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Climate change is testing the resilience of forests worldwide pushing physiological tolerance to climatic extremes. Plant functional traits have been shown to be adapted to climate and have evolved patterns of trait correlations (similar patterns of distribution) and coordinations (mechanistic trade‐off). We predicted that traits would differentiate between populations associated with climatic gradients, suggestive of adaptive variation, and correlated traits would adapt to future climate scenarios in similar ways. We measured genetically determined trait variation and described patterns of correlation for seven traits: photochemical reflectance index (PRI), normalized difference vegetation index (NDVI), leaf size (LS), specific leaf area (SLA), δ13C (integrated water‐use efficiency, WUE), nitrogen concentration (NCONC), and wood density (WD). All measures were conducted in an experimental plantation on 960 trees sourced from 12 populations of a key forest canopy species in southwestern Australia. Significant differences were found between populations for all traits. Narrow‐sense heritability was significant for five traits (0.15–0.21), indicating that natural selection can drive differentiation; however, SLA (0.08) and PRI (0.11) were not significantly heritable. Generalized additive models predicted trait values across the landscape for current and future climatic conditions (>90% variance). The percent change differed markedly among traits between current and future predictions (differing as little as 1.5% (δ13C) or as much as 30% (PRI)). Some trait correlations were predicted to break down in the future (SLA:NCONC, δ13C:PRI, and NCONC:WD). Synthesis: Our results suggest that traits have contrasting genotypic patterns and will be subjected to different climate selection pressures, which may lower the working optimum for functional traits. Further, traits are independently associated with different climate factors, indicating that some trait correlations may be disrupted in the future. Genetic constraints and trait correlations may limit the ability for functional traits to adapt to climate change. We tested whether functional traits of an important tree species in southwestern Australia were genetically determined and able to undergo selection. Our results suggest that some traits are heritable (Water Use Efficiency) while others are not (SLA), indicating that in the future, under different climates, selection will differentially effect traits. Therefore, it is likely that current trait combinations will change with climate.

Background: There is a lack of common surveillance systems providing comparable figures and temporal trends of the prevalence of overweight (OW), obesity and related risk factors among European preschool and school children. Comparability of available data is limited in terms of sampling design, methodological approaches and quality assurance. The IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health Effects in Children and infantS) study provides one of the largest European data sets of young children based on state-of-the-art methodology. Objective: To assess the European distribution of weight status according to different classification systems based on body mass index (BMI) in children (2.0–9.9 years). To describe the prevalence of weight categories by region, sex, age and socioeconomic position. Design: Between 2007 and 2010, 18 745 children from eight European countries participated in an extensive, highly standardised protocol including, among other measures, anthropometric examinations and parental reports on socio-demographic characteristics. Results: The combined prevalence of OW/obesity ranges from more than 40% in southern Europe to less than 10% in northern Europe. Overall, the prevalence of OW was higher in girls (21.1%) as compared with boys (18.6%). The prevalence of OW shows a negative gradient with social position, with some variation of the strength and consistency of this association across Europe. Overall, population groups with low income and/or lower education levels show the highest prevalence of obesity. The use of different reference systems to classify OW results in substantial differences in prevalence estimates and can even reverse the reported difference between boys and girls. Conclusions: There is a higher prevalence of obesity in populations from southern Europe and in population groups with lower education and income levels. Our data confirm the need to develop and reinforce European public health policies to prevent early obesity and to reduce these health inequalities and regional disparities.

