Background: Adverse outcome pathway (AOP) networks are versatile tools in toxicology and risk assessment that capture and visualize mechanisms driving toxicity originating from various data sources. They share a common structure consisting of a set of molecular initiating events and key events, connected by key event relationships, leading to the actual adverse outcome. AOP networks are to be considered living documents that should be frequently updated by feeding in new data. Such iterative optimization exercises are typically done manually, which not only is a time-consuming effort, but also bears the risk of overlooking critical data. The present study introduces a novel approach for AOP network optimization of a previously published AOP network on chemical-induced cholestasis using artificial intelligence to facilitate automated data collection followed by subsequent quantitative confidence assessment of molecular initiating events, key events, and key event relationships. Methods: Artificial intelligence-assisted data collection was performed by means of the free web platform Sysrev. Confidence levels of the tailored Bradford-Hill criteria were quantified for the purpose of weight-of-evidence assessment of the optimized AOP network. Scores were calculated for biological plausibility, empirical evidence, and essentiality, and were integrated into a total key event relationship confidence value. The optimized AOP network was visualized using Cytoscape with the node size representing the incidence of the key event and the edge size indicating the total confidence in the key event relationship. Results: This resulted in the identification of 38 and 135 unique key events and key event relationships, respectively. Transporter changes was the key event with the highest incidence, and formed the most confident key event relationship with the adverse outcome, cholestasis. Other important key events present in the AOP network include: nuclear receptor changes, intracellular bile acid accumulation, bile acid synthesis changes, oxidative stress, inflammation and apoptosis. Conclusions: This process led to the creation of an extensively informative AOP network focused on chemical-induced cholestasis. This optimized AOP network may serve as a mechanistic compass for the development of a battery of in vitro assays to reliably predict chemical-induced cholestatic injury.
In this paper, we explore the design of web-based advice robots to enhance users' confidence in acting upon the provided advice. Drawing from research on algorithm acceptance and explainable AI, we hypothesise four design principles that may encourage interactivity and exploration, thus fostering users' confidence to act. Through a value-oriented prototype experiment and valueoriented semi-structured interviews, we tested these principles, confirming three of them and identifying an additional principle. The four resulting principles: (1) put context questions and resulting advice on one page and allow live, iterative exploration, (2) use action or change oriented questions to adjust the input parameters, (3) actively offer alternative scenarios based on counterfactuals, and (4) show all options instead of only the recommended one(s), appear to contribute to the values of agency and trust. Our study integrates the Design Science Research approach with a Value Sensitive Design approach.
Alcohol use disorder (AUD) is a pattern of alcohol use that involves having trouble controlling drinking behaviour, even when it causes health issues (addiction) or problems functioning in daily (social and professional) life. Moreover, festivals are a common place where large crowds of festival-goers experience challenges refusing or controlling alcohol and substance use. Studies have shown that interventions at festivals are still very problematic. ARise is the first project that wants to help prevent AUD at festivals using Augmented Reality (AR) as a tool to help people, particular festival visitors, to say no to alcohol (and other substances). ARise is based on the on the first Augmented Reality Exposure Therapy (ARET) in the world that we developed for clinical treatment of AUD. It is an AR smartphone driven application in which (potential) visitors are confronted with virtual humans that will try to seduce the user to accept an alcoholic beverage. These virtual humans are projected in the real physical context (of a festival), using innovative AR glasses. Using intuitive phone, voice and gesture interactions, it allows users to personalize the safe experience by choosing different drinks and virtual humans with different looks and levels of realism. ARET has been successfully developed and tested on (former) AUD patients within a clinical setting. Research with patients and healthcare specialists revealed the wish to further develop ARET as a prevention tool to reach people before being diagnosed with AUD and to extend the application for other substances (smoking and pills). In this project, festival visitors will experience ARise and provide feedback on the following topics: (a) experience, (b) awareness and confidence to refuse alcohol drinks, (c) intention to use ARise, (d) usability & efficiency (the level of realism needed), and (e) ideas on how to extend ARise with new substances.
