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Neisseria meningitidis protects itself from complement-mediated killing by binding complement factor H (FH). Previous studies associated susceptibility to meningococcal disease (MD) with variation in CFH, but the causal variants and underlying mechanism remained unknown. Here we attempted to define the association more accurately by sequencing the CFH-CFHR locus and imputing missing genotypes in previously obtained GWAS datasets of MD-affected individuals of European ancestry and matched controls. We identified a CFHR3 SNP that provides protection from MD (rs75703017, p value = 1.1 × 10-16) by decreasing the concentration of FH in the blood (p value = 1.4 × 10-11). We subsequently used dual-luciferase studies and CRISPR gene editing to establish that deletion of rs75703017 increased FH expression in hepatocyte by preventing promotor inhibition. Our data suggest that reduced concentrations of FH in the blood confer protection from MD; with reduced access to FH, N. meningitidis is less able to shield itself from complement-mediated killing.

Contains fulltext : 233564.pdf (Publisher’s version ) (Open Access)

IMPORTANCE: A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking. OBJECTIVES: To study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome. DESIGN: Data from two prospective cohort studies. SETTING AND PARTICIPANTS: Cohort 1 is from a single-center study involving children admitted to PICU with meningococcal sepsis (samples obtained at three time points). Cohort 2 includes patients from a multicenter study involving children admitted to the hospital with invasive bacterial infections of differing etiologies (samples obtained within 48 hr after hospital admission). MAIN OUTCOMES AND MEASURES: Primary outcome measure was mortality. Secondary outcome measures were PICU-free days at day 28 and hospital length of stay. RESULTS: In cohort 1 (n = 59), nonsurvivors more frequently had A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels above the detection limit than survivors at admission to PICU (8/11 [73%] and 6/23 [26%], respectively; p = 0.02) and at t = 24 hours (2/3 [67%] and 3/37 [8%], respectively; p = 0.04). In cohort 2 (n = 240), A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels in patients within 48 hours after hospital admission were more frequently above the detection limit than in healthy controls (110/240 [46%] and 14/64 [22%], respectively; p = 0.001). Nonsurvivors more often had detectable A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels than survivors (16/21 [76%] and 94/219 [43%], respectively; p = 0.003), which was mostly attributable to patients with Neisseria meningitidis. CONCLUSIONS AND RELEVANCE: In children with bacterial infection, detection of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 within 48 hours after hospital admission is associated with death, part

Contains fulltext : 233564.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 233564.pdf (Publisher’s version ) (Open Access)

Introduction: Observational studies have shown a relationship between omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) and depression in adolescents. However, n-3 LCPUFA supplementation studies investigating the potential improvement in depressive feelings in adolescents from the general population are missing. Methods: A one-year double-blind, randomized, placebo controlled krill oil supplementation trial was conducted in two cohorts. Cohort I started with 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or placebo, after three months this increased to 800 mg EPA and DHA per day, whilst cohort II started with this higher dose. Omega-3 Index (O3I) was monitored via finger-prick blood measurements. At baseline, six and 12 months participants completed the Centre for Epidemiologic Studies Depression Scale (CES-D) and the Rosenberg Self Esteem questionnaire (RSE). Adjusted mixed models were run with treatment allocation/O3I as predictor of CES-D and RSE scores. Results: Both intention-to-treat and assessing the change in O3I analyses did not show significant effects on CES-D or RSE scores. Conclusion: There is no evidence for less depressive feelings, or higher self-esteem after one year of krill oil supplementation. However, due to a lack of adherence and drop-out issues, these results should be interpreted with caution.

