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The TNO InTESTine™ system is developed to study the absorption and translocation of pharmaceutical, biological and nutritional compounds across the intestinal wall in a physiologically relevant model. In this medium-throughput system, fresh ex vivo intestinal tissue from human or animal origin is mounted into a two compartment model with an apical and basolateral side. In order to study regional differences in absorption, tissue from different intestinal regions (duodenum, jejunum, ileum & colon) can be tested in parallel under controlled conditions.

The development and introduction of new dietary protein sources has the potential to improve food supply sustainability. Understanding the potential allergenicity of these new or modified proteins is crucial to ensure protection of public health. Exposure to new proteins may result in de novo sensitization, with or without clinical allergy, or clinical reactions through cross-reactivity. In this paper we review the potential of current methodologies (in silico, in vitro degradation, in vitro IgE binding, animal models and clinical studies) to address these outcomes for risk assessment purposes for new proteins, and especially to identify and characterise the risk of sensitization for IgE mediated allergy from oral exposure. Existing tools and tests are capable of assessing potential crossreactivity. However, there are few possibilities to assess the hazard due to de novo sensitization. The only methods available are in vivo models, but many limitations exist to use them for assessing risk. We conclude that there is a need to understand which criteria adequately define allergenicity for risk assessment purposes, and from these criteria develop a more suitable battery of tests to distinguish between proteins of high and low allergenicity, which can then be applied to assess new proteins with unknown risks. © 2017 The Authors Chemicals/CAS: immunoglobulin E, 37341-29-0

Objectives A novel triage approach to routine assessments was introduced to improve the efficiency of Preventive Child Healthcare (PCH): PCH assistants carried out pre-assessments of all children and sent the children with suspected health problems to follow-up assessments conducted by a physician or nurse. This two-step approach differed from the usual approach, in which physicians or nurses assessed all children. This study was aimed to examine the impact of triage and task shifting on care for children at risk identified by PCH or parents and schools. Design and participants An observational prospective cohort design was used, with an analysis of the basic registration data from the preventive health assessments for 1897 children aged 5 to 6, and 10 to 11, years from a sample of 41 schools stratified by socioeconomic status, region of PCH service and urbanisation. Setting A comparison was made between two PCH services in the Netherlands that used the triage approach and two PCH services that provided the usual approach. Main outcome measures The primary outcome measures were the referral rates to either additional PCH assessments or external services. The secondary outcome measures were the rates of PCH assessments requested by, for example, parents and schools. Results Overall, a higher referral rate to additional PCH assessments was found for the triage approach than for the usual approach (OR 1.3, 95% CI 1.0 to 1.6), mainly in the age group of 5 to 6 years (OR 1.9, 95% CI 1.3 to 2.7). We found a lower rate of referral to external services in the triage approach (OR 0.4, 95% CI 0.3 to 0.7) and a higher referral rate to PCH assessments on request (OR=4.6, 95% CI 3.0 to 7.0). Conclusions The triage approach provides extra opportunities to deliver PCH assessments and PCH assessments on request for children at risk. Further research is needed into the cost benefits of the triage approach.

Background. Triage in Preventive Child Health Care (PCH) assessments could further the efficient use of human resources and budgets and therefore make extra care possible for children with specific needs. We assessed the costs of routine PCH assessments with and without triage for children aged 5/6 years and 10/11 years. In a triage approach, PCH assistants conduct pre-assessments to identify children requiring follow-up assessments by a physician or nurse. In the usual approach, all children are assessed by a physician and an assistant (children aged 5/6 years) or a nurse (children aged 10/11 years). Methods. All the direct costs of conducting routine PCH assessments with the triage and usual approach were assessed using a bottom-up micro-costing approach. In four PCH services in the Netherlands, two using triage and two the usual approach, professionals completed questionnaires about time spent on assessments, including time related to non-attendance at assessments, the referral of children and administration. Results. The projected costs for PCH professionals working on PCH assessments amounted to €5.2 million per cohort of 100,000 children aged 5/6 years in the triage approach, and €7.6 million in the usual approach. The projected costs in both approaches for children aged 10/11 years were about €4 million per 100,000 children. Conclusion. The triage approach to PCH resulted in a projected cost reduction of about one-third, compared with usual practice, for routine assessments by physicians of children aged 5/6 years. There are minimal cost savings in the group of children aged 10/11 years when nurses are involved and so other considerations such as workforce shortages would be required to justify a change to a triage approach. Further research is needed to investigate the differences in costs of care after the completion of the routine assessments.

