Causal Pathways from Enteropathogens to Environmental Enteropathy: Findings from the MAL-ED Birth Cohort Study

Background Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Methods Non-diarrheal stool samples (N = 22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N = 6363) and plasma alpha-1-acid glycoprotein (AGP) (N = 2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0–2 years of age. Findings Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. Interpretation The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation

Micronutrient intake and the probability of nutrient adequacy among children 9-24 months of age : results from the MAL-ED birth cohort study

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Medium Resolution Lunar Topography: An Updated View of the Lunar Surface from Stereophotogrammetrically Derived DTMs

Digital Terrain Models (DTMs) are essential for lunar exploration, supporting critical applications such as landing site selection, mission planning, and in-situ resource utilization. This study presents a comprehensive reprocessing of the Kaguya Terrain Camera (TC) dataset using the NASA Ames Stereo Pipeline to generate over 130,000 medium-resolution DTMs with nearly global lunar coverage to ±70°. We observed significant bowing in the DTMs derived using the publicly available interior orientation and have used a novel technique, in the planetary sciences, to re-estimate the boresight and eight-parameter distortion coefficients. We present a jitter correction methodology to correct for vertical alignment errors in the DTMs. DTMs are aligned to the Lunar Orbiter Laser Altimeter (LOLA) point cloud and absolute errors are mean centered to zero with a mean standard deviation of 24 meters. We achieved horizontal accuracies inside the orthoimage resolution (mean of 30 meters per pixel) and 2—4 meters vertically. The methods and insights gained from this large-scale processing effort establish a framework for automating DTM derivation with other planetary data sets

Study of different subcooling control strategies in order to enhance the performance of a heat pump

[EN] The performance of vapor-compression systems working with subcritical refrigerants varies with the degree of subcooling. There is an optimal subcooling that maximizes efficiency. However, it depends on the operating conditions and the control of the system needs to be adapted. Most of the works available in literature are able to operate in optimal conditions only at the design point or if a system is designed to be able to adapt its subcooling, only complex control algorithms that usually are difficult to set and time-costly, are used. This work focuses on the study of the main variables influencing the optimal subcooling and analyzes two different control methodologies from the theoretical point of view. Based on the theoretical study a final control strategy is selected and tested experimentally. The reliability, stability and robustness of the selected strategy are experimentally demonstrated for a wide set of operating conditions. (c) 2018 Elsevier Ltd and IIR. All rights reserved.Part of the work presented was carried by Estefania Hervas Blasco with the financial support of a PhD scholarship from the Spanish government SFPI1500 x 074478XV0. The authors would like also to acknowledge the Spanish 'MINISTERIO DE ECONOMIA Y COMPETITIVIDAD', through the project. "MAXIMIZACION DE LA EFICIENCIA Y MINIMIZACION DEL IMPACTO AMBIENTAL DE BOMBAS DE CALOR PARA LA DESCARBONIZACION DE LA CALEFACCION/ACS EN LOS EDIFICIOS DECONSUMO CASI NULO" with the reference ENE2017-83665-C2-1-P for the given support.Hervas-Blasco, E.; Pitarch, M.; Navarro-Peris, E.; Corberán, JM. (2018). Study of different subcooling control strategies in order to enhance the performance of a heat pump. International Journal of Refrigeration. 88:324-336. https://doi.org/10.1016/j.ijrefrig.2018.02.003S3243368

Accuracies of genomic breeding values in American Angus beef cattle using K-means clustering for cross-validation

<p>Abstract</p> <p>Background</p> <p>Genomic selection is a recently developed technology that is beginning to revolutionize animal breeding. The objective of this study was to estimate marker effects to derive prediction equations for direct genomic values for 16 routinely recorded traits of American Angus beef cattle and quantify corresponding accuracies of prediction.</p> <p>Methods</p> <p>Deregressed estimated breeding values were used as observations in a weighted analysis to derive direct genomic values for 3570 sires genotyped using the Illumina BovineSNP50 BeadChip. These bulls were clustered into five groups using K-means clustering on pedigree estimates of additive genetic relationships between animals, with the aim of increasing within-group and decreasing between-group relationships. All five combinations of four groups were used for model training, with cross-validation performed in the group not used in training. Bivariate animal models were used for each trait to estimate the genetic correlation between deregressed estimated breeding values and direct genomic values.</p> <p>Results</p> <p>Accuracies of direct genomic values ranged from 0.22 to 0.69 for the studied traits, with an average of 0.44. Predictions were more accurate when animals within the validation group were more closely related to animals in the training set. When training and validation sets were formed by random allocation, the accuracies of direct genomic values ranged from 0.38 to 0.85, with an average of 0.65, reflecting the greater relationship between animals in training and validation. The accuracies of direct genomic values obtained from training on older animals and validating in younger animals were intermediate to the accuracies obtained from K-means clustering and random clustering for most traits. The genetic correlation between deregressed estimated breeding values and direct genomic values ranged from 0.15 to 0.80 for the traits studied.</p> <p>Conclusions</p> <p>These results suggest that genomic estimates of genetic merit can be produced in beef cattle at a young age but the recurrent inclusion of genotyped sires in retraining analyses will be necessary to routinely produce for the industry the direct genomic values with the highest accuracy.</p

Intestinal permeability and inflammation mediate the association between nutrient density of complementary foods and biochemical measures of micronutrient status in young children: results from the MAL-ED study