Background The prenatal exposure to maternal n-6 and n-3 polyunsaturated fatty acids (PUFAs) might influence the development of social competence and internalizing and externalizing behaviours of the child, because of the numerous functions of PUFAs within the nervous system.Methods: To analyse the association of selected maternal PUFAs (i.e., AA, EPA, DHA, total n-6, total n-3, and the n-6:n-3 ratio) measured during gestation with childhood social competence and problem behaviours, we examined 311 mother-child pairs from the Maastricht Essential Fatty Acid Birth (MEFAB) cohort. For each woman, PUFA-specific changes in relative concentrations were calculated by identifying the best-fitting curve of PUFA concentration by linear splines of gestational age. The associations of changes in maternal PUFAs in early and late pregnancy with childhood social competence, total problems, internalizing and externalizing behaviours, measured with the Child Behaviour Checklist 4/18 at age 7, were investigated with linear regression analyses adjusted for maternal and children's socio-demographic characteristics.Results: In late gestation (i.e., from gestational week 30), an increase in AA was associated with higher social competence, while a decrease in total n-6 was associated with lower externalizing behaviours. No other significant associations were found.Discussion: In this prospective study, increasing maternal AA and decreasing total n-6 were associated with improved social competence and externalizing behaviours, respectively, in 7-year old children. Nonetheless, the clinical significance of the identified associations is modest and further investigations are warranted to clarify the relationship between maternal AA and total n-6 during pregnancy and childhood social and behavioural development.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes.

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics.

Purpose: Depression is common in adolescents and long-chain polyunsaturated fatty acids (LCPUFA) are suggested to be associated with depression. However, research in adolescents is limited. Furthermore, self-esteem has never been studied in relation to LCPUFA. The objective here was to determine associations of depression and self-esteem with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), Omega-3 Index (O3I), n-6 docosapentaenoic acid (n-6 DPA, also called Osbond acid, ObA), n-3 docosapentaenoic acid (DPA), and arachidonic acid (AA) concentrations in blood of adolescents attending lower general secondary education (LGSE). Methods: Baseline cross-sectional data from a krill oil supplementation trial in adolescents attending LGSE with an O3I ≤ 5% were analysed using regression models built with the BayesFactor package in R. Fatty acids and O3I were determined in blood. Participants filled out the Centre for Epidemiologic Studies Depression (CES-D) scale and the Rosenberg Self-Esteem scale (RSE). Results: Scores indicative of depression (CES-D ≥ 16) were found in 29.4% of the respondents. Of all fatty acids, we found extreme evidence [Bayes factor (BF) > 100] for a weak negative association between ObA and depression score [− 0.16; 95% credible interval (CI) −0.28 to −0.04; BF₁₀ = 245], and substantial evidence for a weak positive association between ObA and self-esteem score (0.09; 95% CI, −0.03 to 0.20; BF₁₀ = 4). When all fatty acids were put in one model as predictors of CES-D or RSE, all of the 95% CI contained 0, i.e., no significant association. Conclusion: No evidence was found for associations of DHA, EPA and O3I with depression or self-esteem scores in LGSE adolescents with O3I ≤ 5%. The associations of higher ObA status with lower depression and higher self-esteem scores warrant more research.

Long-chain polyunsaturated fatty acids (LCPUFA) are important for brain development and function, maybe especially during adolescence. Observational studies have demonstrated an association between fish consumption (a source of LCPUFA) and cognition in adolescents, but intervention trials are lacking. The goal of the current study was to investigate the effect of one year of krill oil (a source of LCPUFA) supplementation on the cognitive performance of adolescents with a low Omega-3 Index (O3I ≤ 5%). A double-blind, randomized, and placebo-controlled supplementation trial with repeated measurements (baseline (T0), three months (T1), six months (T2), and 12 months (T3)) in adolescents (267 randomized) was executed. Participants were randomized to 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day in Cohort I or placebo and 800 mg EPA + DHA per day in Cohort II or placebo. O3I was monitored by a finger prick at all time points. At T0, T2, and T3, participants executed a neurocognitive test battery. Covariate corrected mixed models were run with either condition (krill or placebo) or O3I as predictors. Krill oil supplementation led to a small but significant increase in mean O3I, but few participants increased to the intended O3I range (8–11%). There was no significant effect of supplementation on the neurocognitive tests, nor a relationship between O3I and neurocognitive test scores. The increase in O3I was small in most participants, probably due to non-compliance. Possibly the increase in O3I was too small to demonstrate an effect. More research on the influence of LCPUFAs on cognition in adolescents is needed.

