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Agricultural soil (Ap-horizon, 0–20 cm) samples were collected from 33 European countries as part of the GEMAS (GEochemical Mapping of Agricultural and grazing land Soil) soil-mapping project. The Mg data derived from total concentrations (XRF) and two acid digestion methods, aqua regia (AR) and Mobile Metal Ion (MMI®), were used to provide an overview of its spatial distribution in soil at the continental-scale. Magnesium is one of the most abundant elements in the Earth's crust and essential nutrient for plants and animals and its presence in soil is, therefore, important for soil quality evaluation. In this study, the geochemical behaviour of Mg in European agricultural soil was investigated in relation to a variety of soil parent materials, climatic zones, and landscapes. The chemical composition of soil reflects mostly the primary mineralogy of the source bedrock, and the superimposed effects of pre- and post-depositional chemical weathering, controlled by element mobility and formation of secondary phases such as clays. Low Mg concentrations in agricultural soil occur in regions with quartz-rich glacial sediments (Poland, Baltic States, N. Germany), and in soil developed on quartz-rich sandstone parent materials (e.g., central Sweden). High Mg concentrations occur in soil developed over mafic lithologies such as ophiolite belts and in carbonate-rich regions, including karst areas. The maximum extent of the last glaciation is well defined by a Mg concentration break, which is marked by low Mg concentrations in Fennoscandia and north-central Europe, and high Mg concentrations in Mediterranean region. Lithology of parent materials seems to play a key role in the Mg nutritional status of agricultural soil at the European scale. Influence from agricultural practice and use of fertilisers appears to be subordinate. Comparison of the continental-scale spatial distribution of Mg in agricultural soil by using the results from three analytical methods (XRF, AR and MMI®) provides complementary information about Mg mobility and its residence time in soil. Thus, allowing evaluation of soil weathering grade and impact of land use exploitation.

Agricultural soil (Ap-horizon, 0–20 cm) samples were collected from a large part of Europe (33 countries, 5.6 million km2) as part of the GEMAS (GEochemical Mapping of Agricultural and grazing land Soil) soil mapping project. The soil data have been used to provide a general view of element mobility and source rocks at the continental scale, either by reference to average crustal abundances or to normalised patterns of element mobility during weathering processes. The survey area includes a diverse group of soil parent materials with varying geological history, a wide range of climate zones, and landscapes. Total concentrations of Rb, Ga, and Cs in European soil were determined by XRF (X-ray fluorescence spectrometry). In addition, hot aqua regia available element concentrations were analysed by inductively coupled plasma-mass spectrometry ICP-MS. Their spatial distribution patterns are shown in geochemical maps. The spatial distribution of Rb, Ga and Cs in Ap soil is quite comparable for the aqua regia and XRF results. The Cs spatial pattern reflects best the large difference between trace element concentrations in northern Europe with predominantly low concentrations and southern Europe with approximately two times higher values. The maximum extent of the last glaciation is visible as a clear concentration break on the map. Lithology of the underlying bedrock is inferred as the major source of geochemical anomalies. In search for characterising the soil parent material and degree of weathering, the soil data were examined for Ga and Cs using two methods. First, the estimated degree of extractability DEi of an element in a sample was calculated by dividing aqua regia available concentrations by the total concentrations obtained by XRF analysis for Al, Na, Ca, K, Rb, Ga and Cs. The different DEi were investigated for 10 geological parent material subgroups (alkaline rocks, granite, calcareous rocks, basalt-mafic rocks, unclassified lithologies, Precambrian granitic gneiss bedrocks, loess, organic soils, schist and soil developed on coarse-grained sandy deposits). The role of clay as main carrier of Ga and Cs phases was inferred for soils developed on several types of bedrock such as granite, gneiss and alkaline rocks. Additionally, an affinity of Cs for loess and carbonate rocks has been observed.

