The evolution of mammalian brain size.

Relative brain size has long been considered a reflection of cognitive capacities and has played a fundamental role in developing core theories in the life sciences. Yet, the notion that relative brain size validly represents selection on brain size relies on the untested assumptions that brain-body allometry is restrained to a stable scaling relationship across species and that any deviation from this slope is due to selection on brain size. Using the largest fossil and extant dataset yet assembled, we find that shifts in allometric slope underpin major transitions in mammalian evolution and are often primarily characterized by marked changes in body size. Our results reveal that the largest-brained mammals achieved large relative brain sizes by highly divergent paths. These findings prompt a reevaluation of the traditional paradigm of relative brain size and open new opportunities to improve our understanding of the genetic and developmental mechanisms that influence brain size.

Measuring temporal liking simultaneously to Temporal Dominance of Sensations in several intakes. An application to Gouda cheeses in 6 Europeans countries.

The idea of having untrained consumers performing Temporal Dominance of Sensations (TDS) and dynamic liking in the same session was recently introduced (Thomas, van der Stelt, Prokop, Lawlor, & Schlich, 2016). In the present study, a variation of the data acquisition protocol was done, aiming to record TDS and liking simultaneously on the same screen in a single session during multiple product intakes. This method, called Simultaneous Temporal Drivers of Liking (S-TDL), was used to describe samples of Gouda cheese in an international experiment. To test this idea, consumers from six European countries (n=667) assessed 4 Gouda cheeses with different ages and fat contents during one sensory evaluation session. Ten sensory attributes and a 9-point hedonic scale were presented simultaneously on the computer screen. While performing TDS, consumers could reassess their liking score as often as they wanted. This new type of sensory data was coded by individual average liking scores while a given attribute was perceived as dominant (Liking While Dominant; LWD). Although significant differences in preference were observed among countries, there were global preferences for a longer dominance of melting, fatty and tender textures. The cheese flavour attribute was the best positive TDL, whereas bitter was a strong negative TDL. A cluster analysis of the 667 consumers identified three significant liking clusters, each with different most and least preferred samples. For the TDL computation by cluster, significant specific TDL were observed. These results showed the importance of overall liking segmentation before TDL analysis to determine which attributes should have a longer dominance duration in order to please specific consumer targets.

Inflammation profile in overweight/obese adolescents in Europe: an analysis in relation to iron status.

BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the relationship between inflammatory parameters (CRP, c-reactive protein; AGP, α1-acid glycoprotein), iron status indicators (SF, serum ferritin; sTfR, soluble transferrin receptor) and body mass index (BMI) z-score, fat-free mass (FFM) and fat mass (FM) in European adolescents. Differences in intake for some nutrients (total iron, haem and non-haem iron, vitamin C, calcium, proteins) were assessed according to BMI categories, and the association of nutrient intakes with BMI z-score, FM and FFM was evaluated. METHODS: A total of 876 adolescents participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence-Cross Sectional Study were included in the study sample. RESULTS: Mean CRP values (standard error; s.e.) were significantly higher in overweight/obese adolescents (1.7±0.3 and 1.4±0.3 mg/l in boys and girls, respectively) than in thin/normal-weight adolescents (1.1±0.2 and 1.0±0.1 mg/l in boys and girls, respectively) (P<0.05). For boys, mean SF values (s.e.) were significantly higher in overweight/obese adolescents (46.9±2.7 µg/l) than in thin/normal-weight adolescents (35.7±1.7 µg/l) (P<0.001), whereas median sTfR values did not differ among BMI categories for both boys and girls. Multilevel regression analyses showed that BMI z-score and FM were significantly related to CRP and AGP (P<0.05). Dietary variables did not differ significantly among BMI categories, except for the intake of vegetable proteins, which, for boys, was higher in thin/normal-weight adolescents than in overweight/obese adolescents (P<0.05). CONCLUSIONS: The adiposity of the European adolescents was sufficient to cause chronic inflammation but not sufficient to impair iron status and cause iron deficiency.

Evaluation of food and nutrient intake assessment using concentration biomarkers in European adolescents from the Healthy Lifestyle in Europe by Nutrition in Adolescence study.

