Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We used molecular diagnostics to assess whether particular enteropathogens were associated with ...linear growth across seven low-resource settings.
We used quantitative PCR to detect 29 enteropathogens in diarrhoeal and non-diarrhoeal stools collected from children in the first 2 years of life obtained during the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite cohort study. Length was measured monthly. We estimated associations between aetiology-specific diarrhoea and subclinical enteropathogen infection and quantity and attained length in 3 month intervals, at age 2 and 5 years, and used a longitudinal model to account for temporality and time-dependent confounding.
Among 1469 children who completed 2 year follow-up, 35 622 stool samples were tested and yielded valid results. Diarrhoeal episodes attributed to bacteria and parasites, but not viruses, were associated with small decreases in length after 3 months and at age 2 years. Substantial decrements in length at 2 years were associated with subclinical, non-diarrhoeal, infection with Shigella (length-for-age Z score LAZ reduction −0·14, 95% CI −0·27 to −0·01), enteroaggregative Escherichia coli (−0·21, −0·37 to −0·05), Campylobacter (−0·17, −0·32 to −0·01), and Giardia (−0·17, −0·30 to −0·05). Norovirus, Cryptosporidium, typical enteropathogenic E coli, and Enterocytozoon bieneusi were also associated with small decrements in LAZ. Shigella and E bieneusi were associated with the largest decreases in LAZ per log increase in quantity per g of stool (−0·13 LAZ, 95% CI −0·22 to −0·03 for Shigella; −0·14, −0·26 to −0·02 for E bieneusi). Based on these models, interventions that successfully decrease exposure to Shigella, enteroaggregative E coli, Campylobacter, and Giardia could increase mean length of children by 0·12–0·37 LAZ (0·4–1·2 cm) at the MAL-ED sites.
Subclinical infection and quantity of pathogens, particularly Shigella, enteroaggregative E coli, Campylobacter, and Giardia, had a substantial negative association with linear growth, which was sustained during the first 2 years of life, and in some cases, to 5 years. Successfully reducing exposure to certain pathogens might reduce global stunting.
Bill & Melinda Gates Foundation.
Background
Goats are increasingly popular as both production animals and pets. The frequency of and factors associated with periparturient reproductive complications in goats are largely unreported.
...Objectives
(1) To report the frequency of periparturient reproductive complications in does presented to university veterinary hospitals and (2) to identify factors associated with uterine tears in the study population.
Animals
A total of 198 periparturient does presented to 9 university veterinary hospitals from October 2021 to June 2022.
Methods
Multicenter, cross‐sectional study, with data collected from questionnaires completed by attending veterinarians. Logistic regression was used to identify factors associated with diagnosis of uterine tears.
Results
Ninety‐three (47%) does had at least 1 periparturient reproductive complication. Periparturient complications included retained fetal membranes (n = 38, 26%), vaginal or perineal trauma (n = 33, 19%), uterine tears (n = 32, 18%), metritis (n = 22, 13%), uterine or vaginal hemorrhage (n = 8, 5%), Cesarean section complications (n = 8, 8%), and uterine prolapse (n = 1, 0.5%). A positive interaction effect was found between small breeds (Nigerian Dwarf and Pygmy) and manipulation on the farm by a layperson upon diagnosis of uterine tears (odd ratios OR, 5.48; 95% confidence interval CI, 1.41, 21.25; P = .01).
Conclusions and Clinical Importance
Periparturient reproductive complications were common. Small breed combined with manipulation on the farm by layperson was associated with diagnosis of uterine tears. Clients should be educated that in the event of dystocia, small breed does are at greater risk of uterine tears and prompt veterinary intervention is critical.
Optimum management of childhood diarrhoea in low-resource settings has been hampered by insufficient data on aetiology, burden, and associated clinical characteristics. We used quantitative ...diagnostic methods to reassess and refine estimates of diarrhoea aetiology from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study.
