carried out by the gut microbiota . The specific bacterial strains responsible for this initial hydrolysis have not been extensively studied yet. For the intestinal uptake of the bioac- tive compounds both passive and active mechanisms have been described, as well as efflux transporters that lower the absolute influx of bioactives through the intestinal absorp- tion. Nevertheless, our knowledge of the carriers involved for the various compounds is still very sparse. When ab- sorbed, hydrophilic plant food bioactives typically undergo first pass metabolism in the intestine and in the liver with phase I (oxidation/reduction reactions) and mainly phase II (␤-glucuronidation, sulfation, methylation, glutathione con- jugation) biotransformations . A substantial enterohep- atic recirculation exists for some metabolites. Lipophilic bioactive compounds may be absorbed through the lymphatic system and thereby escape the first pass metabolism by the liver. For a number of plant food bioactives, the gut microbiota in addition to the intestine and liver handles the production of a wide range of metabolites, which can be more or less spe- cific of their precursors . The gut microbiota composition, specific bacteria strains and the functionalities responsible for all these metabolic biotransformations, as well as their occurrence and distribution in humans have not been exten- sively investigated. Further research in this specific area will be essential for a better understanding of the inter-individualvariation.
together (heavy dashed line), as well as regression lines for indi- vidual sites (light dotted lines).
The data points in Fig. 3 clearly separate the Californian from Nubian samples, for both calculus and bone. Our main goal here is not to reconstruct regional or individual differences in dietary be- haviors from calculus, but rather, to explore patterns in calculus isotopes relative to those recorded in bone. Nevertheless, if dental calculus stable isotope signatures reﬂect diet, as bone does, these differences suggest quite different diets in the two continents. Of course, it is not surprising to ﬁnd such dietary differences in sites representing hunter-gatherers in California, on the one hand, and agriculturalists in Nubia, on the other. However, if the differences are due to other, non-dietary factors such as environment, popu- lation genetic history, or the composition of oral bacteria commu- nities, we would expect similar differences in such widely divergent samples. This study is currently unable to address this issue, but note that the different sites within California, populations with more similar genetic and environmental histories, also tend to cluster in the graph. In any case, these data point to unique calculus isotopic values from region to region and site to site, and that these patterns tend to mimic those in bone collagen. We note three additional patterns below.
of metabolism follows the Arrhenius law, predicting an expo- nential increase of chemical reaction rate with temperature. Interestingly, the MTE predicts that the sensitivity of meta- bolic rate to temperature (i.e. the activation energy of the Arrhenius thermal reaction norm, which indicates how fast metabolic rate increases with temperature) should vary little across taxa around an average value of 0.65 eV (Gillooly et al. 2001). This prediction is based on the assumption that cell kinetics driving organisms’ functions react with temperature following a unique canonical value for all living organisms. The MTE thus assumes a low and inconsistent variability of activation energy across time and space implying that indi- viduals within and among species respond to temperature with the same sensitivity. This universal thermal dependence (UTD) hypothesis and its assumptions have thus major implications for our understanding of ecological and evolu- tionary consequences of climate change. Without variations among individuals, evolution would not occur as natural selection primarily acts at the level of individual differences (Labocha et al. 2004). If variations are significant but incon- sistent through time, then there would be very little poten- tial for evolutionary response to climate change because the consistency of among-individual variability and the degree to which natural selection drives trait evolution are intricately related (Brodie and Russell 1999). For evolutionary response to occur, among individual trait variation has to be signifi- cant and consistent through time (i.e. repeatable) and across generations (i.e. heritable) (Dohm 2002). In other words, natural selection can still occur if the trait heritability is null but this would not lead to evolution. An alternative hypoth- esis to the UTD has been proposed by Clarke (2004) who argues that the temperature effect on the metabolic rate is not a universal process but rather the result of an evolutionary tradeoff between the energetic expenditures associated to an environmental temperature and the physiological function- ing inherent to each individual. According to this alternative hypothesis, activation energy is expected to vary substantially and consistently among individuals to allow natural selec- tion and evolutionary adaptation to local thermal conditions (Murren et al. 2014). Therefore, as an alternative to the UTD hypothesis, we hypothesise that the large intraspecific vari- ability of activation energy of metabolic rate is repeatable among individuals. Assessing whether activation energy of metabolic rate varies among individuals and environmental conditions is thus crucial to test these two alternative hypoth- eses and assess the potentiality for evolutionary responses to new selective pressures such as climate change.
