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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.

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.

TNO combines state of the art technologies, such as organoids, high throughput sequencing and computational modelling to gain insight and discover functionalities in complex biological systems, to unlock our microbiome for your applications. Our microbiome analysis and modelling techniques can help in solving questions, such as: How does this ingredient influence the microbiome composition? Can my ingredient suppress outgrowth of pathogens? Will these fibers be metabolized by our microbiome?

PMCAMx-2008, a detailed three-dimensional chemical transport model, was applied for the first time in Europe to simulate fine organic aerosol concen-trations during the months of May 2008, February 2009, July 2009 and January 2010. The model includes a state-of-the-art organic aerosol module which is based on the volatility basis set framework treating both primary and secondary organic components as semivolatile and photochemically reactive. The model predicts that fresh primary OA (POA) is a small contributor to organic PM concentrations in Europe during the summer and spring, and that oxygenated species (oxidized primary and biogenic secondary) dominate the ambient OA. During the winter model results suggest a significant underestimation of OA emissions from wood burning. Use of very high resolution emissions inventory does not result in a significant improvement of the predictions of the model over the Megacity of Paris.

An attempt has been made by a combination of theory, observations, and especially modeling to determine the concentrations of trace gases and aerosols in the troposphere, without the influence of human beings.

NETs (neutrophil extracellular traps) have been described as a fundamental innate immune defence mechanism. Duringformation of NETs, the nuclear membrane is disrupted by an asyet unknown mechanism. In the present study we investigated the role of human cathelicidin LL-37 in nuclear membrane disruption and formation of NETs. Immunofluorescence microscopy revealed that 5 μMLL-37 significantly facilitated NET formation by primary human blood-derived neutrophils alone, in the presence of the classical chemical NET inducer PMA or in the presence of Staphylococcus aureus. Parallel assays with a random LL-37 fragment library indicated that the NET induction is mediated by the hydrophobic character of the peptide. The translocalization of LL-37 towards the nucleus and the disruption of the nuclear membrane were visualized using confocal fluorescence microscopy. In conclusion, the present study demonstrates a novel role for LL-37 in the formation of NETs.

The NOx-emission trend has been evaluated over Europe using the LOTOS-EUROS model and the NO2 tropospheric columns from OMI.

Neutrophil extracellular traps (NETs) have been described as a fundamental innate immune defence mechanism. They consist of a nuclear DNA backbone associated with different antimicrobial peptides (AMPs) which are able to engulf and kill pathogens. The AMP LL-37, a member of the cathelicidin family, is highly present in NETs. However, the function of LL-37 within NETs is still unknown because it loses its antimicrobial activity when bound to DNA in the NETs. Using im-munofluorescence microscopy, we demonstrate that NETs treated with LL-37 are distinctly more resistant to S. aureus nuclease degradation than nontreated NETs. Biochemical assays utilising a random LL-37-fragment library indicated that the blocking effect of LL-37 on nuclease activity is based on the cationic character of the AMP, which facilitates the binding to neutrophil DNA, thus protecting it from degradation by the nuclease. In good correlation to these data, the cationic AMPs human beta defensin-3 and human neutro-phil peptide-1 showed similar protection of neutrophil-de-rived DNA against nuclease degradation. In conclusion, this study demonstrates a novel role of AMPs in host immune defence: beside its direct antimicrobial activity against various pathogens, cationic AMPs can stabilise neutrophil-de-rived DNA or NETs against bacterial nuclease degradation.

Purpose: Concern about the environmental impact of agriculture caused by intensification is growing as large amounts of nutrients and contaminants are introduced into the environment. The aim of this paper is to identify the geogenic and agricultural controls on the elemental composition of European, grazing and agricultural soils. Materials and methods: Robust factor analysis was applied to data series for Al, B, Ca, Cd, Co, Cu, Fe, K, Mg, Mn, Na, Ni, P, S, Se, Sr, U, Zn (ICP-MS) and SiO2, K2O, Na2O, Fe2O3, Al2O3 (XRF) based on the European GEMAS dataset. In addition, the following general soil properties were included: clay content, pH, chemical index of alteration (CIA), loss on ignition (LOI), cation exchange capacity (CEC), total organic carbon (TOC) and total carbon and total sulfur. Furthermore, this dataset was coupled to a dataset containing information of historic P2O5 fertilization across Europe. Also, a mass balance was carried out for Cd, Cu and Zn to determine if concentrations of these elements found in the soils have their origin in historic P2O5 fertilization. Results and discussion: Seven geogenic factors and one agricultural factor were found of which four prominent ones (all geogenic): chemical weathering, reactive iron-aluminum oxide minerals, clay minerals and carbonate minerals. Results for grazing and agricultural soils were near identical, which further proofs the prominence of geogenic controls on the elemental composition. When the cumulative amount of P2O5 fertilization was considered, no extra agriculture-related factors became visible. The mass balance confirms these observations. Conclusions: Overall, the geological controls are more important for the soil chemistry in agricultural and grazing land soils than the anthropogenic controls. © 2013 Springer-Verlag Berlin Heidelberg.