Whole grains are a key component of a healthy diet, and enabling consumers to easily choose foods with a high whole-grain content is an important step for better prevention of chronic disease. Several definitions exist for whole-grain foods, yet these do not account for the diversity of food products that contain cereals. With the goal of creating a relatively simple whole-grain food definition that aligns with whole-grain intake recommendations and can be applied across all product categories, the Healthgrain Forum, a not-for-profit consortium of academics and industry working with cereal foods, established a working group to gather input from academics and industry to develop guidance on labeling the whole-grain content of foods. The Healthgrain Forum recommends that a food may be labeled as “whole grain” if it contains $30% whole-grain ingredients in the overall product and contains more whole grain than refined grain ingredients, both on a dry-weight basis. For the purposes of calculation, added bran and germ are not considered refined-grain ingredients. Additional recommendations are also made on labeling whole-grain content in mixed-cereal foods, such as pizza and ready meals, and a need to meet healthy nutrition criteria. This definition allows easy comparison across product categories because it is based on dry weight and strongly encourages a move from generic whole-grain labels to reporting the actual percentage of whole grain in a product. Although this definition is for guidance only, we hope that it will encourage more countries to adopt regulation around the labeling of whole grains and stimulate greater awareness and consumption of whole grains in the general population. Adv Nutr 2017;8:525–31.

We studied a novel triage approach to the organisation of routine assessments by Preventive Child Health care (PCH), including task-shifting among professionals. In the triage approach, access to PCH, and the detection of the health problems studied, were comparable with the usual approach. The efficient deployment of PCH professionals using triage and task-shifting reduced the costs and involvement of PCH physicians and nurses in routine assessments, particularly in the youngest age group (5 to 6 years). The associated release of workforce and budgets may create more opportunities for the delivery of care to children and their families with specific health-care needs. In our study, in the triage approach PCH physicians and nurses provided more demand-driven care at the request of parents and others such as school professionals. We have emphasised the importance of making the PCH programme more flexible to create time for PCH professionals to collaborate with professionals from the school system, and from the youth care and primary care systems, with the aim of improving joint commitment to early detection, and the delivery of more coordinated care. More research is needed into the outcomes of referral to extra care and into the cost benefits of the triage approach.

Lactulose, a disaccharide of galactose and fructose, used as a laxative or ammonia-lowering drug and as a functional food ingredient, enhances growth of Bifidobacterium and Lactobacillus at clinically relevant dosages. The prebiotic effect of subclinical dosages of Lactulose, however, remains to be elucidated. This study analyses changes in the microbiota and their metabolites after a 5 days Lactulose treatment using the TIM-2 system, a computer-controlled model of the proximal large intestine representing a complex, high density, metabolically active, anaerobic microbiota of human origin. Subclinical dosages of 2-5 g Lactulose were used. While 2 g Lactulose already increased the short-chain fatty acid levels of the intestinal content, 5 g Lactulose were required daily for 5 days in this study to exert the full beneficial prebiotic effect consisting of higher bacterial counts of Bifidobacterium, Lactobacillus, and Anaerostipes, a rise in acetate, butyrate and lactate, as well as a decrease in branched-chain fatty acids, pH (suggested by an increase in NaOH usage), and ammonia. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Worldwide there is a growing need for citizens to prepare for environmental risks to mitigate potential adversity. In order to predict preparedness, behavioral models typically used variables at an individual level of analysis, such as risk perception and assessment of the effectiveness of possible actions (response-efficacy). The present study elaborated on these findings by also incorporating affect and social (participation and community efficacy) and institutional (trust and empowerment) level variables. The goal of the research was to examine to what extent these different variables could predict flood preparedness of 629 Dutch citizens resident in The Hague (an area below sea level). The results showed that affect had both a direct and an indirect effect on level of preparedness. The indirect pathway was mediated by people's assessment of the probability of a future event. This supports the notion that preparatory behavior is influenced by both a cognitive and an affective route. At the social level, a direct effect for participation was found: the more residents participated in their community the more they prepared. At the institutional level, the influence of empowerment on preparedness was mediated by participation. Overall, the results point to the need to address both cognition and affect in communicating risks and to make better use of social networks in facilitating citizen preparedness for hazards. © 2017 Elsevier Ltd

