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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.

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.

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.

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.

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.

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?

In deze rapportage wordt een indicatie van de zorgvraag in 2030 van de gemeente Rotterdam beschreven. Hiertoe zijn prognoses gemaakt van het functioneren, het voorkomen van chronische aandoeningen, psychosociale problematiek en verstandelijke beperkingen in de toekomstige bevolking van Rotterdam.

In deze rapportage wordt een indicatie van de zorgvraag in 2030 van de provincie Friesland beschreven. Hiertoe zijn prognoses gemaakt van het functioneren, het voorkomen van chronische aandoeningen, psychosociale problematiek en verstandelijke beperkingen in de toekomstige bevolking van de provincie Friesland.

In deze rapportage wordt een indicatie van de zorgvraag in 2030 van de gemeente Amstelveen beschreven. Hiertoe zijn prognoses gemaakt van het functioneren, het voorkomen van chronische aandoeningen, psychosociale problematiek en verstandelijke beperkingen in de toekomstige bevolking van Amstelveen.

In deze rapportage wordt een indicatie van de zorgvraag in 2030 van de gemeente Amsterdamn. Hiertoe zijn prognoses gemaakt van het functioneren, het voorkomen van chronische aandoeningen, psychosociale problematiek en verstandelijke beperkingen in de toekomstige bevolking van Amsterdam.

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.

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.

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

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.

Buiten vastgestelde kaders denken draagt wezenlijk bij aan het verbeteren van onze veiligheid. In Nederland is dit echter uitermate moeilijk. Eerste stap om de huidige praktijk te verbeteren vormt het standaard inschakelen van het RIVM

Vraagstelling : Volgens internationale regelgeving moeten stuurhuisruiten van binnenvaartschepen een minimale lichtdoorlatendheid van 75% hebben. De scheepvaartsector vraagt zich af of deze eis omlaag kan omdat een groot deel van de schepen voorzien is van groen getinte ruiten met een lagere lichtdoorlatendheid. In deze studie onderzoeken we in hoeverre de minimaal toegestane lichtdoorlatendheid van stuurhuisruiten van binnenvaartschepen verlaagd kan worden van 75% naar lagere waarden van groen-getinte en bruin-getinte (brons) ruiten. Daarnaast wordt een aanzet te geven voor een meetprotocol om de lichtdoorlatendheid van stuurhuisruiten te kunnen vaststellen in de praktijk. ---- Werkwijze : Om inzicht te krijgen in de visuele taak van de schipper en om fotometrische metingen aan boord te kunnen uitvoeren is een elftal binnenvaartschepen bezocht. We hebben een aantal lichttechnische parameters bepaald, zoals soort ruit, (kleur, aantal lagen), lichtdoorlatendheid ruit, schuinstand ruit, plafondreflectie. Daarnaast zijn door middel van modelberekeningen de detectieafstanden bepaald van een navigatielicht bij nacht en een onverlichte boei overdag, bij verschillende waarden van de lichtdoorlatendheid van de stuurhuisruit. Hierbij is uitgegaan van de parameters gemeten op de schepen, standaard lichtomstandigheden en de voorgeschreven lichtsterkten van signaallichten. Op basis van marktonderzoek, modelberekeningen en analyses is een voorstel gemaakt voor een meetprotocol. ---- Resultaten : Uit metingen op de schepen blijkt dat stuurhuisruiten met de kleuren blank, groen en brons een gemiddelde lichtdoorlatendheid hebben van respectievelijk 82%, 64% en 47%. Hiermee voldoen de groen en brons getinte ruiten niet aan de huidige norm van minimaal 75%. De gemiddelde reflectiefactor van het plafond van stuurhuizen is bepaald op 0,555. Uit de modelberekeningen blijkt dat de zichtbaarheid van objecten overdag nauwelijks wordt beïnvloed door de lichtdoorlatendheid, mits deze hoger is dan 20%. Vergeleken met een normale ruit (75%) vermindert de detectieafstand voor brons en groen getinte ruiten met respectievelijk 0,7% en 0,2%. ’s Nachts neemt de detectieafstand wel noemenswaardig af bij afnemende lichtdoorlatendheid en wordt deze ook beïnvloed door de reflectie van het plafond en de interne stuurhuisverlichting. Vergeleken met een normale ruit vermindert de detectieafstand voor brons en groen getinte ruiten met respectievelijk 17% en 6%. De negatieve invloed van groen getinte ruiten op de detectieafstand bij nacht is te compenseren door aanpassingen van het interieur van stuurhuizen. Voor brons getinte ruiten is dit niet te compenseren. Bij het meten van de lichtdoorlatendheid van stuurhuisruiten in de praktijk zouden de handzame meetinstrumenten ingezet kunnen worden die ook voor het meten van autoruiten worden gebruikt. Deze instrumenten zijn echter alleen goed bruikbaar mits ze worden gekalibreerd voor de grotere dikten van de stuurhuisruiten en er een goede afscherming is voor strooilicht. Daarnaast moet een correctie worden uitgevoerd voor het schuin staan van de ruiten. ---- Conclusies : Getinte stuurhuisruiten hebben overdag een verwaarloosbare invloed op het waarnemen objecten buiten het stuurhuis. ’s Nachts is die invloed groter maar kan voor groen getinte ruiten worden gecompenseerd door aanpassing van het stuurhuisinterieur. Het meten van de lichtdoorlatendheid van stuurhuisruiten in de praktijk met bestaande meetinstrumenten is alleen mogelijk als deze voor dit doel zijn gemodificeerd en gekalibreerd.

