ADHD-associated dopamine transporter, latrophilin and neurofibromin share a dopamine-related locomotor signature in Drosophila

PubMed Central

van der Voet, M; Harich, B; Franke, B; Schenck, A

2016-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neuropsychiatric disorder with hyperactivity as one of the hallmarks. Aberrant dopamine signaling is thought to be a major theme in ADHD, but how this relates to the vast majority of ADHD candidate genes is illusive. Here we report a Drosophila dopamine-related locomotor endophenotype that is shared by pan-neuronal knockdown of orthologs of the ADHD-associated genes Dopamine transporter (DAT1) and Latrophilin (LPHN3), and of a gene causing a monogenic disorder with frequent ADHD comorbidity: Neurofibromin (NF1). The locomotor signature was not found in control models and could be ameliorated by methylphenidate, validating its relevance to symptoms of the disorder. The Drosophila ADHD endophenotype can be further exploited in high throughput to characterize the growing number of candidate genes. It represents an equally useful outcome measure for testing chemical compounds to define novel treatment options. PMID:25962619

A linkage and family-based association analysis of a potential neurocognitive endophenotype of bipolar disorder.

PubMed

Savitz, Jonathan; van der Merwe, Lize; Solms, Mark; Ramesar, Rajkumar

2007-01-01

The identification of the genetic variants underpinning bipolar disorder (BPD) has been impeded by a complex pattern of inheritance characterized by genetic and phenotypic heterogeneity, genetic epistasis, and gene-environment interactions. In this paper two strategies were used to ameliorate these confounding factors. A unique South African sample including 190 individuals of the relatively, reproductively isolated Afrikaner population was assessed with a battery of neuropsychological tests in an attempt to identify a BPD-associated quantitative trait or endophenotype. BPD individuals performed significantly worse than their unaffected relatives on visual and verbal memory tasks, a finding congruent with the literature. Afocused linkage and family-based association study was carried out using this memory-related endophenotype. In the largest 77-strong Afrikaner pedigree significant evidence for linkage was detected on chromosome 22q11, a region previously implicated in BPD. The quantitative transmission disequilibrium tests-based association analysis suggested that functional variants of the DRD4 and MAO-A genes modulate memory-related cognition. We speculate that polymorphisms at these loci may predispose to a subtype of BPD characterized by memory-related deficits.

Lexical decision as an endophenotype for reading comprehension: An exploration of an association

PubMed Central

NAPLES, ADAM; KATZ, LEN; GRIGORENKO, ELENA L.

2012-01-01

Based on numerous suggestions in the literature, we evaluated lexical decision (LD) as a putative endophenotype for reading comprehension by investigating heritability estimates and segregation analyses parameter estimates for both of these phenotypes. Specifically, in a segregation analysis of a large sample of families, we established that there is little to no overlap between genes contributing to LD and reading comprehension and that the genetic mechanism behind LD derived from this analysis appears to be more complex than that for reading comprehension. We conclude that in our sample, LD is not a good candidate as an endophenotype for reading comprehension, despite previous suggestions from the literature. Based on this conclusion, we discuss the role and benefit of the endophenotype approach in studies of complex human cognitive functions. PMID:23062302

The Consortium on the Genetics of Schizophrenia: Neurocognitive Endophenotypes

PubMed Central

Gur, Raquel E.; Calkins, Monica E.; Gur, Ruben C.; Horan, William P.; Nuechterlein, Keith H.; Seidman, Larry J.; Stone, William S.

2007-01-01

The Consortium on the Genetics of Schizophrenia (COGS) is a 7-site collaboration that examines the genetic architecture of quantitative endophenotypes in families with schizophrenia. Here we review the background and rationale for selecting neurocognitive tasks as endophenotypic measures in genetic studies. Criteria are outlined for the potential of measures as endophenotypic vulnerability markers. These include association with illness, state independence (ie, adequate test-retest stability, adequate between-site reliability, impairments in patients not due to medications, impairments observed regardless of illness state), heritability, findings of higher rates in relatives of probands than in the general population, and cosegregation within families. The COGS required that, in addition, the measures be “neurocognitive” and thus linked to neurobiology and that they be feasible in multisite studies. The COGS neurocognitive assessment includes measures of attention, verbal memory, working memory, and a computerized neurocognitive battery that also includes facial processing tasks. Here we describe data demonstrating that these neurobehavioral measures meet criteria for endophenotypic candidacy. We conclude that quantitative neurocognitive endophenotypes need further evidence for efficacy in identifying genetic effects but have the potential of providing unprecedented insight into gene-environment interaction related to dimensions of brain and behavior in health and disease. PMID:17101692

Endophenotypes, Epigenetics, Polygenicity and More: Irv Gottesman’s Dynamic Legacy

PubMed Central

Braff, David L.; Tamminga, Carol A.

2017-01-01

First, we describe the hallmark contributions of Irv Gottesman’s pioneering scholarship for schizophrenia research including concepts of polygenicity, gene × environment interactions, epigenetics and the endophenotype concept. Gottesman and colleagues’ twin studies showed that genes, not social factors, mediate schizophrenia risk. He then showed that schizophrenia is highly polygenic. Next, he introduced the concept of epigenetics into schizophrenia research. Gottesman then introduced the quantitative endophenotype concept. Endophenotypes are laboratory-based measures that show deficits in schizophrenia patients and lesser deficits in their first degree “unaffected” relatives and are viewed as being more proximal to genes and having a simpler genetic architecture than are “fuzzy” qualitative diagnostic disorders. Endophenotypes offer an exciting path to gene discovery, neural circuits, genetic architecture and new treatment pathways of schizophrenia and related psychotic disorders. Second, we were asked to discuss 2 of many endophenotype Consortia and related studies, in order to illustrate the impact of Gottesman’s work. We describe the Consortium on the Genetics of Schizophrenia (COGS) exploring neurocognitive and neurophysiological endophenotypes in family and case-control studies. Association, linkage, sequencing and epigenetic studies are described. The Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP) uses an array of endophenotypes including brain imaging in studies across the psychosis dimension, allowing for dimensional analyses. BSNIP results have led to the concept of biotypes, advancing the field. Irv Gottesman was imaginatively prescient in generating novel insights and predicting many major issues which challenge schizophrenia researchers who still use his concepts to guide current research approaches. PMID:27872267

The Consortium on the Genetics of Endophenotypes in Schizophrenia: Model Recruitment, Assessment, and Endophenotyping Methods for a Multisite Collaboration

PubMed Central

Calkins, Monica E.; Dobie, Dorcas J.; Cadenhead, Kristin S.; Olincy, Ann; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Light, Gregory A.; Mintz, Jim; Nuechterlein, Keith H.; Radant, Allen D.; Schork, Nicholas J.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Stone, William S.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.

2007-01-01

Background: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing, National Institute of Mental Health–funded, 7-site collaboration investigating the occurrence and genetic architecture of quantitative endophenotypes related to schizophrenia. The purpose of this article is to provide a description of the COGS structure and methods, including participant recruitment and assessment. Methods: The hypothesis-driven recruitment strategy ascertains families that include a proband with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia, and at least one unaffected full sibling available for genotyping and endophenotyping, along with parents available for genotyping and (optional depending on age) endophenotyping. The family structure is selected to provide contrast in quantitative endophenotypic traits and thus to maximize the power of the planned genetic analyses. Probands are recruited from many sources including clinician referrals, local National Alliance for the Mentally Ill chapters, and advertising via the media. All participants undergo a standardized protocol that includes clinical characterization, a blood draw for genotyping, and endophenotype assessments (P50 suppression, prepulse inhibition, antisaccade performance, continuous performance tasks, letter-number span, verbal memory, and a computerized neurocognitive battery). Investigators participate in weekly teleconferences to coordinate and evaluate recruitment, clinical assessment, endophenotyping, and continuous quality control of data gathering and analyses. Data integrity is maintained through use of a highly quality-assured, centralized web-based database. Results: As of February 2006, 355 families have been enrolled and 688 participants have been endophenotyped, including schizophrenia probands (n = 154, M:F = 110:44), first-degree biological relatives (n = 343, M:F = 151:192), and community comparison subjects (n = 191, M:F = 81

A Review of Selected Candidate Endophenotypes for Depression

PubMed Central

Goldstein, Brandon L.; Klein, Daniel N.

2014-01-01

Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria. PMID:25006008

Neurocognitive performance as an endophenotype for bipolar disorder.

PubMed

Raust, Aurelie; Daban, Claire; Cochet, Barbara; Henry, Chantal; Bellivier, Frank; Scott, Jan

2014-01-01

Identification of the underlying liability to develop bipolar disorders (BD) is hindered by the genetic complexity and phenotypic heterogeneity of the disease. The use of endophenotypes has been acknowledged as a promising approach that may detect the hidden manifestations of a genetic liability for an illness. One of the most commonly proposed endophenotypes in BD is neurocognitive performance. We identified and examined previously published review articles that had any data pertaining to endophenotypes in BD and combined this with an extensive review of studies of cognitive deficits in BD from 2000 onwards. Using criteria for a valid endophenotype, we identifed that the domains of executive functioning and verbal memory are the most promising candidate endophenotypes for BD. However, they do not meet the criteria for specificity as similar deficits present in schizophrenia and/or severe or psychotic major depressions. Further research is needed as the findings regarding endophenotypes show between-study heterogeneity. In the future, examination of quantitative traits may offer a more promising approach to the study of endophenotypes rather than solely focusing on diagnostic categories.

A review of selected candidate endophenotypes for depression.

PubMed

Goldstein, Brandon L; Klein, Daniel N

2014-07-01

Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gene expression levels as endophenotypes in genome-wide association studies of Alzheimer disease

PubMed Central

Zou, F.; Carrasquillo, M. M.; Pankratz, V. S.; Belbin, O.; Morgan, K.; Allen, M.; Wilcox, S. L.; Ma, L.; Walker, L. P.; Kouri, N.; Burgess, J. D.; Younkin, L. H.; Younkin, Samuel G.; Younkin, C. S.; Bisceglio, G. D.; Crook, J. E.; Dickson, D. W.; Petersen, R. C.; Graff-Radford, N.; Younkin, Steven G.; Ertekin-Taner, N.

2010-01-01

Background: Late-onset Alzheimer disease (LOAD) is a common disorder with a substantial genetic component. We postulate that many disease susceptibility variants act by altering gene expression levels. Methods: We measured messenger RNA (mRNA) expression levels of 12 LOAD candidate genes in the cerebella of 200 subjects with LOAD. Using the genotypes from our LOAD genome-wide association study for the cis-single nucleotide polymorphisms (SNPs) (n = 619) of these 12 LOAD candidate genes, we tested for associations with expression levels as endophenotypes. The strongest expression cis-SNP was tested for AD association in 7 independent case-control series (2,280 AD and 2,396 controls). Results: We identified 3 SNPs that associated significantly with IDE (insulin degrading enzyme) expression levels. A single copy of the minor allele for each significant SNP was associated with ∼twofold higher IDE expression levels. The most significant SNP, rs7910977, is 4.2 kb beyond the 3′ end of IDE. The association observed with this SNP was significant even at the genome-wide level (p = 2.7 × 10−8). Furthermore, the minor allele of rs7910977 associated significantly (p = 0.0046) with reduced LOAD risk (OR = 0.81 with a 95% CI of 0.70-0.94), as expected biologically from its association with elevated IDE expression. Conclusions: These results provide strong evidence that IDE is a late-onset Alzheimer disease (LOAD) gene with variants that modify risk of LOAD by influencing IDE expression. They also suggest that the use of expression levels as endophenotypes in genome-wide association studies may provide a powerful approach for the identification of disease susceptibility alleles. GLOSSARY AD = Alzheimer disease; CI = confidence interval; GWAS = genome-wide association study; LOAD = late-onset Alzheimer disease; mRNA = messenger RNA; OR = odds ratio; SNP = single nucleotide polymorphism. PMID:20142614

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: A review of human brain oscillations as effective endophenotypes

PubMed Central

Rangaswamy, Madhavi; Porjesz, Bernice

2010-01-01

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders. PMID:18634760

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: a review of human brain oscillations as effective endophenotypes.

PubMed

Rangaswamy, Madhavi; Porjesz, Bernice

2008-10-15

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders.

Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study.

PubMed

Greenwood, Tiffany A; Lazzeroni, Laura C; Calkins, Monica E; Freedman, Robert; Green, Michael F; Gur, Raquel E; Gur, Ruben C; Light, Gregory A; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Stone, William S; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

2016-01-01

The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) has previously reported our efforts to characterize the genetic architecture of 12 primary endophenotypes for schizophrenia. We now report the characterization of 13 additional measures derived from the same endophenotype test paradigms in the COGS-1 families. Nine of the measures were found to discriminate between schizophrenia patients and controls, were significantly heritable (31 to 62%), and were sufficiently independent of previously assessed endophenotypes, demonstrating utility as additional endophenotypes. Genotyping via a custom array of 1536 SNPs from 94 candidate genes identified associations for CTNNA2, ERBB4, GRID1, GRID2, GRIK3, GRIK4, GRIN2B, NOS1AP, NRG1, and RELN across multiple endophenotypes. An experiment-wide p value of 0.003 suggested that the associations across all SNPs and endophenotypes collectively exceeded chance. Linkage analyses performed using a genome-wide SNP array further identified significant or suggestive linkage for six of the candidate endophenotypes, with several genes of interest located beneath the linkage peaks (e.g., CSMD1, DISC1, DLGAP2, GRIK2, GRIN3A, and SLC6A3). While the partial convergence of the association and linkage likely reflects differences in density of gene coverage provided by the distinct genotyping platforms, it is also likely an indication of the differential contribution of rare and common variants for some genes and methodological differences in detection ability. Still, many of the genes implicated by COGS through endophenotypes have been identified by independent studies of common, rare, and de novo variation in schizophrenia, all converging on a functional genetic network related to glutamatergic neurotransmission that warrants further investigation. Copyright © 2015 Elsevier B.V. All rights reserved.

Genome-wide association study identifies four novel loci associated with Alzheimer's endophenotypes and disease modifiers.

PubMed

Deming, Yuetiva; Li, Zeran; Kapoor, Manav; Harari, Oscar; Del-Aguila, Jorge L; Black, Kathleen; Carrell, David; Cai, Yefei; Fernandez, Maria Victoria; Budde, John; Ma, Shengmei; Saef, Benjamin; Howells, Bill; Huang, Kuan-Lin; Bertelsen, Sarah; Fagan, Anne M; Holtzman, David M; Morris, John C; Kim, Sungeun; Saykin, Andrew J; De Jager, Philip L; Albert, Marilyn; Moghekar, Abhay; O'Brien, Richard; Riemenschneider, Matthias; Petersen, Ronald C; Blennow, Kaj; Zetterberg, Henrik; Minthon, Lennart; Van Deerlin, Vivianna M; Lee, Virginia Man-Yee; Shaw, Leslie M; Trojanowski, John Q; Schellenberg, Gerard; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Peskind, Elaine R; Li, Ge; Di Narzo, Antonio F; Kauwe, John S K; Goate, Alison M; Cruchaga, Carlos

2017-05-01

More than 20 genetic loci have been associated with risk for Alzheimer's disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case-control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ 42 ), tau, and phosphorylated tau (ptau 181 ) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau 181 , including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ 42 near GLIS1 on 1p32.3 (β = -0.059, P = 2.08 × 10 -8 ) and within SERPINB1 on 6p25 (β = -0.025, P = 1.72 × 10 -8 ) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10 -2 ), disease progression (GLIS1: β = 0.277, P = 1.92 × 10 -2 ), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10 -3 ). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ 42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau 181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings

Cognitive dysfunction and anxious-impulsive personality traits are endophenotypes for drug dependence.

PubMed

Ersche, Karen D; Turton, Abigail J; Chamberlain, Samuel R; Müller, Ulrich; Bullmore, Edward T; Robbins, Trevor W

2012-09-01

Not everyone who takes drugs becomes addicted, but the likelihood of developing drug addiction is greater in people with a family history of drug or alcohol dependence. Relatively little is known about how genetic risk mediates the development of drug dependence. By comparing the phenotypic profile of individuals with and without a family history of addiction, the authors sought to clarify the extent to which cognitive dysfunction and personality traits are shared by family members--and therefore likely to have predated drug dependence--and which aspects are specific to drug-dependent individuals. The authors assessed cognitive function and personality traits associated with drug dependence in stimulant-dependent individuals (N=50), their biological siblings without a history of drug dependence (N=50), and unrelated healthy volunteers (N=50). Cognitive function was significantly impaired in the stimulant-dependent individuals across a range of domains. Deficits in executive function and response control were identified in both the stimulant-dependent individuals and in their non-drug-dependent siblings. Drug-dependent individuals and their siblings also exhibited elevated anxious-impulsive personality traits relative to healthy comparison volunteers. Deficits in executive function and response regulation as well as anxious-impulsive personality traits may represent endophenotypes associated with the risk of developing cocaine or amphetamine dependence. The identification of addiction endophenotypes may be useful in facilitating the rational development of therapeutic and preventive strategies.

Subtyping Children with Speech Sound Disorders by Endophenotypes

ERIC Educational Resources Information Center

Lewis, Barbara A.; Avrich, Allison A.; Freebairn, Lisa A.; Taylor, H. Gerry; Iyengar, Sudha K.; Stein, Catherine M.

2011-01-01

Purpose: The present study examined associations of 5 endophenotypes (i.e., measurable skills that are closely associated with speech sound disorders and are useful in detecting genetic influences on speech sound production), oral motor skills, phonological memory, phonological awareness, vocabulary, and speeded naming, with 3 clinical criteria…

Executive functioning and local-global visual processing: candidate endophenotypes for autism spectrum disorder?

PubMed

Van Eylen, Lien; Boets, Bart; Cosemans, Nele; Peeters, Hilde; Steyaert, Jean; Wagemans, Johan; Noens, Ilse

2017-03-01

Heterogeneity within autism spectrum disorder (ASD) hampers insight in the etiology and stimulates the search for endophenotypes. Endophenotypes should meet several criteria, the most important being the association with ASD and the higher occurrence rate in unaffected ASD relatives than in the general population. We evaluated these criteria for executive functioning (EF) and local-global (L-G) visual processing. By administering an extensive cognitive battery which increases the validity of the measures, we examined which of the cognitive anomalies shown by ASD probands also occur in their unaffected relatives (n = 113) compared to typically developing (TD) controls (n = 100). Microarrays were performed, so we could exclude relatives from probands with a de novo mutation in a known ASD susceptibility copy number variant, thus increasing the probability that genetic risk variants are shared by the ASD relatives. An overview of studies investigating EF and L-G processing in ASD relatives was also provided. For EF, ASD relatives - like ASD probands - showed impairments in response inhibition, cognitive flexibility and generativity (specifically, ideational fluency), and EF impairments in daily life. For L-G visual processing, the ASD relatives showed no anomalies on the tasks, but they reported more attention to detail in daily life. Group differences were similar for siblings and for parents of ASD probands, and yielded larger effect sizes in a multiplex subsample. The group effect sizes for the comparison between ASD probands and TD individuals were generally larger than those of the ASD relatives compared to TD individuals. Impaired cognitive flexibility, ideational fluency and response inhibition are strong candidate endophenotypes for ASD. They could help to delineate etiologically more homogeneous subgroups, which is clinically important to allow assigning ASD probands to different, more targeted, interventions. © 2016 Association for Child and Adolescent

Prioritizing schizophrenia endophenotypes for future genetic studies: An example using data from the COGS-1 family study.

PubMed

Millard, Steven P; Shofer, Jane; Braff, David; Calkins, Monica; Cadenhead, Kristin; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel; Gur, Ruben; Lazzeroni, Laura C; Light, Gregory A; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William S; Sprock, Joyce; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Ming; Turetsky, Bruce; Radant, Allen; Tsuang, Debby W

2016-07-01

Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the first phase of the Consortium on the Genetics of Schizophrenia, a large, multi-site family study, to determine whether a subset could distinguish SZ probands and CCS just as well as using all 16. Participants included 345 SZ probands and 517 CCS with a valid measure for at least one endophenotype. We used both logistic regression and random forest models to choose a subset of endophenotypes, adjusting for age, gender, smoking status, site, parent education, and the reading subtest of the Wide Range Achievement Test. As a sensitivity analysis, we re-fit models using multiple imputations to determine the effect of missing values. We identified four important endophenotypes: antisaccade, Continuous Performance Test-Identical Pairs 3-digit version, California Verbal Learning Test, and emotion identification. The logistic regression model that used just these four endophenotypes produced essentially the same results as the model that used all 16 (84% vs. 85% accuracy). While a subset of endophenotypes cannot replace clinical diagnosis nor encompass the complexity of the disease, it can aid in the design of future endophenotypic and genetic studies by reducing study cost and subject burden, simplifying sample enrichment, and improving the statistical power of locating those genetic regions associated with schizophrenia that may be the easiest to identify initially. Published by Elsevier B.V.

Prioritizing Schizophrenia Endophenotypes for Future Genetic Studies: An Example Using Data from the COGS-1 Family Study

PubMed Central

Millard, Steven P.; Shofer, Jane; Braff, David; Calkins, Monica; Cadenhead, Kristin; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel; Gur, Ruben; Lazzeroni, Laura C.; Light, Gregory A.; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William; Sprock, Joyce; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Ming; Turetsky, Bruce; Radant, Allen; Tsuang, Debby W.

2016-01-01

Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the first phase of the Consortium on the Genetics of Schizophrenia, a large, multi-site family study, to determine whether a subset could distinguish SZ probands and CCS just as well as using all 16. Participants included 345 SZ probands and 517 CCS with a valid measure for at least one endophenotype. We used both logistic regression and random forest models to choose a subset of endophenotypes, adjusting for age, gender, smoking status, site, parent education, and the reading subtest of the Wide Range Achievement Test. As a sensitivity analysis, we re-fit models using multiple imputations to determine the effect of missing values. We identified four important endophenotypes: antisaccade, Continuous Performance Test-Identical Pairs 3-digit version, California Verbal Learning Test, and emotion identification. The logistic regression model that used just these four endophenotypes produced essentially the same results as the model that used all 16 (84% vs. 85% accuracy). While a subset of endophenotypes cannot replace clinical diagnosis nor encompass the complexity of the disease, it can aid in the design of future endophenotypic and genetic studies by reducing study cost and subject burden, simplifying sample enrichment, and improving statistical power of locating genetic regions associated with schizophrenia that may be the easiest to identify initially. PMID:27132484

Consortium on the Genetics of Schizophrenia (COGS) assessment of endophenotypes for schizophrenia: an introduction to this Special Issue of Schizophrenia Research.

PubMed

Swerdlow, Neal R; Gur, Raquel E; Braff, David L

2015-04-01

The COGS is a multi-site NIMH-sponsored investigation of the genetic basis of 12 primary and multiple secondary quantitative endophenotypes in schizophrenia. Since 2003, COGS has completed studies using a family-based ascertainment strategy (COGS-1), and a case-control ascertainment strategy (COGS-2) (cumulative "n">4000). COGS-1 family study confirmed robust deficits in, and heritability of, these endophenotypes in schizophrenia, and provided evidence for a coherent genetic architecture underlying the risk for neurocognitive and neurophysiological deficits in this disorder. COGS-2 case-control findings, many reported herein, establish a foundation for fine genomic mapping and other analyses of these endophenotypes and risk genes for SZ. Several reports in this Special Issue compare findings of endophenotype deficits generated by fundamentally different COGS-1 vs. COGS-2 ascertainment strategies. Despite the expectation that family-based and case-control designs would establish demographically and potentially biologically distinct patient cohorts, findings generally revealed comparable patterns of endophenotype deficits across studies. The COGS-2 case-control design facilitated the accrual of a larger "n", permitting detailed analyses of factors moderating endophenotype performance. Some COGS-2 endophenotypes not assessed in COGS-1 are also reported, as is a new factor analytic strategy for identifying shared vs. unique factors among the COGS endophenotypes which can be used to develop composite variables with distinct genetic signatures. The path to date of COGS-1 endophenotype and genetic findings, followed by replication and extension in COGS-2, establishes benchmarks for endophenotype deficits in SZ and their moderation by specific factors, and clear expectations for informative findings from upcoming COGS-2 genetic analyses. Published by Elsevier B.V.

Consortium on the Genetics of Schizophrenia (COGS) assessment of endophenotypes for schizophrenia: An introduction to this Special Issue of schizophrenia research

PubMed Central

Swerdlow, Neal R.; Gur, Raquel E.; Braff, David L.

2014-01-01

Background The COGS is a multi-site NIMH-sponsored investigation of the genetic basis of 12 primary and multiple secondary quantitative endophenotypes in schizophrenia. Methods Since 2003, COGS has completed studies using a family-based ascertainment strategy (COGS-1), and a case–control ascertainment strategy (COGS-2) (cumulative “n” > 4000). Results COGS-1 family study confirmed robust deficits in, and heritability of, these endophenotypes in schizophrenia, and provided evidence for a coherent genetic architecture underlying the risk for neurocognitive and neurophysiological deficits in this disorder. COGS-2 case–control findings, many reported herein, establish a foundation for fine genomic mapping and other analyses of these endophenotypes and risk genes for SZ. Several reports in this Special Issue compare findings of endophenotype deficits generated by fundamentally different COGS-1 vs. COGS-2 ascertainment strategies. Despite the expectation that family-based and case–control designs would establish demographically and potentially biologically distinct patient cohorts, findings generally revealed comparable patterns of endophenotype deficits across studies. The COGS-2 case–control design facilitated the accrual of a larger “n”, permitting detailed analyses of factors moderating endophenotype performance. Some COGS-2 endophenotypes not assessed in COGS-1 are also reported, as is a new factor analytic strategy for identifying shared vs. unique factors among the COGS endophenotypes which can be used to develop composite variables with distinct genetic signatures. Discussion The path to date of COGS-1 endophenotype and genetic findings, followed by replication and extension in COGS-2, establishes benchmarks for endophenotype deficits in SZ and their moderation by specific factors, and clear expectations for informative findings from upcoming COGS-2 genetic analyses. PMID:25454799

Lipoprotein lipase variants associated with an endophenotype of hypertension: hypertension combined with elevated triglycerides.

PubMed

Chen, Pei; Jou, Yuh-Shan; Fann, Cathy S J; Chen, Jaw-Wen; Chung, Chia-Min; Lin, Chin-Yu; Wu, Sheng-Yeu; Kang, Mei-Jyh; Chen, Ying-Chuang; Jong, Yuh-Shiun; Lo, Huey-Ming; Kang, Chih-Sen; Chen, Chien-Chung; Chang, Huan-Cheng; Huang, Nai-Kuei; Wu, Yi-Lin; Pan, Wen-Harn

2009-01-01

Previously, we observed that young-onset hypertension was independently associated with elevated plasma triglyceride(s) (TG) levels to a greater extent than other metabolic risk factors. Thus, focusing on the endophenotype--hypertension combined with elevated TG--we designed a family-based haplotype association study to explore its genetic connection with novel genetic variants of lipoprotein lipase gene (LPL), which encodes a major lipid metabolizing enzyme. Young-onset hypertension probands and their families were recruited, numbering 1,002 individuals from 345 families. Single-nucleotide polymorphism discovery for LPL, linkage disequilibrium (LD) analysis, transmission disequilibrium tests (TDT), bin construction, haplotype TDT association and logistic regression analysis were performed. We found that the CC- haplotype (i) spanning from intron 2 to intron 4 and the ACATT haplotype (ii) spanning from intron 5 to intron 6 were significantly associated with hypertension-related phenotypes: hypertension (ii, P=0.05), elevated TG (i, P=0.01), and hypertension combined with elevated TG (i, P=0.001; ii, P<0.0001), according to TDT. The risk of this hypertension subtype increased with the number of risk haplotypes in the two loci, using logistic regression model after adjusting within-family correlation. The relationships between LPL variants and hypertension-related disorders were also confirmed by an independent association study. Finally, we showed a trend that individuals with homozygous risk haplotypes had decreased LPL expression after a fatty meal, as opposed to those with protective haplotypes. In conclusion, this study strongly suggests that two LPL intronic variants may be associated with development of the hypertension endophenotype with elevated TG. Copyright 2008 Wiley-Liss, Inc.

Genomewide Association Scan of a Mortality Associated Endophenotype for a Long and Healthy Life in the Long Life Family Study.

PubMed

Singh, Jatinder; Minster, Ryan L; Schupf, Nicole; Kraja, Aldi; Liu, YongMei; Christensen, Kaare; Newman, Anne B; Kammerer, Candace M

2017-10-01

Identification of genes or fundamental biological pathways that regulate aging phenotypes and longevity could lead to possible interventions to increase healthy longevity. Using data from the Long Life Family Study, we performed genomewide association analyses on an endophenotype construct, LF1, comprising a linear combination of traits across health domains. LF1 primarily reflected traits from the pulmonary and physical activity domains. We detected a significant association between LF1 and a locus on chromosome 10p15 (p-value = 4.65 × 10-8) and suggestive evidence (p-value < 5 × 10-6) for association on chromosomes 1, 2, 8, 12, 15, 18, and 22. Using data from the Health, Aging and Body Composition Study, we subsequently replicated the association for the 1p13 region near the NBPF6 locus (p-value = 3.65 × 10-4). Our analyses indicate that loci influencing a healthy aging endophenotype construct predominantly comprised of pulmonary and physical function domains may be located on chromosome 1p13 near the NBPF6 locus. Further investigation of this possible locus and other suggestive loci may reveal novel biological pathways that influence healthy aging. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Literacy Outcomes of Children with Early Childhood Speech Sound Disorders: Impact of Endophenotypes

ERIC Educational Resources Information Center

Lewis, Barbara A.; Avrich, Allison A.; Freebairn, Lisa A.; Hansen, Amy J.; Sucheston, Lara E.; Kuo, Iris; Taylor, H. Gerry; Iyengar, Sudha K.; Stein, Catherine M.

2011-01-01

Purpose: To demonstrate that early childhood speech sound disorders (SSD) and later school-age reading, written expression, and spelling skills are influenced by shared endophenotypes that may be in part genetic. Method: Children with SSD and their siblings were assessed at early childhood (ages 4-6 years) and followed at school age (7-12 years).…

Genome-wide association study identifies four novel loci associated with Alzheimer’s endophenotypes and disease modifiers

PubMed Central

Deming, Yuetiva; Li, Zeran; Kapoor, Manav; Harari, Oscar; Del-Aguila, Jorge L.; Black, Kathleen; Carrell, David; Cai, Yefei; Fernandez, Maria Victoria; Budde, John; Ma, Shengmei; Saef, Benjamin; Howells, Bill; Huang, Kuanlin; Bertelsen, Sarah; Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Kim, Sungeun; Saykin, Andrew J.; De Jager, Philip L.; Albert, Marilyn; Moghekar, Abhay; O’Brien, Richard; Riemenschneider, Matthias; Petersen, Ronald C.; Blennow, Kaj; Zetterberg, Henrik; Minthon, Lennart; Van Deerlin, Vivianna M.; Lee, Virginia Man-Yee; Shaw, Leslie M.; Trojanowski, John Q.; Schellenberg, Gerard; Haines, Jonathan L.; Mayeux, Richard; Pericak-Vance, Margaret A.; Farrer, Lindsay A.; Peskind, Elaine R.; Li, Ge; Di Narzo, Antonio F.; Kauwe, John S. K.; Goate, Alison M.; Cruchaga, Carlos

2017-01-01

More than 20 genetic loci have been associated with risk for Alzheimer’s disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case–control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = −0.059, P = 2.08 × 10−8) and within SERPINB1 on 6p25 (β = −0.025, P = 1.72 × 10−8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10−2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10−2), and age at onset (SER-PINB1: β = 0.043, P = 4.62 × 10−3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform

Genome-wide scans of genetic variants for psychophysiological endophenotypes: a methodological overview.

PubMed

Iacono, William G; Malone, Stephen M; Vaidyanathan, Uma; Vrieze, Scott I

2014-12-01

This article provides an introductory overview of the investigative strategy employed to evaluate the genetic basis of 17 endophenotypes examined as part of a 20-year data collection effort from the Minnesota Center for Twin and Family Research. Included are characterization of the study samples, descriptive statistics for key properties of the psychophysiological measures, and rationale behind the steps taken in the molecular genetic study design. The statistical approach included (a) biometric analysis of twin and family data, (b) heritability analysis using 527,829 single nucleotide polymorphisms (SNPs), (c) genome-wide association analysis of these SNPs and 17,601 autosomal genes, (d) follow-up analyses of candidate SNPs and genes hypothesized to have an association with each endophenotype, (e) rare variant analysis of nonsynonymous SNPs in the exome, and (f) whole genome sequencing association analysis using 27 million genetic variants. These methods were used in the accompanying empirical articles comprising this special issue, Genome-Wide Scans of Genetic Variants for Psychophysiological Endophenotypes. Copyright © 2014 Society for Psychophysiological Research.

Endophenotypes in the personality disorders

PubMed Central

Siever, Larry J.

2005-01-01

The identification of endophenotypes in the personality disorders may provide a basis for the identification of underlying genotypes that influence the traits and dimensions of the personality disorders, as well as susceptibility to major psychiatric illnesses. Clinical dimensions of personality disorders that lend themselves to the study of corresponding endophenotypes include affective instability impulsiwity aggression, emotional information processing, cognitive disorganization, social deficits, and psychosis. For example, the propensity to aggression can be evaluated by psychometric measures, interview, laboratory paradigms, neurochemical imaging, and pharmacological studies. These suggest that aggression is a measurable trait that may be related to reduced serotonergic activity. Hyperresponsiveness of amygdala and other limbic structures may be related to affective instability, while structural and functional brain alterations underlie the cognitive disorganization in psychoticlike symptoms of schizotypal personality disorder. Thus, an endophenotypic approach not only provides clues to underlying candidate genes contributing to these behavioral dimensions, but may also point the way to a better understanding of pathophysiological mechanisms. PMID:16262209

Endophenotypes for Intelligence in Children and Adolescents

ERIC Educational Resources Information Center

van Leeuwen, Marieke; van den Berg, Stephanie M.; Hoekstra, Rosa A.; Boomsma, Dorret I.

2007-01-01

The aim of this study was to identify promising endophenotypes for intelligence in children and adolescents for future genetic studies in cognitive development. Based on the available set of endophenotypes for intelligence in adults, cognitive tasks were chosen covering the domains of working memory, processing speed, and selective attention. This…

Downregulated Kynurenine 3-Monooxygenase Gene Expression and Enzyme Activity in Schizophrenia and Genetic Association With Schizophrenia Endophenotypes

PubMed Central

Wonodi, Ikwunga; Stine, O. Colin; Sathyasaikumar, Korrapati V.; Roberts, Rosalinda C.; Mitchell, Braxton D.; Hong, L. Elliot; Kajii, Yasushi; Thaker, Gunvant K.; Schwarcz, Robert

2013-01-01

Context Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, is an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors and modulates glutamate, dopamine, and acetylcholine signaling. Cortical kynurenic acid concentrations are elevated in the brain and cerebrospinal fluid of schizophrenia patients. The proximal cause may be an impairment of kynurenine 3-monooxygenase (KMO), a rate-limiting enzyme at the branching point of the kynurenine pathway. Objectives To examine KMO messenger RNA expression and KMO enzyme activity in postmortem tissue from the frontal eye field (FEF; Brodmann area 6) obtained from schizophrenia individuals compared with healthy control individuals and to explore the relationship between KMO single-nucleotide polymorphisms and schizophrenia oculomotor endophenotypes. Design Case-control postmortem and clinical study. Setting Maryland Brain Collection, outpatient clinics. Participants Postmortem specimens from schizophrenia patients (n=32) and control donors (n=32) and a clinical sample of schizophrenia patients (n=248) and healthy controls (n=228). Main Outcome Measures Comparison of quantitative KMO messenger RNA expression and KMO enzyme activity in postmortem FEF tissue between schizophrenia patients and controls and association of KMO single-nucleotide polymorphisms with messenger RNA expression in postmortem FEF and schizophrenia and oculomotor endophenotypes (ie, smooth pursuit eye movements and oculomotor delayed response). Results In postmortem tissue, we found a significant and correlated reduction in KMO gene expression and KMO enzyme activity in the FEF in schizophrenia patients. In the clinical sample, KMO rs2275163 was not associated with a diagnosis of schizophrenia but showed modest effects on predictive pursuit and visuospatial working memory endophenotypes. Conclusion Our results provide converging lines of evidence implicating reduced KMO activity in the etiopathophysiology

Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes.

PubMed

Wonodi, Ikwunga; Stine, O Colin; Sathyasaikumar, Korrapati V; Roberts, Rosalinda C; Mitchell, Braxton D; Hong, L Elliot; Kajii, Yasushi; Thaker, Gunvant K; Schwarcz, Robert

2011-07-01

Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, is an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors and modulates glutamate, dopamine, and acetylcholine signaling. Cortical kynurenic acid concentrations are elevated in the brain and cerebrospinal fluid of schizophrenia patients. The proximal cause may be an impairment of kynurenine 3-monooxygenase (KMO), a rate-limiting enzyme at the branching point of the kynurenine pathway. To examine KMO messenger RNA expression and KMO enzyme activity in postmortem tissue from the frontal eye field (FEF; Brodmann area 6) obtained from schizophrenia individuals compared with healthy control individuals and to explore the relationship between KMO single-nucleotide polymorphisms and schizophrenia oculomotor endophenotypes. Case-control postmortem and clinical study. Maryland Brain Collection, outpatient clinics. Postmortem specimens from schizophrenia patients (n = 32) and control donors (n = 32) and a clinical sample of schizophrenia patients (n = 248) and healthy controls (n = 228). Comparison of quantitative KMO messenger RNA expression and KMO enzyme activity in postmortem FEF tissue between schizophrenia patients and controls and association of KMO single-nucleotide polymorphisms with messenger RNA expression in postmortem FEF and schizophrenia and oculomotor endophenotypes (ie, smooth pursuit eye movements and oculomotor delayed response). In postmortem tissue, we found a significant and correlated reduction in KMO gene expression and KMO enzyme activity in the FEF in schizophrenia patients. In the clinical sample, KMO rs2275163 was not associated with a diagnosis of schizophrenia but showed modest effects on predictive pursuit and visuospatial working memory endophenotypes. Our results provide converging lines of evidence implicating reduced KMO activity in the etiopathophysiology of schizophrenia and related neurocognitive deficits.

Redefining the endophenotype concept to accommodate transdiagnostic vulnerabilities and etiological complexity.

PubMed

Beauchaine, Theodore P; Constantino, John N

2017-09-11

In psychopathology research, endophenotypes are a subset of biomarkers that indicate genetic vulnerability independent of clinical state. To date, an explicit expectation is that endophenotypes be specific to single disorders. We evaluate this expectation considering recent advances in psychiatric genetics, recognition that transdiagnostic vulnerability traits are often more useful than clinical diagnoses in psychiatric genetics, and appreciation for etiological complexity across genetic, neural, hormonal and environmental levels of analysis. We suggest that the disorder-specificity requirement of endophenotypes be relaxed, that neural functions are preferable to behaviors as starting points in searches for endophenotypes, and that future research should focus on interactive effects of multiple endophenotypes on complex psychiatric disorders, some of which are 'phenocopies' with distinct etiologies.

Neural Correlates of Three Promising Endophenotypes of Depression: Evidence from the EMBARC Study

PubMed Central

Webb, Christian A; Dillon, Daniel G; Pechtel, Pia; Goer, Franziska K; Murray, Laura; Huys, Quentin JM; Fava, Maurizio; McGrath, Patrick J; Weissman, Myrna; Parsey, Ramin; Kurian, Benji T; Adams, Phillip; Weyandt, Sarah; Trombello, Joseph M; Grannemann, Bruce; Cooper, Crystal M; Deldin, Patricia; Tenke, Craig; Trivedi, Madhukar; Bruder, Gerard; Pizzagalli, Diego A

2016-01-01

Major depressive disorder (MDD) is clinically, and likely pathophysiologically, heterogeneous. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes. Guided by the NIMH Research Domain Criteria initiative, we used source localization of scalp-recorded EEG resting data to examine the neural correlates of three emerging endophenotypes of depression: neuroticism, blunted reward learning, and cognitive control deficits. Data were drawn from the ongoing multi-site EMBARC study. We estimated intracranial current density for standard EEG frequency bands in 82 unmedicated adults with MDD, using Low-Resolution Brain Electromagnetic Tomography. Region-of-interest and whole-brain analyses tested associations between resting state EEG current density and endophenotypes of interest. Neuroticism was associated with increased resting gamma (36.5–44 Hz) current density in the ventral (subgenual) anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC). In contrast, reduced cognitive control correlated with decreased gamma activity in the left dorsolateral prefrontal cortex (dlPFC), decreased theta (6.5–8 Hz) and alpha2 (10.5–12 Hz) activity in the dorsal ACC, and increased alpha2 activity in the right dlPFC. Finally, blunted reward learning correlated with lower OFC and left dlPFC gamma activity. Computational modeling of trial-by-trial reinforcement learning further indicated that lower OFC gamma activity was linked to reduced reward sensitivity. Three putative endophenotypes of depression were found to have partially dissociable resting intracranial EEG correlates, reflecting different underlying neural dysfunctions. Overall, these findings highlight the need to parse the heterogeneity of MDD by focusing on promising endophenotypes linked to specific pathophysiological abnormalities. PMID:26068725

Subjective Responses to Alcohol Consumption as Endophenotypes: Advancing Behavioral Genetics in Etiological and Treatment Models of Alcoholism

PubMed Central

Ray, Lara A.; MacKillop, James; Monti, Peter M.

2015-01-01

Individual differences in subjective responses to alcohol consumption represent genetically-mediated biobehavioral mechanisms of alcoholism risk (i.e., endophenotype). The objective of this review is three-fold: (1) to provide a critical review the literature on subjective response to alcohol and to discuss the rationale for its conceptualization as an endophenotype for alcoholism; (2) to examine the literature on the neurobiological substrates and associated genetic factors subserving individual differences in subjective response to alcohol; and (3) to discuss the treatment implications of this approach and to propose a framework for conceptualizing, and systematically integrating, endophenotypes into alcoholism treatment. PMID:20590398

Infant social attention: an endophenotype of ASD-related traits?

PubMed

Jones, Emily J H; Venema, Kaitlin; Earl, Rachel K; Lowy, Rachel; Webb, Sara J

2017-03-01

. Alterations in social attention may be infant endophenotypes of social motivation traits related to ASD. © 2016 Association for Child and Adolescent Mental Health.

Whole-brain functional hypoconnectivity as an endophenotype of autism in adolescents

PubMed Central

Moseley, R.L.; Ypma, R.J.F.; Holt, R.J.; Floris, D.; Chura, L.R.; Spencer, M.D.; Baron-Cohen, S.; Suckling, J.; Bullmore, E.; Rubinov, M.

2015-01-01

Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives. PMID:26413477

Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome.

PubMed

Darrow, Sabrina M; Hirschtritt, Matthew E; Davis, Lea K; Illmann, Cornelia; Osiecki, Lisa; Grados, Marco; Sandor, Paul; Dion, Yves; King, Robert; Pauls, David; Budman, Cathy L; Cath, Danielle C; Greenberg, Erica; Lyon, Gholson J; Yu, Dongmei; McGrath, Lauren M; McMahon, William M; Lee, Paul C; Delucchi, Kevin L; Scharf, Jeremiah M; Mathews, Carol A

2017-04-01

Phenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts. Assessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated. The authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not. The analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette

Identification of two heritable cross-disorder endophenotypes for Tourette Syndrome

PubMed Central

Darrow, Sabrina M.; Hirschtritt, Matthew E.; Davis, Lea K.; Illmann, Cornelia; Osiecki, Lisa; Grados, Marco; Sandor, Paul; Dion, Yves; King, Robert; Pauls, David; Budman, Cathy L.; Cath, Danielle C.; Greenberg, Erica; Lyon, Gholson J.; Yu, Dongmei; McGrath, Lauren M.; McMahon, William M.; Lee, Paul C.; Delucchi, Kevin L.; Scharf, Jeremiah M.; Mathews, Carol A.

2016-01-01

Objective Phenotypic heterogeneity in Tourette syndrome (TS) is partly due to complex genetic relationships between TS, obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts. Method 3494 individuals recruited for genetic studies were assessed for TS, OCD, and ADHD symptoms. Symptom-level factor and latent class analyses were conducted in TS families and replicated in an independent sample. Classes were characterized by comorbidity rates and proportion of parents. Heritability and TS-, OCD-, and ADHD-associated polygenic load were estimated. Results We identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high (disinhibition factor= 0.35, SE=0.03, p= 4.2 ×10−34; symmetry factor= 0.39, SE=0.03, p= 7.2 ×10−31; symmetry class=0.38, SE=0.10, p=0.001). Mothers of TS probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a TS genome-wide association study (GWAS) were associated with symmetry (p= 0.02), while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were associated with disinhibition (p =0.03), while TS and ADHD risk scores were not. Conclusions We identified two heritable TS-related endophenotypes that cross traditional diagnostic boundaries. The symmetry phenotype correlated with TS polygenic load, and was present in otherwise “TS-unaffected” mothers, suggesting that this phenotype may reflect additional TS (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses. PMID:27809572

Facial recognition deficits as a potential endophenotype in bipolar disorder.

PubMed

Vierck, Esther; Porter, Richard J; Joyce, Peter R

2015-11-30

Bipolar disorder (BD) is considered a highly heritable and genetically complex disorder. Several cognitive functions, such as executive functions and verbal memory have been suggested as promising candidates for endophenotypes. Although there is evidence for deficits in facial emotion recognition in individuals with BD, studies investigating these functions as endophenotypes are rare. The current study investigates emotion recognition as a potential endophenotype in BD by comparing 36 BD participants, 24 of their 1st degree relatives and 40 healthy control participants in a computerised facial emotion recognition task. Group differences were evaluated using repeated measurement analysis of co-variance with age as a covariate. Results revealed slowed emotion recognition for both BD and their relatives. Furthermore, BD participants were less accurate than healthy controls in their recognition of emotion expressions. We found no evidence of emotion specific differences between groups. Our results provide evidence for facial recognition as a potential endophenotype in BD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neurocognitive Endophenotypes in Schizophrenia: Modulation by Nicotinic Receptor Systems

PubMed Central

Mackowick, Kristen M.; Barr, Mera S.; Wing, Victoria C.; Rabin, Rachel A.; Ouellet-Plamondon, Clairelaine; George, Tony P.

2013-01-01

Cigarette smoking is the leading preventable cause of death in the Western world, with a considerably higher prevalence observed in schizophrenia compared to the general population. Despite the negative health consequences of smoking heavily, it has been proposed that individuals with schizophrenia may maintain smoking behaviours to remediate symptoms associated with the disorder. Neurocognitive deficits are a core feature of schizophrenia and are present in approximately 80% of patients. Further, these deficits constitute an endophenotype of schizophrenia, as they are stable across disease phases, and heritable. The neurocognitive deficits that are present in schizophrenia are especially debilitating, since they are associated with poor clinical and functional outcomes and community integration. Interestingly, these deficits may also constitute a vulnerability factor towards the initiation and maintenance of tobacco use. Contributing to the potential shared vulnerability between schizophrenia and tobacco dependence is a dysregulation of the nicotinic acetylcholine receptor (nAChR) system. Pre-clinical evidence has shown that nicotine affects several neurotransmitter systems, including dopamine (DA), glutamate, and γ-aminobutyric acid (GABA), and certain neuropsychological deficits associated with these neurotransmitters (reaction time, spatial working memory, sustained attention, and sensory gating) are improved after nicotine administration in patients with schizophrenia. These positive effects on neurocognition appear to be more pronounced in smokers with schizophrenia, and may be an important mechanism that explains the co-morbidity of schizophrenia and tobacco dependence. PMID:23871750

Testing for Neuropsychological Endophenotypes in Siblings Discordant for ADHD

PubMed Central

Bidwell, L. Cinnamon; Willcutt, Erik G.; DeFries, John C.; Pennington, Bruce F.

2007-01-01

Objective Neurocognitive deficits associated with attention deficit-hyperactivity disorder (ADHD) may be useful intermediate endophenotypes for determining specific genetic pathways that contribute to ADHD. Methods This study administered 17 measures from prominent neuropsychological theories of ADHD (executive function, processing speed, arousal regulation and motivation/delay aversion) in dizygotic (DZ) twin pairs discordant for ADHD and control twin pairs (ages 8–18) in order to compare performance between twins affected with ADHD (n = 266), their unaffected co-twins (n = 228), and control children from twin pairs without ADHD or learning difficulties (n = 332). Results ADHD subjects show significant impairment on executive function, processing speed, and response variability measures compared to control subjects. Unaffected cotwins of ADHD subjects are significantly impaired on nearly all the same measures as their ADHD siblings, even when subclinical symptoms of ADHD are controlled. Conclusion Executive function, processing speed, and response variability deficits may be useful endophenotypes for genetic studies of ADHD. PMID:17585884

Potential cognitive endophenotypes in multigenerational families: segregating ADHD from a genetic isolate

PubMed Central

Pineda, David A.; Lopera, Francisco; Puerta, Isabel C.; Trujillo-Orrego, Natalia; Aguirre-Acevedo, Daniel C.; Hincapié-Henao, Liliana; Arango, Clara P.; Acosta, Maria T.; Holzinger, Sandra I.; Palacio, Juan David; Pineda-Alvarez, Daniel E.; Velez, Jorge I.; Martinez, Ariel F.; Lewis, John E.

2014-01-01

Endophenotypes are neurobiological markers cosegregating and associated with illness. These biomarkers represent a promising strategy to dissect ADHD biological causes. This study was aimed at contrasting the genetics of neuropsychological tasks for intelligence, attention, memory, visual-motor skills, and executive function in children from multigenerational and extended pedigrees that cluster ADHD in a genetic isolate. In a sample of 288 children and adolescents, 194 (67.4%) ADHD affected and 94 (32.6%) unaffected, a battery of neuropsychological tests was utilized to assess the association between genetic transmission and the ADHD phenotype. We found significant differences between affected and unaffected children in the WISC block design, PIQ and FSIQ, continuous vigilance, and visual-motor skills, and these variables exhibited a significant heritability. Given the association between these neuropsychological variables and ADHD, and also the high genetic component underlying their transmission in the studied pedigrees, we suggest that these variables be considered as potential cognitive endophenotypes suitable as quantitative trait loci (QTLs) in future studies of linkage and association. PMID:21779842

Behavioural and molecular endophenotypes in psychotic disorders reveal heritable abnormalities in glutamatergic neurotransmission

PubMed Central

Scoriels, L; Salek, R M; Goodby, E; Grainger, D; Dean, A M; West, J A; Griffin, J L; Suckling, J; Nathan, P J; Lennox, B R; Murray, G K; Bullmore, E T; Jones, P B

2015-01-01

Psychotic disorders such as schizophrenia are biologically complex and carry huge population morbidity due to their prevalence, persistence and associated disability. Defined by features such as delusions and hallucinations, they involve cognitive dysfunction and neurotransmitter dysregulations that appear mostly to involve the dopaminergic and glutamatergic systems. A number of genetic and environmental factors are associated with these disorders but it has been difficult to identify the biological pathways underlying the principal symptoms. The endophenotype concept of stable, heritable traits that form a mechanistic link between genes and an overt expression of the disorder has potential to reduce the complexity of psychiatric phenotypes. In this study, we used a genetically sensitive design with individuals with a first episode of psychosis, their non-affected first-degree relatives and non-related healthy controls. Metabolomic analysis was combined with neurocognitive assessment to identify multilevel endophenotypic patterns: one concerned reaction times during the performance of cognitive and emotional tests that have previously been associated with the glutamate neurotransmission system, the other involved metabolites involved directly and indirectly in the co-activation of the N-methyl-D-aspartate receptor, a major receptor of the glutamate system. These cognitive and metabolic endophenotypes may comprise a single construct, such that genetically mediated dysfunction in the glutamate system may be responsible for delays in response to cognitive and emotional functions in psychotic disorders. This focus on glutamatergic neurotransmission should guide drug discovery and experimental medicine programmes in schizophrenia and related disorders. PMID:25826115

Multivariate modelling of endophenotypes associated with the metabolic syndrome in Chinese twins.

PubMed

Pang, Z; Zhang, D; Li, S; Duan, H; Hjelmborg, J; Kruse, T A; Kyvik, K O; Christensen, K; Tan, Q

2010-12-01

The common genetic and environmental effects on endophenotypes related to the metabolic syndrome have been investigated using bivariate and multivariate twin models. This paper extends the pairwise analysis approach by introducing independent and common pathway models to Chinese twin data. The aim was to explore the common genetic architecture in the development of these phenotypes in the Chinese population. Three multivariate models including the full saturated Cholesky decomposition model, the common factor independent pathway model and the common factor common pathway model were fitted to 695 pairs of Chinese twins representing six phenotypes including BMI, total cholesterol, total triacylglycerol, fasting glucose, HDL and LDL. Performances of the nested models were compared with that of the full Cholesky model. Cross-phenotype correlation coefficients gave clear indication of common genetic or environmental backgrounds in the phenotypes. Decomposition of phenotypic correlation by the Cholesky model revealed that the observed phenotypic correlation among lipid phenotypes had genetic and unique environmental backgrounds. Both pathway models suggest a common genetic architecture for lipid phenotypes, which is distinct from that of the non-lipid phenotypes. The declining performance with model restriction indicates biological heterogeneity in development among some of these phenotypes. Our multivariate analyses revealed common genetic and environmental backgrounds for the studied lipid phenotypes in Chinese twins. Model performance showed that physiologically distinct endophenotypes may follow different genetic regulations.

Epigenetics in Developmental Disorder: ADHD and Endophenotypes

PubMed Central

Archer, Trevor; Oscar-Berman, Marlene; Blum, Kenneth

2011-01-01

Heterogeneity in attention-deficit/hyperactivity disorder (ADHD), with complex interactive operations of genetic and environmental factors, is expressed in a variety of disorder manifestations: severity, co-morbidities of symptoms, and the effects of genes on phenotypes. Neurodevelopmental influences of genomic imprinting have set the stage for the structural-physiological variations that modulate the cognitive, affective, and pathophysiological domains of ADHD. The relative contributions of genetic and environmental factors provide rapidly proliferating insights into the developmental trajectory of the condition, both structurally and functionally. Parent-of-origin effects seem to support the notion that genetic risks for disease process debut often interact with the social environment, i.e., the parental environment in infants and young children. The notion of endophenotypes, markers of an underlying liability to the disorder, may facilitate detection of genetic risks relative to a complex clinical disorder. Simple genetic association has proven insufficient to explain the spectrum of ADHD. At a primary level of analysis, the consideration of epigenetic regulation of brain signalling mechanisms, dopamine, serotonin, and noradrenaline is examined. Neurotrophic factors that participate in the neurogenesis, survival, and functional maintenance of brain systems, are involved in neuroplasticity alterations underlying brain disorders, and are implicated in the genetic predisposition to ADHD, but not obviously, nor in a simple or straightforward fashion. In the context of intervention, genetic linkage studies of ADHD pharmacological intervention have demonstrated that associations have fitted the “drug response phenotype,” rather than the disorder diagnosis. Despite conflicting evidence for the existence, or not, of genetic associations between disorder diagnosis and genes regulating the structure and function of neurotransmitters and brain-derived neurotrophic

Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

PubMed Central

He, Liang; Kernogitski, Yelena; Kulminskaya, Irina; Loika, Yury; Arbeev, Konstantin G.; Loiko, Elena; Bagley, Olivia; Duan, Matt; Yashkin, Arseniy; Ukraintseva, Svetlana V.; Kovtun, Mikhail; Yashin, Anatoliy I.; Kulminski, Alexander M.

2016-01-01

Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan. Here, we performed pleiotropic meta-analyses of genetic variants using five NIH-funded datasets by integrating univariate summary statistics for age-related diseases and endophenotypes. We investigated three groups of traits: (1) endophenotypes such as blood glucose, blood pressure, lipids, hematocrit, and body mass index, (2) time-to-event outcomes such as the age-at-onset of diabetes mellitus (DM), cancer, cardiovascular diseases (CVDs) and neurodegenerative diseases (NDs), and (3) both combined. In addition to replicating previous findings, we identify seven novel genome-wide significant loci (< 5e-08), out of which five are low-frequency variants. Specifically, from Group 2, we find rs7632505 on 3q21.1 in SEMA5B, rs460976 on 21q22.3 (1 kb from TMPRSS2) and rs12420422 on 11q24.1 predominantly associated with a variety of CVDs, rs4905014 in ITPK1 associated with stroke and heart failure, rs7081476 on 10p12.1 in ANKRD26 associated with multiple diseases including DM, CVDs, and NDs. From Group 3, we find rs8082812 on 18p11.22 and rs1869717 on 4q31.3 associated with both endophenotypes and CVDs. Our follow-up analyses show that rs7632505, rs4905014, and rs8082812 have age-dependent effects on coronary heart disease or stroke. Functional annotation suggests that most of these SNPs are within regulatory regions or DNase clusters and in linkage disequilibrium with expression quantitative trait loci, implying their potential regulatory influence on

Case-control and family-based association studies of candidate genes in autistic disorder and its endophenotypes: TPH2 and GLO1.

PubMed

Sacco, Roberto; Papaleo, Veruska; Hager, Jorg; Rousseau, Francis; Moessner, Rainald; Militerni, Roberto; Bravaccio, Carmela; Trillo, Simona; Schneider, Cindy; Melmed, Raun; Elia, Maurizio; Curatolo, Paolo; Manzi, Barbara; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Reichelt, Karl-Ludvig; Persico, Antonio M

2007-03-08

The TPH2 gene encodes the enzyme responsible for serotonin (5-HT) synthesis in the Central Nervous System (CNS). Stereotypic and repetitive behaviors are influenced by 5-HT, and initial studies report an association of TPH2 alleles with childhood-onset obsessive-compulsive disorder (OCD) and with autism. GLO1 encodes glyoxalase I, the enzyme which detoxifies alpha-oxoaldehydes such as methylglyoxal in all living cells. The A111E GLO1 protein variant, encoded by SNP C419A, was identified in autopsied autistic brains and proposed to act as an autism susceptibility factor. Hyperserotoninemia, macrocephaly, and peptiduria represent some of the best-characterized endophenotypes in autism research. Family-based and case-control association studies were performed on clinical samples drawn from 312 simplex and 29 multiplex families including 371 non-syndromic autistic patients and 156 unaffected siblings, as well as on 171 controls. TPH2 SNPs rs4570625 and rs4565946 were genotyped using the TaqMan assay; GLO1 SNP C419A was genotyped by PCR and allele-specific restriction digest. Family-based association analyses were performed by TDT and FBAT, case-control by chi2, endophenotypic analyses for 5-HT blood levels, cranial circumference and urinary peptide excretion rates by ANOVA and FBAT. TPH2 alleles and haplotypes are not significantly associated in our sample with autism (rs4570625: TDT P = 0.27, and FBAT P = 0.35; rs4565946: TDT P = 0.45, and FBAT P = 0.55; haplotype P = 0.84), with any endophenotype, or with the presence/absence of prominent repetitive and stereotyped behaviors (motor stereotypies: P = 0.81 and 0.84, verbal stereotypies: P = 0.38 and 0.73 for rs4570625 and rs4565946, respectively). Also GLO1 alleles display no association with autism (191 patients vs 171 controls, P = 0.36; TDT P = 0.79, and FBAT P = 0.37), but unaffected siblings seemingly carry a protective gene variant marked by the A419 allele (TDT P < 0.05; patients vs unaffected siblings TDT and

Case-control and family-based association studies of candidate genes in autistic disorder and its endophenotypes: TPH2 and GLO1

PubMed Central

Sacco, Roberto; Papaleo, Veruska; Hager, Jorg; Rousseau, Francis; Moessner, Rainald; Militerni, Roberto; Bravaccio, Carmela; Trillo, Simona; Schneider, Cindy; Melmed, Raun; Elia, Maurizio; Curatolo, Paolo; Manzi, Barbara; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Reichelt, Karl-Ludvig; Persico, Antonio M

2007-01-01

Background The TPH2 gene encodes the enzyme responsible for serotonin (5-HT) synthesis in the Central Nervous System (CNS). Stereotypic and repetitive behaviors are influenced by 5-HT, and initial studies report an association of TPH2 alleles with childhood-onset obsessive-compulsive disorder (OCD) and with autism. GLO1 encodes glyoxalase I, the enzyme which detoxifies α-oxoaldehydes such as methylglyoxal in all living cells. The A111E GLO1 protein variant, encoded by SNP C419A, was identifed in autopsied autistic brains and proposed to act as an autism susceptibility factor. Hyperserotoninemia, macrocephaly, and peptiduria represent some of the best-characterized endophenotypes in autism research. Methods Family-based and case-control association studies were performed on clinical samples drawn from 312 simplex and 29 multiplex families including 371 non-syndromic autistic patients and 156 unaffected siblings, as well as on 171 controls. TPH2 SNPs rs4570625 and rs4565946 were genotyped using the TaqMan assay; GLO1 SNP C419A was genotyped by PCR and allele-specific restriction digest. Family-based association analyses were performed by TDT and FBAT, case-control by χ2, endophenotypic analyses for 5-HT blood levels, cranial circumference and urinary peptide excretion rates by ANOVA and FBAT. Results TPH2 alleles and haplotypes are not significantly associated in our sample with autism (rs4570625: TDT P = 0.27, and FBAT P = 0.35; rs4565946: TDT P = 0.45, and FBAT P = 0.55; haplotype P = 0.84), with any endophenotype, or with the presence/absence of prominent repetitive and stereotyped behaviors (motor stereotypies: P = 0.81 and 0.84, verbal stereotypies: P = 0.38 and 0.73 for rs4570625 and rs4565946, respectively). Also GLO1 alleles display no association with autism (191 patients vs 171 controls, P = 0.36; TDT P = 0.79, and FBAT P = 0.37), but unaffected siblings seemingly carry a protective gene variant marked by the A419 allele (TDT P < 0.05; patients vs

[18F]FDOPA PET as an Endophenotype for Parkinson’s Disease Linkage Studies

PubMed Central

Racette, Brad A.; Good, Laura; Antenor, Jo Ann; McGee-Minnich, Lori; Moerlein, Stephen M.; Videen, Tom O.; Perlmutter, Joel S.

2008-01-01

Parkinson Disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than three standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to “PET definite PD”. The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14±0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36±1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree. PMID:16528749

Speed, Variability, and Timing of Motor Output in ADHD: Which Measures are Useful for Endophenotypic Research?