Objective: The aim of the study was to assess the associations of individual and combined physical fitness components with single and clustering of cardio-metabolic risk factors in children. Subjects/methods: This 2-year longitudinal study included a total of 1635 European children aged 6–11 years. The test battery included cardio-respiratory fitness (20-m shuttle run test), upper-limb strength (handgrip test), lower-limb strength (standing long jump test), balance (flamingo test), flexibility (back-saver sit-and-reach) and speed (40-m sprint test). Metabolic risk was assessed through z -score standardization using four components: waist circumference, blood pressure (systolic and diastolic), blood lipids (triglycerides and high-density lipoprotein) and insulin resistance (homeostasis model assessment). Mixed model regression analyses were adjusted for sex, age, parental education, sugar and fat intake, and body mass index. Results: Physical fitness was inversely associated with clustered metabolic risk ( P <0.001). All coefficients showed a higher clustered metabolic risk with lower physical fitness, except for upper-limb strength ( β =0.057; P= 0.002) where the opposite association was found. Cardio-respiratory fitness ( β =−0.124; P <0.001) and lower-limb strength ( β =−0.076; P= 0.002) were the most important longitudinal determinants. The effects of cardio-respiratory fitness were even independent of the amount of vigorous-to-moderate activity ( β =−0.059; P= 0.029). Among all the metabolic risk components, blood pressure seemed not well predicted by physical fitness, while waist circumference, blood lipids and insulin resistance all seemed significantly predicted by physical fitness. Conclusion: Poor physical fitness in children is associated with the development of cardio-metabolic risk factors. Based on our results, this risk might be modified by improving mainly cardio-respiratory fitness and lower-limb muscular strength.

Objectives: The aim of this study is to present age- and sex-specific reference values of insulin, glucose, glycosylated haemoglobin (HbA1c) and the homeostasis model assessment to quantify insulin resistance (HOMA-IR) for pre-pubertal children. Methods: The reference population consists of 7074 normal weight 3- to 10.9-year-old pre-pubertal children from eight European countries who participated in at least one wave of the IDEFICS (‘identification and prevention of dietary- and lifestyle-induced health effects in children and infants’) surveys (2007–2010) and for whom standardised laboratory measurements were obtained. Percentile curves of insulin (measured by an electrochemiluminescence immunoassay), glucose, HbA1c and HOMA-IR were calculated as a function of age stratified by sex using the general additive model for location scale and shape (GAMLSS) method. Results: Levels of insulin, fasting glucose and HOMA-IR continuously show an increasing trend with age, whereas HbA1c shows an upward trend only beyond the age of 8 years. Insulin and HOMA-IR values are higher in girls of all age groups, whereas glucose values are slightly higher in boys. Median serum levels of insulin range from 17.4 and 13.2 pmol l −1 in 3–<3.5-year-old girls and boys, respectively, to 53.5 and 43.0 pmol l −1 in 10.5–<11-year-old girls and boys. Median values of glucose are 4.3 and 4.5 mmol l −1 in the youngest age group and 49.3 and 50.6 mmol l −1 in the oldest girls and boys. For HOMA-IR, median values range from 0.5 and 0.4 in 3–<3.5-year-old girls and boys to 1.7 and 1.4 in 10.5–<11-year-old girls and boys, respectively. Conclusions: Our study provides the first standardised reference values for an international European children’s population and provides the, up to now, largest data set of healthy pre-pubertal children to model reference percentiles for markers of insulin resistance. Our cohort shows higher values of Hb1Ac as compared with a single Swedish study while our percentiles for the other glucose metabolic markers are in good accordance with previous studies.

Objectives: To provide sex- and age-specific percentile values for levels of physical activity (PA) and sedentary time of European children aged 2.0–10.9 years from eight European countries (Sweden, Germany, Hungary, Italy, Cyprus, Spain, Belgium and Estonia). Methods: Free-living PA and sedentary time were objectively assessed using ActiGraph GT1M or ActiTrainer activity monitors in all children who had at least 3 days' worth of valid accelerometer data, with at least 8 h of valid recording time each day. The General Additive Model for Location Scale and Shape was used for calculating percentile curves. Results: Reference values for PA and sedentary time in the European children according to sex and age are displayed using smoothed percentile curves for 7684 children (3842 boys and 3842 girls). The figures show similar trends in boys and girls. The percentage of children complying with recommendations regarding moderate-to-vigorous physical activity (MVPA) is also presented and varied considerably between sexes and country. For example, the percentage of study participants who were physically active (as assessed by MVPA) for 60 or more minutes per day ranged from 2.0% (Cyprus) to 14.7% (Sweden) in girls and from 9.5% (Italy) to 34.1% (Belgium) in boys. Conclusion: This study provides the most up-to-date sex- and age-specific reference data on PA in young children in Europe. The percentage compliance to MVPA recommendations for these European children varied considerably between sexes and country and was generally low. These results may have important implications for public health policy and PA counselling.