Mapping of road traffic noise in urban areas according to standardized engineering calculation methods systematically results in an underestimation of noise levels at areas shielded from direct exposure to noise, such as inner yards. In most engineering methods, road traffic lanes are represented by point sources and noise levels are computed utilizing point-to-point propagation paths. For a better prediction of noise levels in shielded urban areas, an extension of engineering methods by an attenuation term Acan has been proposed, including multiple reflections of the urban environment both in the source and in the receiver area. The present work has two main contributions for the ease of computing Acan. Firstly, it is shown by numerical calculations that Acan may be divided into independent source and receiver environment terms, As and Ar. Based on an equivalent free field analogy, the distance dependence of these terms may moreover be expressed analytically. Secondly, an analytical expression is proposed to compute As and Ar for 3D configurations from using 2D configurations only. The expression includes dependence of the street width-to-height ratio, the difference in building heights and the percentage of facade openings in the horizontal plane. For the expression to be valid, the source should be separated from the receiver environment by at least four times the street width. © S. Hirzel Verlag EAA.

The respiratory route is an important portal for human exposure to a large variety of substances. Consequently, there is an urgent need for realistic in vitro strategies for evaluation of the absorption of airborne substances with regard to safety and efficacy assessment. The present study investigated feasibility of a 3D human airway epithelial model to study respiratory absorption, in particular to differentiate between low and high absorption of substances. Bronchial epithelial models (MucilAir™), cultured at the air–liquid interface, were exposed to eight radiolabeled model substances via the apical epithelial surface. Absorption was evaluated by measuring radioactivity in the apical compartment, the epithelial cells and the basolateral culture medium. Antipyrine, caffeine, naproxen and propranolol were highly transported across the epithelial cell layer (>5%), whereas atenolol, mannitol, PEG-400 and insulin were limitedly transported (

Mood contagion is an automatic mechanism that induces a congruent mood state by means of the observation of another person's emotional expression. In this paper, we address the question whether robot mood displayed during an imitation game can (a) be recognized by participants and (b) produce contagion effects. Robot mood was displayed by applying a generic framework for mood expression using body language. By modulating the set of available behavior parameters in this framework for controlling pose and motion dynamics, the gestures performed by the humanoid robot NAO were adjusted to display either a positive or negative mood. In the study performed, we varied both mood as well as task difficulty. Our results show that participants are able to differentiate between positive and negative robot mood. Moreover, self-reported mood matches the mood of the robot in the easy task condition. Additional evidence for mood contagion is provided by the fact that we were able to replicate an expected effect of negative mood on task performance: in the negative mood condition participants performed better on difficult tasks than in the positive mood condition, even though participants' self-reported mood did not match that of the robot.

The Chemistry Transport Model (CTM) REM-Calgrid (RCG) has been applied to investigate the non-linear relationship between emission changes and modelled SIA (=SO4 + NO3 + NH4) concentrations for a high PM10 episode in spring 2009. Emissions were reduced for the model domain only and the model domain including Boundary Conditions. It was found that the effectiveness of emission reductions increases with increasing emission reduction area whereas results were least dependent on the size of emission reduction area for ammonia emission changes.