PubMed Central

Altink, Marieke E.; Oosterlaan, Jaap; Beem, Leo; Buschgens, Cathelijne J. M.; Buitelaar, Jan; Sergeant, Joseph A.

2007-01-01

Attention-Deficit/Hyperactivity Disorder (ADHD) shares a genetic basis with motor coordination problems and probably motor timing problems. In line with this, comparable problems in motor timing should be observed in first degree relatives and might, therefore, form a suitable endophenotypic candidate. This hypothesis was investigated in 238 ADHD-families (545 children) and 147 control-families (271 children). A motor timing task was administered, in which children had to produce a 1,000 ms interval. In addition to this task, two basic motor tasks were administered to examine speed and variability of motor output, when no timing component was required. Results indicated that variability in motor timing is a useful endophenotypic candidate: It was clearly associated with ADHD, it was also present in non-affected siblings, and it correlated within families. Accuracy (under- versus over-production) in motor timing appeared less useful: Even though accuracy was associated with ADHD (probands and affected siblings had a tendency to under-produce the 1,000 ms interval compared to controls), non-affected siblings did not differ from controls and sibling correlations were only marginally significant. Slow and variable motor output without timing component also appears present in ADHD, but not in non-affected siblings, suggesting these deficits not to be related to a familial vulnerability for ADHD. Deficits in motor timing could not be explained by deficits already present in basic motor output without a timing component. This suggests abnormalities in motor timing were predominantly related to deficient motor timing processes and not to general deficient motor functioning. The finding that deficits in motor timing run in ADHD-families suggests this to be a fruitful domain for further exploration in relation to the genetic underpinnings of ADHD. PMID:18071893

The Leiden Family Lab study on Social Anxiety Disorder: A multiplex, multigenerational family study on neurocognitive endophenotypes.

PubMed

Bas-Hoogendam, Janna Marie; Harrewijn, Anita; Tissier, Renaud L M; van der Molen, Melle J W; van Steenbergen, Henk; van Vliet, Irene M; Reichart, Catrien G; Houwing-Duistermaat, Jeanine J; Slagboom, P Eline; van der Wee, Nic J A; Westenberg, P Michiel

2018-06-01

Social anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so-called "endophenotypes". These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety. The LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD. The sample (n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self-reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms. By the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD. © 2018 The Authors International Journal of Methods in Psychiatric Research Published by John Wiley & Sons Ltd.

Common variant rs356182 near SNCA defines a Parkinson's disease endophenotype.

PubMed

Cooper, Christine A; Jain, Nimansha; Gallagher, Michael D; Weintraub, Daniel; Xie, Sharon X; Berlyand, Yosef; Espay, Alberto J; Quinn, Joseph; Edwards, Karen L; Montine, Thomas; Van Deerlin, Vivianna M; Trojanowski, John; Zabetian, Cyrus P; Chen-Plotkin, Alice S

2017-01-01

Parkinson's disease (PD) presents clinically with several motor subtypes that exhibit variable treatment response and prognosis. Here, we investigated genetic variants for their potential association with PD motor phenotype and progression. We screened 10 SNPs, previously associated with PD risk, for association with tremor-dominant (TD) versus postural-instability gait disorder (PIGD) motor subtypes. SNPs that correlated with the TD/PIGD ratio in a discovery cohort of 251 PD patients were then evaluated in a multi-site replication cohort of 559 PD patients. SNPs associated with motor phenotype in both cross-sectional cohorts were next evaluated for association with (1) rates of motor progression in a longitudinal subgroup of 230 PD patients and (2) brain alpha-synuclein ( SNCA ) expression in the GTEx (Genotype-Tissue Expression project) consortium database. Genotype at rs356182, near SNCA , correlated with the TD/PIGD ratio in both the discovery (Bonferroni-corrected P = 0.04) and replication cohorts ( P = 0.02). The rs356182 GG genotype was associated with a more tremor-predominant phenotype and predicted a slower rate of motor progression (1-point difference in annual rate of UPDRS-III motor score change, P = 0.01). The rs356182 genotype was associated with SNCA expression in the cerebellum ( P = 0.005). Our study demonstrates that the GG genotype at rs356182 provides molecular definition for a clinically important endophenotype associated with (1) more tremor-predominant motor phenomenology, (2) slower rates of motor progression, and (3) decreased brain expression of SNCA . Such molecularly defined endophenotyping in PD may benefit both clinical trial design and tailoring of clinical care as we enter the era of precision medicine.

Neural markers of errors as endophenotypes in neuropsychiatric disorders

PubMed Central

Manoach, Dara S.; Agam, Yigal

2013-01-01

Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach. PMID:23882201

Neural markers of errors as endophenotypes in neuropsychiatric disorders.

PubMed

Manoach, Dara S; Agam, Yigal

2013-01-01

Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.

Impressions of Humanness for Android Robot May Represent an Endophenotype for Autism Spectrum Disorders

ERIC Educational Resources Information Center

Kumazaki, Hirokazu; Warren, Zachary; Swanson, Amy; Yoshikawa, Yuichiro; Matsumoto, Yoshio; Ishiguro, Hiroshi; Sarkar, Nilanjan; Minabe, Yoshio; Kikuchi, Mitsuru

2018-01-01

Identification of meaningful endophenotypes may be critical to unraveling the etiology and pathophysiology of autism spectrum disorders (ASD). We investigated whether impressions of "humanness" for android robot might represent a candidate characteristic of an ASD endophenotype. We used a female type of android robot with an appearance…

Infant social attention: an endophenotype of ASD-related traits?

PubMed Central

Jones, Emily J.H.; Venema, Kaitlin; Earl, Rachel K.; Lowy, Rachel; Webb, Sara J.

2018-01-01

Background As a neurodevelopmental disorder, symptoms of ASD likely emerge from a complex interaction between preexisting genetic vulnerabilities and the child’s environment. One way to understand causal paths to ASD is to identify dimensional ASD-related traits that vary in the general population and that predispose individuals with other risk factors toward ASD. Moving beyond behavioral traits to explore underlying neurocognitive processes may further constrain the underlying genetics. Endophenotypes are quantitative, heritable, trait-related differences that are generally assessed with laboratory-based methods, can be identified in the general population, and may be more closely tied to particular causal chains that have a more restricted set of genetic roots. The most fruitful endophenotypes may be those observed in infancy, prior to the emergence of behavioral symptoms that they are hypothesized to cause. Social motivation is an ASD-related trait that is highly heritable. In this study, we investigate whether infant endophenotypes of social attention relate to familial risk for lower social motivation in the general population. Methods We examined whether infant social attention (measured using habituation, EEG power, and event-related potential tasks previously used in infants/toddlers with ASD) varies quantitatively with parental social motivation in 117 six-month-old and 106 twelve-month-old typically developing infants assessed cross-sectionally. To assess heritable aspects of social motivation, primary caregiver biological parents completed two self-report measures of social avoidance and discomfort that have shown high heritability in previous work. Results Parents with higher social discomfort and avoidance had infants who showed shorter looks to faces but not objects; reduced theta power during naturalistic social attention; and smaller P400 responses to faces versus objects. Conclusions Early reductions in social attention are continuously related

Temperament and Character as Schizophrenia-Related Endophenotypes in Non-psychotic Siblings

PubMed Central

Smith, Matthew J.; Cloninger, C. Robert; Harms, Michael P.; Csernansky, John G.

2008-01-01

Background Quantitative endophenotypes are needed to better understand the pathogenesis of schizophrenia. The psychobiological model of temperament and character suggests that personality traits are heritable and regulated by brain systems influencing schizophrenia susceptibility. Thus, measures of temperament and character may serve as schizophrenia-related endophenotypes in individuals with schizophrenia and their non-psychotic siblings. Methods Individuals with schizophrenia (n=35), their non-psychotic siblings (n=34), controls (n=63), and their siblings (n=56) participated in a study of the clinical, cognitive and neuromorphological characteristics of schizophrenia. A mixed-model approach assessed group differences on the Temperament and Character Inventory (TCI). Neurocognitive deficits and psychopathology were correlated with the TCI. Configurations of TCI domains were examined using a generalized linear model. Results Individuals with schizophrenia and their siblings had higher harm avoidance than controls and their siblings. Individuals with schizophrenia had lower self-directedness and cooperativeness, and higher self-transcendence than their non-psychotic siblings, controls, and the siblings of controls. Neurocognition was not related to temperament and character in individuals with schizophrenia or either control group. In non-psychotic siblings, self-directedness and cooperativeness were correlated with working memory and crystallized IQ. Conclusion Evidence supports harm avoidance as a schizophrenia-related endophenotype. An increased risk of schizophrenia may be associated with asociality (configured as high harm avoidance and low reward dependence), schizotypy (configured as low self-directedness, low cooperativeness, and high self-transcendence), and neurocognitive deficits (poor executive functioning, working/episodic memory, attention, and low IQ). The non-psychotic siblings demonstrated features of a mature character profile including strong

Temperament and character as schizophrenia-related endophenotypes in non-psychotic siblings.

PubMed

Smith, Matthew J; Cloninger, C Robert; Harms, Michael P; Csernansky, John G

2008-09-01

Quantitative endophenotypes are needed to better understand the pathogenesis of schizophrenia. The psychobiological model of temperament and character suggests that personality traits are heritable and regulated by brain systems influencing schizophrenia susceptibility. Thus, measures of temperament and character may serve as schizophrenia-related endophenotypes in individuals with schizophrenia and their non-psychotic siblings. Individuals with schizophrenia (n=35), their non-psychotic siblings (n=34), controls (n=63), and their siblings (n=56) participated in a study of the clinical, neurocognitive and neuromorphological characteristics of schizophrenia. A mixed-model approach assessed group differences on the Temperament and Character Inventory (TCI). Neurocognitive deficits and psychopathology were correlated with the TCI. Configurations of TCI domains were examined using a generalized linear model. Individuals with schizophrenia and their non-psychotic siblings had higher harm avoidance than controls and their siblings. Individuals with schizophrenia had lower self-directedness and cooperativeness, and higher self-transcendence than their non-psychotic siblings, controls, and the siblings of controls. Neurocognition was not related to temperament and character in individuals with schizophrenia or either control group. In non-psychotic siblings, self-directedness and cooperativeness were correlated with working memory and crystallized IQ. Evidence supports harm avoidance as a schizophrenia-related endophenotype. An increased risk of schizophrenia may be associated with asociality (configured as high harm avoidance and low reward dependence), schizotypy (configured as low self-directedness, low cooperativeness, and high self-transcendence), and neurocognitive deficits (poor executive functioning, working/episodic memory, attention, and low IQ). The non-psychotic siblings demonstrated features of a mature character profile including strong crystallized IQ, which

Comparison of the Heritability of Schizophrenia and Endophenotypes in the COGS-1 Family Study

PubMed Central

Light, Gregory; Greenwood, Tiffany A.; Swerdlow, Neal R.; Calkins, Monica E.; Freedman, Robert; Green, Michael F.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Nuechterlein, Keith H.; Olincy, Ann; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Sugar, Catherine A.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.

2014-01-01

Background: Twin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a “heritability gap” between the diagnosis and related endophenotypes. Methods: Nuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families. Results: The heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively. Conclusions: Endophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis. PMID:24903414

Comparison of the heritability of schizophrenia and endophenotypes in the COGS-1 family study.

PubMed

Light, Gregory; Greenwood, Tiffany A; Swerdlow, Neal R; Calkins, Monica E; Freedman, Robert; Green, Michael F; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Sugar, Catherine A; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

2014-11-01

Twin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a "heritability gap" between the diagnosis and related endophenotypes. Nuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families. The heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively. Endophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2014.

Multivariate synaptic and behavioral profiling reveals new developmental endophenotypes in the prefrontal cortex

PubMed Central

Iafrati, Jillian; Malvache, Arnaud; Gonzalez Campo, Cecilia; Orejarena, M. Juliana; Lassalle, Olivier; Bouamrane, Lamine; Chavis, Pascale

2016-01-01

The postnatal maturation of the prefrontal cortex (PFC) represents a period of increased vulnerability to risk factors and emergence of neuropsychiatric disorders. To disambiguate the pathophysiological mechanisms contributing to these disorders, we revisited the endophenotype approach from a developmental viewpoint. The extracellular matrix protein reelin which contributes to cellular and network plasticity, is a risk factor for several psychiatric diseases. We mapped the aggregate effect of the RELN risk allele on postnatal development of PFC functions by cross-sectional synaptic and behavioral analysis of reelin-haploinsufficient mice. Multivariate analysis of bootstrapped datasets revealed subgroups of phenotypic traits specific to each maturational epoch. The preeminence of synaptic AMPA/NMDA receptor content to pre-weaning and juvenile endophenotypes shifts to long-term potentiation and memory renewal during adolescence followed by NMDA-GluN2B synaptic content in adulthood. Strikingly, multivariate analysis shows that pharmacological rehabilitation of reelin haploinsufficient dysfunctions is mediated through induction of new endophenotypes rather than reversion to wild-type traits. By delineating previously unknown developmental endophenotypic sequences, we conceived a promising general strategy to disambiguate the molecular underpinnings of complex psychiatric disorders and for the rational design of pharmacotherapies in these disorders. PMID:27765946

Influence of the Novelty-Seeking Endophenotype on the Rewarding Effects of Psychostimulant Drugs in Animal Models

PubMed Central

Carmen Arenas, M.; Aguilar, María A.; Montagud-Romero, Sandra; Mateos-García, Ana; Navarro-Francés, Concepción I.; Miñarro, José; Rodríguez-Arias, Marta

2016-01-01

Novelty seeking (NS), defined as a tendency to pursue novel and intense emotional sensations and experiences, is one of the most relevant individual factors predicting drug use among humans. High novelty seeking (HNS) individuals present an increased risk of drug use compared to low novelty seekers. The NS endophenotype may explain some of the differences observed among individuals exposed to drugs of abuse in adolescence. However, there is little research about the particular response of adolescents to drugs of abuse in function of this endophenotype, and the data that do exist are inconclusive. The present work reviews the literature regarding the influence of NS on psychostimulant reward, with particular focus on adolescent subjects. First, the different animal models of NS and the importance of this endophenotype in adolescence are discussed. Later, studies that have used the most common animal models of reward (self-administration, conditioned place preference paradigms) to evaluate how the NS trait influences the rewarding effects of psychostimulants are reviewed. Finally, possible explanations for the enhanced risk of developing substance dependence among HNS individuals are discussed. In conclusion, the studies referred to in this review show that the HNS trait is associated with: (1) increased initial sensitivity to the rewarding effects of psychostimulants, (2) a higher level of drug craving when the subject is exposed to the environmental cues associated with the drug, and (3) enhanced long-term vulnerability to relapse to drug consumption after prolonged abstinence. PMID:26391743

Integrating Behavioral Economics and Behavioral Genetics: Delayed Reward Discounting as an Endophenotype for Addictive Disorders

PubMed Central

MacKillop, James

2013-01-01

Delayed reward discounting is a behavioral economic index of impulsivity, referring to how much an individual devalues a reward based on its delay in time. As a behavioral process that varies considerably across individuals, delay discounting has been studied extensively as a model for self-control, both in the general population and in clinical samples. There is growing interest in genetic influences on discounting and, in particular, the prospect of discounting as an endophenotype for addictive disorders (i.e., a heritable mechanism partially responsible for conferring genetic risk). This review assembles and critiques the evidence supporting this hypothesis. Via numerous cross-sectional studies and a small number of longitudinal studies, there is considerable evidence that impulsive discounting is associated with addictive behavior and appears to play an etiological role. Moreover, there is increasing evidence from diverse methodologies that impulsive delay discounting is temporally stable, heritable, and that elevated levels are present in nonaffected family members. These findings suggest that impulsive discounting meets the criteria for being considered an endophenotype. In addition, recent findings suggest that genetic variation related to dopamine neurotransmission is significantly associated with variability in discounting preferences. A significant caveat, however, is that the literature is modest in some domains and, in others, not all the findings have been supportive or consistent. In addition, important methodological considerations are necessary in future studies. Taken together, although not definitive, there is accumulating support for the hypothesis of impulsive discounting as an endophenotype for addictive behavior and a need for further systematic investigation. PMID:23344986

Altered Reward Reactivity as a Behavioural Endophenotype in Eating Disorders: A Pilot Investigation in Twins.

PubMed

Kanakam, Natalie; Krug, Isabel; Collier, David; Treasure, Janet

2017-05-01

Altered reward reactivity is a potential risk endophenotype for eating disorders (EDs). The aim of this study was to examine reward reactivity in female twins with EDs and compare it with a twin control group. A sample of 112 twins [n = 51 met lifetime DSM-IV ED criteria (anorexia nervosa n = 26; bulimic disorders n = 24), n = 19 unaffected cotwins and n = 42 control twins] was administered measures assessing reward reactivity, including the Game of Dice Task, the Behavioural Inhibition/Activation (BIS/BAS) Scales and the Appetitive Motivation Scale (AMS). Within pair, correlations for monozygotic and dizygotic twins were calculated and generalised estimating equations compared probands with non-ED cotwins and controls. The BAS and the AMS were reduced in EDs and negatively associated with restrictive symptoms. In addition, monozygotic twins pairs demonstrated significant within pair similarity for the BAS and AMS. Conversely, there was less evidence to support the BIS or risky decision-making as measured by the Game of Dice Task as an endophenotype in EDs. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Does Performance on the Standard Antisaccade Task Meet the Co-Familiality Criterion for an Endophenotype?

ERIC Educational Resources Information Center

Levy, Deborah L.; Bowman, Elizabeth A.; Abel, Larry; Krastoshevsky, Olga; Krause, Verena; Mendell, Nancy R.

2008-01-01

The "co-familiality" criterion for an endophenotype has two requirements: (1) clinically unaffected relatives as a group should show both a shift in mean performance and an increase in variance compared with controls; (2) performance scores should be heritable. Performance on the antisaccade task is one of several candidate endophenotypes for…

Randomization and resilience of brain functional networks as systems-level endophenotypes of schizophrenia.

PubMed

Lo, Chun-Yi Zac; Su, Tsung-Wei; Huang, Chu-Chung; Hung, Chia-Chun; Chen, Wei-Ling; Lan, Tsuo-Hung; Lin, Ching-Po; Bullmore, Edward T

2015-07-21

Schizophrenia is increasingly conceived as a disorder of brain network organization or dysconnectivity syndrome. Functional MRI (fMRI) networks in schizophrenia have been characterized by abnormally random topology. We tested the hypothesis that network randomization is an endophenotype of schizophrenia and therefore evident also in nonpsychotic relatives of patients. Head movement-corrected, resting-state fMRI data were acquired from 25 patients with schizophrenia, 25 first-degree relatives of patients, and 29 healthy volunteers. Graphs were used to model functional connectivity as a set of edges between regional nodes. We estimated the topological efficiency, clustering, degree distribution, resilience, and connection distance (in millimeters) of each functional network. The schizophrenic group demonstrated significant randomization of global network metrics (reduced clustering, greater efficiency), a shift in the degree distribution to a more homogeneous form (fewer hubs), a shift in the distance distribution (proportionally more long-distance edges), and greater resilience to targeted attack on network hubs. The networks of the relatives also demonstrated abnormal randomization and resilience compared with healthy volunteers, but they were typically less topologically abnormal than the patients' networks and did not have abnormal connection distances. We conclude that schizophrenia is associated with replicable and convergent evidence for functional network randomization, and a similar topological profile was evident also in nonpsychotic relatives, suggesting that this is a systems-level endophenotype or marker of familial risk. We speculate that the greater resilience of brain networks may confer some fitness advantages on nonpsychotic relatives that could explain persistence of this endophenotype in the population.

The Leiden Family Lab study on Social Anxiety Disorder: A multiplex, multigenerational family study on neurocognitive endophenotypes

PubMed Central

Harrewijn, Anita; Tissier, Renaud L.M.; van der Molen, Melle J.W.; van Steenbergen, Henk; van Vliet, Irene M.; Reichart, Catrien G.; Houwing‐Duistermaat, Jeanine J.; Slagboom, P. Eline; van der Wee, Nic J.A.; Westenberg, P. Michiel

2018-01-01

abstract Objectives Social anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so‐called “endophenotypes”. These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety. Methods The LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD. Results The sample (n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self‐reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms. Conclusions By the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD. PMID:29700902

A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin.

PubMed

Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Holmans, Peter; Bertelsen, Sarah; Holtzman, David; Morris, John C; Bales, Kelly; Pickering, Eve H; Kauwe, John; Goate, Alison; Cruchaga, Carlos

2016-01-01

Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer's disease (AD). However, the role of CLU on AD pathogenesis is not totally understood. We used cerebrospinal fluid (CSF) and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not plasma, CLU levels were significantly associated with AD status and CSF tau/amyloid-beta ratio, and highly correlated with CSF apolipoprotein E (APOE) levels. Several loci showed almost genome-wide significant associations including LINC00917 (p = 3.98 × 10(-7)) and interleukin 6 (IL6, p = 9.94 × 10(-6), in the entire data set and in the APOE ε4- individuals p = 7.40 × 10(-8)). Gene ontology analyses suggest that CSF CLU levels may be associated with wound healing and immune response which supports previous functional studies that demonstrated an association between CLU and IL6. CLU may play a role in AD by influencing immune system changes that have been observed in AD or by disrupting healing after neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Cannabis and cognitive dysfunction: parallels with endophenotypes of schizophrenia?

PubMed

Solowij, Nadia; Michie, Patricia T

2007-01-01

Currently, there is a lot of interest in cannabis use as a risk factor for the development of schizophrenia. Cognitive dysfunction associated with long-term or heavy cannabis use is similar in many respects to the cognitive endophenotypes that have been proposed as vulnerability markers of schizophrenia. In this overview, we examine the similarities between these in the context of the neurobiology underlying cognitive dysfunction, particularly implicating the endogenous cannabinoid system, which plays a significant role in attention, learning and memory, and in general, inhibitory regulatory mechanisms in the brain. Closer examination of the cognitive deficits associated with specific parameters of cannabis use and interactions with neurodevelopmental stages and neural substrates will better inform our understanding of the nature of the association between cannabis use and psychosis. The theoretical and clinical significance of further research in this field is in enhancing our understanding of underlying pathophysiology and improving the provision of treatments for substance use and mental illness.

[Attention deficit hyperactivity disorder: its aetiological factors and endophenotypes].

PubMed

Ferrando-Lucas, M T

2006-02-13

Attention deficit hyperactivity disorder (ADHD) is one of the most frequent reasons for patients' visits in everyday practice. The academic and social distortion it produces in those affected by this condition have turned it into a subject that is receiving growing attention from researchers and the progress being made in the neurosciences means that it is being investigated from a wide range of approaches. Genetic aspects, as well as anatomical and neurobiological markers, are some of the new lines of research that are being used together with a more precise neuropsychological approach to obtain a more comprehensive understanding of ADHD. Such knowledge now involves genetic factors, centres of cognitive disorder and the search for endophenotypes that account for the complexity of its semiology. The primary cognitive deficits in ADHD appear to be the underlying problem in the disorder, special attention also being given to both the executive functions and the distortion of the capacity to inhibit responses. Furthermore, anatomical factors have been related to the type and severity of the symptomatology of the disorder, although the dispersion of the results and the genetic findings that focus their attention on anomalous alleles for dopamine transporting and receptor genes suggest that the disorder is more complex. The different aetiological factors that have been associated to the disorder and the variability in the semiology of ADHD place us before a situation in disarray; the determination of endophenotypes, however, could enable us carry out a better systematisation of a disorder that is currently still a long way from being fully understood.

Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism

PubMed Central

2013-01-01

Background Autism spectrum conditions (ASC) are associated with deficits in social interaction and communication, alongside repetitive, restricted, and stereotyped behavior. ASC is highly heritable. The gamma-aminobutyric acid (GABA)-ergic system has been associated consistently with atypicalities in autism, in both genetic association and expression studies. A key component of the GABA-ergic system is encoded by the GABRB3 gene, which has been previously implicated both in ASC and in individual differences in empathy. Methods In this study, 45 genotyped single nucleotide polymorphisms (SNPs) within GABRB3 were tested for association with Asperger syndrome (AS), and related quantitative traits measured through the following tests: the Empathy Quotient (EQ), the Autism Spectrum Quotient (AQ), the Systemizing Quotient-Revised (SQ-R), the Embedded Figures Test (EFT), the Reading the Mind in the Eyes Test (RMET), and the Mental Rotation Test (MRT). Two-loci, three-loci, four-loci haplotype analyses, and one seven-loci haplotype analysis were also performed in the AS case–control sample. Results Three SNPs (rs7180158, rs7165604, rs12593579) were significantly associated with AS, and two SNPs (rs9806546, rs11636966) were significantly associated with EQ. Two SNP-SNP pairs, rs12438141-rs1035751 and rs12438141-rs7179514, showed significant association with variation in the EFT scores. One SNP-SNP pair, rs7174437-rs1863455, was significantly associated with variation in the MRT scores. Additionally, a few haplotypes, including a 19 kb genomic region that formed a linkage disequilibrium (LD) block in our sample and contained several nominally significant SNPs, were found to be significantly associated with AS. Conclusion The current study confirms the role of GABRB3 as an important candidate gene in both ASC and normative variation in related endophenotypes. PMID:24321478

Executive functions as a potential neurocognitive endophenotype in anxiety disorders: A systematic review considering DSM-IV and DSM-5 diagnostic criteria classification.

PubMed

Muller, Juliana de Lima; Torquato, Kamilla Irigaray; Manfro, Gisele Gus; Trentini, Clarissa Marceli

2015-01-01

Evidence in the literature indicates that neurocognitive impairments may represent endophenotypes in psychiatric disorders. This study aimed to conduct a systematic review on executive functions as a potential neurocognitive endophenotype in anxiety disorder diagnosis according to the DSM-IV and DSM-5 classifications. A literature search of the LILACS, Cochrane Library, Index Psi Periódicos Técnico-Científicos, PubMed and PsycInfo databases was conducted, with no time limits. Of the 259 studies found, 14 were included in this review. Only studies on obsessive-compulsive disorder (OCD) were found. The executive function components of decision-making, planning, response inhibition, behavioral reversal/alternation, reversal learning and set-shifting/cognitive flexibility were considered to be a neurocognitive endophenotypes in OCD. Further studies on executive functions as a neurocognitive endophenotype in other anxiety disorders are needed since these may have different neurocognitive endophenotypes and require other prevention and treatment approaches.

A potential endophenotype for Alzheimer’s disease: cerebrospinal fluid clusterin

PubMed Central

Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Holmans, Peter; Bertelsen, Sarah; Holtzman, David; Morris, John C; Bales, Kelly; Pickering, Eve H; Kauwe, John; Goate, Alison; Cruchaga, Carlos

2016-01-01

Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer’s disease (AD). However the role of CLU on AD pathogenesis is not totally understood. We used CSF and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not plasma, CLU levels were significantly associated with AD status and CSF tau/Aβ ratio, and highly correlated with CSF apolipoprotein E (APOE) levels. Several loci showed almost genome-wide significant associations including LINC00917 (p=3.98×10−7) and interleukin 6 (IL6, p=9.94×10−6, in the entire dataset and in the APOE ε4- individuals p=7.40×10−8). Gene-ontology analyses suggest that CSF CLU levels may be associated with wound healing and immune response which supports previous functional studies that demonstrated an association between CLU and IL6. CLU may play a role in AD by influencing immune system changes that have been observed in AD or by disrupting healing after neurodegeneration. PMID:26545630

Atypical patterns of respiratory sinus arrhythmia index an endophenotype for depression

PubMed Central

Yaroslavsky, Ilya; Rottenberg, Jonathan; Kovacs, Maria

2015-01-01

Can atypical patterns of parasympathetic nervous system activity serve as endophenotypes for depression? Using respiratory sinus arrhythmia (RSA) as an index of parasympathetic nervous system function, we examined this question in two studies: one involving mothers with and without depression histories and their offspring (at high and low risk for depression, respectively), and a further study of adolescent sibling pairs concordant and discordant for major depression. In both studies, subjects were exposed to sad mood induction; subjects’ RSA was monitored during rest periods and in response to the mood induction. We used Gottesman and Gould’s (2003) criteria for an endophenotype and a priori defined “atypical” and “normative” RSA patterns (combinations of resting RSA and RSA reactivity). We found that atypical RSA patterns (a) predicted current depressive episodes and remission status among women with histories of juvenile onset depression and healthy controls, (b) predicted longitudinal trajectories of depressive symptoms among high- and low-risk young offspring, (c) were concordant across mothers and their juvenile offspring, (d) were more prevalent among never-depressed youth at high risk for depression than their low-risk peers, and (e) were more concordant across adolescent sibling pairs in which both versus only one had a history of major depression. Thus, the results support atypical RSA patterns as an endophenotype for depression. Possible mechanisms by which RSA patterns increase depression risk and their genetic contributors are discussed. PMID:25422965

Neurocognitive endophenotypes for bipolar disorder identified in multiplex multigenerational families.

PubMed

Glahn, David C; Almasy, Laura; Barguil, Marcela; Hare, Elizabeth; Peralta, Juan Manuel; Kent, Jack W; Dassori, Albana; Contreras, Javier; Pacheco, Adriana; Lanzagorta, Nuria; Nicolini, Humberto; Raventós, Henriette; Escamilla, Michael A

2010-02-01

Although genetic influences on bipolar disorder are well established, localization of genes that predispose to the illness has proven difficult. Given that genes predisposing to bipolar disorder may be transmitted without expression of the categorical clinical phenotype, a strategy for identifying risk genes is to identify and map quantitative intermediate phenotypes or endophenotypes. To adjudicate neurocognitive endophenotypes for bipolar disorder. All participants underwent diagnostic interviews and comprehensive neurocognitive evaluations. Neurocognitive measures found to be heritable were entered into analyses designed to determine which test results are impaired in affected individuals, are sensitive to the genetic liability for the illness, and are genetically correlated with affection status. Central valley of Costa Rica; Mexico City, Mexico; and San Antonio, Texas. Seven hundred nine Latino individuals participated in the study. Of these, 660 were members of extended pedigrees with at least 2 siblings diagnosed as having bipolar disorder (n = 230). The remaining subjects were community control subjects drawn from each site who did not have a personal or family history of bipolar disorder or schizophrenia. Neurocognitive test performance. Two of the 22 neurocognitive variables were not significantly heritable and were excluded from subsequent analyses. Patients with bipolar disorder were impaired on 6 cognitive measures compared with nonrelated healthy controls. Nonbipolar first-degree relatives were impaired on 5 of these, and the following 3 tests were genetically correlated with affection status: Digit Symbol Coding Task, Object Delayed Response Task, and immediate facial memory. This large-scale extended pedigree study of cognitive functioning in bipolar disorder identifies measures of processing speed, working memory, and declarative (facial) memory as candidate endophenotypes for bipolar disorder.

Temporal discrimination, a cervical dystonia endophenotype: penetrance and functional correlates.

PubMed

Kimmich, Okka; Molloy, Anna; Whelan, Robert; Williams, Laura; Bradley, David; Balsters, Joshua; Molloy, Fiona; Lynch, Tim; Healy, Daniel G; Walsh, Cathal; O'Riordan, Seán; Reilly, Richard B; Hutchinson, Michael

2014-05-01

The pathogenesis of adult-onset primary dystonia remains poorly understood. There is variable age-related and gender-related expression of the phenotype, the commonest of which is cervical dystonia. Endophenotypes may provide insight into underlying genetic and pathophysiological mechanisms of dystonia. The temporal discrimination threshold (TDT)-the shortest time interval at which two separate stimuli can be detected as being asynchronous-is abnormal both in patients with cervical dystonia and in their unaffected first-degree relatives. Functional magnetic resonance imaging (fMRI) studies have shown that putaminal activation positively correlates with the ease of temporal discrimination between two stimuli in healthy individuals. We hypothesized that abnormal temporal discrimination would exhibit similar age-related and gender-related penetrance as cervical dystonia and that unaffected relatives with an abnormal TDT would have reduced putaminal activation during a temporal discrimination task. TDTs were examined in a group of 192 healthy controls and in 158 unaffected first-degree relatives of 84 patients with cervical dystonia. In 24 unaffected first-degree relatives, fMRI scanning was performed during a temporal discrimination task. The prevalence of abnormal TDTs in unaffected female relatives reached 50% after age 48 years; whereas, in male relatives, penetrance of the endophenotype was reduced. By fMRI, relatives who had abnormal TDTs, compared with relatives who had normal TDTs, had significantly less activation in the putamina and in the middle frontal and precentral gyri. Only the degree of reduction of putaminal activity correlated significantly with worsening of temporal discrimination. These findings further support abnormal temporal discrimination as an endophenotype of cervical dystonia involving disordered basal ganglia circuits. © 2014 International Parkinson and Movement Disorder Society.

A Review of the Differences in Developmental, Psychiatric, and Medical Endophenotypes Between Males and Females with Autism Spectrum Disorder

PubMed Central

Rubenstein, Eric; Wiggins, Lisa D.; Lee, Li-Ching

2015-01-01

Autism spectrum disorder (ASD) is over four times more prevalent in males compared to females. Increased understanding of sex differences in ASD endophenotypes could add insight into possible etiologies and the assessment and management of the disorder. Consequently, the purpose of this review is to describe current literature regarding sex differences in the developmental, psychiatric, and medical endophenotypes of ASD in order to illustrate current knowledge and areas in need of further research. Our review found that repetitive behaviors and restricted interests are more common in males than females with ASD. Intellectual disability is more common in females than males with ASD. Attention to detail may be more common in males than females with ASD and epilepsy may be more common in females than males with ASD, although limited research in these areas prevent definitive conclusions from being drawn. There does not appear to be a sex difference in other developmental, psychiatric, and medical symptoms associated with ASD, or the research was contradictory or too sparse to establish a sex difference. Our review is unique in that it offers detailed discussion of sex differences in three major endophenotypes of ASD. Further research is needed to better understand why sex differences exist in certain ASD traits and to evaluate whether phenotypic sex differences are related to different pathways of development, assessment, and treatment of the disorder. PMID:26146472

A Cognitive Endophenotype of Autism in Families with Multiple Incidence

ERIC Educational Resources Information Center

Nyden, Agneta; Hagberg, Bibbi; Gousse, Veronique; Rastam, Maria

2011-01-01

Twin and family studies have established that there is a strong genetic basis for autism spectrum disorders. To facilitate the identification of susceptibility genes and to study pathways from gene-brain to cognition a more refined endophenotype-based approach may be useful. The purpose of the present study was to examine the neurocognitive…

Impressions of Humanness for Android Robot may Represent an Endophenotype for Autism Spectrum Disorders.

PubMed

Kumazaki, Hirokazu; Warren, Zachary; Swanson, Amy; Yoshikawa, Yuichiro; Matsumoto, Yoshio; Ishiguro, Hiroshi; Sarkar, Nilanjan; Minabe, Yoshio; Kikuchi, Mitsuru

2018-02-01

Identification of meaningful endophenotypes may be critical to unraveling the etiology and pathophysiology of autism spectrum disorders (ASD). We investigated whether impressions of "humanness" for android robot might represent a candidate characteristic of an ASD endophenotype. We used a female type of android robot with an appearance similar to that of a real person. Significant differences in overall impressions of 'humanness' for android robot were found between adolescents with ASD and typical development (TD) controls, as well as parents of children with ASD and parents of TD controls. Our current work does suggest robotic systems could potentially play an intelligent role in dissecting ASD heterogeneity.

Dopaminergic foundations of schizotypy as measured by the German version of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE)—a suitable endophenotype of schizophrenia

PubMed Central

Grant, Phillip; Kuepper, Yvonne; Mueller, Eva A.; Wielpuetz, Catrin; Mason, Oliver; Hennig, Juergen

2013-01-01

The concept of schizotypy or “psychosis proneness” captures individual differences in perceptual, cognitive, and affective experiences that may relate to a range of psychotic disorders. The concept is an important way to assess the contribution of pre-existing psychological and genetically based biological features to the development of illnesses such as schizophrenia (so called endophenotypes). The Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) is a widely used multi-dimensional measure of the construct and consists of four scales which mirror several groups of psychotic symptoms: Unusual Experiences (UnEx; positive symptoms), Cognitive Disorganization (CogDis; cognitive symptoms), Introvertive Anhedonia (IntAn; negative symptoms), and Impulsive Nonconformity (ImpNon; impulsive and antisocial symptoms). For the purpose of evaluating the suitability of schizotypy as an endophenotype of schizophrenia the current version of the O-LIFE was translated into German: its psychometric properties (including re-test reliability and construct validity) were examined in a large sample (n > 1200) and compared to those of the English original. The German version was both highly reliable and consistent with the original. The study aimed to show that schizotypy as measured by the O-LIFE can indeed be regarded as an endophenotype of schizophrenia in terms of genetic associations regarding relevant dopamine-related candidate polymorphisms of schizotypy [i.e., Val158Met-polymorphism of the COMT gene, uVNTR of the MAOA gene, Taq1A-polymorphism of the DRD2 gene, VNTR of the SLC6A3 (DAT) gene]. We also wanted to compare the genetic associations of the O-LIFE to those published using other operationalizations of schizotypy. Our results show a large number of significant associations and borderline-significant trends between the O-LIFE sub-scales and a range of genes, thereby supporting using the O-LIFE in the search for endophenotypic markers. PMID:23355817

Neurocognitive Endophenotypes for Bipolar Disorder Identified in Multiplex Multigenerational Families

PubMed Central

Glahn, David C.; Almasy, Laura; Barguil, Marcela; Hare, Elizabeth; Peralta, Juan Manuel; Kent, Jack W.; Dassori, Alabana; Contreras, Javier; Pacheco, Adriana; Lanzagorta, Nuria; Nicolini, Humberto; Raventós, Henriette; Escamilla, Michael A.

2012-01-01

Context Although genetic influences on bipolar disorder are well established, localization of genes that predispose to the illness has proven difficult. Given that genes predisposing to bipolar disorder may be transmitted without expression of the categorical clinical phenotype, one strategy for identifying risk genes is the use of quantitative endophenotypes. Objective The goal of the current study is to adjudicate neurocognitive endophenotypes for bipolar disorder. Design, Setting, and Participants 709 Latino individuals from the central valley of Costa Rica, Mexico City, Mexico, or San Antonio, Texas participated in the study. 660 of these persons were members of extended pedigrees with at least two siblings diagnosed with bipolar disorder (n=230). The remaining subjects were community controls drawn from each site and without personal or family history of bipolar disorder or schizophrenia. All subjects received psychodiagnostic interviews and comprehensive neurocognitive evaluations. Neurocognitive measures found to be heritable were entered into analyses designed to determine which tests are impaired in affected individuals, sensitive to genetic liability for the illness and genetically correlated with affection status. Main Outcome Measures The main outcome measure was neurocognitive test performance. Results Two of the 21 neurocognitive variables were not significantly heritable and were excluded from subsequent analyses. Patients with bipolar disorder were impaired on 6 of these cognitive measures compared to non-related healthy subjects. Non-bipolar first-degree relatives were impaired on five of these and three tests were genetically correlated with affection status: digit symbol coding, object delayed response, and immediate facial memory. Conclusions This large-scale extended pedigree study of cognitive functioning in bipolar disorder identified measures of processing speed, working memory and declarative (facial) memory as candidate endophenotypes for

Revisiting the Suitability of Antisaccade Performance as an Endophenotype in Schizophrenia

ERIC Educational Resources Information Center

Mazhari, Shahrzad; Price, Greg; Dragovic, Milan; Waters, Flavie A.; Clissa, Peter; Jablensky, Assen

2011-01-01

Poor performance on the antisaccade task has been proposed as a candidate endophenotype in schizophrenia. Caveats to this proposal, however, include inconsistent findings in first-degree relatives of individuals with schizophrenia, and substantial heterogeneity in individuals with the disorder. In this study, we examined antisaccade performance in…

Evidence of an association between 10/10 genotype of DAT1 and endophenotypes of attention deficit/hyperactivity disorder.

PubMed

Agudelo, J A; Gálvez, J M; Fonseca, D J; Mateus, H E; Talero-Gutiérrez, C; Velez-Van-Meerbeke, A

2015-04-01

Genetic variance of attention deficit-hyperactivity disorder (ADHD) is a strong determinant of this disorder. The 40 base pairs (bp) variable number tandem repeat (VNTR) located in the 3' untranslated region (UTR) of DAT1 gene increases the expression of the dopamine transporter. Therefore, DAT1 has been associated with susceptibility to ADHD. To determine the association between the VNTR of DAT1 and the phenotype of ADHD or its endophenotypes in a sample of children aged between 6 and 15 years from Bogotá. We selected 73 patients with ADHD and 54 controls. WISC test was applied in all subjects and executive functions were assessed. The VNTR of DAT1 was polymerase chain reaction-amplified. Data regarding population genetics and statistical analysis were obtained. Correlation and association tests between genotype and neuropsychological testing were performed. The DAT1 polymorphism was not associated with ADHD (P=.85). Nevertheless, the 10/10 genotype was found to be correlated with the processing speed index (P<.05). In the hyperactivity subtype, there was a genotypic correlation with some subtests of executive function (cognitive flexibility) (P≤.01). In the combined subtype, the 10/10 genotype was associated with verbal comprehension index of WISC (P<.05). A correlation was found between DAT1 VNTR and the subtest "processing speed index" of WISC and the subtest "cognitive flexibility" of executive functions. To our knowledge, this is the first report to assess DAT1 gene in a Colombian population. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Atypical activation during the Embedded Figures Task as a functional magnetic resonance imaging endophenotype of autism

PubMed Central

Holt, Rosemary J.; Chura, Lindsay R.; Calder, Andrew J.; Suckling, John; Bullmore, Edward T.; Baron-Cohen, Simon

2012-01-01

Atypical activation during the Embedded Figures Task has been demonstrated in autism, but has not been investigated in siblings or related to measures of clinical severity. We identified atypical activation during the Embedded Figures Task in participants with autism and unaffected siblings compared with control subjects in a number of temporal and frontal brain regions. Autism and sibling groups, however, did not differ in terms of activation during this task. This suggests that the pattern of atypical activation identified may represent a functional endophenotype of autism, related to familial risk for the condition shared between individuals with autism and their siblings. We also found that reduced activation in autism relative to control subjects in regions including associative visual and face processing areas was strongly correlated with the clinical severity of impairments in reciprocal social interaction. Behavioural performance was intact in autism and sibling groups. Results are discussed in terms of atypical information processing styles or of increased activation in temporal and frontal regions in autism and the broader phenotype. By separating the aspects of atypical activation as markers of familial risk for the condition from those that are autism-specific, our findings offer new insight into the factors that might cause the expression of autism in families, affecting some children but not others. PMID:23065480

Delta-beta correlation as a candidate endophenotype of social anxiety: A two-generation family study.

PubMed

Harrewijn, Anita; van der Molen, Melle J W; van Vliet, Irene M; Houwing-Duistermaat, Jeanine J; Westenberg, P Michiel

2018-02-01

Social anxiety disorder (SAD) is characterized by an extreme and intense fear and avoidance of social situations. In this two-generation family study we examined delta-beta correlation during a social performance task as candidate endophenotype of SAD. Nine families with a target participant (diagnosed with SAD), their spouse and children, as well as target's siblings with spouse and children performed a social performance task in which they gave a speech in front of a camera. EEG was measured during resting state, anticipation, and recovery. Our analyses focused on two criteria for endophenotypes: co-segregation within families and heritability. Co-segregation analyses revealed increased negative delta-low beta correlation during anticipation in participants with (sub)clinical SAD compared to participants without (sub)clinical SAD. Heritability analyses revealed that delta-low beta and delta-high beta correlation during anticipation were heritable. Delta-beta correlation did not differ between participants with and without (sub)clinical SAD during resting state or recovery, nor between participants with and without SAD during all phases of the task. It should be noted that participants were seen only once, they all performed the EEG tasks in the same order, and some participants were too anxious to give a speech. Delta-low beta correlation during anticipation of giving a speech might be a candidate endophenotype of SAD, possibly reflecting increased crosstalk between cortical and subcortical regions. If validated as endophenotype, delta-beta correlation during anticipation could be useful in studying the genetic basis, as well as improving treatment and early detection of persons at risk for developing SAD. Copyright © 2017 Elsevier B.V. All rights reserved.

Temperament and character as endophenotype in adults with autism spectrum disorders or attention deficit/hyperactivity disorder.

PubMed

Sizoo, Bram B; van der Gaag, Rutger Jan; van den Brink, Wim

2015-05-01

Autism spectrum disorder and attention deficit/hyperactivity disorder overlap in several ways, raising questions about the nature of this comorbidity. Rommelse et al. published an innovative review of candidate endophenotypes for autism spectrum disorder and attention deficit/hyperactivity disorder in cognitive and brain domains. They found that all the endophenotypic impairments that were reviewed in attention deficit/hyperactivity disorder were also present in autism spectrum disorder, suggesting a continuity model with attention deficit/hyperactivity disorder as "a light form of autism spectrum disorder." Using existing data, 75 adults with autism spectrum disorder and 53 with attention deficit/hyperactivity disorder were directly compared on autistic symptoms with the autism spectrum quotient, and on the endophenotypic measure of temperament and character, using the Abbreviated (Dutch: Verkorte) Temperament and Character Inventory. Based on the hypothesis that attention deficit/hyperactivity disorder and autism spectrum disorder are disorders on a continuous spectrum, autism spectrum quotient scores and abbreviated Temperament and Character Inventory scores were expected to be different from normal controls in both disorders in a similar direction. In addition, the autism spectrum quotient and abbreviated Temperament and Character Inventory scores were expected to be closely correlated. These conditions applied to only two of the seven Abbreviated Temperament and Character Inventory scales (harm avoidance and self-directedness), suggesting that temperament and character as an endophenotype of autism spectrum disorder and attention deficit/hyperactivity disorder provides only partial support for the continuity hypothesis of autism spectrum disorder and attention deficit/hyperactivity disorder. © The Author(s) 2014.

Interval Timing Deficits Assessed by Time Reproduction Dual Tasks as Cognitive Endophenotypes for Attention-Deficit/Hyperactivity Disorder

PubMed Central

Hwang-Gu, Shoou-Lian; Gau, Susan Shur-Fen

2015-01-01

The literature has suggested timing processing as a potential endophenotype for attention deficit/hyperactivity disorder (ADHD); however, whether the subjective internal clock speed presented by verbal estimation and limited attention capacity presented by time reproduction could be endophenotypes for ADHD is still unknown. We assessed 223 youths with DSM-IV ADHD (age range: 10-17 years), 105 unaffected siblings, and 84 typically developing (TD) youths using psychiatric interviews, intelligence tests, verbal estimation and time reproduction tasks (single task and simple and difficult dual tasks) at 5-second, 12-second, and 17-second intervals. We found that youths with ADHD tended to overestimate time in verbal estimation more than their unaffected siblings and TD youths, implying that fast subjective internal clock speed might be a characteristic of ADHD, rather than an endophenotype for ADHD. Youths with ADHD and their unaffected siblings were less precise in time reproduction dual tasks than TD youths. The magnitude of estimated errors in time reproduction was greater in youths with ADHD and their unaffected siblings than in TD youths, with an increased time interval at the 17-second interval and with increased task demands on both simple and difficult dual tasks versus the single task. Increased impaired time reproduction in dual tasks with increased intervals and task demands were shown in youths with ADHD and their unaffected siblings, suggesting that time reproduction deficits explained by limited attention capacity might be a useful endophenotype of ADHD. PMID:25992899

Evidence for the Late MMN as a Neurophysiological Endophenotype for Dyslexia

PubMed Central

Neuhoff, Nina; Bruder, Jennifer; Bartling, Jürgen; Warnke, Andreas; Remschmidt, Helmut; Müller-Myhsok, Bertram; Schulte-Körne, Gerd

2012-01-01

Dyslexia affects 5–10% of school-aged children and is therefore one of the most common learning disorders. Research on auditory event related potentials (AERP), particularly the mismatch negativity (MMN) component, has revealed anomalies in individuals with dyslexia to speech stimuli. Furthermore, candidate genes for this disorder were found through molecular genetic studies. A current challenge for dyslexia research is to understand the interaction between molecular genetics and brain function, and to promote the identification of relevant endophenotypes for dyslexia. The present study examines MMN, a neurophysiological correlate of speech perception, and its potential as an endophenotype for dyslexia in three groups of children. The first group of children was clinically diagnosed with dyslexia, whereas the second group of children was comprised of their siblings who had average reading and spelling skills and were therefore “unaffected” despite having a genetic risk for dyslexia. The third group consisted of control children who were not related to the other groups and were also unaffected. In total, 225 children were included in the study. All children showed clear MMN activity to/da/−/ba/contrasts that could be separated into three distinct MMN components. Whilst the first two MMN components did not differentiate the groups, the late MMN component (300–700 ms) revealed significant group differences. The mean area of the late MMN was attenuated in both the dyslexic children and their unaffected siblings in comparison to the control children. This finding is indicative of analogous alterations of neurophysiological processes in children with dyslexia and those with a genetic risk for dyslexia, without a manifestation of the disorder. The present results therefore further suggest that the late MMN might be a potential endophenotype for dyslexia. PMID:22606227

A depressive endophenotype of mild cognitive impairment and Alzheimer's disease.

PubMed

Johnson, Leigh A; Hall, James R; O'Bryant, Sid E

2013-01-01

Alzheimer's disease (AD) is a devastating public health problem that affects over 5.4 million Americans. Depression increases the risk of Mild Cognitive Impairment (MCI) and AD. By understanding the influence of depression on cognition, the potential exists to identify subgroups of depressed elders at greater risk for cognitive decline and AD. The current study sought to: 1) clinically identify a sub group of geriatric patients who suffer from depression related cognitive impairment; 2) cross validate this depressive endophenotype of MCI/AD in an independent cohort. Data was analyzed from 519 participants of Project FRONTIER. Depression was assessed with the GDS30 and cognition was assessed using the EXIT 25 and RBANS. Five GDS items were used to create the Depressive endophenotype of MCI and AD (DepE). DepE was significantly negatively related to RBANS index scores of Immediate Memory (B=-2.22, SE=.37, p<0.001), visuospatial skills (B=-1.11, SE=0.26, p<0.001), Language (B=-1.03, SE=0.21, p<0.001), Attention (B=-2.56, SE=0.49, p<0.001), and Delayed Memory (B=-1.54, SE = 037, p<0.001), and higher DepE scores were related to poorer executive functioning (EXIT25; B=0.65, SE=0.19, p=0.001). DepE scores significantly increased risk for MCI diagnosis (odds ratio [OR] = 2.04; 95% CI=1.54-2.69). Data from 235 participants in the TARCC (Texas Alzheimer's Research & Care Consortium) were analyzed for cross-validation of findings in an independent cohort. The DepE was significantly related to poorer scores on all measures, and a significantly predicted of cognitive change over 12- and 24-months. The current findings suggest that a depressive endophenotype of MCI and AD exists and can be clinically identified using the GDS-30. Higher scores increased risk for MCI and was cross-validated by predicting AD in the TARCC. A key purpose for the search for distinct subgroups of individuals at risk for AD and MCI is to identify novel treatment and preventative opportunities.

Action Monitoring in boys with ADHD, their Nonaffected Siblings and Normal Controls: Evidence for an Endophenotype

PubMed Central

Albrecht, Bjoern; Brandeis, Daniel; Uebel, Henrik; Heinrich, Hartmut; Mueller, Ueli C.; Hasselhorn, Marcus; Steinhausen, Hans-Christoph; Rothenberger, Aribert; Banaschewski, Tobias

2008-01-01

Background Attention deficit/hyperactivity disorder is a very common and highly heritable child psychiatric disorder associated with dysfunctions in fronto-striatal networks that control attention and response organisation. Aim of this study was to investigate whether features of action monitoring related to dopaminergic functions represent endophenotypes which are brain functions on the pathway from genes and environmental risk factors to behaviour. Methods Action monitoring and error processing as indicated by behavioural and electrophysiological parameters during a flanker task were examined in boys with ADHD combined type according to DSM-IV (N=68), their nonaffected siblings (N=18) and healthy controls with no known family history of ADHD (N=22). Results Boys with ADHD displayed slower and more variable reaction-times. Error negativity (Ne) was smaller in boys with ADHD compared to healthy controls, while nonaffected siblings displayed intermediate amplitudes following a linear model predicted by genetic concordance. The three groups did not differ on error positivity (Pe). N2 amplitude enhancement due to conflict (incongruent flankers) was reduced in the ADHD group. Nonaffected siblings also displayed intermediate N2 enhancement. Conclusions Converging evidence from behavioural and ERP findings suggests that action monitoring and initial error processing, both related to dopaminergically modulated functions of anterior cingulate cortex, might be an endophenotype related to ADHD. PMID:18339358

[Posttraumatic stress disorder endophenotypes: several clinical dimensions for specific treatments].

PubMed

Auxéméry, Y

2012-01-01

Posttraumatic stress disorder is a syndrome with a very complex clinical that it is useful to describe according to a multidimensional approach. Following a critical review of the international literature, we have been able to highlight the genetic supports of posttraumatic stress disorder in the perspective of returning to the source of the clinical of this syndrome in order to steer its treatment better. We consider in succession the neuromodulation pathways involving dopamine, serotonine and noradrenaline to describe the hyperdomaminergic, hyposerotoninergic and hypernoradrenergic endophenotypes of posttraumatic stress disorder. Neurogenetic studies have affirmed two essential proposals. On the one hand, the pharmacological treatment of psychotraumatic disorders can be very closely adjusted to the different endophenotypes. On the other hand, the psychotherapeutic approach retains all its importance in the sense that it is the subjective implication that generated the trauma, subjectivity interacting with a genetic heritage and environmental factors integrating a social context. The changing definition of posttraumatic stress disorder over time comes from scientific exploration in part determined by a sociocultural context and, reciprocally, the psychic trauma is caused by the collapse of reassuring social values which were considered as immutable. The clinical is not developed according to fixed references: the evolution of neurogenetic techniques changes our perception of psychic traumas and the therapeutic possibilities.

Neuropsychological Endophenotype Approach to Genome-wide Linkage Analysis Identifies Susceptibility Loci for ADHD on 2q21.1 and 13q12.11

PubMed Central

Rommelse, Nanda N.J.; Arias-Vásquez, Alejandro; Altink, Marieke E.; Buschgens, Cathelijne J.M.; Fliers, Ellen; Asherson, Philip; Faraone, Stephen V.; Buitelaar, Jan K.; Sergeant, Joseph A.; Oosterlaan, Jaap; Franke, Barbara

2008-01-01

ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were performed in the Dutch subsample of the International Multi-Center ADHD Genetics (IMAGE) study comprising 238 DSM-IV combined-type ADHD probands and their 112 affected and 195 nonaffected siblings. Eight candidate neuropsychological ADHD endophenotypes with heritabilities > 0.2 were used as quantitative traits. In addition, an overall component score of neuropsychological functioning was used. A total of 5407 autosomal single-nucleotide polymorphisms (SNPs) were used to run multipoint regression-based linkage analyses. Two significant genome-wide linkage signals were found, one for Motor Timing on chromosome 2q21.1 (LOD score: 3.944) and one for Digit Span on 13q12.11 (LOD score: 3.959). Ten suggestive linkage signals were found (LOD scores ≥ 2) on chromosomes 2p, 2q, 3p, 4q, 8q, 12p, 12q, 14q, and 17q. The suggestive linkage signal for the component score that was found at 2q14.3 (LOD score: 2.878) overlapped with the region significantly linked to Motor Timing. Endophenotype approaches may increase power to detect susceptibility loci in ADHD and possibly in other complex disorders. PMID:18599010

[Emotional endophenotypes and bipolar disorder].

PubMed

Dubois, M; Azorin, J-M; Fakra, E; Adida, M; Belzeaux, R

2012-12-01

Emotion can be described as a multidimensional affective state, accompanied with physiological, cognitive and subjective manifestations. Most bipolar patients spontaneously claim they have a higher sensitivity than average, which may lead to extreme emotional reactions, even during intercrisis periods. Few studies have focused on this particular affective dimension. Moreover, the emotional reactivity is a way to raise the question of bipolar patients' vulnerability to stress during euthymic periods. The aim of this study is to examine the emotional reactivity of euthymic bipolar patients in comparison with a control group, using a test of emotional induction with short films, in order to determine whether this particular affective dimension can be a potential endophenotype. Our hypothesis is that euthymic bipolar patients have a higher emotional reactivity than controls. 20 euthymic bipolar patients and 15 healthy control subjects were recruited. The emotional reactivity was assessed using a method of emotional induction, based on viewing a set of positive, negative and neutral short films. The subjects have to appreciate the valence (pleasant, unpleasant or neutral) and the arousal (degree of emotion triggered by each film), while physiological parameters (heart rate and galvanic skin response) were measured. On average, euthymic bipolar patients report the same valence for each set of films and the same arousal to positive and negative movies as control subjects. Neutral pictures, however, were considered more moving by euthymic bipolar patients than by control subjects. Bipolar patient showed a higher heart rate than the control group, and no statistically difference was shown considering the galvanic skin response. Euthymic bipolar patients seem to present an emotional hypereactivity which occurs especially during neutral situations.These results partly corroborate other authors outcomes, using a new and more ecologic methodology through an emotional induction

[Temperamental endophenotypes].

PubMed

Azorin, J-M; Fakra, E; Adida, M; Belzeaux, R; Cermolacce, M; Mazzola, P; Corréard, N; Dubois, M; Pringuey, D; Sokolowsky, M; Kaladjian, A

2012-12-01

Temperament has been defined as the heritable biologically determined core of personality that remains stable throughout the life span and establishes the baseline level of reactivity, mood, and energy of a person. If the link between temperament and mental disorder goes back to the Greco-Roman medicine, Kraepelin was among the first authors to pay attention to the temperamental bases of bipolar disorder. He proposed four temperamental types that he described in the premorbid histories of the majority of manic-depressive patients, and found overrepresented in the biologic relatives of these patients. Building on this ancestry, Akiskal formulated the modern concept of affective temperament, and described five temperaments: depressive, hyperthymic, cyclothymic, irritable, and anxious. According to Akiskal's model, bipolar disorder lies along a continuum from temperament to full-blown episodes of affective illness. A series of recent studies have shown the role played by temperaments in the outbreak of bipolar episodes, their clinical presentation, as well as the illness course and comorbidities. Furthermore modern familial and genetic studies have confirmed the first observations of Kraepelin. It has been recently proposed that affective temperaments may carry distinct evolutionary advantages on the individual or a group level, so that affective disorders would be genetic reservoirs for adaptative temperaments and the price to be paid for the chance of exceptionality. Apart from these theoretical perspectives, paying attention to temperamental components may have important implications for the treatment of bipolar disorder. Finally recent studies confirmed as well, that the concept of affective temperament fulfilled the criteria required to be considered as an endophenotype. Copyright © 2012 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

ω-3 Long-Chain Polyunsaturated Fatty Acids and Fatty Acid Desaturase Activity Ratios as Eventual Endophenotypes for ADHD.

PubMed

Henríquez-Henríquez, Marcela; Solari, Sandra; Várgas, Gisela; Vásquez, Luis; Allende, Fidel; Castañón S, Carla; Tenorio, Marcela; Quiroga Gutiérrez, Teresa

2015-11-01

Epidemiological studies suggest that long-chain polyunsaturated fatty acids (LC-PUFAs) may be suitable as endophenotypes for ADHD. To be appropriated vulnerability traits, endophenotypes should be altered in unaffected relatives of index cases. Serum profiles of LC-PUFAs in unaffected relatives of ADHD patients remain understudied. The main objective of this study was to compare serum LC-PUFAs in ADHD patients, unaffected relatives of index cases, and general-population unaffected participants. LC-PUFA profiles of 72 participants (27 ADHD patients, 27 unaffected relatives, and 18 general-population participants) were obtained by gas chromatography-mass spectrometry (GC-MS). Groups were compared by parametrical statistics. Unaffected females from the general population presented lower Docosapentaenoic acid (DPA; p = .0012) and a-linolenic acid (ALA; p = .0091) levels compared with ADHD females and unaffected relatives. In addition, docosahexaenoic acid (DHA)/ALA and DHA/DPA ratios, addressing desaturase activity, were significantly lower in ADHD patients and unaffected relatives of ADHD patients in the female-subgroup (p = .022 and .04, respectively). DHA/ALA, DHA/DPA, serum DPA, and serum ALA may be suitable as endophenotypes for ADHD women. © The Author(s) 2012.

Eye movement dysfunction in first-degree relatives of patients with schizophrenia: a meta-analytic evaluation of candidate endophenotypes.

PubMed

Calkins, Monica E; Iacono, William G; Ones, Deniz S

2008-12-01

Several forms of eye movement dysfunction (EMD) are regarded as promising candidate endophenotypes of schizophrenia. Discrepancies in individual study results have led to inconsistent conclusions regarding particular aspects of EMD in relatives of schizophrenia patients. To quantitatively evaluate and compare the candidacy of smooth pursuit, saccade and fixation deficits in first-degree biological relatives, we conducted a set of meta-analytic investigations. Among 18 measures of EMD, memory-guided saccade accuracy and error rate, global smooth pursuit dysfunction, intrusive saccades during fixation, antisaccade error rate and smooth pursuit closed-loop gain emerged as best differentiating relatives from controls (standardized mean differences ranged from .46 to .66), with no significant differences among these measures. Anticipatory saccades, but no other smooth pursuit component measures were also increased in relatives. Visually-guided reflexive saccades were largely normal. Moderator analyses examining design characteristics revealed few variables affecting the magnitude of the meta-analytically observed effects. Moderate effect sizes of relatives v. controls in selective aspects of EMD supports their endophenotype potential. Future work should focus on facilitating endophenotype utility through attention to heterogeneity of EMD performance, relationships among forms of EMD, and application in molecular genetics studies.

Executive functions as endophenotypes in ADHD: evidence from the Cambridge Neuropsychological Test Battery (CANTAB).

