Online Consultation: ICTs and Development

As part of a series of global dialogues, in September 2011 IDS Knowledge Services brought together and facilitated an online community to discuss the relationship between living well and ICTs. The online forum was held over three days, 27 -- 29 September. It was hosted on the Eldis Communities platform and was facilitated by Abigail Murphy and Kelly Shephard. Technical support was provided by Adrian Bannister, Knowledge Services, IDS. The objective of the forum was to bring together a wide range of voices that would help to shape the Bellagio Summit in November.This document reflects on the approach taken and summarises the views expressed

Genetic ancestry of participants in the National Children's Study.

BackgroundThe National Children's Study (NCS) is a prospective epidemiological study in the USA tasked with identifying a nationally representative sample of 100,000 children, and following them from their gestation until they are 21 years of age. The objective of the study is to measure environmental and genetic influences on growth, development, and health. Determination of the ancestry of these NCS participants is important for assessing the diversity of study participants and for examining the effect of ancestry on various health outcomes.ResultsWe estimated the genetic ancestry of a convenience sample of 641 parents enrolled at the 7 original NCS Vanguard sites, by analyzing 30,000 markers on exome arrays, using the 1000 Genomes Project superpopulations as reference populations, and compared this with the measures of self-reported ethnicity and race. For 99% of the individuals, self-reported ethnicity and race agreed with the predicted superpopulation. NCS individuals self-reporting as Asian had genetic ancestry of either South Asian or East Asian groups, while those reporting as either Hispanic White or Hispanic Other had similar genetic ancestry. Of the 33 individuals who self-reported as Multiracial or Non-Hispanic Other, 33% matched the South Asian or East Asian groups, while these groups represented only 4.4% of the other reported categories.ConclusionsOur data suggest that self-reported ethnicity and race have some limitations in accurately capturing Hispanic and South Asian populations. Overall, however, our data indicate that despite the complexity of the US population, individuals know their ancestral origins, and that self-reported ethnicity and race is a reliable indicator of genetic ancestry

Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD.

Purpose3-Methylcrotonyl-CoA carboxylase deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism that has a highly variable clinical phenotype, ranging from acute metabolic acidosis to nonspecific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD.MethodsWe performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases.ResultsWe determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD.ConclusionOur study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes.Genet Med 17 8, 660-667

The Effects of Substance Use and Depressive Symptoms on High-Risk Sexual Behaviors in Sexually Active Vermont Adolescents

Background: There is a high prevalence of substance use, depressive symptoms, and high-risk sexual behaviors (HRSB) among adolescents, but the relationships between these variables is less clear. Objective: To identify associations between these behaviors and outcomes, this study aims to address how depressive symptoms paired with substance use impacts HRSB in adolescents. Methods: Adolescent self-reported depressive and suicidal symptoms, substance use, and HRSB were obtained from the 2015 Vermont Youth Risk Behavior Survey (YRBS) (n= 17,041). The associations between exposures (substance use and depressive symptoms) with HRSB were studied. Variables were calculated using prevalence ratios with 95% confidence intervals (CI) and logistic regression to determine adjusted odds ratios (OR). Results: Adolescents who attempted suicide more than once were \u3e5 times more likely to engage in 4+ HRSB (OR=5.19, P\u3c.001). Low-level drug users were 1.76 times more likely to engage in 4+ HRSB (p=\u3c0.05) and high-level users 6.69 times more likely (p\u3c.001). Reporting sexual intercourse with same sex partners was significantly associated with HRSB, while reported sexual orientation was not. Conclusions: There are associations between both self-reported depressive symptoms and substance use with high-risk sexual behavior in adolescents

Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD

Purpose: 3-Methylcrotonyl-CoA carboxylase deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism that has a highly variable clinical phenotype, ranging from acute metabolic acidosis to nonspecific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD. Methods: We performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases. Results: We determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD. Conclusion: Our study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes

Can Physicians Identify Inappropriate Nuclear Stress Tests? An Examination of Inter-Rater Reliability for the 2009 Appropriate Use Criteria for Radionuclide Imaging

Background—We sought to determine inter-rater reliability of the 2009 Appropriate Use Criteria for radionuclide imaging and whether physicians at various levels of training can effectively identify nuclear stress tests with inappropriate indications. Methods and Results—Four hundred patients were randomly selected from a consecutive cohort of patients undergoing nuclear stress testing at an academic medical center. Raters with different levels of training (including cardiology attending physicians, cardiology fellows, internal medicine hospitalists, and internal medicine interns) classified individual nuclear stress tests using the 2009 Appropriate Use Criteria. Consensus classification by 2 cardiologists was considered the operational gold standard, and sensitivity and specificity of individual raters for identifying inappropriate tests were calculated. Inter-rater reliability of the Appropriate Use Criteria was assessed using Cohen κ statistics for pairs of different raters. The mean age of patients was 61.5 years; 214 (54%) were female. The cardiologists rated 256 (64%) of 400 nuclear stress tests as appropriate, 68 (18%) as uncertain, 55 (14%) as inappropriate; 21 (5%) tests were unable to be classified. Inter-rater reliability for noncardiologist raters was modest (unweighted Cohen κ, 0.51, 95% confidence interval, 0.45–0.55). Sensitivity of individual raters for identifying inappropriate tests ranged from 47% to 82%, while specificity ranged from 85% to 97%. Conclusions—Inter-rater reliability for the 2009 Appropriate Use Criteria for radionuclide imaging is modest, and there is considerable variation in the ability of raters at different levels of training to identify inappropriate tests