Kinderen van ouders met psychische problemen of verslavingsproblemen (KOPP/KOV) ervaren vaak chronische stress, mentale en lichamelijke gezondheidsproblemen. Ook hun financiële situatie, sociale welzijn en studiesucces kunnen worden beïnvloed door het leven met ouders met psychische en/of verslavingsproblematiek. Vaak zijn zij niet in beeld bij professionals of krijgen alleen verbale therapieën, zoals cognitieve gedragstherapie, terwijl lichaamsgerichte activiteiten geschikter lijken voor mensen die niet makkelijk over gevoelens praten. Sport en bewegen worden weinig ingezet in preventieve en behandelprogramma’s voor KOPP/KOV, alhoewel sport en bewegen positief zijn geassocieerd met gezondheid en welzijn. Boksen heeft aantrekkingskracht op jongeren in kwetsbare posities, heeft de potentie om het zelfvertrouwen, de persoonlijke groei en mentale gezondheid van KOPP/KOV te bevorderen en victimisatie te voorkomen of beperken. Voorwaarde is dat de manier waarop, en context waarin, het boksen wordt aangeboden zijn afgestemd op de wensen, behoeften en mogelijkheden van de doelgroep. Vanuit boks-, sport-, welzijns- en zorgprofessionals is er op dit moment een duidelijke vraag maar ook discussie over de manier waarop boksen ingezet kan worden als adequate preventieve interventie voor KOPP/KOV. Om deze handelingsverlegenheid weg te nemen, vragen bokstrainers maar ook buurtsportcoaches, welzijns- en zorgprofessionals om hulp bij het komen tot een passende en veilige boksinterventie die de mentale gezondheid van KOPP/KOV bevordert. Vanuit ondernemers perspectief zijn er daarnaast ook vragen rondom financiering en scholing van de trainers. Met een ontwerpgerichte aanpak wordt in dit project de volgende onderzoeksvraag beantwoord: “Aan welke inhoudelijke en organisatorische criteria moet een boksinterventie ter bevordering van de mentale gezondheid van KOPP/KOVV in de leeftijd 16-24 jaar voldoen?”. Het beantwoorden van deze vraag zal resulteren in een boksinterventie die kan worden aangeboden in samenwerking tussen ondernemers binnen de boks- en sportwereld én welzijns- en zorgprofessionals, en inzicht geven in de werkzame elementen, bruikbaarheid en haalbaarheid van deze lichaamsgerichte interventie voor KOPP/KOV.
The Dutch main water systems face pressing environmental, economic and societal challenges due to climatic changes and increased human pressure. There is a growing awareness that nature-based solutions (NBS) provide cost-effective solutions that simultaneously provide environmental, social and economic benefits and help building resilience. In spite of being carefully designed and tested, many projects tend to fail along the way or never get implemented in the first place, wasting resources and undermining trust and confidence of practitioners in NBS. Why do so many projects lose momentum even after a proof of concept is delivered? Usually, failure can be attributed to a combination of eroding political will, societal opposition and economic uncertainties. While ecological and geological processes are often well understood, there is almost no understanding around societal and economic processes related to NBS. Therefore, there is an urgent need to carefully evaluate the societal, economic, and ecological impacts and to identify design principles fostering societal support and economic viability of NBS. We address these critical knowledge gaps in this research proposal, using the largest river restoration project of the Netherlands, the Border Meuse (Grensmaas), as a Living Lab. With a transdisciplinary consortium, stakeholders have a key role a recipient and provider of information, where the broader public is involved through citizen science. Our research is scientifically innovative by using mixed methods, combining novel qualitative methods (e.g. continuous participatory narrative inquiry) and quantitative methods (e.g. economic choice experiments to elicit tradeoffs and risk preferences, agent-based modeling). The ultimate aim is to create an integral learning environment (workbench) as a decision support tool for NBS. The workbench gathers data, prepares and verifies data sets, to help stakeholders (companies, government agencies, NGOs) to quantify impacts and visualize tradeoffs of decisions regarding NBS.