Introduction: One of the most detrimental factors influencing development is growing up in poverty. According to the World Health Organization, extreme poverty is the leading cause of mortality and morbidity. Unfortunately, some children encounter more unhealthy and potentially detrimental circumstances than others, increasing their risk for later health problems. Poor perinatal outcomes are more often observed in deprived neighborhoods, with both more perinatal mortality and morbidity (prematurity and small for gestational age) in these neighborhoods. Additionally, growing up in families with a lower socio-economic status exposes children to more unsafe environments, making them more at risk for insecure attachment to their parents, behavioral problems, addiction, mental illnesses, deficits in cognitive development and domestic violence. In sum, children growing up in deprivation are more unhealthy, as a consequence of an increased risk of unfavorable perinatal outcomes in combination with growing up in a multidimensional unforgiving environment. We assume that the poor health status of these children is reflected in higher healthcare expenses, since they require more medical care than their healthy peers. Here, we aim to investigate the effects of deprivation on healthcare costs of young children in the Netherlands. Methods: This is a cross-sectional study, using data from several national registries. All children in the Netherlands, aged zero to three years old in 2014, were included. Healthcare costs included all expenses covered by obligatory basic health insurance. Deprivation was studied using monthly household income per 1000 euro’s and neighborhood deprivation scores. The final linear regression model was built for healthcare costs as function of both deprivation variables, perinatal morbidity, ethnicity, a 3-way interaction of household income, perinatal morbidity and ethnicity (including subsequent 2-way interactions) and the 2-way interaction of deprivation index and perinatal morbidity. Results: A total of 583,625 children were included in the analyses. Both household income (β = -4.72, 95% CI [-7.22, -2.23]) and deprivation score (β = 19.31, 95% CI [11.11, 27.51]) were significantly related to healthcare costs. Discussion and conclusion: This research shows that growing up with a lower household income and a higher neighborhood deprivation is significantly associated with higher healthcare costs in early life. These findings support the assumption that children growing up in deprivation have a poorer health status, resulting in (health) inequities already in early childhood. This inequity is particularly detrimental since the gap between poor and rich is widening, not only regarding income disparity, but also in the case of health inequality. Limitations: This research excluded children who died during, or soon after pregnancy, since these children have limited healthcare costs. Nevertheless, this outcome may be of even greater societal relevance when targeting the inequality gap. Suggestions for future research: Future research should focus attention on interventions targeting vulnerable population, before, during and after pregnancy, in order to gain highly necessary knowledge on how to provide an optimal start in life for all children. Lessons learned: More attention should be focused on marginalized populations in order to break through the intergenerational cycle of poor health.

IntroductionResearch focusing on the associations between non-medical determinants and unfavourable perinatal health outcomes is increasing. Despite increasing knowledge on this theme, it still remains unclear to what extent social, environmental and lifestyle factors contribute to these unfavourable outcomes. Therefore, we aim to provide a systematic review, preferably with meta-analysis, in order to provide insight into the associations between non-medical determinants and perinatal mortality, preterm birth and being small for gestational age (SGA).Methods and analysisObservational studies performed in European countries studying the associations between non-medical determinants and unfavourable perinatal health outcomes will be included. Primary outcomes of interest are perinatal mortality, preterm birth and SGA. To retrieve potential eligible articles, a systematic literature search was performed in the following online databases on 5 October 2018: MEDLINE, Embase, Web of Science, Cochrane and Google Scholar. Additionally, a reference list check and citation search will be performed. Data of the included articles will be extracted using a standardised and piloted data extraction form. Risk of bias will be assessed using the Newcastle-Ottawa Scale. The study selection and data extraction process will be performed by two reviewers independently. Disagreements will be resolved through discussion with a third reviewer. The pooled effects will be calculated separately for each association found between one of the outcome measures and the non-medical determinants using a random effects model. Heterogeneity of the studies will be assessed using the I2statistic.Ethics and disseminationNo ethical approval is necessary for a systematic review with meta-analysis. The findings will be published in a peer-reviewed journal.PROSPERO registration numberCRD42018056105.

Item does not contain fulltext BACKGROUND: Laparoscopic pancreatoduodenectomy may improve postoperative recovery compared with open pancreatoduodenectomy. However, there are concerns that the extensive learning curve of this complex procedure could increase the risk of complications. We aimed to assess whether laparoscopic pancreatoduodenectomy could reduce time to functional recovery compared with open pancreatoduodenectomy. METHODS: This multicentre, patient-blinded, parallel-group, randomised controlled phase 2/3 trial was performed in four centres in the Netherlands that each do 20 or more pancreatoduodenectomies annually; surgeons had to have completed a dedicated training programme for laparoscopic pancreatoduodenectomy and have done 20 or more laparoscopic pancreatoduodenectomies before trial participation. Patients with a benign, premalignant, or malignant indication for pancreatoduodenectomy, without signs of vascular involvement, were randomly assigned (1:1) to undergo either laparoscopic or open pancreatoduodenectomy using a central web-based system. Randomisation was stratified for annual case volume and preoperative estimated risk of pancreatic fistula. Patients were blinded to treatment allocation. Analysis was done according to the intention-to-treat principle. The main objective of the phase 2 part of the trial was to assess the safety of laparoscopic pancreatoduodenectomy (complications and mortality), and the primary outcome of phase 3 was time to functional recovery in days, defined as all of the following: adequate pain control with only oral analgesia; independent mobility; ability to maintain more than 50% of the daily required caloric intake; no need for intravenous fluid administration; and no signs of infection (temperature

