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Potential users of Safe and Sustainable by Design (SSbD) approaches, in particular small and medium sized enterprises, struggle to find their way in the sheer amount of existing knowledge, testing methods and tools. To better guide them in making decisions throughout their entire design process of advanced nanomaterials, a user-friendly online intelligent SSbD Decision Support System (DSS) is developed within the HARMLESS project. Previous experience and stakeholder analysis is used to integrate existing as well as numerous newly generated NAM-based data & models and integrated approaches to testing and assessment (IATAs) into a unified HARMLESS SSbD framework. We propose a modular approach in which all data, knowledge and models are captured in stand-alone, interconnected FAIR components. HARMLESS will A) use eNanoMapper as a database to store experimental data, B) launch a new FAIR Data Point to capture all knowledge and decision rules, C) launch a novel Model FAIRpoint with runnable algorithms and D) launch a new Decision Support System interface. The DSS interface connects to the HARMLESS FAIR components, but can also connect to external components (e.g. NanoCommons Data Warehouse, Jaqpot, NanoInformaTIX). The decision support process is based on a well-established concept of Risk Informed Decision Making adopted by NASA and US NRC, based on the fusion of deterministic and probabilistic risk assessment. To this end, Bayesian network modelling is used to integrate existing and new knowledge, data and models into an integrative reasoning model that captures uncertainty. This information is presented in an interactive visualization presenting an overview of all important decision criteria augmented with SSbD advice allowing the user to interactively work with the tool to improve their design. Oral presentation, by Wouter Fransmann (TNO), at the nanoSAFE 2023 Conference (5-9.06.2023, Grenoble, France) on 6th June 2023-Session:Methods, Tools, & Technologies for SSbD Purposes

There has been an increasing use of manufactured nanomaterials in industrial applications and consumer products. It has instigated concerns about the sustainability, risks and uncertainties regarding the interactions of the nanomaterials with humans and the environment. Consequently, significant resources in Europe have been invested into tool and method development to support risk mitigation and management, facilitating the research and innovation process of manufactured nanomaterials. Extended risk analysis, including socio-economic impact and sustainability assessment is moving the conventional risk-based approach towards a wider safety-and-sustainability-by-design perspective. Despite growing tool and method developments, the level of awareness and use by stakeholders is still limited. Regulatory compliance and acceptance, reliability and trust, user-friendliness and compatibility with the users’ needs are important factors traditionally known to hinder their widespread use. Therefore, a framework is presented to quantify the readiness of different tools and methods towards their wider regulatory acceptance and downstream use by different stakeholders. The framework, developed within Gov4Nano, diagnoses barriers which hinder regulatory acceptance and wider usability of a tool/method based on their Transparency, Reliability, Accessibility, Applicability and Completeness (TRAAC framework). An online TRAAC tool is being developed within HARMLESS that will be freely available on https://diamonds.tno.nl/#traac. Fourteen tools and methods were assessed using the TRAAC framework as proof-of-concept. The results provide insights into any gaps, opportunities, and challenges in the context of each of the 5 pillars of the TRAAC framework.

Background The EU Horizon2020 “safe-by-design for Nano” (SBD4Nano) project aims to develop a tool to assist users in the safe-by-design process and decisions to reduce risk as a result from working with- or using newly developed products containing manufactured nanomaterials (MNs). Therefore, TNO set out to develop an easy-to-use quantitative exposure assessment tool that helps users with different levels of expertise to reduce the exposure from MNs following an integrated Tiered safe-by-design approach. Method Based on previous projects, literature, expert knowledge, a Tiered set of model determinants and corresponding calculations were integrated into a conceptual model. Also, an exposure database based on the EU GRACIOUS template was created containing a large set of exposure measurements collected from diverse literature studies. Machine learning was applied to these exposure measurements to validate and refine the model. Lastly, a safe-by-design module was added to assist users modify their material or process design to reduce exposure. Results An online tool is realized that will be freely available on https://diamonds.tno.nl/#neq. The NEQ offers a Tiered approach by smartly adapting the questions based on the depth of information the user can provide allowing anywhere between a Tier-1 and a Tier-2 approach. After answering questions, the user is presented an exposure estimate including uncertainty of the current design. The user is guided to enter a new design that reduces the exposure and/or its uncertainty.