Background Drought adaptation is critical to many tree species persisting under climate change, however our knowledge of the genetic basis for trees to adapt to drought is limited. This knowledge gap impedes our fundamental understanding of drought response and application to forest production and conservation. To improve our understanding of the genomic determinants, architecture, and trait constraints, we assembled a reference genome and detected ~ 6.5 M variants in 432 phenotyped individuals for the foundational tree Corymbia calophylla . Results We found 273 genomic variants determining traits with moderate heritability ( h 2 SNP  = 0.26–0.64). Significant variants were predominantly in gene regulatory elements distributed among several haplotype blocks across all chromosomes. Furthermore, traits were constrained by frequent epistatic and pleiotropic interactions. Conclusions Our results on the genetic basis for drought traits in Corymbia calophylla have several implications for the ability to adapt to climate change: (1) drought related traits are controlled by complex genomic architectures with large haplotypes, epistatic, and pleiotropic interactions; (2) the most significant variants determining drought related traits occurred in regulatory regions; and (3) models incorporating epistatic interactions increase trait predictions. Our findings indicate that despite moderate heritability drought traits are likely constrained by complex genomic architecture potentially limiting trees response to climate change.

Objective: To estimate the prevalence of the metabolic syndrome (MetS) using reference standards obtained in European children and to develop a quantitative MetS score and describe its distribution in children. Design and methods: Population-based survey in eight European countries, including 18745 children 2.0 to 10.9 years, recruited during a second survey. Anthropometry (weight, height and waist circumference), blood pressure and serum-fasting triglycerides, HDL cholesterol, glucose and insulin were measured. We applied three widely accepted definitions of the pediatric MetS and we suggest a new definition, to guide pediatricians in decisions about close monitoring or even intervention (values of at least three of the MetS components exceeding the 90th or 95th percentile, respectively). We used a z -score standardisation to calculate a continuous score combining the MetS components. Results: Among the various definitions of MetS, the highest prevalence (5.5%) was obtained with our new definition requiring close observation (monitoring level). Our more conservative definition, requiring pediatric intervention gives a prevalence of 1.8%. In general, prevalences were higher in girls than in boys. The prevalence of metabolic syndrome is highest among obese children. All definitions classify a small percentage of thin or normal weight children as being affected. The metabolic syndrome score shows a positive trend with age, particularly regarding the upper percentiles of the score. Conclusions: According to different definitions of pediatric MetS, a non-negligible proportion of mostly prepubertal children are classified as affected. We propose a new definition of MetS that should improve clinical guidance. The continuous score developed may also serve as a useful tool in pediatric obesity research. It has to be noted, however, that the proposed cutoffs are based on a statistical definition that does not yet allow to quantify the risk of subsequent disease.

