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.
MULTIFILE
Parental involvement is a crucial force in children’s development, learning and success at school and in life [1]. Participation, defined by the World Health Organization as ‘a person’s involvement in life situations’ [2] for children means involvement in everyday activities, such as recreational, leisure, school and household activities [3]. Several authors use the term social participation emphasising the importance of engagement in social situations [4, 5]. Children’s participation in daily life is vital for healthy development, social and physical competencies, social-emotional well-being, sense of meaning and purpose in life [6]. Through participation in different social contexts, children gather the knowledge and skills needed to interact, play, work, and live with other people [4, 7, 8]. Unfortunately, research shows that children with a physical disability are at risk of lower participation in everyday activities [9]; they participate less frequently in almost all activities compared with children without physical disabilities [10, 11], have fewer friends and often feel socially isolated [12-14]. Parents, in particular, positively influence the participation of their children with a physical disability at school, at home and in the community [15]. They undertake many actions to improve their child’s participation in daily life [15, 16]. However, little information is available about what parents of children with a physical disability do to enable their child’s participation, what they come across and what kind of needs they have. The overall aim of this thesis was to investigate parents’ actions, challenges, and needs while enhancing the participation of their school-aged child with a physical disability. In order to achieve this aim, two steps have been made. In the first step, the literature has been examined to explore the topic of this thesis (actions, challenges and needs) and to clarify definitions for the concepts of participation and social participation. Second, for the purposes of giving breadth and depth of understanding of the topic of this thesis a mixed methods approach using three different empirical research methods [17-19], was applied to gather information from parents regarding their actions, challenges and needs.
The importance of professional skills in future engineering jobs is beyond discussion. Increasing numbers of universities have integrated training for such skills in their engineering curricula to prepare students to become highly qualified employees. HU University of Applied Sciences Utrecht also implemented professional skills training in the IT Bachelor program to help our students develop towards successful and highly demanded IT engineers. However, these courses consistently score low in our student satisfaction surveys. To find the cause of this negative evaluation, we previously studied the motivation, attitude and anxiety of IT students towards learning soft, or professional, skills. This former quantitative study indicates that our IT students tend to have a positive motivation and attitude toward learning professional skills, while ’anxiety’ in learning professional skills increases from the first to the third year. In this qualitative study, we try to find causes for the increasing anxiety among IT students. We interviewed six third and fourth year IT students and after analysing these interviews we found that these students have experienced the need for professional skills during their internship. Besides, they emphasize the need of obtaining these skills for future employment. From the analysis of the interviews, it also appears that IT students rather felt difficulty in obtaining communication skills then anxiety. A possible cause for this difficulty mentioned by students was the character of students and the influence of the teacher. To overcome this difficulty obtaining communication skills, students suggested that training skills in an authentic engineering situation is more effective than doing exercises with simulated cases. However, the results of this study did not yield a conclusive insight in the cause of increased anxiety, hence further research is needed.
