395 research outputs found

    Childhood body mass index trajectories: modeling, characterizing, pairwise correlations and socio-demographic predictors of trajectory characteristics

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    Background: Modeling childhood body mass index (BMI) trajectories, versus estimating change in BMI between specific ages, may improve prediction of later body-size-related outcomes. Prior studies of BMI trajectories are limited by restricted age periods and insufficient use of trajectory information. Methods: Among 3,289 children seen at 81,550 pediatric well-child visits from infancy to 18 years between 1980 and 2008, we fit individual BMI trajectories using mixed effect models with fractional polynomial functions. From each child's fitted trajectory, we estimated age and BMI at infancy peak and adiposity rebound, and velocity and area under curve between 1 week, infancy peak, adiposity rebound, and 18 years. Results: Among boys, mean (SD) ages at infancy BMI peak and adiposity rebound were 7.2 (0.9) and 49.2 (11.9) months, respectively. Among girls, mean (SD) ages at infancy BMI peak and adiposity rebound were 7.4 (1.1) and 46.8 (11.0) months, respectively. Ages at infancy peak and adiposity rebound were weakly inversely correlated (r = -0.09). BMI at infancy peak and adiposity rebound were positively correlated (r = 0.76). Blacks had earlier adiposity rebound and greater velocity from adiposity rebound to 18 years of age than whites. Higher birth weight z-score predicted earlier adiposity rebound and higher BMI at infancy peak and adiposity rebound. BMI trajectories did not differ by birth year or type of health insurance, after adjusting for other socio-demographics and birth weight z-score. Conclusions: Childhood BMI trajectory characteristics are informative in describing childhood body mass changes and can be estimated conveniently. Future research should evaluate associations of these novel BMI trajectory characteristics with adult outcomes

    Cross-sectional associations between sleep duration, sedentary time, physical activity, and adiposity indicators among Canadian preschool-aged children using compositional analyses

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    Abstract Background Sleep duration, sedentary behaviour, and physical activity are three co-dependent behaviours that fall on the movement/non-movement intensity continuum. Compositional data analyses provide an appropriate method for analyzing the association between co-dependent movement behaviour data and health indicators. The objectives of this study were to examine: (1) the combined associations of the composition of time spent in sleep, sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) with adiposity indicators; and (2) the association of the time spent in sleep, sedentary behaviour, LPA, or MVPA with adiposity indicators relative to the time spent in the other behaviours in a representative sample of Canadian preschool-aged children. Methods Participants were 552 children aged 3 to 4 years from cycles 2 and 3 of the Canadian Health Measures Survey. Sedentary time, LPA, and MVPA were measured with Actical accelerometers (Philips Respironics, Bend, OR USA), and sleep duration was parental reported. Adiposity indicators included waist circumference (WC) and body mass index (BMI) z-scores based on World Health Organization growth standards. Compositional data analyses were used to examine the cross-sectional associations. Results The composition of movement behaviours was significantly associated with BMI z-scores (p = 0.006) but not with WC (p = 0.718). Further, the time spent in sleep (BMI z-score: γ sleep  = −0.72; p = 0.138; WC: γ sleep  = −1.95; p = 0.285), sedentary behaviour (BMI z-score: γ SB  = 0.19; p = 0.624; WC: γ SB  = 0.87; p = 0.614), LPA (BMI z-score: γ LPA  = 0.62; p = 0.213, WC: γ LPA  = 0.23; p = 0.902), or MVPA (BMI z-score: γ MVPA  = −0.09; p = 0.733, WC: γ MVPA  = 0.08; p = 0.288) relative to the other behaviours was not significantly associated with the adiposity indicators. Conclusions This study is the first to use compositional analyses when examining associations of co-dependent sleep duration, sedentary time, and physical activity behaviours with adiposity indicators in preschool-aged children. The overall composition of movement behaviours appears important for healthy BMI z-scores in preschool-aged children. Future research is needed to determine the optimal movement behaviour composition that should be promoted in this age group

    e3 service: A Critical Reflection and Future Research

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    Commercial services are of utmost importance for the economy. Due to the widespread use of information and communication technologies, many of these services may be delivered online by means of service value networks. To automate this delivery, however, issues such as composition, integration, and operationalization need to be addressed. In this paper, the authors share their long-term vision on composition of service value networks and describe relationships with fields such as cloud computing and enterprise computing. As a demonstration of the state of the art, capabilities and limitations of e 3 service are described and research challenges are defined

    Evaluation of the in vitro skin permeation of antiviral drugs from penciclovir 1% cream and acyclovir 5% cream used to treat herpes simplex virus infection