Being open to multiple interpretations allows the ecosystem services concept to operate as a boundary object, facilitating communication and cooperation between different user groups. Yet there is a risk the resultant pluralism limits the capacity of ecosystem services assessments to directly inform decision and policy making, and that the concept could be used to support environmentally or socially harmful activities. Here, we report results from a large mixed methods survey conducted among academics, policymakers and practitioners working in the field of ecosystem services across Europe. We use these results to explore the trade-off that exists between the role of ecosystem services as a boundary object and the needs of policy and decision makers of more standardisation. We conclude this can be done by working towards the standardisation of ecosystem service assessments within specific jurisdictions, whilst maintaining forums for debate, collaboration, and critical reflection within the broader ecosystem services community. We also aim to deduce guiding principles to ensure the ecosystem services concept is not used to support detrimental activities. The consideration of shared and cultural values, the expansion of inter- and transdisciplinary work and the integration of the concept of sustainability are identified as valuable guiding principles to this end.

Background The prenatal exposure to maternal n-6 and n-3 polyunsaturated fatty acids (PUFAs) might influence the development of social competence and internalizing and externalizing behaviours of the child, because of the numerous functions of PUFAs within the nervous system.Methods: To analyse the association of selected maternal PUFAs (i.e., AA, EPA, DHA, total n-6, total n-3, and the n-6:n-3 ratio) measured during gestation with childhood social competence and problem behaviours, we examined 311 mother-child pairs from the Maastricht Essential Fatty Acid Birth (MEFAB) cohort. For each woman, PUFA-specific changes in relative concentrations were calculated by identifying the best-fitting curve of PUFA concentration by linear splines of gestational age. The associations of changes in maternal PUFAs in early and late pregnancy with childhood social competence, total problems, internalizing and externalizing behaviours, measured with the Child Behaviour Checklist 4/18 at age 7, were investigated with linear regression analyses adjusted for maternal and children's socio-demographic characteristics.Results: In late gestation (i.e., from gestational week 30), an increase in AA was associated with higher social competence, while a decrease in total n-6 was associated with lower externalizing behaviours. No other significant associations were found.Discussion: In this prospective study, increasing maternal AA and decreasing total n-6 were associated with improved social competence and externalizing behaviours, respectively, in 7-year old children. Nonetheless, the clinical significance of the identified associations is modest and further investigations are warranted to clarify the relationship between maternal AA and total n-6 during pregnancy and childhood social and behavioural development.

Aims: Evidence for drug use in newborns is sparse, which may cause large differences in drug prescriptions. We aimed to investigate the differences between neonatal intensive care units (NICUs) in the Netherlands in currently prescribed drugs. Methods: This multicentre study included neonates admitted during 12 months to four different NICUs. Drugs were classified in accordance with the Anatomical Therapeutic Chemical (ATC) classification system and assessed for on/off-label status in relation to neonatal age. The treatment protocols for four common indications for drug use were compared: pain, intubation, convulsions and hypotension. Results: A total of 1491 neonates (GA range 23+6–42+2 weeks) were included with a total of 32 182 patient days, 181 different drugs and 10 895 prescriptions of which 23% was off-label in relation to neonatal age. Overall, anti-infective drugs were most frequently used with a total of 3161 prescriptions, of which 4% was off-label in relation to neonatal age. Nervous system drugs included 2500 prescriptions of which 31% was off-label in relation to neonatal age. Nervous system drugs, blood and blood forming organs, and cardiovascular drugs showed the largest differences between NICUs with ranges of 919–2278, 554–1465, and 238–952 total prescriptions per 1000 patients per ATC class, respectively. Conclusions: We showed that drug use varies widely in neonatal clinical practice. The drug classes with the highest proportion of off-label drugs in relation to neonatal age showed the largest differences between NICUs, i.e. cardiovascular and nervous system drugs. Drug research in neonates should receive high priority to guarantee safe and appropriate medicines and optimal treatment.

Research has shown the importance of goal orientation in predicting academic performance for children, adolescents, and college students in traditional educational settings. Studies on this relationship within adult distance education, however, are lacking. To fill this gap, the present study was conducted to investigate the relationship between goal orientation and academic performance in adult distance learners. A sample of N = 1128 distance university students (age 18–75 years) filled out an online questionnaire. Their exam grades were collected from the files of the Open University of the Netherlands (OUNL). A mixed model regression showed performance approach goal orientation to be a positive predictor of academic performance, whereas performance avoidance and work avoidance were negative predictors of academic performance. Non-significant results were found for mastery approach as well as for mastery avoidance. Implications of these results are discussed.