The translation has been made for the purpose of a training in Bangladesh. The Dutch foundation Safe Crossings has initiated in 2012 a programme for infrastructural speed reducing measures on national highways in Bangladesh. A pilot project on 3 locations is being implemented in cooperation with national authorities and researchers. The pilot project will be evaluated by the Centre for Injury Prevention and Research Bangladesh CIPRB. Road safety for all has advised CIPRB to use the so called conflict observation technique DOCTOR for the evaluation. At the request of , and in cooperation with Safe Crossing Richard van der Horst has provided in 2013 the CIPRB researchers in Dhaka with a training in this technique. Road safety for all has decided to publish the English manual for two reasons. Firstly, it is believed that it will be of use for researchers abroad, notably in low and middle income countries. Secondly, in road safety research a renewed interest in traffic conflict techniques has been identified in Europe.

The atmospheric organic aerosol composition is characterized by a great diversity of functional groups and chemical species challenging simple classification schemes. Traditional off-line chemical methods identified chemical classes based on the retention behavior on chromatographic columns and absorbing beds. Such approach led to the isolation of complex mixtures of compounds such as the humic-like substances (HULIS). More recently, on-line aerosol mass spectrometry (AMS) was employed to identify chemical classes by extracting fragmentation patterns from experimental data series using statistical methods (factor analysis), providing simplified schemes for oxygenated organic aerosols (OOAs) classification on the basis of the distribution of oxygen-containing functionalities. The analysis of numerous AMS datasets suggested the occurrence of very oxidized OOAs which were postulated to correspond to the HULIS. However, only a few efforts were made to test the correspondence of the AMS classes of OOAs with the traditional classification from the off-line methods. In this paper, we consider a case study representative for polluted continental regional background environments. We examine the AMS factors for OOAs identified by positive matrix factorization (PMF) and compare to chemical classes of water-soluble organic carbon (WSOC) analysed off-line on a set of filters collected in parallel. WSOC fractionation was performed by means of factor analysis applied to H-NMR spectroscopic data, and by applying an ion-exchange chromatographic method for direct quantification of HULIS. Results show that the very oxidized low-volatility OOAs from AMS correlate with the NMR factor showing HULIS features and also with true “chromatographic” HULIS. On the other hand, UV/VIS-absorbing polyacids (or HULIS sensu stricto) isolated on ion-exchange beds were only a fraction of the AMS and NMR organic carbon fractions showing functional groups attributable to highly substituted carboxylic acids, suggesting that unspeciated low-molecular weight organic acids contribute to HULIS in the broad sense.