To study and forecast atmospheric tracer concentrations at ground level, an assimilation system is available around the LOTOS-EUROS model based on the Ensemble Kalman filter technique. For applications focusing on air-quality related to aerosols, the available observation data is usually limited to ground based observations of total PM2.5 or PM10, and model uncertainty is specified for the emissions. In this study, the key parameters of the assimilation system have been varied: the assumed temporal variation in the emission uncertainty, the amplitude of the representation error, the localization length of the analysis, the averaging period of the observations, and the number of ensemble members in the filter. Although in theory these parameters are all important, the most important parameters are those related to the representation error between simulations and observations

Modelling has been performed of the European nitrogen budget, and the effects of including the bi-directional surface-atmosphere exchange of ammonia have been investigated

Background: Synthetic Amorphous Silica (SAS) is commonly used in food and drugs. Recently, a consumer intake of silica from food was estimated at 9.4 mg/kg bw/day, of which 1.8 mg/kg bw/day was estimated to be in the nano-size range. Food products containing SAS have been shown to contain silica in the nanometer size range (i.e. 5 - 200 nm) up to 43% of the total silica content. Concerns have been raised about the possible adverse effects of chronic exposure to nanostructured silica.Methods: Rats were orally exposed to 100, 1000 or 2500 mg/kg bw/day of SAS, or to 100, 500 or 1000 mg/kg bw/day of NM-202 (a representative nanostructured silica for OECD testing) for 28 days, or to the highest dose of SAS or NM-202 for 84 days.Results: SAS and NM-202 were extensively characterized as pristine materials, but also in the feed matrix and gut content of the animals, and after in vitro digestion. The latter indicated that the intestinal content of the mid/high-dose groups had stronger gel-like properties than the low-dose groups, implying low gelation and high bioaccessibility of silica in the human intestine at realistic consumer exposure levels. Exposure to SAS or NM-202 did not result in clearly elevated tissue silica levels after 28-days of exposure. However, after 84-days of exposure to SAS, but not to NM-202, silica accumulated in the spleen. Biochemical and immunological markers in blood and isolated cells did not indicate toxicity, but histopathological analysis, showed an increased incidence of liver fibrosis after 84-days of exposure, which only reached significance in the NM-202 treated animals. This observation was accompanied by a moderate, but significant increase in the expression of fibrosis-related genes in liver samples. Conclusions: although only few adverse effects were observed, additional studies are warranted to further evaluate the biological relevance of observed fibrosis in liver and possible accumulation of silica in the spleen in the NM-202 and SAS exposed animals respectively. In these studies, dose-effect relations should be studied at lower dosages, more representative of the current exposure of consumers, since only the highest dosages were used for the present 84-day exposure study. © 2014 van der Zande et al.; licensee BioMed Central Ltd.

The capacity of Particulate Matter (PM) to oxidise target molecules, defined as its oxidative potential (OP), has been proposed as a biologically more relevant metric than PM mass. Different assays exist for measuring OP and their methodologies vary in the choice of extraction solvent and filter type. Little is known about the impact of extraction and filter type on reported OP. Four a-cellular assays; electron spin resonance (ESR), dithiothreitol (DTT), ascorbate acid depletion (AA) and reductive acridinium triggering (CRAT) assay were chosen to evaluate whether these differences affect the OP measurement, the correlation between OP from different assays and the association with PM chemical composition. We analysed 15 urban 48-72h PM2.5 samples collected on quartz and Teflon filters. The choice of extraction solvent had only a significant effect on OPDTT, while all OP measures for quartz filters were heavily attenuated. OP values derived from quartz were, however, highly correlated with those derived from Teflon. OPDTT correlated highly with OPCRAT, and OPESR correlated highly with OPAA. These correlations were affected by the choice of filter type. Correlations between OP and PM chemical composition were not affected by filter type and extraction solvent. These findings indicate that the measurement of relative OP reactivity is not greatly influenced by filter type and extraction solvent for the investigated assays. This robustness is also promising for exploratory use in monitoring and subsequent epidemiological studies. © 2013 The Authors.

Europe’s passenger-car efficiency regulation has very effectively driven down the official average CO2 emissions and fuel consumption of new passenger cars in the EU. The 2015 target of 130 grams of CO2 per kilometer (g/km) was met two years ahead of schedule and manufacturers are making good progress towards the 2020/21 target of 95 g/km. But beneath this apparent success there is cause for concern. The basis for the regulation are results obtained under laboratory conditions using the New European Driving Cycle (NEDC)—the so-called certification or “type-approval” values. To make real progress, however, the results recorded in the laboratory must translate dependably into CO2 reductions and fuel-consumption savings experienced on the road. This study, which builds on and extends the analysis begun in 2012 and continued in 2013, demonstrates that the year-over-year improvements reported via the type-approval tests are not reliably matched in everyday driving—and that the gap between the vehicle emissions testing laboratory and the real world of the road is getting wider.