PubMed

Gau, Susan Shur-Fen; Shang, Chi-Yung

2010-07-01

Little is known about executive functions among unaffected siblings of children with attention deficit/hyperactivity disorder (ADHD), and there is lack of such information from non-Western countries. We examined verbal and nonverbal executive functions in adolescents with ADHD, unaffected siblings and controls to test whether executive functions could be potential endophenotypes for ADHD. We assessed 279 adolescents (age range: 11-17 years) with a childhood diagnosis of DSM-IV ADHD, 136 biological siblings (108 unaffected, 79.4%), and 173 unaffected controls by using psychiatric interviews, the Wechsler Intelligence Scale for Children - 3rd edition (WISC-III), including digit spans, and the tasks involving executive functions of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-dimensional/Extra-dimensional Shifts (IED), Spatial Span (SSP), Spatial Working Memory (SWM), and Stockings of Cambridge (SOC). Compared with the controls, adolescents with ADHD and unaffected siblings had a significantly shorter backward digit span, more extra-dimensional shift errors in the IED, shorter spatial span length in the SSP, more total errors and poorer strategy use in the SWM, and fewer problems solved in the minimum number of moves and shorter initial thinking time in the SOC. The magnitudes of the differences in the SWM and SOC increased with increased task difficulties. In general, neither persistent ADHD nor comorbidity was associated with increased deficits in executive functions among adolescents with ADHD. The lack of much difference in executive dysfunctions between unaffected siblings and ADHD adolescents suggests that executive dysfunctions may be useful cognitive endophenotypes for ADHD genetic studies.

Polymorphisms of the oxytocin receptor gene and overeating: the intermediary role of endophenotypic risk factors

PubMed Central

Davis, C; Patte, K; Zai, C; Kennedy, J L

2017-01-01

Background/Objectives: Oxytocin (OXT) is an evolutionarily ancient neuropeptide with strong links to affiliative and prosocial behaviors, and the management of stress. Increases in OXT also tend to decrease food intake, especially of sweet carbohydrates. The social correlates of low OXT levels mesh with the social deficits and stress proneness identified in interpersonal models of overeating, as well as the increased appetite for highly palatable foods typically seen in chronic overeaters. The objectives of this study were to investigate links between polymorphisms of the oxytocin receptor (OXTR) gene and overeating, and to examine OXTR links with relevant endophenotypes of overeating related to reward and stress sensitivity, and to food preferences. Subject/Methods: The sample comprised 460 adults between the ages of 25 and 50 years recruited from the community, and representing a broad range of body weights. Overeating, reward and punishment sensitivity, and food preferences, were quantified as composite variables using well-validated questionnaires. In addition, seven single-nucleotide polymorphisms (rs237878, rs237885, rs2268493, rs2268494, rs2254298, rs53576, rs2268498) of the OXTR gene were genotyped. Results: Analyses identified a four-marker haplotype that was significantly related to food preferences. Individual genotype analyses also found that at least one of the markers was related to each of the phenotypic variables. In addition, an empirically derived structural equation model linking genetic and phenotype variables produced a good fit to the data. Conclusions: The results of this preliminary study have demonstrated that OXTR variation is associated with overeating, and with endophenotypic traits such as sweet and fatty food preferences, and reward and punishment sensitivity. In general, the genetic findings also favor the view that overeating may be associated with relatively low basal OXT levels. PMID:28530679

Polymorphisms of the oxytocin receptor gene and overeating: the intermediary role of endophenotypic risk factors.

PubMed

Davis, C; Patte, K; Zai, C; Kennedy, J L

2017-05-22

Oxytocin (OXT) is an evolutionarily ancient neuropeptide with strong links to affiliative and prosocial behaviors, and the management of stress. Increases in OXT also tend to decrease food intake, especially of sweet carbohydrates. The social correlates of low OXT levels mesh with the social deficits and stress proneness identified in interpersonal models of overeating, as well as the increased appetite for highly palatable foods typically seen in chronic overeaters. The objectives of this study were to investigate links between polymorphisms of the oxytocin receptor (OXTR) gene and overeating, and to examine OXTR links with relevant endophenotypes of overeating related to reward and stress sensitivity, and to food preferences. The sample comprised 460 adults between the ages of 25 and 50 years recruited from the community, and representing a broad range of body weights. Overeating, reward and punishment sensitivity, and food preferences, were quantified as composite variables using well-validated questionnaires. In addition, seven single-nucleotide polymorphisms (rs237878, rs237885, rs2268493, rs2268494, rs2254298, rs53576, rs2268498) of the OXTR gene were genotyped. Analyses identified a four-marker haplotype that was significantly related to food preferences. Individual genotype analyses also found that at least one of the markers was related to each of the phenotypic variables. In addition, an empirically derived structural equation model linking genetic and phenotype variables produced a good fit to the data. The results of this preliminary study have demonstrated that OXTR variation is associated with overeating, and with endophenotypic traits such as sweet and fatty food preferences, and reward and punishment sensitivity. In general, the genetic findings also favor the view that overeating may be associated with relatively low basal OXT levels.

Family and twin strategies as a head start in defining prodromes and endophenotypes for hypothetical early-interventions in schizophrenia.

PubMed

Gottesman, I I; Erlenmeyer-Kimling, L

2001-08-01

In an effort to share the experiences of 'genotype-hunters'-who have approached the difficult task of forecasting future schizophrenia in the young offspring or other relatives of index cases, in new samples guided by the prior probabilities of 15% in offspring or 50% in identical co-twins-with 'early-interventionists'-who focus on purported prodromal symptoms in children who would be treated pharmacologically to prevent the development of schizophrenia-we provide a focused review that emphasizes the hazards of false positives in both approaches. Despite the advantages prospective high-risk strategies have had from clinical and laboratory findings that implicate some prodromal signs and endophenotypes, e.g. attention, memory, and information processing evaluations, the yields are not sufficient for practical applications involving antipsychotic drugs for undiagnosed children. Even more caution than usual is required, given the suggestions that the developing neocortex is vulnerable to dopaminergic exposure.

Heart rate variability as candidate endophenotype of social anxiety: A two-generation family study.

PubMed

Harrewijn, A; Van der Molen, M J W; Verkuil, B; Sweijen, S W; Houwing-Duistermaat, J J; Westenberg, P M

2018-09-01

Social anxiety disorder (SAD) is the extreme fear and avoidance of one or more social situations. The goal of the current study was to investigate whether heart rate variability (HRV) during resting state and a social performance task (SPT) is a candidate endophenotype of SAD. In this two-generation family study, patients with SAD with their partner and children, and their siblings with partner and children took part in a SPT (total n = 121, 9 families, 3-30 persons per family, age range: 8-61 years, 17 patients with SAD). In this task, participants had to watch and evaluate the speech of a female peer, and had to give a similar speech. HRV was measured during two resting state phases, and during anticipation, speech and recovery phases of the SPT. We tested two criteria for endophenotypes: co-segregation with SAD within families and heritability. HRV did not co-segregate with SAD within families. Root mean square of successive differences during the first resting phase and recovery, and high frequency power during all phases of the task were heritable. It should be noted that few participants were diagnosed with SAD. Results during the speech should be interpreted with caution, because the duration was short and there was a lot of movement. HRV during resting state and the SPT is a possible endophenotype, but not of SAD. As other studies have shown that HRV is related to different internalizing disorders, HRV might reflect a transdiagnostic genetic vulnerability for internalizing disorders. Future research should investigate which factors influence the development of psychopathology in persons with decreased HRV. Copyright © 2018 Elsevier B.V. All rights reserved.

New insights into the endophenotypic status of cognition in bipolar disorder: genetic modelling study of twins and siblings.

PubMed

Georgiades, Anna; Rijsdijk, Fruhling; Kane, Fergus; Rebollo-Mesa, Irene; Kalidindi, Sridevi; Schulze, Katja K; Stahl, Daniel; Walshe, Muriel; Sahakian, Barbara J; McDonald, Colm; Hall, Mei-Hua; Murray, Robin M; Kravariti, Eugenia

2016-06-01

Twin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder. To quantify the shared genetic variability between bipolar disorder and cognitive measures. Structural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder. Using a parsimonious AE model, verbal episodic and spatial working memory showed statistically significant genetic correlations with bipolar disorder (rg = |0.23|-|0.27|), which lost statistical significance after covarying for affective symptoms. Using an ACE model, IQ and visual-spatial learning showed statistically significant genetic correlations with bipolar disorder (rg = |0.51|-|1.00|), which remained significant after covarying for affective symptoms. Verbal episodic and spatial working memory capture a modest fraction of the bipolar diathesis. IQ and visual-spatial learning may tap into genetic substrates of non-affective symptomatology in bipolar disorder. © The Royal College of Psychiatrists 2016.

EEG-LORETA endophenotypes of the common idiopathic generalized epilepsy syndromes.

PubMed

Clemens, B; Puskás, S; Besenyei, M; Emri, M; Opposits, G; Kis, S A; Hollódy, K; Fogarasi, A; Kondákor, I; Füle, K; Bense, K; Fekete, I

2012-05-01

activity in the right parahippocampal gyrus at 16-18Hz. Increased theta activity in the posterior parts of the cortex is the endophenotype for JME. Increased theta activity in the fronto-temporal limbic areas is the endophenotype for ABS. Statistically not significant findings might indicate diffuse biochemical abnormality of the cortex in JME and ABS. EEG-LORETA endophenotypes may correspond to the selective propensity to generate absence and myoclonic seizures in the ABS and JME syndromes. Copyright © 2011 Elsevier B.V. All rights reserved.

Variants in Adjacent Oxytocin/Vasopressin Gene Region and Associations with ASD Diagnosis and Other Autism Related Endophenotypes.

PubMed

Francis, Sunday M; Kistner-Griffin, Emily; Yan, Zhongyu; Guter, Stephen; Cook, Edwin H; Jacob, Suma

2016-01-01

There has been increasing interest in oxytocin (peptide: OT, gene: OXT) as a treatment pathway for neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). Neurodevelopmental disorders affect functional, social, and intellectual abilities. With advances in molecular biology, research has connected multiple gene regions to the clinical presentation of ASD. Studies have also shown that the neuropeptide hormones OT and arginine vasopressin (AVP) influence mammalian social and territorial behaviors and may have treatment potential for neurodevelopmental disorders. Published data examining molecular and phenotypic variation in ASD, such as cognitive abilities, are limited. Since most studies have focused on the receptors in the OT-AVP system, we investigated genetic variation within peptide genes for association with phenotypic ASD features that help identify subgroups within the spectrum. In this study, TDT analysis was carried out utilizing FBAT in 207 probands (156 trios) and a European Ancestry (EA) subsample (108 trios).The evolutionarily related and adjacent genes of OXT and AVP were studied for associations between the tagged single nucleotide polymorphisms and ASD diagnosis, social abilities, restrictive and repetitive behaviors, and IQ for cognitive abilities. Additionally, relationships with whole blood serotonin (WB5HT) were explored because of the developmental relationships connecting plasma levels of OT and WB5HT within ASD. RESULTS indicate significant association between OXT rs6084258 (p = 0.001) and ASD. Associations with several endophenotypes were also noted: OXT rs6133010 was associated with IQ (full scale IQ, p = 0.008; nonverbal IQ, p = 0.010, verbal IQ, p = 0.006); and OXT rs4813625 and OXT rs877172 were associated with WB5HT levels (EA, p = 0.027 and p = 0.033, respectively). Additionally, we measured plasma OT (pOT) levels in a subsample (N = 54). RESULTS show the three polymorphisms, OXT rs6084258, OXT rs11697250, and OXT rs877172

Prefrontal cortex, dopamine, and jealousy endophenotype.

PubMed

Marazziti, Donatella; Poletti, Michele; Dell'Osso, Liliana; Baroni, Stefano; Bonuccelli, Ubaldo

2013-02-01

Jealousy is a complex emotion characterized by the perception of a threat of loss of something that the person values,particularly in reference to a relationship with a loved one, which includes affective, cognitive, and behavioral components. Neural systems and cognitive processes underlying jealousy are relatively unclear, and only a few neuroimaging studies have investigated them. The current article discusses recent empirical findings on delusional jealousy, which is the most severe form of this feeling, in neurodegenerative diseases. After reviewing empirical findings on neurological and psychiatric disorders with delusional jealousy, and after considering its high prevalence in patients with Parkinson's disease under dopamine agonist treatment, we propose a core neural network and core cognitive processes at the basis of (delusional) jealousy, characterizing this symptom as possible endophenotype. In any case,empirical investigation of the neural bases of jealousy is just beginning, and further studies are strongly needed to elucidate the biological roots of this complex emotion.

Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder.

PubMed

Rommelse, Nanda N J; Franke, Barbara; Geurts, Hilde M; Hartman, Catharina A; Buitelaar, Jan K

2010-03-01

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting criteria for ADHD. This review will provide an overview on all available studies [family based, twin, candidate gene, linkage, and genome wide association (GWA) studies] shedding light on the role of shared genetic underpinnings of ADHD and ASD. It is concluded that family and twin studies do provide support for the hypothesis that ADHD and ASD originate from partly similar familial/genetic factors. Only a few candidate gene studies, linkage studies and GWA studies have specifically addressed this co-occurrence, pinpointing to some promising pleiotropic genes, loci and single nucleotide polymorphisms (SNPs), but the research field is in urgent need for better designed and powered studies to tackle this complex issue. We propose that future studies examining shared familial etiological factors for ADHD and ASD use a family-based design in which the same phenotypic (ADHD and ASD), candidate endophenotypic, and environmental measurements are obtained from all family members. Multivariate multi-level models are probably best suited for the statistical analysis.

Intra-Individual Response Variability Assessed by Ex-Gaussian Analysis may be a New Endophenotype for Attention-Deficit/Hyperactivity Disorder.

PubMed

Henríquez-Henríquez, Marcela Patricia; Billeke, Pablo; Henríquez, Hugo; Zamorano, Francisco Javier; Rothhammer, Francisco; Aboitiz, Francisco

2014-01-01

Intra-individual variability of response times (RTisv) is considered as potential endophenotype for attentional deficit/hyperactivity disorder (ADHD). Traditional methods for estimating RTisv lose information regarding response times (RTs) distribution along the task, with eventual effects on statistical power. Ex-Gaussian analysis captures the dynamic nature of RTisv, estimating normal and exponential components for RT distribution, with specific phenomenological correlates. Here, we applied ex-Gaussian analysis to explore whether intra-individual variability of RTs agrees with criteria proposed by Gottesman and Gould for endophenotypes. Specifically, we evaluated if normal and/or exponential components of RTs may (a) present the stair-like distribution expected for endophenotypes (ADHD > siblings > typically developing children (TD) without familiar history of ADHD) and (b) represent a phenotypic correlate for previously described genetic risk variants. This is a pilot study including 55 subjects (20 ADHD-discordant sibling-pairs and 15 TD children), all aged between 8 and 13 years. Participants resolved a visual Go/Nogo with 10% Nogo probability. Ex-Gaussian distributions were fitted to individual RT data and compared among the three samples. In order to test whether intra-individual variability may represent a correlate for previously described genetic risk variants, VNTRs at DRD4 and SLC6A3 were identified in all sibling-pairs following standard protocols. Groups were compared adjusting independent general linear models for the exponential and normal components from the ex-Gaussian analysis. Identified trends were confirmed by the non-parametric Jonckheere-Terpstra test. Stair-like distributions were observed for μ (p = 0.036) and σ (p = 0.009). An additional "DRD4-genotype" × "clinical status" interaction was present for τ (p = 0.014) reflecting a possible severity factor. Thus, normal and exponential RTisv components are

Are Endophenotypes Based on Measures of Executive Functions Useful for Molecular Genetic Studies of ADHD?

ERIC Educational Resources Information Center

Doyle, Alysa E.; Faraone, Stephen V.; Seidman, Larry J.; Willcutt, Erik G.; Nigg, Joel T.; Waldman, Irwin D.; Pennington, Bruce F.; Peart, Joanne; Biederman, Joseph

2005-01-01

Background: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or…

Electrophysiological Endophenotypes and the Error-Related Negativity (ERN) in Autism Spectrum Disorder: A Family Study

ERIC Educational Resources Information Center

Clawson, Ann; South, Mikle; Baldwin, Scott A.; Larson, Michael J.

2017-01-01

We examined the error-related negativity (ERN) as an endophenotype of ASD by comparing the ERN in families of ASD probands to control families. We hypothesized that ASD probands and families would display reduced-amplitude ERN relative to controls. Participants included 148 individuals within 39 families consisting of a mother, father, sibling,…

Temperament and Character as Endophenotype in Adults with Autism Spectrum Disorders or Attention Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Sizoo, Bram B.; van der Gaag, Rutger Jan; van den Brink, Wim

2015-01-01

Autism spectrum disorder and attention deficit/hyperactivity disorder overlap in several ways, raising questions about the nature of this comorbidity. Rommelse et al. published an innovative review of candidate endophenotypes for autism spectrum disorder and attention deficit/hyperactivity disorder in cognitive and brain domains. They found that…

Disentangling the adult attention-deficit hyperactivity disorder endophenotype: parametric measurement of attention.

PubMed

Finke, Kathrin; Schwarzkopf, Wolfgang; Müller, Ulrich; Frodl, Thomas; Müller, Hermann J; Schneider, Werner X; Engel, Rolf R; Riedel, Michael; Möller, Hans-Jürgen; Hennig-Fast, Kristina

2011-11-01

Attention deficit hyperactivity disorder (ADHD) persists frequently into adulthood. The decomposition of endophenotypes by means of experimental neuro-cognitive assessment has the potential to improve diagnostic assessment, evaluation of treatment response, and disentanglement of genetic and environmental influences. We assessed four parameters of attentional capacity and selectivity derived from simple psychophysical tasks (verbal report of briefly presented letter displays) and based on a "theory of visual attention." These parameters are mathematically independent, quantitative measures, and previous studies have shown that they are highly sensitive for subtle attention deficits. Potential reductions of attentional capacity, that is, of perceptual processing speed and working memory storage capacity, were assessed with a whole report paradigm. Furthermore, possible pathologies of attentional selectivity, that is, selection of task-relevant information and bias in the spatial distribution of attention, were measured with a partial report paradigm. A group of 30 unmedicated adult ADHD patients and a group of 30 demographically matched healthy controls were tested. ADHD patients showed significant reductions of working memory storage capacity of a moderate to large effect size. Perceptual processing speed, task-based, and spatial selection were unaffected. The results imply a working memory deficit as an important source of behavioral impairments. The theory of visual attention parameter working memory storage capacity might constitute a quantifiable and testable endophenotype of ADHD.

Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression

PubMed Central

Knorr, Ulla; Vinberg, Maj; Klose, Marianne; Feldt-Rasmussen, Ulla; Hilsted, Linda; Gade, Anders; Haastrup, Eva; Paulson, Olaf; Wetterslev, Jørn; Gluud, Christian; Gether, Ulrik; Kessing, Lars

2009-01-01

Background Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We hypothesize that potential endophenotypes for depression may be affected by selective serotonin re-uptake inhibitor antidepressants in healthy first-degree relatives of depressed patients. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test from baseline to the end of intervention. Methods The AGENDA trial is designed as a participant, investigator, observer, and data-analyst-blinded randomized trial. Participants are 80 healthy first-degree relatives of patients with depression. Participants are randomized to escitalopram 10 mg per day versus placebo for four weeks. Randomization is stratified by gender and age. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test at entry before intervention to after four weeks of intervention. With the inclusion of 80 participants, a 60% power is obtained to detect a clinically relevant difference in the primary outcome between the intervention and the placebo group. Secondary outcome measures are changes from baseline to four weeks in scores of: 1) cognition and 2) neuroticism. Tertiary outcomes measures are changes from baseline to four weeks in scores of: 1) depression and anxiety symptoms; 2) subjective evaluations of depressive symptoms, perceived stress, quality of life, aggression, sleep, and pain; and 3) salivary cortisol at eight different timepoints during an ordinary day. Assessments are undertaken by assessors blinded to the randomization group. Trial registration Local Ethics Committee: H-KF 307413 Danish Medicines Agency: 2612-3162. EudraCT: 2006-001750-28. Danish Data Agency: 2006-41-6737. Clinical

Trait anxiety affects decision-making differently in healthy men and women: towards gender-specific endophenotypes of anxiety.

PubMed

de Visser, L; van der Knaap, L J; van de Loo, A J A E; van der Weerd, C M M; Ohl, F; van den Bos, R

2010-05-01

Excessive levels of trait anxiety are a risk factor for psychiatric conditions, including anxiety disorders and substance abuse. High trait anxiety has been associated with altered cognitive functioning, in particular with an attentional bias towards aversive stimuli. Decision-making is a crucial aspect of cognitive functioning that relies on the correct processing and control of emotional stimuli. Interestingly, anxiety and decision-making share underlying neural substrates, involving cortico-limbic pathways, including the amygdala, striatum and medial and dorsolateral prefrontal cortices. In the present study, we investigated the relationship between trait anxiety, measured by the State-Trait Anxiety Inventory, and complex decision-making, measured by the Iowa Gambling Task, in healthy male and female volunteers. The main focus of this study was the inclusion of gender as a discriminative factor. Indeed, we found distinct gender-specific effects of trait anxiety: in men, both low and high anxiety groups showed impaired decision-making compared to medium anxiety individuals, whereas in women only high anxiety individuals performed poorly. Furthermore, anxiety affected decision-making in men early in the task, i.e. the exploration phase, as opposed to an effect on performance in women during the second part of the test, i.e. the exploitation phase. These findings were related to different profiles of trait anxiety in men and women, and were independent of performance in the Wisconsin Card Sorting Test and cortisol levels. Our data show gender-specific effects of trait anxiety on emotional decision-making. We suggest gender-specific endophenotypes of anxiety to exist, that differentially affect cognitive functioning. 2010 Elsevier Ltd. All rights reserved.

Intra-individual reaction time variability based on ex-Gaussian distribution as a potential endophenotype for attention-deficit/hyperactivity disorder.

PubMed

Lin, H-Y; Hwang-Gu, S-L; Gau, S S-F

2015-07-01

Intra-individual variability in reaction time (IIV-RT), defined by standard deviation of RT (RTSD), is considered as an endophenotype for attention-deficit/hyperactivity disorder (ADHD). Ex-Gaussian distributions of RT, rather than RTSD, could better characterize moment-to-moment fluctuations in neuropsychological performance. However, data of response variability based on ex-Gaussian parameters as an endophenotypic candidate for ADHD are lacking. We assessed 411 adolescents with clinically diagnosed ADHD based on the DSM-IV-TR criteria as probands, 138 unaffected siblings, and 138 healthy controls. The output parameters, mu, sigma, and tau, of an ex-Gaussian RT distribution were derived from the Conners' continuous performance test. Multi-level models controlling for sex, age, comorbidity, and use of methylphenidate were applied. Compared with unaffected siblings and controls, ADHD probands had elevated sigma value, omissions, commissions, and mean RT. Unaffected siblings formed an intermediate group in-between probands and controls in terms of tau value and RTSD. There was no between-group difference in mu value. Conforming to a context-dependent nature, unaffected siblings still had an intermediate tau value in-between probands and controls across different interstimulus intervals. Our findings suggest IIV-RT represented by tau may be a potential endophenotype for inquiry into genetic underpinnings of ADHD in the context of heterogeneity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Consumer and relationship factors associated with shared decision making in mental health consultations.

PubMed

Matthias, Marianne S; Fukui, Sadaaki; Kukla, Marina; Eliacin, Johanne; Bonfils, Kelsey A; Firmin, Ruth L; Oles, Sylwia K; Adams, Erin L; Collins, Linda A; Salyers, Michelle P

2014-12-01

This study explored the association between shared decision making and consumers' illness management skills and consumer-provider relationships. Medication management appointments for 79 consumers were audio recorded. Independent coders rated overall shared decision making, minimum level of shared decision making, and consumer-provider agreement for 63 clients whose visit included a treatment decision. Mental health diagnoses, medication adherence, patient activation, illness management, working alliance, and length of consumer-provider relationships were also assessed. Correlation analyses were used to determine relationships among measures. Overall shared decision making was not associated with any variables. Minimum levels of shared decision making were associated with higher scores on the bond subscale of the Working Alliance Inventory, indicating a higher degree of liking and trust, and with better medication adherence. Agreement was associated with shorter consumer-provider relationships. Consumer-provider relationships and shared decision making might have a more nuanced association than originally thought.

Motor sequencing deficit as an endophenotype of speech sound disorder: a genome-wide linkage analysis in a multigenerational family.

PubMed

Peter, Beate; Matsushita, Mark; Raskind, Wendy H

2012-10-01

The aim of this pilot study was to investigate a measure of motor sequencing deficit as a potential endophenotype of speech sound disorder (SSD) in a multigenerational family with evidence of familial SSD. In a multigenerational family with evidence of a familial motor-based SSD, affectation status and a measure of motor sequencing during oral motor testing were obtained. To further investigate the role of motor sequencing as an endophenotype for genetic studies, parametric and nonparametric linkage analyses were carried out using a genome-wide panel of 404 microsatellites. In seven of the 10 family members with available data, SSD affectation status and motor sequencing status coincided. Linkage analysis revealed four regions of interest, 6p21, 7q32, 7q36, and 8q24, primarily identified with the measure of motor sequencing ability. The 6p21 region overlaps with a locus implicated in rapid alternating naming in a recent genome-wide dyslexia linkage study. The 7q32 locus contains a locus implicated in dyslexia. The 7q36 locus borders on a gene known to affect the component traits of language impairment. The results are consistent with a motor-based endophenotype of SSD that would be informative for genetic studies. The linkage results in this first genome-wide study in a multigenerational family with SSD warrant follow-up in additional families and with fine mapping or next-generation approaches to gene identification.

Motor sequencing deficit as an endophenotype of speech sound disorder: A genome-wide linkage analysis in a multigenerational family

PubMed Central

Peter, Beate; Matsushita, Mark; Raskind, Wendy H.

2012-01-01

Objectives The purpose of this pilot study was to investigate a measure of motor sequencing deficit as a potential endophenotype of speech sound disorder (SSD) in a multigenerational family with evidence of familial SSD. Methods In a multigenerational family with evidence of a familial motor-based SSD, affectation status and a measure of motor sequencing during oral motor testing were obtained. To further investigate the role of motor sequencing as an endophenotype for genetic studies, parametric and nonparametric linkage analyses were conducted using a genome-wide panel of 404 microsatellites. Results In seven of the ten family members with available data, SSD affectation status and motor sequencing status coincided. Linkage analysis revealed four regions of interest, 6p21, 7q32, 7q36, and 8q24, primarily identified with the measure of motor sequencing ability. The 6p21 region overlaps with a locus implicated in rapid alternating naming in a recent genome-wide dyslexia linkage study. The 7q32 locus contains a locus implicated in dyslexia. The 7q36 locus borders on a gene known to affect component traits of language impairment. Conclusions Results are consistent with a motor-based endophenotype of SSD that would be informative for genetic studies. The linkage results in this first genome-wide study in a multigenerational family with SSD warrant follow-up in additional families and with fine mapping or next-generation approaches to gene identification. PMID:22517379

Eye Movement Dysfunction in First-Degree Relatives of Patients with Schizophrenia: A Meta-Analytic Evaluation of Candidate Endophenotypes

ERIC Educational Resources Information Center

Calkins, Monica E.; Iacono, William G.; Ones, Deniz S.

2008-01-01

Several forms of eye movement dysfunction (EMD) are regarded as promising candidate endophenotypes of schizophrenia. Discrepancies in individual study results have led to inconsistent conclusions regarding particular aspects of EMD in relatives of schizophrenia patients. To quantitatively evaluate and compare the candidacy of smooth pursuit,…

Behavioural endophenotypes in mice lacking the auxiliary GABAB receptor subunit KCTD16.

PubMed

Cathomas, Flurin; Sigrist, Hannes; Schmid, Luca; Seifritz, Erich; Gassmann, Martin; Bettler, Bernhard; Pryce, Christopher R

2017-01-15

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the pathophysiology of a number of neuropsychiatric disorders. The GABA B receptors are G-protein coupled receptors consisting of principle subunits and auxiliary potassium channel tetramerization domain (KCTD) subunits. The KCTD subunits 8, 12, 12b and 16 are cytosolic proteins that determine the kinetics of the GABA B receptor response. Previously, we demonstrated that Kctd12 null mutant mice (Kctd12 -/- ) exhibit increased auditory fear learning and that Kctd12 +/- mice show altered circadian activity, as well as increased intrinsic excitability in hippocampal pyramidal neurons. KCTD16 has been demonstrated to influence neuronal excitability by regulating GABA B receptor-mediated gating of postsynaptic ion channels. In the present study we investigated for behavioural endophenotypes in Kctd16 -/- and Kctd16 +/- mice. Compared with wild-type (WT) littermates, auditory and contextual fear conditioning were normal in both Kctd16 -/- and Kctd16 +/- mice. When fear memory was tested on the following day, Kctd16 -/- mice exhibited less extinction of auditory fear memory relative to WT and Kctd16 +/- mice, as well as more contextual fear memory relative to WT and, in particular, Kctd16 +/- mice. Relative to WT, both Kctd16 +/- and Kctd16 -/- mice exhibited normal circadian activity. This study adds to the evidence that auxillary KCTD subunits of GABA B receptors contribute to the regulation of behaviours that could constitute endophenotypes for hyper-reactivity to aversive stimuli in neuropsychiatric disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Is attention to detail a similarly strong candidate endophenotype for anorexia nervosa and bulimia nervosa?

PubMed

Roberts, Marion E; Tchanturia, Kate; Treasure, Janet L

2013-08-01

To investigate whether attention to detail is a similarly strong candidate endophenotype of anorexia (AN) and bulimia nervosa (BN), and to explore the incidence and clinical correlates of attention to detail. A total of 266 women (including AN, BN, recovered AN, unaffected sisters of AN/BN & control women) undertook a thorough clinical assessment and were administered two neuropsychological measures of attention to detail (Group Embedded Figure Test; Rey-Osterrieth Complex Figure). Superior attention to detail was found across all AN groups including recovered AN and unaffected AN sisters. Those with BN and their unaffected sisters showed a profile more consistent with poor global integration. The combined effect of superior attention to detail and poor global integration ("weak coherence") was present in 42.3% of active cases and corresponded with a more severe illness, elevated obsessive-compulsive symptoms, and a higher likelihood of comorbid clinical anxiety and self-harm. Attention to detail is a stronger candidate endophenotype of AN compared to BN, where poor global integration may be more relevant. The unique contribution of both aspects of weak coherence (superior attention to detail/poor global integration) requires further exploration and understanding in both eating disorders. Integrating cognitive remediation of these traits into treatment for the subset of patients it is relevant for may improve outcome.

High interleukin-6 and impulsivity: determining the role of endophenotypes in attempted suicide

PubMed Central

Isung, J; Aeinehband, S; Mobarrez, F; Nordström, P; Runeson, B; Åsberg, M; Piehl, F; Jokinen, J

2014-01-01

The dysregulation of inflammation has been associated with depression and, more recently, with suicidal behaviors. The reports regarding the relationship between interleukin-6 (IL-6) and suicide attempts are inconsistent. Personality traits such as impulsivity and aggression are considered endophenotypes and important factors that underlie suicidal behaviors. The aim of the current study was to assess whether plasma and cerebrospinal fluid (CSF) levels of IL-6 are associated with personality traits among suicide attempters. We assessed the relationships among personality traits, IL-6 and violent suicide attempts. The plasma and CSF levels of IL-6 were measured in suicide attempters (plasma=58, CSF=39) using antibody-based immunoassay systems. Personality domains were assessed using the Karolinska Scale of Personality (KSP). IL-6 levels in plasma and CSF were used to predict personality domains via regression models. Plasma IL-6 was significantly and positively correlated with extraversion as well as the KSP subscales impulsivity and monotony avoidance. CSF IL-6 was positively correlated with monotony avoidance. Violent suicide attempts tended to be associated with high plasma IL-6 levels. Plasma and CSF levels of IL-6 were not significantly associated with each other. These results indicate that impulsivity and the choice of a violent suicide attempt method might be related to higher levels of IL-6 in individuals who attempt suicide. The neuroinflammation hypothesis of suicidal behavior on the basis of elevated IL-6 levels might be partly explained by the positive association between IL-6 and impulsivity, which is a key element of the suicidal phenotype. PMID:25335166

High interleukin-6 and impulsivity: determining the role of endophenotypes in attempted suicide.

PubMed

Isung, J; Aeinehband, S; Mobarrez, F; Nordström, P; Runeson, B; Asberg, M; Piehl, F; Jokinen, J

2014-10-21

The dysregulation of inflammation has been associated with depression and, more recently, with suicidal behaviors. The reports regarding the relationship between interleukin-6 (IL-6) and suicide attempts are inconsistent. Personality traits such as impulsivity and aggression are considered endophenotypes and important factors that underlie suicidal behaviors. The aim of the current study was to assess whether plasma and cerebrospinal fluid (CSF) levels of IL-6 are associated with personality traits among suicide attempters. We assessed the relationships among personality traits, IL-6 and violent suicide attempts. The plasma and CSF levels of IL-6 were measured in suicide attempters (plasma=58, CSF=39) using antibody-based immunoassay systems. Personality domains were assessed using the Karolinska Scale of Personality (KSP). IL-6 levels in plasma and CSF were used to predict personality domains via regression models. Plasma IL-6 was significantly and positively correlated with extraversion as well as the KSP subscales impulsivity and monotony avoidance. CSF IL-6 was positively correlated with monotony avoidance. Violent suicide attempts tended to be associated with high plasma IL-6 levels. Plasma and CSF levels of IL-6 were not significantly associated with each other. These results indicate that impulsivity and the choice of a violent suicide attempt method might be related to higher levels of IL-6 in individuals who attempt suicide. The neuroinflammation hypothesis of suicidal behavior on the basis of elevated IL-6 levels might be partly explained by the positive association between IL-6 and impulsivity, which is a key element of the suicidal phenotype.

Factors associated with bed-sharing for African American and White mothers in Wisconsin.

PubMed

Salm Ward, Trina C; Ngui, Emmanuel M

2015-04-01

Mother-infant bed-sharing has been associated with a higher risk of sleep-related infant deaths, which affects African Americans at a disproportionately higher rate. Although "separate but proximate sleep surfaces" for infants has been recommended since 2005, bed-sharing remains a common practice, especially among African Americans. This study examined factors associated with bed-sharing among African American and White mothers. Separate logistic regression models were constructed for African American and White respondents to the 2007-2010 Wisconsin Pregnancy Risk Assessment and Monitoring System. The sample consisted of 806 African Americans and 1,680 Whites (N = 2,486). A significantly larger proportion of African Americans (70.6 %) reported bed-sharing than Whites (53.4 %). For both races, partner-related stress was significantly associated with bed-sharing; no significant differences were found between the two racial groups. For African Americans, partner stress (OR 1.8: 1.2-2.6) and maternal education of 13-15 years (OR 2.0: 1.2-3.4) or ≥16 years (OR 2.7: 1.1-6.3) was associated with increased odds of bed-sharing. For Whites, partner stress (OR 1.3: 1-1.8), breastfeeding (OR 2.5: 1.9-3.1), income of $35,000-$49,999 (OR 1.6: 1.2-2.3), being unmarried (OR 1.5: 1.1-2.2), needing money for food (OR 1.6: 1.1-2.3), and non-supine sleep (OR 1.8: 1.2-2.6) were associated with increased odds of bed-sharing. Differences were found in bed-sharing factors between racial groups which suggests a need for culturally-relevant, tailored safe infant sleep interventions. Providers should ask families about their infant's sleeping environment and address safety issues within that environment. More research is needed on the context and reasons for bed-sharing.

Navigating the complex path between the oxytocin receptor gene (OXTR) and cooperation: an endophenotype approach.

PubMed

Haas, Brian W; Anderson, Ian W; Smith, Jessica M

2013-11-28

Although cooperation represents a core facet of human social behavior there exists considerable variability across people in terms of the tendency to cooperate. One factor that may contribute to individual differences in cooperation is a key gene within the oxytocin (OT) system, the OT reception gene (OXTR). In this article, we aim to bridge the gap between the OXTR gene and cooperation by using an endophenotype approach. We present evidence that the association between the OXTR gene and cooperation may in part be due to how the OXTR gene affects brain systems involved in emotion recognition, empathy/theory of mind, social communication and social reward seeking. There is evidence that the OXTR gene is associated with the functional anatomy of the amygdala, visual cortex (VC), anterior cingulate and superior temporal gyrus (STG). However, it is currently unknown how the OXTR gene may be linked to the functional anatomy of other relevant brain regions that include the fusiform gyrus (FG), superior temporal sulcus (STS), ventromedial prefrontal cortex (VMPFC), temporoparietal junction (TPJ) and nucleus accumbens (NAcc). We conclude by highlighting potential future research directions that may elucidate the path between OXTR and complex behaviors such as cooperation.

Navigating the complex path between the oxytocin receptor gene (OXTR) and cooperation: an endophenotype approach

PubMed Central

Haas, Brian W.; Anderson, Ian W.; Smith, Jessica M.

2013-01-01

Although cooperation represents a core facet of human social behavior there exists considerable variability across people in terms of the tendency to cooperate. One factor that may contribute to individual differences in cooperation is a key gene within the oxytocin (OT) system, the OT reception gene (OXTR). In this article, we aim to bridge the gap between the OXTR gene and cooperation by using an endophenotype approach. We present evidence that the association between the OXTR gene and cooperation may in part be due to how the OXTR gene affects brain systems involved in emotion recognition, empathy/theory of mind, social communication and social reward seeking. There is evidence that the OXTR gene is associated with the functional anatomy of the amygdala, visual cortex (VC), anterior cingulate and superior temporal gyrus (STG). However, it is currently unknown how the OXTR gene may be linked to the functional anatomy of other relevant brain regions that include the fusiform gyrus (FG), superior temporal sulcus (STS), ventromedial prefrontal cortex (VMPFC), temporoparietal junction (TPJ) and nucleus accumbens (NAcc). We conclude by highlighting potential future research directions that may elucidate the path between OXTR and complex behaviors such as cooperation. PMID:24348360

Schizotypy and smooth pursuit eye movements as potential endophenotypes of obsessive-compulsive disorder.

PubMed

Bey, Katharina; Meyhöfer, Inga; Lennertz, Leonhard; Grützmann, Rosa; Heinzel, Stephan; Kaufmann, Christian; Klawohn, Julia; Riesel, Anja; Ettinger, Ulrich; Kathmann, Norbert; Wagner, Michael

2018-05-02

Patients with obsessive-compulsive disorder (OCD) show dysfunctions of the fronto-striatal circuitry, which imply corresponding oculomotor deficits including smooth pursuit eye movements (SPEM). However, evidence for a deficit in SPEM is inconclusive, with some studies reporting reduced velocity gain while others did not find any SPEM dysfunctions in OCD patients. Interestingly, psychosis-like traits have repeatedly been linked to both OCD and impaired SPEM. Here, we examined a large sample of n = 168 patients with OCD, n = 93 unaffected first-degree relatives and n = 171 healthy control subjects to investigate whether elevated levels of schizotypy and SPEM deficits represent potential endophenotypes of OCD. We applied a SPEM task with high demands on predictive pursuit that is more sensitive to assess executive dysfunctions than a standard task with continuous visual feedback, as episodes of target blanking put increased demands on basal ganglia and prefrontal involvement. Additionally, we examined the relation between schizotypy and SPEM performance in OCD patients and their relatives. Results indicate that OCD patients and unaffected relatives do not show deficient performance in either standard or predictive SPEM. Yet, both patients and relatives exhibited elevated levels of schizotypy, and schizotypy was significantly correlated with velocity gain during standard trials in unmedicated and depression-free OCD patients. These findings highlight the role of schizotypy as a candidate endophenotype of OCD and add to the growing evidence for predisposing personality traits in OCD. Furthermore, intact gain may represent a key characteristic that distinguishes the OCD and schizophrenia patient populations.

EEG correlates of visual short-term memory as neuro-cognitive endophenotypes of ADHD.

PubMed

Wiegand, Iris; Hennig-Fast, Kristina; Kilian, Beate; Müller, Hermann J; Töllner, Thomas; Möller, Hans-Jürgen; Engel, Rolf R; Finke, Kathrin

2016-05-01

Attention deficit hyperactivity disorder (ADHD) frequently persists into adulthood. A reduction in visual short-term memory (vSTM) storage capacity was recently suggested as a potential neuro-cognitive endophenotype, i.e., a testable marker of an individual's liability for developing ADHD. This study aimed at identifying markers of the brain abnormalities underlying vSTM reductions in adult ADHD. We combined behavioral parameter-based assessment with electrophysiology in groups of adult ADHD patients and healthy age-matched controls. Amplitudes of ERP markers of vSTM storage capacity, the contralateral delay activity (CDA) and the P3b, were analyzed according to (i) differences between individuals with higher vs. lower storage capacity K and (ii) differences between ADHD patients and control participants. We replicated the finding of reduced storage capacity in adult ADHD. Across groups, individuals with higher relative to lower storage capacity showed a larger CDA and P3b. We further found differences between the patient and control groups in the ERPs: The CDA amplitude was attenuated in an early time window for ADHD patients compared to control participants, and was negatively correlated with ADHD patients' symptom severity ratings. Furthermore, the P3b was larger in ADHD patients relative to control participants. These electrophysiological findings indicate altered brain mechanisms underlying visual storage capacity in ADHD, which are characterized by deficient encoding and maintenance, and increased recruitment of control processes. Accordingly, (quantifiable) ERP markers of vSTM in adult ADHD bear candidacy as neuro-cognitive endophenotypes of the disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cognitive endophenotypes of attention deficit/hyperactivity disorder and intra-subject variability in patients with autism spectrum disorder.

PubMed

Biscaldi, M; Bednorz, N; Weissbrodt, K; Saville, C W N; Feige, B; Bender, S; Klein, C

2016-07-01

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have previously been studied mainly in isolation from each other. However the two conditions may be aetiologically related and thus show overlap in aetiologically relevant functions. In order to address this question of potential aetiological overlap between ADHD and ASD, the present study set out to investigate putative endophenotypes of ADHD in N=33 typically developing (TD) children and N=28 patients with ASD that were (ASD+) or were not (ASD-) co-morbid for ADHD. With regard to both the cognitive endophenotype candidates (working memory, inhibition, temporal processing) and intra-subject variability (ISV) the pattern of abnormalities was inconsistent. Furthermore, the overall profile of ASD-TD differences was extremely similar to the pattern of differences between the ASD+ and ASD- sub-groups, suggesting that any abnormalities found were due to the comorbid ASD subgroup. This held in particular for ISV, which did not show in patients with ASD the task-general increase that is common in ADHD samples. Altogether, the present results do not support the hypothesis of aetiological overlap between ASD and ADHD. Copyright © 2016 Elsevier B.V. All rights reserved.

Visual processing as a potential endophenotype in youths with attention-deficit/hyperactivity disorder: A sibling study design using the counting Stroop functional MRI.

PubMed

Fan, Li-Ying; Shang, Chi-Yung; Tseng, Wen-Yih Isaac; Gau, Susan Shur-Fen; Chou, Tai-Li

2018-05-10

Deficits in inhibitory control and visual processing are common in youths with attention-deficit/hyperactivity disorder (ADHD), but little is known about endophenotypes for unaffected siblings of youths with ADHD. This study aimed to investigate the potential endophenotypes of brain activation and performance in inhibitory control and visual processing among ADHD probands, their unaffected siblings, and neurotypical youths. We assessed 27 ADHD probands, 27 unaffected siblings, and 27 age-, gender-, and IQ-matched neurotypical youths using the counting Stroop functional magnetic resonance imaging and two tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): rapid visual information processing (RVP) for inhibitory control and spatial span (SSP) for visual processing. ADHD probands showed greater activation than their unaffected siblings and neurotypical youths in the right inferior frontal gyrus (IFG) and anterior cingulate cortex. Increased activation in the right IFG was positively correlated with the mean latency of the RVP in ADHD probands. Moreover, ADHD probands and their unaffected siblings showed less activation in the left superior parietal lobule (SPL) than neurotypical youths. Increased activation in the left SPL was positively correlated with the spatial length of the SSP in neurotypical youths. Our findings suggest that less activation in the left SPL might be considered as a candidate imaging endophenotype for visual processing in ADHD. © 2018 Wiley Periodicals, Inc.

Establishing the resting state default mode network derived from functional magnetic resonance imaging tasks as an endophenotype: A twins study.

PubMed

Korgaonkar, Mayuresh S; Ram, Kaushik; Williams, Leanne M; Gatt, Justine M; Grieve, Stuart M

2014-08-01

The resting state default mode network (DMN) has been shown to characterize a number of neurological and psychiatric disorders. Evidence suggests an underlying genetic basis for this network and hence could serve as potential endophenotype for these disorders. Heritability is a defining criterion for endophenotypes. The DMN is measured either using a resting-state functional magnetic resonance imaging (fMRI) scan or by extracting resting state activity from task-based fMRI. The current study is the first to evaluate heritability of this task-derived resting activity. 250 healthy adult twins (79 monozygotic and 46 dizygotic same sex twin pairs) completed five cognitive and emotion processing fMRI tasks. Resting state DMN functional connectivity was derived from these five fMRI tasks. We validated this approach by comparing connectivity estimates from task-derived resting activity for all five fMRI tasks, with those obtained using a dedicated task-free resting state scan in an independent cohort of 27 healthy individuals. Structural equation modeling using the classic twin design was used to estimate the genetic and environmental contributions to variance for the resting-state DMN functional connectivity. About 9-41% of the variance in functional connectivity between the DMN nodes was attributed to genetic contribution with the greatest heritability found for functional connectivity between the posterior cingulate and right inferior parietal nodes (P<0.001). Our data provide new evidence that functional connectivity measures from the intrinsic DMN derived from task-based fMRI datasets are under genetic control and have the potential to serve as endophenotypes for genetically predisposed psychiatric and neurological disorders. Copyright © 2014 Wiley Periodicals, Inc.

Replication of genetic associations as pseudoreplication due to shared genealogy.

PubMed

Rosenberg, Noah A; Vanliere, Jenna M

2009-09-01

The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between marker loci and disease-susceptibility loci can be considered as "pseudoreplicates" rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence.

Replication of genetic associations as pseudoreplication due to shared genealogy

PubMed Central

Rosenberg, Noah A.; VanLiere, Jenna M.

2009-01-01

The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between marker loci and disease-susceptibility loci can be considered “pseudoreplicates” rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence. PMID:19191270

Social and emotional processing as a behavioural endophenotype in eating disorders: a pilot investigation in twins.

PubMed

Kanakam, Natalie; Krug, Isabel; Raoult, Charlotte; Collier, David; Treasure, Janet

2013-07-01

Emotional processing difficulties are potential risk markers for eating disorders that are also present after recovery. The aim of this study was to examine these traits in twins with eating disorders. The Reading the Mind in the Eyes test, Emotional Stroop task and the Difficulties in Emotion Regulation Scale were administered to 112 twins with and without eating disorders (DSM IV-TR eating disorder criteria). Generalised estimating equations compared twins with eating disorders against unaffected co-twins and control twins, and within-pair correlations were calculated for clinical monozygotic (n = 50) and dizygotic twins (n = 20). Emotion recognition difficulties, attentional biases to social threat and difficulties in emotion regulation were greater in twins with eating disorders, and some were present in their unaffected twin siblings. Evidence for a possible genetic basis was highest for emotion recognition and attentional biases to social stimuli. Emotion recognition difficulties and sensitivity to social threat appear to be endophenotypes associated with eating disorders. However, the limited statistical power means that these findings are tentative and require further replication. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism.

PubMed

Chen, Rui; Davis, Lea K; Guter, Stephen; Wei, Qiang; Jacob, Suma; Potter, Melissa H; Cox, Nancy J; Cook, Edwin H; Sutcliffe, James S; Li, Bingshan

2017-01-01

Autism spectrum disorder (ASD) is one of the most highly heritable neuropsychiatric disorders, but underlying molecular mechanisms are still unresolved due to extreme locus heterogeneity. Leveraging meaningful endophenotypes or biomarkers may be an effective strategy to reduce heterogeneity to identify novel ASD genes. Numerous lines of evidence suggest a link between hyperserotonemia, i.e., elevated serotonin (5-hydroxytryptamine or 5-HT) in whole blood, and ASD. However, the genetic determinants of blood 5-HT level and their relationship to ASD are largely unknown. In this study, pursuing the hypothesis that de novo variants (DNVs) and rare risk alleles acting in a recessive mode may play an important role in predisposition of hyperserotonemia in people with ASD, we carried out whole exome sequencing (WES) in 116 ASD parent-proband trios with most (107) probands having 5-HT measurements. Combined with published ASD DNVs, we identified USP15 as having recurrent de novo loss of function mutations and discovered evidence supporting two other known genes with recurrent DNVs ( FOXP1 and KDM5B ). Genes harboring functional DNVs significantly overlap with functional/disease gene sets known to be involved in ASD etiology, including FMRP targets and synaptic formation and transcriptional regulation genes. We grouped the probands into High-5HT and Normal-5HT groups based on normalized serotonin levels, and used network-based gene set enrichment analysis (NGSEA) to identify novel hyperserotonemia-related ASD genes based on LoF and missense DNVs. We found enrichment in the High-5HT group for a gene network module (DAWN-1) previously implicated in ASD, and this points to the TGF-β pathway and cell junction processes. Through analysis of rare recessively acting variants (RAVs), we also found that rare compound heterozygotes (CHs) in the High-5HT group were enriched for loci in an ASD-associated gene set. Finally, we carried out rare variant group-wise transmission

Sharing information about cancer with one's family is associated with improved quality of life.

PubMed

Lai, Carlo; Borrelli, Beatrice; Ciurluini, Paola; Aceto, Paola

2017-10-01

The aim of this study was to investigate the association between cancer patients' ability to share information about their illness with their social network and attachment style dimensions, alexithymia, and quality of life. We hypothesised that ability to share information about one's cancer with family, friends, and medical teams would be positively associated with quality of life and secure attachment and negatively associated with alexithymia. Forty-five cancer patients were recruited from the Psycho-oncology Unit of the San Camillo-Forlanini Hospital in Rome. We collected anamnestic data and self-report data on social sharing ability, quality of life, alexithymia, and attachment. Sharing with family (B = 4.66; SE = 1.82; β = .52; SE = 0.20; t(41) = 2.6; P = .0143) was the only predictor of global health status, and attachment security was the only predictor of mean social sharing (B = 0.25; SE = 0.06; β = .63; SE = 0.14; t(41) = 4.4; P < .0001). Encouraging patients to share information about their experience of cancer may help to improve their quality of life. Attachment security seems to promote social sharing. Psychological assessments of cancer patients should cover both ability to share information about one's cancer with family and attachment security. Copyright © 2016 John Wiley & Sons, Ltd.

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia.

PubMed

van der Velde, Jorien; Gromann, Paula M; Swart, Marte; de Haan, Lieuwe; Wiersma, Durk; Bruggeman, Richard; Krabbendam, Lydia; Aleman, André

2015-05-01

Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies. We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings. The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites. These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia.

Factors associated with bed and room sharing in Chinese school-aged children.

PubMed

Li, S; Jin, X; Yan, C; Wu, S; Jiang, F; Shen, X

2009-03-01

Co-sleeping (bed or room sharing) has potential implications for children's development. Previous studies showed that co-sleeping was more prevalent in non-Western countries than in Western countries, which demonstrated that co-sleeping was marked with ethnic and socio-cultural background characteristics. The purpose of this study was to survey the prevalence of bed and room sharing and to examine related factors among school-aged children in an Asian country - China. A cross-sectional questionnaire survey was conducted in 10 districts of Shanghai, China from November to December 2005. A total of 4108 elementary school children, 49.2% boys and 50.8% girls with a mean age of 8.79 years, participated. Parent-administered questionnaires were used to collect information about children's sleeping arrangements and socio-demographic characteristics. The prevalence of routine bed sharing, room sharing and sleeping alone in Chinese school-aged children was 21.0%, 19.1% and 47.7%, respectively. Bed and room sharing didn't show significant gender difference but gradually decreased with increasing age. Multivariate logistic regression identified those factors associated with bed and room sharing: younger age, large family, children without their own bedroom and parents' approval of a co-sleeping arrangement. Co-sleeping arrangement was a common practice in Chinese school-aged children. Associated factors were characterized by intrinsic socio-cultural values and socio-economic status in China.

Parent-adolescent dyads: association of parental autonomy support and parent-adolescent shared diabetes care responsibility.

PubMed

Hanna, K M; Dashiff, C J; Stump, T E; Weaver, M T

2013-09-01

Parent-adolescent shared responsibility for diabetes care is advocated by experts to achieve beneficial diabetes and psychosocial outcomes for adolescents with type 1 diabetes. Parental autonomy support may be a way to facilitate this sharing. In this dyadic study, we examined parental diabetes-specific autonomy support experienced by adolescents with type 1 diabetes and their parents (n = 89 dyads), and its association with their experience of shared diabetes care responsibility. Path analysis was used to test an Actor-Partner Interdependence Model for parental autonomy support effects on shared responsibility. This was a secondary analysis of data from 89 parent-early/mid-adolescent dyads. Actor effects were identified. Parents' and adolescents' perceptions of parental autonomy support were associated with their respective reports of shared diabetes care responsibility. One partner effect was identified. Adolescents' reports of parental autonomy support were associated with parents' reports of shared responsibility. Parents and adolescents held similar views of autonomy support but discrepant views of shared responsibility. Older adolescents perceived less parental autonomy support. Increasing parental autonomy support may facilitate parent-adolescent sharing of diabetes care responsibility. Adolescent and parent perceptions influence each other and need to be considered when working with them to strengthen parental autonomy support. © 2012 John Wiley & Sons Ltd.

Association between salivary serotonin and the social sharing of happiness

PubMed Central

Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori

2017-01-01

Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others), we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend (absent, positive, or negative). Results indicated that the presence of a happy friend significantly enhanced participants’ happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking), which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers’ attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels. PMID:28683075

Association between salivary serotonin and the social sharing of happiness.

PubMed

Matsunaga, Masahiro; Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori

2017-01-01

Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others), we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend (absent, positive, or negative). Results indicated that the presence of a happy friend significantly enhanced participants' happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking), which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers' attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels.

maLPA1-null mice as an endophenotype of anxious depression

PubMed Central

Moreno-Fernández, R D; Pérez-Martín, M; Castilla-Ortega, E; Rosell del Valle, C; García-Fernández, M I; Chun, J; Estivill-Torrús, G; Rodríguez de Fonseca, F; Santín, L J; Pedraza, C

2017-01-01

Anxious depression is a prevalent disease with devastating consequences and a poor prognosis. Nevertheless, the neurobiological mechanisms underlying this mood disorder remain poorly characterized. The LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1–6) through which lysophosphatidic acid acts as an intracellular signalling molecule. The loss of this receptor induces anxiety and several behavioural and neurobiological changes that have been strongly associated with depression. In this study, we sought to investigate the involvement of the LPA1 receptor in mood. We first examined hedonic and despair-like behaviours in wild-type and maLPA1 receptor null mice. Owing to the behavioural response exhibited by the maLPA1-null mice, the panic-like reaction was assessed. In addition, c-Fos expression was evaluated as a measure of the functional activity, followed by interregional correlation matrices to establish the brain map of functional activation. maLPA1-null mice exhibited anhedonia, agitation and increased stress reactivity, behaviours that are strongly associated with the psychopathological endophenotype of depression with anxiety features. Furthermore, the functional brain maps differed between the genotypes. The maLPA1-null mice showed increased limbic-system activation, similar to that observed in depressive patients. Antidepressant treatment induced behavioural improvements and functional brain normalisation. Finally, based on validity criteria, maLPA1-null mice are proposed as an animal model of anxious depression. Here, for we believe the first time, we have identified a possible relationship between the LPA1 receptor and anxious depression, shedding light on the unknown neurobiological basis of this subtype of depression and providing an opportunity to explore new therapeutic targets for the treatment of mood disorders, especially for the anxious subtype of depression. PMID:28375206

maLPA1-null mice as an endophenotype of anxious depression.

PubMed

Moreno-Fernández, R D; Pérez-Martín, M; Castilla-Ortega, E; Rosell Del Valle, C; García-Fernández, M I; Chun, J; Estivill-Torrús, G; Rodríguez de Fonseca, F; Santín, L J; Pedraza, C

2017-04-04

Anxious depression is a prevalent disease with devastating consequences and a poor prognosis. Nevertheless, the neurobiological mechanisms underlying this mood disorder remain poorly characterized. The LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts as an intracellular signalling molecule. The loss of this receptor induces anxiety and several behavioural and neurobiological changes that have been strongly associated with depression. In this study, we sought to investigate the involvement of the LPA1 receptor in mood. We first examined hedonic and despair-like behaviours in wild-type and maLPA1 receptor null mice. Owing to the behavioural response exhibited by the maLPA1-null mice, the panic-like reaction was assessed. In addition, c-Fos expression was evaluated as a measure of the functional activity, followed by interregional correlation matrices to establish the brain map of functional activation. maLPA1-null mice exhibited anhedonia, agitation and increased stress reactivity, behaviours that are strongly associated with the psychopathological endophenotype of depression with anxiety features. Furthermore, the functional brain maps differed between the genotypes. The maLPA1-null mice showed increased limbic-system activation, similar to that observed in depressive patients. Antidepressant treatment induced behavioural improvements and functional brain normalisation. Finally, based on validity criteria, maLPA1-null mice are proposed as an animal model of anxious depression. Here, for we believe the first time, we have identified a possible relationship between the LPA1 receptor and anxious depression, shedding light on the unknown neurobiological basis of this subtype of depression and providing an opportunity to explore new therapeutic targets for the treatment of mood disorders, especially for the anxious subtype of depression.

Anonymizing patient genomic data for public sharing association studies.

PubMed

Fernandez-Lozano, Carlos; Lopez-Campos, Guillermo; Seoane, Jose A; Lopez-Alonso, Victoria; Dorado, Julian; Martín-Sanchez, Fernando; Pazos, Alejandro

2013-01-01

The development of personalized medicine is tightly linked with the correct exploitation of molecular data, especially those associated with the genome sequence along with these use of genomic data there is an increasing demand to share these data for research purposes. Transition of clinical data to research is based in the anonymization of these data so the patient cannot be identified, the use of genomic data poses a great challenge because its nature of identifying data. In this work we have analyzed current methods for genome anonymization and propose a one way encryption method that may enable the process of genomic data sharing accessing only to certain regions of genomes for research purposes.

L-type Ca2+ channels in mood, cognition and addiction: integrating human and rodent studies with a focus on behavioural endophenotypes.

PubMed

Kabir, Z D; Lee, A S; Rajadhyaksha, A M

2016-10-15

Brain Ca v 1.2 and Ca v 1.3 L-type Ca 2+ channels play key physiological roles in various neuronal processes that contribute to brain function. Genetic studies have recently identified CACNA1C as a candidate risk gene for bipolar disorder (BD), schizophrenia (SCZ), major depressive disorder (MDD) and autism spectrum disorder (ASD), and CACNA1D for BD and ASD, suggesting a contribution of Ca v 1.2 and Ca v 1.3 Ca 2+ signalling to the pathophysiology of neuropsychiatric disorders. Once considered sole clinical entities, it is now clear that BD, SCZ, MDD and ASD share common phenotypic features, most likely due to overlapping neurocircuitry and common molecular mechanisms. A major future challenge lies in translating the human genetic findings to pathological mechanisms that are translatable back to the patient. One approach for tackling such a daunting scientific endeavour for complex behaviour-based neuropsychiatric disorders is to examine intermediate biological phenotypes in the context of endophenotypes within distinct behavioural domains. This will better allow us to integrate findings from genes to behaviour across species, and improve the chances of translating preclinical findings to clinical practice. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The Role of Double Dissociation Studies in the Search for Candidate Endophenotypes for the Comorbidity of Attention Deficit Hyperactivity Disorder and Reading Disability

ERIC Educational Resources Information Center

de Jong, Christien G. W.; Oosterlaan, Jaap; Sergeant, Joseph A.

2006-01-01

The neuropsychological underpinnings of Attention Deficit Hyperactivity Disorder (ADHD) and Reading Disability (RD) and their comorbidity may be studied usefully with the double dissociation design. The results of studies using the double dissociation method may be linked to the search for an endophenotype of ADHD and RD and their comorbidity.…

Genetic Deletion of Akt3 Induces an Endophenotype Reminiscent of Psychiatric Manifestations in Mice

PubMed Central

Bergeron, Yan; Bureau, Geneviève; Laurier-Laurin, Marie-Élaine; Asselin, Eric; Massicotte, Guy; Cyr, Michel

2017-01-01

The protein kinase B (PKB/Akt), found in three distinctive isoforms (PKBα/Akt1, PKBβ/Akt2, PKBγ/Akt3), is implicated in a variety of cellular processes such as cell development, growth and survival. Although Akt3 is the most expressed isoform in the brain, its role in cerebral functions is still unclear. In the present study, we investigated the behavioral, electrophysiological and biochemical consequences of Akt3 deletion in mice. Motor abilities, spatial navigation, recognition memory and LTP are intact in the Akt3 knockout (KO) mice. However, the prepulse inhibition, three-chamber social, forced swim, tail suspension, open field, elevated plus maze and light-dark transition tests revealed an endophenotype reminiscent of psychiatric manifestations such as schizophrenia, anxiety and depression. Biochemical investigations revealed that Akt3 deletion was associated with reduced levels of phosphorylated GSK3α/β at serine 21/9 in several brain regions, although Akt1 and Akt2 levels were unaffected. Notably, chronic administration of lithium, a mood stabilizer, restored the decreased phosphorylated GSK3α/β levels and rescued the depressive and anxiety-like behaviors in the Akt3 KO mice. Collectively, our data suggest that Akt3 might be a critical molecule underlying psychiatric-related behaviors in mice. PMID:28442992

Cognitive deficits as an endophenotype for anorexia nervosa: an accepted fact or a need for re-examination?

PubMed

Talbot, Amy; Hay, Phillipa; Buckett, Geoffrey; Touyz, Stephen

2015-01-01

To investigate whether impaired set shifting and weak central coherence represent state or trait characteristics and, therefore, candidate endophenotypes of anorexia nervosa (AN). Forty-nine individuals with lifetime AN (24 acutely unwell, 10 weight recovered, and 15 fully recovered) and 43 healthy controls completed the Wisconsin Card Sorting Test (WCST), the Matching Familiar Figures Test, and the Rey Complex Figure Task measuring cognitive flexibility, local processing, and global processing, respectively. Participants also completed questionnaires assessing eating disorder, anxiety and depressive symptoms, obsessional traits, interpersonal functioning, and quality of life. Body mass index was calculated from height and weight measurements. Participants with lifetime AN demonstrated poorer set shifting ability than healthy controls as evidenced by a greater number of perseverative errors on the WCST. When participants were grouped according to illness status, only those in the two recovered groups demonstrated poorer set shifting ability than healthy controls while patients with acute AN performed comparably to all other groups. There were no significant differences between groups on measures of local and global processing. No relationship was found between specific clinical features of AN and cognitive performance. The results of this study are consistent with a global trend toward set shifting difficulties in patients with AN but do not support weak central coherence as a candidate endophenotype for AN. These findings have clinical implications in terms of treatment selection and planning, particularly in relation to the use of cognitive remediation therapy with patients with AN. © 2014 Wiley Periodicals, Inc.