The advent of satellite data has provided a source of independent information to monitor trends in tropospheric nitrogen dioxide levels. To interpret these trends, one needs to know the sensitivity of the satellite retrieved NO2 column to anthropogenic emissions. We have applied a chemistry transport model to investigate the sensitivity of the modeled NO2 column, sampled at the OMI (Ozone Monitoring Instrument) overpass time and location and weighted by the OMI averaging kernel, to emission sources across Europe. The most important contribution (~35%) in Western Europe is made by road transport. Off-road transport and industrial combustion each contribute 10%-15% across continental Europe. In Eastern Europe, power plant contributions are of comparable magnitude as those of road transport. To answer the question if the OMI-NO2 trends can be translated directly into emission changes, we assessed the anticipated changes in OMI-NO2 between 2005 and 2020. Although the results indicated that for many countries, it is indeed possible, for medium- and small-sized coastal countries, the contribution of the increasing shipping emissions in adjacent sea areas may mask a significant part of national emission reductions. This study highlights the need for a combined use of models, a priori emission estimates and satellite data to verify emission trends. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Conference abstract of the World Congress on Integrated Care, Singapore, November 7-9, 2013.

A 3D geological raster model has been constructed of the onshore of the Netherlands. The model displays geological units for the upper 500 m in 3D in an internally consistent way. The units are based on the lithostratigraphical classification of the Netherlands. This classification is used to interpret a selection of boreholes from the national subsurface database. Additional geological information regarding faults, the areal extent of each unit and conceptual genetic models have been combined in an automated workflow to interpolate the basal surfaces of each unit on 100 × 100 metre (x,y dimensions) raster cells. The combination of all interpolated basal surfaces results in a 3D Digital Geological Model (DGM) of the subsurface. A measure of uncertainty of each of these surfaces is also given. The automated workflow ensures an easily updatable subsurface model. The outputs are available for end users through www.dinoloket.nl.

Conference abstract of the World Congress on Integrated Care, Singapore, November 7-9, 2013.

Objective:Niacin potently lowers triglycerides, mildly decreases LDL-cholesterol, and largely increases HDL-cholesterol. Despite evidence for an atheroprotective effect of niacin from previous small clinical studies, the large outcome trials, AIM-HIGH and HPS2-THRIVE did not reveal additional beneficial effects of niacin (alone or in combination with laropiprant) on top of statin treatment. We aimed to address this apparent discrepancy by investigating the effects of niacin without and with simvastatin on atherosclerosis development and determine the underlying mechanisms, in APOE*3Leiden.CETP mice, a model for familial dysbetalipoproteinemia (FD).Approach and Results:Mice were fed a western-type diet containing cholesterol without or with niacin (120 mg/kg/day), simvastatin (36 mg/kg/day) or their combination for 18 weeks. Similarly as in FD patients, niacin reduced total cholesterol by -39% and triglycerides by -50%, (both P

Objective: Macrophage foam cells play a crucial role in several pathologies including multiple sclerosis, glomerulosclerosis, and atherosclerosis. Angiopoietin-like protein 4 (Angptl4) was previously shown to inhibit chyle-induced foam cell formation in mesenteric lymph nodes. Here we characterized the regulation of Angptl4 expression in macrophages and examined the impact of Angptl4 on atherosclerosis development. Approach and Results: Macrophage activation elicited by pathogen-recognition receptor agonists decreased Angptl4 expression, whereas lipid loading by intralipid and oxidized low-density lipoprotein increased Angptl4 expression. Consistent with an antilipotoxic role of Angptl4, recombinant Angptl4 significantly decreased uptake of oxidized low-density lipoprotein by macrophages, via lipolysis-dependent and -independent mechanisms. Angptl4 protein was detectable in human atherosclerotic lesions and localized to macrophages. Transgenic overexpression of Angptl4 in atherosclerosis-prone apolipoprotein E*3-Leiden mice did not significantly alter plasma cholesterol and triglyceride levels. Nevertheless, Angptl4 overexpression reduced lesion area by 34% (P