Objective Hypercholesterolaemia, a risk factor for atherosclerosis (ATH), has been suggested to have a role in the development of osteoarthritis (OA). To test this hypothesis, the effect of cholesterol and different cholesterol-lowering treatments on OA was investigated in a mouse model resembling human lipoprotein metabolism. Methods Female ApolipoproteinE*3Leiden.human Cholesteryl Ester Transfer Protein mice received a westerntype diet with 0.1% (w/w) cholesterol (LC), 0.3% (w/w) cholesterol alone (HC) or treated with 3 mg/kg/day atorvastatin or 0.3 mg/kg/day ezetimibe. One group remained on chow (control). After 39 weeks, OA grades of the knees and the extent of ATH were determined. Plasma cholesterol levels were measured throughout the study. Results LC and HC groups developed significantly more OA at the medial side than the control group in a dosedependent manner. Atorvastatin but not ezetimibe treatment significantly suppressed OA development. As expected, features of ATH were significantly increased in the LC and HC groups compared with the control group and suppressed by atorvastatin (48%) and ezetimibe (55%) treatment. There were significant correlations between the development of OA on the medial side of the joint and cholesterol exposure (r=0.4) or ATH features (r=0.3). Conclusions Dietary cholesterol and accordingly increased plasma levels play a role in the development of OA. The correlation found between OA, cholesterol and ATH demonstrates that these variables are connected, but indicates the contribution of other ongoing processes in the development of OA. The suppressive effect on OA development of atorvastatin but not of ezetimibe, which had similar cholesterol exposure levels, corroborates these findings.

Based on comprehensive regression analysis, the authors find that weak wage growth and a smaller labour share of national income significantly reduce labour productivity growth. They conclude that supply-side labour market reforms have contributed to reducing labour productivity growth: this cannot be explained by a deregulation-induced inflow of low-productivity labour as proposed by OECD researchers. They also discuss why deregulation, easier firing and higher labour turnover may damage learning and knowledge accumulation in companies, notably by weakening the functioning of the “routinized” innovation model (“Schumpeter II”). Finally, their findings raise doubts about the relevance of Baumol's law and Verdoorn's law.

This study examines the global variation in particle size distribution simulated by twelve global aerosol microphysics models to quantify model diversity and to identify any common biases against observations. Evaluation against size distribution measurements from a new European network of aerosol supersites shows that the mean model agrees quite well with the observations at many sites on the annual mean, but there are some seasonal biases common to many sites. TNO contributed to this study with aerosol observations from supersite Cabauw.

Anaerobic microorganisms which are frequently associated with corrosion fail Control of bacterial activity are posing major challenge in Saudi Arabia's massive seawater flooding systems. Biocides are used to control bacteria throughout the oil industry. A study to explore the feasibility to develop a detection technique for biocide batch treatments, preferably on-line and in real time, for their potential use in seawater flooding system network is described. Several methods to measure key components of the biocide composition were investigated in the initial stage. Three different techniques were explored during the feasibility phase study to detect and measure concentrations of biocide in seawater. This helped our plans for designing a sensor based on such detection techniques. The techniques explored were to monitor change in temperature, change in pH, and change in chromophore concentration (colorimetric) in the enzymatic reaction. The investigated methods included the use of acetylcholine esterase, based on the pH change as a result of acetate formation, the production of reaction heat (thermal) or on the colorimetric detection of the chromophore concentration based on the conversion of acetylthiocholine in combination with a chromophore. It was found that the colorimetric system was the most versatile system to perform the measurement to be able to show the feasibility of the method in real sea water samples and to demonstrate the effects of the biocides on the measurement system.