To better understand the influence of urban green infrastructure (UGI) on outdoor human thermal comfort, a survey and physical measurements were performed at the campus of the University of Groningen, The Netherlands, in spring and summer 2015. Three hundred eighty-nine respondents were interviewed in five different green spaces. We aimed to analyze people’s thermal comfort perception and preference in outdoor urban green spaces, and to specify the combined effects between the thermal environmental and personal factors. The results imply that non-physical environmental and subjective factors (e.g., natural view, quiet environment, and emotional background) were more important in perceiving comfort than the actual thermal conditions. By applying a linear regression and probit analysis, the comfort temperature was found to be 22.2 °C and the preferred temperature was at a surprisingly high 35.7 °C. This can be explained by the observation that most respondents, who live in temperate regions, have a natural tendency to describe their preferred state as “warmer” even when feeling “warm” already. Using the Kruskal-Wallis H test, the four significant factors influencing thermal comfort were people’s exposure time in green spaces, previous thermal environment and activity, and their thermal history. However, the effect of thermal history needs further investigation due to the unequal sample sizes of respondents from different climate regions. By providing evidence for the role of the objective and subjective factors on human thermal comfort, the relationship between UGI, microclimate, and thermal comfort can assist urban planning to make better use of green spaces for microclimate regulation.

The goal of this study was to investigate whether single executive function (EF) tests were predictive for learning performance in mainly young and middle-aged adults. The tests measured shifting and updating. Processing speed was also measured. In an observational study, cognitive performance and learning performance were measured objectively in 851 adult students and analyzed using multiple linear regression. EFs and processing speed were measured via cognitive tests. Learning performance was evaluated after 14 months. The results show that updating performance is predictive for learning performance, with a small effect size, while shifting performance was not. This means that a single updating test has predictive value for learning performance acquired over a longer period of time. However, as the effect size is rather small, the test on its own does not serve as a proper selection tool for determining whether a student will be successful or not.

To better understand the influence of urban green infrastructure (UGI) on outdoor human thermal comfort, a survey and physical measurements were performed at the campus of the University of Groningen, The Netherlands, in spring and summer 2015. Three hundred eighty-nine respondents were interviewed in five different green spaces. We aimed to analyze people’s thermal comfort perception and preference in outdoor urban green spaces, and to specify the combined effects between the thermal environmental and personal factors. The results imply that non-physical environmental and subjective factors (e.g., natural view, quiet environment, and emotional background) were more important in perceiving comfort than the actual thermal conditions. By applying a linear regression and probit analysis, the comfort temperature was found to be 22.2 °C and the preferred temperature was at a surprisingly high 35.7 °C. This can be explained by the observation that most respondents, who live in temperate regions, have a natural tendency to describe their preferred state as “warmer” even when feeling “warm” already. Using the Kruskal-Wallis H test, the four significant factors influencing thermal comfort were people’s exposure time in green spaces, previous thermal environment and activity, and their thermal history. However, the effect of thermal history needs further investigation due to the unequal sample sizes of respondents from different climate regions. By providing evidence for the role of the objective and subjective factors on human thermal comfort, the relationship between UGI, microclimate, and thermal comfort can assist urban planning to make better use of green spaces for microclimate regulation.

RU Radboud Universiteit, 23 juni 2016, Promotores : de Groot, R., Hermans, P.W.M. Co-promotores : Ferwerda, J.G., Jonge, M.I. de, Contains fulltext : 157668.pdf (publisher's version ) (Open Access), Respiratory syncytial virus (RSV) can cause severe respiratory tract infections in young children. It is largely unknown why some children will develop very severe infections by RSV, whereas the majority will only get a common cold. In this doctoral thesis, we studied whether maternal antibodies and bacteria that are present in the nose have an influence on severity of disease. Antibodies do not only reduce infection, but may also simultaneously enhance the inflammatory response. We found that the amount of antibodies in the nose, as compared to antibodies in the blood, correlates better with viral load and inflammation. We also studied the role of bacterial colonization in RSV infected children and found that presence of specific bacteria may enhance the inflammatory response, whereas other bacteria are able to reduce infection. Further insight in the role of antibodies and colonizing bacteria may help to develop more effective preventive strategies.