Background The organisation of health assessments by preventive health services focusing on children’s health and educational performance needs to be improved due to evolving health priorities such as mental health problems, reduced budgets and shortages of physicians and nurses. We studied the impact on the school professionals’ perception of access to school health services (SHS) when a triage approach was used for population-based health assessments in primary schools. The triage approach involves pre-assessments by SHS assistants, with only those children in need of follow-up being assessed by a physician or nurse. The triage approach was compared with the usual approach in which all children are assessed by physicians and nurses. Methods We conducted a cross-sectional study, comparing school professionals’ perceptions of the triage and the usual approach to SHS. The randomly selected school professionals completed digital questionnaires about contact frequency, the approachability of SHS and the appropriateness of support from SHS. School care coordinators and teachers were invited to participate in the study, resulting in a response of 444 (35.7%) professionals from schools working with the triage approach and 320 (44.6%) professionals working with the usual approach. Results Respondents from schools using the triage approach had more contacts with SHS and were more satisfied with the appropriateness of support from SHS than respondents in the approach-as-usual group. No significant differences were found between the two groups in terms of the perceived approachability of SHS. Conclusions School professionals were more positive about access to SHS when a triage approach to routine assessments was in place than when the usual approach was used. Countries with similar population-based SHS systems could benefit from a triage approach which gives physicians and nurses more opportunities to attend schools for consultations and assessments of children on demand.

Background and aims Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation would be accelerated by concomitant statin treatment, thereby further reducing hypercholesterolemia and atherosclerosis. Methods APOE*3-Leiden.CETP mice were fed a Western-type diet and treated without or with the selective β3-adrenergic receptor (AR) agonist CL316,243 that activates BAT, atorvastatin (statin) or both. Results β3-AR agonism increased energy expenditure as a result of an increased fat oxidation by activated BAT, which was not further enhanced by statin addition. Accordingly, statin treatment neither influenced the increased uptake of triglyceride-derived fatty acids from triglyceride-rich lipoprotein-like particles by BAT nor further lowered plasma triglyceride levels induced by β3-AR agonism. Statin treatment increased the hepatic uptake of the formed cholesterol-enriched remnants generated by β3-AR agonism. Consequently, statin treatment further lowered plasma cholesterol levels. Importantly, statin, in addition to β3-AR agonism, also further reduced the atherosclerotic lesion size as compared to β3-AR agonism alone, without altering lesion severity and composition. Conclusions Statin treatment accelerates the hepatic uptake of remnants generated by BAT activation, thereby increasing the lipid-lowering and anti-atherogenic effects of BAT activation in an additive fashion. We postulate that, in clinical practice, combining statin treatment with BAT activation is a promising new avenue to combat hyperlipidemia and cardiovascular disease.

The increasing prevalence of rheumatoid arthritis has driven the development of new approaches and technologies for investigating the pathophysiology of this devastating, chronic disease. From the perspective of systems biology, combining comprehensive personal data such as metabolomics profiling with ultra-weak photon emission (UPE) data may provide key information regarding the complex pathophysiology underlying rheumatoid arthritis. In this article, we integrated UPE with metabolomics-based technologies in order to investigate collagen-induced arthritis, a mouse model of rheumatoid arthritis, at the systems level, and we investigated the biological underpinnings of the complex dataset. Using correlation networks, we found that elevated inflammatory and ROS-mediated plasma metabolites are strongly correlated with a systematic reduction in amine metabolites, which is linked to muscle wasting in rheumatoid arthritis. We also found that increased UPE intensity is strongly linked to metabolic processes (with correlation co-efficiency | r | value > 0.7), which may be associated with lipid oxidation that related to inflammatory and/or ROS-mediated processes. Together, these results indicate that UPE is correlated with metabolomics and may serve as a valuable tool for diagnosing chronic disease by integrating inflammatory signals at the systems level. Our correlation network analysis provides important and valuable information regarding the disease process from a system-wide perspective.