We re-analysed stool specimens from the multisite MAL-ED cohort study of children aged 0–2 years done at eight locations (Dhaka, Bangladesh; Vellore, India; Bhaktapur, Nepal; Naushero Feroze, Pakistan; Venda, South Africa; Haydom, Tanzania; Fortaleza, Brazil; and Loreto, Peru), which included active surveillance for diarrhoea and routine non-diarrhoeal stool collection. We used quantitative PCR to test for 29 enteropathogens, calculated population-level pathogen-specific attributable burdens, derived stringent quantitative cutoffs to identify aetiology for individual episodes, and created aetiology prediction scores using clinical characteristics.
We analysed 6625 diarrhoeal and 30 968 non-diarrhoeal surveillance stools from 1715 children. Overall, 64·9% of diarrhoea episodes (95% CI 62·6–71·2) could be attributed to an aetiology by quantitative PCR compared with 32·8% (30·8–38·7) using the original study microbiology. Viral diarrhoea (36·4% of overall incidence, 95% CI 33·6–39·5) was more common than bacterial (25·0%, 23·4–28·4) and parasitic diarrhoea (3·5%, 3·0–5·2). Ten pathogens accounted for 95·7% of attributable diarrhoea: Shigella (26·1 attributable episodes per 100 child-years, 95% CI 23·8–29·9), sapovirus (22·8, 18·9–27·5), rotavirus (20·7, 18·8–23·0), adenovirus 40/41 (19·0, 16·8–23·0), enterotoxigenic Escherichia coli (18·8, 16·5–23·8), norovirus (15·4, 13·5–20·1), astrovirus (15·0, 12·0–19·5), Campylobacter jejuni or C coli (12·1, 8·5–17·2), Cryptosporidium (5·8, 4·3–8·3), and typical enteropathogenic E coli (5·4, 2·8–9·3). 86·2% of the attributable incidence for Shigella was non-dysenteric. A prediction score for shigellosis was more accurate (sensitivity 50·4% 95% CI 46·7–54·1, specificity 84·0% 83·0–84·9) than current guidelines, which recommend treatment only of bloody diarrhoea to cover Shigella (sensitivity 14·5% 95% CI 12·1–17·3, specificity 96·5% 96·0–97·0).
Quantitative molecular diagnostics improved estimates of pathogen-specific burdens of childhood diarrhoea in the community setting. Viral causes predominated, including a substantial burden of sapovirus; however, Shigella had the highest overall burden with a high incidence in the second year of life. These data could improve the management of diarrhoea in these low-resource settings.
Bill & Melinda Gates Foundation.
Widespread sharing of data from electronic health records and patient-reported outcomes can strengthen the national capacity for conducting cost-effective clinical trials and allow research to be ...embedded within routine care delivery. While pragmatic clinical trials (PCTs) have been performed for decades, they now can draw on rich sources of clinical and operational data that are continuously fed back to inform research and practice. The Health Care Systems Collaboratory program, initiated by the NIH Common Fund in 2012, engages healthcare systems as partners in discussing and promoting activities, tools, and strategies for supporting active participation in PCTs. The NIH Collaboratory consists of seven demonstration projects, and seven problem-specific working group 'Cores', aimed at leveraging the data captured in heterogeneous 'real-world' environments for research, thereby improving the efficiency, relevance, and generalizability of trials. Here, we introduce the Collaboratory, focusing on its Phenotype, Data Standards, and Data Quality Core, and present early observations from researchers implementing PCTs within large healthcare systems. We also identify gaps in knowledge and present an informatics research agenda that includes identifying methods for the definition and appropriate application of phenotypes in diverse healthcare settings, and methods for validating both the definition and execution of electronic health records based phenotypes.