We present Sr-87/Sr-86 isotope ratios for similar to 1200 selected soil samples, collected by the GEMAS consortium from grazing (Gr) and agricultural (Ap) soils in Europe with the aim to better understand the strontium isotope distribution in the bioavailable fraction of the top-soil and its potential for provenancing applications. Spatial analysis shows that there is a clear distinction between coastal (100 km) samples in their variance and that this variance is mirrored in the sodium concentration, suggesting an important but highly variable contribution from seaspray. We present two Sr-87/Sr-86 maps at 25 km x 25 km scale: one based solely on the measured data using a classical kriging approach and one based on a Random Forest model using complementary GEMAS data to predict the strontium isotope composition at the remaining 3000+ GEMAS sampling locations, including appropriate uncertainty assessment. Using a forensic Bayesian likelihood ratio approach, a tool was developed in R to create provenancing likelihood ratio maps. The maps delineate areas of high and low likelihood and allow investigators to direct their resources to areas of interest. For actual forensic case work either the measured or the modelled data can be used as reference data for the overall distribution of Sr-87/Sr-86 values in Europe. (C) 2019 Elsevier B.V. All tights reserved.

The demand for ‘high-tech’ element resources (e.g., rare earth elements, lithium, platinum group elements) has increased with their continued consumption in developed countries and the emergence of developing economies. To provide a sound knowledge base for future generations, it is necessary to identify the spatial distribution of critical elements at a broad-scale, and to delineate areas for follow-up surveys. Subsequently, this knowledge can be used to study possible environmental consequences of the increased use of these resources. In this paper, three critical industrial elements (Sb, W, Li) from low-sampling density geochemical mapping at the continental-scale are presented. The geochemical distribution and spatial patterns have been obtained from agricultural soil samples (Ap-horizon, 0–20 cm; N = 2108 samples) collected at a density of 1 site per 2500 km2 and analysed by ICP-MS after a hot aqua regia digestion as part of the GEMAS (GEochemical Mapping of Agricultural and grazing land Soil) soil-mapping project in 33 European countries. Most of the geochemical maps show exclusively natural background element concentrations with minor, or without, anthropogenic influence. The maximum extent of the last glaciation is marked as a discrete element concentration break, and a distinct difference occurs in element concentration levels between the soil of northern and southern Europe, most likely an effect of soil genesis, age and weathering. The Sb, W and Li concentrations in soil provide a general overview of element spatial distribution in relation to complexity of the underlying bedrock and element mobility in the surface environment at the continental-scale. The chemical composition of agricultural soil represents largely the primary mineralogy of the source bedrock, the effects of pre- and post-depositional chemical weathering, formation of secondary products, such as clays, and element mobility, either by leaching or mineral sorting. Observed geochemical patterns of Li, W and Sb can be often linked with known mineralisation as recorded in the ProMine Mineral Database, where elements in question occur either as main or secondary resources. Anthropogenic impact has only been identified locally, predominantly in the vicinity of large urban agglomerations. Unexplained high element concentrations may potentially indicate new sources for high-tech elements and should be investigated at a more detailed scale.

IntroductionSocial vulnerability is known to be related to ill health. When a pregnant woman is socially vulnerable, the ill health does not only affect herself, but also the health and development of her (unborn) child. To optimise care for highly vulnerable pregnant women, in Rotterdam, a holistic programme was developed in close collaboration between the university hospital, the local government and a non-profit organisation. This programme aims to organise social and medical care from pregnancy until the second birthday of the child, while targeting adult and child issues simultaneously. In 2014, a pilot in the municipality of Rotterdam demonstrated the significance of this holistic approach for highly vulnerable pregnant women. In the ‘Mothers of Rotterdam’ study, we aim to prospectively evaluate the effectiveness of the holistic approach, referred to as targeted social care.Methods and analysisThe Mothers of Rotterdam study is a pragmatic prospective cohort study planning to include 1200 highly vulnerable pregnant women for the comparison between targeted social care and care as usual. Effectiveness will be compared on the following outcomes: (1) child development (does the child show adaptive development at year 1?) and (2) maternal mental health (is maternal distress reduced at the end of the social care programme?). Propensity scores will be used to correct for baseline differences between both social care programmes.Ethics and disseminationThe prospective cohort study was approved by the Erasmus Medical Centre Ethics Committee (ref. no. MEC-2016–012) and the first results of the study are expected to be available in the second half of 2019 through publication in peer-reviewed international journals.Trial registration numberNTR6271; Pre-results.

Epidemiological studies have shown an association between physical activity and sleep, but it is unclear what the temporal order of this association is and whether it differs for depressed patients and healthy controls. Using a multiple repeated observations design, 27 depressed and 27 pair-matched nondepressed participants completed daily measurements of subjective sleep quality and duration during 30 consecutive days while an accelerometer continuously registered their physical activity. Changes in sleep duration, not quality, predicted next-day changes in physical activity (B = -0.21, p

