Obesity treatment is by large ineffective long term, and more emphasis on the prevention of excessive weight gain in childhood and adolescence is warranted. To inform energy balance related behaviour (EBRB) change interventions, insight in the potential personal, family and school environmental correlates of these behaviours is needed. Studies on such multilevel correlates of EBRB among schoolchildren in Europe are lacking. The ENERGY survey aims to (1) provide up-to-date prevalence rates of measured overweight, obesity, self-reported engagement in EBRBs, and objective accelerometer-based assessment of physical activity and sedentary behaviour and blood-sample biomarkers of metabolic function in countries in different regions of Europe, (2) to identify personal, family and school environmental correlates of these EBRBs. This paper describes the design, methodology and protocol of the survey.
A school-based cross-sectional survey was carried out in 2010 in seven different European countries; Belgium, Greece, Hungary, the Netherlands, Norway, Slovenia, and Spain. The survey included measurements of anthropometrics, child, parent and school-staff questionnaires, and school observations to measure and assess outcomes (i.e. height, weight, and waist circumference), EBRBs and potential personal, family and school environmental correlates of these behaviours including the social-cultural, physical, political, and economic environmental factors. In addition, a selection of countries conducted accelerometer measurements to objectively assess physical activity and sedentary behaviour, and collected blood samples to assess several biomarkers of metabolic function.
The ENERGY survey is a comprehensive cross-sectional study measuring anthropometrics and biomarkers as well as assessing a range of EBRBs and their potential correlates at the personal, family and school level, among 10-12 year old children in seven European countries. This study will result in a unique dataset, enabling cross country comparisons in overweight, obesity, risk behaviours for these conditions as well as the correlates of engagement in these risk behaviours.
Despite large differences between countries and regions , prevalence of overweight and obesity among children and adolescents has risen across Europe in recent decades [1,2]. The most recent reports show that approximately 20% of the children in several European countries are overweight or obese [1,2]. Childhood overweight and obesity track into adulthood  and are linked to ill health . Obesity treatment is by large ineffective long term, and more emphasis on the prevention of excessive weight gain in childhood and adolescence is warranted.
Although genetic factors may influence the susceptibility of individuals to gain weight , there is consensus that changes in lifestyle behaviour are driving the obesity epidemic  rather than changes in biologic or genetic factors. A long-term positive energy balance - i.e. energy intake through food intake exceeds energy expenditure for body functions and physical activity - leads to storage of excess energy as fat, leading to weight gain, and eventually to the development of overweight and obesity. Prevention of unnecessary weight gain should thus target modifiable energy intake and energy expenditure behaviours, i.e. physical activity, sedentary, and dietary behaviours, also referred to as energy balance related behaviours (EBRBs). Recent research and reviews of the literature indicate that among schoolchildren specific EBRB are of specific relevance for obesity prevention [7-9]. These behaviours concern screen viewing behaviour (TV viewing and sedentary computer activities), intake of sugar sweetened beverages and breakfast consumption, and daily activities, i.e. active commuting to school, physical activity during recess, participation in sports and recreational physical activity. Additionally, recent evidence suggests that sleeping habits may also be relevant for energy balance . According to socio ecological and cognitive behavioural models, to inform EBRB change interventions, we need insight in the potential personal, family and school environmental correlates of these behaviours [11-14].
Studies on such multilevel correlates of EBRBs among schoolchildren in Europe are lacking. As part of the European Commission-funded "EuropeaN Energy balance Research to prevent excessive weight Gain among Youth" (ENERGY)-project , a cross-European school-based, family-involved survey study was conducted. This study aims to (1) provide up-to-date prevalence rates of measured overweight, obesity, self reported engagement in EBRBs, and objective accelerometer assessment of physical activity and sedentary behaviour and blood-sample biomarkers of metabolic function in countries in different regions of Europe, (2) to identify personal, family-environmental and school-environmental correlates of these EBRBs. This paper describes the design, methodology and protocol of the cross-sectional study.
A school-based cross-sectional survey was carried out between March and July 2010 in seven different European countries; Belgium, Greece, Hungary, the Netherlands, Norway, Slovenia, and Spain. The survey included anthropometric measurements, child questionnaires, parent questionnaires, school-staff questionnaires and school observations to measure EBRBs and potential individual and environmental correlates of these behaviours.