doi: 10.1111/oik.05228 127 1 6 7 0 – 1678
The metabolic theory of ecology predicts resource consumption rates of animals from their body mass, but other phenotypic traits might affect individual resource consumption rate. In this paper, we used a hierarchical framework to examine relation- ships between phenotypic traits thought to constrain variation in per capita resource consumption rate. Physiological and behavioural traits were assumed to be impor- tant in mediating the control of morphology and sex on consumption. We conducted a longitudinal study aiming to relate the consumption rate of submerged leaf litter to sex, morphological, physiological and behavioural traits in an aquatic detritivore population. Then, we analysed the pattern of trait covariation using structural equa- tion modelling (SEM). We observed broad and repeatable inter-individualvariation in leaf consumption rate and other phenotypic traits. We found that expressing litter consumption rate relative to the time individuals spent feeding revealed and increased the effect of body mass and sex differences, respectively. Accordingly, SEM analyses showed that time allocated to resource acquisition mediated body mass and sex effects on apparent litter consumption rate whose variation was also accounted for by an indicator of activity-specific metabolic rate. Substantial variation in resource consump- tion rate was due to sex difference whereas body mass was of secondary importance. Individual phenotypic trait variations strongly altered consumer–resource relation- ships. Therefore, we encourage studies on consumers’ intraspecific variability to advance knowledge about phenotypic determinants of individual resource consump- tion, an important link between individuals and ecosystems.
Among the factors that might affect the inter-individualvariation of anthocyanins bioavailability, the microbiota composition has emerged as one of the most important and less well known. In the last fifteen years or so, the number of research papers regarding the microbiota effect on different pathological or physiological conditions has increased in an exponential way. Microbiota catabolism leads to production of new anthocyanin metabolites in the human gut. These metabolites may be absorbed by the colon epithelium and induce modulation of the microbiota composition. The bioavailability of anthocyanins depends on gut microflora and their biotransformation mechanisms. Gut microbiota vary on a person-to-person basis and in this sense, an inter-individual variability in anthocyanin ADME could be expected. In general, it is now assumed that if anthocyanins have a beneficial effect on human health, this effect is mediated by what is called breakdown metabolites, formed by the different bacteria existing in the microbiota. However, when searching in electronic databases (Medline PubMed and Web of Science) for anthocyanins and microbiota, less than 200 articles were initially selected. After removal of duplicates and an initial screening, 43 articles were selected for further reading. After detailed analysis of the full text, 12 articles were rejected, due to lack of relevant outcomes, aspects of the study design, and so forth. Finally, articles published between 2005 and 2018 were incorporated in this review (see Tables 3 – 5 ). Other articles were not selected because, for example, the polyphenol composition of the dietary sources of anthocyanins was too complex or because anthocyanins did not represent a big proportion with respect to the total polyphenol content (i.e., grape juice or red wine extract), although they suggested a role of the human intestinal microbiota on anthocyanins metabolism [ 56 , 57 ].
Despite limited, results from these seven studies suggest that some individual characteristics may influence the beneficial effect of HCAs. Firstly, determinants of health or pathophysiological status, like baseline cholesterol levels [ 26 , 28 ], insulinogenic index [ 46 ] or glycemic response [ 35 ] could play an important role in the variation among study participants in the biological response to HCAs regarding CM outcomes, being associated with an increased beneficial effect following HCA intake. This was not only demonstrated in the stratified analyses conducted by Martinez-Lopez et al., Sarriá et al., Iwai et al. and Jokura et al., [ 26 , 28 , 35 , 46 ] but also in the assessments conducted within this systematic review for all outcomes in the chronic studies, which demonstrated that effectiveness of HCAs, regardless of specific source, was greater in those at higher risk (i.e., greater baseline cholesterol, glycemic or SBP). This supports previous studies that suggested that the pathophysiological status can lead to inter-individualvariation in response to polyphenols [ 74 , 75 ]. Some recent systematic reviews and meta-analyses have also indicated that the health status or BMI may influence the impact of several polyphenols (flavonols, flavan-3-ols, anthocyanins and ellagitannins) on blood lipid levels [ 18 , 19 , 24 ]. Regarding sex differences, the response to HCAs has been shown to be different between men and women following artichoke leaf extract consumption [ 54 ]. So far, a sex effect in response to plant-food bioactive compounds such as HCAs has been reported in very few studies [ 76 ], mainly focusing on flavanol-rich products, with some but limited differences in the response between men and women. However, results are often contrasting; for instance, a decreased augmentation index was observed only in women after cocoa consumption for four weeks [ 77 ], while the antioxidant status was improved mostly in men after a four-week consumption of