Assessing performance of mental health services (MHS) providers merely by their outcomes is insufficient. Process factors, such as treatment cost or duration, should also be considered in a meaningful and thorough analysis of quality of care. The present study aims to examine various performance indicators based on treatment outcome and two process factors: duration and cost of treatment. Data of patients with depression or anxiety from eight Dutch MHS providers were used. Treatment outcome was operationalized as case mix corrected pre-to-posttreatment change scores and as reliable change (improved) and clinical significant change (recovered). Duration and cost were corrected for case mix differences as well. Three performance indicators were calculated and compared: outcome as such, duration per outcome, and cost per outcome. The results showed that performance indicators, which also take process variability into account, reveal larger differences between MHS providers than mere outcome. We recommend to use the three performance indicators in a complementary way. Average pre-to-posttreatment change allows for a simple and straightforward ranking of MHS providers. Duration per outcome informs patients on how MHS providers compare in how quickly symptomatic relief is achieved. Cost per outcome informs MHS providers on how they compare regarding the efficiency of their care. The substantial variation among MHS providers in outcome, treatment duration and cost calls for further exploration of its causes, dissemination of best practices, and continuous quality improvement.

A reliable overview of measured concentrations of TC, TN and TS, TOC/TN ratios, and their regional distribution patterns in agricultural soil at the continental scale and based on measured data has been missing - despite much previous work on local and the European scales. Detection and mapping of natural (ambient) background element concentrations and variability in Europe was the focus of this work. While total C and S data had been presented in the GEMAS atlas already, this work delivers more precise (lower limit of determination) and fully quantitative data, and for the first time high-quality TN data. Samples were collected from the uppermost 20 cm of ploughed soil (Ap horizon) at 2108 sites with an even sampling density of one site per 2500 km2 for one individual land-use class (agricultural) across Europe (33 countries). Laboratory-independent quality control from sampling to analysis guaranteed very good data reliability and accuracy. Total carbon concentrations ranged from 0.37 to 46.3 wt% (median: 2.20 wt%) and TOC from 0.40 to 46.0 wt% (median: 1.80 wt%). Total nitrogen ranged from 0.018 to 2.64 wt% (median: 0.169 wt%) and TS from 0.008 to 9.74 wt% (median: 0.034 wt%), all with large variations in most countries. The TOC/TN ratios ranged from 1.8 to 252 (median: 10.1), with the largest variation in Spain and the smallest in some eastern European countries. Distinct and repetitive patterns emerge at the European scale, reflecting mostly geogenic and longer-term climatic influence responsible for the spatial distribution of TC, TN and TS. Different processes become visible at the continental scale when examining TC, TN and TS concentrations in agricultural soil Europe-wide. This facilitates large-scale land-use management and allows specific areas (subregional to local) to be identified that may require more detailed research.

The GEMAS (geochemical mapping of agricultural soil) project collected 2108 Ap horizon soil samples from regularly ploughed fields in 33 European countries, covering 5.6 million km(2). The

International audience; Agricultural soil (Ap-horizon, 0–20 cm) and grazing land soil (Gr-horizon, 0–10 cm) samples were collected from a large part of Europe (33 countries, 5.6 million km2) as part of the GEMAS (GEochemical Mapping of Agricultural and grazing land Soil) soil mapping project. GEMAS soil data have been used to provide a general view of element mobility and source rocks at the continental scale, either by reference to average crustal abundances or to normalized patterns of element mobility during weathering processes. The survey area includes a diverse group of soil parent materials with varying geological history, a wide range of climate zones, and landscapes.The concentrations of Ge in European soil were determined by ICP-MS after an aqua extraction, and their spatial distribution patterns generated by means of a GIS software.The median values of Ge and its spatial distribution in Ap and Gr soils are almost the same (0.037 vs. 0.034 mg/kg, respectively). The majority of Ge anomalies is related to the type of soil parent material, namely lithology of the bedrock and minor influence of soil parameters such as pH, TOC and clay content. Metallogenic belts with sulphide mineralisation provide the primary source of Ge in soil in several regions in Europe, e.g. in Scandinavia, Germany, France, Spain and Balkan countries.Comparison with total Ge concentrations obtained from the Baltic Soil Survey shows that aqua regia is a very selective method with rather low-efficiency and cannot provide a complete explanation for Ge geochemical behaviour in soil. Additionally, large differences in Ge distribution are to be expected when different soil depth horizons are analysed.

The international guideline for complex posttraumatic stress disorder (ptsd) from the International Society for Traumatic Stress Studies (istss) recommends treatment in phases, starting with stabilisation treatment. Different forms of stabilisation training have been developed the past few years, one being short-term group stabilisation training.br/AIM: To map out the effects of the short-term group training.br/METHOD: The research implemented a pre-post design. The training consisted of five group sessions. Questionnaires (bsi, OQ 45 and svl-15) were completed both prior to and after the training. Four domains were assessed: psychosymptomatology in general, depressive symptoms, problems with interpersonal functioning and ptsd-related symptoms. The effect of the training was calculated by paired t-tests.br/RESULTS: The questionnaires of the 47 participants who had completed the training were analysed. No significant decrease was observed during the stabilisation training concerning the symptoms of the four evaluated domains.br/CONCLUSION: Contrary our expectations, a short-term group-based stabilisation training does not seem to have added value when treating patients with complex ptsd. The results correspond with a recent trend in which the effectiveness of other stabilising methods is questioned. Alternative treatment options are discussed.