Chlamydia trachomatis infections during pregnancy may have serious consequences for women and their offspring. Chlamydial infections are largely asymptomatic. Hence, prevention is based on screening. The objective of this study was to estimate the cost-effectiveness of C. trachomatis screening during pregnancy. We used a health-economic decision analysis model, which included potential health outcomes of C. trachomatis infection for women, partners and infants, and premature delivery. We estimated the cost-effectiveness from a societal perspective using recent prevalence data from a population-based prospective cohort study among pregnant women in the Netherlands. We calculated the averted costs by linking health outcomes with health care costs and productivity losses. Cost-effectiveness was expressed as net costs per major outcome prevented and was estimated in base-case analysis, sensitivity, and scenario analysis. In the base-case analysis, the costs to detect 1000 pregnant women with C. trachomatis were estimated at €527,900. Prevention of adverse health outcomes averted €626,800 in medical costs, resulting in net cost savings. Sensitivity analysis showed that net cost savings remained with test costs up to €22 (test price €19) for a broad range of variation in underlying assumptions. Scenario analysis showed even more cost savings with targeted screening for women less than 30 years of age or with first pregnancies only. Antenatal screening for C. trachomatis is a cost-saving intervention when testing all pregnant women in the Netherlands. Savings increase even further when testing women younger than 30 years of age or with pregnancies only.

Respiratory syncytial virus (RSV) causes infections that range from common cold to severe lower respiratory tract infection requiring high-level medical care. Prediction of the course of disease in individual patients remains challen

BACKGROUND: Unhealthy lifestyles in early childhood are a major global health challenge. These lifestyles often persist from generation to generation and contribute to a vicious cycle of health-related and social problems. This design article presents a study evaluating the effects of two novel healthy school interventions. The main outcome measure will be changes in children's body mass index (BMI). In addition, lifestyle behaviours, academic achievement, child well-being, socio-economic differences, and societal costs will be examined.METHODS: In close collaboration with various stakeholders, a quasi-experimental study was developed, for which children of four intervention schools (n = 1200) in the southern part of the Netherlands are compared with children of four control schools (n = 1200) in the same region. The interventions started in November 2015. In two of the four intervention schools, a whole-school approach named 'The Healthy Primary School of the Future', is implemented with the aim of improving physical activity and dietary behaviour. For this intervention, pupils are offered an extended curriculum, including a healthy lunch, more physical exercises, and social and educational activities, next to the regular school curriculum. In the two other intervention schools, a physical-activity school approach called 'The Physical Activity School', is implemented, which is essentially similar to the other intervention, except that no lunch is provided. The interventions proceed during a period of 4 years. Apart from the effectiveness of both interventions, the process, the cost-effectiveness, and the expected legal implications are studied. Data collection is conducted within the school system. The baseline measurements started in September 2015 and yearly follow-up measurements are taking place until 2019.DISCUSSION: A whole-school approach is a new concept in the Netherlands. Due to its innovative, multifaceted nature and sound scientific fou

RU Radboud Universiteit, 23 juni 2016, Promotores : de Groot, R., Hermans, P.W.M. Co-promotores : Ferwerda, J.G., Jonge, M.I. de, Contains fulltext : 157668.pdf (publisher's version ) (Open Access), Respiratory syncytial virus (RSV) can cause severe respiratory tract infections in young children. It is largely unknown why some children will develop very severe infections by RSV, whereas the majority will only get a common cold. In this doctoral thesis, we studied whether maternal antibodies and bacteria that are present in the nose have an influence on severity of disease. Antibodies do not only reduce infection, but may also simultaneously enhance the inflammatory response. We found that the amount of antibodies in the nose, as compared to antibodies in the blood, correlates better with viral load and inflammation. We also studied the role of bacterial colonization in RSV infected children and found that presence of specific bacteria may enhance the inflammatory response, whereas other bacteria are able to reduce infection. Further insight in the role of antibodies and colonizing bacteria may help to develop more effective preventive strategies.