The project adhered to the Helsinki Declaration and the conventions of the Council of Europe on human rights and biomedicine. All participating countries obtained ethical clearance from the relevant ethical committees and ministries; in Belgium the survey was approved by the Medical Ethics Committee of the University Hospital Ghent; in Greece the survey was approved by the Bioethics Committee of Harokopio University; in Hungary the survey was approved by the Scientific and Ethics Committee of Health Sciences Council; in the Netherlands the survey was approved by the Medical Ethics Committee of the VU University medical center; in Norway the survey was approved by the National Committees for Research Ethics in Norway; in Slovenia the survey was approved by the National Medical Ethics Committee of the Republic of Slovenia; and in Spain the survey was approved by Clinical Research Ethics Committee of the Government of Aragón. Furthermore, research permission was, if necessary, obtained from local school authorities (local school boards and/or headmasters).
Sampling procedures and recruitment
Each country was represented by a local partner institute and each partner was responsible for the data collection in that country, with one of the partners acting as the overall coordinating centre. The procedure for sampling, data collection, and data handling for all parts of the survey was the same in all countries according to standardised protocols (see additional file 1 for the fieldwork protocol on recruitment and data collection).
The survey was carried out at schools among 10-12 year old children. Based on previous cross-European studies (e.g. the Pro-Children study ) a minimum sample of 1,000 school-children per country and one parent (the main caretaker) for each child was aimed. This minimum was required to enable analyses of the associations between correlates and specific EBRBs and to allow for within-country analyses as well as between-country comparisons. A total of 7,000 observations is sufficient to run prediction models with at least 10 predicting variables. In addition, it was calculated that with a power of 90% a between country difference of 5% in overweight prevalence rates will be detected as a significant difference (assuming an average overweight rate of 15%). For each country, the aim was to include 20 schools and 2 classes per school, resulting in approximately 50 children per school. In order to recruit at least 1,000 children it was necessary to over-sample. With an anticipated non-response rate of 10%, it was decided that approximately 1,100 schoolchildren were needed.
Sampling was national in Greece, Hungary, the Netherlands, and Slovenia. In Spain, schools in the region of Aragón were selected, Belgium selected schools from Flanders, the northern Dutch-speaking part of Belgium, and Norway selected schools from the southern regions of the country. Due to the differences in population distribution within the different regions, the sampling of schools was random, multi-staged, and stratified by degree of urbanization and consisted of 7 steps. First, the percentage of people living in municipalities with more than 20,000 inhabitants was calculated (Steps 1), then tertiles were formed based on this urbanization degree (Step 2), after which one province was randomly selected from each tertile (Step 3). From each of the three selected provinces one municipality was randomly selected (step 4). For these three selected municipalities, a list of all schools (Step 5) were created and sent to the coordinating partner. The coordinator then randomly selected the schools (Step 6). Based on the random selection of schools the countries started recruiting the schools following the provided rank order. If inclusion was insufficient additional schools were recruited from municipalities (i.e. in Belgium, Greece, and Hungary) or regions (i.e. in the Netherlands, Norway) (Step 7).
A school recruitment letter was sent to the headmaster or principal of the sampled schools, followed by a personal call, and if recruited a personal visit in order to answer any remaining questions and to explain the timeframe of the survey in their school. Following the school's agreement, parents received a letter explaining the study purpose and were asked for written consent for their child's and their own participation in the ENERGY-project. Passive informed consent was allowed in the Netherlands. If no parental consent was available for a child, the child did not participate in the study.
Accelerometer data for the assessment of physical activity and sedentary behaviour was collected in a selection of schools in Belgium, Greece, Hungary, and the Netherlands. The goal was to collect accelerometer data from at least 200 children per country from four schools (50 students per school). The selection of schools was balanced across the three cities as much as possible (selected from the three tertiles). The protocol of the accelerometer data collection is described in more detail elsewhere (Yıldırım, Verloigne, De Bourdeaudhuij, Androutsos, Manios, Felso, Kovacs, Doessegger, Bringolf-Isler, Te Velde, Chinapaw, unpublished data). Blood samples were collected in a selection of schools in Hungary and the Netherlands. The goal was to collect data from approximately 200 children who also wore accelerometers.
Table 1 shows the recruitment rate and response rate on the school, child and parent level.