Sleep and physical activity are related, but the direction of this relationship is unclear and it is not known whether the direction differs in depressed and non-depressed persons.To study the bidirectional relationship between physical activity and sleep in daily life by making repeated measurements in depressed and non-depressed people.Every day for 30 consecutive days each depressed (N = 27) and non-depressed (N = 27) participant in our study had to complete an electronic questionnaire relating to subjective sleep quality and sleep duration and were required to wear an accelerometer that recorded physical activity.Multi-level analysis showed that an increase in subjective sleep duration resulted in a decrease in physical activity. The differences between individuals with regard to the direction and strength of this relationship were significant. Changes in physical activity did not predict changes in sleep quality or sleep duration. We did not find any differences in the relationships for depressed and non-depressed participants.Change in sleep duration predicts change in physical activity, although there was significant heterogeneity in the results for individuals. Our findings underline the importance of further research and of the development of interventions that are tailored to the precise needs of the individual patient.

Drop-out is a complex problem in mental health care and in STEPPS. Research has revealed a variety of predicting factors and has produced contradictory results.To investigate whether the information available at the start of STEPPS can pinpoint predictors of drop-out.The ROM data for 150 patients were used to test the link between the following factors: age, gender, education, employment, substance abuse, anxiety, hostility, interpersonal relations, responsibility and social concordance with drop-out. The method used for testing was logistic regression analysis.Factors that contributed significantly to the prediction of drop-out were gender and employment status. These factors made up 16% of the explained variation (R2 Nagelkerkes) in drop-out. Gender was the strongest predictive factor. Concerning the other factors, no differences were found between groups (drop-out and non-dropouts).In its present form STEPPS does not suit a large number of the male participants. Drop-out during STEPPS is hard to predict on the basis of ROM-questionnaires. Future research should focus on preconditions and marginal conditions that influence patients to complete their training.

Introduction: Within the Netherlands, large differences in perinatal outcomes are observed between groups with different ethnicities and socioeconomic status. Pregnant women with multiple social problems are more at risk of poor perinatal outcomes. This is also true for the municipality of Rotterdam, thus a holistic program was developed to optimize care for highly vulnerable pregnant women. The Mothers of Rotterdam MoR is an unique program that combines social and medical care from pregnancy until the second birthday of the child. MoR has a central registration point where socialcare can be requested for pregnant women living in Rotterdam who are social vulnerable. Registration is easily accessible and pregnant women can also apply for care themselves. An intake by a social professional in the home environment is scheduled with each pregnant woman to assess the amount and intensity of their problems. This study aims to determine how problems, registered at referral, represent those determined by a social professional after the home visit. Methods: A prospective cohort study containing 128 participants, who were referred to MoR between 01-01-2016 and 30-05-2017, was conducted to investigate the differences in problems indicated at referral and after the home visit. The referring party filled out a checklist including potential social- and medical problems. This checklist consisted of 47 problems divided over 8 domains. The social professional of MoR filled out the same checklist after the first home visit. The problem scores were constructed by counting the number of problems indicated on the checklist. A Wilcoxon signed rank test was used to test the differences between the problems scored on both checklists. Results: 176 pregnant women received care from MoR. 13 of them 7.4% were self-referred pregnant women. From 128 pregnant women both checklists were available for evaluation. 95 pregnant women 74% were referred by a medical professional and 33 pregnant women 26% were referred by a social professional. The social professionals scored a significantly higher number of problems p=0.004 after the first home visit than the referring party. Discussion: The setting in which the checklist is completed, behind a desk versus in the home environment, contributes to the assessment of the problems. A medical professional has less knowledge of social problems and besides their medical responsibility, they have less time to pay attention to this. Conclusions: Social professionals detect more problems after a home visit than medical and social professional at referral. Lessons learned: A home visit by a social professional is of added value in the identification of all social problems that are present in our population of socially vulnerable pregnant women. Limitations: The information about the checklist at registration is missing from the self-referral pregnant women and therefore not analyzed. suggestions for future research: We suggest to validate the items on the checklist and to use prediction modeling to optimize the checklist. This can help a medical or social professional to make a quick and accurate assessment of the problems.