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In this Editorial to Issue 12–3 (2016) of International Journal of Biodiversity, Ecosystem Services & Management (IJBESM), we introduce this Issue’sarti-cles, which can be of relevance to a wide range of stakeholders, such as local and (inter)national deci-sion-makers, large international firms, farmers, fishery managers and protected area managers. We discuss how various stakeholders could use the findings and, if applicable, how researchers can optimise dissemina-tion and utilisation of their findings. Finally, we wel-come a new Editorial Board member and look ahead at the publication of a Special Issue that will address the use of ecosystem services in planning at different scales.

BACKGROUND: Unhealthy lifestyles in early childhood are a major global health challenge. These lifestyles often persist from generation to generation and contribute to a vicious cycle of health-related and social problems. This design article presents a study evaluating the effects of two novel healthy school interventions. The main outcome measure will be changes in children's body mass index (BMI). In addition, lifestyle behaviours, academic achievement, child well-being, socio-economic differences, and societal costs will be examined.METHODS: In close collaboration with various stakeholders, a quasi-experimental study was developed, for which children of four intervention schools (n = 1200) in the southern part of the Netherlands are compared with children of four control schools (n = 1200) in the same region. The interventions started in November 2015. In two of the four intervention schools, a whole-school approach named 'The Healthy Primary School of the Future', is implemented with the aim of improving physical activity and dietary behaviour. For this intervention, pupils are offered an extended curriculum, including a healthy lunch, more physical exercises, and social and educational activities, next to the regular school curriculum. In the two other intervention schools, a physical-activity school approach called 'The Physical Activity School', is implemented, which is essentially similar to the other intervention, except that no lunch is provided. The interventions proceed during a period of 4 years. Apart from the effectiveness of both interventions, the process, the cost-effectiveness, and the expected legal implications are studied. Data collection is conducted within the school system. The baseline measurements started in September 2015 and yearly follow-up measurements are taking place until 2019.DISCUSSION: A whole-school approach is a new concept in the Netherlands. Due to its innovative, multifaceted nature and sound scientific fou

Cities are a key nexus of the relationship between people and nature and are huge centers of demand for ecosystem services and also generate extremely large environmental impacts. Current projections of rapid expansion of urban areas present fundamental challenges and also opportunities to design more livable, healthy and resilient cities (e.g. adaptation to climate change effects). We present the results of an analysis of benefits of ecosystem services in urban areas. Empirical analyses included estimates of monetary benefits from urban ecosystem services based on data from 25 urban areas in the USA, Canada, and China. Our results show that investing in ecological infrastructure in cities, and the ecological restoration and rehabilitation of ecosystems such as rivers, lakes, and woodlands occurring in urban areas, may not only be ecologically and socially desirable, but also quite often, economically advantageous, even based on the most traditional economic approaches.

Background: Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. Methods: From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. Findings: The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15. years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5. years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. Interpretatio

Background: Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. Methods: In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second c

A strong electronic reconstruction resulting in a quenching of the Fe magnetic moments has recently been predicted to be at the origin of the giant magnetocaloric effect displayed by Fe2P-based materials. To verify this scenario, x-ray magnetic circular dichroism experiments have been carried out at the L edges of Mn and Fe for two typical compositions of the (Mn,Fe)2(P,Si,B) system. The dichroic absorption spectra of Mn and Fe have been measured in the vicinity of the first-order ferromagnetic transition. The experimental spectra are compared with first-principles calculations and charge-transfer multiplet simulations in order to derive the magnetic moments. Even though signatures of a metamagnetic behavior are observed either as a function of the temperature or the magnetic field, the similarity of the Mn and Fe moment evolution suggests that the quenching of the Fe moment is weaker than previously predicted., RST/Radiation, Science and Technology, Applied Sciences

Background Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. Methods In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. Results Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. Conclusion By combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection., Intelligent Systems, Electrical Engineering, Mathematics and Computer Science

BACKGROUND: Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. METHODS: From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. FINDINGS: The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. INTERPRETATION: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of