Table 1. Overview of data collection and response rates per country
The children confidentially completed the child questionnaire during one school hour in the presence of the research assistant or project worker. Questionnaire administration did not take place on Mondays in order to avoid that weekend days were reported in answering the 24h recall questions. A research assistant guided the completion of the questionnaire and answered any questions from the participating children. In addition, anthropometric measurements were conducted. In order to measure the school environment, two observers independently conducted audits of the schools, school cafeterias, and school recreation facilities. A brief interview with a cafeteria manager and/or school representative was part of the audit. In addition a school representative at each school was asked to complete a school management questionnaire about the availability of food and physical activity related facilities within the school environment and about school policies. During the school visit, the children of a selection of schools in Greece, the Netherlands, Hungary, and Belgium were asked to wear accelerometers for six consecutive days. The children brought the devices back to school at least six days later and returned it to their teacher. From the children that were selected for wearing accelerometers in the Netherlands and Hungary, also blood samples were taken after an overnight fast. After these measurements, the children received breakfast.
The children received the parent questionnaire in a closed envelop to take home for completion by one of their parents. Completed parent questionnaires were brought back to the school by the children and were collected by the teacher.
The following measurement instruments and measures were administered: child questionnaire, parent questionnaire, accelerometers, anthropometric measures, school management questionnaire, interview with those responsible for the cafeteria/food retail and the vending machine, and a school environment audit instrument.
Development of measurement instruments
The selection of EBRBs and correlates measured in the questionnaires were based on the results of the literature reviews and secondary data analyses conducted in the earlier studies of the ENERGY project . The ENERGY-questionnaires were developed based on and using items from existing validated and relevant European questionnaires. If no established or valid questionnaires were available the ENERGY-team used existing items from relevant earlier or ongoing projects. If no such questionnaires or items were available, new items or questionnaire parts were constructed.
Since the measurement instruments had to be standardised for all participating countries, the child, parent, and school management questionnaires and staff interviews were developed in English, and translated into the language of each participating country. The English version of the child and parent questionnaire is shown on the ENERGY website (see http://projectenergy.eu webcite). The child and parent questionnaire were then back-translated by an official translator in order to detect any potential differences between the two. In case of differences, these were discussed within the ENERGY team and adaptations were made accordingly.
Pre-testing of measurement instruments
The child and parent questionnaires, audit instrument, school management questionnaire and staff interview were then first pre-tested among small samples in all participating countries to examine comprehensibility and duration of completion. Based on these results, the original version was adapted if necessary.
For the child questionnaire pre-test, five to ten 10-12 year old children from one primary school were requested to complete the questionnaire. In structured focus group interviews following a predefined check-list, the pupils were asked for their general opinion about the questionnaire, the comprehensibility and feasibility of the questionnaire and their opinion about the design of the questionnaire. In the pre-test of the parent questionnaire, a total of five to ten parents who had children aged 10-12 years old were recruited via schools. A telephone interview with the parents was conducted following a checklist in order to assess the parents' general opinion about the questionnaire, the comprehensibility and feasibility of the questionnaire and their opinion about its design. For the pre-testing of the school management questionnaire, two to three representatives of the school management (e.g. headmasters, adjunct head-masters) were asked to complete the questionnaire. Subsequently, they were interviewed by telephone about how the questions could be improved for content or phrasing, about the comprehensibility and feasibility of the questionnaire and about the design of the questionnaire. The audit instrument was pre-tested by conducting observations at one school by two observers separately. Two researchers per country were asked for their opinion and experience with regard to completing the audit instrument. Important aspects of the pre-test were the completeness of the forms and feasibility. One researcher performed the interview with the person responsible for the cafeteria/school shop and the vending machines. After the interview, the person(s) of the cafeteria/school shop and vending machine were asked to evaluate the interview.
After the pre-tests of the child questionnaire, parent questionnaire, school management questionnaire, staff interview and audit instrument, the measurements were adapted based on the results of the pre-tests.
Reliability and construct validity test
The reliability and content validity of the child and parent questionnaires were tested separately in all participating countries, in five schools per country using approximately 100 children and 50 parents per country for the reliability study and 15 children and 20 parents for the construct validity study. For the reliability test, a test‐retest design was used by comparing data from two completions of the questionnaire conducted one week apart, on the same weekday, under equal circumstances. To determine the (construct) validity of the questionnaire, the degree of agreement between the questionnaire and information from cognitive interviews administered after completion of the first questionnaire was assessed. The results of the test-retest study is described in more detail elsewhere (Singh, Chinapaw, Terwee, Vik, van Lippevelde, Fernandez, Kovacs, Jan, Manios, van der Sluis and Brug, unpublished data.; Singh, Vik, Chinapaw, Verloigne, Fernandez, Kovacs, Jan, Manios, Martens, and Brug, unpublished data).