Introduction: Evidence shows that low socioeconomic status SES is related to decreased mental health of the individual. Exposure to determinants such as low income, unemployment, being a single parent, and living in a deprived neighbourhood increases levels of chronic stress. This results in diminishing overall resources to cope with stressful situations, making them more vulnerable for unhealthy and unfavourable behaviour, and a decreased health status of the individual. These negative effects do not only create a vulnerability in the individual for poor health, but effect the next generation already during pregnancy. Therefore, policies targeting highly vulnerable pregnant women potentially have far-reaching effects. Within the Netherlands, Rotterdam has the highest percentage of children growing up in poverty 25%, in a family living on welfare 19%, with a low parental level of education 20%, and with one or both parents being unemployed 10%. Furthermore, 57% of the children in Rotterdam grow up in a deprived neighbourhood. Description of policy context, objective and targeted population: In the Netherlands, social care is usually carried out by a community social care team: a multidisciplinary team of professionals located in the neighbourhood of their clients. Based on the needs of the client, care is either focused on adult issues such as financial problems or problems regarding children and adolescents such as underperformance at school. This strict separation of the social care in adult- and child-care is suboptimal in the care of highly vulnerable pregnant women, since impact of risk and adversity is not limited to one generation and can simultaneously affect both parents and children. Within Rotterdam, the Erasmus Medical Centre, the municipality, and a non-profit organization are combining their expertise to improve the psycho-social situation of highly vulnerable pregnant women. Ultimately, this will result in a healthy development of the unborn child. This targeted social care integrates medical and social care in a long-term and intensive support program. This support focusses on all issues a women and her child can encounter during pregnancy and after giving birth: health, housing, employment, social functioning, mother-child interaction and child development. In the “Mothers of Rotterdam” study, we aim to prospectively evaluate the effectiveness of the holistic approach compared to regular care provided by the community social care teams. Highlights and transferability: This program promotes societal valorisation of knowledge through valuable collaboration between academics, government and a non-profit organization by supporting the healthy development of future generations. Due to the pragmatic character of the study, randomization of participants is not possible, but is determined by a natural experiment. Therefore, this ecologically valid study design allows for results directly generalizable to the actual population, although it increases the risk of true effects being masked by unmeasured confounders. Conclusion: This study will provide unique insights into a notoriously difficult to reach population of highly vulnerable pregnant women, their problems and potential care pathways for these problems.

Tendon injuries are notorious for their slow and functionally inferior healing. Intratendinous application of platelet-rich plasma (PRP) has been reported to stimulate the repair process of tendon injuries, but there is little conclusive evidence for its effectiveness. A placebo-controlled experimental trial was performed to test the hypothesis that a single intratendinous PRP treatment enhances the quality of tendon repair, as evidenced by improved biochemical, biomechanical, and histological tissue properties. In six horses, tendon lesions were created surgically in the Superficial Digital Flexor Tendons (SDFT) of both front limbs, one of which was treated with PRP and the other with saline. After 24 weeks, the tendons were harvested for biochemical, biomechanical, and histological evaluations. Collagen, glycosaminoglycan, and DNA content (cellularity) was higher in PRP-treated tendons (p = 0.039, 0.038, and 0.034, respectively). The repair tissue in the PRP group showed a higher strength at failure (p = 0.021) and Elastic Modulus (p = 0.019). Histologically, PRP-treated tendons featured better organization of the collagen network (p = 0.031) and signs of increased metabolic activity (p = 0.031). It was concluded that PRP increases metabolic activity and seems to advance maturation of repair tissue over nontreated experimentally induced tendon lesions, which suggests that PRP might be beneficial in the treatment of clinical tendon injuries. (C) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:211-217, 2010

Background & aims: Optimal nutritional therapy for energy and protein in critically ill, mechanically ventilated patients can be defined as: providing calories matched with the measured energy expenditure and delivery of protein in an amount of 1.2-1.5 g/kg pre-admission weight/day. Several enteral nutritional products are available with different energy/protein proportions. We developed an algorithm to choose the nutritional formula that combines optimal energy and protein supply for individual patients. Methods: The energy and protein values of three nutritional formulas were used together with an aimed provision of 1.2-1.5 g protein/kg/day to construct a nomogram. From that, an algorithm followed, which was tested retrospectively in 203 mechanically ventilated patients with a normal BMI and known values for energy expenditure and weight. Results: In the nomogram cut-off points for energy/weight ratios were: 19.0-23.8 for a normal energy/high protein formula, 23.8-29.8 for a high energy/high protein formula and 30-37.5 for the normal energy/normal protein formula. The algorithm uses energy expenditure/body weight ratio of the patients to choose one of the three formulas. This resulted in an adequate provision of protein in 93% of the patients. Conclusion: The algorithm leads to provision of adequate amounts of protein and energy in the majority of critically ill, mechanically ventilated patients.

Objective The aim of this study was to investigate to what extent atypical antipsychotics, conventional antipsychotics and anticholinergics are prescribed simultaneously in daily clinical practice in Europe. Method A pharmaco-epidemiological study was carried out in which hospital pharmacists from 45 hospitals in Belgium, Denmark, France, Germany, The Netherlands and Scotland participated. Prescription data for 2,725 patients (mainly inpatients) who had been using an atypical antipsychotic for more than 6 weeks were analysed. Main outcome measure The frequencies of simultaneous prescription of atypical antipsychotics with other antipsychotics and/or anticholinergics. Results In this sample of patients with an atypical antipsychotic 42.1% was prescribed another antipsychotic (24.1% if low-potent antipsychotics were not included in the analysis) and 30.1% was prescribed an anticholinergic. In total 47.1% of patients were prescribed an atypical antipsychotic without any other antipsychotic or anticholinergic. Conclusion It is common practice to prescribe a combination of atypical antipsychotics and conventional antipsychotics and/or anticholinergics. This suggests that monotherapy involving an atypical antipsychotic is not considered to be an adequate treatment for a substantial number of patients in clinical practice.