Dit rapport beschrijft de opzet en resultaten van een kennisoverdrachtproject over de meerwaarde van serious gaming in het onderwijs. In dit kennisoverdrachtsproject heeft TNO de vijf MKB-bedrijven begeleid in het evalueren van hun eigen game middels het uitvoeren van vijf vergelijkbare experimenten op basis van een eerder door TNO ontwikkelde methodiek. De bevindingen van deze vijf experimenten hebben inzicht opgeleverd in de effectiviteit van serious games, niet alleen per specifieke game maar ook over serious gaming in het algemeen. De doelstelling van de experimenten was bepalen wat het leereffect is bij de studenten. Hierbij is niet alleen gekeken naar de leerprestaties maar ook naar de manier van leren. Zo is bekend dat serious gaming kan leiden tot een hogere motivatie, meer inzicht in de leerstof, en een andere leerhouding zoals zelfsturend leren. De resultaten kunnen tevens inzicht opleveren in mogelijke verbeterpunten in de game zelf en in de manier waarop de game tijdens de lessen wordt ingezet: de didactiek. Het kennisoverdrachtproject beperkt zich tot het klassikaal onderwijs. Er heeft één basisschool deelgenomen, één middelbare school en drie hogescholen. Vier van de vijf deelnemende partners hebben economisch gerelateerde of business games ingebracht en één van de partners heeft een rekenspel geleverd voor het primair onderwijs. De spellen zijn zowel analoog als digitaal aangezien de didactische kenmerken en verwachte leereffecten vergelijkbaar zijn. Alle spellen zijn gericht op samenwerkend leren. De serious gaming bedrijven hebben reeds hun product geïmplementeerd op de betreffende scholen die deelgenomen hebben aan het onderzoek. De eindresultaten zijn tevens gepresenteerd op een seminar van SURFnet op 27 februari 2013.

De Nederlandse overheid spant zich samen met TNO in om brandstofverbruik en schadelijke emissies van wegvoertuigen te beperken, zodat ons milieu beschermd wordt, zonder beperking van onze mobiliteit

TNO recently developed InTESTine™ in order to study the absorption and translocation of pharmaceutical, biological and nutritional compounds across the intestinal wall in a physiologically relevant model. This system uses fresh ex vivo intestinal tissue mounted into a two compartment model. So far, this has been the missing link in our toolbox to accurately predict absorption, oral bioavailability and PK of compounds.

Objective: The scavenger receptor CD36 facilitates the cellular uptake of long-chain fatty acids. As CD36-deficiency attenuates the development of high fat diet (HFD)-induced obesity, the role of CD36-deficiency in preadipocyte recruitment and adipocyte function was set out to characterize. Design and methods: Fat cell size and number were determined in gonadal, visceral, and subcutaneous adipose tissue of CD36(-/-) and WT mice after 6 weeks on HFD. Basal lipolysis and insulin-inhibited lipolysis were investigated in gonadal adipose tissue. Results: CD36(-/-) mice showed a reduction in adipocyte size in all fat pads. Gonadal adipose tissue also showed a lower total number of adipocytes because of a lower number of very small adipocytes (diameter

Background: The False Discovery Rate (FDR) controls the expected number of false positives among the positive test results. It is not straightforward how to conduct a FDR controlling procedure in experiments with a factorial structure, while at the same time there are between-subjects and within-subjects factors. This is because there are P-values for different tests in one and the same response along with P-values for the same test and different responses. Findings: We propose a procedure resulting in a single P-value per response, calculated over the tests of all the factorial effects. FDR control can then be based on the set of single P-values. Conclusions: The proposed procedure is very easy to apply and is recommended for all designs with factors applied at different levels of the randomization, such as cross-over designs with added between-subjects factors.

