Carbohydrate Intake in Early Childhood and Body Composition and Metabolic Health: Results from the Generation R Study

High sugar intake in childhood has been linked to obesity. However, the role of macronutrient substitutions and associations with metabolic health remain unclear. We examined associations of carbohydrate intake and its subtypes with body composition and metabolic health among 3573 children participating in a population-based cohort in the Netherlands. Intake of total carbohydrate, monosaccharides and disaccharides, and polysaccharides at age 1 year was assessed with a food-frequency questionnaire. We repeatedly measured children’s height and weight to calculate BMI between their ages of 1 and 10 years. At ages 6 and 10 years, fat and fat-free mass were measured with dual-energy X-ray-absorptiometry and blood concentrations of triglycerides, cholesterol, and insulin were obtained. For all outcomes, we calculated age and sexspecific SD-scores. In multivariable-adjusted linear mixed models, we found no associations of intake of carbohydrates or its subtypes with children’s BMI or body composition. A higher intake of monosaccharides and disaccharides was associated with higher triglyceride concentrations (0.02 SDS per 10 g/day, 95% CI: 0.01, 0.04). Higher monosaccharide and disaccharide intake was also associated with lower HDL-cholesterol (−0.03 SDS, 95% CI: −0.04; −0.01), especially when it replaced polysaccharides. Overall, our findings suggest associations of higher monosaccharide and disaccharide intake in early childhood with higher triglyceride and lower HDL-choleste

When public service is the name of the game: the evolution of British and Spanish Public Service Broadcasters in online journalism

This chapter places the online migration of public service broadcasters against that of commercial news media to argue that the former’s public-service remit itself – based on a relative freedom from commercial concerns – has been a crucial contributor to their remarkable and distinctive online news successes. In order to do so, we explore the key moments, decisions and strategies of two of the biggest European PSBs – the British Broadcasting Corporation (BBC) and Radio Television Española (RTVE) – in the history of their online news operation. These PSBs are based on two very different funding and regulation models, with two notions of what a PSB should be, and therefore experienced quite opposite trajectories in the online news environment. Both, however, enjoyed quick successes after their launch, thanks to their underlying public service principles. The implications for the future of online news will be briefly discussed in the context of recent commercial media’s attacks on what they call the unfair competitive advantage of public service broadcasters in the online world

Evaluating the impact of incentives on clinical trial participation: Protocol for a mixed methods, community-engaged study

Background: Monetary incentives in research are frequently used to support participant recruitment and retention. However, there are scant empirical data regarding how researchers decide upon the type and amount of incentives offered. Likewise, there is little guidance to assist study investigators and institutional review boards (IRBs) in their decision-making on incentives. Monetary incentives, in addition to other factors such as the risk of harm or other intangible benefits, guide individuals' decisions to enroll in research studies. These factors emphasize the need for evidence-informed guidance for study investigators and IRBs when determining the type and amount of incentives to provide to research participants. Objective: The specific aims of our research project are to (1) characterize key stakeholders' views on and assessments of incentives in biomedical HIV research; (2) reach consensus among stakeholders on the factors that are considered when choosing research incentives, including consensus on the relative importance of such factors; and (3) pilot-test the use of the guidance developed via aims 1 and 2 by presenting stakeholders with vignettes of hypothetical research studies for which they will choose corresponding incentive types. Methods: Our 2-year study will involve monthly, active engagement with a stakeholder advisory board of people living with HIV, researchers, and IRB members. For aim 1, we will conduct a nationwide survey (N=300) among people living with HIV to understand their views regarding the incentives used in HIV research. For aim 2, we will collect qualitative data by conducting focus groups with people living with HIV (n=60) and key informant interviews with stakeholders involved in HIV research (people living with HIV, IRB members, and biomedical HIV researchers: n=36) to extend and deepen our understanding of how incentives in HIV research are perceived. These participants will also complete a conjoint analysis experiment to gain an understanding of the relative importance of key HIV research study attributes and the impact that these attributes have on study participation. The data from the nationwide survey (aim 1) will be triangulated with the qualitative and conjoint analysis data (aim 2) to create 25 vignettes that describe hypothetical HIV research studies. Finally, individuals from each stakeholder group will select the most appropriate incentive that they feel should be used in each of the 25 vignettes (aim 3). Results: The stakeholder advisory board began monthly meetings in March 2021. All study aims are expected to be completed by December 2022. Conclusions: By studying the role of incentives in HIV clinical trial participation, we will establish a decision-making paradigm to guide the choice of incentives for HIV research and, eventually, other types of similar research and facilitate the ethical recruitment of clinical research participants