Background/Objectives: A low fitness status during childhood and adolescence is associated with important health-related outcomes, such as increased future risk for obesity and cardiovascular diseases, impaired skeletal health, reduced quality of life and poor mental health. Fitness reference values for adolescents from different countries have been published, but there is a scarcity of reference values for pre-pubertal children in Europe, using harmonised measures of fitness in the literature. The IDEFICS study offers a good opportunity to establish normative values of a large set of fitness components from eight European countries using common and well-standardised methods in a large sample of children. Therefore, the aim of this study is to report sex- and age-specific fitness reference standards in European children. Subjects/Methods: Children (10 302) aged 6–10.9 years (50.7% girls) were examined. The test battery included: the flamingo balance test, back-saver sit-and-reach test (flexibility), handgrip strength test, standing long jump test (lower-limb explosive strength) and 40-m sprint test (speed). Moreover, cardiorespiratory fitness was assessed by a 20-m shuttle run test. Percentile curves for the 1st, 3rd, 10th, 25th, 50th, 75th, 90th, 97th and 99th percentiles were calculated using the General Additive Model for Location Scale and Shape (GAMLSS). Results: Our results show that boys performed better than girls in speed, lower- and upper-limb strength and cardiorespiratory fitness, and girls performed better in balance and flexibility. Older children performed better than younger children, except for cardiorespiratory fitness in boys and flexibility in girls. Conclusions: Our results provide for the first time sex- and age-specific physical fitness reference standards in European children aged 6–10.9 years.

Background: The European IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) study was set up to determine the aetiology of overweight, obesity and related disorders in children, and to develop and evaluate a tailored primary prevention programme. Objective: This paper focuses on the aetiological element of the multicentre study, the measures and examinations, sociodemographic characteristics of the study sample and proportions of participation. Design: Prospective cohort study with an embedded intervention study that started with a baseline survey in eight countries in 2007–2008. Subjects and measurements: Baseline participants of the prospective cohort study were 16 224 children aged 2–9 years. Parents reported sociodemographic, behavioural, medical, nutritional and other lifestyle data for their children and families. Examinations of children included anthropometry, blood pressure, fitness, accelerometry, DNA from saliva and physiological markers in blood and urine. The built environment, sensory taste perception and other mechanisms of children's food choices and consumer behaviour were studied in subgroups. Results: Between 1507 and 2567, children with a mean age of 6.0 years and an even sex distribution were recruited from each country. Of them, 82% lived in two-parent families. The distribution of standardised income levels differed by study sample, with low-income groups being strongly represented in Cyprus, Italy and Germany. At least one 24-h dietary recall was obtained for two-thirds of the children. Blood pressure and anthropometry were assessed in more than 90%. A 3-day accelerometry was performed in 46%, motor fitness was assessed in 41%, cardiorespiratory fitness in 35% and ~11% participated in taste perception tests. The proportion of children donating venous blood, urine and saliva was 57, 86 and 88%, respectively. Conclusion: The IDEFICS cohort provides valuable data to investigate the interplay of social, environmental, genetic, physiological and behavioural factors in the development of major diet- and lifestyle-related disorders affecting children at present.

We report that Mucin1 (MUC1), a transmembrane glycoprotein that is overexpressed in >80% of pancreatic ductal adenocarcinoma (PDA), induced a pro-angiogenic tumor microenvironment by increasing the levels of neuropilin-1 (NRP1, a co-receptor of vascular endothelial growth factor (VEGF)) and its ligand VEGF. Expression of tumor-associated MUC1 (tMUC1) positively correlated with NRP1 levels in human and mouse PDA. Further, tMUC1 hi PDA cells secreted high levels of VEGF and expressed high levels of VEGF receptor 2 (VEGFR2) and its phosphorylated forms as compared with tMUC1 low/null PDA. This enabled the tMUC1 hi /NRP1 hi PDA cells to (a) induce endothelial cell tube formation, (b) generate long ectopic blood vessels and (c) enhance distant metastasis in a zebrafish xenograft model. Concurrently, the proteins associated with epithelial-to-mesenchymal transition, N-cadherin and Vimentin, were highly induced in these tMUC1/NRP1 hi PDA cells. Hence, blocking signaling via the NRP1–VEGF axis significantly reduced tube formation, new vessel generation and metastasis induced by tMUC1 hi PDA cells. Finally, we show that blocking the interaction between VEGF 165 and NRP1 with a NRP1 antagonist significantly reduced VEGFR signaling and PDA tumor growth in vivo . Taken together, our data suggest a novel molecular mechanism by which tMUC1 may modulate NRP1-dependent VEGFR signaling in PDA cells.