The child questionnaire assessed self-reported levels of EBRBs, and personal and family environmental correlates.
Energy Balance Related Behaviours
Table 2 shows the EBRBs (i.e. dietary behaviours, physical activity, sedentary, and dieting behaviour) assessed in the child questionnaire. Dietary intake was assessed with food frequency questions referring to a general week and a 24-hour recall question . Physical activity behaviours (i.e., commuting to school, activity during recess, sports/physical activity behaviour during leisure time) and sedentary behaviour (i.e., television viewing and computer time) were assessed with frequency questions referring to a general week and a 24-hour recall question . In addition, dieting behaviour was assessed by two items, one using a frequency score of the last year and one on the current dieting behaviour informed by the restrained eating questions from the Three Factor Eating Questionnaire .
Table 2. Dietary, Physical activity, sedentary, sleeping and dieting behaviour measured in the child en parent questionnaire
Child characteristics, such as gender, date of birth, ethnicity, and family status of the child were assessed using one question. Attitude, knowledge of health promotion recommendation with regard to the specific EBRB, self-efficacy, health beliefs, preference/liking and habit strength were assessed for all dietary behaviours, physical activity/sport behaviours, and television viewing using one question with a five-point answer format. These items were informed by the Pro Children questionnaire . Table 3 shows the assessed personal variables, their description and the questionnaire items.
Table 3. Measurement items of each specific correlates per EBRB of the Child Questionnaire
Family environmental variables
Table 3 shows the assessed family environmental variables, their description and the items used in the ENERGY questionnaire. In line with the ANGELO framework , these family environmental variables can be distinguished into social-cultural environmental factors (i.e. parental subjective norm, parent modelling, and parental support), political environmental factors (i.e. parental rules), physical environmental variables (i.e. situations where the EBRB was performed and home availability), and economic or financial environmental factors (i.e. buying habits of soft drinks or fruit squash from children's pocket money, and the influence of price changes). All family environmental variables were assessed by single items, with the exception of parental rules (assessed by three items) by means of a 5-point Likert scale. The items on the environmental variables were informed by the Pro Children Questionnaire  and the ENDORSE study questionnaire  and informed by recent reviews of the literature [20,21]. The additional items on the economic environment were developed for this project, informed by insights from a recent study .
School environmental variables
Social-cultural factors related to the school environment (i.e. peer subjective norm and peer modelling) were assessed by single items using 5-point Likert scales. The items were again informed by the ProChildren  and ENDORSE questionnaire .
In the parent questionnaire, self-reported levels of EBRBs as well as personal and family environmental variables were assessed.
Energy Balance Related Behaviours
Questions on EBRBs were similar to the child questionnaire (Table 3). Dietary intake, physical activity behaviours, and sedentary behaviour were assessed with frequency questions referring to a general week and were relevant to adult life . In addition, dieting behaviour was assessed using two questions using a five point Likert scale, and a rating scale with scores from 1 (no restrained eating) to 8 (much restrained eating) how much the parent restraint him/herself in eating, informed by restrained eating questions from the Three Factor Eating Questionnaire . Finally the parents were asked about the sleeping habits of their child by means of three questions informed by the HBSC questionnaire .
Parental status, age, marital status, weight, height, educational level, occupational status, ethnicity child, and date of birth child, were assessed using one question.
Family environmental variables
Table 4 shows the family environmental variables included in the parent questionnaire, its description and the questionnaire items. The items were again based on and informed by the Pro Children and ENDORSE parent Questionnaires [18,19]. The family environmental correlates could be distinguished into social environmental correlates (i.e. parental practices including parental beliefs, parental rules and parental modelling, automaticity of the behaviour and the nagging behaviour of the child), physical environmental variables (i.e. home availability), and economic environmental variables (i.e. influence of pricing on child's behaviour; influence of pricing on own behaviour; price consciousness of the child and amount of provided pocket money for food products). The variables were assessed by one or more items using a five-point answering format, except the amount of provided pocket money for food and beverage products that was measured with an 8 point scale, ranging from 0 (I do not give money to my child) to 8 (more than €51 Euro per week (or the approximate equal amount in the local currency)).
