doorontwikkeld en betaalbaarder geworden. VR biedt de mogelijkheid om veilige realistische BHV-noodsimulaties te ontwikkelen waarbij de cursist het gevoel heeft daar echt te zijn. Ondanks de toename in VR-BHV-trainingen, is er weinig onderzoek gedaan naar het effect van VR in BHV-trainingen en zijn resultaten tegenstrijdig. Daarnaast zijn er nieuwe technologische ontwikkelingen die het mogelijk maken om kijkgedrag te meten in VR m.b.v. Eye-Tracking. Tijdens een BHV-training kan met Eye-Tracking gemeten worden hoe een instructie wordt opgevolgd, of cursisten worden afgeleid en belangrijke elementen (gevaar en oplossingen) waarnemen tijdens de simulatie. Echter, een BHV-training met VR en Eye-Tracking (interacties) bestaat niet. In dit project wordt een prototype ontwikkeld waarin Eye-Tracking wordt verwerkt in een 2021 ontwikkelde VR-BHV-training, waarin noodsituaties zoals een kantoorbrand worden gesimuleerd (de BHVR-toepassing). Door middel van een experiment zal het prototype getest worden om zo voor een deel de vraag te beantwoorden in hoeverre en op welke manier Eye-Tracking in VR een meerwaarde biedt voor (RI&E) BHV-trainingen. Dit project sluit daarmee aan op het missie-gedreven innovatiebeleid ‘De Veiligheidsprofessional’ en helpt het MKB dat vaak middelen en kennis ontbreekt voor onderzoek naar effectiviteit rondom innovatieve-technologieën in educatie/training. Het project levert onder meer een prototype op, een productie-rapport en onderzoeks-artikel, en staat open voor nieuwe deelnemers bij het schrijven van een grotere aanvraag rondom de toepassing en effect van VR en Eye-Tracking in BHV-trainingen.
The Netherlands has approximately 220,000 industrial accidents per year (with 60 people who die). That is why every employer is obliged to organize company emergency response (BHV), including emergency response training. Despite this, only one-third of all companies map out their occupational risks via a Risk Inventory & Evaluation (RI&E) and the share of employees with an occupational accident remains high. That is why there is continuous innovation to optimize emergency response training, for example by means of Virtual Reality (VR). VR is not new, but it has evolved and become more affordable. VR offers the possibility to develop safe realistic emergency response simulations where the student has the feeling that they are really there. Despite the increase in VR-BHV training, little research has been done on the effect of VR in ER training and results are contradictory. In addition, there are new technological developments that make it possible to measure viewing behavior in VR using Eye-Tracking. During an emergency response training, Eye-Tracking can be used to measure how an instruction is followed, whether students are distracted and observe important elements (danger and solutions) during the simulation. However, emergency response training with VR and Eye-Tracking (interactions) does not exist. In this project, a prototype is being developed in which Eye-Tracking is incorporated into a VR-BHV training that was developed in 2021, in which emergency situations such as an office fire are simulated (the BHVR application). The prototype will be tested by means of an experiment in order to partly answer the question to what extent and in what way Eye-Tracking in VR offers added value for (RI&E) emergency response training. This project is therefore in line with the mission-driven innovation policy 'The Safety Professional' and helps SMEs that often lack resources and knowledge for research into the effectiveness of innovative technologies in education/training. The project will include a prototype, a production report and research article, and is open to new participants when writing a larger application about the application and effect of VR and Eye-Tracking in emergency response training.
The IMPULS-2020 project DIGIREAL (BUas, 2021) aims to significantly strengthen BUAS’ Research and Development (R&D) on Digital Realities for the benefit of innovation in our sectoral industries. The project will furthermore help BUas to position itself in the emerging innovation ecosystems on Human Interaction, AI and Interactive Technologies. The pandemic has had a tremendous negative impact on BUas industrial sectors of research: Tourism, Leisure and Events, Hospitality and Facility, Built Environment and Logistics. Our partner industries are in great need of innovative responses to the crises. Data, AI combined with Interactive and Immersive Technologies (Games, VR/AR) can provide a partial solution, in line with the key-enabling technologies of the Smart Industry agenda. DIGIREAL builds upon our well-established expertise and capacity in entertainment and serious games and digital media (VR/AR). It furthermore strengthens our initial plans to venture into Data and Applied AI. Digital Realities offer great opportunities for sectoral industry research and innovation, such as experience measurement in Leisure and Hospitality, data-driven decision-making for (sustainable) tourism, geo-data simulations for Logistics and Digital Twins for Spatial Planning. Although BUas already has successful R&D projects in these areas, the synergy can and should significantly be improved. We propose a coherent one-year Impuls funded package to develop (in 2021): 1. A multi-year R&D program on Digital Realities, that leads to, 2. Strategic R&D proposals, in particular a SPRONG/sleuteltechnologie proposal; 3. Partnerships in the regional and national innovation ecosystem, in particular Mind Labs and Data Development Lab (DDL); 4. A shared Digital Realities Lab infrastructure, in particular hardware/software/peopleware for Augmented and Mixed Reality; 5. Leadership, support and operational capacity to achieve and support the above. The proposal presents a work program and management structure, with external partners in an advisory role.