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    <p>Abstract</p> <p>Background</p> <p>Herpes simplex virus infection (HSV) is a common and ubiquitous infection of the skin which causes mucocutaneous lesions called cold sores (herpes labialis) or fever blisters. It is estimated that approximately 80% of the population worldwide are carriers of the Herpes simplex virus, approximately 40% suffer from recurrent recurrent infections. This study evaluates the <it>in vitro </it>skin permeation and penetration of penciclovir and acyclovir from commercialized creams for the treatment of herpes labialis (cold sores), using non viable excised human abdominal skin samples, which were exposed to 5 mg/cm<sup>2 </sup>of acyclovir 5% cream or penciclovir 1% cream.</p> <p>Methods</p> <p>After 24 h of cream application, excess cream was washed off and layers of stratum corneum were removed by successive tape stripping. Amounts of active ingredients having penetrated through the skin were measured, as well as the amounts in the washed-off cream, in skin strips and creams remaining in the skin. Molecular modelling was used to evaluate physico-chemical differences between the drugs. Western blot analysis enabled to determine whether the marker of basal cells keratin 5 could be detected in the various tape strips.</p> <p>Results</p> <p>Application of penciclovir 1% cream yielded higher concentration of drug in the deeper layers of the epidermis as well as a higher drug flux through the skin. Molecular modelling showed two higher hydrophobic moieties for acyclovir. Presence of the basal cell marker keratin 5 was underscored in the deeper tape strips from the skin, giving evidence that both drugs can reach their target cells.</p> <p>Conclusion</p> <p>Penciclovir 1% cream has the tendency to facilitate the diffusion of the drug through the stratum corneum into the deeper epidermis layers, in which it could reach the target basal cells at effective therapeutical concentration. The small difference in the surface properties between both molecules might also contribute to favour the passage of penciclovir through the epidermis into the deeper basal cells.</p

    Broad and Gag-Biased HIV-1 Epitope Repertoires Are Associated with Lower Viral Loads

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    Background: HLA class-I alleles differ in their ability to control HIV replication through cell-mediated immune responses. No consistent associations have been found between the breadth of Cytotoxic T Lymphocytes (CTL) responses and the control of HIV-1, and it is unknown whether the size or distribution of the viral proteome-wide epitope repertoire, i.e., the intrinsic ability to present fewer, more or specific viral epitopes, could affect clinical markers of disease progression. Methodology/Principal Findings: We used an epitope prediction model to identify all epitope motifs in a set of 302 HIV-1 full-length proteomes according to each individual's HLA (Human Leukocyte Antigen) genotype. The epitope repertoire, i.e., the number of predicted epitopes per HIV-1 proteome, varied considerably between HLA alleles and thus among individual proteomes. In a subgroup of 270 chronically infected individuals, we found that lower viral loads and higher CD4 counts were associated with a larger predicted epitope repertoire. Additionally, in Gag and Rev only, more epitopes were restricted by alleles associated with low viral loads than by alleles associated with higher viral loads. Conclusions/Significance: This comprehensive analysis puts forth the epitope repertoire as a mechanistic component of the multi-faceted HIV-specific CTL response. The favorable impact on markers of disease status of the propensity to present more HLA binding peptides and specific proteins gives impetus to vaccine design strategies that seek to elicit responses to a broad array of HIV-1 epitopes, and suggest a particular focus on Gag

    Assessing validity of a short food frequency questionnaire on present dietary intake of elderly Icelanders

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    <p>Abstract</p> <p>Background</p> <p>Few studies exist on the validity of food frequency questionnaires (FFQs) administered to elderly people. The aim of this study was to assess the validity of a short FFQ on present dietary intake, developed specially for the AGES-Reykjavik Study, which includes 5,764 elderly individuals. Assessing the validity of FFQs is essential before they are used in studies on diet-related disease risk and health outcomes.</p> <p>Method</p> <p>128 healthy elderly participants (74 y ± 5.7; 58.6% female) answered the AGES-FFQ, and subsequently filled out a 3-day weighed food record. Validity of the AGES-FFQ was assessed by comparing its answers to the dietary data obtained from the weighed food records, using Spearman's rank correlation, Chi-Square/Kendall's tau, and a Jonckheere-Terpstra test for trend.</p> <p>Result</p> <p>For men a correlation ≥ 0.4 was found for potatoes, fresh fruits, oatmeal/muesli, cakes/cookies, candy, dairy products, milk, pure fruit juice, cod liver oil, coffee, tea and sugar in coffee/tea (r = 0.40-0.71). A lower, but acceptable, correlation was also found for raw vegetables (r = 0.33). The highest correlation for women was found for consumption of rye bread, oatmeal/muesli, raw vegetables, candy, dairy products, milk, pure fruit juice, cod liver oil, coffee and tea (r = 0.40-0.61). An acceptable correlation was also found for fish topping/salad, fresh fruit, blood/liver sausage, whole-wheat bread, and sugar in coffee/tea (r = 0.28-0.37). Questions on meat/fish meals, cooked vegetables and soft drinks did not show a significant correlation to the reference method. Pearson Chi-Square and Kendall's tau showed similar results, as did the Jonckheere-Terpstra trend test.</p> <p>Conclusion</p> <p>A majority of the questions in the AGES-FFQ had an acceptable correlation and may be used to rank individuals according to their level of intake of several important foods/food groups. The AGES-FFQ on present diet may therefore be used to study the relationship between consumption of several specific foods/food groups and various health-related endpoints gathered in the AGES-Reykjavik Study.</p

    Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for “Holes” in the T Cell Repertoire

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    Background: Cytotoxic T cell (CTL) cross-reactivity is believed to play a pivotal role in generating immune responses but the extent and mechanisms of CTL cross-reactivity remain largely unknown. Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious sequence identity. The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands. Principal Findings: First, we analyzed peptide scans of the HIV epitope SLFNTVATL (SFL9) and found that TCR specificity is position dependent and that biochemically similar amino acid substitutions do not drastically affect recognition. Inspired by this, we developed a general model of TCR peptide recognition using amino acid similarity matrices and found that such a model was able to predict the cross-reactivity of a diverse set of CTL epitopes. With this model, we were able to demonstrate that seemingly distinct T cell epitopes, i.e., ones with low sequence identity, are in fact more biochemically similar than expected. Additionally, an analysis of HIV immunogenicity data with our model showed that CTLs have the tendency to respond mostly to peptides that do not resemble self-antigens. Conclusions: T cell cross-reactivity can thus, to an extent greater than earlier appreciated, be explained by amino acid similarity. The results presented in this paper will help resolving some of the long-lasting discussions in the field of T cel

    Simulation of Organ Patterning on the Floral Meristem Using a Polar Auxin Transport Model

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    An intriguing phenomenon in plant development is the timing and positioning of lateral organ initiation, which is a fundamental aspect of plant architecture. Although important progress has been made in elucidating the role of auxin transport in the vegetative shoot to explain the phyllotaxis of leaf formation in a spiral fashion, a model study of the role of auxin transport in whorled organ patterning in the expanding floral meristem is not available yet. We present an initial simulation approach to study the mechanisms that are expected to play an important role. Starting point is a confocal imaging study of Arabidopsis floral meristems at consecutive time points during flower development. These images reveal auxin accumulation patterns at the positions of the organs, which strongly suggests that the role of auxin in the floral meristem is similar to the role it plays in the shoot apical meristem. This is the basis for a simulation study of auxin transport through a growing floral meristem, which may answer the question whether auxin transport can in itself be responsible for the typical whorled floral pattern. We combined a cellular growth model for the meristem with a polar auxin transport model. The model predicts that sepals are initiated by auxin maxima arising early during meristem outgrowth. These form a pre-pattern relative to which a series of smaller auxin maxima are positioned, which partially overlap with the anlagen of petals, stamens, and carpels. We adjusted the model parameters corresponding to properties of floral mutants and found that the model predictions agree with the observed mutant patterns. The predicted timing of the primordia outgrowth and the timing and positioning of the sepal primordia show remarkable similarities with a developing flower in nature

    From bit to it: How a complex metabolic network transforms information into living matter

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    Organisms live and die by the amount of information they acquire about their environment. The systems analysis of complex metabolic networks allows us to ask how such information translates into fitness. A metabolic network transforms nutrients into biomass. The better it uses information on available nutrient availability, the faster it will allow a cell to divide. I here use metabolic flux balance analysis to show that the accuracy I (in bits) with which a yeast cell can sense a limiting nutrient's availability relates logarithmically to fitness as indicated by biomass yield and cell division rate. For microbes like yeast, natural selection can resolve fitness differences of genetic variants smaller than 10-6, meaning that cells would need to estimate nutrient concentrations to very high accuracy (greater than 22 bits) to ensure optimal growth. I argue that such accuracies are not achievable in practice. Natural selection may thus face fundamental limitations in maximizing the information processing capacity of cells. The analysis of metabolic networks opens a door to understanding cellular biology from a quantitative, information-theoretic perspective

    Influences of Forest Structure, Climate and Species Composition on Tree Mortality across the Eastern US

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    Few studies have quantified regional variation in tree mortality, or explored whether species compositional changes or within-species variation are responsible for regional patterns, despite the fact that mortality has direct effects on the dynamics of woody biomass, species composition, stand structure, wood production and forest response to climate change. Using Bayesian analysis of over 430,000 tree records from a large eastern US forest database we characterised tree mortality as a function of climate, soils, species and size (stem diameter). We found (1) mortality is U-shaped vs. stem diameter for all 21 species examined; (2) mortality is hump-shaped vs. plot basal area for most species; (3) geographical variation in mortality is substantial, and correlated with several environmental factors; and (4) individual species vary substantially from the combined average in the nature and magnitude of their mortality responses to environmental variation. Regional variation in mortality is therefore the product of variation in species composition combined with highly varied mortality-environment correlations within species. The results imply that variation in mortality is a crucial part of variation in the forest carbon cycle, such that including this variation in models of the global carbon cycle could significantly narrow uncertainty in climate change predictions
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