The complete genome sequence of a single nucleocapsid nucleopolyhedrovirus recently isolated from Chrysodeixis chalcites (ChchNPV) was determined. The viral genome has a size of 149 622 bp and an overall G+C content of 39·1 mol%. The sequence contains 151 predicted open reading frames (ORFs) with a minimal size of 50 codons. The similarity of these ORFs with those of other completely sequenced baculoviruses was calculated using a newly developed database, named gecco. Phylogenetic analysis of the whole genome confirmed the evolutionary relationship of ChchNPV with group II NPVs, as did the absence of the NPV group I-specific gp64 gene. It is the first group II NPV to encode proliferating cell nuclear antigen. Most noteworthy is the presence of two ORFs encoding a class II cyclobutane pyrimidine dimer DNA photolyase. These two ORFs share only 45 % amino acid identity and have different promoter motifs. Twenty-two additional unique baculovirus genes were identified, including a gene encoding a novel putative RING finger protein with a possible homologue in poxviruses.

We introduce a method using the rheology of concentrated solutions to differentiate sensitively between nonbranched and branched architecture polymer melts. By modeling the concentration dependent shift in zero-shear viscosity using molecular tube theory for melt rheology, it is feasible to quantify the degree of long chain branching as well as the distribution of sizes of such branches, providing the class of branched material is known. The technique detects branched chains with the order of one entanglement length and greater. We apply the technique, already validated against monodisperse controlled-architecture polymers [D. R. Daniels et al. Rheol. Acta 40, 403 (2001)], to a series of industrially produced metallocene-catalyzed polyethylenes with an octene comonomer and two low density polyethylenes, diluted by the short chain alkane squalane. The dilution method compares favorably with direct solution methods, and holds promise of much greater sensitivity.

Background: Total parenteral nutrition (TPN) is an invasive and advanced rescue feeding technique that has acceptable short-term survival although at costs of substantial risks. Survival after the clinical use of TPN .6 mo is unknown. Objective: We determined long-term survival after clinical TPN use in a consecutive cohort who were attending an academic hospital. Design: The study included a prospective cohort with a retrospective analysis of all 537 consecutive episodes of TPN in 437 patients between January 2010 and April 2012. Follow-up was until October 2013 with a total follow-up of 608 patient-years. Survival was analyzed by using Kaplan-Meier and Cox regression. Results: Survival was 58% in 437 patients with a first-time use of TPN at an average of 1.5 y after the initiation of TPN. The mortality rate was 30 deaths/100 patient-years. Older age, admission at an intensive care unit or a nonsurgical department, lower body mass index, and an underlying malignancy were positively associated with mortality. Conclusion: TPN use, if correctly indicated, is a clinical sign of intestinal failure and a surrogate marker for markedly increased risk of mortality even .1.5 y after TPN use. This trial was registered at clinicaltrials.gov as NCT02189993 with protocol identification name TPN-01. Am J Clin Nutr doi: 10.3945/ajcn.114.087015.

Background Body-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors. Methods We pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57 161 coronary heart disease and 31 093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m2, or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators. Findings The HR for each 5 kg/m2 higher BMI was 1·27 (95% CI 1·23-1·31) for coronary heart disease and 1·18 (1·14-1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12-1·18) for coronary heart disease and 1·04 (1·01-1·08) for stroke, suggesting that 46% (95% CI 42-50) of the excess risk of BMI for coronary heart disease and 76% (65-91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28-35) of the excess risk for coronary heart disease and 65% (56-75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to

Objective The purpose of this study was to assess the frequency of persistent drug-induced movement disorders namely, tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia in a representative sample of long-stay patients with chronic severe mental illness. Method Naturalistic study of 209, mainly white, antipsychotic-treated patients, mostly diagnosed with psychotic disorder. Of this group, the same rater examined 194 patients at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. Results The frequencies of persistent movement disorders in the sample were 28.4% for TD, 56.2% for parkinsonism, 4.6% for akathisia and 5.7% for tardive dystonia. Two-thirds of the participants displayed at least one type of persistent movement disorder. Conclusions Persistent movement disorder continues to be the norm for long-stay patients with chronic mental illness and long-term antipsychotic treatment. Measures are required to remedy this situation.