manner for a wider chemical coverage. Among the most commonly used are HMDB ( www.hmdb.ca ), Metlin ( https ://metli n.scrip ps.edu/ ), PubChem ( https ://pubch em.ncbi.nlm. nih.gov/ ), ChemSpider ( www.chems pider .com/ ), MassBank ( http://massb ank.eu/ ), MoNA ( http://mona.fiehn lab.ucdav is.edu/ ), NIST, Golm Metabolome database, LipidMaps ( https ://www.lipid maps.org/ ), mzCloud ( https ://www.mzclo ud.org/ ), GNPS ( https ://gnps.ucsd.edu/ ), ReSpect ( http:// spect ra.psc.riken .jp/ ) and FooDB ( http://foodb .ca/ ). The detected signals are not easily identified when the corre- sponding compounds are not yet present in one of these data- bases, which is the case for many metabolites of less studied food phytochemicals. PhytoHub ( http://phyto hub.eu/ ) is an online database conceived to facilitate the identification of food phytochemicals and their metabolites in metabolomics profiles [ 42 ]. It contains > 1700 compounds and is con- tinuously updated by invited experts. The literature survey conducted by WG1 of the COST Action POSITIVe led to a major upgrade of PhytoHub. About 200 metabolites of polyphenols not yet recorded in any database were added, associated with the original literature. PhytoHub can now be searched to get the list of metabolites observed or expected in biofluids after consumption of a given food. For exam- ple, when searched for apple, a list of 195 metabolites is obtained, along with the information necessary to identify them in urine or plasma metabolomic profiles. In addition, for compounds whose metabolism has not yet been studied in humans, the most likely host and microbial metabolites can be predicted by Biotransformer ( http://biotr ansfo rmer. ca/ ), a new open-access tool that applies prediction rules elaborated from machine-learning algorithms and expert knowledge including PhytoHub data [ 43 ]. Integration of more chemical, biological and spectral data for phytochemi- cal metabolites in metabolomic databases will be key for a better understanding of food phytochemical ADME and associated inter-individualvariation.
Finally, our results have direct consequences for several problems in consumer theory and aggregation. In the paper, we consider the well-known Debreu-Mantel-Sonnenschein theorem on aggregate excess demand. The question, here, is whether it is possible, for any arbitrary, smooth function Z (p) that satisfies homogeneity and the Walras Law, to find n individual excess demand functions z 1 (p) , ..., z n (p) such that
To evaluate the inter-subject variability of the TVA (robust versus variable signal within and between subjects), we computed a prob- ability map based on individual thresholded data. For each subject, the t-map vocal N non-vocal was thresholded at q = .05 corrected (correc- tion for multiple comparisons based on spatial extent ( Chumbley et al., 2010 )). However, rather than using a default cluster forming threshold for all subjects, this threshold was set individually using a Gamma – Gaussian mixture model. The voxel T-distribution is ﬁtted with 3 differ- ent non-central models (Gaussian only, positive gamma and Gaussian, positive and negative gamma plus Gaussian) effectively separating the null voxel distribution from the ‘active’ voxel distribution ( Gorgolewski et al., 2012 ). This method is more sensitive (less false negative) and allows a better delineation of the cluster spatial extent. Once the 218 thresholded maps were obtained, they were binarized, summed and normalized to 100 to create a probability map.
Are individual differences in numerical performance sustained by variations in gray matter volume in schoolchildren? To our knowledge, this challenging question for neuroeducation has not yet been investigated in typical development. We used the Voxel-Based Morphom- etry method to search for possible structural brain differences between two groups of 10-year-old schoolchildren (N = 22) whose performance differed only in numerical transcod- ing between analog and symbolic systems. The results indicated that children with low numerical proficiency have less gray matter volume in the parietal (particularly in the left intraparietal sulcus and the bilateral angular gyri) and occipito-temporal areas. All the identi- fied regions have previously been shown to be functionally involved in transcoding between analog and symbolic numerical systems. Our data contribute to a better understanding of the intertwined relationships between mathematics learning and brain structure in healthy schoolchildren.