Diet quality in childhood: the Generation R Study

Purpose: We aimed to evaluate diet quality of 8-year-old children in the Netherlands, to identify sociodemographic and lifestyle correlates of child diet quality, and to examine tracking of diet quality from ea

Rapid hepatic clearance of full length CCN-2/CTGF: a putative role for LRP1-mediated endocytosis

CCN-2 (connective tissue growth factor; CTGF) is a key factor in fibrosis. Plasma CCN-2 has biomarker potential in numerous fibrotic disorders, but it is unknown which pathophysiological factors determine plasma CCN-2 levels. The proteolytic amino-terminal fragment of CCN-2 is primarily eliminated by the kidney. Here, we investigated elimination and distribution profiles of full length CCN-2 by intravenous administration of recombinant CCN-2 to rodents. After bolus injection in mice, we observed a large initial distribution volume (454 mL/kg) and a fast initial clearance (120 mL/kg/min). Immunosorbent assay and immunostaining showed that CCN-2 distributed mainly to the liver and was taken up by hepatocytes. Steady state clearance in rats, determined by continuous infusion of CCN-2, was fast (45 mL/kg/min). Renal CCN-2 clearance, determined by arterial and renal vein sampling, accounted for only 12 % of total clearance. Co-infusion of CCN-2 with receptor-associated protein (RAP), an antagonist of LDL-receptor family proteins, showed that RAP prolonged CCN-2 half-life and completely prevented CCN-2 internalization by hepatocytes. This suggests that hepatic uptake of CCN-2 is mediated by a RAP-sensitive mechanism most likely involving LRP1, a member of the LDL-receptor family involved in hepatic clearance of various plasma proteins. Surface plasmon resonance binding studies confirmed that CCN-2 is an LRP1 ligand. Co-infusion of CCN-2 with an excess of the heparan sulphate-binding protamine lowered the large initial distribution volume of CCN-2 by 88 % and reduced interstitial staining of CCN-2, suggesting binding of CCN-2 to heparan sulphate proteoglycans (HSPGs). Protamine did not affect clearance rate, indicating that RAP-sensitive clearance of CCN-2 is HSPG independent. In conclusion, unlike its amino-terminal fragment which is cleared by the kidney, fu

Morphology of the archaellar motor and associated cytoplasmic cone in Thermococcus kodakaraensis

Archaeal swimming motility is driven by archaella: rotary motors attached to long extracellular filaments. The structure of these motors, and particularly how they are anchored in the absence of a peptidoglycan cell wall, is unknown. Here, we use electron cryotomography to visualize the archaellar basal body in vivo in Thermococcus kodakaraensis KOD1. Compared to the homologous bacterial type IV pilus (T4P), we observe structural similarities as well as several unique features. While the position of the cytoplasmic ATPase appears conserved, it is not braced by linkages that extend upward through the cell envelope as in the T4P, but rather by cytoplasmic components that attach it to a large conical frustum up to 500 nm in diameter at its base. In addition to anchoring the lophotrichous bundle of archaella, the conical frustum associates with chemosensory arrays and ribosome‐excluding material and may function as a polar organizing center for the coccoid cells

Associations of family feeding and mealtime practices with children's overall diet quality: Results from a prospective population-based cohort