Hoe kan de verblijfskwaliteit en veiligheidsperceptie van de publieke ruimte versterkt worden door de toepassing van “interactieve objecten”? (objecten die met beeld, licht, geluid en sensoren real time reageren op de gebruikers en de ruimte daarop afstemmen). De ontwikkeling van deze zogenaamde responsieve ruimte staat nog in de kinderschoenen maar is beloftevol vanwege de meerwaarde voor de leefbaarheid en het onderscheidend vermogen van de plek en de bedrijven. In Co-ReUs worden drie verschillende mkb groepen samengebracht: stedenbouwbureaus, creatieve conceptontwikkelaars en lokale ondernemers. We gebruiken de ArenA-Boulevard als proeftuin: een als ongezellig ervaren ruimte (lage verblijfskwaliteit en slechte veiligheidsperceptie). De mkb-ers lossen hiermee hun eigen praktijkproblemen op: Stedenbouwbureaus houden zich bezig met het ontwerp van de publieke ruimte. Zij merken dat hun instrumentarium (herontwerp, herbestrating etc.) te kapitaalintensief en te weinig flexibel is om de verblijfskwaliteit en veiligheidsperceptie op dit soort plekken op te lossen. De bureaus hebben behoefte aan een lichter, gerichter en responsiever instrumentarium. Ze hebben echter beperkte (technologische) kennis hoe interactieve objecten precies een bijdrage kunnen leveren. Creatieve conceptontwikkelaars hebben een ander probleem: zij hebben wél de beschikking over interactieve objecten (geluid, beeld, licht, sensoren) maar die zijn vooral kunstzinnig en evenementiëel. De objecten zijn stuk voor stuk niet ontwikkeld vanuit een stedenbouwkundige opgave waardoor ze hiervoor geen panklare oplossing vormen. Lokale mkb-ers hebben ook een probleem: zij weten niet goed hoe zij op een gecoördineerde manier invloed kunnen uitoefenen op de activering van de publieke ruimte. Project Co-ReUs: 1) analyseert hoe de ruimte wordt gebruikt (nulmeting en Programma van Eisen voor de inzet van interactieve objecten; 2) ontwikkelt ruimtelijk-interactieve interventies in co-creatie met de drie mkb groepen. 3) deze worden op het plein geplaatst en nametingen brengen de effecten in beeld. Het resultaat is een actiegerichte Handleiding met Roadmap voor de ontwikkeling van responsieve publieke ruimtes.
Hoewel drones worden gebruikt in steeds toenemende civiele toepassingen voor een goede daad, zijn kwaadwillende drones ook steeds meer en steeds vaker worden ingezet om schade aan te richten. Huis, tuin en keukendrones zijn in staat om door te dringen tot zwaarbeveiligde gebieden en daar verwoestende schade aan te brengen. Ze zijn goedkoop, precies en kunnen steeds grotere afstanden afleggen. Kwaadwillende drones vormen een groot gevaar voor de nationale veiligheid. In dit KIEM-project onderzoeken wij de vraag in hoeverre is het mogelijk om drones te ontwikkelen die volledig autonoom een ongecontroleerde omgeving (luchtruim) veilig kunnen houden? Counter drones moeten kamikaze-drones kunnen signaleren en uitschakelen. Bestaande systemen zijn nog onvoldoende in staat om kwaadwillende drones op tijd uit te schakelen. Bij Defensie, de Nationale Politie en het gevangeniswezen is dringend behoefte aan systemen die kwaadwillende drones kunnen detecteren en uitschakelen. Er zijn thans enkele (Europese) systemen waarmee drones kunnen worden gedetecteerd, onder andere met radiofrequentiesignalen (voelen), optische- en radartechnologie (zien) en akoestische systemen (horen). Geen van deze systemen vormen de ‘silver bullet’ voor het bestrijden van kwaadwillende drones, vooral kleine en laagvliegende drones. Met een feasibility study wordt nagegaan wat de state-of-the-art is van de huidige counter dronetechnologieën en op welke technologiedomeinen het consortium waarde kan toevoegen aan de ontwikkeling van effectieve counter drones. Saxion en haar partners zet zich de komende jaren in op Sleuteltechnologieën als: Human Robotic Interaction, Perception, Navigation, Systems Development, Mechatronics en Cognition. Technologieën die terugkomen in counter drones, maar ook worden doorontwikkeld voor andere toepassingsgebieden. Het project bestaat uit 4 fasen: een onderzoek naar de huidige counter dronetechnologieën (IST), onderzoek naar gewenste/toekomstige counter dronetechnologieën (SOLL), een gap-analyse (TOR) én een omgevingsanalyse om na te gaan wat er elders in Europa al aan onderzoek plaatsvindt. Tevens wordt een netwerk ontwikkeld om counter droneontwikkeling mogelijk te maken.
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.
