The Building Blocks of Interoperability. A Multisite Analysis of Patient Demographic Attributes Available for Matching.

BackgroundPatient matching is a key barrier to achieving interoperability. Patient demographic elements must be consistently collected over time and region to be valuable elements for patient matching.ObjectivesWe sought to determine what patient demographic attributes are collected at multiple institutions in the United States and see how their availability changes over time and across clinical sites.MethodsWe compiled a list of 36 demographic elements that stakeholders previously identified as essential patient demographic attributes that should be collected for the purpose of linking patient records. We studied a convenience sample of 9 health care systems from geographically distinct sites around the country. We identified changes in the availability of individual patient demographic attributes over time and across clinical sites.ResultsSeveral attributes were consistently available over the study period (2005-2014) including last name (99.96%), first name (99.95%), date of birth (98.82%), gender/sex (99.73%), postal code (94.71%), and full street address (94.65%). Other attributes changed significantly from 2005-2014: Social security number (SSN) availability declined from 83.3% to 50.44% (p<0.0001). Email address availability increased from 8.94% up to 54% availability (p<0.0001). Work phone number increased from 20.61% to 52.33% (p<0.0001).ConclusionsOverall, first name, last name, date of birth, gender/sex and address were widely collected across institutional sites and over time. Availability of emerging attributes such as email and phone numbers are increasing while SSN use is declining. Understanding the relative availability of patient attributes can inform strategies for optimal matching in healthcare

Spitzer Survey of the Large Magellanic Cloud, Surveying the Agents of a Galaxy's Evolution (SAGE) I: Overview and Initial Results

We are performing a uniform and unbiased, ~7x7 degrees imaging survey of the Large Magellanic Cloud (LMC), using the IRAC and MIPS instruments on board the Spitzer Space Telescope in order to survey the agents of a galaxy's evolution (SAGE), the interstellar medium (ISM) and stars in the LMC. The detection of diffuse ISM with column densities >1.2x10^21 H cm^-2 permits detailed studies of dust processes in the ISM. SAGE's point source sensitivity enables a complete census of newly formed stars with masses >3 solar masses that will determine the current star formation rate in the LMC. SAGE's detection of evolved stars with mass loss rates >1x10^-8 solar masses per year will quantify the rate at which evolved stars inject mass into the ISM of the LMC. The observing strategy includes two epochs in 2005, separated by three months, that both mitigate instrumental artifacts and constrain source variability. The SAGE data are non-proprietary. The data processing includes IRAC and MIPS pipelines and a database for mining the point source catalogs, which will be released to the community in support of Spitzer proposal cycles 4 and 5. We present initial results on the epoch 1 data with a special focus on the N79 and N83 region. The SAGE epoch 1 point source catalog has ~4 million sources. The point source counts are highest for the IRAC 3.6 microns band and decrease dramatically towards longer wavelengths consistent with the fact that stars dominate the point source catalogs and that the dusty objects, e.g. young stellar objects and dusty evolved stars that detected at the longer wavelengths, are rare in comparison. We outline a strategy for identifying foreground MW stars, that may comprise as much as 18% of the source list, and background galaxies, that may comprise ~12% of the source list.Comment: Accepted by the Astronomical Journa

Spitzer survey of the Large Magellanic Cloud, surveying the agents of a galaxy's evolution (SAGE). IV. Dust properties in the interstellar medium

The goal of this paper is to present the results of a preliminary analysis of the extended infrared (IR) emission by dust in the interstellar medium (ISM) of the Large Magellanic Cloud (LMC). We combine Spitzer Surveying the Agents of Galaxy Evolution (SAGE) and Infrared Astronomical Satellite (IRAS) data and correlate the infrared emission with gas tracers of H I, CO, and Hα. We present a global analysis of the infrared emission as well as detailed modeling of the spectral energy distribution (SED) of a few selected regions. Extended emission by dust associated with the neutral, molecular, and diffuse ionized phases of the ISM is detected at all IR bands from 3.6 μm to 160 μm. The relative abundance of the various dust species appears quite similar to that in the Milky Way (MW) in all the regions we have modeled. We construct maps of the temperature of large dust grains. The temperature map shows variations in the range 12.1-34.7 K, with a systematic gradient from the inner to outer regions, tracing the general distribution of massive stars and individual H II regions as well as showing warmer dust in the stellar bar. This map is used to derive the far-infrared (FIR) optical depth of large dust grains. We find two main departures in the LMC with respect to expectations based on the MW: (1) excess mid-infrared (MIR) emission near 70 μm, referred to as the 70 μm excess, and (2) departures from linear correlation between the FIR optical depth and the gas column density, which we refer to as FIR excess emission. The 70 μm excess increases gradually from the MW to the LMC to the Small Magellanic Cloud (SMC), suggesting evolution with decreasing metallicity. The excess is associated with the neutral and diffuse ionized gas, with the strongest excess region located in a loop structure next to 30 Dor. We show that the 70 μm excess can be explained by a modification of the size distribution of very small grains with respect to that in the MW, and a corresponding mass increase of ≃13% of the total dust mass in selected regions. The most likely explanation is that the 70 μm excess is due to the production of large very small grains (VSG) through erosion of larger grains in the diffuse medium. This FIR excess could be due to intrinsic variations of the dust/gas ratio, which would then vary from 4.6 to 2.3 times lower than the MW values across the LMC, but X_(CO) values derived from the IR emission would then be about three times lower than those derived from the Virial analysis of the CO data. We also investigate the possibility that the FIR excess is associated with an additional gas component undetected in the available gas tracers. Assuming a constant dust abundance in all ISM phases, the additional gas component would have twice the known H I mass. We show that it is plausible that the FIR excess is due to cold atomic gas that is optically thick in the 21 cm line, while the contribution by a pure H_2 phase with no CO emission remains a possible explanation

IQuaD dental trial; improving the quality of dentistry : a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care

Peer reviewedPublisher PD

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis.

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease

Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10$^{−35}$ and <10$^{−8}$ respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10$^{−6}$). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10$^{−20}$) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

Meta-analysis of genome-wide association studies for extraversion:Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Understanding the Return of Genomic Sequencing Results Process: Content Review of Participant Summary Letters in the eMERGE Research Network

A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine the features of genetic results letters produced at each Electronic Medical Records and Genomics (eMERGE3) Network site to assess their readability and content. Letters were collected from each site, and a qualitative analysis of letter content and a quantitative analysis of readability statistics were performed. Because letters were produced independently at each eMERGE site, significant heterogeneity in readability and content was found. The content of letters varied widely from a baseline of notifying participants that results existed to more detailed information about positive or negative results, as well as materials for sharing with family members. Most letters were significantly above the Centers for Disease Control-suggested reading level for health communication. While continued effort should be applied to make letters easier to understand, the ongoing challenge of explaining complex genomic information, the implications of negative test results, and the uncertainty that comes with some types of test and result makes simplifying letter text challenging