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia

PubMed Central

van der Velde, Jorien; Gromann, Paula M.; Swart, Marte; de Haan, Lieuwe; Wiersma, Durk; Bruggeman, Richard; Krabbendam, Lydia; Aleman, André

2015-01-01

Background Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies. Methods We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. Results We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings. Limitations The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites. Conclusion These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia. PMID:25768029

Fabp7 Maps to a Quantitative Trait Locus for a Schizophrenia Endophenotype

PubMed Central

Watanabe, Akiko; Toyota, Tomoko; Owada, Yuji; Hayashi, Takeshi; Iwayama, Yoshimi; Matsumata, Miho; Ishitsuka, Yuichi; Nakaya, Akihiro; Maekawa, Motoko; Ohnishi, Tetsuo; Arai, Ryoichi; Sakurai, Katsuyasu; Yamada, Kazuo; Kondo, Hisatake; Hashimoto, Kenji; Osumi, Noriko; Yoshikawa, Takeo

2007-01-01

Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the N-methyl-D-aspartic acid (NMDA) receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming. PMID:18001149

Shared-Reading versus Oral Storytelling: Associations with Preschoolers' Prosocial Skills and Problem Behaviours

ERIC Educational Resources Information Center

Curenton, Stephanie M.; Craig, Michelle Jones

2011-01-01

Dyadic shared-reading and oral storytelling practices and their association to American preschoolers' (N = 33) prosocial and problem behaviour was examined. The frequency (how often dyads read) and history (the child's age at first reading) were examined within shared-reading; emotion state talk and evaluative judgments were examined in both…

Syringe possession arrests are associated with receptive syringe sharing in two Mexico-US border cities

PubMed Central

Pollini, Robin A.; Brouwer, Kimberly C.; Lozada, Remedios M.; Ramos, Rebeca; Cruz, Michelle F.; Magis-Rodriguez, Carlos; Case, Patricia; Burris, Scott; Pu, Minya; Frost, Simon D. W.; Palinkas, Lawrence A.; Miller, Cari; Strathdee, Steffanie A.

2008-01-01

Aims To identify factors associated with receptive syringe sharing among injection drug users (IDUs) and elucidate the association between syringe possession arrests and syringe sharing. Design Cross-sectional study. Setting Mexican border cities of Tijuana, Baja California and Ciudad Juarez, Chihuahua. Participants IDUs in Tijuana (n = 222) and Ciudad Juarez (n = 206) were recruited using respondent-driven sampling (RDS). IDUs were ≥18 years and had injected illicit drugs in the past month. Measurements An interviewer-administered survey was used to collect quantitative data on socio-demographic, behavioral and contextual characteristics, including self-reported syringe sharing and arrests for syringe possession. Associations with receptive syringe sharing were investigated using logistic regression with RDS adjustment. Findings Overall, 48% of participants reported ever being arrested for carrying an unused/sterile syringe, even though syringe purchase and possession is legal in Mexico. Arrest for possessing unused/sterile syringes was associated independently with receptive syringe sharing [adjusted odds ratio (AOR) = 2.05; 95% confidence interval (CI): 1.26, 3.35], as was injecting in a shooting gallery (AOR = 3.60; 95% CI: 2.21, 5.87), injecting in the street (AOR = 2.05; 95% CI: 1.18, 3.54) and injecting methamphetamine (AOR = 2.77; 95% CI: 1.41, 5.47) or cocaine (AOR = 1.96; 95% CI: 1.15, 3.36). More than half of participants (57%) had been arrested for possessing a used syringe; in a second model, arrest for used syringe possession was also associated independently with receptive sharing (AOR = 2.87; 95% CI: 1.76, 4.69). Conclusions We documented high levels of syringe-related arrests in two Mexican–US border cities and an independent association between these arrests and risky injection practices. Public health collaborations with law enforcement to modify the risk environment in which drug use occurs are essential to facilitate safer injection

The prevalence and characteristics associated with mother-infant bed-sharing in Klang district, Malaysia.

PubMed

Tan, K L; Ghani, S N; Moy, F M

2009-12-01

This was a cross-sectional study to determine the prevalence and characteristics of mother-infant bed-sharing practice in Klang district, Malaysia. Data was collected by face-to-face interview using a structured questionnaire for a four month period in 2006. A total of 682 mother-infant pairs attending government health clinics were included in the study. Data regarding socio-demographic characteristics of the mothers, information on the infants, bed-sharing and breastfeeding practices were collected. The mean maternal age was 28.4 +/- 5.1 years while the mean infant gestational age was 38.8 +/- 1.8 weeks. The study showed the prevalence of bed-sharing was 73.5% (95% CI: 70.0, 76.7). In multivariate analysis; area of interview, maternal occupation, family income, breastfeeding and infant birth weight were associated with bed-sharing after adjusted for maternal ethnicity, age, marital status, educational level, parity, infant gender and infant gestational age. In conclusion, bed-sharing is a common practice in Klang district, Malaysia, not specific to ethnicity, but strongly associated with low family income and breastfeeding.

Trends and factors associated with infant bed sharing, 1993-2010: the National Infant Sleep Position Study.

PubMed

Colson, Eve R; Willinger, Marian; Rybin, Denis; Heeren, Timothy; Smith, Lauren A; Lister, George; Corwin, Michael J

2013-11-01

A strong association between infant bed sharing and sudden infant death syndrome or unintentional sleep-related death in infants has been established. Occurrences of unintentional sleep-related deaths among infants appear to be increasing. To determine the trends and factors associated with infant bed sharing from 1993 through 2010, including the association of physician advice on bed sharing. National Infant Sleep Position study conducted with annual telephone surveys. The 48 contiguous states. Nighttime caregivers of infants born within 7 months of each survey administration. Approximately 1000 interviews were completed annually. Infant bed sharing as a usual practice. Of 18 986 participants, 11.2% reported an infant sharing a bed as a usual practice. Bed sharing increased from 1993 (6.5%) to 2010 (13.5%). Although bed sharing increased significantly among white respondents from 1993 to 2000 (P < .001), the increase from 2001 to 2010 was not significant (P = .48). Black and Hispanic respondents reported an increase in bed sharing throughout the study period, with no difference between the earlier and later periods (P = .63 and P = .77, respectively). After accounting for the study year, factors associated with increase in infant bed sharing as a usual practice included maternal educational level of less than high school compared with college or greater (adjusted odds ratio, 1.42 [95% CI, 1.12-1.79]); black (3.47 [2.97-4.05]), Hispanic (1.33 [1.10-1.61]), and other (2.46 [2.03-2.97]) maternal race or ethnicity compared with white race; household income of less than $20,000 (1.69 [1.44-1.99]) and $20,000 to $50,000 (1.29 [1.14-1.45]) compared with greater than $50,000; living in the West (1.61 [1.38-1.88]) or the South (1.47 [1.30-1.66]) compared with the Midwest; infants younger than 8 weeks (1.45 [1.21-1.73]) or ages 8 to 15 weeks (1.31 [1.17-1.45]) compared with 16 weeks or older; and being born prematurely compared with full-term (1.41 [1.22-1.62]). Almost 46

Personality traits as an endophenotype in genetic studies on suicidality in bipolar disorder.

PubMed

Pawlak, J; Dmitrzak-Węglarz, M; Maciukiewicz, M; Kapelski, P; Czerski, P; Leszczyńska-Rodziewicz, A; Zaremba, D; Hauser, J

2017-04-01

Introduction The influence of personality traits on suicidal behaviour risk has been well documented. Personality traits and suicidal behaviour are partially genetically determined and personality has been described as an endophenotype of suicidal behaviour. The aim of this study was to investigate a possible association between personality traits with suicidal behaviour and selected serotonergic gene polymorphisms. In the study we included 156 patients meeting DSM-IV criteria for bipolar disorder (BP) and 93 healthy controls. The personality dimensions were assessed using the Temperament and Character Inventory (TCI). We genotyped two selected polymorphisms of the tryptophan hydroxylase 1 (TPH1) gene (rs1800532 218A>C and rs1799913 779A>C) and polymorphism in the promoter region of serotonin transporter gene (5-HTTLPR, rs25531) related to serotoninergic neurotransmission. Multiple poisson regression, logistic regression and Kruskal-Wallis tests were applied. We found numerous differences between the BP patients and the control group in terms of their TCI dimensions/subdimensions. Significant differences were found between patients with, and without, suicidal attempts in fatigability and asthenia (Ha4), as well as in harm avoidance (Ha). We also found that the interactions between TCI subdimensions (the interaction of disordiness (Ns4) and spiritual acceptance (St3), disordiness (Ns4) and integrated conscience (C5), extravagance (Ns3) and resourcefulness (Sd3)) were significantly contributing for suicidal behaviour risk. We found association between all studied genetic polymorphisms and several TCI dimensions and subdimensions. Our results confirm that personality traits are partially determined by genes. Both personality traits and the interactions between temperament and character traits, may be helpful in predicting suicidal behaviour.

Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment.

PubMed

Alboni, S; van Dijk, R M; Poggini, S; Milior, G; Perrotta, M; Drenth, T; Brunello, N; Wolfer, D P; Limatola, C; Amrein, I; Cirulli, F; Maggi, L; Branchi, I

2017-04-01

Selective serotonin reuptake inhibitors (SSRIs) represent the most common treatment for major depression. However, their efficacy is variable and incomplete. In order to elucidate the cause of such incomplete efficacy, we explored the hypothesis positing that SSRIs may not affect mood per se but, by enhancing neural plasticity, render the individual more susceptible to the influence of the environment. Consequently, SSRI administration in a favorable environment promotes a reduction of symptoms, whereas in a stressful environment leads to a worse prognosis. To test such hypothesis, we exposed C57BL/6 mice to chronic stress in order to induce a depression-like phenotype and, subsequently, to fluoxetine treatment (21 days), while being exposed to either an enriched or a stressful condition. We measured the most commonly investigated molecular, cellular and behavioral endophenotypes of depression and SSRI outcome, including depression-like behavior, neurogenesis, brain-derived neurotrophic factor levels, hypothalamic-pituitary-adrenal axis activity and long-term potentiation. Results showed that, in line with our hypothesis, the endophenotypes investigated were affected by the treatment according to the quality of the living environment. In particular, mice treated with fluoxetine in an enriched condition overall improved their depression-like phenotype compared with controls, whereas those treated in a stressful condition showed a distinct worsening. Our findings suggest that the effects of SSRI on the depression- like phenotype is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions.

Genetic and environmental influences on adolescent rumination and its association with depressive symptoms.

PubMed

Chen, Jie; Li, Xinying

2013-11-01

Rumination is an important cognitive vulnerability for adolescent and adult depression. However, little is known about the aetiological origins of rumination, as well as its association with depression. Adolescent rumination (self-report) and depressive symptoms (self- and parent-report) were assessed in 674 pairs of same-gender Chinese adolescent twins (11-17 years of age). Females accounted for 53.7 % of the sample. There were significant correlations between self-reported rumination and self-reported depression (r = 0.41), as well as parent-reported adolescent depression (r = 0.22). Genetic influences were significant and modest on all three measures, ranging from 24 % to 42 %. The three measures were also significantly influenced by shared environment, ranging from 20 % to 28 %, and non-shared environmental factors, ranging from 30 % to 56 %. Moreover, the genetic correlations between rumination and depression were significant (within-rater: r(g) = 0.99; cross-rater: r(g) = 0.59) and largely accounted for the phenotypic correlations (within-rater: 68 %; cross-rater: 77 %), while non-shared environmental correlations were also significant (within-rater: r(e) = 0.26; cross-rater: r(e) = 0.12) and accounted for the remainder of the phenotypic correlations (within-rater: 32 %; cross-rater: 23 %). The shared environmental correlations were non-significant. No significant gender and age differences were found in aetiological models. These findings suggest that rumination may be an endophenotype reflecting genetic risk for depression.

Comprehensive behavioral study of mGluR3 knockout mice: implication in schizophrenia related endophenotypes

PubMed Central

2014-01-01

Background We previously performed systematic association studies of glutamate receptor gene family members with schizophrenia, and found positive associations of polymorphisms in the GRM3 (a gene of metabotropic glutamate receptor 3: mGluR3) with the disorder. Physiological roles of GRM3 in brain functions and its functional roles in the pathogenesis of schizophrenia remain to be resolved. Results We generated mGluR3 knockout (KO) mice and conducted comprehensive behavioral analyses. KO mice showed hyperactivity in the open field, light/dark transition, and 24-hour home cage monitoring tests, impaired reference memory for stressful events in the Porsolt forced swim test, impaired contextual memory in cued and contextual fear conditioning test, and impaired working memory in the T-Maze forced alternation task test. Hyperactivity and impaired working memory are known as endophenotypes of schizophrenia. We examined long-term synaptic plasticity by assessing long-term potentiation (LTP) in the CA1 region in the hippocampi of KO and wild-type (WT) mice. We observed no differences in the amplitude of LTP between the two genotypes, suggesting that mGluR3 is not essential for LTP in the CA1 region of the mouse hippocampus. As hyperactivity is typically associated with increased dopaminergic transmission, we performed in vivo microdialysis measurements of extracellular dopamine in the nucleus accumbens of KO and WT mice. We observed enhancements in the methamphetamine (MAP)-induced release of dopamine in KO mice. Conclusions These results demonstrate that a disturbance in the glutamate-dopamine interaction may be involved in the pathophysiology of schizophrenia-like behavior, such as hyperactivity in mGluR3 KO mice. PMID:24758191

The association of consumer cost-sharing and direct-to-consumer advertising with prescription drug use.

PubMed

Hansen, Richard A; Schommer, Jon C; Cline, Richard R; Hadsall, Ronald S; Schondelmeyer, Stephen W; Nyman, John A

2005-06-01

Previous research on the impact of various cost-sharing strategies on prescription drug use has not considered the impact of direct-to-consumer (DTC) advertising. To explore the association of cost-containment strategies with prescription drug use and to determine if the association is moderated by DTC prescription drug advertising. The study population included 288 280 employees and dependents aged 18 to 65 years with employer-sponsored health insurance contributing to the MEDSTAT MarketScan administrative data set. Person-level enrollment and claims data were obtained for beneficiaries enrolled continuously during July 1997 through December 1998. Direct-to-consumer advertising data were obtained from Competitive Media Reporting and linked to the MEDSTAT enrollment files. Localized DTC advertising expenditures for one class of medication were evaluated and matched with prescription claims for eligible MEDSTAT contributors. The association of various types and levels of cost-sharing incentives with incident product use was evaluated, controlling for the level of DTC advertising, health status, and other demographic covariates. The relationship of cost-sharing amounts with drug use was modified by the level of DTC advertising in a geographic market. This relationship was dependent on the type of cost-sharing, distinguishing between co-payments for provider visits and co-payments for prescription drugs. Compared with low-advertising markets, individuals residing in markets with high levels of advertising and paying provider co-payments of $10.00 or more were more likely to use the advertised product. In the same markets, higher prescription drug co-payments were associated with a decreased likelihood of using the advertised product. A similar relationship was not observed for the nonadvertised competitor. Among insured individuals, response to cost-sharing strategies is moderated by DTC prescription drug advertising. The relative ability of cost-sharing strategies to

Shared liking and association valence for representational art but not abstract art.

PubMed

Schepman, Astrid; Rodway, Paul; Pullen, Sarah J; Kirkham, Julie

2015-01-01

We examined the finding that aesthetic evaluations are more similar across observers for representational images than for abstract images. It has been proposed that a difference in convergence of observers' tastes is due to differing levels of shared semantic associations (Vessel & Rubin, 2010). In Experiment 1, student participants rated 20 representational and 20 abstract artworks. We found that their judgments were more similar for representational than abstract artworks. In Experiment 2, we replicated this finding, and also found that valence ratings given to associations and meanings provided in response to the artworks converged more across observers for representational than for abstract art. Our empirical work provides insight into processes that may underlie the observation that taste for representational art is shared across individual observers, while taste for abstract art is more idiosyncratic.

Practicing what we preach: developing a data sharing policy for the Journal of the Medical Library Association.

PubMed

Read, Kevin B; Amos, Liz; Federer, Lisa M; Logan, Ayaba; Plutchak, T Scott; Akers, Katherine G

2018-04-01

Providing access to the data underlying research results in published literature allows others to reproduce those results or analyze the data in new ways. Health sciences librarians and information professionals have long been advocates of data sharing. It is time for us to practice what we preach and share the data associated with our published research. This editorial describes the activity of a working group charged with developing a research data sharing policy for the Journal of the Medical Library Association.

Practicing what we preach: developing a data sharing policy for the Journal of the Medical Library Association

PubMed Central

Read, Kevin B.; Amos, Liz; Federer, Lisa M.; Logan, Ayaba; Plutchak, T. Scott; Akers, Katherine G.

2018-01-01

Providing access to the data underlying research results in published literature allows others to reproduce those results or analyze the data in new ways. Health sciences librarians and information professionals have long been advocates of data sharing. It is time for us to practice what we preach and share the data associated with our published research. This editorial describes the activity of a working group charged with developing a research data sharing policy for the Journal of the Medical Library Association. PMID:29632437

The extent of interorganizational resource sharing among local health departments: the association with organizational characteristics and institutional factors.

PubMed

Vest, Joshua R; Shah, Gulzar H

2012-11-01

Resource sharing, arrangements between local health departments (LHDs) for joint programs or to share staff, is a growing occurrence. The post-9/11 influx of federal funding and new public health preparedness responsibilities dramatically increased the occurrence of these inter-LHD relationships, and several states have pursed more intrastate collaboration. This article describes the current state of resource sharing among LHDs and identifies the factors associated with resource sharing. Using the National Association of County & City Health Officials' 2010 Profile Survey, we determined the self-reported number of shared programmatic activities and the number of shared organizational functions for a sample of LHDs. Negative binomial regression models described the relationships between factors suggested by interorganizational theory and the counts of sharing activities. We examined the extent of resource sharing using 2 different count variables: (1) number of shared programmatic activities and (2) number of shared organizational functions. About one-half of all LHDs are engaged in resource sharing. The extent of sharing was lower for those serving larger populations, with city jurisdictions, or of larger size. Sharing was more extensive for state-governed LHDs, those covering multiple jurisdictions, states with centralized governance, and in instances of financial constraint. Many LHDs are engaged in a greater extent of resource sharing than others. Leaders of LHDs can work within the context of these factors to leverage resource sharing to meet their organizational needs.

A genetic predisposition score for muscular endophenotypes predicts the increase in aerobic power after training: the CAREGENE study.

PubMed

Thomaes, Tom; Thomis, Martine; Onkelinx, Steven; Fagard, Robert; Matthijs, Gert; Buys, Roselien; Schepers, Dirk; Cornelissen, Véronique; Vanhees, Luc

2011-10-03

It is widely accepted that genetic variability might explain a large part of the observed heterogeneity in aerobic capacity and its response to training. Significant associations between polymorphisms of different genes with muscular strength, anaerobic phenotypes and body composition have been reported. Muscular endophenotypes are positively correlated with aerobic capacity, therefore, we tested the association of polymorphisms in twelve muscular related genes on aerobic capacity and its response to endurance training. 935 Coronary artery disease patients (CAD) who performed an incremental exercise test until exhaustion at baseline and after three months of training were included. Polymorphisms of the genes were detected using the invader assay. Genotype-phenotype association analyses were performed using ANCOVA. Different models for a genetic predisposition score (GPS) were constructed based on literature and own data and were related to baseline and response VO(2) scores. Carriers of the minor allele in the R23K polymorphism of the glucocorticoid receptor gene (GR) and the ciliary neurotrophic factor gene (CNTF) had a significantly higher increase in peakVO(2) after training (p < 0.05). Carriers of the minor allele (C34T) in the adenosine monophosphate deaminase (AMPD1) gene had a significantly lower relative increase (p < 0.05) in peakVO(2). GPS of data driven models were significantly associated with the increase in peakVO(2) after training. In CAD patients, suggestive associations were found in the GR, CNTF and the AMPD1 gene with an improved change in aerobic capacity after three months of training. Additionally data driven models with a genetic predisposition score (GPS) showed a significant predictive value for the increase in peakVO(2).

A genetic predisposition score for muscular endophenotypes predicts the increase in aerobic power after training: the CAREGENE study

PubMed Central

2011-01-01

Background It is widely accepted that genetic variability might explain a large part of the observed heterogeneity in aerobic capacity and its response to training. Significant associations between polymorphisms of different genes with muscular strength, anaerobic phenotypes and body composition have been reported. Muscular endophenotypes are positively correlated with aerobic capacity, therefore, we tested the association of polymorphisms in twelve muscular related genes on aerobic capacity and its response to endurance training. Methods 935 Coronary artery disease patients (CAD) who performed an incremental exercise test until exhaustion at baseline and after three months of training were included. Polymorphisms of the genes were detected using the invader assay. Genotype-phenotype association analyses were performed using ANCOVA. Different models for a genetic predisposition score (GPS) were constructed based on literature and own data and were related to baseline and response VO2 scores. Results Carriers of the minor allele in the R23K polymorphism of the glucocorticoid receptor gene (GR) and the ciliary neurotrophic factor gene (CNTF) had a significantly higher increase in peakVO2 after training (p < 0.05). Carriers of the minor allele (C34T) in the adenosine monophosphate deaminase (AMPD1) gene had a significantly lower relative increase (p < 0.05) in peakVO2. GPS of data driven models were significantly associated with the increase in peakVO2 after training. Conclusions In CAD patients, suggestive associations were found in the GR, CNTF and the AMPD1 gene with an improved change in aerobic capacity after three months of training. Additionally data driven models with a genetic predisposition score (GPS) showed a significant predictive value for the increase in peakVO2. PMID:21967077

Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders

PubMed Central

Hagihara, Hideo; Catts, Vibeke S; Katayama, Yuta; Shoji, Hirotaka; Takagi, Tsuyoshi; Huang, Freesia L; Nakao, Akito; Mori, Yasuo; Huang, Kuo-Ping; Ishii, Shunsuke; Graef, Isabella A; Nakayama, Keiichi I; Shannon Weickert, Cynthia; Miyakawa, Tsuyoshi

2018-01-01

Although the brains of patients with schizophrenia and bipolar disorder exhibit decreased brain pH relative to those of healthy controls upon postmortem examination, it remains controversial whether this finding reflects a primary feature of the diseases or is a result of confounding factors such as medication and agonal state. To date, systematic investigation of brain pH has not been undertaken using animal models that can be studied without confounds inherent in human studies. In the present study, we first reevaluated the pH of the postmortem brains of patients with schizophrenia and bipolar disorder by conducting a meta-analysis of existing data sets from 10 studies. We then measured pH, lactate levels, and related metabolite levels in brain homogenates from five neurodevelopmental mouse models of psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. All mice were drug naive with the same agonal state, postmortem interval, and age within each strain. Our meta-analysis revealed that brain pH was significantly lower in patients with schizophrenia and bipolar disorder than in control participants, even when a few potential confounding factors (postmortem interval, age, and history of antipsychotic use) were considered. In animal experiments, we observed significantly lower pH and higher lactate levels in the brains of model mice relative to controls, as well as a significant negative correlation between pH and lactate levels. Our findings suggest that lower pH associated with increased lactate levels is not a mere artifact, but rather implicated in the underlying pathophysiology of schizophrenia and bipolar disorder. PMID:28776581

Sharing self-related information is associated with intrinsic functional connectivity of cortical midline brain regions

PubMed Central

Meshi, Dar; Mamerow, Loreen; Kirilina, Evgeniya; Morawetz, Carmen; Margulies, Daniel S.; Heekeren, Hauke R.

2016-01-01

Human beings are social animals and they vary in the degree to which they share information about themselves with others. Although brain networks involved in self-related cognition have been identified, especially via the use of resting-state experiments, the neural circuitry underlying individual differences in the sharing of self-related information is currently unknown. Therefore, we investigated the intrinsic functional organization of the brain with respect to participants’ degree of self-related information sharing using resting state functional magnetic resonance imaging and self-reported social media use. We conducted seed-based correlation analyses in cortical midline regions previously shown in meta-analyses to be involved in self-referential cognition: the medial prefrontal cortex (MPFC), central precuneus (CP), and caudal anterior cingulate cortex (CACC). We examined whether and how functional connectivity between these regions and the rest of the brain was associated with participants’ degree of self-related information sharing. Analyses revealed associations between the MPFC and right dorsolateral prefrontal cortex (DLPFC), as well as the CP with the right DLPFC, the left lateral orbitofrontal cortex and left anterior temporal pole. These findings extend our present knowledge of functional brain connectivity, specifically demonstrating how the brain’s intrinsic functional organization relates to individual differences in the sharing of self-related information. PMID:26948055

31 CFR 50.36 - Allocation of premium income associated with entities that do share profits and losses with...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Allocation of premium income associated with entities that do share profits and losses with private sector insurers. 50.36 Section 50.36... income associated with entities that do share profits and losses with private sector insurers. (a...

[Early diagnosis of autism: Phenotype-endophenotype].

PubMed

Kotsopoulos, S

2015-01-01

Autism Spectrum Disorders have for some time been the focus of intense interest for clinicians and researchers because of the high prevalence of the disorders among children in the community (approximately 1%), their severity and pervasiveness. Particular attention has been paid to the early diagnosis of the disorder and to the intensive therapeutic intervention. Currently the best prognosis for autism lays in the early diagnosis and intervention. Postponing the diagnosis and the intervention beyond infancy is considered loss of precious time. The diagnosis of autism, which begins early in life, was until recently considered that could be reliability made at the age of 3 years. Recent follow up studies however on children at risk for autism (children who had an older sibling with autism) have shown that the clinical signs of autism emerge at the end of the first year and become distinct by the end of the second year when the diagnosis can reliably be made. From a clinical perspective it is noted that the early clinical signs of risk for autism are related to social communication (e.g. limited or absent response when calling his/her name and to joint attention), stereotype behaviours and body movements or unusual handling of objects (e.g. intensive observation of objects and stereotype movements of hands and tapping or spinning), incongruent regulation of emotions (reduced positive and increased negative emotion). There is also delay in developmental characteristics such as the language (both receptive and expressive) and motor (particularly in postural control - characteristic is the drop of the head backwards when the infant is held in horizontal position). Studies on various aspects of the endophenotype of certain clinical signs among infants at risk for Autism Spectrum Disorders, such as avoidance of eye contact, delay in verbal communication and increase of the head circumference, may provide useful information and may assist the clinician on follow up in the

The Utility of P300 as a Schizophrenia Endophenotype and Predictive Biomarker: Clinical and Socio-Demographic Modulators in COGS-2

PubMed Central

Turetsky, Bruce I.; Dress, Erich M.; Braff, David L.; Calkins, Monica E.; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Nuechterlein, Keith H.; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Light, Gregory

2014-01-01

Reduced auditory P300 amplitude is a robust schizophrenia deficit exhibiting the qualities of a viable genetic endophenotype. These include heritability, test-retest reliability, and trait-like stability. Recent evidence suggests that P300 may also serve as a predictive biomarker for transition to psychosis during the schizophrenia prodrome. Historically, the utility of the P300 has been limited by its clinical nonspecificity, cross-site measurement variability, and required EEG expertise. The Consortium on the Genetics of Schizophrenia (COGS-2) study provided an opportunity to examine the consistency of the measure across multiple sites with varying degrees of EEG experience, and to identify important modulating factors that contribute to measurement variability. Auditory P300 was acquired from 649 control and 587 patients at 5 sites. An overall patient deficit was observed with effect size 0.62. Each site independently observed a significant patient deficit, but site differences also existed. In patients, site differences reflected clinical differences in positive symptomatology and functional capacity. In controls, site differences reflected differences in racial stratification, smoking and substance use history. These factors differentially suppressed the P300 response, but only in control subjects. This led to an attenuated patient-control difference among smokers and among African Americans with history of substance use. These findings indicate that the P300 can be adequately assessed quantitatively, across sites, without substantial EEG expertise. Measurements are suitable for both genetic endophenotype analyses and studies of psychosis risk and conversion. However, careful attention must be given to selection of appropriate comparison samples to avoid misleading false negative results. PMID:25306203

Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers

PubMed Central

Tonomura, Noriko; Elvers, Ingegerd; Thomas, Rachael; Megquier, Kate; Turner-Maier, Jason; Howald, Cedric; Sarver, Aaron L.; Swofford, Ross; Frantz, Aric M.; Ito, Daisuke; Mauceli, Evan; Arendt, Maja; Noh, Hyun Ji; Koltookian, Michele; Biagi, Tara; Fryc, Sarah; Williams, Christina; Avery, Anne C.; Kim, Jong-Hyuk; Barber, Lisa; Burgess, Kristine; Lander, Eric S.; Karlsson, Elinor K.; Azuma, Chieko

2015-01-01

Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6%) and hemangiosarcoma (20%). We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers. PMID:25642983

Deconstructing the “Resting” State: Exploring the Temporal Dynamics of Frontal Alpha Asymmetry as an Endophenotype for Depression

PubMed Central

Allen, John J. B.; Cohen, Michael X

2010-01-01

Asymmetry in frontal electrocortical alpha-band (8–13 Hz) activity recorded during resting situations (i.e., in absence of a specific task) has been investigated in relation to emotion and depression for over 30 years. This asymmetry reflects an aspect of endogenous cortical dynamics that is stable over repeated measurements and that may serve as an endophenotype for mood or other psychiatric disorders. In nearly all of this research, EEG activity is averaged across several minutes, obscuring transient dynamics that unfold on the scale of milliseconds to seconds. Such dynamic states may ultimately have greater value in linking brain activity to surface EEG asymmetry, thus improving its status as an endophenotype for depression. Here we introduce novel metrics for characterizing frontal alpha asymmetry that provide a more in-depth neurodynamical understanding of recurrent endogenous cortical processes during the resting-state. The metrics are based on transient “bursts” of asymmetry that occur frequently during the resting-state. In a sample of 306 young adults, 143 with a lifetime diagnosis of major depressive disorder (62 currently symptomatic), three questions were addressed: (1) How do novel peri-burst metrics of dynamic asymmetry compare to conventional fast-Fourier transform-based metrics? (2) Do peri-burst metrics adequately differentiate depressed from non-depressed participants? and, (3) what EEG dynamics surround the asymmetry bursts? Peri-burst metrics correlated with traditional measures of asymmetry, and were sensitive to both current and past episodes of major depression. Moreover, asymmetry bursts were characterized by a transient lateralized alpha suppression that is highly consistent in phase across bursts, and a concurrent contralateral transient alpha enhancement that is less tightly phase-locked across bursts. This approach opens new possibilities for investigating rapid cortical dynamics during resting-state EEG. PMID:21228910

Who shares? Who doesn't? Factors associated with openly archiving raw research data.

PubMed

Piwowar, Heather A

2011-01-01

Many initiatives encourage investigators to share their raw datasets in hopes of increasing research efficiency and quality. Despite these investments of time and money, we do not have a firm grasp of who openly shares raw research data, who doesn't, and which initiatives are correlated with high rates of data sharing. In this analysis I use bibliometric methods to identify patterns in the frequency with which investigators openly archive their raw gene expression microarray datasets after study publication. Automated methods identified 11,603 articles published between 2000 and 2009 that describe the creation of gene expression microarray data. Associated datasets in best-practice repositories were found for 25% of these articles, increasing from less than 5% in 2001 to 30%-35% in 2007-2009. Accounting for sensitivity of the automated methods, approximately 45% of recent gene expression studies made their data publicly available. First-order factor analysis on 124 diverse bibliometric attributes of the data creation articles revealed 15 factors describing authorship, funding, institution, publication, and domain environments. In multivariate regression, authors were most likely to share data if they had prior experience sharing or reusing data, if their study was published in an open access journal or a journal with a relatively strong data sharing policy, or if the study was funded by a large number of NIH grants. Authors of studies on cancer and human subjects were least likely to make their datasets available. These results suggest research data sharing levels are still low and increasing only slowly, and data is least available in areas where it could make the biggest impact. Let's learn from those with high rates of sharing to embrace the full potential of our research output.

STRESS RISK FACTORS AND STRESS-RELATED PATHOLOGY: NEUROPLASTICITY, EPIGENETICS AND ENDOPHENOTYPES

PubMed Central

Radley, Jason J.; Kabbaj, Mohamed; Jacobson, Lauren; Heydendael, Willem; Yehuda, Rachel; Herman, James P.

2013-01-01

This review highlights a symposium on stress risk factors and stress susceptibility, presented at the Neurobiology of Stress workshop in Boulder, Colorado, June 2010. This symposium addressed factors linking stress plasticity and reactivity to stress pathology in animal models and in humans. Dr. Jason Radley discussed studies demonstrating prefrontal cortical neuroplasticity and prefrontal control of hypothalamo-pituitary-adrenocortical axis function in rat, highlighting emerging evidence for a critical role of this region in normal and pathological stress integration. Dr. Mohamed Kabbaj summarized his studies of possible epigenetic mechanisms underlying behavioral differences in rat populations bred for differential stress reactivity. Dr. Lauren Jacobson described studies using a mouse model to explore the diverse actions of antidepressant action in brain, suggesting mechanisms whereby antidepressants may be differentially effective in treating specific depression endophenotypes. Dr. Rachel Yehuda discussed the role of glucocorticoids in post-traumatic stress disorder (PTSD), indicating that low cortisol may be a trait that predisposes the individual to development of the disorder. Furthermore, she presented evidence indicating that traumatic events can have transgenerational impact on cortisol reactivity and development of PTSD symptoms. Together, the symposium highlighted emerging themes regarding the role of brain reorganization, individual differences and epigenetics in determining stress plasticity and pathology. PMID:21848436

Shared understanding in psychiatrist-patient communication: association with treatment adherence in schizophrenia.

PubMed

McCabe, Rosemarie; Healey, Patrick G T; Priebe, Stefan; Lavelle, Mary; Dodwell, David; Laugharne, Richard; Snell, Amelia; Bremner, Stephen

2013-10-01

Effective doctor-patient communication, including a shared understanding, is associated with treatment adherence across medicine. However, communication is affected by a diagnosis of schizophrenia and reaching a shared understanding can be challenging. During conversation, people detect and deal with possible misunderstanding using a conversational process called repair. This study tested the hypothesis that more frequent repair in psychiatrist-patient communication is associated with better treatment adherence in schizophrenia. Routine psychiatric consultations involving patients with (DSM-IV) schizophrenia or schizoaffective disorder were audio-visually recorded. Consultations were coded for repair and patients' symptoms and insight assessed. Adherence was assessed six months later. A principal components analysis reduced the repair data for further analysis. Random effects models examined the association between repair and adherence, adjusting for symptoms, consultation length and the amount patients spoke. 138 consultations were recorded, 118 were followed up. Patients requesting clarification of the psychiatrist's talk and the clarification provided by the psychiatrist was associated with adherence six months later (OR 5.82, 95% CI 1.31-25.82, p=0.02). The quality of doctor-patient communication also appears to influence adherence in schizophrenia. Future research should investigate how patient clarification can be encouraged among patients and facilitated by psychiatrists' communication. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The utility of P300 as a schizophrenia endophenotype and predictive biomarker: clinical and socio-demographic modulators in COGS-2.

PubMed

Turetsky, Bruce I; Dress, Erich M; Braff, David L; Calkins, Monica E; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Nuechterlein, Keith H; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Light, Gregory

2015-04-01

Reduced auditory P300 amplitude is a robust schizophrenia deficit exhibiting the qualities of a viable genetic endophenotype. These include heritability, test-retest reliability, and trait-like stability. Recent evidence suggests that P300 may also serve as a predictive biomarker for transition to psychosis during the schizophrenia prodrome. Historically, the utility of the P300 has been limited by its clinical nonspecificity, cross-site measurement variability, and required EEG expertise. The Consortium on the Genetics of Schizophrenia (COGS-2) study provided an opportunity to examine the consistency of the measure across multiple sites with varying degrees of EEG experience, and to identify important modulating factors that contribute to measurement variability. Auditory P300 was acquired from 649 controls and 587 patients at 5 sites. An overall patient deficit was observed with effect size 0.62. Each site independently observed a significant patient deficit, but site differences also existed. In patients, site differences reflected clinical differences in positive symptomatology and functional capacity. In controls, site differences reflected differences in racial stratification, smoking and substance use history. These factors differentially suppressed the P300 response, but only in control subjects. This led to an attenuated patient-control difference among smokers and among African Americans with history of substance use. These findings indicate that the P300 can be adequately assessed quantitatively, across sites, without substantial EEG expertise. Measurements are suitable for both genetic endophenotype analyses and studies of psychosis risk and conversion. However, careful attention must be given to selection of appropriate comparison samples to avoid misleading false negative results. Copyright © 2014 Elsevier B.V. All rights reserved.

Bicycling injury hospitalisation rates in Canadian jurisdictions: analyses examining associations with helmet legislation and mode share

PubMed Central

Teschke, Kay; Koehoorn, Mieke; Shen, Hui; Dennis, Jessica

2015-01-01

Objectives The purpose of this study was to calculate exposure-based bicycling hospitalisation rates in Canadian jurisdictions with different helmet legislation and bicycling mode shares, and to examine whether the rates were related to these differences. Methods Administrative data on hospital stays for bicycling injuries to 10 body region groups and national survey data on bicycling trips were used to calculate hospitalisation rates. Rates were calculated for 44 sex, age and jurisdiction strata for all injury causes and 22 age and jurisdiction strata for traffic-related injury causes. Inferential analyses examined associations between hospitalisation rates and sex, age group, helmet legislation and bicycling mode share. Results In Canada, over the study period 2006–2011, there was an average of 3690 hospitalisations per year and an estimated 593 million annual trips by bicycle among people 12 years of age and older, for a cycling hospitalisation rate of 622 per 100 million trips (95% CI 611 to 633). Hospitalisation rates varied substantially across the jurisdiction, age and sex strata, but only two characteristics explained this variability. For all injury causes, sex was associated with hospitalisation rates; females had rates consistently lower than males. For traffic-related injury causes, higher cycling mode share was consistently associated with lower hospitalisation rates. Helmet legislation was not associated with hospitalisation rates for brain, head, scalp, skull, face or neck injuries. Conclusions These results suggest that transportation and health policymakers who aim to reduce bicycling injury rates in the population should focus on factors related to increased cycling mode share and female cycling choices. Bicycling routes designed to be physically separated from traffic or along quiet streets fit both these criteria and are associated with lower relative risks of injury. PMID:26525719

The Association between Various Shared Activities and the Quality of Parent-Child Relationships.

ERIC Educational Resources Information Center

DiBlassio, Jamie; Calore, Kristen; Chambliss, Catherine

This study examined the association between various shared activities and the quality of parent-child relationships. Participating in the study were 211 undergraduate students attending a small liberal arts college. They completed a questionnaire in which they rated the quality of their relationship with their parents, the amount of contact they…

Count Your Calories and Share Them: Health Benefits of Sharing mHealth Information on Social Networking Sites.

PubMed

Oeldorf-Hirsch, Anne; High, Andrew C; Christensen, John L

2018-04-23

This study investigates the relationship between sharing tracked mobile health (mHealth) information online, supportive communication, feedback, and health behavior. Based on the Integrated Theory of mHealth, our model asserts that sharing tracked health information on social networking sites benefits users' perceptions of their health because of the supportive communication they gain from members of their online social networks and that the amount of feedback people receive moderates these associations. Users of mHealth apps (N = 511) completed an online survey, and results revealed that both sharing tracked health information and receiving feedback from an online social network were positively associated with supportive communication. Network support both corresponded with improved health behavior and mediated the association between sharing health information and users' health behavior. As users received greater amounts of feedback from their online social networks, however, the association between sharing tracked health information and health behavior decreased. Theoretical implications for sharing tracked health information and practical implications for using mHealth apps are discussed.

An Autistic Endophenotype and Testosterone Are Involved in an Atypical Decline in Selective Attention and Visuospatial Processing in Middle-Aged Women.

PubMed

Ángel, Romero-Martínez; Luis, Moya-Albiol

2015-12-15

Mothers of offspring with autism spectrum disorders (ASD) could present mild forms of their children's cognitive characteristics, resulting from prenatal brain exposure and sensitivity to testosterone (T). Indeed, their cognition is frequently characterized by hyper-systemizing, outperforming in tests that assess cognitive domains such as selective attention, and fine motor and visuospatial skills. In the general population, all these start to decline around the mid-forties. This study aimed to characterize whether middle-aged women who are biological mothers of individuals with ASD had better performance in the aforementioned cognitive skills than mothers of normative children (in both groups n = 22; mean age = 45), using the standardized Stroop and mirror-drawing tests. We also examined the role of T in their performance in the aforementioned tests. ASD mothers outperformed controls in both tests, giving more correct answers and making fewer mistakes. In addition, they presented higher T levels, which have been associated with better cognitive performance. Cognitive decline in specific skills with aging could be delayed in these middle-aged women, corresponding to a cognitive endophenotype, T playing an important role in this process.

An Autistic Endophenotype and Testosterone Are Involved in an Atypical Decline in Selective Attention and Visuospatial Processing in Middle-Aged Women

PubMed Central

Ángel, Romero-Martínez; Luis, Moya-Albiol

2015-01-01

Mothers of offspring with autism spectrum disorders (ASD) could present mild forms of their children’s cognitive characteristics, resulting from prenatal brain exposure and sensitivity to testosterone (T). Indeed, their cognition is frequently characterized by hyper-systemizing, outperforming in tests that assess cognitive domains such as selective attention, and fine motor and visuospatial skills. In the general population, all these start to decline around the mid-forties. This study aimed to characterize whether middle-aged women who are biological mothers of individuals with ASD had better performance in the aforementioned cognitive skills than mothers of normative children (in both groups n = 22; mean age = 45), using the standardized Stroop and mirror-drawing tests. We also examined the role of T in their performance in the aforementioned tests. ASD mothers outperformed controls in both tests, giving more correct answers and making fewer mistakes. In addition, they presented higher T levels, which have been associated with better cognitive performance. Cognitive decline in specific skills with aging could be delayed in these middle-aged women, corresponding to a cognitive endophenotype, T playing an important role in this process. PMID:26694433

Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases.

PubMed

Kubben, Nard; Misteli, Tom

2017-10-01

Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson-Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

Is periodontitis a comorbidity of COPD or can associations be explained by shared risk factors/behaviors?

PubMed Central

Hobbins, Stephanie; Chapple, Iain LC; Sapey, Elizabeth; Stockley, Robert A

2017-01-01

COPD is recognized as having a series of comorbidities potentially related to common inflammatory processes. Periodontitis is one of the most common human inflammatory diseases and has previously been associated with COPD in numerous observational studies. As periodontitis and COPD are both chronic, progressive conditions characterized by neutrophilic inflammation with subsequent proteolytic destruction of connective tissue, it has been proposed that they share common pathophysiological processes. The mechanisms proposed to link COPD and periodontitis include mechanical aspiration of oral contents into the respiratory tree, overspill of locally produced inflammatory mediators into the systemic circulation or oral or lung-derived bacteremia activating an acute-phase response and also reactive oxygen species (ROS) and cytokine release by systemic neutrophils at distant sites. Studies of systemic neutrophils in COPD and chronic periodontitis describe altered cellular functions that would predispose to inflammation and tissue destruction both in the lung and in the mouth, again potentially connecting these conditions. However, COPD and periodontitis also share risk factors such as age, chronic tobacco smoke exposure, and social deprivation that are not always considered in observational and interventional studies. Furthermore, studies reporting associations have often utilized differing definitions of both COPD and periodontitis. This article reviews the current available evidence supporting the hypothesis that COPD and inflammatory periodontal disease (periodontitis) could be pathologically associated, including a review of shared inflammatory mechanisms. It highlights the potential limitations of previous studies, in particular, the lack of uniformly applied case definitions for both COPD and periodontitis and poor recognition of shared risk factors. Understanding associations between these conditions may inform why patients with COPD suffer such a burden of comorbid

Is periodontitis a comorbidity of COPD or can associations be explained by shared risk factors/behaviors?

PubMed

Hobbins, Stephanie; Chapple, Iain Lc; Sapey, Elizabeth; Stockley, Robert A

2017-01-01

COPD is recognized as having a series of comorbidities potentially related to common inflammatory processes. Periodontitis is one of the most common human inflammatory diseases and has previously been associated with COPD in numerous observational studies. As periodontitis and COPD are both chronic, progressive conditions characterized by neutrophilic inflammation with subsequent proteolytic destruction of connective tissue, it has been proposed that they share common pathophysiological processes. The mechanisms proposed to link COPD and periodontitis include mechanical aspiration of oral contents into the respiratory tree, overspill of locally produced inflammatory mediators into the systemic circulation or oral or lung-derived bacteremia activating an acute-phase response and also reactive oxygen species (ROS) and cytokine release by systemic neutrophils at distant sites. Studies of systemic neutrophils in COPD and chronic periodontitis describe altered cellular functions that would predispose to inflammation and tissue destruction both in the lung and in the mouth, again potentially connecting these conditions. However, COPD and periodontitis also share risk factors such as age, chronic tobacco smoke exposure, and social deprivation that are not always considered in observational and interventional studies. Furthermore, studies reporting associations have often utilized differing definitions of both COPD and periodontitis. This article reviews the current available evidence supporting the hypothesis that COPD and inflammatory periodontal disease (periodontitis) could be pathologically associated, including a review of shared inflammatory mechanisms. It highlights the potential limitations of previous studies, in particular, the lack of uniformly applied case definitions for both COPD and periodontitis and poor recognition of shared risk factors. Understanding associations between these conditions may inform why patients with COPD suffer such a burden of comorbid

A review of associations between family or shared meal frequency and dietary and weight status outcomes across the lifespan.

PubMed

Fulkerson, Jayne A; Larson, Nicole; Horning, Melissa; Neumark-Sztainer, Dianne

2014-01-01

To summarize the research literature on associations between family meal frequency and dietary outcomes as well as weight status across the lifespan. Reviewed literature of family or shared meals with dietary and weight outcomes in youth, adults, and older adults. Across the lifespan, eating with others, particularly family, is associated with healthier dietary outcomes. Among children and adolescents, these findings appear to be consistent for both boys and girls, whereas mixed findings are seen by gender for adult men and women. The findings of associations between family or shared meals and weight outcomes across the lifespan are less consistent and more complicated than those of dietary outcomes. Now is the time for the field to improve understanding of the mechanisms involved in the positive associations seen with family meal frequency, and to move forward with implementing interventions aimed at increasing the frequency of, and improving the quality of, food served at family meals, and evaluating their impact. Given the more limited findings of associations between family or shared meals and weight outcomes, capitalizing on the positive benefits of family and shared meals while addressing the types of foods served, portion sizes, and other potential mechanisms may have a significant impact on obesity prevention and reduction. Future research recommendations are provided. Copyright © 2014 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Factors associated with the practice of nursing staff sharing information about patients' nutritional status with their colleagues in hospitals.

PubMed

Kawasaki, Y; Tamaura, Y; Akamatsu, R; Sakai, M; Fujiwara, K

2018-01-01

Nursing staff have an important role in patients' nutritional care. The aim of this study was to demonstrate how the practice of sharing a patient's nutritional status with colleagues was affected by the nursing staff's attitude, knowledge and their priority to provide nutritional care. The participants were 492 nursing staff. We obtained participants' demographic data, the practice of sharing patients' nutritional information and information about participants' knowledge, attitude and priority of providing nutritional care by the questionnaire. We performed partial correlation analyses and linear regression analyses to describe the relationship between the total scores of the practice of sharing patients' nutritional information based on their knowledge, attitude and priority to provide nutritional care. Among the 492 participants, 396 nursing staff (80.5%) completed the questionnaire and were included in analyses. Mean±s.d. of total score of the 396 participants was 8.4±3.1. Nursing staff shared information when they had a high nutritional knowledge (r=0.36, P<0.01) and attitude (r=0.13, P<0.05); however, their correlation coefficients were low. In the linear regression analyses, job categories (β=-0.28, P<0.01), knowledge (β=0.33, P<0.01) and attitude (β=0.10, P<0.05) were independently associated with the practice of sharing information. Nursing staff's priority to provide nutritional care practice was not significantly associated with the practice of sharing information. Knowledge and attitude were independently associated with the practice of sharing patients' nutrition information with colleagues, regardless of their priority to provide nutritional care. An effective approach should be taken to improve the practice of providing nutritional care practice.

Image Sharing in Radiology-A Primer.

PubMed

Chatterjee, Arindam R; Stalcup, Seth; Sharma, Arjun; Sato, T Shawn; Gupta, Pushpender; Lee, Yueh Z; Malone, Christopher; McBee, Morgan; Hotaling, Elise L; Kansagra, Akash P

2017-03-01

By virtue of its information technology-oriented infrastructure, the specialty of radiology is uniquely positioned to be at the forefront of efforts to promote data sharing across the healthcare enterprise, including particularly image sharing. The potential benefits of image sharing for clinical, research, and educational applications in radiology are immense. In this work, our group-the Association of University Radiologists (AUR) Radiology Research Alliance Task Force on Image Sharing-reviews the benefits of implementing image sharing capability, introduces current image sharing platforms and details their unique requirements, and presents emerging platforms that may see greater adoption in the future. By understanding this complex ecosystem of image sharing solutions, radiologists can become important advocates for the successful implementation of these powerful image sharing resources. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Meta-Analysis of Genome-Wide Association Studies in Celiac Disease and Rheumatoid Arthritis Identifies Fourteen Non-HLA Shared Loci

PubMed Central

Zhernakova, Alexandra; Stahl, Eli A.; Trynka, Gosia; Raychaudhuri, Soumya; Festen, Eleanora A.; Franke, Lude; Westra, Harm-Jan; Fehrmann, Rudolf S. N.; Kurreeman, Fina A. S.; Thomson, Brian; Gupta, Namrata; Romanos, Jihane; McManus, Ross; Ryan, Anthony W.; Turner, Graham; Brouwer, Elisabeth; Posthumus, Marcel D.; Remmers, Elaine F.; Tucci, Francesca; Toes, Rene; Grandone, Elvira; Mazzilli, Maria Cristina; Rybak, Anna; Cukrowska, Bozena; Coenen, Marieke J. H.; Radstake, Timothy R. D. J.; van Riel, Piet L. C. M.; Li, Yonghong; de Bakker, Paul I. W.; Gregersen, Peter K.; Worthington, Jane; Siminovitch, Katherine A.; Klareskog, Lars; Huizinga, Tom W. J.

2011-01-01

Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD) and rheumatoid arthritis (RA), but the extent of this sharing has not been systematically explored. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases. We hypothesized that there are additional shared risk alleles and that combining genome-wide association study (GWAS) data from each disease would increase power to identify these shared risk alleles. We performed a meta-analysis of two published GWAS on CD (4,533 cases and 10,750 controls) and RA (5,539 cases and 17,231 controls). After genotyping the top associated SNPs in 2,169 CD cases and 2,255 controls, and 2,845 RA cases and 4,944 controls, 8 additional SNPs demonstrated P<5×10−8 in a combined analysis of all 50,266 samples, including four SNPs that have not been previously confirmed in either disease: rs10892279 near the DDX6 gene (Pcombined = 1.2×10−12), rs864537 near CD247 (Pcombined = 2.2×10−11), rs2298428 near UBE2L3 (Pcombined = 2.5×10−10), and rs11203203 near UBASH3A (Pcombined = 1.1×10−8). We also confirmed that 4 gene loci previously established in either CD or RA are associated with the other autoimmune disease at combined P<5×10−8 (SH2B3, 8q24, STAT4, and TRAF1-C5). From the 14 shared gene loci, 7 SNPs showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (LD) block around the SNP. These associations implicate antigen presentation and T-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases. PMID:21383967

Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

PubMed

Zhernakova, Alexandra; Stahl, Eli A; Trynka, Gosia; Raychaudhuri, Soumya; Festen, Eleanora A; Franke, Lude; Westra, Harm-Jan; Fehrmann, Rudolf S N; Kurreeman, Fina A S; Thomson, Brian; Gupta, Namrata; Romanos, Jihane; McManus, Ross; Ryan, Anthony W; Turner, Graham; Brouwer, Elisabeth; Posthumus, Marcel D; Remmers, Elaine F; Tucci, Francesca; Toes, Rene; Grandone, Elvira; Mazzilli, Maria Cristina; Rybak, Anna; Cukrowska, Bozena; Coenen, Marieke J H; Radstake, Timothy R D J; van Riel, Piet L C M; Li, Yonghong; de Bakker, Paul I W; Gregersen, Peter K; Worthington, Jane; Siminovitch, Katherine A; Klareskog, Lars; Huizinga, Tom W J; Wijmenga, Cisca; Plenge, Robert M

2011-02-01

Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD) and rheumatoid arthritis (RA), but the extent of this sharing has not been systematically explored. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases. We hypothesized that there are additional shared risk alleles and that combining genome-wide association study (GWAS) data from each disease would increase power to identify these shared risk alleles. We performed a meta-analysis of two published GWAS on CD (4,533 cases and 10,750 controls) and RA (5,539 cases and 17,231 controls). After genotyping the top associated SNPs in 2,169 CD cases and 2,255 controls, and 2,845 RA cases and 4,944 controls, 8 additional SNPs demonstrated P<5 × 10(-8) in a combined analysis of all 50,266 samples, including four SNPs that have not been previously confirmed in either disease: rs10892279 near the DDX6 gene (P(combined) =  1.2 × 10(-12)), rs864537 near CD247 (P(combined) =  2.2 × 10(-11)), rs2298428 near UBE2L3 (P(combined) =  2.5 × 10(-10)), and rs11203203 near UBASH3A (P(combined) =  1.1 × 10(-8)). We also confirmed that 4 gene loci previously established in either CD or RA are associated with the other autoimmune disease at combined P<5 × 10(-8) (SH2B3, 8q24, STAT4, and TRAF1-C5). From the 14 shared gene loci, 7 SNPs showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (LD) block around the SNP. These associations implicate antigen presentation and T-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases.

Mice Lacking the Circadian Modulators SHARP1 and SHARP2 Display Altered Sleep and Mixed State Endophenotypes of Psychiatric Disorders

PubMed Central

Shahmoradi, Ali; Reinecke, Lisa; Kroos, Christina; Wichert, Sven P.; Oster, Henrik; Wehr, Michael C.; Taneja, Reshma; Hirrlinger, Johannes; Rossner, Moritz J.

2014-01-01

Increasing evidence suggests that clock genes may be implicated in a spectrum of psychiatric diseases, including sleep and mood related disorders as well as schizophrenia. The bHLH transcription factors SHARP1/DEC2/BHLHE41 and SHARP2/DEC1/BHLHE40 are modulators of the circadian system and SHARP1/DEC2/BHLHE40 has been shown to regulate homeostatic sleep drive in humans. In this study, we characterized Sharp1 and Sharp2 double mutant mice (S1/2-/-) using online EEG recordings in living animals, behavioral assays and global gene expression profiling. EEG recordings revealed attenuated sleep/wake amplitudes and alterations of theta oscillations. Increased sleep in the dark phase is paralleled by reduced voluntary activity and cortical gene expression signatures reveal associations with psychiatric diseases. S1/2-/- mice display alterations in novelty induced activity, anxiety and curiosity. Moreover, mutant mice exhibit impaired working memory and deficits in prepulse inhibition resembling symptoms of psychiatric diseases. Network modeling indicates a connection between neural plasticity and clock genes, particularly for SHARP1 and PER1. Our findings support the hypothesis that abnormal sleep and certain (endo)phenotypes of psychiatric diseases may be caused by common mechanisms involving components of the molecular clock including SHARP1 and SHARP2. PMID:25340473

The importance of social networks in their association to drug equipment sharing among injection drug users: a review.

PubMed

De, Prithwish; Cox, Joseph; Boivin, Jean-François; Platt, Robert W; Jolly, Ann M

2007-11-01

To examine the scientific evidence regarding the association between characteristics of social networks of injection drug users (IDUs) and the sharing of drug injection equipment. A search was performed on MEDLINE, EMBASE, BIOSIS, Current Contents, PsycINFO databases and other sources to identify published studies on social networks of IDUs. Papers were selected based on their examination of social network factors in relation to the sharing of syringes and drug preparation equipment (e.g. containers, filters, water). Additional relevant papers were found from the reference list of identified articles. Network correlates of drug equipment sharing are multi-factorial and include structural factors (network size, density, position, turnover), compositional factors (network member characteristics, role and quality of relationships with members) and behavioural factors (injecting norms, patterns of drug use, severity of drug addiction). Factors appear to be related differentially to equipment sharing. Social network characteristics are associated with drug injection risk behaviours and should be considered alongside personal risk behaviours in prevention programmes. Recommendations for future research into the social networks of IDUs are proposed.

Food-Sharing Networks in Lamalera, Indonesia: Status, Sharing, and Signaling

PubMed Central

Nolin, David A.

2012-01-01

Costly signaling has been proposed as a possible mechanism to explain food sharing in foraging populations. This sharing-as-signaling hypothesis predicts an association between sharing and status. Using exponential random graph modeling (ERGM), this prediction is tested on a social network of between-household food-sharing relationships in the fishing and sea-hunting village of Lamalera, Indonesia. Previous analyses (Nolin 2010) have shown that most sharing in Lamalera is consistent with reciprocal altruism. The question addressed here is whether any additional variation may be explained as sharing-as-signaling by high-status households. The results show that high-status households both give and receive more than other households, a pattern more consistent with reciprocal altruism than costly signaling. However, once the propensity to reciprocate and household productivity are controlled, households of men holding leadership positions show greater odds of unreciprocated giving when compared to households of non-leaders. This pattern of excessive giving by leaders is consistent with the sharing-as-signaling hypothesis. Wealthy households show the opposite pattern, giving less and receiving more than other households. These households may reciprocate in a currency other than food or their wealth may attract favor-seeking behavior from others. Overall, status covariates explain little variation in the sharing network as a whole, and much of the sharing observed by high-status households is best explained by the same factors that explain sharing by other households. This pattern suggests that multiple mechanisms may operate simultaneously to promote sharing in Lamalera and that signaling may motivate some sharing by some individuals even within sharing regimes primarily maintained by other mechanisms. PMID:22822299

Structural Brain Abnormalities in Adolescents with Autism Spectrum Disorder and Patients with Attention Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Brieber, Sarah; Neufang, Susanne; Bruning, Nicole; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Fink, Gereon R.; Konrad, Kerstin

2007-01-01

Background: Although autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are two distinct neurodevelopmental diseases, they share behavioural, neuropsychological and neurobiological characteristics. For the identification of endophenotypes across diagnostic categories, further investigations of phenotypic overlap…

Maternal Psychological Control and Its Association with Mother and Child Perceptions of Adolescent Adjustment: More Evidence on the Strength of Shared Perspectives.

PubMed

Valdes, Olivia M; Laursen, Brett; Guimond, Fanny A; Hartl, Amy C; Denner, Jill

2016-10-01

Mothers and adolescents hold distinct albeit correlated views of their relationship and of one another. The present study focuses on disentangling these independent views. Concurrent associations between maternal psychological control and children's adjustment are examined at two time points in order to identify the degree to which associations reflect (a) views that are shared by mothers and adolescents, and (b) views that are unique to mothers and adolescents. A total of 123 (56 % female) U.S. Latino/a adolescents (M = 10.4 years old at the outset) and their mothers reported on maternal psychological control, children's conduct problems, and children's anxiety, twice within a 5-month period. Data were collected at the close of primary school when the adolescents were in grade 5 and again at the beginning of middle school, when they were in grade 6. Results from conventional correlations indicated that mother- and adolescent-reports yielded similar associations between maternal psychological control and adolescent adjustment. Common fate model analyses partitioned results into variance shared across mother and adolescent reports and variance unique to mother and adolescent reports. Results differed for anxiety and conduct problems. Shared views indicated that greater maternal psychological control was associated with heightened child conduct problems; there were no associations unique to either reporter. In contrast, unique reporter views indicated that greater maternal psychological control was associated with child anxiety; there were no associations involving shared views. Although mother- and adolescent-reports agree that maternal psychological control is correlated with children's adjustment, there is considerable divergence in results when associations are partitioned according to shared and unique reporter views. Associations between maternal psychological control and children's anxiety are more apt to be inflated by same-reporter variance bias than are

Sharing Family Life Information Through Video Calls and Other Information and Communication Technologies and the Association With Family Well-Being: Population-Based Survey

PubMed Central

Shen, Chen; Chu, Joanna TW; Wan, Alice; Viswanath, Kasisomayajula; Chan, Sophia Siu Chee; Lam, Tai Hing

2017-01-01

Background The use of information and communication technologies (ICTs) for information sharing among family members is increasing dramatically. However, little is known about the associated factors and the influence on family well-being. Objective The authors investigated the pattern and social determinants of family life information sharing with family and the associations of different methods of sharing with perceived family health, happiness, and harmony (3Hs) in Hong Kong, where mobile phone ownership and Internet access are among the most prevalent, easiest, and fastest in the world. Methods A territory-wide population-based telephone survey was conducted from January to August 2016 on different methods of family life information (ie, information related to family communication, relationships with family members, emotion and stress management) sharing with family members, including face-to-face, phone, instant messaging (IM), social media sites, video calls, and email. Family well-being was assessed by three single items on perceived family health, happiness, and harmony, with higher scores indicating better family well-being. Adjusted prevalence ratios were used to assess the associations of sociodemographic factors with family life information sharing, and adjusted beta coefficients for family well-being. Results Of 2017 respondents, face-to-face was the most common method to share family life information (74.45%, 1502/2017), followed by IM (40.86%, 824/2017), phone (28.10%, 567/2017), social media sites (11.91%, 240/2017), video calls (5.89%, 119/2017), and email (5.48%, 111/2017). Younger age and higher education were associated with the use of any (at least one) method, face-to-face, IM, and social media sites for sharing family life information (all P for trend <.01). Higher education was most strongly associated with the use of video calls (adjusted prevalence ratio=5.61, 95% CI 2.29-13.74). Higher household income was significantly associated with the

12 CFR 701.35 - Share, share draft, and share certificate accounts.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Share, share draft, and share certificate... AFFECTING CREDIT UNIONS ORGANIZATION AND OPERATION OF FEDERAL CREDIT UNIONS § 701.35 Share, share draft, and share certificate accounts. (a) Federal credit unions may offer share, share draft, and share...