Accurate food and nutrient intake assessment is essential for investigating diet-disease relationships. In the present study, food and nutrient intake assessment among European adolescents using 24 h recalls (mean of two recalls) and a FFQ (separately and the combination of both) were evaluated using concentration biomarkers. Biomarkers included were vitamin C, ß-carotene, DHA+EPA, vitamin B12 (cobalamin and holo-transcobalamin) and folate (erythrocyte folate and plasma folate). For the evaluation of the food intake assessment 390 adolescents were included, while 697 were included for the nutrient intake assessment evaluation. Spearman rank and Pearson correlations, and validity coefficients, which are correlations between intake estimated and habitual true intake, were calculated. Correlations were higher between frequency of food consumption (from the FFQ) and concentration biomarkers than between mean food intake (from the recalls) and concentration biomarkers, especially for DHA+EPA (r 0·35 v. r 0·27). Most correlations were higher among girls than boys. For boys, the highest validity coefficients were found for frequency of fruit consumption (0·88) and for DHA+EPA biomarker (0·71). In girls, the highest validity coefficients were found for fruit consumption frequency (0·76), vegetable consumption frequency (0·74), mean fruit intake (0·90) and DHA+EPA biomarker (0·69). After exclusion of underreporters, correlations slightly improved. Correlations between usual food intakes, adjusted for food consumption frequency, and concentration biomarkers were higher than correlations between mean food intakes and concentration biomarkers. In conclusion, two non-consecutive 24 h recalls in combination with a FFQ seem to be appropriate to rank subjects according to their usual food intake.

Influence of maternal educational level on the association between the rs3809508 neuromedin B gene polymorphism and the risk of obesity in the HELENA study.

OBJECTIVE: Neuromedin B (NMB) is a bombesin-like peptide, which inhibits food intake and modulates stress-related behaviour. An NMB gene polymorphism (P73T) has been earlier associated with obesity and abnormal eating behaviour in adults. METHODS: The association between four NMB polymorphisms and obesity-related phenotypes was investigated in the Healthy Lifestyle in Europe by Nutrition in Adolescence cross-sectional study (n=1144, 12-17-year-old European adolescents). This population was genotyped for the NMB rs1107179, rs17598561, rs3809508 and rs1051168 (P73T) polymorphisms. Obesity was defined according to Cole et al. (BMJ 2000; 320:1240-1243) criteria; eating behaviour was assessed by the Eating Behaviour and Weight Problems Inventory for Children (EWI-C) and the food choices and preferences questionnaires. Familial socioeconomic status (SES) was assessed through the parents' educational level. RESULTS: Only the genotype distribution of rs3809508 differed according to obesity status, as the TT genotype was more frequent in obese than in non-obese adolescents (8.6% vs 3.1%, P=0.05; adjusted odds ratio for obesity (95% confidence interval): 2.85 (1.11-7.31), P=0.03). Moreover, TT subjects had higher body mass index (22.8+/-4.4 kg m(-2) vs 21.3+/-3.7 kg m(-2), P=0.02), waist circumference (75.8+/-9.7 cm vs 72.2+/-9.3 cm, P=0.006), waist-to-hip ratio (0.84+/-0.14 vs 0.79+/-0.07, P<0.0001) and waist-to-height ratio (0.47+/-0.06 vs 0.44+/-0.55, P=0.002) than C allele carriers. The effects of this single nucleotide polymorphism on all anthropometric values were influenced by the maternal SES, in that a low maternal educational level aggravated the phenotype of adolescents carrying the TT genotype (interactions: P<0.02). No association with EWI-C scores was found, although sweet craving was a more frequent cause of between-meal food intake in TT subjects than in C allele carriers (24.3% vs 9.2%, P=0.01). CONCLUSION: In European adolescents, the TT genotype of the NMB rs3809508 polymorphism was associated with a higher risk of obesity. Moreover, the effects of this polymorphism on anthropometric values were influenced by the maternal educational level.

Quality assurance of ethical issues and regulatory aspects relating to good clinical practices in the HELENA Cross-Sectional Study.