TNO’s intestinal screening model (TNO i-screen) helps to quickly identify food ingredients that modulate the intestinal microbiota composition. For manufacturers, searching for health-promoting ingredients is a complex and time-consuming process. Large numbers of substances have to be screened, while for some components almost no proper identification methods are available. When a functional ingredient has finally been selected, extensive in vitro and human volunteer studies are required to demonstrate its safety and to validate its efficacy prior to marketing it as beneficial to health.

Leugendetectie is een multidisciplinair onderzoeksveld dat zich op dit moment snel ontwikkelt dankzij technologische ontwikkelingen en interesse uit verschillende vakgebieden zoals informatica en behavioral economics. Door leugenonderzoekers wordt onder liegen verstaan het bewust creëren van een verkeerd beeld bij een ander, zonder waarschuwing vooraf (in tegenstelling tot bijvoorbeeld het bijwonen van een goochelshow). Dit beeld kan zowel gecreëerd worden door het fabriceren van onjuiste informatie, als door het weglaten van essentiële informatie. Onderzoek laat zien dat mensen niet zo goed zijn in het detecteren van leugens in het lab. Uit een meta-analyse van ruim 200 leugenonderzoeken bleek dat mensen niet veel beter scoren dan kans niveau1. Om detectieaccuraatheden te verhogen hebben in het afgelopen decennium verschillende ontwikkelingen plaatsgevonden die de betrouwbaarheid van leugendetectie kunnen verhogen of die ervoor zorgen dat leugendetectie beter in de praktijk kan worden toegepast. De belangrijkste recente ontwikkelingen zijn te groeperen rondom vier thema’s die hieronder worden besproken.

TNO’s intestinal screening model (TNO i-screen) helps to quickly identify pharmacological compounds that are metabolized by intestinal microbiota. For pharmaceutical companies, searching for novel pharmaceuticals is a complex and time-consuming process. When a novel drug has been selected, extensive in vitro and clinical studies are required to demonstrate its metabolism, safety and efficacy prior to releasing it to the market. Increasing evidence has shown that gut microbiota are involved in the metabolic transformation of many drugs, influencing drug pharmacokinetics and thus, efficacy and safety profiles.

In this paper, we reconstruct the vertical profile of volcanic ash emissions by assimilating satellite data and ground‐based observations using a modified trajectory‐based 4D‐Var (Trj4DVar) approach. In our previous work, we found that the lack of vertical resolution in satellite ash column data can result in a poor estimation of the injection layer where the ash is emitted into the atmosphere. The injection layer is crucial for the forecast of volcanic ash clouds. To improve estimation, Trj4DVar was implemented, and it has shown increased performance in twin experiments using synthetic observations. However, there are some cases with real satellite data where Trj4DVar has difficulty in obtaining an accurate estimation of the injection layer. To remedy this, we propose a modification of Trj4DVar, test it with synthetic twin experiments, and evaluate real data performance. The results show that the modified Trj4DVar is able to accurately estimate the injection height (location of the maximal emission rate) by incorporating the plume height (top of the ash plume) and mass eruption rate data obtained from ground‐based observations near the source into the assimilation system. This will produce more accurate emission estimations and more reliable forecasts of volcanic ash clouds. Also provided are two strategies on the preprocessing and proper use of satellite data.

The genus Aureobasidium, which is known as a wood staining mould, has been detected on oil treated woods in the specific stain formation called biofinish. This biofinish is used to develop a new protective, self-healing and decorative biotreatment for wood. In order to understand and control biofinish formation on oil treated wood, the occurrence of different Aureobasidium species on various wood surfaces was studied. Phenotypic variability within Aureobasidium strains presented limitations of morphological identification of Aureobasidium species. PCR amplification and Sanger sequencing of ITS and RPB2 were used to identify the culturable Aureobasidium species composition in mould stained wood surfaces with and without a biofinish. The analysed isolates showed that several Aureobasidium species were present and that Aureobasidium melanogenum was predominantly detected, regardless of the presence of a biofinish and the type of substrate. A. melanogenum was detected on wood samples exposed in the Netherlands, Cameroon, South Africa, Australia and Norway. ITS-specific PCR amplification, cloning and sequencing of DNA extracted from biofinish samples confirmed results of the culturing based method: A. melanogenum is predominant within the Aureobasidium population of biofinishes on pine sapwood treated with raw linseed oil and the outdoor placement in the Netherlands.