12 CFR 701.35 - Share, share draft, and share certificate accounts.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Share, share draft, and share certificate... AFFECTING CREDIT UNIONS ORGANIZATION AND OPERATION OF FEDERAL CREDIT UNIONS § 701.35 Share, share draft, and share certificate accounts. (a) Federal credit unions may offer share, share draft, and share...

Shared meals among young adults are associated with better diet quality and predicted by family meal patterns during adolescence.

PubMed

Larson, Nicole; Fulkerson, Jayne; Story, Mary; Neumark-Sztainer, Dianne

2013-05-01

To describe shared meal patterns and examine associations with dietary intake among young adults. Population-based, longitudinal cohort study (Project EAT: Eating and Activity in Teens and Young Adults). Participants completed surveys and FFQ in high-school classrooms in Minneapolis/St. Paul, MN, USA in 1998-1999 (mean age = 15·0 years, 'adolescence') and follow-up measures online or by mail in 2008-2009 (mean age = 25·3 years, 'young adulthood'). There were 2052 participants who responded to the 10-year follow-up survey and reported on frequency of having shared meals. Among young adults, the frequency of shared meals during the past week was as follows: never (9·9 %), one or two times (24·7 %), three to six times (39·1 %) and seven or more times (26·3 %). Having more frequent family meals during adolescence predicted a higher frequency of shared meals in young adulthood above and beyond other relevant sociodemographic factors such as household composition and parental status. Compared with young adults who never had family meals during adolescence, those young adults who reported seven or more family meals per week during adolescence had an average of one additional shared meal per week. Having more frequent shared meals in young adulthood was associated with greater intake of fruit among males and females, and with higher intakes of vegetables, milk products and some key nutrients among females. Nutrition professionals should encourage families of adolescents to share meals often and establish the tradition of eating together, and work with young adults to ensure that healthy food and beverage choices are offered at mealtimes.

Shared meals among young adults are associated with better diet quality and predicted by family meal patterns during adolescence

PubMed Central

Fulkerson, Jayne; Story, Mary; Neumark-Sztainer, Dianne

2012-01-01

Objective To describe shared meal patterns and examine associations with dietary intake among young adults. Design Population-based, longitudinal cohort study (Project EAT: Eating and Activity in Teens and Young Adults). Setting Participants completed surveys and food frequency questionnaires in Minneapolis/St. Paul, Minnesota high school classrooms in 1998–1999 (mean age=15.0, “adolescence”) and follow-up measures online or by mail in 2008–2009 (mean age=25.3, “young adulthood”). Subjects There were 2,052 participants who responded to the 10-year follow-up survey and reported on frequency of having shared meals. Results Among young adults, the frequency of shared meals during the past week was as follows: never (9.9%), one or two times (24.7%), three to six times (39.1%), and seven or more times (26.3%). Having more frequent family meals during adolescence predicted a higher frequency of shared meals in young adulthood above and beyond other relevant sociodemographic factors such as household composition and parental status. Compared to young adults who never had family meals during adolescence, those young adults who reported seven or more family meals per week during adolescence had an average of one additional shared meal per week. Having more frequent shared meals in young adulthood was associated with greater intake of fruit among males and females, and with higher intakes of vegetables, milk products, and some key nutrients among females. Conclusions Nutrition professionals should encourage families of adolescents to share meals often and establish the tradition of eating together, and work with young adults to ensure that healthy food and beverage choices are offered at mealtimes. PMID:22857517

Sensation seeking and impulsive traits as personality endophenotypes for antisocial behavior: Evidence from two independent samples

PubMed Central

Mann, Frank D.; Engelhardt, Laura; Briley, Daniel A.; Grotzinger, Andrew D.; Patterson, Megan W.; Tackett, Jennifer L.; Strathan, Dixie B.; Heath, Andrew; Lynskey, Michael; Slutske, Wendy; Martin, Nicholas G.; Tucker-Drob, Elliot M.; Harden, K. Paige

2017-01-01

Sensation seeking and impulsivity are personality traits that are correlated with risk for antisocial behavior (ASB). This paper uses two independent samples of twins to (a) test the extent to which sensation seeking and impulsivity statistically mediate genetic influence on ASB, and (b) compare this to genetic influences accounted for by other personality traits. In Sample 1, delinquent behavior, as well as impulsivity, sensation seeking and Big Five personality traits, were measured in adolescent twins from the Texas Twin Project. In Sample 2, adult twins from the Australian Twin Registry responded to questionnaires that assessed individual differences in Eysenck's and Cloninger's personality dimensions, and a structured telephone interview that asked participants to retrospectively report DSM-defined symptoms of conduct disorder. Bivariate quantitative genetic models were used to identify genetic overlap between personality traits and ASB. Across both samples, novelty/sensation seeking and impulsive traits accounted for larger portions of genetic variance in ASB than other personality traits. We discuss whether sensation seeking and impulsive personality are causal endophenotypes for ASB, or merely index genetic liability for ASB. PMID:28824215

Association between drug insurance cost sharing strategies and outcomes in patients with chronic diseases: a systematic review.

PubMed

Mann, Bikaramjit S; Barnieh, Lianne; Tang, Karen; Campbell, David J T; Clement, Fiona; Hemmelgarn, Brenda; Tonelli, Marcello; Lorenzetti, Diane; Manns, Braden J

2014-01-01

Prescription drugs are used in people with hypertension, diabetes, and cardiovascular disease to manage their illness. Patient cost sharing strategies such as copayments and deductibles are often employed to lower expenditures for prescription drug insurance plans, but the impact on health outcomes in these patients is unclear. To determine the association between drug insurance and patient cost sharing strategies on medication adherence, clinical and economic outcomes in those with chronic diseases (defined herein as diabetes, hypertension, hypercholesterolemia, coronary artery disease, and cerebrovascular disease). Studies were included if they examined various cost sharing strategies including copayments, coinsurance, fixed copayments, deductibles and maximum out-of-pocket expenditures. Value-based insurance design and reference based pricing studies were excluded. Two reviewers independently identified original intervention studies (randomized controlled trials, interrupted time series, and controlled before-after designs). MEDLINE, EMBASE, Cochrane Library, CINAHL, and relevant reference lists were searched until March 2013. Two reviewers independently assessed studies for inclusion, quality, and extracted data. Eleven studies, assessing the impact of seven policy changes, were included: 2 separate reports of one randomized controlled trial, 4 interrupted time series, and 5 controlled before-after studies. Outcomes included medication adherence, clinical events (myocardial infarction, stroke, death), quality of life, healthcare utilization, or cost. The heterogeneity among the studies precluded meta-analysis. Few studies reported the impact of cost sharing strategies on mortality, clinical and economic outcomes. The association between patient copayments and medication adherence varied across studies, ranging from no difference to significantly lower adherence, depending on the amount of the copayment. Lowering cost sharing in patients with chronic diseases

Involvement of shared mucosal-associated microbiota in the duodenum and rectum in diarrhea-predominant irritable bowel syndrome.

PubMed

Li, Gangping; Yang, Min; Jin, Yu; Li, Ying; Qian, Wei; Xiong, Hanhua; Song, Jun; Hou, Xiaohua

2018-06-01

Most studies of diarrhea-predominant irritable bowel syndrome (IBS-D) focused on microbiota dysbiosis in a single segment of the intestine such as the colon. However, the intestine as a whole is involved in IBS-D and knowledge about the role of microbiota shared by the duodenum and rectum in IBS-D is limited. Here, we investigated the characteristics of mucosal microbiota shared by the duodenum and rectum in IBS-D patients. We collected duodenal and rectal mucosal samples from 33 adult IBS-D patients and 15 healthy control (HC) subjects. The 454 pyrosequencing method and multiple bioinformatics analyses were used to examine bacterial 16S rRNA. Clinical data including symptoms and Bristol Stool Form were analyzed. Mucosal microbiota in duodenal samples differed from rectal samples in HC, while less difference was shown in IBS-D. More numbers in terms of shared operational taxonomic units and genera found in IBS-D compared with HC. The frequency of genera in the duodenum and rectum of HC differed from that of IBS-D. We identified 24 genera shared in the duodenum and rectum, which both changed dramatically in IBS-D. Among these 24 genera, half had similar trends in frequency differences, and the other half had opposite trends. The frequency of Faecalibacterium and Hyphomicrobium were associated with clinical data of IBS-D patients. Shared mucosal-associated microbiota in the duodenum and rectum appear to contribute to the etiology and pathophysiology of whole intestine of IBS-D and to be potential therapeutic targets. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Sharing Family Life Information Through Video Calls and Other Information and Communication Technologies and the Association With Family Well-Being: Population-Based Survey.

PubMed

Shen, Chen; Wang, Man Ping; Chu, Joanna Tw; Wan, Alice; Viswanath, Kasisomayajula; Chan, Sophia Siu Chee; Lam, Tai Hing

2017-11-23

The use of information and communication technologies (ICTs) for information sharing among family members is increasing dramatically. However, little is known about the associated factors and the influence on family well-being. The authors investigated the pattern and social determinants of family life information sharing with family and the associations of different methods of sharing with perceived family health, happiness, and harmony (3Hs) in Hong Kong, where mobile phone ownership and Internet access are among the most prevalent, easiest, and fastest in the world. A territory-wide population-based telephone survey was conducted from January to August 2016 on different methods of family life information (ie, information related to family communication, relationships with family members, emotion and stress management) sharing with family members, including face-to-face, phone, instant messaging (IM), social media sites, video calls, and email. Family well-being was assessed by three single items on perceived family health, happiness, and harmony, with higher scores indicating better family well-being. Adjusted prevalence ratios were used to assess the associations of sociodemographic factors with family life information sharing, and adjusted beta coefficients for family well-being. Of 2017 respondents, face-to-face was the most common method to share family life information (74.45%, 1502/2017), followed by IM (40.86%, 824/2017), phone (28.10%, 567/2017), social media sites (11.91%, 240/2017), video calls (5.89%, 119/2017), and email (5.48%, 111/2017). Younger age and higher education were associated with the use of any (at least one) method, face-to-face, IM, and social media sites for sharing family life information (all P for trend <.01). Higher education was most strongly associated with the use of video calls (adjusted prevalence ratio=5.61, 95% CI 2.29-13.74). Higher household income was significantly associated with the use of any method, face-to-face, and

Bed-sharing, breastfeeding and maternal moods in Barbados.

PubMed

Galler, Janina R; Harrison, Robert H; Ramsey, Frank

2006-12-01

Bed-sharing among Barbadian mothers and infants was studied in relationship to maternal and infant characteristics. This prospective study followed 226 healthy, well-nourished mother-infant dyads at birth, 7 weeks, 3 months, and 6 months postpartum. At each age, approximately half of the infants shared the same beds as their mothers. Bed-sharing was associated with demographic characteristics, especially fewer home conveniences, and also maternal characteristics, including less information seeking by the mother and younger maternal age at first pregnancy. Bed-sharing was also associated with lower infant birth weights. Maternal moods were significantly correlated with bed-sharing, such that mothers who reported having more despair and anxiety were also more likely to sleep with their infants. Bed-sharing was also significantly associated with increased breastfeeding at all infant ages, but this relationship was no longer significant once the effects of maternal moods were controlled. This study emphasizes the importance of assessing maternal moods in studies evaluating the risk and benefits of bed-sharing.

Recurrent major depression and right hippocampal volume: A bivariate linkage and association study.

PubMed

Mathias, Samuel R; Knowles, Emma E M; Kent, Jack W; McKay, D Reese; Curran, Joanne E; de Almeida, Marcio A A; Dyer, Thomas D; Göring, Harald H H; Olvera, Rene L; Duggirala, Ravi; Fox, Peter T; Almasy, Laura; Blangero, John; Glahn, David C

2016-01-01

Previous work has shown that the hippocampus is smaller in the brains of individuals suffering from major depressive disorder (MDD) than those of healthy controls. Moreover, right hippocampal volume specifically has been found to predict the probability of subsequent depressive episodes. This study explored the utility of right hippocampal volume as an endophenotype of recurrent MDD (rMDD). We observed a significant genetic correlation between the two traits in a large sample of Mexican American individuals from extended pedigrees (ρg = -0.34, p = 0.013). A bivariate linkage scan revealed a significant pleiotropic quantitative trait locus on chromosome 18p11.31-32 (LOD = 3.61). Bivariate association analysis conducted under the linkage peak revealed a variant (rs574972) within an intron of the gene SMCHD1 meeting the corrected significance level (χ(2) = 19.0, p = 7.4 × 10(-5)). Univariate association analyses of each phenotype separately revealed that the same variant was significant for right hippocampal volume alone, and also revealed a suggestively significant variant (rs12455524) within the gene DLGAP1 for rMDD alone. The results implicate right-hemisphere hippocampal volume as a possible endophenotype of rMDD, and in so doing highlight a potential gene of interest for rMDD risk. © 2015 Wiley Periodicals, Inc.

12 CFR 701.35 - Share, share draft, and share certificate accounts.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AFFECTING CREDIT UNIONS ORGANIZATION AND OPERATION OF FEDERAL CREDIT UNIONS § 701.35 Share, share draft, and share certificate accounts. (a) Federal credit unions may offer share, share draft, and share...) A Federal credit union shall accurately represent the terms and conditions of its share, share draft...

12 CFR 701.35 - Share, share draft, and share certificate accounts.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AFFECTING CREDIT UNIONS ORGANIZATION AND OPERATION OF FEDERAL CREDIT UNIONS § 701.35 Share, share draft, and share certificate accounts. (a) Federal credit unions may offer share, share draft, and share...) A Federal credit union shall accurately represent the terms and conditions of its share, share draft...

12 CFR 701.35 - Share, share draft, and share certificate accounts.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AFFECTING CREDIT UNIONS ORGANIZATION AND OPERATION OF FEDERAL CREDIT UNIONS § 701.35 Share, share draft, and share certificate accounts. (a) Federal credit unions may offer share, share draft, and share...) A Federal credit union shall accurately represent the terms and conditions of its share, share draft...

Sharing without caring? Respect for moral others compensates for low sympathy in children's sharing.

PubMed

Zuffianò, Antonio; Colasante, Tyler; Peplak, Joanna; Malti, Tina

2015-06-01

We examined links between sharing, respect for moral others, and sympathy in an ethnically diverse sample of 7- and 15-year-olds (N = 146). Sharing was assessed through children's allocation of resources in the dictator game. Children reported their respect towards hypothetical characters performing moral acts. Sympathy was evaluated via caregiver and child reports. Respect and caregiver-reported sympathy interacted in predicting sharing: Higher levels of respect were associated with higher levels of sharing for children with low, but not medium or high, levels of sympathy. The motivational components of other-oriented respect may compensate for low levels of sympathetic concern in the promotion of sharing. © 2015 The British Psychological Society.

Promoting physical activity through the shared use of school recreational spaces: a policy statement from the American Heart Association.

PubMed

Young, Deborah R; Spengler, John O; Frost, Natasha; Evenson, Kelly R; Vincent, Jeffrey M; Whitsel, Laurie

2014-09-01

Most Americans are not sufficiently physically active, even though regular physical activity improves health and reduces the risk of many chronic diseases. Those living in rural, non-White, and lower-income communities often have insufficient access to places to be active, which can contribute to their lower level of physical activity. The shared use of school recreational facilities can provide safe and affordable places for communities. Studies suggest that challenges to shared use include additional cost, liability protection, communication among constituencies interested in sharing space, and decision-making about scheduling and space allocation. This American Heart Association policy statement has provided recommendations for federal, state, and local decision-makers to support and expand opportunities for physical activity in communities through the shared use of school spaces.

A Qualitative Analysis of Real-Time Continuous Glucose Monitoring Data Sharing with Care Partners: To Share or Not to Share?

PubMed

Litchman, Michelle L; Allen, Nancy A; Colicchio, Vanessa D; Wawrzynski, Sarah E; Sparling, Kerri M; Hendricks, Krissa L; Berg, Cynthia A

2018-01-01

Little research exists regarding how real-time continuous glucose monitoring (RT-CGM) data sharing plays a role in the relationship between patients and their care partners. To (1) identify the benefits and challenges related to RT-CGM data sharing from the patient and care partner perspective and (2) to explore the number and type of individuals who share and follow RT-CGM data. This qualitative content analysis was conducted by examining publicly available blogs focused on RT-CGM and data sharing. A thematic analysis of blogs and associated comments was conducted. A systematic appraisal of personal blogs examined 39 blogs with 206 corresponding comments. The results of the study provided insight about the benefits and challenges related to individuals with diabetes sharing their RT-CGM data with a care partner(s). The analysis resulted in three themes: (1) RT-CGM data sharing enhances feelings of safety, (2) the need to communicate boundaries to avoid judgment, and (3) choice about sharing and following RT-CGM data. RT-CGM data sharing occurred within dyads (n = 46), triads (n = 15), and tetrads (n = 2). Adults and children with type 1 diabetes and their care partners are empowered by the ability to share and follow RT-CGM data. Our findings suggest that RT-CGM data sharing between an individual with diabetes and their care partner can complicate relationships. Healthcare providers need to engage patients and care partners in discussions about best practices related to RT-CGM sharing and following to avoid frustrations within the relationship.

Share capitalism and worker wellbeing.

PubMed

Bryson, Alex; Clark, Andrew E; Freeman, Richard B; Green, Colin P

2016-10-01

We show that worker wellbeing is determined not only by the amount of compensation workers receive but also by how compensation is determined. While previous theoretical and empirical work has often been preoccupied with individual performance-related pay, we find that the receipt of a range of group-performance schemes (profit shares, group bonuses and share ownership) is associated with higher job satisfaction. This holds conditional on wage levels, so that pay methods are associated with greater job satisfaction in addition to that coming from higher wages. We use a variety of methods to control for unobserved individual and job-specific characteristics. We suggest that half of the share-capitalism effect is accounted for by employees reciprocating for the "gift"; we also show that share capitalism helps dampen the negative wellbeing effects of what we typically think of as "bad" aspects of job quality.

Can Genetic Analysis of Putative Blood Alzheimer’s Disease Biomarkers Lead to Identification of Susceptibility Loci?

PubMed Central

Huebinger, Ryan M.; Shewale, Shantanu J.; Koenig, Jessica L.; Mitchel, Jeffrey S.; O’Bryant, Sid E.; Waring, Stephen C.; Diaz-Arrastia, Ramon; Chasse, Scott

2015-01-01

Although 24 Alzheimer’s disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10-7. Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel

Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci?

PubMed

Barber, Robert C; Phillips, Nicole R; Tilson, Jeffrey L; Huebinger, Ryan M; Shewale, Shantanu J; Koenig, Jessica L; Mitchel, Jeffrey S; O'Bryant, Sid E; Waring, Stephen C; Diaz-Arrastia, Ramon; Chasse, Scott; Wilhelmsen, Kirk C

2015-01-01

Although 24 Alzheimer's disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10(-7). Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel

Root-associated fungal communities in three Pyroleae species and their mycobiont sharing with surrounding trees in subalpine coniferous forests on Mount Fuji, Japan.

PubMed

Jia, Shuzheng; Nakano, Takashi; Hattori, Masahira; Nara, Kazuhide

2017-11-01

Pyroleae species are perennial understory shrubs, many of which are partial mycoheterotrophs. Most fungi colonizing Pyroleae roots are ectomycorrhizal (ECM) and share common mycobionts with their Pyroleae hosts. However, such mycobiont sharing has neither been examined in depth before nor has the interspecific variation in sharing among Pyroleae species. Here, we examined root-associated fungal communities in three co-existing Pyroleae species, including Pyrola alpina, Pyrola incarnata, and Orthilia secunda, with reference to co-existing ECM fungi on the surrounding trees in the same soil blocks in subalpine coniferous forests. We identified 42, 75, and 18 fungal molecular operational taxonomic units in P. alpina, P. incarnata, and O. secunda roots, respectively. Mycobiont sharing with surrounding trees, which was defined as the occurrence of the same mycobiont between Pyroleae and surrounding trees in each soil block, was most frequent among P. incarnata (31 of 44 plants). In P. alpina, sharing was confirmed in 12 of 37 plants, and the fungal community was similar to that of P. incarnata. Mycobiont sharing was least common in O. secunda, found in only 5 of 32 plants. Root-associated fungi of O. secunda were dominated by Wilcoxina species, which were absent from the surrounding ECM roots in the same soil blocks. These results indicate that mycobiont sharing with surrounding trees does not equally occur among Pyroleae plants, some of which may develop independent mycorrhizal associations with ECM fungi, as suggested in O. secunda at our research sites.

Promoting Physical Activity Through the Shared Use of School Recreational Spaces: A Policy Statement From the American Heart Association

PubMed Central

Young, Deborah R.; Spengler, John O.; Frost, Natasha; Evenson, Kelly R.; Vincent, Jeffrey M.; Whitsel, Laurie

2014-01-01

Most Americans are not sufficiently physically active, even though regular physical activity improves health and reduces the risk of many chronic diseases. Those living in rural, non-White, and lower-income communities often have insufficient access to places to be active, which can contribute to their lower level of physical activity. The shared use of school recreational facilities can provide safe and affordable places for communities. Studies suggest that challenges to shared use include additional cost, liability protection, communication among constituencies interested in sharing space, and decision-making about scheduling and space allocation. This American Heart Association policy statement has provided recommendations for federal, state, and local decision-makers to support and expand opportunities for physical activity in communities through the shared use of school spaces. PMID:24134355

The Association Between Law Enforcement Encounters and Syringe Sharing Among IDUs on Skid Row: A Mixed Methods Analysis

PubMed Central

Simon-Freeman, Rebecca; Bluthenthal, Ricky N.

2013-01-01

The legal environment is one factor that influences injection drug users' (IDUs) risk for HIV and other bloodborne pathogens such as hepatitis C virus (HCV). We examined the association between law enforcement encounters (i.e., arrests and citations) and receptive syringe sharing among IDUs in the context of an intensified policing effort. We conducted a mixed methods analysis of 30 qualitative and 187 quantitative interviews with IDUs accessing services at a Los Angeles, CA syringe exchange program from 2008 to 2009. Qualitative findings illustrate concerns related to visibility, drug withdrawal, and previous history of arrest/incarceration. In quantitative analysis, the number of citations received, current homelessness, and perceiving that being arrested would be a “big problem” were independently associated with recent syringe sharing. Findings illustrate some of the unintended public health consequences associated with intensified street-level policing, including risk for HIV and HCV transmission. PMID:23620243

Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression.

PubMed

Zeng, Yanni; Navarro, Pau; Xia, Charley; Amador, Carmen; Fernandez-Pujals, Ana M; Thomson, Pippa A; Campbell, Archie; Nagy, Reka; Clarke, Toni-Kim; Hafferty, Jonathan D; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; MacIntyre, Donald J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M

2016-12-01

Both genetic and environmental factors contribute to risk of depression, but estimates of their relative contributions are limited. Commonalities between clinically-assessed major depressive disorder (MDD) and self-declared depression (SDD) are also unclear. Using data from a large Scottish family-based cohort (GS:SFHS, N=19,994), we estimated the genetic and environmental variance components for MDD and SDD. The components representing the genetic effect associated with genome-wide common genetic variants (SNP heritability), the additional pedigree-associated genetic effect and non-genetic effects associated with common environments were estimated in a linear mixed model (LMM). Both MDD and SDD had significant contributions from components representing the effect from common genetic variants, the additional genetic effect associated with the pedigree and the common environmental effect shared by couples. The estimate of correlation between SDD and MDD was high (r=1.00, se=0.20) for common-variant-associated genetic effect and lower for the additional genetic effect from the pedigree (r=0.57, se=0.08) and the couple-shared environmental effect (r=0.53, se=0.22). Both genetics and couple-shared environmental effects were major factors influencing liability to depression. SDD may provide a scalable alternative to MDD in studies seeking to identify common risk variants. Rarer variants and environmental effects may however differ substantially according to different definitions of depression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Collaborative Sharing of Multidimensional Space-time Data Using HydroShare

NASA Astrophysics Data System (ADS)

Gan, T.; Tarboton, D. G.; Horsburgh, J. S.; Dash, P. K.; Idaszak, R.; Yi, H.; Blanton, B.

2015-12-01

libraries for working with NetCDF files. We describe the design and implementation of these features and illustrate how NetCDF files from a modeling application may be curated in HydroShare and thus enhance reproducibility of the associated research. We also discuss future development planned for multidimensional space-time data in HydroShare.

Association of Cost Sharing With Mental Health Care Use, Involuntary Commitment, and Acute Care.

PubMed

Ravesteijn, Bastian; Schachar, Eli B; Beekman, Aartjan T F; Janssen, Richard T J M; Jeurissen, Patrick P T

2017-09-01

A higher out-of-pocket price for mental health care may lead not only to cost savings but also to negative downstream consequences. To examine the association of higher patient cost sharing with mental health care use and downstream effects, such as involuntary commitment and acute mental health care use. This difference-in-differences study compared changes in mental health care use by adults, who experienced an increase in cost sharing, with changes in youths, who did not experience the increase and thus formed a control group. The study examined all 2 780 558 treatment records opened from January 1, 2010, through December 31, 2012, by 110 organizations that provide specialist mental health care in the Netherlands. Data analysis was performed from January 18, 2016, to May 9, 2017. On January 1, 2012, the Dutch national government increased the out-of-pocket price of mental health services for adults by up to €200 (US$226) per year for outpatient treatment and €150 (US$169) per month for inpatient treatment. The number of treatment records opened each day in regular specialist mental health care, involuntary commitment, and acute mental health care, and annual specialist mental health care spending. This study included 1 448 541 treatment records opened from 2010 to 2012 (mean [SD] age, 41.4 [16.7] years; 712 999 men and 735 542 women). The number of regular mental health care records opened for adults decreased abruptly and persistently by 13.4% (95% CI, -16.0% to -10.8%; P < .001) per day when cost sharing was increased in 2012. The decrease was substantial and significant for severe and mild disorders and larger in low-income than in high-income neighborhoods. Simultaneously, in 2012, daily record openings increased for involuntary commitment by 96.8% (95% CI, 87.7%-105.9%; P < .001) and for acute mental health care by 25.1% (95% CI, 20.8%-29.4%; P < .001). In contrast to our findings for adults, the use of regular care among youths

Genome-wide association study of CSF levels of 59 alzheimer's disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation.

PubMed

Kauwe, John S K; Bailey, Matthew H; Ridge, Perry G; Perry, Rachel; Wadsworth, Mark E; Hoyt, Kaitlyn L; Staley, Lyndsay A; Karch, Celeste M; Harari, Oscar; Cruchaga, Carlos; Ainscough, Benjamin J; Bales, Kelly; Pickering, Eve H; Bertelsen, Sarah; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M

2014-10-01

Cerebrospinal fluid (CSF) 42 amino acid species of amyloid beta (Aβ42) and tau levels are strongly correlated with the presence of Alzheimer's disease (AD) neuropathology including amyloid plaques and neurodegeneration and have been successfully used as endophenotypes for genetic studies of AD. Additional CSF analytes may also serve as useful endophenotypes that capture other aspects of AD pathophysiology. Here we have conducted a genome-wide association study of CSF levels of 59 AD-related analytes. All analytes were measured using the Rules Based Medicine Human DiscoveryMAP Panel, which includes analytes relevant to several disease-related processes. Data from two independently collected and measured datasets, the Knight Alzheimer's Disease Research Center (ADRC) and Alzheimer's Disease Neuroimaging Initiative (ADNI), were analyzed separately, and combined results were obtained using meta-analysis. We identified genetic associations with CSF levels of 5 proteins (Angiotensin-converting enzyme (ACE), Chemokine (C-C motif) ligand 2 (CCL2), Chemokine (C-C motif) ligand 4 (CCL4), Interleukin 6 receptor (IL6R) and Matrix metalloproteinase-3 (MMP3)) with study-wide significant p-values (p<1.46×10-10) and significant, consistent evidence for association in both the Knight ADRC and the ADNI samples. These proteins are involved in amyloid processing and pro-inflammatory signaling. SNPs associated with ACE, IL6R and MMP3 protein levels are located within the coding regions of the corresponding structural gene. The SNPs associated with CSF levels of CCL4 and CCL2 are located in known chemokine binding proteins. The genetic associations reported here are novel and suggest mechanisms for genetic control of CSF and plasma levels of these disease-related proteins. Significant SNPs in ACE and MMP3 also showed association with AD risk. Our findings suggest that these proteins/pathways may be valuable therapeutic targets for AD. Robust associations in cognitively normal

12 CFR 563b.505 - May my directors, officers, and their associates freely trade shares?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 5 2011-01-01 2011-01-01 false May my directors, officers, and their associates freely trade shares? 563b.505 Section 563b.505 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY CONVERSIONS FROM MUTUAL TO STOCK FORM Standard Conversions Post-Conversion § 563b.505 May my directors, officers, and their...

12 CFR 563b.505 - May my directors, officers, and their associates freely trade shares?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 6 2012-01-01 2012-01-01 false May my directors, officers, and their associates freely trade shares? 563b.505 Section 563b.505 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY CONVERSIONS FROM MUTUAL TO STOCK FORM Standard Conversions Post-Conversion § 563b.505 May my directors, officers, and their...

Animal Models of Maladaptive Traits: Disorders in Sensorimotor Gating and Attentional Quantifiable Responses as Possible Endophenotypes

PubMed Central

Vargas, Juan P.; Díaz, Estrella; Portavella, Manuel; López, Juan C.

2016-01-01

Traditional diagnostic scales are based on a number of symptoms to evaluate and classify mental diseases. In many cases, this process becomes subjective, since the patient must calibrate the magnitude of his/her symptoms and therefore the severity of his/her disorder. A completely different approach is based on the study of the more vulnerable traits of cognitive disorders. In this regard, animal models of mental illness could be a useful tool to characterize indicators of possible cognitive dysfunctions in humans. Specifically, several cognitive disorders such as schizophrenia involve a dysfunction in the mesocorticolimbic dopaminergic system during development. These variations in dopamine levels or dopamine receptor sensibility correlate with many behavioral disturbances. These behaviors may be included in a specific phenotype and may be analyzed under controlled conditions in the laboratory. The present study provides an introductory overview of different quantitative traits that could be used as a possible risk indicator for different mental disorders, helping to define a specific endophenotype. Specifically, we examine different experimental procedures to measure impaired response in attention linked to sensorimotor gating as a possible personality trait involved in maladaptive behaviors. PMID:26925020

Block design reconstruction skills: not a good candidate for an endophenotypic marker in autism research.

PubMed

de Jonge, Maretha; Kemner, Chantal; Naber, Fabienne; van Engeland, Herman

2009-04-01

Superior performance on block design tasks is reported in autistic individuals, although it is not consistently found in high-functioning individuals or individuals with Asperger Syndrome. It is assumed to reflect weak central coherence: an underlying cognitive deficit, which might also be part of the genetic makeup of the disorder. We assessed block design reconstruction skills in high-functioning individuals with autism spectrum disorders (ASD) from multi-incidence families and in their parents. Performance was compared to relevant matched control groups. We used a task that was assumed to be highly sensitive to subtle performance differences. We did not find individuals with ASD to be significantly faster on this task than the matched control group, not even when the difference between reconstruction time of segmented and pre-segmented designs was compared. However, we found individuals with ASD to make fewer errors during the process of reconstruction which might indicate some dexterity in mental segmentation. However, parents of individuals with ASD did not perform better on the task than control parents. Therefore, based on our data, we conclude that mental segmentation ability as measured with a block design reconstruction task is not a neurocognitive marker or endophenotype useful in genetic studies.

An 8 year study of risk factors for SIDS: bed‐sharing versus non‐bed‐sharing

PubMed Central

McGarvey, C; McDonnell, M; Hamilton, K; O'Regan, M; Matthews, T

2006-01-01

Background It is unclear if it is safe for babies to bed share with adults. In Ireland 49% of sudden infant death syndrome (SIDS) cases occur when the infant is bed‐sharing with an adult. Objective To evaluate the effect of bed‐sharing during the last sleep period on risk factors for SIDS in Irish infants. Design An 8 year (1994–2001) population based case control study of 287 SIDS cases and 831 controls matched for date, place of birth, and sleep period. Odds ratios and 95% confidence intervals were calculated by conditional logistic regression. Results The risk associated with bed‐sharing was three times greater for infants with low birth weight for gestation (UOR 16.28 v 4.90) and increased fourfold if the combined tog value of clothing and bedding was ⩾10 (UOR 9.68 v 2.34). The unadjusted odds ratio for bed‐sharing was 13.87 (95% CI 9.58 to 20.09) for infants whose mothers smoked and 2.09 (95% CI 0.98 to 4.39) for non‐smokers. Age of death for bed‐sharing and sofa‐sharing infants (12.8 and 8.3 weeks, respectively) was less than for infants not sharing a sleep surface (21.0 weeks, p<0.001) and fewer bed‐sharing cases were found prone (5% v 32%; p = 0.001). Conclusion Risk factors for SIDS vary according to the infant's sleeping environment. The increased risk associated with maternal smoking, high tog value of clothing and bedding, and low z scores of weight for gestation at birth is augmented further by bed‐sharing. These factors should be taken into account when considering sleeping arrangements for young infants. PMID:16243855

Influence of sex and stress exposure across the lifespan on endophenotypes of depression: focus on behavior, glucocorticoids, and hippocampus

PubMed Central

Gobinath, Aarthi R.; Mahmoud, Rand; Galea, Liisa A.M.

2015-01-01

Sex differences exist in vulnerability, symptoms, and treatment of many neuropsychiatric disorders. In this review, we discuss both preclinical and clinical research that investigates how sex influences depression endophenotypes at the behavioral, neuroendocrine, and neural levels across the lifespan. Chronic exposure to stress is a risk factor for depression and we discuss how stress during the prenatal, postnatal, and adolescent periods differentially affects males and females depending on the method of stress and metric examined. Given that the integrity of the hippocampus is compromised in depression, we specifically focus on sex differences in how hippocampal plasticity is affected by stress and depression across the lifespan. In addition, we examine how female physiology predisposes depression in adulthood, specifically in postpartum and perimenopausal periods. Finally, we discuss the underrepresentation of women in both preclinical and clinical research and how this limits our understanding of sex differences in vulnerability, presentation, and treatment of depression. PMID:25610363

Knowledge-driven binning approach for rare variant association analysis: application to neuroimaging biomarkers in Alzheimer's disease.

PubMed

Kim, Dokyoon; Basile, Anna O; Bang, Lisa; Horgusluoglu, Emrin; Lee, Seunggeun; Ritchie, Marylyn D; Saykin, Andrew J; Nho, Kwangsik

2017-05-18

Rapid advancement of next generation sequencing technologies such as whole genome sequencing (WGS) has facilitated the search for genetic factors that influence disease risk in the field of human genetics. To identify rare variants associated with human diseases or traits, an efficient genome-wide binning approach is needed. In this study we developed a novel biological knowledge-based binning approach for rare-variant association analysis and then applied the approach to structural neuroimaging endophenotypes related to late-onset Alzheimer's disease (LOAD). For rare-variant analysis, we used the knowledge-driven binning approach implemented in Bin-KAT, an automated tool, that provides 1) binning/collapsing methods for multi-level variant aggregation with a flexible, biologically informed binning strategy and 2) an option of performing unified collapsing and statistical rare variant analyses in one tool. A total of 750 non-Hispanic Caucasian participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort who had both WGS data and magnetic resonance imaging (MRI) scans were used in this study. Mean bilateral cortical thickness of the entorhinal cortex extracted from MRI scans was used as an AD-related neuroimaging endophenotype. SKAT was used for a genome-wide gene- and region-based association analysis of rare variants (MAF (minor allele frequency) < 0.05) and potential confounding factors (age, gender, years of education, intracranial volume (ICV) and MRI field strength) for entorhinal cortex thickness were used as covariates. Significant associations were determined using FDR adjustment for multiple comparisons. Our knowledge-driven binning approach identified 16 functional exonic rare variants in FANCC significantly associated with entorhinal cortex thickness (FDR-corrected p-value < 0.05). In addition, the approach identified 7 evolutionary conserved regions, which were mapped to FAF1, RFX7, LYPLAL1 and GOLGA3, significantly associated

What Factors are Associated with Consumer Initiation of Shared Decision Making in Mental Health Visits?

PubMed Central

Matthias, Marianne S.; Fukui, Sadaaki; Salyers, Michelle P.

2016-01-01

Understanding consumer initiation of shared decision making (SDM) is critical to improving SDM in mental health consultations, particularly because providers do not always invite consumer participation in treatment decisions. This study examined the association between consumer initiation of nine elements of SDM as measured by the SDM scale, and measures of consumer illness self-management and the consumer-provider relationship. In 63 mental health visits, three SDM elements were associated with self-management or relationship factors: discussion of consumer goals, treatment alternatives, and pros and cons of a decision. Limitations, implications, and future directions are discussed. PMID:26427999

What Factors are Associated with Consumer Initiation of Shared Decision Making in Mental Health Visits?

PubMed

Matthias, Marianne S; Fukui, Sadaaki; Salyers, Michelle P

2017-01-01

Understanding consumer initiation of shared decision making (SDM) is critical to improving SDM in mental health consultations, particularly because providers do not always invite consumer participation in treatment decisions. This study examined the association between consumer initiation of nine elements of SDM as measured by the SDM scale, and measures of consumer illness self-management and the consumer-provider relationship. In 63 mental health visits, three SDM elements were associated with self-management or relationship factors: discussion of consumer goals, treatment alternatives, and pros and cons of a decision. Limitations, implications, and future directions are discussed.

Loss of function studies in mice and genetic association link receptor protein tyrosine phosphatase α to schizophrenia

PubMed Central

Takahashi, Nagahide; Nielsen, Karin Sandager; Aleksic, Branko; Petersen, Steffen; Ikeda, Masashi; Kushima, Itaru; Vacaresse, Nathalie; Ujike, Hiroshi; Iwata, Nakao; Dubreuil, Véronique; Mirza, Naheed; Sakurai, Takeshi; Ozaki, Norio; Buxbaum, Joseph D.; Sap, Jan

2011-01-01

Background Solid evidence links schizophrenia (SZ) susceptibility to neurodevelopmental processes involving tyrosine phosphorylation-mediated signaling. Mouse studies implicate the Ptpra gene, encoding protein tyrosine phosphatase RPTPα, in the control of radial neuronal migration, cortical cytoarchitecture, and oligodendrocyte differentiation. The human gene encoding RPTPα, PTPRA, maps to a chromosomal region (20p13) associated with susceptibility to psychotic illness. Methods We characterized neurobehavioral parameters, as well as gene expression in the central nervous system, of mice with a null mutation in the Ptpra gene. We searched for genetic association between polymorphisms in PTPRA and schizophrenia risk (2 independent cohorts; total of 1420 cases and 1377 controls), and we monitored PTPRA expression in prefrontal dorsolateral cortex of SZ patients (35 cases, 2 control groups of 35 cases) Results We find that Ptpra−/− mice reproduce neurobehavioral endophenotypes of human SZ: sensitization to metamphetamine-induced hyperactivity, defective sensorimotor gating, and defective habituation to a startle response. Ptpra loss of function also leads to reduced expression of multiple myelination genes, mimicking the hypomyelination-associated changes in gene expression observed in post mortem patient brains. We further report that a polymorphism at the PTPRA locus is genetically associated with SZ, and that PTPRA mRNA levels are reduced in post mortem dorsolateral prefrontal cortex of subjects with SZ. Conclusion The implication of this well-studied signaling protein in SZ risk and endophenotype manifestation provides novel entry points into the etiopathology of this disease. PMID:21831360

Association of Cost Sharing With Mental Health Care Use, Involuntary Commitment, and Acute Care

PubMed Central

Schachar, Eli B.; Beekman, Aartjan T. F.; Janssen, Richard T. J. M.; Jeurissen, Patrick P. T.

2017-01-01

Importance A higher out-of-pocket price for mental health care may lead not only to cost savings but also to negative downstream consequences. Objective To examine the association of higher patient cost sharing with mental health care use and downstream effects, such as involuntary commitment and acute mental health care use. Design, Setting, and Participants This difference-in-differences study compared changes in mental health care use by adults, who experienced an increase in cost sharing, with changes in youths, who did not experience the increase and thus formed a control group. The study examined all 2 780 558 treatment records opened from January 1, 2010, through December 31, 2012, by 110 organizations that provide specialist mental health care in the Netherlands. Data analysis was performed from January 18, 2016, to May 9, 2017. Exposures On January 1, 2012, the Dutch national government increased the out-of-pocket price of mental health services for adults by up to €200 (US$226) per year for outpatient treatment and €150 (US$169) per month for inpatient treatment. Main Outcomes and Measures The number of treatment records opened each day in regular specialist mental health care, involuntary commitment, and acute mental health care, and annual specialist mental health care spending. Results This study included 1 448 541 treatment records opened from 2010 to 2012 (mean [SD] age, 41.4 [16.7] years; 712 999 men and 735 542 women). The number of regular mental health care records opened for adults decreased abruptly and persistently by 13.4% (95% CI, −16.0% to −10.8%; P < .001) per day when cost sharing was increased in 2012. The decrease was substantial and significant for severe and mild disorders and larger in low-income than in high-income neighborhoods. Simultaneously, in 2012, daily record openings increased for involuntary commitment by 96.8% (95% CI, 87.7%-105.9%; P < .001) and for acute mental health care by 25.1% (95% CI, 20

ASSOCIATION BETWEEN GAB2 HAPLOTYPE AND HIGHER GLUCOSE METABOLISM IN ALZHEIMER'S DISEASE-AFFECTED BRAIN REGIONS IN COGNITIVELY NORMAL APOEε4 CARRIERS

PubMed Central

Liang, Winnie S.; Chen, Kewei; Lee, Wendy; Sidhar, Kunal; Corneveaux, Jason J.; Allen, April N.; Myers, Amanda; Villa, Stephen; Meechoovet, Bessie; Pruzin, Jeremy; Bandy, Daniel; Fleisher, Adam S.; Langbaum, Jessica B.S.; Huentelman, Matthew J.; Jensen, Kendall; Dunckley, Travis; Caselli, Richard J.; Kaib, Susan; Reiman, Eric M.

2010-01-01

In a genome-wide association study (GWAS) of late-onset Alzheimer's disease (AD), we found an association between common haplotypes of the GAB2 gene and AD risk in carriers of the apolipoprotein E (APOE) ε4 allele, the major late-onset AD susceptibility gene. We previously proposed the use of fluorodeoxyglucose positron emission tomography (FDG-PET) measurements as a quantitative presymptomatic endophenotype, more closely related to disease risk than the clinical syndrome itself, to help evaluate putative genetic and non-genetic modifiers of AD risk. In this study, we examined the relationship between the presence or absence of the relatively protective GAB2 haplotype and PET measurements of regional-to-whole brain FDG uptake in several AD-affected brain regions in 158 cognitively normal late-middle-aged APOEε4 homozygotes, heterozygotes, and non-carriers. GAB2 haplotypes were characterized using Affymetrix Genome-Wide Human SNP 6.0 Array data from each of these subjects. As predicted, the possibly protective GAB2 haplotype was associated with higher regional-to-whole brain FDG uptake in AD-affected brain regions in APOEε4 carriers. While additional studies are needed, this study supports the association between the possibly protective GAB2 haplotype and the risk of late-onset AD in APOEε4 carriers. It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk. PMID:20888920

How Patient Cost-Sharing Trends Affect Adherence and Outcomes

PubMed Central

Eaddy, Michael T.; Cook, Christopher L.; O’Day, Ken; Burch, Steven P.; Cantrell, C. Ron

2012-01-01

Objective We sought to assess the relationship between patient cost sharing; medication adherence; and clinical, utilization, and economic outcomes. Methodology: We conducted a literature review of articles and abstracts published from January 1974 to May 2008. Articles were identified using PubMed, Ovid, medline, Web of Science, and Google Scholar databases. The following terms were used in the search: adherence, compliance, copay, cost sharing, costs, noncompliance, outcomes, hospitalization, utilization, economics, income, and persistence. Results: We identified and included 160 articles in the review. Although the types of interventions, measures, and populations studied varied widely, we were able to identify relatively clear relationships between cost sharing, adherence, and outcomes. Of the articles that evaluated the relationship between changes in cost sharing and adherence, 85% showed that an increasing patient share of medication costs was significantly associated with a decrease in adherence. For articles that investigated the relationship between adherence and outcomes, the majority noted that increased adherence was associated with a statistically significant improvement in outcomes. Conclusion: Increasing patient cost sharing was associated with declines in medication adherence, which in turn was associated with poorer health outcomes. PMID:22346336

The Persistence of Cognitive Deficits in Remitted and Unremitted ADHD: A Case for the State-Independence of Response Inhibition

ERIC Educational Resources Information Center

McAuley, Tara; Crosbie, Jennifer; Charach, Alice; Schachar, Russell

2014-01-01

Background: Response inhibition, working memory, and response variability are possible endophenotypes of ADHD based on their association with the disorder and evidence of heritability. One of the critical although rarely studied criteria for a valid endophenotype is that it persists despite waxing and waning of the overt manifestations of the…

Probing Compulsive and Impulsive Behaviors, from Animal Models to Endophenotypes: A Narrative Review

PubMed Central

Fineberg, Naomi A; Potenza, Marc N; Chamberlain, Samuel R; Berlin, Heather A; Menzies, Lara; Bechara, Antoine; Sahakian, Barbara J; Robbins, Trevor W; Bullmore, Edward T; Hollander, Eric

2010-01-01

Failures in cortical control of fronto-striatal neural circuits may underpin impulsive and compulsive acts. In this narrative review, we explore these behaviors from the perspective of neural processes and consider how these behaviors and neural processes contribute to mental disorders such as obsessive–compulsive disorder (OCD), obsessive–compulsive personality disorder, and impulse-control disorders such as trichotillomania and pathological gambling. We present findings from a broad range of data, comprising translational and human endophenotypes research and clinical treatment trials, focussing on the parallel, functionally segregated, cortico-striatal neural projections, from orbitofrontal cortex (OFC) to medial striatum (caudate nucleus), proposed to drive compulsive activity, and from the anterior cingulate/ventromedial prefrontal cortex to the ventral striatum (nucleus accumbens shell), proposed to drive impulsive activity, and the interaction between them. We suggest that impulsivity and compulsivity each seem to be multidimensional. Impulsive or compulsive behaviors are mediated by overlapping as well as distinct neural substrates. Trichotillomania may stand apart as a disorder of motor-impulse control, whereas pathological gambling involves abnormal ventral reward circuitry that identifies it more closely with substance addiction. OCD shows motor impulsivity and compulsivity, probably mediated through disruption of OFC-caudate circuitry, as well as other frontal, cingulate, and parietal connections. Serotonin and dopamine interact across these circuits to modulate aspects of both impulsive and compulsive responding and as yet unidentified brain-based systems may also have important functions. Targeted application of neurocognitive tasks, receptor-specific neurochemical probes, and brain systems neuroimaging techniques have potential for future research in this field. PMID:19940844

Is negative self-referent bias an endophenotype for depression? An fMRI study of emotional self-referent words in twins at high vs. low risk of depression.

PubMed

Miskowiak, K W; Larsen, J E; Harmer, C J; Siebner, H R; Kessing, L V; Macoveanu, J; Vinberg, M

2018-01-15

Negative cognitive bias and aberrant neural processing of self-referent emotional words seem to be trait-marks of depression. However, it is unclear whether these neurocognitive changes are present in unaffected first-degree relatives and constitute an illness endophenotype. Fifty-three healthy, never-depressed monozygotic or dizygotic twins with a co-twin history of depression (high-risk group: n = 26) or no first-degree family history of depression (low-risk group: n = 27) underwent neurocognitive testing and functional magnetic imaging (fMRI) as part of a follow-up cohort study. Participants performed a self-referent emotional word categorisation task and free word recall task followed by a recognition task during fMRI. Participants also completed questionnaires assessing mood, personality traits and coping strategies. High-risk and low-risk twins (age, mean ± SD: 40 ± 11) were well-balanced for demographic variables, mood, coping and neuroticism. High-risk twins showed lower accuracy during self-referent categorisation of emotional words independent of valence and more false recollections of negative words than low-risk twins during free recall. Functional MRI yielded no differences between high-risk and low-risk twins in retrieval-specific neural activity for positive or negative words or during the recognition of negative versus positive words within the hippocampus or prefrontal cortex. The subtle display of negative recall bias is consistent with the hypothesis that self-referent negative memory bias is an endophenotype for depression. High-risk twins' lower categorisation accuracy adds to the evidence for valence-independent cognitive deficits in individuals at familial risk for depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Sibling composition and household room sharing are associated with menarcheal status among rural Bengalee girls of West Bengal, India.

PubMed

Biswas, Sadaruddin; Koziel, Slawomir; Chakraborty, Raja; Bose, Kaushik

2013-08-01

Menarche, the first menstruation, is one of the most important events in a woman's reproductive life. The timing of menarche varies across populations and depends upon social interaction and family environment. It is also associated with several biological as well as social factors. The objective of this study was to explore the relationship between sibling composition and age at menarche (AAM) and to assess the association between the pattern of room sharing with family members of different sexes and menarcheal occurrence among rural Bengalee girls from West Bengal, India. The total sample comprised 577 Bengalee girls, 6-17 years of age, from various schools and madrasas in two blocks of the Nadia District of West Bengal State in India. The effects of room sharing on the occurrence of menarche, and of sibling composition on the menarcheal age, were assessed by analyses of covariance. The room-sharing pattern had a significant effect on menarcheal status (yes÷no): a significantly higher percentage of girls who shared a room with the mother and÷or sisters were postmenarcheal compared with those who shared a room with male family members. AAM did not differ significantly between girls having brothers or sisters. However, sibling order had a significant impact on AAM. Girls who had a younger sibling only (brother or sister) had a higher mean AAM, and girls who had both younger brothers and younger sisters had significantly higher mean AAM, than did the girls who had no younger sibling (singletons or having only elder siblings). There was no difference in AAM between the girls who had younger sister(s) and those who had younger brother(s). These differences were also independent of body mass index. In conclusion, the room sharing characteristics and the sibling sex composition, particularly their order, had significant effect on menarche in adolescent rural Bengalee girls. Copyright © 2013 Wayne State University Press, Detroit, Michigan 48201-1309.

Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?

PubMed Central

Wandschneider, Britta; Centeno, Maria; Vollmar, Christian; Symms, Mark; Thompson, Pamela J.; Duncan, John S.

2014-01-01

Juvenile myoclonic epilepsy is a heritable idiopathic generalized epilepsy syndrome, characterized by myoclonic jerks and frequently triggered by cognitive effort. Impairment of frontal lobe cognitive functions has been reported in patients with juvenile myoclonic epilepsy and their unaffected siblings. In a recent functional magnetic resonance imaging study we reported abnormal co-activation of the motor cortex and increased functional connectivity between the motor system and prefrontal cognitive networks during a working memory paradigm, providing an underlying mechanism for cognitively triggered jerks. In this study, we used the same task in 15 unaffected siblings (10 female; age range 18–65 years, median 40) of 11 of those patients with juvenile myoclonic epilepsy (six female; age range 22–54 years, median 35) and compared functional magnetic resonance imaging activations with 20 age- and gender-matched healthy control subjects (12 female; age range 23–46 years, median 30.5). Unaffected siblings showed abnormal primary motor cortex and supplementary motor area co-activation with increasing cognitive load, as well as increased task-related functional connectivity between motor and prefrontal cognitive networks, with a similar pattern to patients (P < 0.001 uncorrected; 20-voxel threshold extent). This finding in unaffected siblings suggests that altered motor system activation and functional connectivity is not medication- or seizure-related, but represents a potential underlying mechanism for impairment of frontal lobe functions in both patients and siblings, and so constitutes an endophenotype of juvenile myoclonic epilepsy. PMID:25001494

Association of Polyaminergic Loci With Anxiety, Mood Disorders, and Attempted Suicide

PubMed Central

Fiori, Laura M.; Wanner, Brigitte; Jomphe, Valérie; Croteau, Jordie; Vitaro, Frank

2010-01-01

Background The polyamine system has been implicated in a number of psychiatric conditions, which display both alterations in polyamine levels and altered expression of genes related to polyamine metabolism. Studies have identified associations between genetic variants in spermidine/spermine N1-acetyltransferase (SAT1) and both anxiety and suicide, and several polymorphisms appear to play important roles in determining gene expression. Methodology/Principal Findings We genotyped 63 polymorphisms, spread across four polyaminergic genes (SAT1, spermine synthase (SMS), spermine oxidase (SMOX), and ornithine aminotransferase like-1 (OATL1)), in 1255 French-Canadian individuals who have been followed longitudinally for 22 years. We assessed univariate associations with anxiety, mood disorders, and attempted suicide, as assessed during early adulthood. We also investigated the involvement of gene-environment interactions in terms of childhood abuse, and assessed internalizing and externalizing symptoms as endophenotypes mediating these interactions. Overall, each gene was associated with at least one main outcome: anxiety (SAT1, SMS), mood disorders (SAT1, SMOX), and suicide attempts (SAT1, OATL1). Several SAT1 polymorphisms displayed disease-specific risk alleles, and polymorphisms in this gene were involved in gene-gene interactions with SMS to confer risk for anxiety disorders, as well as gene-environment interactions between childhood physical abuse and mood disorders. Externalizing behaviors demonstrated significant mediation with regards to the association between OATL1 and attempted suicide, however there was no evidence that externalizing or internalizing behaviors were appropriate endophenotypes to explain the associations with mood or anxiety disorders. Finally, childhood sexual abuse did not demonstrate mediating influences on any of our outcomes. Conclusions/Significance These results demonstrate that genetic variants in polyaminergic genes are associated with

Association of polyaminergic loci with anxiety, mood disorders, and attempted suicide.

PubMed

Fiori, Laura M; Wanner, Brigitte; Jomphe, Valérie; Croteau, Jordie; Vitaro, Frank; Tremblay, Richard E; Bureau, Alexandre; Turecki, Gustavo

2010-11-30

The polyamine system has been implicated in a number of psychiatric conditions, which display both alterations in polyamine levels and altered expression of genes related to polyamine metabolism. Studies have identified associations between genetic variants in spermidine/spermine N1-acetyltransferase (SAT1) and both anxiety and suicide, and several polymorphisms appear to play important roles in determining gene expression. We genotyped 63 polymorphisms, spread across four polyaminergic genes (SAT1, spermine synthase (SMS), spermine oxidase (SMOX), and ornithine aminotransferase like-1 (OATL1)), in 1255 French-Canadian individuals who have been followed longitudinally for 22 years. We assessed univariate associations with anxiety, mood disorders, and attempted suicide, as assessed during early adulthood. We also investigated the involvement of gene-environment interactions in terms of childhood abuse, and assessed internalizing and externalizing symptoms as endophenotypes mediating these interactions. Overall, each gene was associated with at least one main outcome: anxiety (SAT1, SMS), mood disorders (SAT1, SMOX), and suicide attempts (SAT1, OATL1). Several SAT1 polymorphisms displayed disease-specific risk alleles, and polymorphisms in this gene were involved in gene-gene interactions with SMS to confer risk for anxiety disorders, as well as gene-environment interactions between childhood physical abuse and mood disorders. Externalizing behaviors demonstrated significant mediation with regards to the association between OATL1 and attempted suicide, however there was no evidence that externalizing or internalizing behaviors were appropriate endophenotypes to explain the associations with mood or anxiety disorders. Finally, childhood sexual abuse did not demonstrate mediating influences on any of our outcomes. These results demonstrate that genetic variants in polyaminergic genes are associated with psychiatric conditions, each of which involves a set of separate

Complying with physician gain-sharing restrictions.

PubMed

O'Hare, P K

1998-05-01

Many IDSs are considering implementing gain-sharing programs as a way to motivate their physicians to provide high-quality, cost-effective services. Before embarking on such programs, however, IDSs need to understand the legal requirements associated with such programs to ensure that the gain-sharing arrangement is in compliance with Federal law.

The Association of Patient Chronic Disease Burden and Self-Management Requirements With Shared Decision Making in Primary Care Visits

PubMed Central

Drum, Melinda; Cooper, Lisa A.

2014-01-01

Background: Shared decision making (SDM) is associated with positive health outcomes and may be particularly relevant for patients with chronic disease. Objectives: To investigate whether (1) patients with chronic diseases, particularly those requiring self-management, are more likely to engage in SDM behaviors than patients without chronic diseases and (2) patients with chronic diseases are more likely to have their physicians engage them in SDM. Design: A cross-sectional study of patients who were enrolled in a randomized controlled trial to improve patient–physician communication. Participants: Adult patients with hypertension at community health clinics in Baltimore, Maryland. Approach: We used multivariable regression models to examine the associations of the following predictor variables: (1) chronic disease burden and (2) diseases requiring self-management with the following outcome variables measuring SDM components: (1) patient information sharing, (2) patient decision making, and (3) physician SDM facilitation. Key Results: Patients with greater chronic disease burden and more diseases requiring self-management reported more information sharing (β = .07, P = .03 and β = .12, P = .046, respectively) and decision making (β = .06, P = .02 and β = .21, P < .001) as did patients who reported poor general health. Physician facilitation of SDM was not associated with chronic disease burden or with diseases requiring self-management but was associated with higher patient income. Conclusions: Patients with chronic diseases, particularly those requiring self-management, may be more likely to engage in SDM behaviors, but physicians may not be more likely to engage such patients in SDM. Targeting patients with chronic disease for SDM may improve health outcomes among the chronically ill, particularly among vulnerable patients (eg, minorities, low-income patients) who suffer disproportionately from such conditions. PMID:26640812

Cost Sharing, Health Care Expenditures, and Utilization: An International Comparison.

PubMed

Perkowski, Patryk; Rodberg, Leonard

2016-01-01

Health systems implement cost sharing to help reduce health care expenditure and utilization by discouraging the use of unnecessary health care services. We examine cost sharing in 28 countries in the Organisation for Economic Co-operation and Development from 1999 through 2009 in the areas of medical care, hospital care, and pharmaceuticals. We investigate associations between cost sharing, health care expenditures, and health care utilization and find no significant association between cost sharing and health care expenditures or utilization in these countries. © The Author(s) 2015.

Share capitalism and worker wellbeing⋆, ⋆⋆

PubMed Central

Clark, Andrew E.; Freeman, Richard B.; Green, Colin P.

2017-01-01

We show that worker wellbeing is determined not only by the amount of compensation workers receive but also by how compensation is determined. While previous theoretical and empirical work has often been preoccupied with individual performance-related pay, we find that the receipt of a range of group-performance schemes (profit shares, group bonuses and share ownership) is associated with higher job satisfaction. This holds conditional on wage levels, so that pay methods are associated with greater job satisfaction in addition to that coming from higher wages. We use a variety of methods to control for unobserved individual and job-specific characteristics. We suggest that half of the share-capitalism effect is accounted for by employees reciprocating for the “gift”; we also show that share capitalism helps dampen the negative wellbeing effects of what we typically think of as “bad” aspects of job quality. PMID:28725118

Risk Factors for Addiction and Their Association with Model-Based Behavioral Control.

PubMed

Reiter, Andrea M F; Deserno, Lorenz; Wilbertz, Tilmann; Heinze, Hans-Jochen; Schlagenhauf, Florian

2016-01-01

Addiction shows familial aggregation and previous endophenotype research suggests that healthy relatives of addicted individuals share altered behavioral and cognitive characteristics with individuals suffering from addiction. In this study we asked whether impairments in behavioral control proposed for addiction, namely a shift from goal-directed, model-based toward habitual, model-free control, extends toward an unaffected sample (n = 20) of adult children of alcohol-dependent fathers as compared to a sample without any personal or family history of alcohol addiction (n = 17). Using a sequential decision-making task designed to investigate model-free and model-based control combined with a computational modeling analysis, we did not find any evidence for altered behavioral control in individuals with a positive family history of alcohol addiction. Independent of family history of alcohol dependence, we however observed that the interaction of two different risk factors of addiction, namely impulsivity and cognitive capacities, predicts the balance of model-free and model-based behavioral control. Post-hoc tests showed a positive association of model-based behavior with cognitive capacity in the lower, but not in the higher impulsive group of the original sample. In an independent sample of particularly high- vs. low-impulsive individuals, we confirmed the interaction effect of cognitive capacities and high vs. low impulsivity on model-based control. In the confirmation sample, a positive association of omega with cognitive capacity was observed in highly impulsive individuals, but not in low impulsive individuals. Due to the moderate sample size of the study, further investigation of the association of risk factors for addiction with model-based behavior in larger sample sizes is warranted.

Sharing-based social capital associated with harvest production and wealth in the Canadian Arctic

PubMed Central

2018-01-01

Social institutions that facilitate sharing and redistribution may help mitigate the impact of resource shocks. In the North American Arctic, traditional food sharing may direct food to those who need it and provide a form of natural insurance against temporal variability in hunting returns within households. Here, network properties that facilitate resource flow (network size, quality, and density) are examined in a country food sharing network comprising 109 Inuit households from a village in Nunavik (Canada), using regressions to investigate the relationships between these network measures and household socioeconomic attributes. The results show that although single women and elders have larger networks, the sharing network is not structured to prioritize sharing towards households with low food availability. Rather, much food sharing appears to be driven by reciprocity between high-harvest households, meaning that poor, low-harvest households tend to have less sharing-based social capital than more affluent, high-harvest households. This suggests that poor, low-harvest households may be more vulnerable to disruptions in the availability of country food. PMID:29529040

Data Sharing: Convert Challenges into Opportunities.

PubMed

Figueiredo, Ana Sofia

2017-01-01

Initiatives for sharing research data are opportunities to increase the pace of knowledge discovery and scientific progress. The reuse of research data has the potential to avoid the duplication of data sets and to bring new views from multiple analysis of the same data set. For example, the study of genomic variations associated with cancer profits from the universal collection of such data and helps in selecting the most appropriate therapy for a specific patient. However, data sharing poses challenges to the scientific community. These challenges are of ethical, cultural, legal, financial, or technical nature. This article reviews the impact that data sharing has in science and society and presents guidelines to improve the efficient sharing of research data.

31 CFR 50.36 - Allocation of premium income associated with entities that do share profits and losses with...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Allocation of premium income associated with entities that do share profits and losses with private sector insurers. 50.36 Section 50.36 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM...