Food parenting practices are considered to have a key influence on children's dietary habits, with potential long term effects. In this study, we explored the associations of parental feeding practices and family mealtime practices in early childhood with children's overall diet quality at school age among 3626 parents and their children in a population-based cohort study in Rotterdam, the Netherlands. Parental feeding practices (monitoring, pressure to eat, and restriction) and family mealtime practices (meal skipping behaviors and family meal frequency) at age 4 years were assessed by parental questionnaires. Children's dietary intake was assessed at age 8 years using a food-frequency questionnaire, from which diet quality scores (range 0–10) were calculated, reflecting adherence to age-specific dietary guidelines. Using multivariable linear regression models, we found that monitoring was associated with higher diet quality of children (β = 0.12; 95%CI: 0.08, 0.16), whereas pressure to eat was associated with lower diet quality (β = −0.08; 95%CI: −0.12, −0.04)), both independent of child BMI. Restriction was associated with a higher child diet quality, but this associati

Diet quality throughout early life in relation to allergic sensitization and atopic diseases in childhood

Early-life nutrition is an important modifiable determinant in the development of a child’s immune system, and may thereby influence the risk of allergic sensitization and atopic diseases. However, associations between overall dietary patterns and atopic diseases in childhood remain unclear. We examined associations of diet quality in early life with allergic sensitization, self-reported physician-diagnosed inhalant and food allergies, eczema, and asthma among 5225 children participating in a population-based cohort in the Netherlands. Diet was assessed during pregnancy, infancy, and childhood using validated food-frequency questionnaires. We calculated food-based diet quality scores (0–10 or 0–15), reflecting adherence to dietary guidelines. At age 10 years, allergic sensitization was assessed with skin prick tests. Information on physician-diagnosed inhalant and food allergies, eczema, and asthma was obtained with questionnaires. We observed no associations between diet quality during pregnancy and allergic sensitization (odds ratio (OR) = 1.05 per point in the diet score, 95% confidence interval (CI): 0.99, 1.13), allergies (0.96, 95% CI: 0.88, 1.04), eczema (0.99, 95% CI: 0.93, 1.06), or asthma (0.93, 95% CI: 0.85, 1.03) in childhood. Also, diet quality in infancy or childhood were not associated with atopic outcomes in childhood. Our findings do not support our hypothesis that a healthy dietary pattern in early life is associated with a lower risk of allergic sensitization or atopic diseases in childhood

The Alexander-Orbach conjecture holds in high dimensions

We examine the incipient infinite cluster (IIC) of critical percolation in regimes where mean-field behavior has been established, namely when the dimension d is large enough or when d>6 and the lattice is sufficiently spread out. We find that random walk on the IIC exhibits anomalous diffusion with the spectral dimension d_s=4/3, that is, p_t(x,x)= t^{-2/3+o(1)}. This establishes a conjecture of Alexander and Orbach. En route we calculate the one-arm exponent with respect to the intrinsic distance.Comment: 25 pages, 2 figures. To appear in Inventiones Mathematica

Diet quality in early and mid-childhood in relation to trajectories of growth and body composition.

Background: A balanced diet in childhood is important for growth and development. We aimed to examine associations of overall diet quality in both early and mid-childhood with trajectories of growth and body composition until age 10 years. Methods: We included 3991 children from the Generation R Study, a population-based, prospective cohort in Rotterdam, the Netherlands. At child's ages of 1 and 8 years, dietary intake was assessed using food-frequency questionnaires to calculate diet quality scores (0e10), which measure adherence to agespecific dietary guidelines. Height and weight were measured repeatedly between ages 1 and 10 years. Body composition was assessed using dual-energy X-ray absorptiometry at ages 6 and 10 years. We calculated sex- and age-specific SD-scores for body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI), and body fat percentage (BF%). Results: After adjustment for socioeconomic and lifestyle factors, results from linear mixed models showed that higher diet quality at 1 year was associated with higher height, weight, and BMI up to age 10 years. Using linear regression analyses, similar associations were observed for diet quality at 8 years. For diet quality at both time points, positive associations with BMI were fully driven by a higher FFMI (b