Background: Environmental enteric dysfunction (EED) is thought to increase the risk of micronutrient deficiencies, but few studies adjust for dietary intakes and systemic inflammation. Objective: We tested whether EED is associated with micronutrient deficiency risk independent of diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status. Methods: Using data from 1283 children in the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort we evaluated the risk of anemia, low retinol, zinc, and ferritin, and high transferrin receptor (TfR) at 15 mo. We characterized gut inflammation and permeability by myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT) concentrations from asymptomatic fecal samples averaged from 9 to 15 mo, and averaged the lactulose:mannitol ratio z-score (LMZ) at 9 and 15 mo. Nutrient intakes from complementary foods were quantified monthly from 9 to 15 mo and densities were averaged for analyses. α-1-Acid glycoprotein at 15 mo characterized systemic inflammation. Relations between variables were modeled using a Bayesian network. Results: A greater risk of anemia was associated with LMZ [1.15 (95% CI: 1.01, 1.31)] and MPO [1.16 (1.01, 1.34)]. A greater risk of low ferritin was associated with AAT [1.19 (1.03, 1.37)] and NEO [1.22 (1.04, 1.44)]. A greater risk of low retinol was associated with LMZ [1.24 (1.08, 1.45)]. However, MPO was associated with a lower risk of high transferrin receptor [0.86 (0.74, 0.98)], NEO with a lower risk of low retinol [0.75 (0.62, 0.89)], and AAT with a lower risk of low plasma zinc [0.83 (0.70, 0.99)]. Greater nutrient intake densities (vitamins A and B6, calcium, protein, and zinc) were negatively associated with EED. Inverse associations between nutrient densities and micronutrient deficiency largely disappeared after adjustment for EED, suggesting that EED mediates these associations. Conclusions: EED is independently associated with an increased risk of low ferritin, low retinol, and anemia. Greater nutrient density from complementary foods may reduce EED, and the control of micronutrient deficiencies may require control of EED

Novel analytical method, Birth Date Selection Mapping, detects response of the Angus (Bos taurus) genome to selection on complex traits

Background: Several methods have recently been developed to identify regions of the genome that have been exposed to strong selection. However, recent theoretical and empirical work suggests that polygenic models are required to identify the genomic regions that are more moderately responding to ongoing selection on complex traits. We examine the effects of multi-trait selection on the genome of a population of US registered Angus beef cattle born over a 50-year period representing approximately 10 generations of selection. We present results from the application of a quantitative genetic model, called Birth Date Selection Mapping, to identify signatures of recent ongoing selection.Results: We show that US Angus cattle have been systematically selected to alter their mean additive genetic merit for most of the 16 production traits routinely recorded by breeders. Using Birth Date Selection Mapping, we estimate the time-dependency of allele frequency for 44,817 SNP loci using genomic best linear unbiased prediction, generalized least squares, and BayesCpi analyses. Finally, we reconstruct the primary phenotypes that have historically been exposed to selection from a genome-wide analysis of the 16 production traits and gene ontology enrichment analysis.Conclusions: We demonstrate that Birth Date Selection Mapping utilizing mixed models corrects for time-dependent pedigree sampling effects that lead to spurious SNP associations and reveals genomic signatures of ongoing selection on complex traits. Because multiple traits have historically been selected in concert and most quantitative trait loci have small effects, selection has incrementally altered allele frequencies throughout the genome. Two quantitative trait loci of large effect were not the most strongly selected of the loci due to their antagonistic pleiotropic effects on strongly selected phenotypes. Birth Date Selection Mapping may readily be extended to temporally-stratified human or model organism populations.Peer reviewedAnimal Scienc

Relationship between growth and illness, enteropathogens and dietary intakes in the first 2 years of life: Findings from the MAL-ED birth cohort study

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. Background Dietary and illness factors affect risk of growth faltering; the role of enteropathogens is less clear. As part of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study, we quantify the effects of enteropathogen infection, diarrhoea and diet on child growth. Methods Newborns were enrolled and followed until 24 months. Length and weight were assessed monthly. Illnesses and breastfeeding practices were documented biweekly; from 9 to 24 months, non-breast milk intakes were quantified monthly. Routinely collected non-diarrhoeal stools were analysed for a broad array of enteropathogens. A linear piecewise spline model was used to quantify associations of each factor with growth velocity in seven of eight MAL-ED sites; cumulative effects on attained size at 24 months were estimated for mean, low (10th percentile) and high (90th percentile) exposure levels. Additionally, the six most prevalent enteropathogens were evaluated for their effects on growth. results Diarrhoea did not have a statistically significant effect on growth. Children with high enteropathogen exposure were estimated to be 1.21±0.33 cm (p<0.001; 0.39 length for age (LAZ)) shorter and 0.08±0.15 kg (p=0.60; 0.08 weight-for-age (WAZ)) lighter at 24 months, on average, than children with low exposure. Campylobacter and enteroaggregativeEscherichia coli detections were associated with deficits of 0.83±0.33 and 0.85±0.31 cm in length (p=0.011 and 0.001) and 0.22±0.15 and 0.09±0.14 kg in weight (p=0.14 and 0.52), respectively. Children with low energy intakes and protein density were estimated to be 1.39±0.33 cm (p<0.001; 0.42 LAZ) shorter and 0.81±0.15 kg (p<0.001; 0.65 WAZ) lighter at 24 months than those with high intakes. conclusions Reducing enteropathogen burden and improving energy and protein density of complementary foods could reduce stunting