BACKGROUND Various multifaceted factors need to be addressed to improve the health and quality of life of people with type 2 diabetes (T2D). Therefore, we developed a web-based decision support tool that comprises a more holistic diagnosis (including 4 domains: body, thinking and feeling, behavior, and environment) and personalized advice. This 360° diagnostic tool enables people with T2D and health care professionals at the general practice to obtain an overview of the most important T2D-related issues and, subsequently, determine the most suitable intervention for the person with T2D. OBJECTIVE This study aimed to describe the systematic and iterative development and evaluation of the web-based 360° diagnostic tool. METHODS We defined the requirements for the web-based 360° diagnostic tool based on previously developed tools, a literature review, and inputs from a multidisciplinary team of experts. As part of the conceptualization, we defined 3 requirements: diagnostics; feedback; and advice, consultation, and follow-up. Next, we developed and designed the content for each of these requirements. We evaluated the diagnostic part of the tool (ie, measurement instruments and visualization) with a qualitative design, in a usability study with a think-aloud strategy and interview questions, among 8 people with T2D at a Dutch general practice. RESULTS For each of the 4 domains, specific parameters and underlying elements were selected, and measurement instruments (including clinical data and questionnaires) were chosen. Cutoff values were defined to identify high-, middle-, and low-ranking scores, and decision rules were developed and implemented using R scripts and algorithms. A traffic light color visual design was created (profile wheel) to provide an overview of the scores per domain. We mapped the interventions that could be added to the tool and developed a protocol designed as a card deck with motivational interview steps. Furthermore, the usability study showed that people with T2D perceived the tool as easy to use, useful, easy to understand, and insightful. CONCLUSIONS Preliminary evaluation of the 360° diagnostic tool by experts, health care professionals, and people with T2D showed that the tool was considered relevant, clear, and practical. The iterative process provided insights into the areas of improvement, which were implemented. The strengths, shortcomings, future use, and challenges are also discussed.

Patients with Cystic Fibrosis (CF) suffer from pancreatic insufficiency, lipid malabsorption and gastrointestinal complaints, next to progressive pulmonary disease. Altered mucosal homoeostasis due to malfunctioning chloride channels results in an adapted microbial composition of the gastrointestinal and the respiratory tract. Additionally, antibiotic treatment has the potential to distort resident microbial communities dramatically. This study aims to investigate early life development of the gut microbial community composition of children with CF compared to healthy infants and to study the independent effects of antibiotics taking into account other clinical and lifestyle factors.Faecal samples from 20 infants with CF and 45 healthy infants were collected regularly during the first 18 months of life and microbial composition was determined using 16S rRNA based sequencing.We observed significant differences in the overall microbiota composition between infants with CF and healthy infants (p0.001). Akkermansia and Anaerostipes were significantly more abundant in control infants, whereas Streptococci and E. coli were significantly more abundant in infants with CF, also after correction for several clinical factors (p0.05). Antibiotic use in infants with CF was associated with a lower alpha diversity, a reduced abundance of Bifidobacterium and Bacteroides, and a higher abundance of Enterococcus.Microbial development of the gut is different in infants with CF compared to healthy infants from the first months of life on, and further deviates over time, in part as a result of antibiotic treatment. The resulting dysbiosis may have significant functional consequences for the microbial ecosystem in CF patients.

Introduction: Progressive lung damage, associated with bacterial infection and neutrophil mediated inflammation, is the major cause of morbidity and death in CF. Ivacaftor improves lung function in CF patients with the G551D mutation and this may be associated with changes in airway bacterial community composition. Objectives: To determine the effect of ivacaftor on CF airway bacterial community composition and to examine the relationship with lung function and measures of systemic inflammation. Methods: Sputum and blood samples from CF patients (n = 20) were collected prior to and every three months (for 12 months) after initiation of ivacaftor therapy. Molecular based analysis (Illumina MiSeq) was used to define airway bacterial community composition. ELISA’s were used to quantify measures of systemic inflammation in blood (IL-8, IL-6 & CRP). Results: Mean relative abundance of Pseudomonas decreased after ivacaftor therapy whilst relative abundance of Streptococcus, Haemophilus, Rothia and Prevotella increased. There was no correlation between relative abundance of individual taxa and lung function. However, there was a significant inverse correlation between the relative abundance of both Streptococcus and Prevotella and IL-8 (p < 0.05). There was no association between relative abundance of individual taxa and IL-6 or CRP. Conclusion: Alterations in CF airway bacterial community composition post-ivacaftor therapy are associated with reduced levels of the potent neutrophil chemoattractant IL-8. This may result in decreased neutrophil influx into the airways and improve lung function by limiting neutrophil mediated inflammation. Acknowledgement: Funding: DEL NI Studentship & CFMATTERS (603038)