Table 4. Measurement items of each specific correlates per EBRB of the Parent Questionnaire
School management questionnaire
The school management questionnaire was developed to describe the variation in food and physical activity related facilities and items within the school environment and to get insight into school policies and was informed by the Pro Children staff questionnaire , ENDORSE study , ANGELO framework  and the IDEA study . The questionnaire was completed by the school manager. Table 5 shows the items and answer format of the school management questionnaire. In addition to general characteristics of the school, the questionnaire addressed the physical environment (i.e. Opportunities to eat/drink and be physically active, such as offering/practicing any additional opportunities to be physically active; perceived safety to walk or bike to school; scheduled times to eat main meals or a "snack"); the social environment related to healthy eating and physical activity (i.e. role modelling teachers; social support teachers; social support parents); and the political environment concerning regulations and practices pertaining to food/drinks, physical activity, and health. Lastly, economic environmental variables related to eating/drinking and physical activity were assessed (i.e. which economic factors/sponsorships have been used, whether the school participated in national or regional campaigns using rewards for the pupils).
Table 5. School management questionnaire
Audit instrument for school environment
Partly based on the audit instrument used in the ENDORSE study , the ENERGY-team developed an audit instrument to assess the availability, accessibility, and commercial advertising of food and drinks and also identify the opportunities to stimulate physical activity within the school environment. At each school, two research assistants completed the audit instrument independently.
Table 6 shows the items and answer formats of the audit instrument. The audit instrument consisted of nine parts: (1) food/drink available in the cafeteria; (2) food/drink available in vending machines; (3) subscription programs; (4) commercial advertising; (5) bicycle parking; (6) equipment for recess; (7) indoor physical activity facilities; (8) outdoor physical activity facilities; and (9) other information of outdoor areas. The audit instrument had a 'tick box' answering format and included observation of objective characteristics. When subjective characteristics such as 'state of maintenance of the school yard', or 'condition of the bicycling parking' were reported, photographs were taken.
Table 6. Audit instrument for school environment
In each country, at least two trained research assistants measured body height, weight, and waist circumference according to a standardized protocol. The children were measured without shoes and were allowed to wear light clothing, such as a t-shirt and shorts/short pants. Body height was measured with a Seca Leicester Portable stadiometer with an accuracy of 0.1 cm. Weight was measured with a calibrated electronic scale SECA 861 with an accuracy of 0.1 kg. The waist circumference was measured with the circumference measuring band SECA 201 to the nearest 0.1 cm.
Two readings of each measurement (weight, height and waist) were obtained to assure accuracy. If the two readings differed more than 1% then a third measurement was taken. All three measurements were recorded and the outlier was excluded during the data cleaning process. The researcher was not allowed to provide the child with their weight and waist circumference measurement results.
Training of research assistants
Since the precision of the anthropometrical measurements play an important role, the ENERGY-project team aimed to minimise the measurement error within and across countries. Therefore at one of the ENERGY meetings, at least one researcher per participating country was trained for the anthropometry measures. The intra-rater reliability rates ranged from 0.999 to 1.00 for weight and height measurements and 0.942 to 0.999 for waist measurements. The inter-rater reliability was 1.00 for weight and height measurements and 0.990 for waist circumference measurements.
Additional measurement instruments in a selection of countries
Blood samples were taken in order to assess the following blood parameters: fasting plasma glucose, C-peptide, total cholesterol, high density lipoprotein cholesterol, and triglycerides. Capillary blood was collected with a finger prick using a well-validated collection kit developed for ambulatory purposes (Demecal, Haarlem, The Netherlands) . These procedures are similar to the procedures of the Amsterdam Birth Cohort Development (ABCD) study .
Triaxis (GT3X) and Uniaxis (GT1M) Actigraph models were used to collect data on physical activity and sedentary behaviour. Trained research assistants taught the children how to correctly wear the accelerometers on the right side of the waist. Children were asked to wear the accelerometer for six consecutive days (including at least one weekend day) except at night while sleeping or during any water activities (e.g., bathing, swimming). Time intervals (epochs) were set to 15 seconds. Teachers were informed about the procedures and asked to remind the children to wear the devices every day. Additionally, the children and parents received a brochure about accelerometer use and a diary. We asked children to write down the time of getting up in the morning and going to bed for sleeping; the time and reason why the device was removed for 5 minutes or more for any activity such as swimming, or showering; and whether the wearing day was a school day, half-school day or non-school day.