31 CFR 50.36 - Allocation of premium income associated with entities that do share profits and losses with...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Allocation of premium income associated with entities that do share profits and losses with private sector insurers. 50.36 Section 50.36 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM...

31 CFR 50.36 - Allocation of premium income associated with entities that do share profits and losses with...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Allocation of premium income associated with entities that do share profits and losses with private sector insurers. 50.36 Section 50.36 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM...

Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative.

PubMed

Constantin, Tamas; Foeldvari, Ivan; Anton, Jordi; de Boer, Joke; Czitrom-Guillaume, Severine; Edelsten, Clive; Gepstein, Raz; Heiligenhaus, Arnd; Pilkington, Clarissa A; Simonini, Gabriele; Uziel, Yosef; Vastert, Sebastian J; Wulffraat, Nico M; Haasnoot, Anne-Mieke; Walscheid, Karoline; Pálinkás, Annamária; Pattani, Reshma; Györgyi, Zoltán; Kozma, Richárd; Boom, Victor; Ponyi, Andrea; Ravelli, Angelo; Ramanan, Athimalaipet V

2018-03-28

In 2012, a European initiative called S ingle Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is possibly its most devastating extra-articular manifestation. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment practices differ widely, within and between nations. To provide recommendations for the diagnosis and treatment of JIA-associated uveitis. Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of nine experienced paediatric rheumatologists and three experts in ophthalmology from Europe. Recommendations derived from a validated systematic literature review were evaluated by an Expert Committee and subsequently discussed at two consensus meetings using nominal group techniques. Recommendations were accepted if >80% agreement was reached (including all three ophthalmologists). In total, 22 recommendations were accepted (with >80% agreement among experts): 3 on diagnosis, 5 on disease activity measurements, 12 on treatment and 2 on future recommendations. The SHARE initiative aims to identify best practices for treatment of patients suffering from JIA-associated uveitis. Within this remit, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated by an evidence-informed consensus process to suggest a standard of care for JIA-associated uveitis patients throughout Europe. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Knockdown of phospholipase C-β1 in the medial prefrontal cortex of male mice impairs working memory among multiple schizophrenia endophenotypes

PubMed Central

Kim, Seong-Wook; Seo, Misun; Kim, Duk-Soo; Kang, Moonkyung; Kim, Yeon-Soo; Koh, Hae-Young; Shin, Hee-Sup

2015-01-01

Background Decreased expression of phospholipase C-β1 (PLC-β1) has been observed in the brains of patients with schizophrenia, but, to our knowledge, no studies have shown a possible association between this altered PLC-β1 expression and the pathogenesis of schizophrenia. Although PLC-β1-null (PLC-β1−/−) mice exhibit multiple endophenotypes of schizophrenia, it remains unclear how regional decreases in PLC-β1 expression in the brain contribute to specific behavioural defects. Methods We selectively knocked down PLC-β1 in the medial prefrontal cortex (mPFC) using a small hairpin RNA strategy in mice. Results Silencing PLC-β1 in the mPFC resulted in working memory deficits, as assayed using the delayed non-match-to-sample T-maze task. Notably, however, other schizophrenia- related behaviours observed in PLC-β1−/− mice, including phenotypes related to locomotor activity, sociability and sensorimotor gating, were normal in PLC-β1 knockdown mice. Limitations Phenotypes of PLC-β1 knockdown mice, such as locomotion, anxiety and sensorimotor gating, have already been published in our previous studies. Further, the neural mechanisms underlying the working memory deficit in mice may be different from those in human schizophrenia. Conclusion These results indicate that PLC-β1 signalling in the mPFC is required for working memory. Importantly, these results support the notion that the decrease in PLC-β1 expression in the brains of patients with schizophrenia is a pathogenically relevant molecular marker of the disorder. PMID:25268789

Sharing medicine: the candidacy of medicines and other household items for sharing, Dominican Republic.

PubMed

Dohn, Michael N; Pilkington, Hugo

2014-01-01

People share medicines and problems can result from this behavior. Successful interventions to change sharing behavior will require understanding people's motives and purposes for sharing medicines. Better information about how medicines fit into the gifting and reciprocity system could be useful in designing interventions to modify medicine sharing behavior. However, it is uncertain how people situate medicines among other items that might be shared. This investigation is a descriptive study of how people sort medicines and other shareable items. This study in the Dominican Republic examined how a convenience sample (31 people) sorted medicines and rated their shareability in relation to other common household items. We used non-metric multidimensional scaling to produce association maps in which the distances between items offer a visual representation of the collective opinion of the participants regarding the relationships among the items. In addition, from a pile sort constrained by four categories of whether sharing or loaning the item was acceptable (on a scale from not shareable to very shareable), we assessed the degree to which the participants rated the medicines as shareable compared to other items. Participants consistently grouped medicines together in all pile sort activities; yet, medicines were mixed with other items when rated by their candidacy to be shared. Compared to the other items, participants had more variability of opinion as to whether medicines should be shared. People think of medicines as a distinct group, suggesting that interventions might be designed to apply to medicines as a group. People's differing opinions as to whether it was appropriate to share medicines imply a degree of uncertainty or ambiguity that health promotion interventions might exploit to alter attitudes and behaviors. These findings have implications for the design of health promotion interventions to impact medicine sharing behavior.

Risks associated with borrowing and sharing of prescription analgesics among patients observed by pain management physicians in Croatia: a qualitative study.

PubMed

Markotic, Filipa; Puljak, Livia

2016-01-01

Understanding and improving patient safety is a key issue in medicine. One of the potential threats to patient safety is the sharing of medication among patients, which is a form of self-medication. This study analyzed experiences and attitudes of pain management physicians (PMPs) about sharing prescription analgesics among patients. This qualitative study was conducted by semi-structured interviews among PMPs employed in Croatian pain clinics. The study involved two researchers and 15 PMPs. Among PMPs, 80% have seen patients who share their prescription analgesics with other patients for whom prescription is not intended. Most PMPs consider prescription analgesics sharing a risky and negative behavior. Some of them, however, found certain positive aspects associated to it, such as being a benevolent behavior, helping patients to get medications when they need them, and helping them cope with pain. The majority of physicians specialized in pain management encountered patients sharing prescription analgesics. Most of them considered this as risky behavior with a number of potential consequences. It has been noted that this problem is neglected and that physicians should inquire about medication sharing. Direct-to-consumers advertising was perceived as a factor contributing to such behavior. Patient education and more involvement of physicians in identifying this behavior were cited as potential remedies for preventing sharing of prescription analgesics.

Transforming Education Research Through Open Video Data Sharing.

PubMed

Gilmore, Rick O; Adolph, Karen E; Millman, David S; Gordon, Andrew

2016-01-01

Open data sharing promises to accelerate the pace of discovery in the developmental and learning sciences, but significant technical, policy, and cultural barriers have limited its adoption. As a result, most research on learning and development remains shrouded in a culture of isolation. Data sharing is the rare exception (Gilmore, 2016). Many researchers who study teaching and learning in classroom, laboratory, museum, and home contexts use video as a primary source of raw research data. Unlike other measures, video captures the complexity, richness, and diversity of behavior. Moreover, because video is self-documenting, it presents significant potential for reuse. However, the potential for reuse goes largely unrealized because videos are rarely shared. Research videos contain information about participants' identities making the materials challenging to share. The large size of video files, diversity of formats, and incompatible software tools pose technical challenges. The Databrary (databrary.org) digital library enables researchers who study learning and development to store, share, stream, and annotate videos. In this article, we describe how Databrary has overcome barriers to sharing research videos and associated data and metadata. Databrary has developed solutions for respecting participants' privacy; for storing, streaming, and sharing videos; and for managing videos and associated metadata. The Databrary experience suggests ways that videos and other identifiable data collected in the context of educational research might be shared. Open data sharing enabled by Databrary can serve as a catalyst for a truly multidisciplinary science of learning.

Transforming Education Research Through Open Video Data Sharing

PubMed Central

Gilmore, Rick O.; Adolph, Karen E.; Millman, David S.; Gordon, Andrew

2016-01-01

Open data sharing promises to accelerate the pace of discovery in the developmental and learning sciences, but significant technical, policy, and cultural barriers have limited its adoption. As a result, most research on learning and development remains shrouded in a culture of isolation. Data sharing is the rare exception (Gilmore, 2016). Many researchers who study teaching and learning in classroom, laboratory, museum, and home contexts use video as a primary source of raw research data. Unlike other measures, video captures the complexity, richness, and diversity of behavior. Moreover, because video is self-documenting, it presents significant potential for reuse. However, the potential for reuse goes largely unrealized because videos are rarely shared. Research videos contain information about participants’ identities making the materials challenging to share. The large size of video files, diversity of formats, and incompatible software tools pose technical challenges. The Databrary (databrary.org) digital library enables researchers who study learning and development to store, share, stream, and annotate videos. In this article, we describe how Databrary has overcome barriers to sharing research videos and associated data and metadata. Databrary has developed solutions for respecting participants’ privacy; for storing, streaming, and sharing videos; and for managing videos and associated metadata. The Databrary experience suggests ways that videos and other identifiable data collected in the context of educational research might be shared. Open data sharing enabled by Databrary can serve as a catalyst for a truly multidisciplinary science of learning. PMID:28042361

'Reading the Mind in the Eyes': an fMRI study of adolescents with autism and their siblings.

PubMed

Holt, R J; Chura, L R; Lai, M-C; Suckling, J; von dem Hagen, E; Calder, A J; Bullmore, E T; Baron-Cohen, S; Spencer, M D

2014-11-01

Mentalizing deficits are a hallmark of the autism spectrum condition (ASC) and a potential endophenotype for atypical social cognition in ASC. Differences in performance and neural activation on the 'Reading the Mind in the Eyes' task (the Eyes task) have been identified in individuals with ASC in previous studies. Performance on the Eyes task along with the associated neural activation was examined in adolescents with ASC (n = 50), their unaffected siblings (n = 40) and typically developing controls (n = 40). Based on prior literature that males and females with ASC display different cognitive and associated neural characteristics, analyses were stratified by sex. Three strategies were applied to test for endophenotypes at the level of neural activation: (1) identifying and locating conjunctions of ASC-control and sibling-control differences; (2) examining whether the sibling group is comparable to the ASC or intermediate between the ASC and control groups; and (3) examining spatial overlaps between ASC-control and sibling-control differences across multiple thresholds. Impaired behavioural performance on the Eyes task was observed in males with ASC compared to controls, but only at trend level in females; and no difference in performance was identified between sibling and same-sex control groups in both sexes. Neural activation showed a substantial endophenotype effect in the female groups but this was only modest in the male groups. Behavioural impairment on complex emotion recognition associated with mental state attribution is a phenotypic, rather than an endophenotypic, marker of ASC. However, the neural response during the Eyes task is a potential endophenotypic marker for ASC, particularly in females.

Assured Information Sharing for Ad-Hoc Collaboration

ERIC Educational Resources Information Center

Jin, Jing

2009-01-01

Collaborative information sharing tends to be highly dynamic and often ad hoc among organizations. The dynamic natures and sharing patterns in ad-hoc collaboration impose a need for a comprehensive and flexible approach to reflecting and coping with the unique access control requirements associated with the environment. This dissertation…

Associative-memory representations emerge as shared spatial patterns of theta activity spanning the primate temporal cortex

PubMed Central

Nakahara, Kiyoshi; Adachi, Ken; Kawasaki, Keisuke; Matsuo, Takeshi; Sawahata, Hirohito; Majima, Kei; Takeda, Masaki; Sugiyama, Sayaka; Nakata, Ryota; Iijima, Atsuhiko; Tanigawa, Hisashi; Suzuki, Takafumi; Kamitani, Yukiyasu; Hasegawa, Isao

2016-01-01

Highly localized neuronal spikes in primate temporal cortex can encode associative memory; however, whether memory formation involves area-wide reorganization of ensemble activity, which often accompanies rhythmicity, or just local microcircuit-level plasticity, remains elusive. Using high-density electrocorticography, we capture local-field potentials spanning the monkey temporal lobes, and show that the visual pair-association (PA) memory is encoded in spatial patterns of theta activity in areas TE, 36, and, partially, in the parahippocampal cortex, but not in the entorhinal cortex. The theta patterns elicited by learned paired associates are distinct between pairs, but similar within pairs. This pattern similarity, emerging through novel PA learning, allows a machine-learning decoder trained on theta patterns elicited by a particular visual item to correctly predict the identity of those elicited by its paired associate. Our results suggest that the formation and sharing of widespread cortical theta patterns via learning-induced reorganization are involved in the mechanisms of associative memory representation. PMID:27282247

Data Sharing: Convert Challenges into Opportunities

PubMed Central

Figueiredo, Ana Sofia

2017-01-01

Initiatives for sharing research data are opportunities to increase the pace of knowledge discovery and scientific progress. The reuse of research data has the potential to avoid the duplication of data sets and to bring new views from multiple analysis of the same data set. For example, the study of genomic variations associated with cancer profits from the universal collection of such data and helps in selecting the most appropriate therapy for a specific patient. However, data sharing poses challenges to the scientific community. These challenges are of ethical, cultural, legal, financial, or technical nature. This article reviews the impact that data sharing has in science and society and presents guidelines to improve the efficient sharing of research data. PMID:29270401

Accumulating Evidence for the Association and Shared Pathogenic Mechanisms between Psoriasis and Cardiovascular–Related Co-morbidities

PubMed Central

Shlyankevich, Julia; Mehta, Nehal N.; Krueger, James G.; Strober, Bruce; Gudjonsson, Johann E.; Qureshi, Abrar A.; Tebbey, Paul W.; Kimball, Alexandra Boer

2014-01-01

The International Psoriasis Council (IPC), a global non-profit organization dedicated to advancing psoriasis research and treatment, led an initiative to better define the association of various cardiometabolic comorbidities with psoriasis. In November 2013, a workshop was held in Boston, MA. By assembling a panel of global dermatology, immunology and cardiovascular experts, the objective was to better define the current status of the science that explains the association of psoriasis with various cardiometabolic-related comorbidities. IPC has played a historical role in associating psoriasis with various comorbidities by integrating multidisciplinary expertise to advance the scientific and clinical knowledge through publications and clinical trials. This report synthesizes the current understanding of psoriasis with various cardiometabolic risk factors by exploring the potential shared pathogenic mechanisms and genetic connectivity. PMID:25149424

Rhythmicity in Mice Selected for Extremes in Stress Reactivity: Behavioural, Endocrine and Sleep Changes Resembling Endophenotypes of Major Depression

PubMed Central

Ruschel, Jörg; Palme, Rupert; Holsboer, Florian; Kimura, Mayumi; Landgraf, Rainer

2009-01-01

Background Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including hyper- or hypo-activity of the stress hormone system, plays a critical role in the pathophysiology of mood disorders such as major depression (MD). Further biological hallmarks of MD are disturbances in circadian rhythms and sleep architecture. Applying a translational approach, an animal model has recently been developed, focusing on the deviation in sensitivity to stressful encounters. This so-called ‘stress reactivity’ (SR) mouse model consists of three separate breeding lines selected for either high (HR), intermediate (IR), or low (LR) corticosterone increase in response to stressors. Methodology/Principle Findings In order to contribute to the validation of the SR mouse model, our study combined the analysis of behavioural and HPA axis rhythmicity with sleep-EEG recordings in the HR/IR/LR mouse lines. We found that hyper-responsiveness to stressors was associated with psychomotor alterations (increased locomotor activity and exploration towards the end of the resting period), resembling symptoms like restlessness, sleep continuity disturbances and early awakenings that are commonly observed in melancholic depression. Additionally, HR mice also showed neuroendocrine abnormalities similar to symptoms of MD patients such as reduced amplitude of the circadian glucocorticoid rhythm and elevated trough levels. The sleep-EEG analyses, furthermore, revealed changes in rapid eye movement (REM) and non-REM sleep as well as slow wave activity, indicative of reduced sleep efficacy and REM sleep disinhibition in HR mice. Conclusion/Significance Thus, we could show that by selectively breeding mice for extremes in stress reactivity, clinically relevant endophenotypes of MD can be modelled. Given the importance of rhythmicity and sleep disturbances as biomarkers of MD, both animal and clinical studies on the interaction of behavioural, neuroendocrine and sleep parameters may reveal

[Association of kynurenine-3-monooxygenase gene with schizophrenia].

PubMed

Golimbet, V E; Lezheiko, T V; Alfimova, M V; Abramova, L I; Kondrat'ev, N V

2014-06-01

Neurotoxic products produced during tryptophan metabolism via the kynurenine pathway could be involved in schizophrenia pathogenesis. It has been shown that kynurenine-3-monooxygenase (KMO) is indirectly involved in these products' formation. KMO polymorphic loci rs2275163 (C/T) and rs1053230 (A/G) were examined in 187 schizophrenia patients and 229 healthy subjects. A genetic combination of allele T and genotype GG was observed more often in a patient group compared with healthy controls (p = 0.003, OR 2.0 (95% CI 1.2-2.9). In the latter group, this combination was associated with schizophrenia endophenotype (p = 0.04), which manifested in a higher expression of schizotypal personality traits assessed using the MMPI test.

Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy

PubMed Central

Kouri, Naomi; Ross, Owen A.; Dombroski, Beth; Younkin, Curtis S.; Serie, Daniel J.; Soto-Ortolaza, Alexandra; Baker, Matthew; Finch, Ni Cole A.; Yoon, Hyejin; Kim, Jungsu; Fujioka, Shinsuke; McLean, Catriona A.; Ghetti, Bernardino; Spina, Salvatore; Cantwell, Laura B.; Farlow, Martin R.; Grafman, Jordan; Huey, Edward D.; Ryung Han, Mi; Beecher, Sherry; Geller, Evan T.; Kretzschmar, Hans A.; Roeber, Sigrun; Gearing, Marla; Juncos, Jorge L.; Vonsattel, Jean Paul G.; Van Deerlin, Vivianna M.; Grossman, Murray; Hurtig, Howard I.; Gross, Rachel G.; Arnold, Steven E.; Trojanowski, John Q.; Lee, Virginia M.; Wenning, Gregor K.; White, Charles L.; Höglinger, Günter U.; Müller, Ulrich; Devlin, Bernie; Golbe, Lawrence I.; Crook, Julia; Parisi, Joseph E.; Boeve, Bradley F.; Josephs, Keith A.; Wszolek, Zbigniew K.; Uitti, Ryan J.; Graff-Radford, Neill R.; Litvan, Irene; Younkin, Steven G.; Wang, Li-San; Ertekin-Taner, Nilüfer; Rademakers, Rosa; Hakonarsen, Hakon; Schellenberg, Gerard D.; Dickson, Dennis W.

2015-01-01

Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10−12), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10−8), and 2p22 at SOS1 (rs963731; P=1.76 × 10−7). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10−7) and MAPT H1c (17q21; rs242557; P=7.91 × 10−6). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein). PMID:26077951

Pervasive sharing of genetic effects in autoimmune disease.

PubMed

Cotsapas, Chris; Voight, Benjamin F; Rossin, Elizabeth; Lage, Kasper; Neale, Benjamin M; Wallace, Chris; Abecasis, Gonçalo R; Barrett, Jeffrey C; Behrens, Timothy; Cho, Judy; De Jager, Philip L; Elder, James T; Graham, Robert R; Gregersen, Peter; Klareskog, Lars; Siminovitch, Katherine A; van Heel, David A; Wijmenga, Cisca; Worthington, Jane; Todd, John A; Hafler, David A; Rich, Stephen S; Daly, Mark J

2011-08-01

Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA) which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44%) immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA)<0.01). We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.

The Association between Attitude towards the Implementation of Staff Development Training and the Practice of Knowledge Sharing among Lecturers

ERIC Educational Resources Information Center

Kassim, Abd. Latif; Raman, Arumugam; Don, Yahya; Daud, Yaakob; Omar, Mohd Sofian

2015-01-01

This study was aimed to identify the association of teachers' attitude towards the implementation of Staff Development Training with Knowledge Sharing Practices among the lecturers of the Teacher Training Institution (TTI). In addition, this study was also to examine the differences in attitudes towards the implementation of Staff Development…

Human milk sharing practices in the U.S.

PubMed

Palmquist, Aunchalee E L; Doehler, Kirsten

2016-04-01

The primary objective of this study is to describe human milk sharing practices in the U.S. Specifically, we examine milk sharing social networks, donor compensation, the prevalence of anonymous milk sharing interactions, recipients' concerns about specific milk sharing risks, and lay screening behaviors. Data on human milk sharing practices were collected via an online survey September 2013-March 2014. Chi-square analyses were used to test the association between risk perception and screening practices. A total of 867 (661 donors, 206 recipients) respondents were included in the analyses. Most (96.1%) reported sharing milk face-to-face. Only 10% of respondents reported giving or receiving milk through a non-profit human milk bank, respectively. There were no reports of anonymous purchases of human milk. A small proportion of recipients (4.0%) reported that their infant had a serious medical condition. Screening of prospective donors was common (90.7%) but varied with social relationship and familiarity. Likewise, concern about specific milk sharing risks was varied, and risk perception was significantly associated (P-values = 0.01 or less) with donor screening for all risk variables except diet. Understanding lay perceptions of milk sharing risk and risk reduction strategies that parents are using is an essential first step in developing public health interventions and clinical practices that promote infant safety. © 2015 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.

The lipidome in major depressive disorder: Shared genetic influence for ether-phosphatidylcholines, a plasma-based phenotype related to inflammation, and disease risk.

PubMed

Knowles, E E M; Huynh, K; Meikle, P J; Göring, H H H; Olvera, R L; Mathias, S R; Duggirala, R; Almasy, L; Blangero, J; Curran, J E; Glahn, D C

2017-06-01

The lipidome is rapidly garnering interest in the field of psychiatry. Recent studies have implicated lipidomic changes across numerous psychiatric disorders. In particular, there is growing evidence that the concentrations of several classes of lipids are altered in those diagnosed with MDD. However, for lipidomic abnormalities to be considered potential treatment targets for MDD (rather than secondary manifestations of the disease), a shared etiology between lipid concentrations and MDD should be demonstrated. In a sample of 567 individuals from 37 extended pedigrees (average size 13.57 people, range=3-80), we used mass spectrometry lipidomic measures to evaluate the genetic overlap between twenty-three biologically distinct lipid classes and a dimensional scale of MDD. We found that the lipid class with the largest endophenotype ranking value (ERV, a standardized parametric measure of pleiotropy) were ether-phosphodatidylcholines (alkylphosphatidylcholine, PC(O) and alkenylphosphatidylcholine, PC(P) subclasses). Furthermore, we examined the cluster structure of the twenty-five species within the top-ranked lipid class, and the relationship of those clusters with MDD. This analysis revealed that species containing arachidonic acid generally exhibited the greatest degree of genetic overlap with MDD. This study is the first to demonstrate a shared genetic etiology between MDD and ether-phosphatidylcholine species containing arachidonic acid, an omega-6 fatty acid that is a precursor to inflammatory mediators, such as prostaglandins. The study highlights the potential utility of the well-characterized linoleic/arachidonic acid inflammation pathway as a diagnostic marker and/or treatment target for MDD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Prospective association of the SHARE-operationalized frailty phenotype with adverse health outcomes: evidence from 60+ community-dwelling Europeans living in 11 countries

PubMed Central

2013-01-01

Background Among the many definitions of frailty, the frailty phenotype defined by Fried et al. is one of few constructs that has been repeatedly validated: first in the Cardiovascular Health Study (CHS) and subsequently in other large cohorts in the North America. In Europe, the Survey of Health, Aging and Retirement in Europe (SHARE) is a gold mine of individual, economic and health information that can provide insight into better understanding of frailty across diverse population settings. A recent adaptation of the original five CHS-frailty criteria was proposed to make use of SHARE data and measure frailty in the European population. To test the validity of the SHARE operationalized frailty phenotype, this study aims to evaluate its prospective association with adverse health outcomes. Methods Data are from 11,015 community-dwelling men and women aged 60+ participating in wave 1 and 2 of the Survey of Health, Aging and Retirement in Europe, a population-based survey. Multivariate logistic regression analyses were used to assess the 2-year follow up effect of SHARE-operationalized frailty phenotype on the incidence of disability (disability-free at baseline) and on worsening disability and morbidity, adjusting for age, sex, income and baseline morbidity and disability. Results At 2-year follow up, frail individuals were at increased risk for: developing mobility (OR 3.07, 95% CI, 1.02-9.36), IADL (OR 5.52, 95% CI, 3.76-8.10) and BADL (OR 5.13, 95% CI, 3.53-7.44) disability; worsening mobility (OR 2.94, 95% CI, 2.19- 3.93) IADL (OR 4.43, 95% CI, 3.19-6.15) and BADL disability (OR 4.53, 95% CI, 3.14-6.54); and worsening morbidity (OR 1.77, 95% CI, 1.35-2.32). These associations were significant even among the prefrail, but with a lower magnitude of effect. Conclusions The SHARE-operationalized frailty phenotype is significantly associated with all tested health outcomes independent of baseline morbidity and disability in community-dwelling men and women aged 60

Prospective association of the SHARE-operationalized frailty phenotype with adverse health outcomes: evidence from 60+ community-dwelling Europeans living in 11 countries.

PubMed

Macklai, Nejma S; Spagnoli, Jacques; Junod, Julien; Santos-Eggimann, Brigitte

2013-01-03

Among the many definitions of frailty, the frailty phenotype defined by Fried et al. is one of few constructs that has been repeatedly validated: first in the Cardiovascular Health Study (CHS) and subsequently in other large cohorts in the North America. In Europe, the Survey of Health, Aging and Retirement in Europe (SHARE) is a gold mine of individual, economic and health information that can provide insight into better understanding of frailty across diverse population settings. A recent adaptation of the original five CHS-frailty criteria was proposed to make use of SHARE data and measure frailty in the European population. To test the validity of the SHARE operationalized frailty phenotype, this study aims to evaluate its prospective association with adverse health outcomes. Data are from 11,015 community-dwelling men and women aged 60+ participating in wave 1 and 2 of the Survey of Health, Aging and Retirement in Europe, a population-based survey. Multivariate logistic regression analyses were used to assess the 2-year follow up effect of SHARE-operationalized frailty phenotype on the incidence of disability (disability-free at baseline) and on worsening disability and morbidity, adjusting for age, sex, income and baseline morbidity and disability. At 2-year follow up, frail individuals were at increased risk for: developing mobility (OR 3.07, 95% CI, 1.02-9.36), IADL (OR 5.52, 95% CI, 3.76-8.10) and BADL (OR 5.13, 95% CI, 3.53-7.44) disability; worsening mobility (OR 2.94, 95% CI, 2.19- 3.93) IADL (OR 4.43, 95% CI, 3.19-6.15) and BADL disability (OR 4.53, 95% CI, 3.14-6.54); and worsening morbidity (OR 1.77, 95% CI, 1.35-2.32). These associations were significant even among the prefrail, but with a lower magnitude of effect. The SHARE-operationalized frailty phenotype is significantly associated with all tested health outcomes independent of baseline morbidity and disability in community-dwelling men and women aged 60 and older living in Europe. The

Association of a traditional vs shared meal decision-making and preparation style with eating behavior of Hispanic women in San Diego County.

PubMed

Arredondo, Elva M; Elder, John P; Ayala, Guadalupe X; Slymen, Donald; Campbell, Nadia R

2006-01-01

To examine the influence of meal decision-making and preparation on Hispanic women's dietary practices. One-on-one structured interviews were conducted, assessing meal decision-making and preparation practices, barriers, and behavioral strategies to eating low-fat and high-fiber diets, fat and fiber intake, demographic, and other psychosocial factors. The study population included 357 Hispanic women living in the southern or central regions of San Diego County. Participants were recruited via random-digit dialing to a tailored nutrition communication intervention. Household decision-making style (alone vs with family) by household activity (decides meals, prepares meals, and decides snacks). Multiple logistic regressions were used to evaluate associations between the predictors and dependent variable. All models included adjustments for potential confounders, such as marital status, education, employment, age, and acculturation. A positive statistical association between Hispanic women's acculturation level and shared decision-making style was found. Also, Hispanic women in shared decision-making households faced greater psychosocial barriers to healthful eating and reported less healthful eating compared with Hispanic women in traditional households. Women in shared decision-making households were more likely to eat at fast-food restaurants, less likely to engage in behavioral strategies promoting fiber consumption, eat more saturated fat, and encounter more barriers to reduce dietary fat as compared with Hispanic women in traditional households. Acculturation did not attenuate differences in psychosocial and dietary practices between shared decision-making and traditional households. Study findings suggest intervention efforts should focus on different aspects of healthful eating among Hispanic women in shared-decision, compared with traditional, households.

Water, Water, Everywhere: Defining and Assessing Data Sharing in Academia.

PubMed

Van Tuyl, Steven; Whitmire, Amanda L

2016-01-01

Sharing of research data has begun to gain traction in many areas of the sciences in the past few years because of changing expectations from the scientific community, funding agencies, and academic journals. National Science Foundation (NSF) requirements for a data management plan (DMP) went into effect in 2011, with the intent of facilitating the dissemination and sharing of research results. Many projects that were funded during 2011 and 2012 should now have implemented the elements of the data management plans required for their grant proposals. In this paper we define 'data sharing' and present a protocol for assessing whether data have been shared and how effective the sharing was. We then evaluate the data sharing practices of researchers funded by the NSF at Oregon State University in two ways: by attempting to discover project-level research data using the associated DMP as a starting point, and by examining data sharing associated with journal articles that acknowledge NSF support. Sharing at both the project level and the journal article level was not carried out in the majority of cases, and when sharing was accomplished, the shared data were often of questionable usability due to access, documentation, and formatting issues. We close the article by offering recommendations for how data producers, journal publishers, data repositories, and funding agencies can facilitate the process of sharing data in a meaningful way.

Shared-environmental contributions to high cognitive ability.

PubMed

Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

2009-07-01

Using a combined sample of adolescent twins, biological siblings, and adoptive siblings, we estimated and compared the differential shared-environmentality for high cognitive ability and the shared-environmental variance for the full range of ability during adolescence. Estimates obtained via multiple methods were in the neighborhood of 0.20, and suggest a modest effect of the shared environment on both high and full-range ability. We then examined the association of ability with three measures of the family environment in a subsample of adoptive siblings: parental occupational status, parental education, and disruptive life events. Only parental education showed significant (albeit modest) association with ability in both the biological and adoptive samples. We discuss these results in terms of the need for cognitive-development research to combine genetically sensitive designs and modern statistical methods with broad, thorough environmental measurement.

Information Sharing and Knowledge Sharing as Communicative Activities

ERIC Educational Resources Information Center

Savolainen, Reijo

2017-01-01

Introduction: This paper elaborates the picture of information sharing and knowledge sharing as forms of communicative activity. Method: A conceptual analysis was made to find out how researchers have approached information sharing and knowledge sharing from the perspectives of transmission and ritual. The findings are based on the analysis of one…

Shared Predisposition in the Association Between Cannabis Use and Subcortical Brain Structure.

PubMed

Pagliaccio, David; Barch, Deanna M; Bogdan, Ryan; Wood, Phillip K; Lynskey, Michael T; Heath, Andrew C; Agrawal, Arpana

2015-10-01

Prior neuroimaging studies have suggested that alterations in brain structure may be a consequence of cannabis use. Siblings discordant for cannabis use offer an opportunity to use cross-sectional data to disentangle such causal hypotheses from shared effects of genetics and familial environment on brain structure and cannabis use. To determine whether cannabis use is associated with differences in brain structure in a large sample of twins/siblings and to examine sibling pairs discordant for cannabis use to separate potential causal and predispositional factors linking lifetime cannabis exposure to volumetric alterations. Cross-sectional diagnostic interview, behavioral, and neuroimaging data were collected from community sampling and established family registries from August 2012 to September 2014. This study included data from 483 participants (22-35 years old) enrolled in the ongoing Human Connectome Project, with 262 participants reporting cannabis exposure (ie, ever used cannabis in their lifetime). Cannabis exposure was measured with the Semi-Structured Assessment for the Genetics of Alcoholism. Whole-brain, hippocampus, amygdala, ventral striatum, and orbitofrontal cortex volumes were related to lifetime cannabis use (ever used, age at onset, and frequency of use) using linear regressions. Genetic (ρg) and environmental (ρe) correlations between cannabis use and brain volumes were estimated. Linear mixed models were used to examine volume differences in sex-matched concordant unexposed (n = 71 pairs), exposed (n = 81 pairs), or exposure discordant (n = 89 pairs) sibling pairs. Among 483 study participants, cannabis exposure was related to smaller left amygdala (approximately 2.3%; P = .007) and right ventral striatum (approximately 3.5%; P < .005) volumes. These volumetric differences were within the range of normal variation. The association between left amygdala volume and cannabis use was largely owing to shared genetic factors (�

Does a One-Size-Fits-All Cost-Sharing Approach Incentivize Appropriate Medication Use? A Roundtable on the Fairness and Ethics Associated with Variable Cost Sharing.

PubMed

Graff, Jennifer S; Shih, Chuck; Barker, Thomas; Dieguez, Gabriela; Larson, Cheryl; Sherman, Helen; Dubois, Robert W

2017-06-01

Tiered formularies, in which patients pay copays or coinsurance out-of-pocket (OOP), are used to manage costs and encourage more efficient health care resource use. Formulary tiers are typically based on the cost of treatment rather than the medical appropriateness for the patient. Cost sharing may have unintended consequences on treatment adherence and health outcomes. Use of higher-cost, higher-tier medications can be due to a variety of factors, including unsuccessful treatment because of lack of efficacy or side effects, patient clinical or genetic characteristics, patient preferences to avoid potential side effects, or patient preferences based on the route of administration. For example, patients with rheumatoid arthritis may be required to fail low-cost generic treatments before obtaining coverage for a higher-tier tumor necrosis factor alpha inhibitor for which they would have a larger financial burden. Little is known about stakeholders' views on the acceptability of greater patient cost sharing if the individual patient characteristics lead to the higher-cost treatments. To identify and discuss the trade-offs associated with variable cost sharing in pharmacy benefits. To discuss the trade-offs associated with variable cost sharing in pharmacy benefits, we convened an expert roundtable of patient, payer, and employer representatives (panelists). Panelists reviewed background white papers, including an ethics framework; actuarial analysis; legal review; and stakeholder perspectives representing health plan, employer, and patient views. Using case studies, panelists were asked to consider (a) when it would be more (or less) acceptable to require higher cost sharing; (b) the optimal distribution of financial burdens across patients, all plan members, and employers; and (c) the existing barriers and potential solutions to align OOP costs with medically appropriate treatments. Panelists felt it was least acceptable for patients to have greater OOP costs if the

47 CFR 27.1305 - Shared wireless broadband network.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Shared wireless broadband network. 27.1305... broadband network. The Shared Wireless Broadband Network developed by the 700 MHz Public/Private Partnership must be designed to meet requirements associated with a nationwide, public safety broadband network. At...

47 CFR 90.1405 - Shared wireless broadband network.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Shared wireless broadband network. 90.1405... broadband network. The Shared Wireless Broadband Network developed by the 700 MHz Public/Private Partnership must be designed to meet requirements associated with a nationwide, public safety broadband network. At...

47 CFR 27.1305 - Shared wireless broadband network.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Shared wireless broadband network. 27.1305... broadband network. The Shared Wireless Broadband Network developed by the 700 MHz Public/Private Partnership must be designed to meet requirements associated with a nationwide, public safety broadband network. At...

47 CFR 90.1405 - Shared wireless broadband network.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Shared wireless broadband network. 90.1405... broadband network. The Shared Wireless Broadband Network developed by the 700 MHz Public/Private Partnership must be designed to meet requirements associated with a nationwide, public safety broadband network. At...

47 CFR 27.1305 - Shared wireless broadband network.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 2 2012-10-01 2012-10-01 false Shared wireless broadband network. 27.1305... broadband network. The Shared Wireless Broadband Network developed by the 700 MHz Public/Private Partnership must be designed to meet requirements associated with a nationwide, public safety broadband network. At...

47 CFR 90.1405 - Shared wireless broadband network.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Shared wireless broadband network. 90.1405... broadband network. The Shared Wireless Broadband Network developed by the 700 MHz Public/Private Partnership must be designed to meet requirements associated with a nationwide, public safety broadband network. At...

Prevalence of needle sharing, commercial sex behaviors and associated factors in Chinese male and female injecting drug user populations.

PubMed

Gu, Jing; Wang, Renfan; Chen, Hongyao; Lau, Joseph T F; Zhang, Linglin; Hu, Xianyou; Lei, Zhangquan; Li, Zhenglin; Cai, Hua; Wang, Tao; Tsui, Hiyi

2009-01-01

The objective of this study is to investigate prevalence and associated factors of commercial sex behaviors and condom use at commercial sex, as well as prevalence of needle sharing among injecting drug users (IDUs) in China. In this study, 162 IDUs were recruited by peer workers in Dazhou, Sichuan and were anonymously interviewed by using a structured questionnaire. Univariate and multivariate logistic regression analyses were performed and interaction between gender and the studied independent variables were tested for significance. The results of this study showed that the male and female respondents, respectively 11.7 and 16.9% were HIV positive; 34.0 and 40.7% engaged in commercial sex and 23.3 and 11.9% shared needles with others in the last six months. Percent using a condom in the last episode of commercial sex was 30.3% for males and 76.2% for females. The multivariate analyses showed that higher drug dosage (OR=0.3, 95% CI: 0.1-0.9) and reduced sexual drive (OR=0.3, 95% CI: 0.1-0.9) were associated with lower likelihood for commercial sex among male IDUs while higher drug dosage (OR=9.1, 95% CI: 1.0-86.0), perceived difficulty in finding a job (OR=5.1, 95% CI: 1.3-20.1) and lack of family support (OR=4.0, 95% CI: 1.1-15.4) were associated with commercial sex among female IDUs. Similarly, unknown HIV status (OR=8.2, 95% CI: 1.7-9.2) and having a regular sex partner (OR=3.7, 95% CI: 1.3-10.9) was associated with needle sharing. It is concluded that male and female IDUs were sexually active and often engaged in commercial sex. Drug dosage and reduced sexual drive were relevant but did not stop commercial sex behaviors. More supportive social environment is required to prevent female IDUs to enter sex work.

A game theoretic analysis of research data sharing.

PubMed

Pronk, Tessa E; Wiersma, Paulien H; van Weerden, Anne; Schieving, Feike

2015-01-01

While reusing research data has evident benefits for the scientific community as a whole, decisions to archive and share these data are primarily made by individual researchers. In this paper we analyse, within a game theoretical framework, how sharing and reuse of research data affect individuals who share or do not share their datasets. We construct a model in which there is a cost associated with sharing datasets whereas reusing such sets implies a benefit. In our calculations, conflicting interests appear for researchers. Individual researchers are always better off not sharing and omitting the sharing cost, at the same time both sharing and not sharing researchers are better off if (almost) all researchers share. Namely, the more researchers share, the more benefit can be gained by the reuse of those datasets. We simulated several policy measures to increase benefits for researchers sharing or reusing datasets. Results point out that, although policies should be able to increase the rate of sharing researchers, and increased discoverability and dataset quality could partly compensate for costs, a better measure would be to directly lower the cost for sharing, or even turn it into a (citation-) benefit. Making data available would in that case become the most profitable, and therefore stable, strategy. This means researchers would willingly make their datasets available, and arguably in the best possible way to enable reuse.

The "nuts and bolts" of implementing shared medical appointments: the Harvard Vanguard Medical Associates experience.

PubMed

Berger-Fiffy, Jill

2012-01-01

Harvard Vanguard Medical Associates (Harvard Vanguard) decided to develop a Shared Medical Appointment (SMA) program in 2007 for a variety of reasons. The program has launched 86 SMAs in 17 specialties at 12 sites and has exceeded 13 000 patient visits. Currently, the practice offers 54 SMAs and is believed to be the largest program in the country. This article provides an overview regarding staffing, space and equipment, project planning, promotional materials, training programs, workflow development, and the use of quality improvement (ie, LEAN) tools used to monitor the work to be completed and the metrics to date.

Needle and syringe sharing among Iranian drug injectors

PubMed Central

Rafiey, Hassan; Narenjiha, Hooman; Shirinbayan, Peymaneh; Noori, Roya; Javadipour, Morteza; Roshanpajouh, Mohsen; Samiei, Mercedeh; Assari, Shervin

2009-01-01

Objective The role of needle and syringe sharing behavior of injection drug users (IDUs) in spreading of blood-borne infections – specially HIV/AIDS – is well known. However, very little is known in this regard from Iran. The aim of our study was to determine the prevalence and associates of needle and syringe sharing among Iranian IDUs. Methods In a secondary analysis of a sample of drug dependents who were sampled from medical centers, prisons and streets of the capitals of 29 provinces in the Iran in 2007, 2091 male IDUs entered. Socio-demographic data, drug use data and high risk behaviors entered to a logistic regression to determine independent predictors of lifetime needle and syringe sharing. Results 749(35.8%) reported lifetime experience of needle and syringe sharing. The likelihood of lifetime needle and syringe sharing was increased by female gender, being jobless, having illegal income, drug use by family members, pleasure/enjoyment as causes of first injection, first injection in roofless and roofed public places, usual injection at groin, usual injection at scrotum, lifetime experience of nonfatal overdose, and history of arrest in past year and was decreased by being alone at most injections. Conclusion However this data has been extracted from cross-sectional design and we can not conclude causation, some of the introduced variables with association with needle and syringe sharing may be used in HIV prevention programs which target reducing syringe sharing among IDUs. PMID:19643014

Association between prescription cost sharing and adherence to initial combination antiretroviral therapy in commercially insured antiretroviral-naïve patients with HIV.

PubMed

Johnston, Stephen S; Juday, Timothy; Seekins, Daniel; Espindle, Derek; Chu, Bong-Chul

2012-03-01

In treatment of human immunodeficiency virus (HIV), high levels of adherence to combination antiretroviral therapy (cART) are required to prevent failure of virologic suppression, development of drug resistance, and permanent loss of therapeutic options. No published research has assessed the association between cART prescription cost sharing and adherence to cART. To analyze the association between cART prescription cost sharing and adherence to initial cART in commercially insured antiretroviral (ARV)-naïve patients with HIV. This retrospective observational cohort study used 2002-2008 data from a large U.S. claims database of more than 56 million commercially insured individuals. Study subjects were patients aged 18 years or older who initiated cART during the period January 1, 2003, to December 31, 2007, had no ARV claims during the 6-month period prior to the initiation date, and had at least 1 ICD-9-CM diagnosis code for HIV infection (042, 795.71, V08) from 12 months before to 12 months after cART initiation. A minimum 12-month period of continuous enrollment after cART initiation was used to construct a patient-quarter repeated measures panel dataset in which each quarter of data that a patient contributed represented an observation. The evaluation period extended from cART initiation until the occurrence of 1 of the following events: addition of an ARV that was not part of the initial cART regimen, 30-day gap in possession of an ARV within the initiated cART regimen, hospitalization of 30 or more days, loss to follow-up due to study end (December 31, 2008), or disenrollment. The study's outcome was quarterly adherence to cART, defined as the number of days within the quarter that a patient possessed all components of the initial cART regimen. Each patient's cART cost-sharing amount was calculated per 30-day supply of the entire cART regimen. Adherence was dichotomized for analysis at the clinically meaningful thresholds of 95% and 78%. The dichotomized

Affording to exchange: social capital and online information sharing.

PubMed

Maksl, Adam; Young, Rachel

2013-08-01

The potential harm and benefit associated with sharing personal information online is a topic of debate and discussion. Using survey methods (n=872), we explore whether attainment of social capital online relates to greater comfort with sharing personal information. We found that perceptions of bridging and bonding social capital earned from using Facebook are significant predictors of overall comfort levels with sharing personal information. This research raises timely questions about how the perceived benefits of social networking sites influence how personal information is shared online.

Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes.

PubMed

Napolioni, Valerio; Lombardi, Federica; Sacco, Roberto; Curatolo, Paolo; Manzi, Barbara; Alessandrelli, Riccardo; Militerni, Roberto; Bravaccio, Carmela; Lenti, Carlo; Saccani, Monica; Schneider, Cindy; Melmed, Raun; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Reichelt, Karl-Ludvig; Rousseau, Francis; Lewin, Patricia; Persico, Antonio M

2011-03-01

The integrin-β 3 gene (ITGB3), located on human chromosome 17q21.3, was previously identified as a quantitative trait locus (QTL) for 5-HT blood levels and has been implicated as a candidate gene for autism spectrum disorder (ASD). We performed a family-based association study in 281 simplex and 12 multiplex Caucasian families. ITGB3 haplotypes are significantly associated with autism (HBAT, global P=0.038). Haplotype H3 is largely over-transmitted to the affected offspring and doubles the risk of an ASD diagnosis (HBAT P=0.005; odds ratio (OR)=2.000), at the expense of haplotype H1, which is under-transmitted (HBAT P=0.018; OR=0.725). These two common haplotypes differ only at rs12603582 located in intron 11, which reaches a P-value of 0.072 in single-marker FBAT analyses. Interestingly, rs12603582 is strongly associated with pre-term delivery in our ASD patients (P=0.008). On the other hand, it is SNP rs2317385, located at the 5' end of the gene, that significantly affects 5-HT blood levels (Mann-Whitney U-test, P=0.001; multiple regression analysis, P=0.010). No gene-gene interaction between ITGB3 and SLC6A4 has been detected. In conclusion, we identify a significant association between a common ITGB3 haplotype and ASD. Distinct markers, located toward the 5' and 3' ends of the gene, seemingly modulate 5-HT blood levels and autism liability, respectively. Our results also raise interest into ITGB3 influences on feto-maternal immune interactions in autism. © 2011 Macmillan Publishers Limited All rights reserved 1018-4813/11

Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes

PubMed Central

Napolioni, Valerio; Lombardi, Federica; Sacco, Roberto; Curatolo, Paolo; Manzi, Barbara; Alessandrelli, Riccardo; Militerni, Roberto; Bravaccio, Carmela; Lenti, Carlo; Saccani, Monica; Schneider, Cindy; Melmed, Raun; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Reichelt, Karl-Ludvig; Rousseau, Francis; Lewin, Patricia; Persico, Antonio M

2011-01-01

The integrin-β 3 gene (ITGB3), located on human chromosome 17q21.3, was previously identified as a quantitative trait locus (QTL) for 5-HT blood levels and has been implicated as a candidate gene for autism spectrum disorder (ASD). We performed a family-based association study in 281 simplex and 12 multiplex Caucasian families. ITGB3 haplotypes are significantly associated with autism (HBAT, global P=0.038). Haplotype H3 is largely over-transmitted to the affected offspring and doubles the risk of an ASD diagnosis (HBAT P=0.005; odds ratio (OR)=2.000), at the expense of haplotype H1, which is under-transmitted (HBAT P=0.018; OR=0.725). These two common haplotypes differ only at rs12603582 located in intron 11, which reaches a P-value of 0.072 in single-marker FBAT analyses. Interestingly, rs12603582 is strongly associated with pre-term delivery in our ASD patients (P=0.008). On the other hand, it is SNP rs2317385, located at the 5′ end of the gene, that significantly affects 5-HT blood levels (Mann–Whitney U-test, P=0.001; multiple regression analysis, P=0.010). No gene–gene interaction between ITGB3 and SLC6A4 has been detected. In conclusion, we identify a significant association between a common ITGB3 haplotype and ASD. Distinct markers, located toward the 5′ and 3′ ends of the gene, seemingly modulate 5-HT blood levels and autism liability, respectively. Our results also raise interest into ITGB3 influences on feto–maternal immune interactions in autism. PMID:21102624

Mine or Yours? Development of Sharing in Toddlers in Relation to Ownership Understanding

PubMed Central

Brownell, Celia A.; Iesue, Stephanie S.; Nichols, Sara R.; Svetlova, Margarita

2012-01-01

To examine early developments in other-oriented resource sharing, fifty-one 18- and 24-month-old children were administered six tasks with toys or food that could be shared with an adult playmate who had none. On each task the playmate communicated her desire for the items in a series of progressively more explicit cues. Twenty-four-month-olds shared frequently and spontaneously. Eighteen-month-olds shared when given multiple opportunities and when the partner provided enough communicative support. Younger children engaged in self-focused and hypothesis-testing behavior in lieu of sharing more often than did older children. Ownership understanding, separately assessed, was positively associated with sharing and negatively associated with non-sharing behavior, independent of age and language ability. PMID:23145536

A pleiotropy-informed Bayesian false discovery rate adapted to a shared control design finds new disease associations from GWAS summary statistics.

PubMed

Liley, James; Wallace, Chris

2015-02-01

Genome-wide association studies (GWAS) have been successful in identifying single nucleotide polymorphisms (SNPs) associated with many traits and diseases. However, at existing sample sizes, these variants explain only part of the estimated heritability. Leverage of GWAS results from related phenotypes may improve detection without the need for larger datasets. The Bayesian conditional false discovery rate (cFDR) constitutes an upper bound on the expected false discovery rate (FDR) across a set of SNPs whose p values for two diseases are both less than two disease-specific thresholds. Calculation of the cFDR requires only summary statistics and have several advantages over traditional GWAS analysis. However, existing methods require distinct control samples between studies. Here, we extend the technique to allow for some or all controls to be shared, increasing applicability. Several different SNP sets can be defined with the same cFDR value, and we show that the expected FDR across the union of these sets may exceed expected FDR in any single set. We describe a procedure to establish an upper bound for the expected FDR among the union of such sets of SNPs. We apply our technique to pairwise analysis of p values from ten autoimmune diseases with variable sharing of controls, enabling discovery of 59 SNP-disease associations which do not reach GWAS significance after genomic control in individual datasets. Most of the SNPs we highlight have previously been confirmed using replication studies or larger GWAS, a useful validation of our technique; we report eight SNP-disease associations across five diseases not previously declared. Our technique extends and strengthens the previous algorithm, and establishes robust limits on the expected FDR. This approach can improve SNP detection in GWAS, and give insight into shared aetiology between phenotypically related conditions.

Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality.

PubMed

Eppinga, Ruben N; Hagemeijer, Yanick; Burgess, Stephen; Hinds, David A; Stefansson, Kari; Gudbjartsson, Daniel F; van Veldhuisen, Dirk J; Munroe, Patricia B; Verweij, Niek; van der Harst, Pim

2016-12-01

Resting heart rate is a heritable trait correlated with life span. Little is known about the genetic contribution to resting heart rate and its relationship with mortality. We performed a genome-wide association discovery and replication analysis starting with 19.9 million genetic variants and studying up to 265,046 individuals to identify 64 loci associated with resting heart rate (P < 5 × 10 -8 ); 46 of these were novel. We then used the genetic variants identified to study the association between resting heart rate and all-cause mortality. We observed that a genetically predicted resting heart rate increase of 5 beats per minute was associated with a 20% increase in mortality risk (hazard ratio 1.20, 95% confidence interval 1.11-1.28, P = 8.20 × 10 -7 ) translating to a reduction in life expectancy of 2.9 years for males and 2.6 years for females. Our findings provide evidence for shared genetic predictors of resting heart rate and all-cause mortality.

National Evidence on the Use of Shared Decision Making in Prostate-Specific Antigen Screening

PubMed Central

Han, Paul K. J.; Kobrin, Sarah; Breen, Nancy; Joseph, Djenaba A.; Li, Jun; Frosch, Dominick L.; Klabunde, Carrie N.

2013-01-01

PURPOSE Recent clinical practice guidelines on prostate cancer screening using the prostate-specific antigen (PSA) test (PSA screening) have recommended that clinicians practice shared decision making—a process involving clinician-patient discussion of the pros, cons, and uncertainties of screening. We undertook a study to determine the prevalence of shared decision making in both PSA screening and nonscreening, as well as patient characteristics associated with shared decision making. METHODS A nationally representative sample of 3,427 men aged 50 to 74 years participating in the 2010 National Health Interview Survey responded to questions on the extent of shared decision making (past physician-patient discussion of advantages, disadvantages, and scientific uncertainty associated with PSA screening), PSA screening intensity (tests in past 5 years), and sociodemographic and health-related characteristics. RESULTS Nearly two-thirds (64.3%) of men reported no past physician-patient discussion of advantages, disadvantages, or scientific uncertainty (no shared decision making); 27.8% reported discussion of 1 to 2 elements only (partial shared decision making); 8.0% reported discussion of all 3 elements (full shared decision making). Nearly one-half (44.2%) reported no PSA screening, 27.8% reported low-intensity (less-than-annual) screening, and 25.1% reported high-intensity (nearly annual) screening. Absence of shared decision making was more prevalent in men who were not screened; 88% (95% CI, 86.2%–90.1%) of nonscreened men reported no shared decision making compared with 39% (95% CI, 35.0%–43.3%) of men undergoing high-intensity screening. Extent of shared decision making was associated with black race, Hispanic ethnicity, higher education, health insurance, and physician recommendation. Screening intensity was associated with older age, higher education, usual source of medical care, and physician recommendation, as well as with partial vs no or full shared

National evidence on the use of shared decision making in prostate-specific antigen screening.

PubMed

Han, Paul K J; Kobrin, Sarah; Breen, Nancy; Joseph, Djenaba A; Li, Jun; Frosch, Dominick L; Klabunde, Carrie N

2013-01-01

Recent clinical practice guidelines on prostate cancer screening using the prostate-specific antigen (PSA) test (PSA screening) have recommended that clinicians practice shared decision making-a process involving clinician-patient discussion of the pros, cons, and uncertainties of screening. We undertook a study to determine the prevalence of shared decision making in both PSA screening and nonscreening, as well as patient characteristics associated with shared decision making. A nationally representative sample of 3,427 men aged 50 to 74 years participating in the 2010 National Health Interview Survey responded to questions on the extent of shared decision making (past physician-patient discussion of advantages, disadvantages, and scientific uncertainty associated with PSA screening), PSA screening intensity (tests in past 5 years), and sociodemographic and health-related characteristics. Nearly two-thirds (64.3%) of men reported no past physician-patient discussion of advantages, disadvantages, or scientific uncertainty (no shared decision making); 27.8% reported discussion of 1 to 2 elements only (partial shared decision making); 8.0% reported discussion of all 3 elements (full shared decision making). Nearly one-half (44.2%) reported no PSA screening, 27.8% reported low-intensity (less-than-annual) screening, and 25.1% reported high-intensity (nearly annual) screening. Absence of shared decision making was more prevalent in men who were not screened; 88% (95% CI, 86.2%-90.1%) of nonscreened men reported no shared decision making compared with 39% (95% CI, 35.0%-43.3%) of men undergoing high-intensity screening. Extent of shared decision making was associated with black race, Hispanic ethnicity, higher education, health insurance, and physician recommendation. Screening intensity was associated with older age, higher education, usual source of medical care, and physician recommendation, as well as with partial vs no or full shared decision making. Most US men

Meaning-Related and Print-Related Interactions between Preschoolers and Parents during Shared Book Reading and Their Associations with Emergent Literacy Skills

ERIC Educational Resources Information Center

Han, Jisu; Neuharth-Pritchett, Stacey

2015-01-01

This study examined interactions between preschool children and parents during shared book reading by analyzing parental self-report data. Using confirmatory factor analytic procedures and structural equation modeling, this study developed a scale measuring meaning-related and print-related reading interactions and examined their associations with…

Association analysis of rare variants near the APOE region with CSF and neuroimaging biomarkers of Alzheimer's disease.

PubMed

Nho, Kwangsik; Kim, Sungeun; Horgusluoglu, Emrin; Risacher, Shannon L; Shen, Li; Kim, Dokyoon; Lee, Seunggeun; Foroud, Tatiana; Shaw, Leslie M; Trojanowski, John Q; Aisen, Paul S; Petersen, Ronald C; Jack, Clifford R; Weiner, Michael W; Green, Robert C; Toga, Arthur W; Saykin, Andrew J

2017-05-24

The APOE ε4 allele is the most significant common genetic risk factor for late-onset Alzheimer's disease (LOAD). The region surrounding APOE on chromosome 19 has also shown consistent association with LOAD. However, no common variants in the region remain significant after adjusting for APOE genotype. We report a rare variant association analysis of genes in the vicinity of APOE with cerebrospinal fluid (CSF) and neuroimaging biomarkers of LOAD. Whole genome sequencing (WGS) was performed on 817 blood DNA samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sequence data from 757 non-Hispanic Caucasian participants was used in the present analysis. We extracted all rare variants (MAF (minor allele frequency) < 0.05) within a 312 kb window in APOE's vicinity encompassing 12 genes. We assessed CSF and neuroimaging (MRI and PET) biomarkers as LOAD-related quantitative endophenotypes. Gene-based analyses of rare variants were performed using the optimal Sequence Kernel Association Test (SKAT-O). A total of 3,334 rare variants (MAF < 0.05) were found within the APOE region. Among them, 72 rare non-synonymous variants were observed. Eight genes spanning the APOE region were significantly associated with CSF Aβ 1-42 (p < 1.0 × 10 -3 ). After controlling for APOE genotype and adjusting for multiple comparisons, 4 genes (CBLC, BCAM, APOE, and RELB) remained significant. Whole-brain surface-based analysis identified highly significant clusters associated with rare variants of CBLC in the temporal lobe region including the entorhinal cortex, as well as frontal lobe regions. Whole-brain voxel-wise analysis of amyloid PET identified significant clusters in the bilateral frontal and parietal lobes showing associations of rare variants of RELB with cortical amyloid burden. Rare variants within genes spanning the APOE region are significantly associated with LOAD-related CSF Aβ 1-42 and neuroimaging biomarkers after adjusting for APOE genotype

Is rectal douching and sharing douching equipment associated with anorectal chlamydia and gonorrhoea? A cross-sectional study among men who have sex with men.

PubMed

Achterbergh, Rca; van der Helm, J J; van den Boom, W; Heijman, T; Stolte, I G; van Rooijen, M S; de Vries, Hjc

2017-09-01

Men who have sex with men (MSM) are at high risk for anorectal chlamydia and gonorrhoea infections. Many MSM use rectal douches in preparation for sex, which might break down the mucosal barrier function and facilitate the acquisition of STI. We determined whether rectal douching or sharing douching equipment was associated with anorectal chlamydia and gonorrhoea. In a cross-sectional study among 994 MSM attending the STI outpatient clinic of Amsterdam between February and April 2011, data were collected on rectal douching, sexual behaviour and STI. We used multivariable logistic regression analysis to determine the association between rectal douching, including sharing of douching equipment, and anorectal chlamydia and gonorrhoea for those reporting receptive anal sex. We adjusted for other risk behaviour, that is, condom use, number of partners and HIV status. Of 994 MSM, 46% (n=460) practised rectal douching, of whom 25% (n=117) shared douching equipment. Median age was 39 years (IQR 30-47), median number of sex partners in the 6 months prior to consult was five (IQR 3-10) and 289 (29.0%) participants were HIV positive. The prevalence of anorectal chlamydia and/or gonorrhoea for those reporting receptive anal sex was 9.6% (n=96). In multivariable analysis, HIV positivity (aOR=2.2, 95% CI 1.3 to 3.6), younger age (aOR=2.5, CI 1.4 to 4.5 for those aged <35 years compared with those aged ≥45 years), and more sexual partners (aOR=1.2, 95% CI 1.0 to 1.5 for 1 log increase) were significantly associated with anorectal STI. However, rectal douching or sharing douching equipment were not significantly associated with anorectal chlamydia and/or gonorrhoea (p=0.647). Almost half of MSM used rectal douching and a quarter of these shared douching equipment. Though using douching equipment does not appear to contribute to anorectal chlamydia and gonorrhoea in this study, STI prevalence remains high and prevention strategies like early testing and treatment remain

Shared Decision Making: Improving Care for Children with Autism

ERIC Educational Resources Information Center

Golnik, Allison; Maccabee-Ryaboy, Nadia; Scal, Peter; Wey, Andrew; Gaillard, Philippe

2012-01-01

We assessed the extent to which parents of children with autism spectrum disorder report that they are engaged in shared decision making. We measured the association between shared decision making and (a) satisfaction with care, (b) perceived guidance regarding controversial issues in autism spectrum disorder, and (c) perceived assistance…

How might immunization rates change if cost sharing is eliminated?

PubMed

Shen, Angela K; O'Grady, Michael J; McDevitt, Roland D; Pickreign, Jeremy D; Laudenberger, Laura K; Esber, Allahna; Shortridge, Emily F

2014-01-01

There is a debate regarding the effect of cost sharing on immunization, particularly as the Affordable Care Act will eliminate cost sharing for recommended vaccines. This study estimates changes in immunization rates and spending associated with extending first-dollar coverage to privately insured children for four childhood vaccines. We used the 2008 National Immunization Survey and peer-reviewed literature to generate estimates of immunization status for each vaccine by age group and insurance type. We used the Truven Health Analytics 2006 MarketScan Commercial Claims and Encounters Database of line-item medical claims to estimate changes in immunization rates that would result from eliminating cost sharing, and we used the Kaiser Family Foundation/Health Research and Educational Trust Employer Health Benefits Survey to determine the prevalence of coverage for patients with first-dollar coverage, patients who face office visit cost sharing, and patients who face cost sharing for all vaccine cost components. We assumed that once cost sharing is removed, coverage rates in plans that impose cost sharing will rise to the level of plans that do not. We estimate that immunization rates would increase modestly and result in additional direct spending of $26.0 million to insurers/employers. Further, these payers would have an additional $11.0 million in spending associated with eliminating cost sharing for children already receiving immunizations. The effects of eliminating cost sharing for vaccines vary by vaccine. Overall, immunization rates will rise modestly given high insurance coverage for vaccinations, and these increases would be more substantial for those currently facing cost sharing. However, in addition to the removal of cost sharing for immunizations, these findings suggest other strategies to consider to further increase immunization rates.

Exploratory study of bed-sharing and maternal-infant bonding.

PubMed

Mitchell, Edwin A; Hutchison, B Lynne; Thompson, John Md; Wouldes, Trecia A

2015-08-01

Bed-sharing with an infant is controversial due to the increased risk of sudden unexpected death in infancy versus postulated benefits of the practice such as enhanced breastfeeding and maternal-infant bonding. This study evaluated the association between bed-sharing and maternal-infant bonding. Four hundred randomly selected mothers who had delivered in a large maternity unit in Auckland and whose infants were between the ages of 6 weeks and 4 months were sent a postal questionnaire asking about their bed-sharing practices last night, usually, and in the last 2 weeks. Included in the questionnaire were factors 1 and 2 questions from the Postpartum Bonding Questionnaire to assess maternal-infant bonding. Responders totalled 172 (43%), and infants were a mean age of 11 weeks. Fourteen per cent of infants slept in a bed-sharing situation last night, 8% usually, and 41% had slept with an adult in the last 2 weeks. Nine per cent of mothers scored above the cut-off for factor 1 for impaired maternal-infant bonding. Infants of these mothers were more likely to bed-share last night, usually, and in the last 2 weeks, and were less likely to use a pacifier and to breastfeed. Bed-sharing mothers scored more highly on individual questions relating to being annoyed or irritated by their baby. There is an inverse association between bed-sharing and maternal-infant bonding, which is contrary to the often expressed belief that bed-sharing enhances maternal-infant bonding. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

The science of sharing and the sharing of science.