1.6 Estimating resource use
The most widely used methods for estimating resource use in healthcare settings are the ratio of cost to charge (CCR), diagnosis-related groups (DRG) and activity-based costing (ABC). The ratio of cost to charge is largely used in for-profit healthcare systems and estimates cost using hospital charges. 28 However, this method can often under or over- estimate cost and it is not reliable in evaluating costs for individual patients. 28 Diagnosis- related groups is common in universal health care systems and uses a standardized grid of average cost per patient based on the patient’s principal diagnosis. 29 DRG underestimates cost in trauma patients since it does not account for multiple injuries. 30, 31 Moreover, this method does not allow for inter-hospital comparisons because of standardization. 29, 31 Activity-based costing has been shown to be the most accurate and precise method of the three mentioned above for estimating costs in healthcare systems. 32-35 Activity-based costing involves multiplying the unit costs of specific activity centers by the corresponding units of resources used (e.g. hours in the operating room, days in intensive care unit (ICU)). It is useful for policy-makers and hospital administrators because it relates costs to activities, thereby providing information that is actionable. 32-36 Moreover, it provides an estimate of resource use intensity in accordance with the Grading of Recommendations Assessment, Development and Evaluations (GRADE) guidelines. 32-38
1. Cyclotron Research Centre, University of Liège, Belgium; 2. Surrey Sleep Research Centre, University of Surrey, Guildford, UK.
A variable number tandem repeat polymorphism in PERIOD3 is a genetic marker for inter- individual differences in sleep homeostasis and the effects of sleep loss on cognitive performance, in particular during the circadian alertness nadir. Individuals homozygous for the longer repeat (PER3 5/5 ) are more susceptible than individuals homozygous for the shorter allele (PER3 4/4 ). However, the brain bases of the effects of the polymorphism on cognitive performance are unknown.
4.1 I NTRODUCTION
Le recalage inter-individus basé uniquement sur les intensités des CTs apparaît difficile du fait de la grande variabilité inter-individus et du faible contraste des tissus mous (Acosta et al., 2011). Rajouter d’autres informations, d’autres caractéristiques anatomiques pour guider le processus de recalage pourrait permettre d’améliorer la précision de la mise en correspondance. Quelques approches, majoritairement basées sur la FFD, utilisant l’information complémentaire des segmentations des organes ont été proposées pour le recalage CT/CBCT dans un contexte de recalage intra-individu. Greene et al. ont présenté une méthode de recalage non- rigide contraint par les organes dans le contexte de l’IGRT (Greene et al., 2009). Elle consiste à recaler les images binaires des organes per-traitements vers les images acquises lors de la planification et à utiliser ensuite ces déformations pour contraindre la transformation globale de l’image. Les auteurs ont ainsi montré qu’il était possible d’améliorer la précision du recalage en ajoutant des contraintes liées aux organes sur les points de contrôles de la FFD. Rivest et al. proposent également d’utiliser l’ensemble des organes du même individu pour guider le recalage de structures pelviennes de l’IRM vers le CT (Rivest-Hénault et al., 2014a, 2014b). Une autre méthode, utilisant les multiplicateurs de Lagrange et un modèle bayésien pour imposer des contraintes, a également été proposée (Lu et al., 2011, 2010). Kim et al. proposent d’utiliser des segmentations faites par plusieurs experts ainsi que des points distinctifs de l’anatomie (calcification, marqueurs, etc.) afin de guider le recalage (Kim et al., 2013). Si la FFD apparaît comme la méthode la plus utilisée, quelques articles récents proposent néanmoins des approches similaires basées sur l’algorithme des démons (Cazoulat et al., 2014, 2011; Chen et al., 2010) en ajoutant par exemple des contraintes sur les voxels appartenant aux organes. Dans d’autres applications ou les déformations intra-individu sont importantes, le recalage guidé par les repères anatomiques apporte des meilleurs résultats que le recalage basé intensité (Osorio et al., 2012, 2009).
Keywords: mathematics learning, number processing, educational neuroscience, schoolchildren, gray matter, voxel-based morphometry, neuroeducation
How are individual differences in numerical cognition associated with structural brain variations in schoolchildren? Not only devel- opmental maturation but also experience and learning may mod- ify brain structure. On one hand, brain maturation is characterized by loss of gray matter (GM) with age that varies according to brain region ( Gogtay et al., 2004 ). On the other hand, experience- dependent structural plasticity was demonstrated by an increase of GM in cerebral areas associated with training function in expert groups (e.g., mathematicians, Aydin et al., 2007 ) and was demon- strated during intensive trainings (e.g., motor learning, Draganski et al., 2004 ; or cognitive training, Draganski et al., 2006 ). The aim of the present study is to provide insights into the relationships between individual differences in mathematics and brain structure (GM volume variations) in 10-year-old typically achieving school- children. As suggested by Carew and Magsamen (2010) , linking brain research to education is extremely important for a better understanding of how children learn. It seems central that studies concerning brain plasticity, such as our study, bring information to the educational community in order to contribute to a better quality of education and an adapted pedagogy. However, direct applications within the classroom were still difficult to consider ( Hook and Farah, 2012 ).