An important economic reason for the loss of local breeds is that they tend to be less productive, and hence having less market value than commercial breeds. Nevertheless, local breeds often have ...irreplaceable values, genetically and sociologically. In the breeding programs with local breeds, it is crucial to balance the selection for genetic gain and the maintaining of genetic diversity. These two objectives are often conflicting, and finding the optimal point of the trade-off has been a challenge for breeders. Genomic selection (GS) provides a revolutionary tool for the genetic improvement of farm animals. At the same time, it can increase inbreeding and produce a more rapid depletion of genetic variability of the selected traits in future generations. Optimum-contribution selection (OCS) represents an approach to maximize genetic gain while constraining inbreeding within a targeted range. In the present study, 515 Ningxiang pigs were genotyped with the Illumina Porcine SNP60 array or the GeneSeek Genomic Profiler Porcine 50K array. The Ningxiang pigs were found to be highly inbred at the genomic level. Average locus-wise inbreeding coefficients were 0.41 and 0.37 for the two SNP arrays used, whereas genomic inbreeding coefficients based on runs of homozygosity were 0.24 and 0.25, respectively. Simulated phenotypic data were used to assess the utility of genomic OCS (GOCS) in comparison with GS without inbreeding control. GOCS was conducted under two scenarios, selecting sires only (GOCS_S) or selecting sires and dams (GOCS_SD), while kinships were constrained on selected parents. The genetic gain for average daily body weight gain (ADG) per generation was between 18.99 and 20.55 g with GOCS_S, and between 23.20 and 28.92 with GOCS_SD, and it varied from 25.38 to 48.38 g under GS without controlling inbreeding. While the rate of genetic gain per generation obtained using GS was substantially larger than that obtained by the two scenarios of genomic OCS in the beginning generations of selection, the difference in the genetic gain of ADG between GS and GOCS reduced quickly in latter generations. At generation ten, the difference in the realized rates of genetic gain between GS and GOCS_SD diminished and ended up with even a slightly higher genetic gain with GOCS_SD, due to the rapid loss of genetic variance with GS and fixation of causative genes. The rate of inbreeding was mostly maintained below 5% per generation with genomic OCS, whereas it increased to between 10.5% and 15.3% per generation with GS. Therefore, genomic OCS appears to be a sustainable strategy for the genetic improvement of local breeds such as Ningxiang pigs, but keeping mind that a variety of GOCS methods exist and the optimal forms remain to be exploited further.
Abstract
Objective:
To estimate the total energy and micronutrient intakes of children 9–24 months of age and evaluate the probability of adequacy (PA) of the diet in seven MAL-ED sites.
Design:
...Cohort study. Food intake was registered monthly using 24-h recalls beginning at 9 months. We estimated PA for thirteen nutrients and overall mean PA (MPA) by site and 3-month periods considering estimated breast milk intake.
Setting:
Seven sites in Asia, Africa and Latin America.
Participants:
1669 children followed from birth to 24 months of age.
Results:
Median estimated %energy from breast milk ranged from 4 to 70 % at 9–12 months, and declined to 0–39 % at 21–24 months. Iron bioavailability was low for all sites, but many diets were of moderate bioavailability for zinc. PA was optimal for most nutrients in Brazil and South Africa, except for iron and vitamin E (both), calcium and zinc (South Africa). PA for zinc increased only for children consuming a diet with moderate bioavailability. MPA increased 12–24 months as the quantity of complementary foods increased; however, PA for vitamin A remained low in Bangladesh and Tanzania. PA for vitamins D and E and iron was low for most sites and age groups.
Conclusions:
MPA increased from 12 to 24 months as children consumed higher quantities of food, while nutrient density remained constant for most nutrients. Ways to increase the consumption of foods containing vitamins D, E and A, and calcium are needed, as are ways to increase the bioavailability of iron and zinc.
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.
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.
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.
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.