PubMed

Milkman, Katherine L; Berger, Jonah

2014-09-16

Why do members of the public share some scientific findings and not others? What can scientists do to increase the chances that their findings will be shared widely among nonscientists? To address these questions, we integrate past research on the psychological drivers of interpersonal communication with a study examining the sharing of hundreds of recent scientific discoveries. Our findings offer insights into (i) how attributes of a discovery and the way it is described impact sharing, (ii) who generates discoveries that are likely to be shared, and (iii) which types of people are most likely to share scientific discoveries. The results described here, combined with a review of recent research on interpersonal communication, suggest how scientists can frame their work to increase its dissemination. They also provide insights about which audiences may be the best targets for the diffusion of scientific content.

Planning for Bike Share Connectivity to Rail Transit

PubMed Central

Griffin, Greg Phillip; Sener, Ipek Nese

2016-01-01

Bike sharing can play a role in providing access to transit stations and then to final destinations, but early implementation of these systems in North America has been opportunistic rather than strategic. This study evaluates local intermodal plan goals using trip data and associated infrastructure such as transit stops and bike share station locations in Austin, Texas, and Chicago, Illinois. Bike sharing use data from both cities suggest a weak relationship with existing rail stations that could be strengthened through collaborative, intermodal planning. The study suggests a planning framework and example language that could be tailored to help address the linkage between bike sharing and transit. Rather than an exhaustive study of the practice, this study provides evidence from these two cities that identify opportunities to improve intermodal planning. Cities that are planning or expanding a bike sharing system should consider carefully how to leverage this mode with existing modes of transport. Regardless of a city’s status in implementing a bike sharing system, planners can leverage information on existing transport systems for planning at regional and local levels. PMID:27872554

The science of sharing and the sharing of science

PubMed Central

Milkman, Katherine L.; Berger, Jonah

2014-01-01

Why do members of the public share some scientific findings and not others? What can scientists do to increase the chances that their findings will be shared widely among nonscientists? To address these questions, we integrate past research on the psychological drivers of interpersonal communication with a study examining the sharing of hundreds of recent scientific discoveries. Our findings offer insights into (i) how attributes of a discovery and the way it is described impact sharing, (ii) who generates discoveries that are likely to be shared, and (iii) which types of people are most likely to share scientific discoveries. The results described here, combined with a review of recent research on interpersonal communication, suggest how scientists can frame their work to increase its dissemination. They also provide insights about which audiences may be the best targets for the diffusion of scientific content. PMID:25225360

When Sharing Is a Bad Idea: The Effects of Online Social Network Engagement and Sharing Passwords with Friends on Cyberbullying Involvement.

PubMed

Meter, Diana J; Bauman, Sheri

2015-08-01

Every day, children and adolescents communicate online via social networking sites (SNSs). They also report sharing passwords with peers and friends, a potentially risky behavior in regard to cyber safety. This longitudinal study tested the hypotheses that social network engagement in multiple settings would predict more cyberbullying involvement over time, and that youth who reported sharing passwords would also experience an increase in cyberbullying involvement. Data were collected at two time points one year apart from 1,272 third through eighth grade students. In line with the first study hypothesis, participating in more online SNSs was associated with increased cyberbullying involvement over time, as well as sharing passwords over time. Cyberbullying involvement at T1 predicted decreases in sharing passwords over time, suggesting that youth become aware of the dangers of sharing passwords as a result of their experience. Sharing passwords at T1 was unrelated to cyberbullying involvement at T2. Although it seems that youth may be learning from their previous mistakes, due to the widespread use of social media and normality of sharing passwords among young people, it is important to continue to educate youth about cyber safety and risky online behavior.

Sharing data is a shared responsibility: Commentary on: "The essential nature of sharing in science".

PubMed

Giffels, Joe

2010-12-01

Research data should be made readily available. A robust data-sharing plan, led by the principal investigator of the research project, requires considerable administrative and operational resources. Because external support for data sharing is minimal, principal investigators should consider engaging existing institutional information experts, such as librarians and information systems personnel, to participate in data-sharing efforts.

Weak sharing of genetic association signals in three lung cancer subtypes: evidence at the SNP, gene, regulation, and pathway levels.

PubMed

O'Brien, Timothy D; Jia, Peilin; Caporaso, Neil E; Landi, Maria Teresa; Zhao, Zhongming

2018-02-27

There are two main types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC has many subtypes, but the two most common are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). These subtypes are mainly classified by physiological and pathological characteristics, although there is increasing evidence of genetic and molecular differences as well. Although some work has been done at the somatic level to explore the genetic and biological differences among subtypes, little work has been done that interrogates these differences at the germline level to characterize the unique and shared susceptibility genes for each subtype. We used single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) of European samples to interrogate the similarity of the subtypes at the SNP, gene, pathway, and regulatory levels. We expanded these genotyped SNPs to include all SNPs in linkage disequilibrium (LD) using data from the 1000 Genomes Project. We mapped these SNPs to several lung tissue expression quantitative trait loci (eQTL) and enhancer datasets to identify regulatory SNPs and their target genes. We used these genes to perform a biological pathway analysis for each subtype. We identified 8295, 8734, and 8361 SNPs with moderate association signals for LUAD, LUSC, and SCLC, respectively. Those SNPs had p < 1 × 10 - 3 in the original GWAS or were within LD (r 2 > 0.8, Europeans) to the genotyped SNPs. We identified 215, 320, and 172 disease-associated genes for LUAD, LUSC, and SCLC, respectively. Only five genes (CHRNA5, IDH3A, PSMA4, RP11-650 L12.2, and TBC1D2B) overlapped all subtypes. Furthermore, we observed only two pathways from the Kyoto Encyclopedia of Genes and Genomes shared by all subtypes. At the regulatory level, only three eQTL target genes and two enhancer target genes overlapped between all subtypes. Our results suggest that the three lung cancer subtypes do not share much genetic signal

Sharing and re-use of phylogenetic trees (and associated data) to facilitate synthesis.

PubMed

Stoltzfus, Arlin; O'Meara, Brian; Whitacre, Jamie; Mounce, Ross; Gillespie, Emily L; Kumar, Sudhir; Rosauer, Dan F; Vos, Rutger A

2012-10-22

Recently, various evolution-related journals adopted policies to encourage or require archiving of phylogenetic trees and associated data. Such attention to practices that promote sharing of data reflects rapidly improving information technology, and rapidly expanding potential to use this technology to aggregate and link data from previously published research. Nevertheless, little is known about current practices, or best practices, for publishing trees and associated data so as to promote re-use. Here we summarize results of an ongoing analysis of current practices for archiving phylogenetic trees and associated data, current practices of re-use, and current barriers to re-use. We find that the technical infrastructure is available to support rudimentary archiving, but the frequency of archiving is low. Currently, most phylogenetic knowledge is not easily re-used due to a lack of archiving, lack of awareness of best practices, and lack of community-wide standards for formatting data, naming entities, and annotating data. Most attempts at data re-use seem to end in disappointment. Nevertheless, we find many positive examples of data re-use, particularly those that involve customized species trees generated by grafting to, and pruning from, a much larger tree. The technologies and practices that facilitate data re-use can catalyze synthetic and integrative research. However, success will require engagement from various stakeholders including individual scientists who produce or consume shareable data, publishers, policy-makers, technology developers and resource-providers. The critical challenges for facilitating re-use of phylogenetic trees and associated data, we suggest, include: a broader commitment to public archiving; more extensive use of globally meaningful identifiers; development of user-friendly technology for annotating, submitting, searching, and retrieving data and their metadata; and development of a minimum reporting standard (MIAPA) indicating

Patient cost-sharing and insurance arrangements are associated with hospital readmissions after abdominal surgery: Implications for access and quality health care.

PubMed

Youn, Bora; Soley-Bori, Marina; Soria-Saucedo, Rene; Ryan, Colleen M; Schneider, Jeffrey C; Haynes, Alex B; Cabral, Howard J; Kazis, Lewis E

2016-03-01

Readmission rates after operative procedures are used increasingly as a measure of hospital care quality. Patient access to care may influence readmission rates. The objective of this study was to determine the relationship between patient cost-sharing, insurance arrangements, and the risk of postoperative readmissions. Using the MarketScan Research Database (n = 121,002), we examined privately insured, nonelderly patients who underwent abdominal surgery in 2010. The main outcome measures were risk-adjusted unplanned readmissions within 7 days and 30 days of discharge. Odds of readmissions were compared with multivariable logistic regression models. In adjusted models, $1,284 increase in patient out-of-pocket payments during index admission (a difference of one standard deviation) was associated with 19% decrease in the odds of 7-day readmission (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.78-0.85) and 17% decrease in the odds of 30-day readmission (OR 0.83, 95% CI 0.81-0.86). Patients in the noncapitated point-of-service plans (OR 1.19, 95% CI 1.07-1.33), preferred provider organization plans (OR 1.11, 95% CI 1.03-1.19), and high-deductible plans (OR 1.12, 95% CI 1.00-1.26) were more likely to be readmitted within 30 days compared with patients in the capitated health maintenance organization and point-of-service plans. Among privately insured, nonelderly patients, increased patient cost-sharing was associated with lower odds of 7-day and 30-day readmission after abdominal surgery. Insurance arrangements also were significantly associated with postoperative readmissions. Patient cost sharing and insurance arrangements need consideration in the provision of equitable access for quality care. Copyright © 2016 Elsevier Inc. All rights reserved.

Threshold quantum secret sharing based on single qubit

NASA Astrophysics Data System (ADS)

Lu, Changbin; Miao, Fuyou; Meng, Keju; Yu, Yue

2018-03-01

Based on unitary phase shift operation on single qubit in association with Shamir's ( t, n) secret sharing, a ( t, n) threshold quantum secret sharing scheme (or ( t, n)-QSS) is proposed to share both classical information and quantum states. The scheme uses decoy photons to prevent eavesdropping and employs the secret in Shamir's scheme as the private value to guarantee the correctness of secret reconstruction. Analyses show it is resistant to typical intercept-and-resend attack, entangle-and-measure attack and participant attacks such as entanglement swapping attack. Moreover, it is easier to realize in physic and more practical in applications when compared with related ones. By the method in our scheme, new ( t, n)-QSS schemes can be easily constructed using other classical ( t, n) secret sharing.

Higher-order language dysfunctions as a possible neurolinguistic endophenotype for schizophrenia: Evidence from patients and their unaffected first degree relatives.

PubMed

Pawełczyk, Agnieszka; Łojek, Emila; Żurner, Natalia; Gawłowska-Sawosz, Marta; Pawełczyk, Tomasz

2018-05-31

The purpose of the study was to examine the presence of pragmatic dysfunctions in first episode (FE) subjects and their healthy first degree relatives as a potential endophenotype for schizophrenia. Thirty-four FE patients, 34 parents of the patients (REL) and 32 healthy controls (HC) took part in the study. Pragmatic language functions were evaluated with the Right Hemisphere Language Battery, attention and executive functions were controlled, as well as age and education level. The parents differed from HC but not from their FE offspring with regard to overall level of language and communication and the general knowledge component of language processing. The FE participants differed from HC in comprehension of inferred meaning, emotional prosody, discourse dimensions, overall level of language and communication, language processing with regard to general knowledge and communication competences. The FE participants differed from REL regarding discourse dimensions. Our findings suggest that pragmatic dysfunctions may act as vulnerability markers of schizophrenia; their assessment may help in the diagnosis of early stages of the illness and in understanding its pathophysiology. In future research the adoptive and biological parents of schizophrenia patients should be compared to elucidate which language failures reflect genetic vulnerability and which ones environmental factors. Copyright © 2018. Published by Elsevier B.V.

Simultaneous profiling of seed-associated bacteria and fungi reveals antagonistic interactions between microorganisms within a shared epiphytic microbiome on Triticum and Brassica seeds

PubMed Central

Links, Matthew G; Demeke, Tigst; Gräfenhan, Tom; Hill, Janet E; Hemmingsen, Sean M; Dumonceaux, Tim J

2014-01-01

In order to address the hypothesis that seeds from ecologically and geographically diverse plants harbor characteristic epiphytic microbiota, we characterized the bacterial and fungal microbiota associated with Triticum and Brassica seed surfaces. The total microbial complement was determined by amplification and sequencing of a fragment of chaperonin 60 (cpn60). Specific microorganisms were quantified by qPCR. Bacteria and fungi corresponding to operational taxonomic units (OTU) that were identified in the sequencing study were isolated and their interactions examined. A total of 5477 OTU were observed from seed washes. Neither total epiphytic bacterial load nor community richness/evenness was significantly different between the seed types; 578 OTU were shared among all samples at a variety of abundances. Hierarchical clustering revealed that 203 were significantly different in abundance on Triticum seeds compared with Brassica. Microorganisms isolated from seeds showed 99–100% identity between the cpn60 sequences of the isolates and the OTU sequences from this shared microbiome. Bacterial strains identified as Pantoea agglomerans had antagonistic properties toward one of the fungal isolates (Alternaria sp.), providing a possible explanation for their reciprocal abundances on both Triticum and Brassica seeds. cpn60 enabled the simultaneous profiling of bacterial and fungal microbiota and revealed a core seed-associated microbiota shared between diverse plant genera. PMID:24444052

A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2, TAGAP, and PUS10 As Shared Risk Loci for Crohn's Disease and Celiac Disease

PubMed Central

Boucher, Gabrielle; Beauchamp, Claudine; Trynka, Gosia; Dubois, Patrick C.; Lagacé, Caroline; Stokkers, Pieter C. F.; Hommes, Daan W.; Barisani, Donatella; Palmieri, Orazio; Annese, Vito; van Heel, David A.; Weersma, Rinse K.; Daly, Mark J.; Wijmenga, Cisca; Rioux, John D.

2011-01-01

Crohn's disease (CD) and celiac disease (CelD) are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS) datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls) and CD (3,230 cases, 4,829 controls) were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0×10−5 in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value <1×10−2 in CelD and <1×10−3 in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37×10−8 and 6.39×10−9, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls) and CD (1,835 cases and 1,669 controls) cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071) in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55×10−10 and 1.38×10−11 respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a relatively small effect. PMID:21298027

Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction in mice selectively bred for low levels of anxiety

PubMed Central

Yen, Yi-Chun; Anderzhanova, Elmira; Bunck, Mirjam; Schuller, Julia; Landgraf, Rainer; Wotjak, Carsten T.

2013-01-01

We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB) coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania, and attention deficit hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically examined LAB mice with respect to unique and overlapping endophenotypes of the three diseases. To this end Venn diagrams were used as an instrument for discrimination of possible models. We arranged the endophenotypes in Venn diagrams and translated them into different behavioral tests. LAB mice showed elevated levels of locomotion in the open field (OF) test with deficits in habituation, compared to mice bred for normal (NAB) and high anxiety-related behavior (HAB). Cross-breeding of hypoactive HAB and hyperactive LAB mice resulted in offspring showing a low level of locomotion comparable to HAB mice, indicating that the HAB alleles are dominant over LAB alleles in determining the level of locomotion. In a holeboard test, LAB mice spent less time in hole exploration, as shown in patients with schizophrenia and ADHD; however, LAB mice displayed no impairments in social interaction and prepulse inhibition (PPI), implying a unlikelihood of LAB as an animal model of schizophrenia. Although LAB mice displayed hyperarousal, active coping styles, and cognitive deficits, symptoms shared by mania and ADHD, they failed to reveal the classic manic endophenotypes, such as increased hedonia and object interaction. The neuroleptic haloperidol reduced locomotor activity in all mouse lines. The mood stabilizer lithium and the psychostimulant amphetamine, in contrast, selectively reduced hyperactivity in LAB mice. Based on the behavioral and pharmacological profiles, LAB mice are suggested as a novel rodent model of ADHD-like symptoms

Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction in mice selectively bred for low levels of anxiety.

PubMed

Yen, Yi-Chun; Anderzhanova, Elmira; Bunck, Mirjam; Schuller, Julia; Landgraf, Rainer; Wotjak, Carsten T

2013-01-01

We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB) coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania, and attention deficit hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically examined LAB mice with respect to unique and overlapping endophenotypes of the three diseases. To this end Venn diagrams were used as an instrument for discrimination of possible models. We arranged the endophenotypes in Venn diagrams and translated them into different behavioral tests. LAB mice showed elevated levels of locomotion in the open field (OF) test with deficits in habituation, compared to mice bred for normal (NAB) and high anxiety-related behavior (HAB). Cross-breeding of hypoactive HAB and hyperactive LAB mice resulted in offspring showing a low level of locomotion comparable to HAB mice, indicating that the HAB alleles are dominant over LAB alleles in determining the level of locomotion. In a holeboard test, LAB mice spent less time in hole exploration, as shown in patients with schizophrenia and ADHD; however, LAB mice displayed no impairments in social interaction and prepulse inhibition (PPI), implying a unlikelihood of LAB as an animal model of schizophrenia. Although LAB mice displayed hyperarousal, active coping styles, and cognitive deficits, symptoms shared by mania and ADHD, they failed to reveal the classic manic endophenotypes, such as increased hedonia and object interaction. The neuroleptic haloperidol reduced locomotor activity in all mouse lines. The mood stabilizer lithium and the psychostimulant amphetamine, in contrast, selectively reduced hyperactivity in LAB mice. Based on the behavioral and pharmacological profiles, LAB mice are suggested as a novel rodent model of ADHD-like symptoms.

Shared Resources

Treesearch

David B. Butts

1987-01-01

Wildfires do not respect property boundaries. Whole geographic regions are typically impacted by major wildfire outbreaks. Various fire related resources can be shared to solve such crises; whether they are shared, and how they are shared depends to a great extent upon the rapport among the agencies involved. Major progress has been achieved over the past decade...

Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients.

PubMed

Zaba, Monika; Kirmeier, Thomas; Ionescu, Irina A; Wollweber, Bastian; Buell, Dominik R; Gall-Kleebach, Dominique J; Schubert, Christine F; Novak, Bozidar; Huber, Christine; Köhler, Katharina; Holsboer, Florian; Pütz, Benno; Müller-Myhsok, Bertram; Höhne, Nina; Uhr, Manfred; Ising, Marcus; Herrmann, Leonie; Schmidt, Ulrike

2015-05-01

Analysis of the function of the hypothalamic-pituitary-adrenal (HPA)-axis in patients suffering from posttraumatic stress disorder (PTSD) has hitherto produced inconsistent findings, inter alia in the Trier Social Stress Test (TSST). To address these inconsistencies, we compared a sample of 23 female PTSD patients with either early life trauma (ELT) or adult trauma (AT) or combined ELT and AT to 18 age-matched non-traumatized female healthy controls in the TSST which was preceded by intensive baseline assessments. During the TSST, we determined a variety of clinical, psychological, endocrine and cardiovascular parameters as well as expression levels of four HPA-axis related genes. Using a previously reported definition of HPA-axis responsive versus non-responsive phenotypes, we identified for the first time two clinically and biologically distinct HPA-axis reactivity subgroups of PTSD. One subgroup ("non-responders") showed a blunted HPA-axis response and distinct clinical and biological characteristics such as a higher prevalence of trauma-related dissociative symptoms and of combined AT and ELT as well as alterations in the expression kinetics of the genes encoding for the mineralocorticoid receptor (MR) and for FK506 binding protein 51 (FKBP51). Interestingly, this non-responder subgroup largely drove the relatively diminished HPA axis response of the total cohort of PTSD patients. These findings are limited by the facts that the majority of patients was medicated, by the lack of traumatized controls and by the relatively small sample size. The here for the first time identified and characterized HPA-axis reactivity endophenotypes offer an explanation for the inconsistent reports on HPA-axis function in PTSD and, moreover, suggest that most likely other factors than HPA-axis reactivity play a decisive role in determination of PTSD core symptom severity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis of shared heritability in common disorders of the brain.

PubMed

Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K; Walters, Raymond K; Bras, Jose; Duncan, Laramie; Escott-Price, Valentina; Falcone, Guido J; Gormley, Padhraig; Malik, Rainer; Patsopoulos, Nikolaos A; Ripke, Stephan; Wei, Zhi; Yu, Dongmei; Lee, Phil H; Turley, Patrick; Grenier-Boley, Benjamin; Chouraki, Vincent; Kamatani, Yoichiro; Berr, Claudine; Letenneur, Luc; Hannequin, Didier; Amouyel, Philippe; Boland, Anne; Deleuze, Jean-François; Duron, Emmanuelle; Vardarajan, Badri N; Reitz, Christiane; Goate, Alison M; Huentelman, Matthew J; Kamboh, M Ilyas; Larson, Eric B; Rogaeva, Ekaterina; St George-Hyslop, Peter; Hakonarson, Hakon; Kukull, Walter A; Farrer, Lindsay A; Barnes, Lisa L; Beach, Thomas G; Demirci, F Yesim; Head, Elizabeth; Hulette, Christine M; Jicha, Gregory A; Kauwe, John S K; Kaye, Jeffrey A; Leverenz, James B; Levey, Allan I; Lieberman, Andrew P; Pankratz, Vernon S; Poon, Wayne W; Quinn, Joseph F; Saykin, Andrew J; Schneider, Lon S; Smith, Amanda G; Sonnen, Joshua A; Stern, Robert A; Van Deerlin, Vivianna M; Van Eldik, Linda J; Harold, Denise; Russo, Giancarlo; Rubinsztein, David C; Bayer, Anthony; Tsolaki, Magda; Proitsi, Petra; Fox, Nick C; Hampel, Harald; Owen, Michael J; Mead, Simon; Passmore, Peter; Morgan, Kevin; Nöthen, Markus M; Rossor, Martin; Lupton, Michelle K; Hoffmann, Per; Kornhuber, Johannes; Lawlor, Brian; McQuillin, Andrew; Al-Chalabi, Ammar; Bis, Joshua C; Ruiz, Agustin; Boada, Mercè; Seshadri, Sudha; Beiser, Alexa; Rice, Kenneth; van der Lee, Sven J; De Jager, Philip L; Geschwind, Daniel H; Riemenschneider, Matthias; Riedel-Heller, Steffi; Rotter, Jerome I; Ransmayr, Gerhard; Hyman, Bradley T; Cruchaga, Carlos; Alegret, Montserrat; Winsvold, Bendik; Palta, Priit; Farh, Kai-How; Cuenca-Leon, Ester; Furlotte, Nicholas; Kurth, Tobias; Ligthart, Lannie; Terwindt, Gisela M; Freilinger, Tobias; Ran, Caroline; Gordon, Scott D; Borck, Guntram; Adams, Hieab H H; Lehtimäki, Terho; Wedenoja, Juho; Buring, Julie E; Schürks, Markus; Hrafnsdottir, Maria; Hottenga, Jouke-Jan; Penninx, Brenda; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Martin, Nicholas G; Montgomery, Grant W; Kurki, Mitja I; Hämäläinen, Eija; Huang, Hailiang; Huang, Jie; Sandor, Cynthia; Webber, Caleb; Muller-Myhsok, Bertram; Schreiber, Stefan; Salomaa, Veikko; Loehrer, Elizabeth; Göbel, Hartmut; Macaya, Alfons; Pozo-Rosich, Patricia; Hansen, Thomas; Werge, Thomas; Kaprio, Jaakko; Metspalu, Andres; Kubisch, Christian; Ferrari, Michel D; Belin, Andrea C; van den Maagdenberg, Arn M J M; Zwart, John-Anker; Boomsma, Dorret; Eriksson, Nicholas; Olesen, Jes; Chasman, Daniel I; Nyholt, Dale R; Avbersek, Andreja; Baum, Larry; Berkovic, Samuel; Bradfield, Jonathan; Buono, Russell; Catarino, Claudia B; Cossette, Patrick; De Jonghe, Peter; Depondt, Chantal; Dlugos, Dennis; Ferraro, Thomas N; French, Jacqueline; Hjalgrim, Helle; Jamnadas-Khoda, Jennifer; Kälviäinen, Reetta; Kunz, Wolfram S; Lerche, Holger; Leu, Costin; Lindhout, Dick; Lo, Warren; Lowenstein, Daniel; McCormack, Mark; Møller, Rikke S; Molloy, Anne; Ng, Ping-Wing; Oliver, Karen; Privitera, Michael; Radtke, Rodney; Ruppert, Ann-Kathrin; Sander, Thomas; Schachter, Steven; Schankin, Christoph; Scheffer, Ingrid; Schoch, Susanne; Sisodiya, Sanjay M; Smith, Philip; Sperling, Michael; Striano, Pasquale; Surges, Rainer; Thomas, G Neil; Visscher, Frank; Whelan, Christopher D; Zara, Federico; Heinzen, Erin L; Marson, Anthony; Becker, Felicitas; Stroink, Hans; Zimprich, Fritz; Gasser, Thomas; Gibbs, Raphael; Heutink, Peter; Martinez, Maria; Morris, Huw R; Sharma, Manu; Ryten, Mina; Mok, Kin Y; Pulit, Sara; Bevan, Steve; Holliday, Elizabeth; Attia, John; Battey, Thomas; Boncoraglio, Giorgio; Thijs, Vincent; Chen, Wei-Min; Mitchell, Braxton; Rothwell, Peter; Sharma, Pankaj; Sudlow, Cathie; Vicente, Astrid; Markus, Hugh; Kourkoulis, Christina; Pera, Joana; Raffeld, Miriam; Silliman, Scott; Boraska Perica, Vesna; Thornton, Laura M; Huckins, Laura M; William Rayner, N; Lewis, Cathryn M; Gratacos, Monica; Rybakowski, Filip; Keski-Rahkonen, Anna; Raevuori, Anu; Hudson, James I; Reichborn-Kjennerud, Ted; Monteleone, Palmiero; Karwautz, Andreas; Mannik, Katrin; Baker, Jessica H; O'Toole, Julie K; Trace, Sara E; Davis, Oliver S P; Helder, Sietske G; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Danner, Unna N; van Elburg, Annemarie A; Clementi, Maurizio; Forzan, Monica; Docampo, Elisa; Lissowska, Jolanta; Hauser, Joanna; Tortorella, Alfonso; Maj, Mario; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Papezova, Hana; Yilmaz, Zeynep; Wagner, Gudrun; Cohen-Woods, Sarah; Herms, Stefan; Julià, Antonio; Rabionet, Raquel; Dick, Danielle M; Ripatti, Samuli; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri J; Steen, Vidar M; Pinto, Dalila; Scherer, Stephen W; Aschauer, Harald; Schosser, Alexandra; Alfredsson, Lars; Padyukov, Leonid; Halmi, Katherine A; Mitchell, James; Strober, Michael; Bergen, Andrew W; Kaye, Walter; Szatkiewicz, Jin Peng; Cormand, Bru; Ramos-Quiroga, Josep Antoni; Sánchez-Mora, Cristina; Ribasés, Marta; Casas, Miguel; Hervas, Amaia; Arranz, Maria Jesús; Haavik, Jan; Zayats, Tetyana; Johansson, Stefan; Williams, Nigel; Dempfle, Astrid; Rothenberger, Aribert; Kuntsi, Jonna; Oades, Robert D; Banaschewski, Tobias; Franke, Barbara; Buitelaar, Jan K; Arias Vasquez, Alejandro; Doyle, Alysa E; Reif, Andreas; Lesch, Klaus-Peter; Freitag, Christine; Rivero, Olga; Palmason, Haukur; Romanos, Marcel; Langley, Kate; Rietschel, Marcella; Witt, Stephanie H; Dalsgaard, Soeren; Børglum, Anders D; Waldman, Irwin; Wilmot, Beth; Molly, Nikolas; Bau, Claiton H D; Crosbie, Jennifer; Schachar, Russell; Loo, Sandra K; McGough, James J; Grevet, Eugenio H; Medland, Sarah E; Robinson, Elise; Weiss, Lauren A; Bacchelli, Elena; Bailey, Anthony; Bal, Vanessa; Battaglia, Agatino; Betancur, Catalina; Bolton, Patrick; Cantor, Rita; Celestino-Soper, Patrícia; Dawson, Geraldine; De Rubeis, Silvia; Duque, Frederico; Green, Andrew; Klauck, Sabine M; Leboyer, Marion; Levitt, Pat; Maestrini, Elena; Mane, Shrikant; De-Luca, Daniel Moreno-; Parr, Jeremy; Regan, Regina; Reichenberg, Abraham; Sandin, Sven; Vorstman, Jacob; Wassink, Thomas; Wijsman, Ellen; Cook, Edwin; Santangelo, Susan; Delorme, Richard; Rogé, Bernadette; Magalhaes, Tiago; Arking, Dan; Schulze, Thomas G; Thompson, Robert C; Strohmaier, Jana; Matthews, Keith; Melle, Ingrid; Morris, Derek; Blackwood, Douglas; McIntosh, Andrew; Bergen, Sarah E; Schalling, Martin; Jamain, Stéphane; Maaser, Anna; Fischer, Sascha B; Reinbold, Céline S; Fullerton, Janice M; Guzman-Parra, José; Mayoral, Fermin; Schofield, Peter R; Cichon, Sven; Mühleisen, Thomas W; Degenhardt, Franziska; Schumacher, Johannes; Bauer, Michael; Mitchell, Philip B; Gershon, Elliot S; Rice, John; Potash, James B; Zandi, Peter P; Craddock, Nick; Ferrier, I Nicol; Alda, Martin; Rouleau, Guy A; Turecki, Gustavo; Ophoff, Roel; Pato, Carlos; Anjorin, Adebayo; Stahl, Eli; Leber, Markus; Czerski, Piotr M; Cruceanu, Cristiana; Jones, Ian R; Posthuma, Danielle; Andlauer, Till F M; Forstner, Andreas J; Streit, Fabian; Baune, Bernhard T; Air, Tracy; Sinnamon, Grant; Wray, Naomi R; MacIntyre, Donald J; Porteous, David; Homuth, Georg; Rivera, Margarita; Grove, Jakob; Middeldorp, Christel M; Hickie, Ian; Pergadia, Michele; Mehta, Divya; Smit, Johannes H; Jansen, Rick; de Geus, Eco; Dunn, Erin; Li, Qingqin S; Nauck, Matthias; Schoevers, Robert A; Beekman, Aartjan Tf; Knowles, James A; Viktorin, Alexander; Arnold, Paul; Barr, Cathy L; Bedoya-Berrio, Gabriel; Bienvenu, O Joseph; Brentani, Helena; Burton, Christie; Camarena, Beatriz; Cappi, Carolina; Cath, Danielle; Cavallini, Maria; Cusi, Daniele; Darrow, Sabrina; Denys, Damiaan; Derks, Eske M; Dietrich, Andrea; Fernandez, Thomas; Figee, Martijn; Freimer, Nelson; Gerber, Gloria; Grados, Marco; Greenberg, Erica; Hanna, Gregory L; Hartmann, Andreas; Hirschtritt, Matthew E; Hoekstra, Pieter J; Huang, Alden; Huyser, Chaim; Illmann, Cornelia; Jenike, Michael; Kuperman, Samuel; Leventhal, Bennett; Lochner, Christine; Lyon, Gholson J; Macciardi, Fabio; Madruga-Garrido, Marcos; Malaty, Irene A; Maras, Athanasios; McGrath, Lauren; Miguel, Eurípedes C; Mir, Pablo; Nestadt, Gerald; Nicolini, Humberto; Okun, Michael S; Pakstis, Andrew; Paschou, Peristera; Piacentini, John; Pittenger, Christopher; Plessen, Kerstin; Ramensky, Vasily; Ramos, Eliana M; Reus, Victor; Richter, Margaret A; Riddle, Mark A; Robertson, Mary M; Roessner, Veit; Rosário, Maria; Samuels, Jack F; Sandor, Paul; Stein, Dan J; Tsetsos, Fotis; Van Nieuwerburgh, Filip; Weatherall, Sarah; Wendland, Jens R; Wolanczyk, Tomasz; Worbe, Yulia; Zai, Gwyneth; Goes, Fernando S; McLaughlin, Nicole; Nestadt, Paul S; Grabe, Hans-Jorgen; Depienne, Christel; Konkashbaev, Anuar; Lanzagorta, Nuria; Valencia-Duarte, Ana; Bramon, Elvira; Buccola, Nancy; Cahn, Wiepke; Cairns, Murray; Chong, Siow A; Cohen, David; Crespo-Facorro, Benedicto; Crowley, James; Davidson, Michael; DeLisi, Lynn; Dinan, Timothy; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Haan, Lieuwe; Hougaard, David; Karachanak-Yankova, Sena; Khrunin, Andrey; Klovins, Janis; Kučinskas, Vaidutis; Lee Chee Keong, Jimmy; Limborska, Svetlana; Loughland, Carmel; Lönnqvist, Jouko; Maher, Brion; Mattheisen, Manuel; McDonald, Colm; Murphy, Kieran C; Nenadic, Igor; van Os, Jim; Pantelis, Christos; Pato, Michele; Petryshen, Tracey; Quested, Digby; Roussos, Panos; Sanders, Alan R; Schall, Ulrich; Schwab, Sibylle G; Sim, Kang; So, Hon-Cheong; Stögmann, Elisabeth; Subramaniam, Mythily; Toncheva, Draga; Waddington, John; Walters, James; Weiser, Mark; Cheng, Wei; Cloninger, Robert; Curtis, David; Gejman, Pablo V; Henskens, Frans; Mattingsdal, Morten; Oh, Sang-Yun; Scott, Rodney; Webb, Bradley; Breen, Gerome; Churchhouse, Claire; Bulik, Cynthia M; Daly, Mark; Dichgans, Martin; Faraone, Stephen V; Guerreiro, Rita; Holmans, Peter; Kendler, Kenneth S; Koeleman, Bobby; Mathews, Carol A; Price, Alkes; Scharf, Jeremiah; Sklar, Pamela; Williams, Julie; Wood, Nicholas W; Cotsapas, Chris; Palotie, Aarno; Smoller, Jordan W; Sullivan, Patrick; Rosand, Jonathan; Corvin, Aiden; Neale, Benjamin M

2018-06-22

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Association of the Shared Epitope, Smoking and the Interaction Between the Two With the Presence of Autoantibodies (Anti-CCP and FR) in Patients With Rheumatoid Arthritis in a Hospital in Seville, Spain.

PubMed

García de Veas Silva, José Luis; González Rodríguez, Concepción; Hernández Cruz, Blanca

2017-11-01

To evaluate the association of shared epitope, smoking and their interaction on the presence of autoantibodies (anti-cyclic citrullinated peptide [CCP] antibodies and rheumatoid factor) in patients with rheumatoid arthritis in our geographical area. A descriptive and cross-sectional study was carried out in a cohort of 106 patients diagnosed with RA. Odds ratios (OR) for antibody development were calculated for shared epitope, tobacco exposure and smoking dose. Statistical analysis was performed with univariate and multivariate statistics using ordinal logistic regression. Odds ratios were calculated with 95% confidence interval (95% CI) and a value of P<.05 was considered significant. In univariate analysis, shared epitope (OR=2.68; 95% CI: 1.11-6.46), tobacco exposure (OR=2.79; 95% CI: 1.12-6.97) and heavy smoker (>20 packs/year) (OR=8.93; 95% CI: 1.95-40.82) were associated with the presence of anti-CCP antibodies. For rheumatoid factor, the association was only significant for tobacco exposure (OR=3.89; 95% CI: 1.06-14.28) and smoking dose (OR=8.33; 95% CI: 1.05-66.22). By ordinal logistic regression analysis, an association with high titers of anti-CCP (>200U/mL) was identified with South American mestizos, patients with homozygous shared epitope, positive FR and heavy smokers. Being a South American mestizo, having a shared epitope, rheumatoid factor positivity and a smoking dose>20 packs/year are independent risk factors for the development of rheumatoid arthritis with a high titer of anti-CCP (>200U/mL). In shared epitope-positive rheumatoid arthritis patients, the intensity of smoking is more strongly associated than tobacco exposure with an increased risk of positive anti-CCP. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Shared Governance and Work Engagement in Emergency Nurses.

PubMed

Siller, Jennifer; Dolansky, Mary A; Clavelle, Joanne T; Fitzpatrick, Joyce J

2016-07-01

Lack of work engagement in emergency nurses has been linked to increased job turnover, burnout, and lack of job satisfaction. Shared governance is a vehicle that can be used by emergency nursing leaders to increase work engagement among emergency nurses. Research is lacking about the relationship between perceptions of shared governance and work engagement in emergency nurses. In this study we examined the relationship between ED nurses' perceptions of shared governance and work engagement. A descriptive correlation design was used with a convenience sample of 43 emergency nurses recruited through the ENA Web site. Participants completed a demographic questionnaire, the Index of Professional Nursing Governance Tool, and the Utrecht Work Engagement Scale. The mean total work engagement score indicated average engagement (M = 4.4, standard deviation = 1.2). A significant positive relationship was found between shared governance and work engagement, indicating that as perceptions of shared governance increase, work engagement increases (r (41) = 0.62, P < .001). The study provides beginning evidence on the relationship of shared governance and work engagement in emergency nurses. Understanding the relationship between perceptions of shared governance and work engagement in emergency nurses may assist emergency nursing leaders in developing and testing interventions to enhance it. Copyright © 2016 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

HydroShare: A Platform for Collaborative Data and Model Sharing in Hydrology

NASA Astrophysics Data System (ADS)

Tarboton, D. G.; Idaszak, R.; Horsburgh, J. S.; Ames, D. P.; Goodall, J. L.; Couch, A.; Hooper, R. P.; Dash, P. K.; Stealey, M.; Yi, H.; Bandaragoda, C.; Castronova, A. M.

2017-12-01

HydroShare is an online, collaboration system for sharing of hydrologic data, analytical tools, and models. It supports the sharing of and collaboration around "resources" which are defined by standardized content types for data formats and models commonly used in hydrology. With HydroShare you can: Share your data and models with colleagues; Manage who has access to the content that you share; Share, access, visualize and manipulate a broad set of hydrologic data types and models; Use the web services application programming interface (API) to program automated and client access; Publish data and models and obtain a citable digital object identifier (DOI); Aggregate your resources into collections; Discover and access data and models published by others; Use web apps to visualize, analyze and run models on data in HydroShare. This presentation will describe the functionality and architecture of HydroShare highlighting its use as a virtual environment supporting education and research. HydroShare has components that support: (1) resource storage, (2) resource exploration, and (3) web apps for actions on resources. The HydroShare data discovery, sharing and publishing functions as well as HydroShare web apps provide the capability to analyze data and execute models completely in the cloud (servers remote from the user) overcoming desktop platform limitations. The HydroShare GIS app provides a basic capability to visualize spatial data. The HydroShare JupyterHub Notebook app provides flexible and documentable execution of Python code snippets for analysis and modeling in a way that results can be shared among HydroShare users and groups to support research collaboration and education. We will discuss how these developments can be used to support different types of educational efforts in Hydrology where being completely web based is of value in an educational setting as students can all have access to the same functionality regardless of their computer.

Shared Secrets versus Secrets Kept Private Are Linked to Better Adolescent Adjustment

ERIC Educational Resources Information Center

Frijns, Tom; Finkenauer, Catrin; Keijsers, Loes

2013-01-01

It is a household notion that secrecy is bad while sharing is good. But what about shared secrets? The present research adopts a functional analysis of sharing secrets, arguing that it should negate harmful consequences generally associated with secrecy and serves important interpersonal functions in adolescence. A survey study among 790 Dutch…

Precompetitive Data Sharing as a Catalyst to Address Unmet Needs in Parkinson’s Disease 1

PubMed Central

Stephenson, Diane; Hu, Michele T.; Romero, Klaus; Breen, Kieran; Burn, David; Ben-Shlomo, Yoav; Bhattaram, Atul; Isaac, Maria; Venuto, Charles; Kubota, Ken; Little, Max A.; Friend, Stephen; Lovestone, Simon; Morris, Huw R.; Grosset, Donald; Sutherland, Margaret; Gallacher, John; Williams-Gray, Caroline; Bain, Lisa J.; Avilés, Enrique; Marek, Ken; Toga, Arthur W.; Stark, Yafit; Forrest Gordon, Mark; Ford, Steve

2015-01-01

Abstract Parkinson’s disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson’s UK and co-organized by Critical Path Institute’s (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson’s disease. PMID:26406139

Aggression is associated with greater subsequent alcohol consumption: A shared neural basis in the ventral striatum.

PubMed

Chester, David S; DeWall, C Nathan

2018-05-01

Alcohol use and abuse (e.g., binge drinking) are among the most reliable causes of aggressive behavior. Conversely, people with aggressive dispositions (e.g., intermittent explosive disorder) are at greater risk for subsequent substance abuse. Yet it remains unknown why aggression might promote subsequent alcohol use. Both aggressive acts and alcohol use are rewarding and linked to greater activity in neural reward circuitry. Through this shared instantiation of reward, aggression may then increase subsequent alcohol consumption. Supporting this mechanistic hypothesis, participants' aggressive behavior directed at someone who had recently rejected them, was associated with more subsequent beer consumption on an ad-lib drinking task. Using functional MRI, both aggressive behavior and beer consumption were associated with greater activity in the bilateral ventral striatum during acts of retaliatory aggression. These results imply that aggression is linked to subsequent alcohol abuse, and that a mechanism underlying this effect is likely to be the activation of the brain's reward circuitry during aggressive acts. © 2018 Wiley Periodicals, Inc.

Obsessive-compulsive disorder spectrum as a scientific "metaphor".

PubMed

Pallanti, Stefano; Hollander, Eric

2008-09-01

As a result of clinical, epidemiological, neuroimaging, and therapy studies that took place in the late 1980s, obsessive-compulsive disorder (OCD) has been well-characterized in the field of anxiety disorders. Other disorders attracted attention for their similarities to OCD, and were located in the orbit of the disorder. OCD has become known as the "primary domain" of a scientific "metaphor" comprising the putative cluster of OCD-related disorders (OCRDs). It is a "paradigm" with which to explore basal ganglia dysfunction. The OCRDs share common phenomenology, comorbidities, lifetime course, demographics, possible genetics, and frontostriatal dysfunction (particularly caudate hyperactivity.) The adoption of this metaphor analogy has proven useful. However, 15 years since its emergence, the spectrum of obsessive-compulsive disorders remains controversial. Questions under debate include whether OCD is a unitary or split condition, whether it is an anxiety disorder, and whether there exists only one spectrum or several possible spectrums. Further work is needed to clarify obsessive-compulsive symptoms, subtypes, and endophenotypes. There is need to integrate existing databases, better define associated symptom domains, and create a more comprehensive endophenotyping protocol for OCRDs. There is also a need to integrate biological and psychological perspectives, concepts, and data to drive this evolution. By increasing research in this field, the OCD spectrum may evolve from a fragmented level of conceptualization as a "metaphor" to one that is more comprehensive and structured.

SHARING EDUCATIONAL SERVICES.

ERIC Educational Resources Information Center

Catskill Area Project in Small School Design, Oneonta, NY.

SHARED SERVICES, A COOPERATIVE SCHOOL RESOURCE PROGRAM, IS DEFINED IN DETAIL. INCLUDED IS A DISCUSSION OF THEIR NEED, ADVANTAGES, GROWTH, DESIGN, AND OPERATION. SPECIFIC PROCEDURES FOR OBTAINING STATE AID IN SHARED SERVICES, EFFECTS OF SHARED SERVICES ON THE SCHOOL, AND HINTS CONCERNING SHARED SERVICES ARE DESCRIBED. CHARACTERISTICS OF THE SMALL…

Sharing health information online in South Korea: motives, topics, and antecedents.

PubMed

Kye, S Y; Shim, M; Kim, Y C; Park, K

2017-10-11

This study aimed to examine the motives, topics and antecedents for sharing health information online among Korean Internet users. Eight hundred adults completed a web-based survey exploring the motives; topics; physical, cognitive, affective and environmental factors; and experiences relating to sharing health information online. The motives for not sharing information included information absence and inappropriateness. The most preferred topic was disease. Good subjective health was significantly associated with frequent information sharing while individuals with a history of disease involving themselves or family members were more likely to share health information than were those without such a history. Further, a higher level of depressed mood was related to a higher level of sharing. Internet-related self-efficacy and trust in information delivery channels were positively related to sharing. Future research could extend the factors related to information sharing to include the evaluation of shared information. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Root-Associated Fungi Shared Between Arbuscular Mycorrhizal and Ectomycorrhizal Conifers in a Temperate Forest

PubMed Central

Toju, Hirokazu; Sato, Hirotoshi

2018-01-01

Arbuscular mycorrhizal and ectomycorrhizal symbioses are among the most important drivers of terrestrial ecosystem dynamics. Historically, the two types of symbioses have been investigated separately because arbuscular mycorrhizal and ectomycorrhizal plant species are considered to host discrete sets of fungal symbionts (i.e., arbuscular mycorrhizal and ectomycorrhizal fungi, respectively). Nonetheless, recent studies based on high-throughput DNA sequencing technologies have suggested that diverse non-mycorrhizal fungi (e.g., endophytic fungi) with broad host ranges play roles in relationships between arbuscular mycorrhizal and ectomycorrhizal plant species in forest ecosystems. By analyzing an Illumina sequencing dataset of root-associated fungi in a temperate forest in Japan, we statistically examined whether co-occurring arbuscular mycorrhizal (Chamaecyparis obtusa) and ectomycorrhizal (Pinus densiflora) plant species could share non-mycorrhizal fungal communities. Among the 919 fungal operational taxonomic units (OTUs) detected, OTUs in various taxonomic lineages were statistically designated as “generalists,” which associated commonly with both coniferous species. The list of the generalists included fungi in the genera Meliniomyces, Oidiodendron, Cladophialophora, Rhizodermea, Penicillium, and Mortierella. Meanwhile, our statistical analysis also detected fungi preferentially associated with Chamaecyparis (e.g., Pezicula) or Pinus (e.g., Neolecta). Overall, this study provides a basis for future studies on how arbuscular mycorrhizal and ectomycorrhizal plant species interactively drive community- or ecosystem-scale processes. The physiological functions of the fungi highlighted in our host-preference analysis deserve intensive investigations for understanding their roles in plant endosphere and rhizosphere. PMID:29593682

Root-Associated Fungi Shared Between Arbuscular Mycorrhizal and Ectomycorrhizal Conifers in a Temperate Forest.

PubMed

Toju, Hirokazu; Sato, Hirotoshi

2018-01-01

Arbuscular mycorrhizal and ectomycorrhizal symbioses are among the most important drivers of terrestrial ecosystem dynamics. Historically, the two types of symbioses have been investigated separately because arbuscular mycorrhizal and ectomycorrhizal plant species are considered to host discrete sets of fungal symbionts (i.e., arbuscular mycorrhizal and ectomycorrhizal fungi, respectively). Nonetheless, recent studies based on high-throughput DNA sequencing technologies have suggested that diverse non-mycorrhizal fungi (e.g., endophytic fungi) with broad host ranges play roles in relationships between arbuscular mycorrhizal and ectomycorrhizal plant species in forest ecosystems. By analyzing an Illumina sequencing dataset of root-associated fungi in a temperate forest in Japan, we statistically examined whether co-occurring arbuscular mycorrhizal ( Chamaecyparis obtusa ) and ectomycorrhizal ( Pinus densiflora ) plant species could share non-mycorrhizal fungal communities. Among the 919 fungal operational taxonomic units (OTUs) detected, OTUs in various taxonomic lineages were statistically designated as "generalists," which associated commonly with both coniferous species. The list of the generalists included fungi in the genera Meliniomyces, Oidiodendron, Cladophialophora, Rhizodermea, Penicillium , and Mortierella . Meanwhile, our statistical analysis also detected fungi preferentially associated with Chamaecyparis (e.g., Pezicula ) or Pinus (e.g., Neolecta ). Overall, this study provides a basis for future studies on how arbuscular mycorrhizal and ectomycorrhizal plant species interactively drive community- or ecosystem-scale processes. The physiological functions of the fungi highlighted in our host-preference analysis deserve intensive investigations for understanding their roles in plant endosphere and rhizosphere.

Power Sharing in Postconflict Societies: Implications for Peace and Governance

ERIC Educational Resources Information Center

Cammett, Melani; Malesky, Edmund

2012-01-01

Which components of power sharing contribute to the duration of peace and what explains the linkages between institutional design and stability? The authors argue that certain types of political power sharing are associated with more durable peace than others, primarily through their positive effects on governance and public service delivery. In…

Predictors of Sharing Injection Equipment by HIV-Seropositive Injection Drug Users

PubMed Central

Latkin, Carl A.; Buchanan, Amy S.; Metsch, Lisa R.; Knight, Kelly; Latka, Mary H.; Mizuno, Yuko; Knowlton, Amy R.

2009-01-01

Among HIV-positive injection drug users (IDUs), we examined baseline predictors of lending needles and syringes, and sharing cookers, cotton, and rinse water in the prior 3 months at follow-up. Participants were enrolled in INSPIRE, a secondary prevention intervention for sexually active HIV-positive IDUs in four US cities during 2001–2005. The analyses involved 357 participants who reported injecting drugs in the prior six months at either the 6- or 12-months follow-up visit. About half (49%) reported at least one sharing episode. In adjusted analyses, peer norms supporting safer injection practices, and having primary HIV medical care visits in the prior 6 months were associated with reporting no sharing of injection equipment. Higher levels of psychological distress was associated with a greater likelihood of reporting drug paraphernalia sharing. These findings suggest that intervention approaches for reducing HIV-seropositive IDUs’ transmission of blood-borne infections should include peer-focused interventions to alter norms of drug paraphernalia sharing and promoting primary HIV care and mental health services. PMID:19186356

Predictors of sharing injection equipment by HIV-seropositive injection drug users.

PubMed

Latkin, Carl A; Buchanan, Amy S; Metsch, Lisa R; Knight, Kelly; Latka, Mary H; Mizuno, Yuko; Knowlton, Amy R

2008-12-01

Among HIV-positive injection drug users (IDUs), we examined baseline predictors of lending needles and syringes and sharing cookers, cotton, and rinse water in the prior 3 months at follow-up. Participants were enrolled in Intervention for Seropositive Injectors-Research and Evaluation, a secondary prevention intervention for sexually active HIV-positive IDUs in 4 US cities during 2001-2005. The analyses involved 357 participants who reported injecting drugs in the prior 6 months at either the 6- or 12-month follow-up visit. About half (49%) reported at least 1 sharing episode. In adjusted analyses, peer norms supporting safer injection practices and having primary HIV medical care visits in the prior 6 months were associated with reporting no sharing of injection equipment. Higher levels of psychological distress were associated with a greater likelihood of reporting drug paraphernalia sharing. These findings suggest that intervention approaches for reducing HIV-seropositive IDUs' transmission of blood-borne infections should include peer-focused interventions to alter norms of drug paraphernalia sharing and promoting primary HIV care and mental health services.

A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12.

PubMed

Bianchi, Matteo; Dahlgren, Stina; Massey, Jonathan; Dietschi, Elisabeth; Kierczak, Marcin; Lund-Ziener, Martine; Sundberg, Katarina; Thoresen, Stein Istre; Kämpe, Olle; Andersson, Göran; Ollier, William E R; Hedhammar, Åke; Leeb, Tosso; Lindblad-Toh, Kerstin; Kennedy, Lorna J; Lingaas, Frode; Rosengren Pielberg, Gerli

2015-01-01

Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds--the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10(-11)). Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018-5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans.

Framework for Shared Drinking Water Risk Assessment.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowry, Thomas Stephen; Tidwell, Vincent C.; Peplinski, William John

Central to protecting our nation's critical infrastructure is the development of methodologies for prioritizing action and supporting resource allocation decisions associated with risk-reduction initiatives. Toward this need a web-based risk assessment framework that promotes the anonymous sharing of results among water utilities is demonstrated. Anonymous sharing of results offers a number of potential advantages such as assistance in recognizing and correcting bias, identification of 'unknown, unknowns', self-assessment and benchmarking for the local utility, treatment of shared assets and/or threats across multiple utilities, and prioritization of actions beyond the scale of a single utility. The constructed framework was demonstrated for threemore » water utilities. Demonstration results were then compared to risk assessment results developed using a different risk assessment application by a different set of analysts.« less

Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

PubMed Central

Li, Yun R; Li, Jin; Zhao, Sihai D; Bradfield, Jonathan P; Mentch, Frank D; Maggadottir, S Melkorka; Hou, Cuiping; Abrams, Debra J; Chang, Diana; Gao, Feng; Guo, Yiran; Wei, Zhi; Connolly, John J; Cardinale, Christopher J; Bakay, Marina; Glessner, Joseph T; Li, Dong; Kao, Charlly; Thomas, Kelly A; Qiu, Haijun; Chiavacci, Rosetta M; Kim, Cecilia E; Wang, Fengxiang; Snyder, James; Richie, Marylyn D; Flatø, Berit; Førre, Øystein; Denson, Lee A; Thompson, Susan D; Becker, Mara L; Guthery, Stephen L; Latiano, Anna; Perez, Elena; Resnick, Elena; Russell, Richard K; Wilson, David C; Silverberg, Mark S; Annese, Vito; Lie, Benedicte A; Punaro, Marilynn; Dubinsky, Marla C; Monos, Dimitri S; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Kugathasan, Subra; Ellis, Justine A; Munro, Jane E; Sullivan, Kathleen E; Wise, Carol A; Chapel, Helen; Cunningham-Rundles, Charlotte; Grant, Struan F A; Orange, Jordan S; Sleiman, Patrick M A; Behrens, Edward M; Griffiths, Anne M; Satsangi, Jack; Finkel, Terri H; Keinan, Alon; Prak, Eline T Luning; Polychronakos, Constantin; Baldassano, Robert N; Li, Hongzhe; Keating, Brendan J; Hakonarson, Hakon

2016-01-01

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ2 meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico–replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases. PMID:26301688

To Share or Not to Share: Parental, Sibling, and Situational Influences on Sharing with a Younger Sibling

ERIC Educational Resources Information Center

Van Berkel, Sheila R.; Van der Pol, Lotte D.; Groeneveld, Marleen G.; Hallers-Haalboom, Elizabeth T.; Endendijk, Joyce J.; Mesman, Judi; Bakermans-Kranenburg, Marian J.

2015-01-01

Sharing is an important indicator of internalised prosocial values. We examined predictors of sharing of 302 preschoolers with their younger siblings in a one-year longitudinal study. Sharing was observed during different home visits, once with father and once with mother. We examined the following predictors: both children's externalising…

Cross-Jurisdictional Resource Sharing in Changing Public Health Landscape: Contributory Factors and Theoretical Explanations.

PubMed

Shah, Gulzar H; Badana, Adrian N S; Robb, Claire; Livingood, William C

2016-01-01

Local health departments (LHDs) are striving to meet public health needs within their jurisdictions, amidst fiscal restraints and complex dynamic environment. Resource sharing across jurisdictions is a critical opportunity for LHDs to continue to enhance effectiveness and increase efficiency. This research examines the extent of cross-jurisdictional resource sharing among LHDs, the programmatic areas and organizational functions for which LHDs share resources, and LHD characteristics associated with resource sharing. Data from the National Association of County & City Health Officials' 2013 National Profile of LHDs were used. Descriptive statistics and multinomial logistic regression were performed for the 5 implementation-oriented outcome variables of interest, with 3 levels of implementation. More than 54% of LHDs shared resources such as funding, staff, or equipment with 1 or more other LHDs on a continuous, recurring basis. Results from the multinomial regression analysis indicate that economies of scale (population size and metropolitan status) had significant positive influences (at P ≤ .05) on resource sharing. Engagement in accreditation, community health assessment, community health improvement planning, quality improvement, and use of the Community Guide were associated with lower levels of engagement in resource sharing. Doctoral degree of the top executive and having 1 or more local boards of health carried a positive influence on resource sharing. Cross-jurisdictional resource sharing is a viable and commonly used process to overcome the challenges of new and emerging public health problems within the constraints of restricted budgets. LHDs, particularly smaller LHDs with limited resources, should consider increased resource sharing to address emerging challenges.

[Impact of shared-decision making on patient satisfaction].

PubMed

Suh, Won S; Lee, Chae Kyung

2010-01-01

The purpose of this research is to analyze the impact of shared-decision making on patient satisfaction. The study is significant since it focuses on developing appropriate methodologies and analyzing data to identify patient preferences, with the goals of optimizing treatment selection, and substantiating the relationship between such preferences and their impact on outcomes. A thorough literature review that developed the framework illustrating key dimensions of shared decision making was followed by a quantitative assessment and regression analysis of patient-perceived satisfaction, and the degree of shared-decision making. A positive association was evident between shared-decision making and patient satisfaction. The impact of shared decision making on patient satisfaction was greater than other variable including gender, education, and number of visits. Patients who participate in care-related decisions and who are given an explanation of their health problems are more likely to be satisfied with their care. It would benefit health care organizations to train their medical professionals in this communication method, and to include it in their practice guidelines.

Social capital and knowledge sharing: effects on patient safety.

PubMed

Chang, Chia-Wen; Huang, Heng-Chiang; Chiang, Chi-Yun; Hsu, Chiu-Ping; Chang, Chia-Chen

2012-08-01

This article is a report on a study that empirically examines the influence of social capital on knowledge sharing and the impact of knowledge sharing on patient safety. Knowledge sharing is linked to many desirable managerial outcomes, including learning and problem-solving, which are essential for patient safety. Rather than studying the tangible effects of rewards, this study examines whether social capital (including social interaction, trust and shared vision) directly supports individual knowledge sharing in an organization. This cross-sectional study analysed data collected through a questionnaire survey of nurses from a major medical centre in northern Taiwan. The data were collected over a 9-month period from 2008 to 2009. The data analysis was conducted using the Partial Least Squares Graph v3.0 program to evaluate the measurement properties and the structural relationships specified in the research model. Based on a large-scale survey, empirical results indicate that Registered Nurses' perceptions of trust and shared vision have statistically significant and direct effects on knowledge sharing. In addition, knowledge sharing is significantly and positively associated with patient safety. The findings suggest that hospital administrators should foster group trust and initiate a common vision among Registered Nurses. In addition, administrators and chief knowledge officers of hospitals should encourage positive intentions towards knowledge sharing. © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.

Simultaneous profiling of seed-associated bacteria and fungi reveals antagonistic interactions between microorganisms within a shared epiphytic microbiome on Triticum and Brassica seeds.

PubMed

Links, Matthew G; Demeke, Tigst; Gräfenhan, Tom; Hill, Janet E; Hemmingsen, Sean M; Dumonceaux, Tim J

2014-04-01

In order to address the hypothesis that seeds from ecologically and geographically diverse plants harbor characteristic epiphytic microbiota, we characterized the bacterial and fungal microbiota associated with Triticum and Brassica seed surfaces. The total microbial complement was determined by amplification and sequencing of a fragment of chaperonin 60 (cpn60). Specific microorganisms were quantified by qPCR. Bacteria and fungi corresponding to operational taxonomic units (OTU) that were identified in the sequencing study were isolated and their interactions examined. A total of 5477 OTU were observed from seed washes. Neither total epiphytic bacterial load nor community richness/evenness was significantly different between the seed types; 578 OTU were shared among all samples at a variety of abundances. Hierarchical clustering revealed that 203 were significantly different in abundance on Triticum seeds compared with Brassica. Microorganisms isolated from seeds showed 99-100% identity between the cpn60 sequences of the isolates and the OTU sequences from this shared microbiome. Bacterial strains identified as Pantoea agglomerans had antagonistic properties toward one of the fungal isolates (Alternaria sp.), providing a possible explanation for their reciprocal abundances on both Triticum and Brassica seeds. cpn60 enabled the simultaneous profiling of bacterial and fungal microbiota and revealed a core seed-associated microbiota shared between diverse plant genera. © 2014 AAFC. New Phytologist © 2014 New Phytologist Trust.

Characterization of neurophysiologic and neurocognitive biomarkers for use in genomic and clinical outcome studies of schizophrenia.

PubMed

Light, Gregory A; Swerdlow, Neal R; Rissling, Anthony J; Radant, Allen; Sugar, Catherine A; Sprock, Joyce; Pela, Marlena; Geyer, Mark A; Braff, David L

2012-01-01

Endophenotypes are quantitative, laboratory-based measures representing intermediate links in the pathways between genetic variation and the clinical expression of a disorder. Ideal endophenotypes exhibit deficits in patients, are stable over time and across shifts in psychopathology, and are suitable for repeat testing. Unfortunately, many leading candidate endophenotypes in schizophrenia have not been fully characterized simultaneously in large cohorts of patients and controls across these properties. The objectives of this study were to characterize the extent to which widely-used neurophysiological and neurocognitive endophenotypes are: 1) associated with schizophrenia, 2) stable over time, independent of state-related changes, and 3) free of potential practice/maturation or differential attrition effects in schizophrenia patients (SZ) and nonpsychiatric comparison subjects (NCS). Stability of clinical and functional measures was also assessed. Participants (SZ n = 341; NCS n = 205) completed a battery of neurophysiological (MMN, P3a, P50 and N100 indices, PPI, startle habituation, antisaccade), neurocognitive (WRAT-3 Reading, LNS-forward, LNS-reorder, WCST-64, CVLT-II). In addition, patients were rated on clinical symptom severity as well as functional capacity and status measures (GAF, UPSA, SOF). 223 subjects (SZ n = 163; NCS n = 58) returned for retesting after 1 year. Most neurophysiological and neurocognitive measures exhibited medium-to-large deficits in schizophrenia, moderate-to-substantial stability across the retest interval, and were independent of fluctuations in clinical status. Clinical symptoms and functional measures also exhibited substantial stability. A Longitudinal Endophenotype Ranking System (LERS) was created to rank neurophysiological and neurocognitive biomarkers according to their effect sizes across endophenotype criteria. The majority of neurophysiological and neurocognitive measures exhibited deficits in patients

Characterization of Neurophysiologic and Neurocognitive Biomarkers for Use in Genomic and Clinical Outcome Studies of Schizophrenia

PubMed Central

Light, Gregory A.; Swerdlow, Neal R.; Rissling, Anthony J.; Radant, Allen; Sugar, Catherine A.; Sprock, Joyce; Pela, Marlena; Geyer, Mark A.; Braff, David L.