3.5 Mean comparison of demographic estimates with integrated covariates
It is common, especially in wild populations, to obtain parameters (e.g. survival or detection probability) that can be explained by covariates (e.g. climatic fluctuations). However, scientists could still be interested to compare estimates constraint by integrated covariate between groups of individuals or periods of time. To compare these mean of dependent parameters, using a general procedure taking this dependency into account, thus incorporating the variance-covariance matrix of these estimates, is needed. Some programs (e.g., CONTRAST, (Hines & Sauer 1989; Sauer & Hines 1989), http://www.mbr-pwrc.usgs.gov/software/contrast.html) allow to implement such procedure with the use of the VC matrix of the individual biological parameters (V(!)). However, obtaining this VC matrix is not always obvious. In this section, we present how to get and derive this matrix for a model with an integrated covariate. For an illustrative purpose, we wanted to compare survival estimates of common eiders (Sometaria mollissima) from a Canadian colony (East Bay Migratory Bird Sanctuary, Southampton Island, Nunavut: 64°02’N, 81°47’W) between two groups of individuals wintering under different winter conditions. The study was conducted from 1996 to 2014 corresponding to 18 survival estimates (Guéry et al. 2017). The same method can be applied for any estimates with a binomial distribution (e.g. alive or dead; detected or not; breeding or not), in other situations (e.g. comparing periods of time) and other disciplines (e.g. culture rotations in agricultural techniques).
not only the memory of past selection pressures or phylogenetic affiliation [3,35].
Trait values which maximize species performance have been shown to allow for a within-species homeostasis of the C and N plant substrates, as indicated by a narrow C:N ratio for plant substrates (Figure 2). This result is in line with a recent study showing that the growth of Festuca paniculata tussocks tends to be co-limited by both C and N substrates . In addition, different species expressed different optimal C:N ratios that were correlated with between-species trait variation. Interestingly, LLS and SLA (i.e. the leaf economics spectrum) were apparently the primary drivers explaining between- species variation in optimal C:N ratios. This result echoes the theoretical relationship between LLS and dry-mass return , that results from the cost-benefit law opposing the respiratory cost of deploying and maintaining dense plant tissue and the benefit to keep plant photosynthetic tissue over long period of time. In addition, at a given LLS, the plant height and, inversely, the tiller density represent a secondary independent control on the maximization of plant performance and on optimal C:N substrate ratios (Figure 5). This reveals that species with high plant stature and low TD may tend to conserve C substrate to sustain high respiratory cost per tiller, in comparison with species that share this substrate among a high number of small interconnected tillers.
MATERIAL AND METHODS Study site
The study site is located in the Rustrel Forest in southern France (05° 27' 57.9'' E, 43° 56' 12.2'' N and elevation 520 m; Figure 1) and within the Fontaine de Vaucluse observatory is part of OZCAR ( http://www.ozcar-ri.org/ ), the French network of critical zone observatories. The climate is Mediterranean, characterized by cool and wet winters, hot and dry summers, and a high inter-annual variability. Between 1970 and 2018, annual rainfalls ranged from 407 to 1405 mm with a mean of 909 mm. The rendzina type soil contains 50 to 60 % of coarse material (> 2 mm) and has a highly variable thickness (from 0 to > 80 cm). The forest has been managed as a coppice for centuries and the last clear cut occurred about 80 years ago. Vegetation is dominated by a sparse evergreen overstory of Quercus ilex L., which represents more than 85 % of the basal area (Figure 1). The dominant tree height is about 4 m. The understory is a sparse shrubby layer, which represents less than 15 % of the basal area and includes Buxus sempervirens, Juniperus communis, Juniperus phoenicea, Quercus pubescens, Amelanchier ovalis, and Rhamanus alaternus (Carrière et al., 2017). The Leaf Area Index (LAI), as measured along the ERT transect with hemispherical photographs following Davi et al. (2008), is about 1.85. The underground (soil and subsoil) is highly complex; the medium is heterogeneous due to numerous vertical fractures and karstified carbonate rock. Carrière et al. (2013) showed that north-south oriented faults impose the general spatial structure on geology and pedology. This is well illustrated by the west-east alternation of areas of low and high electrical resistivity values as shown in Figure 1b.