Met literatuur, samenvatting en bijlagen

Met literatuur, samenvatting en bijlage

In 2007 a national guideline on perioperative nutrition was issued in the Netherlands. As external indicator for adequacy of nutritional therapy, the percentage of malnourished patients who reach at least 1.2 grams of protein on day 4 after admission was chosen by the Netherlands Health Care Inspectorate.We developed an algorithm that allows users to ask for advice on which artificial nutritional formula to prescribe and at which rate, assuring provision of adequate amounts of both protein and energy. Feedback on nutritional therapy is given to the users on a daily basis, and to the management per quarter. Both the advice and the feedback have been integrated in our data management system. The advice module is also available on-line.In the baseline situation over the first four quarters (2006) an average of 30.2% of patients who had a full day 4 in our unit reached the protein indicator. In the last six quarters post-implementation, the average percentage reached was 56.5% with values consistently over 50%. Changes were statistically significant at third quarter of 2007 (p0.05) and thereafter (p0.001). Results for day 7 of admission were unaffected, which indicates that targets were reached earlier during hospital stay.Our study shows that integration of nutritional advice and automatically generated feedback to users in a data management system consistently improves delivery of (early) nutrition.

Background Modern omics research involves the application of high-throughput technologies that generate vast volumes of data. These data need to be pre-processed, analyzed and integrated with existing knowledge through the use of diverse sets of software tools, models and databases. The analyses are often interdependent and chained together to form complex workflows or pipelines. Given the volume of the data used and the multitude of computational resources available, specialized pipeline software is required to make high-throughput analysis of large-scale omics datasets feasible. Results We have developed a generic pipeline system called Cyrille2. The system is modular in design and consists of three functionally distinct parts: 1) a web based, graphical user interface (GUI) that enables a pipeline operator to manage the system; 2) the Scheduler, which forms the functional core of the system and which tracks what data enters the system and determines what jobs must be scheduled for execution, and; 3) the Executor, which searches for scheduled jobs and executes these on a compute cluster. Conclusion The Cyrille2 system is an extensible, modular system, implementing the stated requirements. Cyrille2 enables easy creation and execution of high throughput, flexible bioinformatics pipelines.

To obtain a suitable species-specific microflora for a new rat SPF-unit, germ-free WAG/Rij rats were associated with a flora derived originally from selectively decontaminated Cpb:WU (Wistar) rats. Caecal and ileal contents of these rats had been cultured anaerobically (37°C) for 7 days and harvested. This cultured flora was given to germ-free Cpb : SE (Swiss) mice, which were kept in an isolator system and acted as a source of the flora to associate germ-free Wag/Rij rats. In these associated rats, several parameters indicative of the 'quality' of the intestinal micro flora were investigated and compared to those in rats with a mouse derived anaerobic microflora. Parameters included relative caecal weight, colonization resistance and the concentration of faecal bile acids. The cultured rat-derived microflora normalized the observed intestinal parameters better than the mouse derived microflora, and provided better colonization resistance. We conclude that culturing of intestinal contents of selectively decontaminated animals can be a useful way to obtain a species-specific donor-micro flora which can be used to start new SPF units.

Projectnr.: 176107.

Projectnr.: 176080

Projectnr.: 176058

Projectnr.: 176068

[1] Gas transfer rates were determined from vertical profile measurements of atmospheric dimethylsulfide (DMS) gradients over the equatorial Pacific Ocean obtained during the GasEx-2001 cruise. A quadratic relationship between gas transfer velocity and wind speed was derived from the DMS flux measurements; this relationship was in close agreement with a parameterization derived from relaxed eddy accumulation measurements of DMS over the northeastern Pacific Ocean. However, the GasEx-2001 relationship results in gas transfer rates that are a factor 2 higher than gas transfer rates calculated from a parameterization that is based on coincident eddy correlation measurements of CO2 flux. The measurement precision of both the profiling and eddy correlation techniques applied during GasEx-2001 is comparable; the two gas transfer data sets are in agreement within their uncertainty. Differences in the number of samples and the wind speed range over which CO2 and DMS fluxes were measured are likely causes for the observed discrepancy.

[1] Gas transfer rates were determined from relaxed eddy accumulation ( REA) measurements of the flux of dimethylsulfide (DMS) over the northeastern Pacific Ocean. This first application of the REA technique for the measurement of DMS fluxes over the open ocean produced estimates of the gas transfer rate that are on average higher than those calculated from commonly used parameterizations. The relationship between the total gas transfer rate and wind speed was found to be gas k(gas) = 0.53 (+/-0.05) U-10(2). Because of the effect of the airside resistance, the waterside transfer rate was up to 16% higher than kgas. Removal of the airside transfer component from the total transfer rate resulted in a relation between wind speed and waterside transfer of k(660) = 0.61 (+/-0.06) U-10(2). However, DMS fluxes showed a high degree of scatter that could not readily be accounted for by wind speed and atmospheric stability. It has to be concluded that these measurements do not permit an accurate parameterization of gas transfer as a function of wind speed.