Ziekten leiden tot verminderde productiviteit en hoge kosten op het werk. Er zijn inmiddels heel wat gezondheidsbevorderende interventies. Het OSHIA-model maakt het mogelijk om vooraf te bepalen of de kosten van een interventie opwegen tegen de baten. Vakmedia

For risk analysis studies, relatively simple dispersion models are generally applied, such as Gaussian dispersion and dense gas dispersion models. For rail transport risk analyses in the Netherlands, fixed consequence distances are applied for various standard scenarios of hazardous materials releases. The advantage is that the results are uniform and are relatively independent of the party performing the calculations, which facilitates the decision making. The drawback of this method, however, is that the results are mostly (very) conservative and the implementation of safety measures cannot be taken into account. The use of CFD enables to account for local topography of the buildings in a city and additionally enables the investigation of safety measures. This paper describes the use of CFD for a hazardous material release in Tilburg city. The first scenario follows from the standard scenarios for rail transport in the Netherlands as given in guidelines for risk analysis as well as the RBM-II software. The paper describes how the CFD model is set-up for an urban environment and the results are compared to the standard risk analysis scenario. The advantages and disadvantages of both CFD and standard risk analysis methods are discussed. A second scenario is a dense gas release in the same area, which is not part of the standard scenarios. The CFD results for this scenario are compared to wind tunnel experiments.

Statins are thought to reduce vascular inflammation through lipid independent mechanisms. Evaluation of such an effect in atherosclerotic disease is complicated by simultaneous effects on lipid metabolism. Abdominal aortic aneurysms (AAA) are part of the atherosclerotic spectrum of diseases. Unlike atherosclerotic occlusive disease, AAA is not lipid driven, thus allowing direct evaluation of putative anti-inflammatory effects. The anti-inflammatory potency of increasing doses (0, 20 or 40 mg/day) simvastatin or atorvastatin was evaluated in 63 patients that were at least 6 weeks on statin therapy and who underwent open AAA repair. A comprehensive analysis using immunohistochemistry, mRNA and protein analyses was applied on aortic wall samples collected during surgery. The effect of statins on AAA growth was analyzed in a separate prospective study in incorporating 142 patients. Both statins equally effectively and dose-dependently reduced aortic wall expression of NFκB regulated mediators (i.e. IL-6 (P

Ensemble Optimization (EnOpt) is a rapidly emerging method for reservoir model based production optimization. EnOpt uses an ensemble of controls to approximate the gradient of the objective function with respect to the controls. Current implementations of EnOpt use a Gaussian ensemble with a constant standard deviation, i.e. a diagonal covariance matrix with entries that remain constant during the optimization process. The Covariance Matrix Adaptation Evolutionary Strategy (CMA-ES) is a gradient-free optimization method, developed in the 'machine learning' community, which also uses an ensemble of controls but with a covariance matrix that is continually updated during the optimization process. It has shown to be an efficient method for several difficult small dimension optimization problems and has recently been applied in the petroleum industry for well location and production optimization. In this study we investigated the scope to improve the computational efficiency of EnOpt through the use of covariance adaptation (CMA-EnOpt). We optimized water flooding of a multi-layer sector model containing multiple sealing and non-sealing faults. The controls used were inflow control valve settings at predefined time intervals for injectors and producers with undiscounted net present value as the objective function. We compared EnOpt and CMA-EnOpt starting from identical covariance matrices. We achieved slightly higher (0.7%-1.8%) objective function values and modest speed-ups with CMA-EnOpt compared to EnOpt, depending on choice of user-defined parameters in both algorithms. However, the major benefit of CMA-EnOpt is its robustness with respect to the initial choice of the covariance matrix. A poor choice of the initial matrix can be detrimental to EnOpt, whereas the CMA-EnOpt performance is near-independent of the initial choice. Copyright 2013, Society of Petroleum Engineers.

Ultra-weak photon emission (UPE) of a living system received scientific attention because of its potential for monitoring increased levels of reactive oxygen species (ROS) in the pathogenesis of rheumatoid arthritis (RA). In this study, a highly sensitive cryogenic charge-coupled device (CCD) camera was used to monitor in a RA mouse model the photon emission both without and with luminol. For that purpose, arthritis was induced in mice utilizing a repeated co-administration of type II collagen with lipopolysaccharide. Quantitative imaging of ultra-weak photon emission of the front and back paws of the animals was initiated 70 days after the first injection. All of the animals were measured once without luminol and once again immediately after luminol injection. Data illustrated a higher UPE intensity after initiating arthritis by CII-injection of the animals. The increase in UPE intensity was measured with and without using luminol indicating that this imaging technology may be useful for the future study of human RA. © 2013 van Wijk et al.