RATIONALE: Research involving humans is regulated by regulatory authorities through their specific requirements and controls. The Healthy Life Style in Europe by Nutrition in Adolescence Cross-Sectional Study (HELENA-CSS) is a multicenter biomedical research study of adolescents in several representative European cities, which requires satisfying medico-regulatory requirements including Independent Ethics Committee (IEC) approval and agreement by the national or local regulatory authorities. To achieve a high level of quality assurance relating to ethical issues, we followed the good clinical practices (GCP) described at the International Conference on Harmonisation (ICH), which we adapted to the national and local situations of each of the 11 participating cities in 10 European countries. OBJECTIVE: The main objective of the HELENA-CSS is to evaluate reliable and comparable data of nutritional habits and lifestyle in a representative sample of European adolescents. The aim of this paper is to present the methods relating to the ethical and regulatory issues of this study and to describe the current state of the medico-regulatory requirements involved in conducting this kind of study in each country. MATERIALS AND METHODS: Following the GCP-ICH guidelines, a protocol describing the HELENA-CSS was written and approved by all partners. In the pilot study, a case report form adapted to the study objectives and its manual of operation was constructed and used by all partners. All information letters to adolescents and their parents and consent forms were first written in English, then translated into the local language, and adapted to each local situation. All documents were then checked centrally for any deviation and corrected if required. An operation manual relating to ethical issues and other medico-regulatory requirements was also developed. This paper presents the current status of the medico-regulatory requirements from each HELENA-CSS participant country. RESULTS: Before the beginning of the study, most centers had satisfied the medico-regulatory requirements of IEC approval and agreement with other national or local regulatory authorities/organizations. For a few centers, some problems were detected and corrective actions were taken to improve missing information to reach a high level of quality assurance of ethical issues. CONCLUSION: The GCP-ICH guidelines about nontherapeutic biomedical research are interpreted and applied differently across Europe. This study shows that high-quality nontherapeutic biomedical research can address the ethical issues included in the GCP-ICH regulations and can be harmonized among the HELENA European partners.

Design and implementation of the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study.

OBJECTIVE: To provide an overview of the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study (HELENA-CSS) design, with particular attention to its quality control procedures. Other important methodological aspects are described in detail throughout this supplement. DESIGN: Description of the HELENA-CSS sampling and recruitment approaches, standardization and harmonization processes, data collection and analysis strategies and quality control activities. RESULTS: The HELENA-CSS is a multi-centre collaborative study conducted in European adolescents located in urban settings. The data management systems, quality assurance monitoring activities, standardized manuals of operating procedures and training and study management are addressed in this paper. Various quality controls to ensure collection of valid and reliable data will be discussed in this supplement, as well as quantitative estimates of measurement error. CONCLUSION: The great advantage of the HELENA-CSS is the strict standardization of the fieldwork and the blood analyses, which precludes to a great extent the kind of immeasurable confounding bias that often interferes when comparing results from isolated studies.

Assessing, understanding and modifying nutritional status, eating habits and physical activity in European adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study.

OBJECTIVES: To identify the main knowledge gaps and to propose research lines that will be developed within the European Union-funded 'Healthy Lifestyle in Europe by Nutrition in Adolescence' (HELENA) project, concerning the nutritional status, physical fitness and physical activity of adolescents in Europe. DESIGN: Review of the currently existing literature. RESULTS: The main gaps identified were: lack of harmonised and comparable data on food intake; lack of understanding regarding the role of eating attitudes, food choices and food preferences; lack of harmonised and comparable data on levels and patterns of physical activity and physical fitness; lack of comparable data about obesity prevalence and body composition; lack of comparable data about micronutrient and immunological status; and lack of effective intervention methodologies for healthier lifestyles. CONCLUSIONS: The HELENA Study Group should develop, test and describe harmonised and state-of-the-art methods to assess the nutritional status and lifestyle of adolescents across Europe; develop and evaluate an intervention on eating habits and physical activity; and develop and test new healthy food products attractive for European adolescents.

Prophylactic intravenous amphotericin B in neutropenic autologous bone marrow transplant recipients.

This study assessed the efficacy, toxicity, and pharmacology of low-dose amphotericin B given prophylactically to patients (serum concentrations of 0.2-0.4 microgram/ml) undergoing bone marrow transplantation. Yeast isolates from patients' oropharyngeal areas had MICs of 0.1-0.2 microgram/ml, and none were amphotericin B resistant. The effect of low-dose amphotericin B on reducing the numbers of yeast colonizing the oropharyngeal area was significant (P less than .01). The average delay in switching to high-dose prophylactic amphotericin B was only 1 day; the decision to do so because of a perceived fungal infection occurred more frequently for the placebo group (P = .06). Fewer patients from the low-dose amphotericin B group (8.8%) than from the placebo group (14.3%) had fungi isolated from normally sterile body sites (P = .35). Infusion-related side effects but not systemic toxicities were significantly greater (P less than .001) in the amphotericin B group. The 6-week survival was greater in those receiving amphotericin B (P less than .03), but the improved survival could not be attributed to the prevention of fungal infections.