Background. Enteropathogen infections have been associated with enteric dysfunction and impaired growth in children in lowresource settings. In a multisite birth cohort study (MAL-ED), we describe ...the epidemiology and impact of Campylobacter infection in the first 2 years of life. Methods. Children were actively followed up until 24 months of age. Diarrheal and nondiarrheal stool samples were collected and tested by enzyme immunoassay for Campylobacter. Stool and blood samples were assayed for markers of intestinal permeability and inflammation. Results. A total of 1892 children had 7601 diarrheal and 26 267 nondiarrheal stool samples tested for Campylobacter. We describe a high prevalence of infection, with most children (n = 1606; 84.9%) having a Campylobacter-positive stool sample by 1 year of age. Factors associated with a reduced risk of Campylobacter detection included exclusive breastfeeding (risk ratio, 0.57; 95% confidence interval, .47–.67), treatment of drinking water (0.76; 0.70–0.83), access to an improved latrine (0.89; 0.82–0.97), and recent macrolide antibiotic use (0.68; 0.63–0.74). A high Campylobacter burden was associated with a lower length-for-age Z score at 24 months (−1.82; 95% confidence interval, −1.94 to −1.70) compared with a low burden (−1.49; −1.60 to −1.38). This association was robust to confounders and consistent across sites. Campylobacter infection was also associated with increased intestinal permeability and intestinal and systemic inflammation. Conclusions. Campylobacter was prevalent across diverse settings and associated with growth shortfalls. Promotion of exclusive breastfeeding, drinking water treatment, improved latrines, and targeted antibiotic treatment may reduce the burden of Campylobacter infection and improve growth in children in these settings.
The Kaiser Permanente & Strategic Partners Patient Outcomes Research To Advance Learning (PORTAL) network engages four healthcare delivery systems (Kaiser Permanente, Group Health Cooperative, ...HealthPartners, and Denver Health) and their affiliated research centers to create a new national network infrastructure that builds on existing relationships among these institutions. PORTAL is enhancing its current capabilities by expanding the scope of the common data model, paying particular attention to incorporating patient-reported data more systematically, implementing new multi-site data governance procedures, and integrating the PCORnet PopMedNet platform across our research centers. PORTAL is partnering with clinical research and patient experts to create cohorts of patients with a common diagnosis (colorectal cancer), a rare diagnosis (adolescents and adults with severe congenital heart disease), and adults who are overweight or obese, including those with pre-diabetes or diabetes, to conduct large-scale observational comparative effectiveness research and pragmatic clinical trials across diverse clinical care settings.
A variety of statistical methods, such as admixture models, have been used to estimate genomic breed composition (GBC). These methods, however, tend to produce non-zero components to reference breeds ...that shared some genomic similarity with a test animal. These non-essential GBC components, in turn, offset the estimated GBC for the breed to which it belongs. As a result, not all purebred animals have 100% GBC of their respective breeds, which statistically indicates an elevated false-negative rate in the identification of purebred animals with 100% GBC as the cutoff. Otherwise, a lower cutoff of estimated GBC will have to be used, which is arbitrary, and the results are less interpretable. In the present study, three admixture models with regularization were proposed, which produced sparse solutions through suppressing the noise in the estimated GBC due to genomic similarities. The regularization or penalty forms included the L1 norm penalty, minimax concave penalty (MCP), and smooth clipped absolute deviation (SCAD). The performances of these regularized admixture models on the estimation of GBC were examined in purebred and composite animals, respectively, and compared to that of the non-regularized admixture model as the baseline model. The results showed that, given optimal values for λ, the three sparsely regularized admixture models had higher power and thus reduced the false-negative rate for the breed identification of purebred animals than the non-regularized admixture model. Of the three regularized admixture models, the two with a non-convex penalty outperformed the one with L1 norm penalty. In the Brangus, a composite cattle breed, estimated GBC were roughly comparable among the four admixture models, but all the four models underestimated the GBC for these composite animals when non-ancestral breeds were included as the reference. In conclusion, the admixture models with sparse regularization gave more parsimonious, consistent and interpretable results of estimated GBC for purebred animals than the non-regularized admixture model. Nevertheless, the utility of regularized admixture models for estimating GBC in crossbred or composite animals needs to be taken with caution.
PDF