Data Handling and Transformation
The child and parent questionnaires from all countries were shipped to the coordinating centre in the Netherlands and were there scanned and the data were transferred to SPSS files. The data of the audit instrument, school management questionnaire, and anthropometry data was entered manually into an Excel file by the researchers in each country, and converted into SPSS files, sent to the coordinating centre and there merged and checked by a data manager.
The following quality checks on data entry were performed. Of the anthropometry measurements, 10% were entered twice in an Excel sheet by two separate researchers and cross-checked. Of the audit instrument and the school management questionnaire, 20% of the data were entered in the Excel files by two separate researchers, followed by another cross-check. The raw data of the child and parent questionnaires were provided with variable labels, value labels, and missing value labels (see additional file 2 for the codebooks) and cleaned on double records, non-existing participants, missing values on compulsory questions, out-of-range values, and inconsistencies. The final cleaned data files from all measurement sources and countries were combined based on the child and/or school ID to form the final raw data file. The cleaned data file was then submitted to recoding and transformations to create and calculate variables ready for analyses.
Descriptive analyses will be performed first. Subsequently bivariate and multivariate models will be tested using a range of regression and other analyses to test correlates and mediation models of overweight, obesity, metabolic outcomes and EBRBs. Since the data of the children are clustered within classes and schools, which are clustered within countries, data will be analysed using multilevel analyses when appropriate. The analyses will be conducted on the international sample as well as country or region specific analyses.
The ENERGY survey is a comprehensive cross-sectional study collecting data on anthropometrics, physical activity behaviours and biomarkers as well as assessing a range of EBRBs and their potential determinants at the personal, school environment and family environment levels, among 10-12 year old children in seven European countries. This study will result in a unique data set, enabling cross country comparisons in overweight, obesity, risk behaviours for these conditions as well as the correlates of engagement in these risk behaviours.
An important strength of the ENERGY-survey study concerns the number of participating countries from different regions in Europe including countries that lack data on EBRB and potential correlates among schoolchildren. In addition, the data set allows unique comparisons of EBRBs and their correlates between a diversity of countries and regions. Another strength of the study is the range of potential relevant EBRBs included as well as the broad range of potential personal and environmental correlates of these behaviours. The objective measures of height, weight and waist circumference from all participating children, as well as accelerometer measures of physical activity and sedentary behaviour and blood samples from subgroups of respondents, further enriches the data set. All these measurements were obtained according to standard methodology and protocols in all participating countries.
The ENERGY-survey also has several potential weaknesses. Although we have obtained several measurements objectively (e.g. height, weight, waist circumference), other measures are self-reported and thus liable to social desirability and recall bias. In addition, to lower the burden for children and parents, the number of items that could be included in the questionnaire was firmly restricted. Therefore, we chose to assess the correlates with only a few or single-item measures, possibly reducing the reliability and increasing measurement error. However, previous analyses showed that the correlates measured with 1-item questions showed significant associations with EBRBs . A further weakness of the ENERGY survey is its cross-sectional design. This means that we will be able to explore correlates of EBRB and obesity, but not true determinants. Finally, there were some variations in sampling between countries that may reduce the validity of cross country comparisons. Nevertheless, we believe that the ENERGY-project with its cross-European approach is a unique endeavour to study overweight prevalence, associated EBRBs, and their potential personal, family environmental, school environmental and economic environmental correlates in different European countries.
The authors declare that they have no competing interests.
STV and JB developed the concept and design of the ENERGY study. MVS, STV and JB drafted the manuscript. All other co-authors have been involved in the development, coordination and/or implementation of the ENERGY survey. All authors have read and approved the manuscript.
This paper was published on behalf of the ENERGY-consortium. The ENERGY-project is funded by the Seventh Framework Programme (CORDIS FP7) of the European Commission, HEALTH (FP7-HEALTH-2007-B), Grant agreement no. 223254 and with additional support from the Netherlands Organisation for Health Research and Development (Grant number 50-50150-98-002). The contribution of MVS was funded by Netherlands Organisation for Health Research and Development (Grant number 121520002). The content of this article reflects only the authors' views and the European Community is not liable for any use that may be made of the information contained therein.
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