Pollution levels in urban areas and their surrounding rural regions differ due to different sources and density of emissions, different composition of pollutants as well as specific meteorological effects. These concentration differences for PM10 are investigated and compared in this study for three different north-west European urban agglomerations: The German Ruhr area, the Dutch Randstad and the German city of Berlin. Measurement data for PM10 for the years 2003-2008 at urban and rural background stations are selected from the AirBase database to specify the PM10 concentration difference between these urban areas and their surrounding rural regions, here defined as the urban increment. Whereas the absolute and relative measured urban increment averaged over the years 2003-2008 for the Ruhr area (7.4μgm-3, 35%) and Berlin (8.5μgm-3, 46%) are comparable in magnitude, a significantly smaller value is found for the Randstad (3.1μgm-3, 12%). To analyze whether the regional chemistry transport model LOTOS-EUROS is able to reproduce the measured urban increment simulation runs were performed for 2003-2008 on a 0.5°×0.25° lon-lat grid covering Europe and for the year 2008 on a finer grid of 0.125°×0.0625° covering the Netherlands and Germany, both with ECMWF meteorology as input. Although the model underestimates the absolute PM10 urban increment averaged over the years 2003-2008 for the Ruhr area (3.3μgm-3, 33%), the Randstad (1.5μgm-3, 12%) and Berlin (1.7μgm-3, 27%), the relative urban increment for the Ruhr area and the Randstad is in general agreement with the measurements. The tested increase of the horizontal resolution gives no systematic improvement of the simulated urban increment. However, an even higher resolution than used here seems to be more appropriate to capture the urban increment (especially for Berlin).The variability of the PM10 urban increment with weather is tested by means of the summer 2003, such an extreme synoptic situation is expected to occur more often in future. Measured and simulated PM10 concentrations in summer 2003 were compared to the summer average of 2003-2008. The response of the observed urban increment was found to depend on the urban area. In general the model reproduces the main features for the Randstad and Berlin.In order to investigate the impact of a changing climate on the PM10 urban increment, simulations were performed with the off-line coupled model system RACMO2 (regional climate model) - LOTOS-EUROS (air quality model) over Europe. Different sets of simulations were carried out using RACMO2 meteorology with ECHAM5 A1B and with MIROC3.2-hires A1B boundary conditions for the time period 1970-2060, as well as with ERA-interim boundary conditions for the time period 1989-2009. Anthropogenic emissions were kept constant in the LOTOS-EUROS simulations. Simulated concentrations differ between the runs using ECHAM and MIROC boundary conditions and both runs differ from the present-day simulations with ERA-interim forcing. The impact of climate change on the modeled PM10 concentrations and the urban increment was found to be small in both scenario runs. However the concentration differences between the simulations forced by either ECHAM or MIROC indicate that PM10 concentration levels are sensitive to circulation patterns rather than temperature change alone, and that PM10 concentration levels may thus change when circulation patterns change in the future. © 2013 Elsevier Ltd.

Current reference values for selenium, an essential micronutrient, are based on the intake of selenium that is required to achieve maximal glutathione peroxidase activity in plasma or erythrocytes. In order to assess the evidence of relevance to setting dietary reference values for selenium, the EURRECA Network of Excellence focused on systematic searches, review, and evaluation of (i) selenium status biomarkers and evidence for relationships between intake and status biomarkers, (ii) selenium and health (including the effect of intake and/or status biomarkers on cancer risk, immune function, HIV, cognition, and fertility), (iii) bioavailability of selenium from the diet, and (iv) impact of genotype/single nucleotide polymorphisms on status or health outcomes associated with selenium. The main research outputs for selenium and future research priorities are discussed further in this review. © 2013 Copyright Taylor and Francis Group, LLC.

Objective:Evidence is accumulating that synovial tissue plays an active role in osteoarthritis (OA), however, exact understanding of its contribution is lacking. In order to further elucidate its role in the OA process, we aimed to identify the secretion pattern of soluble mediators by synovial tissue and to assess its ability to initiate cartilage degeneration.Methods:Synovial tissue explants (STEs) obtained from donors without history of OA (n = 8) or from end stage OA patients (n = 16) were cultured alone or together with bovine cartilage explants in the absence or presence of IL-1α. The secretion of 48 soluble mediators was measured and the effect on glycosaminoglycan (GAG) release and matrix metalloproteinase (MMP) activity was determined.Results:Normal and OA STEs secreted comparable levels of almost all measured soluble mediators. However, in the presence of IL-1α these mediators were less secreted by OA than by normal STEs of which 15 differed significantly (p