Precision-cut liver slices (PCLS) are an ex vivo model for metabolism and toxicity studies. However, data on the maintenance of the morphological integrity of the various cell types in the slices during prolonged incubation are lacking. Therefore, our aims were to characterize morphological and functional changes in rat PCLS during five days of incubation in a rich medium, RegeneMed®, and a standard medium, Williams' Medium E. Although cells of all types in the slices remain viable, profound changes in morphology were observed, which were more prominent in RegeneMed®. Slices underwent notable fibrosis, bile duct proliferation and fat deposition. Slice thickness increased, resulting in necrotic areas, while slice diameter decreased, possibly indicating cell migration. An increased proliferation of parenchymal and non-parenchymal cells (NPCs) was observed. Glycogen, albumin and Cyp3a1 were maintained albeit to a different level in two media. In conclusion, both hepatocytes and NPCs remain viable and functional, enabling five-day toxicity studies. Tissue remodeling and formation of a new capsule-like cell lining around the slices are evident after 3-4 days. The differences in effects between media emphasize the importance of media selection and of the recognition of morphological changes in PCLS, when interpreting results from toxicological or pharmacological studies. © 2015 Elsevier B.V.

Nanomaterials are expected to find applications in numerous consumer products, posing the challenge to guarantee their safety and environmental sustainability before they can be transferred from research labs to end-consumer products. One emerging solution, called safe design, relies on the implementation, throughout the R&D phase, of key aspects related to the safety and sustainability of nanomaterials, in this way anticipating potential negative health effects. This article proposes a computational screening approach to design safer nanomaterials. The work is based on the calculation of key physicochemical properties of nanomaterials that are related to their safety, functionality and synthetic feasibility. These properties are then used to select a pool of promising structures for further experimental testing and development. The concept is demonstrated on a set of core@shell metal oxide nanoparticles for transparent UV-protecting coating applications. This journal is © The Royal Society of Chemistry.

TrafficQuest ziet het als een van haar opgaven om het verkeersmanagementproces zo goed mogelijk te doorgronden en op basis van het begrip van het proces sturingsprincipes te traceren en uit te werken die toegepast kunnen worden bij het (beter) managen van verkeer in een wegennetwerk”. Eén van de manieren om meer inzicht in de processen te krijgen is een vergelijking met andere domeinen waarin zich soortgelijke processen afspelen. We doen dit in de vorm van een workshop “Analogieën voor Verkeersmanagement”. De gekozen aanpak houdt in dat het domein verkeersmanagement wordt vergeleken met een aantal andere domeinen waarin zich vergelijkbare processen afspelen. We zijn hier op zoek naar analogieën met het verkeersmanagement proces. De gevonden analogieën worden vervolgens gebruikt om: • Processen te analyseren en onderling te vergelijken • Mogelijkheden om processen aan te sturen te inventariseren en te beoordelen • Op basis daarvan het inzicht in het verkeersmanagement proces te vergroten Door het onderling vergelijken van de wijze waarop systemen functioneren en ook door te kijken en te vergelijken hoe het functioneren van deze systemen extern en intern wordt beïnvloed, kunnen interessante parallellen worden getrokken in het functioneren van systemen. In deze studie staat verkeersmanagement/netwerkmanagement centraal (het focus systeem). Verkeersmanagement (ook wel DVM genoemd) heeft als doel verkeersstromen zo te beïnvloeden dat de kwaliteit van de verkeersafwikkeling – gegeven een aantal doelstellingen en randvoorwaarden – optimaal is. Bij verkeersmanagement zijn het de voertuigen en in het bijzonder de bestuurders van die voertuigen die via een reeks van maatregelen geïnformeerd, geadviseerd en gestuurd worden. In andere systemen is vaak ook sprake van stromen die (extern en intern) beïnvloed worden. De wijze waarop deze stromen worden afgewikkeld kan interessante ideeën opleveren voor het management van verkeer en omgekeerd. Kortom analogieën met andere disciplines kunnen helpen om problemen in het eigen vakgebied beter te duiden en processen beter te begrijpen en aan te sturen.