The presence of clay in fault zones has a dramatic effect on both fault mechanics and permeability. Quantification of this effect relies on small scale laboratory experiments or indirect observations from hydrocarbon fields, for which systematic variation of clay content, clay distribution, and deformation conditions can be problematic. Two-dimensional discrete element models of fault zones were deformed in simple shear to assess the effect of shale on failure criteria and sealing capacity using a systematic series of model simulations. Comparison between the evolution of shear stress and development of microcracks shows that changes in shear stress are correlated with alignment of microcracks, resulting in fractures with similar orientations as R- and Y-shears that can accommodate local deformation. Both shale content and distribution have a marked effect on the failure criteria of all fault models, i.e. with increasing volumetric shale content cohesion decreases up to a factor ~20 and friction coefficients drops below ~0.1 for some distributions. A tradeoff between permeability reduction due to the presence of low permeable clay and permeability increase due to local failure of fault rock determines the location of spill points and integrity of fault seals during gas storage

Introduction: The role of glucocorticoids in atherosclerosis development is not clearly established. Human studies show a clear association between glucocorticoid excess and cardiovascular disease, whereas most animal models indicate an inhibitory effect of glucocorticoids on atherosclerosis development. These animal models, however, neither reflect long-term glucocorticoid overexposure nor display human-like lipoprotein metabolism. Aim: To investigate the effects of transient and continuous glucocorticoid excess on atherosclerosis development in a mouse model with human-like lipoprotein metabolism upon feeding a Western-type diet. Methods: Pair-housed female APOE*3-Leiden.CETP (E3L.CETP) mice fed a Western-type containing 0.1% cholesterol for 20 weeks were given corticosterone (50 μg/ml) for either 5 (transient group) or 17 weeks (continuous group), or vehicle (control group) in the drinking water. At the end of the study, atherosclerosis severity, lesion area in the aortic root, the number of monocytes adhering to the endothelial wall and macrophage content of the plaque were measured. Results: Corticosterone treatment increased body weight and food intake for the duration of the treatment and increased gonadal and subcutaneous white adipose tissue weight in transient group by +35% and +31%, and in the continuous group by +140% and 110%. Strikingly, both transient and continuous corticosterone treatment decreased total atherosclerotic lesion area by -39% without lowering plasma cholesterol levels. In addition, there was a decrease of -56% in macrophage content of the plaque with continuous corticosterone treatment, and a similar trend was present with the transient treatment. Conclusion: Increased corticosterone exposure in mice with human-like lipoprotein metabolism has beneficial, long-lasting effects on atherosclerosis, but negatively affects body fat distribution by promoting fat accumulation in the long-term. This indicates that the increased atherosclerosis observed in humans in states of glucocorticoid excess may not be related to cortisol per se, but might be the result of complex indirect effects of cortisol. © 2013 Auvinen et al.

We propose a new workflow for building static reservoir models of siliciclastic fluvio-deltaic systems. The proposed strategy requires a process-based stratigraphic simulation model which incorporates a reservoir-scale alluvial architecture module nested within a low-resolution basin-scale (sequence-stratigraphic) model. The basin-scale model is run with the intent to approximate large-scale basin-fill properties (based on geological/geophysical background information about palaeotopography, sea level, sediment supply, subsidence, and so forth). Subsequently, the model may be stochastically optimised by dedicated post-processing software to mimic sub-grid (reservoir-scale) properties of selected parts of the basin fill. This approach allows us to narrow down the range of possible scenarios (realisations) from the outset, which results in more reliable uncertainty estimates associated with reservoir models. Pilot studies suggest that the improvement of geological credibility of stochastically simulated fluvial reservoir models may go hand-in-hand with a significant reduction of the computational effort of inverting basin-scale (process-based) stratigraphic forward models. The implementation of geological constraints on object-based models is expected to improve estimation of sand-body connectivity and dynamic reservoir behaviour, and will therefore contribute to reduction of the non-uniqueness in current static reservoir models. Furthermore, the uncertainty associated with each basin-scale parameter can be propagated all the way through to reserve estimation. The partitioning of the overall uncertainty into contributions at the basin and reservoir scales may be quantitatively assessed, and the information content of all available data may be quantified. Copyright 2013, Society of Petroleum Engineers.

An overview of regional-scale quality modeling practices and perspectives in North America and Europe, highlighting the differences and commonalities in how regional-scale air quality modeling systems are being used and evaluated across both continents