2012-01-01

Background Endophenotypes are quantitative, laboratory-based measures representing intermediate links in the pathways between genetic variation and the clinical expression of a disorder. Ideal endophenotypes exhibit deficits in patients, are stable over time and across shifts in psychopathology, and are suitable for repeat testing. Unfortunately, many leading candidate endophenotypes in schizophrenia have not been fully characterized simultaneously in large cohorts of patients and controls across these properties. The objectives of this study were to characterize the extent to which widely-used neurophysiological and neurocognitive endophenotypes are: 1) associated with schizophrenia, 2) stable over time, independent of state-related changes, and 3) free of potential practice/maturation or differential attrition effects in schizophrenia patients (SZ) and nonpsychiatric comparison subjects (NCS). Stability of clinical and functional measures was also assessed. Methods Participants (SZ n = 341; NCS n = 205) completed a battery of neurophysiological (MMN, P3a, P50 and N100 indices, PPI, startle habituation, antisaccade), neurocognitive (WRAT-3 Reading, LNS-forward, LNS-reorder, WCST-64, CVLT-II). In addition, patients were rated on clinical symptom severity as well as functional capacity and status measures (GAF, UPSA, SOF). 223 subjects (SZ n = 163; NCS n = 58) returned for retesting after 1 year. Results Most neurophysiological and neurocognitive measures exhibited medium-to-large deficits in schizophrenia, moderate-to-substantial stability across the retest interval, and were independent of fluctuations in clinical status. Clinical symptoms and functional measures also exhibited substantial stability. A Longitudinal Endophenotype Ranking System (LERS) was created to rank neurophysiological and neurocognitive biomarkers according to their effect sizes across endophenotype criteria. Conclusions The majority of neurophysiological and neurocognitive

Examining Data Repository Guidelines for Qualitative Data Sharing.

PubMed

Antes, Alison L; Walsh, Heidi A; Strait, Michelle; Hudson-Vitale, Cynthia R; DuBois, James M

2018-02-01

Qualitative data provide rich information on research questions in diverse fields. Recent calls for increased transparency and openness in research emphasize data sharing. However, qualitative data sharing has yet to become the norm internationally and is particularly uncommon in the United States. Guidance for archiving and secondary use of qualitative data is required for progress in this regard. In this study, we review the benefits and concerns associated with qualitative data sharing and then describe the results of a content analysis of guidelines from international repositories that archive qualitative data. A minority of repositories provide qualitative data sharing guidelines. Of the guidelines available, there is substantial variation in whether specific topics are addressed. Some topics, such as removing direct identifiers, are consistently addressed, while others, such as providing an anonymization log, are not. We discuss the implications of our study for education, best practices, and future research.

Pregnant Women Sharing Pregnancy-Related Information on Facebook: Web-Based Survey Study.

PubMed

Harpel, Tammy

2018-03-22

Research indicates expectant and new mothers use the Internet, specifically social media, to gain information and support during the transition to parenthood. Although parents regularly share information about and photos of their child or children on Facebook, researchers have neither explored the use of Facebook to share pregnancy-related information nor investigated factors that influence such sharing. The aim of this study was to address a gap in the literature by exploring the use of Facebook by pregnant women. Specifically, the study examined the use of Facebook to share pregnancy-related information, as well as any association between prenatal attachment and the aforementioned aspects of sharing pregnancy-related information on Facebook. Pregnant women who were at least 18 years of age were recruited for participation in the study through posts and paid advertisements on Facebook and posts to professional organization listservs. Individuals interested in participating were directed to a secure Web-based survey system where they completed the consent form and the survey that focused on their current pregnancy. Participants completed the Maternal Antenatal Attachment Scale and answered questions that assessed how often they shared pregnancy-related information on Facebook, who they shared it with, why they shared it, and what they shared. A total of 117 pregnant women completed the survey. Descriptive statistics indicated that the pregnancy announcement was most commonly shared (75/108, 69.4%), with most women sharing pregnancy-related information on Facebook less than monthly (52/117, 44.4%) with only family and friends (90/116, 77.6% and 91/116, 78.4%, respectively) and for the purpose of involving others or sharing the experience (62/107, 57.9%). Correlation and regression analyses showed that prenatal attachment, in general, was positively and significantly related to all aspects of sharing pregnancy-related information at the P<.05 level, with the

Pregnant Women Sharing Pregnancy-Related Information on Facebook: Web-Based Survey Study

PubMed Central

2018-01-01

Background Research indicates expectant and new mothers use the Internet, specifically social media, to gain information and support during the transition to parenthood. Although parents regularly share information about and photos of their child or children on Facebook, researchers have neither explored the use of Facebook to share pregnancy-related information nor investigated factors that influence such sharing. Objective The aim of this study was to address a gap in the literature by exploring the use of Facebook by pregnant women. Specifically, the study examined the use of Facebook to share pregnancy-related information, as well as any association between prenatal attachment and the aforementioned aspects of sharing pregnancy-related information on Facebook. Methods Pregnant women who were at least 18 years of age were recruited for participation in the study through posts and paid advertisements on Facebook and posts to professional organization listservs. Individuals interested in participating were directed to a secure Web-based survey system where they completed the consent form and the survey that focused on their current pregnancy. Participants completed the Maternal Antenatal Attachment Scale and answered questions that assessed how often they shared pregnancy-related information on Facebook, who they shared it with, why they shared it, and what they shared. Results A total of 117 pregnant women completed the survey. Descriptive statistics indicated that the pregnancy announcement was most commonly shared (75/108, 69.4%), with most women sharing pregnancy-related information on Facebook less than monthly (52/117, 44.4%) with only family and friends (90/116, 77.6% and 91/116, 78.4%, respectively) and for the purpose of involving others or sharing the experience (62/107, 57.9%). Correlation and regression analyses showed that prenatal attachment, in general, was positively and significantly related to all aspects of sharing pregnancy-related information

Data sharing policy design for consortia: challenges for sustainability.

PubMed

Kaye, Jane; Hawkins, Naomi

2014-01-01

The field of human genomics has led advances in the sharing of data with a view to facilitating translation of research into innovations for human health. This change in scientific practice has been implemented through new policy developed by many principal investigators, project managers and funders, which has ultimately led to new forms of practice and innovative governance models for data sharing. Here, we examine the development of the governance of data sharing in genomics, and explore some of the key challenges associated with the design and implementation of these policies. We examine how the incremental nature of policy design, the perennial problem of consent, the gridlock caused by multiple and overlapping access systems, the administrative burden and the problems with incentives and acknowledgment all have an impact on the potential for data sharing to be maximized. We conclude by proposing ways in which the scientific community can address these problems, to improve the sustainability of data sharing into the future.

Shared decision making for patients living with inflammatory arthritis.

PubMed

Palmer, Deborah; El Miedany, Yasser

Providing adequate care for people with inflammatory arthritis is an ongoing challenge. In recent years significant progress has been made in the treatment of inflammatory arthritic conditions. The availability of a wide range of disease-modifying anti-rheumatic drugs as well as biologic therapies has not only improved treatment, but also made treatment decisions much more complex. This wider range of improved treatment options happened at the same time as a clear move towards patient-centred care and implementing shared decision making for both medical and surgical conditions. Implementing shared decision making has been reported to be associated with higher satisfaction and better adherence to therapy. Electronic shared decision making has more recently been suggested as a tool for clinical practice. The aim of this article is to look at further integrating shared decision making in standard rheumatology practice in view of the available evidence and the outcomes of a study looking at a recently developed patient shared decision guide.

Shared Genetic Background for Regulation of Mood and Sleep: Association of GRIA3 with Sleep Duration in Healthy Finnish Women

PubMed Central

Utge, Siddheshwar; Kronholm, Erkki; Partonen, Timo; Soronen, Pia; Ollila, Hanna M.; Loukola, Anu; Perola, Markus; Salomaa, Veikko; Porkka-Heiskanen, Tarja; Paunio, Tiina

2011-01-01

Study Objectives: Sleeping 7 to 8 hours per night appears to be optimal, since both shorter and longer sleep times are related to increased morbidity and mortality. Depressive disorder is almost invariably accompanied by disturbed sleep, leading to decreased sleep duration, and disturbed sleep may be a precipitating factor in the initiation of depressive illness. Here, we examined whether, in healthy individuals, sleep duration is associated with genes that we earlier found to be associated with depressive disorder. Design: Population-based molecular genetic study. Setting: Regression analysis of 23 risk variants for depressive disorder from 12 genes to sleep duration in healthy individuals. Participants: Three thousand, one hundred, forty-seven individuals (25–75 y) from population-based Health 2000 and FINRISK 2007 samples. Measurements and Results: We found a significant association of rs687577 from GRIA3 on the X-chromosome with sleep duration in women (permutation-based corrected empirical P = 0.00001, β = 0.27; Bonferroni corrected P = 0.0052; f = 0.11). The frequency of C/C genotype previously found to increase risk for depression in women was highest among those who slept for 8 hours or less in all age groups younger than 70 years. Its frequency decreased with the lengthening of sleep duration, and those who slept for 9 to 10 hours showed a higher frequency of C/A or A/A genotypes, when compared with the midrange sleepers (7-8 hours) (permutation-based corrected empirical P = 0.0003, OR = 1.81). Conclusions: The GRIA3 polymorphism that was previously found to be associated with depressive disorder in women showed an association with sleep duration in healthy women. Mood disorders and short sleep may share a common genetic background and biologic mechanisms that involve glutamatergic neurotransmission. Citation: Utge S; Kronholm E; Partonen T; Soronen P; Ollila HM; Loukola A; Perola M; Salomaa V; Porkka-Heiskanen T; Paunio T. Shared genetic background for

To share or not to share: a randomized trial of consent for data sharing in genome research.

PubMed

McGuire, Amy L; Oliver, Jill M; Slashinski, Melody J; Graves, Jennifer L; Wang, Tao; Kelly, P Adam; Fisher, William; Lau, Ching C; Goss, John; Okcu, Mehmet; Treadwell-Deering, Diane; Goldman, Alica M; Noebels, Jeffrey L; Hilsenbeck, Susan G

2011-11-01

Despite growing concerns toward maintaining participants' privacy, individual investigators collecting tissue and other biological specimens for genomic analysis are encouraged to obtain informed consent for broad data sharing. Our purpose was to assess the effect on research enrollment and data sharing decisions of three different consent types (traditional, binary, or tiered) with varying levels of control and choices regarding data sharing. A single-blinded, randomized controlled trial was conducted with 323 eligible adult participants being recruited into one of six genome studies at Baylor College of Medicine in Houston, Texas, between January 2008 and August 2009. Participants were randomly assigned to one of three experimental consent documents (traditional, n = 110; binary, n = 103; and tiered, n = 110). Debriefing in follow-up visits provided participants a detailed review of all consent types and the chance to change data sharing choices or decline genome study participation. Before debriefing, 83.9% of participants chose public data release. After debriefing, 53.1% chose public data release, 33.1% chose restricted (controlled access database) release, and 13.7% opted out of data sharing. Only one participant declined genome study participation due to data sharing concerns. Our findings indicate that most participants are willing to publicly release their genomic data; however, a significant portion prefers restricted release. These results suggest discordance between existing data sharing policies and participants' judgments and desires.

Image Sharing Technologies and Reduction of Imaging Utilization: A Systematic Review and Meta-analysis.

PubMed

Vest, Joshua R; Jung, Hye-Young; Ostrovsky, Aaron; Das, Lala Tanmoy; McGinty, Geraldine B

2015-12-01

Image sharing technologies may reduce unneeded imaging by improving provider access to imaging information. A systematic review and meta-analysis were conducted to summarize the impact of image sharing technologies on patient imaging utilization. Quantitative evaluations of the effects of PACS, regional image exchange networks, interoperable electronic heath records, tools for importing physical media, and health information exchange systems on utilization were identified through a systematic review of the published and gray English-language literature (2004-2014). Outcomes, standard effect sizes (ESs), settings, technology, populations, and risk of bias were abstracted from each study. The impact of image sharing technologies was summarized with random-effects meta-analysis and meta-regression models. A total of 17 articles were included in the review, with a total of 42 different studies. Image sharing technology was associated with a significant decrease in repeat imaging (pooled effect size [ES] = -0.17; 95% confidence interval [CI] = [-0.25, -0.09]; P < .001). However, image sharing technology was associated with a significant increase in any imaging utilization (pooled ES = 0.20; 95% CI = [0.07, 0.32]; P = .002). For all outcomes combined, image sharing technology was not associated with utilization. Most studies were at risk for bias. Image sharing technology was associated with reductions in repeat and unnecessary imaging, in both the overall literature and the most-rigorous studies. Stronger evidence is needed to further explore the role of specific technologies and their potential impact on various modalities, patient populations, and settings. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Image Sharing Technologies and Reduction of Imaging Utilization: A Systematic Review and Meta-analysis

PubMed Central

Vest, Joshua R.; Jung, Hye-Young; Ostrovsky, Aaron; Das, Lala Tanmoy; McGinty, Geraldine B.

2016-01-01

Introduction Image sharing technologies may reduce unneeded imaging by improving provider access to imaging information. A systematic review and meta-analysis were conducted to summarize the impact of image sharing technologies on patient imaging utilization. Methods Quantitative evaluations of the effects of PACS, regional image exchange networks, interoperable electronic heath records, tools for importing physical media, and health information exchange systems on utilization were identified through a systematic review of the published and gray English-language literature (2004–2014). Outcomes, standard effect sizes (ESs), settings, technology, populations, and risk of bias were abstracted from each study. The impact of image sharing technologies was summarized with random-effects meta-analysis and meta-regression models. Results A total of 17 articles were included in the review, with a total of 42 different studies. Image sharing technology was associated with a significant decrease in repeat imaging (pooled effect size [ES] = −0.17; 95% confidence interval [CI] = [−0.25, −0.09]; P < .001). However, image sharing technology was associated with a significant increase in any imaging utilization (pooled ES = 0.20; 95% CI = [0.07, 0.32]; P = .002). For all outcomes combined, image sharing technology was not associated with utilization. Most studies were at risk for bias. Conclusions Image sharing technology was associated with reductions in repeat and unnecessary imaging, in both the overall literature and the most-rigorous studies. Stronger evidence is needed to further explore the role of specific technologies and their potential impact on various modalities, patient populations, and settings. PMID:26614882

Glycemic Control Associated With Secure Patient-Provider Messaging Within a Shared Electronic Medical Record

PubMed Central

Harris, Lynne T.; Koepsell, Thomas D.; Haneuse, Sebastien J.; Martin, Diane P.; Ralston, James D.

2013-01-01

OBJECTIVE To study differences in glycemic control and HbA1c testing associated with use of secure electronic patient-provider messaging. We hypothesized that messaging use would be associated with better glycemic control and a higher rate of adherence to HbA1c testing recommendations. RESEARCH DESIGN AND METHODS Retrospective observational study of secure messaging at Group Health, a large nonprofit health care system. Our analysis included adults with diabetes who had registered for access to a shared electronic medical record (SMR) between 2003 and 2006. We fit log-linear regression models, using generalized estimating equations, to estimate the adjusted rate ratio of meeting three indicators of glycemic control (HbA1c <7%, HbA1c <8%, and HbA1c >9%) and HbA1c testing adherence by level of previous messaging use. Multiple imputation and inverse probability weights were used to account for missing data. RESULTS During the study period, 6,301 adults with diabetes registered for access to the SMR. Of these individuals, 74% used messaging at least once during that time. Frequent use of messaging during the previous calendar quarter was associated with a higher rate of good glycemic control (HbA1c <7%: rate ratio, 1.26 [95% CI, 1.15–1.37]) and a higher rate testing adherence (1.20 [1.15–1.25]). CONCLUSIONS Among SMR users, recent and frequent messaging use was associated with better glycemic control and a higher rate of HbA1c testing adherence. These results suggest that secure messaging may facilitate important processes of care and help some patients to achieve or maintain adequate glycemic control. PMID:23628618

A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12

PubMed Central

Massey, Jonathan; Dietschi, Elisabeth; Kierczak, Marcin; Lund-Ziener, Martine; Sundberg, Katarina; Thoresen, Stein Istre; Kämpe, Olle; Andersson, Göran; Ollier, William E. R.; Hedhammar, Åke; Leeb, Tosso; Lindblad-Toh, Kerstin; Kennedy, Lorna J.; Lingaas, Frode; Rosengren Pielberg, Gerli

2015-01-01

Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds—the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10-11). Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018–5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans. PMID:26261983

Disparities in early exposure to book sharing within immigrant families.

PubMed

Festa, Natalia; Loftus, Pooja D; Cullen, Mark R; Mendoza, Fernando S

2014-07-01

This study examined the early developmental context of children in immigrant families (CIF), measured by the frequency with which parents share books with their children. Trends in the frequency with which parents report book sharing, defined in this analysis as reading or sharing picture books with their young children, were analyzed across immigrant and nonimmigrant households by using data from the 2005, 2007, and 2009 California Health Interview Survey. Stepwise multivariate logistic regression assessed the likelihood that CIF shared books with parents daily. In this study, 57.5% of parents in immigrant families reported daily book sharing (DBS), compared with 75.8% of native-born parents. The lowest percentage of DBS was seen in Hispanic families with 2 foreign-born parents (47.1%). When controlling for independent variables, CIF with 2 foreign-born parents had the lowest odds of sharing books daily (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.54-0.68). When stratified by race/ethnicity, separate multivariate logistic regressions revealed CIF status to be associated with lower odds of DBS for Asian (OR: 0.56; 95% CI: 0.38-0.81) and Hispanic CIF (OR: 0.49; 95% CI: 0.42-0.58). There is an association between the lower odds of DBS and parental immigrant status, especially for Hispanic and Asian children. This relationship holds after controlling for variables thought to explain differences in literacy-related practices, such as parental education and income. Because book sharing is central to children's development of early literacy and language skills, this disparity merits further exploration with the aim of informing future interventions. Copyright © 2014 by the American Academy of Pediatrics.

Ethnic differences in prevalence and determinants of mother-child bed-sharing in early childhood.

PubMed

Luijk, Maartje P C M; Mileva-Seitz, Viara R; Jansen, Pauline W; van IJzendoorn, Marinus H; Jaddoe, Vincent W V; Raat, Hein; Hofman, Albert; Verhulst, Frank C; Tiemeier, Henning

2013-11-01

To date few studies have examined how multiple layers of influences shape the emergence of bed-sharing practices in the first 2 years postpartum. In our report, we examined bed-sharing in a large multiethnic sample, exploring the influences of three broad classes of influence on bed-sharing at single time points and across time: (1) sociodemographic and (2) contextual factors such as breastfeeding, maternal mental health and stress, and (3) child temperament and sleep habits. Frequencies of bed-sharing were assessed at two time points, 2 and 24 months, in a population-based multiethnic (Dutch, Turkish or Moroccan, and Caribbean) sample of 6309 children born in the Netherlands. In Dutch mothers, the majority of mothers did not share their beds with their child, and bed-sharing rates decreased from 2 to 24 months. Other ethnic groups showed higher bed-sharing rates, typified by both increases in bed-sharing (the Turkish and Moroccan group) and persistence of bed-sharing over time (the Caribbean group). There were few family and child characteristics associated with bed-sharing in the non-Dutch ethnic groups. In contrast, bed-sharing in Dutch mothers was associated with child temperament and sleeping problems, maternal depression, and sociodemographic variables like crowding and maternal education. Our results suggest that mothers with a Turkish and Moroccan or Caribbean background were more influenced by cultural values, whereas bed-sharing practices were more reactive in the Dutch group. Copyright © 2013 Elsevier B.V. All rights reserved.

The Value of Sharing Information: A Neural Account of Information Transmission.

PubMed

Baek, Elisa C; Scholz, Christin; O'Donnell, Matthew Brook; Falk, Emily B

2017-07-01

Humans routinely share information with one another. What drives this behavior? We used neuroimaging to test an account of information selection and sharing that emphasizes inherent reward in self-reflection and connecting with other people. Participants underwent functional MRI while they considered personally reading and sharing New York Times articles. Activity in neural regions involved in positive valuation, self-related processing, and taking the perspective of others was significantly associated with decisions to select and share articles, and scaled with preferences to do so. Activity in all three sets of regions was greater when participants considered sharing articles with other people rather than selecting articles to read themselves. The findings suggest that people may consider value not only to themselves but also to others even when selecting news articles to consume personally. Further, sharing heightens activity in these pathways, in line with our proposal that humans derive value from self-reflection and connecting to others via sharing.

Coping with Prescription Drug Cost Sharing: Knowledge, Adherence, and Financial Burden

PubMed Central

Reed, Mary; Brand, Richard; Newhouse, Joseph P; Selby, Joe V; Hsu, John

2008-01-01

Objective Assess patient knowledge of and response to drug cost sharing. Study Setting Adult members of a large prepaid, integrated delivery system. Study Design/Data Collection Telephone interviews with 932 participants (72 percent response rate) who reported knowledge of the structures and amounts of their prescription drug cost sharing. Participants reported cost-related changes in their drug adherence, any financial burden, and other cost-coping behaviors. Actual cost sharing amounts came from administrative databases. Principal Findings Overall, 27 percent of patients knew all of their drug cost sharing structures and amounts. After adjustment for individual characteristics, additional patient cost sharing structures (tiers and caps), and higher copayment amounts were associated with reporting decreased adherence, financial burden, or other cost-coping behaviors. Conclusions Patient knowledge of their drug benefits is limited, especially for more complex cost sharing structures. Patients also report a range of responses to greater cost sharing, including decreasing adherence. PMID:18370979

Application of a Socio-Ecological Model to Mother-Infant Bed-Sharing

ERIC Educational Resources Information Center

Salm Ward, Trina C.; Doering, Jennifer J.

2014-01-01

Mother-infant bed-sharing has been associated with an increased risk of sleep-related infant deaths, and thus, health messaging has aimed to discourage this behavior. Despite this messaging, bed-sharing remains a common practice in the United States, especially among minority families. Moreover, rates of accidental suffocation and strangulation in…

Important Voices: Gifted Children & Parents Share What They Need

ERIC Educational Resources Information Center

Boazman, Janette

2015-01-01

In the gifted community, many voices offer research, information, and advice on what gifted children need. University professors who study gifted children share their findings through research, published articles, and books. State gifted education associations and the National Association for Gifted Children (NAGC) publish important information…

Effect of a syringe aspiration technique versus a mechanical suction technique and use of N-butylscopolammonium bromide on the quantity and quality of bronchoalveolar lavage fluid samples obtained from horses with the summer pasture endophenotype of equine asthma.

PubMed

Bowser, Jacquelyn E; Costa, Lais R R; Rodil, Alba U; Lopp, Christine T; Johnson, Melanie E; Wills, Robert W; Swiderski, Cyprianna E

2018-03-01

OBJECTIVE To evaluate the effect of 2 bronchoalveolar lavage (BAL) sampling techniques and the use of N-butylscopolammonium bromide (NBB) on the quantity and quality of BAL fluid (BALF) samples obtained from horses with the summer pasture endophenotype of equine asthma. ANIMALS 8 horses with the summer pasture endophenotype of equine asthma. PROCEDURES BAL was performed bilaterally (right and left lung sites) with a flexible videoendoscope passed through the left or right nasal passage. During lavage of the first lung site, a BALF sample was collected by means of either gentle syringe aspiration or mechanical suction with a pressure-regulated wall-mounted suction pump. The endoscope was then maneuvered into the contralateral lung site, and lavage was performed with the alternate fluid retrieval technique. For each horse, BAL was performed bilaterally once with and once without premedication with NBB (21-day interval). The BALF samples retrieved were evaluated for volume, total cell count, differential cell count, RBC count, and total protein concentration. RESULTS Use of syringe aspiration significantly increased total BALF volume (mean volume increase, 40 mL [approx 7.5% yield]) and decreased total RBC count (mean decrease, 142 cells/μL), compared with use of mechanical suction. The BALF nucleated cell count and differential cell count did not differ between BAL procedures. Use of NBB had no effect on BALF retrieval. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that retrieval of BALF by syringe aspiration may increase yield and reduce barotrauma in horses at increased risk of bronchoconstriction and bronchiolar collapse. Further studies to determine the usefulness of NBB and other bronchodilators during BAL procedures in horses are warranted.

Longitudinal links between childhood peer acceptance and the neural correlates of sharing.

PubMed

Will, Geert-Jan; Crone, Eveline A; van Lier, Pol A C; Güroğlu, Berna

2018-01-01

Childhood peer acceptance is associated with high levels of prosocial behavior and advanced perspective taking skills. Yet, the neurobiological mechanisms underlying these associations have not been studied. This functional magnetic resonance imaging study examined the neural correlates of sharing decisions in a group of adolescents who had a stable accepted status (n = 27) and a group who had a chronic rejected status (n = 19) across six elementary school grades. Both groups of adolescents played three allocation games in which they could share money with strangers with varying costs and profits to them and the other person. Stably accepted adolescents were more likely to share their money with unknown others than chronically rejected adolescents when sharing was not costly. Neuroimaging analyses showed that stably accepted adolescents, compared to chronically rejected adolescents, exhibited higher levels of activation in the temporo-parietal junction, posterior superior temporal sulcus, temporal pole, pre-supplementary motor area, and anterior insula during costly sharing decisions. These findings demonstrate that stable peer acceptance across childhood is associated with heightened activity in brain regions previously linked to perspective taking and the detection of social norm violations during adolescence, and thereby provide insight into processes underlying the widely established links between peer acceptance and prosocial behavior. © 2016 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

Sharing mates and nest boxes is associated with female "friendship" in European starlings, Sturnus vulgaris.

PubMed

Henry, Laurence; Bourguet, Cécile; Coulon, Marion; Aubry, Christine; Hausberger, Martine

2013-02-01

Breeding decisions in birds involve both mate and nest choice, and there is increasing evidence that social influences may modulate individual choices. Female preferences may be affected by other females' preferences and mutual choice cannot always be excluded, which makes the whole pattern more complex than assumed by most sexual selection models. Social transmission may be facilitated by particular social bonds, therefore prebreeding social networks may influence later mate choices. The other case where females share mate or resources is polygyny, generally viewed to only benefit males. If mutual benefits may arise then mechanisms should evolve to reduce the reproductive cost for females such as to reduce the cost of aggression by sharing their mate with a preferred same-sex social partner. We tested the hypothesis that females' mating decisions may be influenced by the prebreeding social network and that social partner relations established prior to breeding may share decisions (mate/sites) in a facultatively polygynous species, the European starling. Two experiments were designed to test the relative importance of male or nest by following the whole dynamics of the breeding cycle from the prebreeding period until mate and nest selection. In both cases socially isolated females tended to be excluded from breeding, while prebreeding social partners tended to share mates and to nest in close proximity, mate copying leading in some case to polygyny. The final pattern resulted both from female "likes and dislikes" and male preferences for some females. Aggressive interactions between females were rare. Vocal sharing between females may have been a clue for males as to the degree of social integration of these females. PsycINFO Database Record (c) 2013 APA, all rights reserved

The Relations of Family Members’ Unique and Shared Perspectives of Family Dysfunction to Dyad Adjustment

PubMed Central

Jager, Justin; Yuen, Cynthia X.; Bornstein, Marc H.; Putnick, Diane L.; Hendricks, Charlene

2017-01-01

Among a community sample of families (N = 128), this study examined how family members’ shared and unique perspectives of family dysfunction relate to dyad members’ shared views of dyad adjustment within adolescent-mother, adolescent-father, and mother-father dyads. Independent of a family’s family perspective (shared perspective of family dysfunction), the adolescent’s unique perspective was associated with lower security and higher conflict with both mother and father, the father’s unique perspective was associated with lower security and higher conflict with the adolescent as well as lower marital quality with mother, and the mother unique perspective was associated with lower marital quality with the father. Moreover, for adolescent-parent dyads, compared to the parent unique perspective, the adolescent unique perspective was more strongly associated with dyad adjustment. These findings indicate that both shared and unique views of the family system – the adolescent’s unique view in particular - independently relate to the health of family subsystems. They also suggest that research as well as therapeutic interventions that focus on just the shared view of the family may miss important elements of family dysfunction. PMID:24884682

The relations of family members' unique and shared perspectives of family dysfunction to dyad adjustment.

PubMed

Jager, Justin; Yuen, Cynthia X; Bornstein, Marc H; Putnick, Diane L; Hendricks, Charlene

2014-06-01

Among a community sample of families (N = 128), this study examined how family members' shared and unique perspectives of family dysfunction relate to dyad members' shared views of dyad adjustment within adolescent-mother, adolescent-father, and mother-father dyads. Independent of a family's family perspective (shared perspective of family dysfunction), the adolescent's unique perspective was associated with lower security and higher conflict with both mother and father; the father's unique perspective was associated with lower security and higher conflict with the adolescent, as well as lower marital quality with mother; and the mother unique perspective was associated with lower marital quality with the father. Moreover, for adolescent-parent dyads, compared with the parent unique perspective, the adolescent unique perspective was more strongly associated with dyad adjustment. These findings indicate that both shared and unique views of the family system-the adolescent's unique view in particular-independently relate to the health of family subsystems. They also suggest that research, as well as therapeutic interventions, that focus on just the shared view of the family may miss important elements of family dysfunction. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Discovery biology of neuropsychiatric syndromes (DBNS): a center for integrating clinical medicine and basic science.

PubMed

Viswanath, Biju; Rao, Naren P; Narayanaswamy, Janardhanan C; Sivakumar, Palanimuthu T; Kandasamy, Arun; Kesavan, Muralidharan; Mehta, Urvakhsh Meherwan; Venkatasubramanian, Ganesan; John, John P; Mukherjee, Odity; Purushottam, Meera; Kannan, Ramakrishnan; Mehta, Bhupesh; Kandavel, Thennarasu; Binukumar, B; Saini, Jitender; Jayarajan, Deepak; Shyamsundar, A; Moirangthem, Sydney; Vijay Kumar, K G; Thirthalli, Jagadisha; Chandra, Prabha S; Gangadhar, Bangalore N; Murthy, Pratima; Panicker, Mitradas M; Bhalla, Upinder S; Chattarji, Sumantra; Benegal, Vivek; Varghese, Mathew; Reddy, Janardhan Y C; Raghu, Padinjat; Rao, Mahendra; Jain, Sanjeev

2018-04-18

There is emerging evidence that there are shared genetic, environmental and developmental risk factors in psychiatry, that cut across traditional diagnostic boundaries. With this background, the Discovery biology of neuropsychiatric syndromes (DBNS) proposes to recruit patients from five different syndromes (schizophrenia, bipolar disorder, obsessive compulsive disorder, Alzheimer's dementia and substance use disorders), identify those with multiple affected relatives, and invite these families to participate in this study. The families will be assessed: 1) To compare neuro-endophenotype measures between patients, first degree relatives (FDR) and healthy controls., 2) To identify cellular phenotypes which differentiate the groups., 3) To examine the longitudinal course of neuro-endophenotype measures., 4) To identify measures which correlate with outcome, and 5) To create a unified digital database and biorepository. The identification of the index participants will occur at well-established specialty clinics. The selected individuals will have a strong family history (with at least another affected FDR) of mental illness. We will also recruit healthy controls without family history of such illness. All recruited individuals (N = 4500) will undergo brief clinical assessments and a blood sample will be drawn for isolation of DNA and peripheral blood mononuclear cells (PBMCs). From among this set, a subset of 1500 individuals (300 families and 300 controls) will be assessed on several additional assessments [detailed clinical assessments, endophenotype measures (neuroimaging- structural and functional, neuropsychology, psychophysics-electroencephalography, functional near infrared spectroscopy, eye movement tracking)], with the intention of conducting repeated measurements every alternate year. PBMCs from this set will be used to generate lymphoblastoid cell lines, and a subset of these would be converted to induced pluripotent stem cell lines and also undergo

On the viability of supporting institutional sharing of remote laboratory facilities

NASA Astrophysics Data System (ADS)

Lowe, David; Dang, Bridgette; Daniel, Keith; Murray, Stephen; Lindsay, Euan

2015-11-01

Laboratories are generally regarded as critical to engineering education, and yet educational institutions face significant challenges in developing and maintaining high-quality laboratory facilities. Remote laboratories are increasingly being explored as a partial solution to this challenge, with research showing that - for the right learning outcomes - they can be viable adjuncts or alternatives to conventional hands-on laboratories. One consequential opportunity arising from the inherent support for distributed access is the possibility of cross-institutional shared facilities. While both technical feasibility and pedagogic implications of remote laboratories have been well studied within the literature, the organisational and logistical issues associated with shared facilities have received limited consideration. This paper uses an existing national-scale laboratory sharing initiative, along with a related survey and laboratory sharing data, to analyse a range of factors that can affect engagement in laboratory sharing. The paper also discusses the implications for supporting ongoing laboratory sharing.

Online Information Sharing About Risks: The Case of Organic Food.

PubMed

Hilverda, Femke; Kuttschreuter, Margôt

2018-03-23

Individuals have to make sense of an abundance of information to decide whether or not to purchase certain food products. One of the means to sense-making is information sharing. This article reports on a quantitative study examining online information sharing behavior regarding the risks of organic food products. An online survey among 535 respondents was conducted in the Netherlands to examine the determinants of information sharing behavior, and their relationships. Structural equation modeling was applied to test both the measurement model and the structural model. Results showed that the intention to share information online about the risks of organic food was low. Conversations and email were the preferred channels to share information; of the social media Facebook stood out. The developed model was found to provide an adequate description of the data. It explained 41% of the variance in information sharing. Injunctive norms and outcome expectancies were most important in predicting online information sharing, followed by information-related determinants. Risk-perception-related determinants showed a significant, but weak, positive relationship with online information sharing. Implications for authorities communicating on risks associated with food are addressed. © 2018 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

The demands and resources arising from shared office spaces.

PubMed

Morrison, Rachel L; Macky, Keith A

2017-04-01

The prevalence of flexible and shared office spaces is increasing significantly, yet the socioemotional outcomes associated with these environments are under researched. Utilising the job demands-resources (JD-R) model we investigate both the demands and the resources that can accrue to workers as a result of shared work environments and hot-desking. Data were collected from work experienced respondents (n = 1000) assessing the extent to which they shared their office space with others, along with demands comprising distractions, uncooperative behaviours, distrust, and negative relationships, and resources from co-worker friendships and supervisor support. We found that, as work environments became more shared (with hot-desking being at the extreme end of the continuum), not only were there increases in demands, but co-worker friendships were not improved and perceptions of supervisory support decreased. Findings are discussed in relation to employee well-being and recommendations are made regarding how best to ameliorate negative consequences of shared work environments. Copyright © 2016 Elsevier Ltd. All rights reserved.

The HydroShare Collaborative Repository for the Hydrology Community

NASA Astrophysics Data System (ADS)

Tarboton, D. G.; Idaszak, R.; Horsburgh, J. S.; Ames, D. P.; Goodall, J. L.; Couch, A.; Hooper, R. P.; Dash, P. K.; Stealey, M.; Yi, H.; Bandaragoda, C.; Castronova, A. M.

2017-12-01

extensibility it supports. Web apps are hosted on separate servers, which may be 3rd party servers. They are registered in HydroShare using a web app resource that configures the connectivity for them to be discovered and launched directly from resource types they are associated with.

Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence.

PubMed

Chen, Andrew C H; Tang, Yongqiang; Rangaswamy, Madhavi; Wang, Jen C; Almasy, Laura; Foroud, Tatiana; Edenberg, Howard J; Hesselbrock, Victor; Nurnberger, John; Kuperman, Samuel; O'Connor, Sean J; Schuckit, Marc A; Bauer, Lance O; Tischfield, Jay; Rice, John P; Bierut, Laura; Goate, Alison; Porjesz, Bernice

2009-04-05

Evidence suggests the P3 amplitude of the event-related potential and its underlying superimposed event-related oscillations (EROs), primarily in the theta (4-5 Hz) and delta (1-3 Hz) frequencies, as endophenotypes for the risk of alcoholism and other disinhibitory disorders. Major neurochemical substrates contributing to theta and delta rhythms and P3 involve strong GABAergic, cholinergic and glutamatergic system interactions. The aim of this study was to test the potential associations between single nucleotide polymorphisms (SNPs) in glutamate receptor genes and ERO quantitative traits. GRM8 was selected because it maps at chromosome 7q31.3-q32.1 under the peak region where we previously identified significant linkage (peak LOD = 3.5) using a genome-wide linkage scan of the same phenotype (event-related theta band for the target visual stimuli). Neural activities recorded from scalp electrodes during a visual oddball task in which rare target elicited P3s were analyzed in a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) sample comprising 1,049 Caucasian subjects from 209 families (with 472 DSM-IV alcohol dependent individuals). The family-based association test (FBAT) detected significant association (P < 0.05) with multiple SNPs in the GRM8 gene and event-related theta power to target visual stimuli, and also with alcohol dependence, even after correction for multiple comparisons by false discovery rate (FDR). Our results suggest that variation in GRM8 may be involved in modulating event-related theta oscillations during information processing and also in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders. (c) 2008 Wiley-Liss, Inc.

Evidence of Common Genetic Overlap Between Schizophrenia and Cognition

PubMed Central

Hubbard, Leon; Tansey, Katherine E.; Rai, Dheeraj; Jones, Peter; Ripke, Stephan; Chambert, Kimberly D.; Moran, Jennifer L.; McCarroll, Steven A.; Linden, David E. J.; Owen, Michael J.; O’Donovan, Michael C.; Walters, James T. R.; Zammit, Stanley

2016-01-01

Cognitive impairment is a core feature of schizophrenia but there is limited understanding of the genetic relationship between cognition in the general population and schizophrenia. We examine how common variants associated with schizophrenia en masse contribute to childhood cognitive ability in a population-based sample, and the extent to which common genetic variants associated with childhood cognition explain variation in schizophrenia. Schizophrenia polygenic risk scores were derived from the Psychiatric Genomics Consortium (n = 69 516) and tested for association with IQ, attention, processing speed, working memory, problem solving, and social cognition in over 5000 children aged 8 from the Avon Longitudinal Study of Parents and Children birth cohort. Polygenic scores for these cognitive domains were tested for association with schizophrenia in a large UK schizophrenia sample (n = 11 853). Bivariate genome-wide complex trait analysis (GCTA) estimated the amount of shared genetic factors between schizophrenia and cognitive domains. Schizophrenia polygenic risk score was associated with lower performance IQ (P = .001) and lower full IQ (P = .013). Polygenic score for performance IQ was associated with increased risk for schizophrenia (P = 3.56E-04). Bivariate GCTA revealed moderate genetic correlation between schizophrenia and both performance IQ (r G = −.379, P = 6.62E-05) and full IQ (r G = −.202, P = 5.00E-03), with approximately 14% of the genetic component of schizophrenia shared with that for performance IQ. Our results support the presence of shared common genetic factors between schizophrenia and childhood cognitive ability. We observe a genetic relationship between schizophrenia and performance IQ but not verbal IQ or other cognitive variables, which may have implications for studies utilizing cognitive endophenotypes for psychosis. PMID:26678674

The Genetic Covariation between Fear Conditioning and Self-Report Fears

PubMed Central

Hettema, John M.; Annas, Peter; Neale, Michael C.; Fredrikson, Mats; Sci, Dr Med; Kendler, Kenneth S.

2008-01-01

Background Fear conditioning is a traditional model for the acquisition of phobias, while behavioral therapies utilize processes underlying extinction to treat phobic and other anxiety disorders. Furthermore, fear conditioning has been proposed as an endophenotype for genetic studies of anxiety disorders. While prior studies have demonstrated that fear conditioning and self-report fears are heritable, no studies have determined whether they share a common genetic basis. Methods We obtained fear conditioning data from 173 twin pairs from the Swedish Twin Registry who also provided self-report ratings of 16 common fears. Using multivariate structural equation modeling, we analyzed factor-derived scores for the subjective fear ratings together with the electrophysiologic skin conductance responses during habituation, acquisition, and extinction to determine the extent of their genetic covariation. Results Phenotypic correlations between experimental and self-report fear measures were modest and, and counter-intuitively, negative; that is, subjects who reported themselves as more fearful had smaller electrophysiologic responses. Best-fit models estimated a significant (negative) genetic correlation between them, although genetic factors underlying fear conditioning accounted for only 9% of individual differences in self-report fears. Conclusions Experimentally-derived fear conditioning measures share only a small portion of the genetic factors underlying individual differences in subjective fears, cautioning against relying too heavily on the former as an endophenotype for genetic studies of phobic disorders. PMID:17698042

Bed sharing among mother-infant pairs in Klang district, Peninsular Malaysia and its relationship to breast-feeding.

PubMed

Tan, Kok Leong

2009-10-01

The aim of the study was to determine the prevalence of mother-infant bed sharing in Klang district, Peninsular Malaysia and to identify factors associated with bed sharing. This was a cross-sectional study involving 682 mother-infant pairs with infants up to 6 months attending government clinics in Klang district, Peninsular Malaysia. Data were collected by face-to-face interview using a pretested structured questionnaire for a 4-month period in 2006. Data regarding maternal, paternal, obstetric, infant, occupancy, breast-feeding characteristics, and bed-sharing practice were collected. Data on bed sharing were based on practice in the past 1-month period. Bed sharing was defined as an infant sharing a bed with mother, and infant must be within arms reach from the mother, whereas a bed was defined as either a sleeping mattress placed on a bed frame or placed on the floor. The prevalence of bed sharing was estimated. Relationship and magnitude of association between independent factors and bed sharing were examined using odds ratio and 95% confidence interval. Logistic regression analysis was used to control for confounding factors. The prevalence of bed sharing among mothers with infants aged between 1 and 6 months was 73.5% (95% confidence interval: 70.0-76.7). In multivariate analysis, urban/rural differences, mothers' ethnicity, occupation, family income, husbands' support on bed sharing, number of children younger than 12 years staying in the house, and breast-feeding were associated with bed sharing. These factors need to be considered in analyzing the overall risks and benefits of bed sharing, paying attention to breastfeeding practices.

Dominant Groups of Potentially Active Bacteria Shared by Barley Seeds become Less Abundant in Root Associated Microbiome.

PubMed

Yang, Luhua; Danzberger, Jasmin; Schöler, Anne; Schröder, Peter; Schloter, Michael; Radl, Viviane

2017-01-01

Endophytes are microorganisms colonizing plant internal tissues. They are ubiquitously associated with plants and play an important role in plant growth and health. In this work, we grew five modern cultivars of barley in axenic systems using sterile sand mixture as well as in greenhouse with natural soil. We characterized the potentially active microbial communities associated with seeds and roots using rRNA based amplicon sequencing. The seeds of the different cultivars share a great part of their microbiome, as we observed a predominance of a few bacterial OTUs assigned to Phyllobacterium , Paenibacillus , and Trabusiella . Seed endophytes, particularly members of the Enterobacteriacea and Paenibacillaceae, were important members of root endophytes in axenic systems, where there were no external microbes. However, when plants were grown in soil, seed endophytes became less abundant in root associated microbiome. We observed a clear enrichment of Actinobacteriacea and Rhizobiaceae, indicating a strong influence of the soil bacterial communities on the composition of the root microbiome. Two OTUs assigned to Phyllobacteriaceae were found in all seeds and root samples growing in soil, indicating a relationship between seed-borne and root associated microbiome in barley. Even though the role of endophytic bacteria remains to be clarified, it is known that many members of the genera detected in our study produce phytohormones, shape seedling exudate profile and may play an important role in germination and establishment of the seedlings.

37 CFR 10.48 - Sharing legal fees.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the practitioner's firm, partner, or associate may provide for the payment of money, over a reasonable... persons. (b) A practitioner who undertakes to complete unfinished legal business of a deceased... is based in whole or in part on a profit-sharing arrangement, providing such plan does not circumvent...

37 CFR 10.48 - Sharing legal fees.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the practitioner's firm, partner, or associate may provide for the payment of money, over a reasonable... persons. (b) A practitioner who undertakes to complete unfinished legal business of a deceased... is based in whole or in part on a profit-sharing arrangement, providing such plan does not circumvent...

37 CFR 10.48 - Sharing legal fees.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the practitioner's firm, partner, or associate may provide for the payment of money, over a reasonable... persons. (b) A practitioner who undertakes to complete unfinished legal business of a deceased... is based in whole or in part on a profit-sharing arrangement, providing such plan does not circumvent...

The genetic epidemiology of personality disorders

PubMed Central

Reichborn-Kjennerud, Ted

2010-01-01

Genetic epidemiologic studies indicate that all ten personality disorders (PDs) classified on the DSM-IV axis II are modestly to moderately heritable. Shared environmental and nonadditive genetic factors are of minor or no importance. No sex differences have been identified. Multivariate studies suggest that the extensive comorbidity between the PDs can be explained by three common genetic and environmental risk factors. The genetic factors do not reflect the DSM-IV cluster structure, but rather: i) broad vulnerability to PD pathology or negative emotionality; ii) high impulsivity/low agreeableness; and iii) introversion. Common genetic and environmental liability factors contribute to comorbidity between pairs or clusters of axis I and axis II disorders. Molecular genetic studies of PDs, mostly candidate gene association studies, indicate that genes linked to neurotransmitter pathways, especially in the serotonergic and dopaminergic systems, are involved. Future studies, using newer methods like genome-wide association, might take advantage of the use of endophenotypes. PMID:20373672

ShareSync: A Solution for Deterministic Data Sharing over Ethernet

NASA Technical Reports Server (NTRS)

Dunn, Daniel J., II; Koons, William A.; Kennedy, Richard D.; Davis, Philip A.

2007-01-01

As part of upgrading the Contact Dynamics Simulation Laboratory (CDSL) at the NASA Marshall Space Flight Center (MSFC), a simple, cost effective method was needed to communicate data among the networked simulation machines and I/O controllers used to run the facility. To fill this need and similar applicable situations, a generic protocol was developed, called ShareSync. ShareSync is a lightweight, real-time, publish-subscribe Ethernet protocol for simple and deterministic data sharing across diverse machines and operating systems. ShareSync provides a simple Application Programming Interface (API) for simulation programmers to incorporate into their code. The protocol is compatible with virtually all Ethernet-capable machines, is flexible enough to support a variety of applications, is fast enough to provide soft real-time determinism, and is a low-cost resource for distributed simulation development, deployment, and maintenance. The first design cycle iteration of ShareSync has been completed, and the protocol has undergone several testing procedures including endurance and benchmarking tests and approaches the 2001ts data synchronization design goal for the CDSL.

Computing on quantum shared secrets

NASA Astrophysics Data System (ADS)

Ouyang, Yingkai; Tan, Si-Hui; Zhao, Liming; Fitzsimons, Joseph F.

2017-11-01

A (k ,n )-threshold secret-sharing scheme allows for a string to be split into n shares in such a way that any subset of at least k shares suffices to recover the secret string, but such that any subset of at most k -1 shares contains no information about the secret. Quantum secret-sharing schemes extend this idea to the sharing of quantum states. Here we propose a method of performing computation securely on quantum shared secrets. We introduce a (n ,n )-quantum secret sharing scheme together with a set of algorithms that allow quantum circuits to be evaluated securely on the shared secret without the need to decode the secret. We consider a multipartite setting, with each participant holding a share of the secret. We show that if there exists at least one honest participant, no group of dishonest participants can recover any information about the shared secret, independent of their deviations from the algorithm.

How Low-Income Subsidy Recipients Respond to Medicare Part D Cost Sharing.

PubMed

Stuart, Bruce; Hendrick, Franklin B; Xu, Jing; Dougherty, J Samantha

2017-06-01

To determine the magnitude and mechanisms of response to Medicare Part D cost sharing by low-income subsidy (LIS) recipients using oral hypoglycemic agents (OHAs) and statins. Medicare data for a 5 percent random sample of beneficiaries with diabetes enrolled in fee-for-service Part D drug plans in 2008. We evaluated the impact of differences between generic and brand cost sharing rates among cohorts of LIS and non-LIS recipients to determine if wider price spreads increased the generic dispensing rate (GDR) and reduced total drug use and cost. We found little association between cost sharing and aggregate OHA and statin use. In adjusted analyses, non-LIS beneficiaries who paid 46 percent of total OHA costs had 2.5 percent fewer OHA days supply than full benefit dual eligibles who paid just 5 percent of their therapy costs. For statins, the difference in days supply between those facing the lowest and highest cost sharing was 4.6 percent. Higher cost sharing was associated with filling fewer but larger prescriptions for both generics and brands. Higher generic and brand copays had little association with OHA and statin use among LIS recipients. This implies that modest changes in required cost sharing for these medicines would have very little substantive impact on generic dispensing or utilization patterns among LIS recipients and thus would have little effect on total program spending. At the same time, any increases in out-of-pocket costs would be expected to shift costs and place greater financial burden on low-income beneficiaries, particularly those in poor health. © Health Research and Educational Trust.

Shared decision-making during surgical consultation for gallstones at a safety-net hospital.

PubMed

Mueck, Krislynn M; Leal, Isabel M; Wan, Charlie C; Goldberg, Braden F; Saunders, Tamara E; Millas, Stefanos G; Liang, Mike K; Ko, Tien C; Kao, Lillian S

2018-04-01

Understanding patient perspectives regarding shared decision-making is crucial to providing informed, patient-centered care. Little is known about perceptions of vulnerable patients regarding shared decision-making during surgical consultation. The purpose of this study was to evaluate whether a validated tool reflects perceptions of shared decision-making accurately among patients seeking surgical consultation for gallstones at a safety-net hospital. A mixed methods study was conducted in a sample of adult patients with gallstones evaluated at a safety-net surgery clinic between May to July 2016. Semi-structured interviews were conducted after their initial surgical consultation and analyzed for emerging themes. Patients were administered the Shared Decision-Making Questionnaire and Autonomy Preference Scale. Univariate analyses were performed to identify factors associated with shared decision-making and to compare the results of the surveys to those of the interviews. The majority of patients (N = 30) were female (90%), Hispanic (80%), Spanish-speaking (70%), and middle-aged (45.7 ± 16 years). The proportion of patients who perceived shared decision-making was greater in the Shared Decision-Making Questionnaire versus the interviews (83% vs 27%, P < .01). Age, sex, race/ethnicity, primary language, diagnosis, Autonomy Preference Scale score, and decision for operation was not associated with shared decision-making. Contributory factors to this discordance include patient unfamiliarity with shared decision-making, deference to surgeon authority, lack of discussion about different treatments, and confusion between aligned versus shared decisions. Available questionnaires may overestimate shared decision-making in vulnerable patients suggesting the need for alternative or modifications to existing methods. Furthermore, such metrics should be assessed for correlation with patient-reported outcomes, such as satisfaction with decisions and health status

Graphemes Sharing Phonetic Features Tend to Induce Similar Synesthetic Colors.

PubMed

Kang, Mi-Jeong; Kim, Yeseul; Shin, Ji-Young; Kim, Chai-Youn

2017-01-01

Individuals with grapheme-color synesthesia experience idiosyncratic colors when viewing achromatic letters or digits. Despite large individual differences in grapheme-color association, synesthetes tend to associate graphemes sharing a perceptual feature with similar synesthetic colors. Sound has been suggested as one such feature. In the present study, we investigated whether graphemes of which representative phonemes have similar phonetic features tend to be associated with analogous synesthetic colors. We tested five Korean multilingual synesthetes on a color-matching task using graphemes from Korean, English, and Japanese orthography. We then compared the similarity of synesthetic colors induced by those characters sharing a phonetic feature. Results showed that graphemes associated with the same phonetic feature tend to induce synesthetic color in both within- and cross-script analyses. Moreover, this tendency was consistent for graphemes that are not transliterable into each other as well as graphemes that are. These results suggest that it is the perceptual-i.e., phonetic-properties associated with graphemes, not just conceptual associations such as transliteration, that determine synesthetic color.

Graphemes Sharing Phonetic Features Tend to Induce Similar Synesthetic Colors

PubMed Central

Kang, Mi-Jeong; Kim, Yeseul; Shin, Ji-Young; Kim, Chai-Youn

2017-01-01

Individuals with grapheme-color synesthesia experience idiosyncratic colors when viewing achromatic letters or digits. Despite large individual differences in grapheme-color association, synesthetes tend to associate graphemes sharing a perceptual feature with similar synesthetic colors. Sound has been suggested as one such feature. In the present study, we investigated whether graphemes of which representative phonemes have similar phonetic features tend to be associated with analogous synesthetic colors. We tested five Korean multilingual synesthetes on a color-matching task using graphemes from Korean, English, and Japanese orthography. We then compared the similarity of synesthetic colors induced by those characters sharing a phonetic feature. Results showed that graphemes associated with the same phonetic feature tend to induce synesthetic color in both within- and cross-script analyses. Moreover, this tendency was consistent for graphemes that are not transliterable into each other as well as graphemes that are. These results suggest that it is the perceptual—i.e., phonetic—properties associated with graphemes, not just conceptual associations such as transliteration, that determine synesthetic color. PMID:28348537

User perceptions of shared sanitation among rural households in Indonesia and Bangladesh.

PubMed

Nelson, Kali B; Karver, Jonathan; Kullman, Craig; Graham, Jay P

2014-01-01

The practice of sharing sanitation facilities does not meet the current World Health Organization/UNICEF definition for what is considered improved sanitation. Recommendations have been made to categorize shared sanitation as improved sanitation if security, user access, and other conditions can be assured, yet limited data exist on user preferences with respect to shared facilities. This study analyzed user perceptions of shared sanitation facilities in rural households in East Java, Indonesia, and Bangladesh. Cross-sectional studies of 2,087 households in East Java and 3,000 households in Bangladesh were conducted using questionnaires and observational methods. Relative risks were calculated to analyze associations between sanitation access and user perceptions of satisfaction, cleanliness, and safety. In East Java, 82.4% of households with private improved sanitation facilities reported feeling satisfied with their place of defecation compared to 68.3% of households with shared improved facilities [RR 1.19, 95% CI 1.09, 1.31]. In Bangladesh, 87.7% of households with private improved facilities reported feeling satisfied compared to 74.5% of households with shared improved facilities [RR 1.15, 95% CI 1.10, 1.20]. In East Java, 79.5% of households who reported a clean latrine also reported feeling satisfied with their place of defecation; only 38.9% of households who reported a dirty latrine also reported feeling satisfied [RR 1.74, 95% CI 1.45, 2.08]. Simple distinctions between improved and unimproved sanitation facilities tend to misrepresent the variability observed among households sharing sanitation facilities. Our results suggest that private improved sanitation is consistently preferred over any other sanitation option. An increased number of users appeared to negatively affect toilet cleanliness, and lower levels of cleanliness were associated with lower levels of satisfaction. However, when sanitation facilities were clean and shared by a limited number

Job sharing. Part 1.

PubMed

Anderson, K; Forbes, R

1989-01-01

This article is the first of a three part series discussing the impact of nurses job sharing at University Hospital, London, Ontario. This first article explores the advantages and disadvantages of job sharing for staff nurses and their supervising nurse manager, as discussed in the literature. The results of a survey conducted on a unit with a large number of job sharing positions, concur with literature findings. The second article will present the evaluation of a pilot project in which two nurses job share a first line managerial position in the Operating Room. The third article will relate the effects of job sharing on women's perceived general well being. Job sharing in all areas, is regarded as a positive experience by both nurse and administrators.

It's Good to Share: Why Environmental Scientists’ Ethics Are Out of Date

PubMed Central

Soranno, Patricia A.; Cheruvelil, Kendra S.; Elliott, Kevin C.; Montgomery, Georgina M.

2014-01-01

Although there have been many recent calls for increased data sharing, the majority of environmental scientists do not make their individual data sets publicly available in online repositories. Current data-sharing conversations are focused on overcoming the technological challenges associated with data sharing and the lack of rewards and incentives for individuals to share data. We argue that the most important conversation has yet to take place: There has not been a strong ethical impetus for sharing data within the current culture, behaviors, and practices of environmental scientists. In this article, we describe a critical shift that is happening in both society and the environmental science community that makes data sharing not just good but ethically obligatory. This is a shift toward the ethical value of promoting inclusivity within and beyond science. An essential element of a truly inclusionary and democratic approach to science is to share data through publicly accessible data sets. PMID:26955073

It's Good to Share: Why Environmental Scientists' Ethics Are Out of Date.

PubMed

Soranno, Patricia A; Cheruvelil, Kendra S; Elliott, Kevin C; Montgomery, Georgina M

2015-01-01

Although there have been many recent calls for increased data sharing, the majority of environmental scientists do not make their individual data sets publicly available in online repositories. Current data-sharing conversations are focused on overcoming the technological challenges associated with data sharing and the lack of rewards and incentives for individuals to share data. We argue that the most important conversation has yet to take place: There has not been a strong ethical impetus for sharing data within the current culture, behaviors, and practices of environmental scientists. In this article, we describe a critical shift that is happening in both society and the environmental science community that makes data sharing not just good but ethically obligatory. This is a shift toward the ethical value of promoting inclusivity within and beyond science. An essential element of a truly inclusionary and democratic approach to science is to share data through publicly accessible data sets.

Shared Intentionality

ERIC Educational Resources Information Center

Tomasello, Michael; Carpenter, Malinda

2007-01-01

We argue for the importance of processes of shared intentionality in children's early cognitive development. We look briefly at four important social-cognitive skills and how they are transformed by shared intentionality. In each case, we look first at a kind of individualistic version of the skill--as exemplified most clearly in the behavior of…

Job Sharing--Opportunities or Headaches?

ERIC Educational Resources Information Center

Leighton, Patricia

1986-01-01

Discusses the issue of job sharing as a new alternative available to workers. Topics covered include (1) a profile of job sharers, (2) response to job sharing, (3) establishing a job share, (4) job sharing in operation, and (5) legal analysis of job sharing. (CH)

The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project.

PubMed

Blokland, Gabriëlla A M; Del Re, Elisabetta C; Mesholam-Gately, Raquelle I; Jovicich, Jorge; Trampush, Joey W; Keshavan, Matcheri S; DeLisi, Lynn E; Walters, James T R; Turner, Jessica A; Malhotra, Anil K; Lencz, Todd; Shenton, Martha E; Voineskos, Aristotle N; Rujescu, Dan; Giegling, Ina; Kahn, René S; Roffman, Joshua L; Holt, Daphne J; Ehrlich, Stefan; Kikinis, Zora; Dazzan, Paola; Murray, Robin M; Di Forti, Marta; Lee, Jimmy; Sim, Kang; Lam, Max; Wolthusen, Rick P F; de Zwarte, Sonja M C; Walton, Esther; Cosgrove, Donna; Kelly, Sinead; Maleki, Nasim; Osiecki, Lisa; Picchioni, Marco M; Bramon, Elvira; Russo, Manuela; David, Anthony S; Mondelli, Valeria; Reinders, Antje A T S; Falcone, M Aurora; Hartmann, Annette M; Konte, Bettina; Morris, Derek W; Gill, Michael; Corvin, Aiden P; Cahn, Wiepke; Ho, New Fei; Liu, Jian Jun; Keefe, Richard S E; Gollub, Randy L; Manoach, Dara S; Calhoun, Vince D; Schulz, S Charles; Sponheim, Scott R; Goff, Donald C; Buka, Stephen L; Cherkerzian, Sara; Thermenos, Heidi W; Kubicki, Marek; Nestor, Paul G; Dickie, Erin W; Vassos, Evangelos; Ciufolini, Simone; Reis Marques, Tiago; Crossley, Nicolas A; Purcell, Shaun M; Smoller, Jordan W; van Haren, Neeltje E M; Toulopoulou, Timothea; Donohoe, Gary; Goldstein, Jill M; Seidman, Larry J; McCarley, Robert W; Petryshen, Tracey L

2018-05-01

Schizophrenia has a large genetic component, and the pathways from genes to illness manifestation are beginning to be identified. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) Consortium aims to clarify the role of genetic variation in brain abnormalities underlying schizophrenia. This article describes the GENUS Consortium sample collection. We identified existing samples collected for schizophrenia studies consisting of patients, controls, and/or individuals at familial high-risk (FHR) for schizophrenia. Samples had single nucleotide polymorphism (SNP) array data or genomic DNA, clinical and demographic data, and neuropsychological and/or brain magnetic resonance imaging (MRI) data. Data were subjected to quality control procedures at a central site. Sixteen research groups contributed data from 5199 psychosis patients, 4877 controls, and 725 FHR individuals. All participants have relevant demographic data and all patients have relevant clinical data. The sex ratio is 56.5% male and 43.5% female. Significant differences exist between diagnostic groups for premorbid and current IQ (both p<1×10 -10 ). Data from a diversity of neuropsychological tests are available for 92% of participants, and 30% have structural MRI scans (half also have diffusion-weighted MRI scans). SNP data are available for 76% of participants. The ancestry composition is 70% European, 20% East Asian, 7% African, and 3% other. The Consortium is investigating the genetic contribution to brain phenotypes in a schizophrenia sample collection of >10,000 participants. The breadth of data across clinical, genetic, neuropsychological, and MRI modalities provides an important opportunity for elucidating the genetic basis of neural processes underlying schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Shared leadership and group identification in healthcare: The leadership beliefs of clinicians working in interprofessional teams.

PubMed

Forsyth, Craig; Mason, Barbara

2017-05-01

Despite the proposed benefits of applying shared and distributed leadership models in healthcare, few studies have explored the leadership beliefs of clinicians and ascertained whether differences exist between professions. The current article aims to address these gaps and, additionally, examine whether clinicians' leadership beliefs are associated with the strength of their professional and team identifications. An online survey was responded to by 229 healthcare workers from community interprofessional teams in mental health settings across the East of England. No differences emerged between professional groups in their leadership beliefs; all professions reported a high level of agreement with shared leadership. A positive association emerged between professional identification and shared leadership in that participants who expressed the strongest level of profession identification also reported the greatest agreement with shared leadership. The same association was demonstrated for team identification and shared leadership. The findings highlight the important link between group identification and leadership beliefs, suggesting that strategies that promote strong professional and team identifications in interprofessional teams are likely to be conducive to clinicians supporting principles of shared leadership. Future research is needed to strengthen this link and examine the leadership practices of healthcare workers.

Specific electrophysiological components disentangle affective sharing and empathic concern in psychopathy.

PubMed

Decety, Jean; Lewis, Kimberly L; Cowell, Jason M

2015-07-01

Empathic impairment is one of the hallmarks of psychopathy, a personality dimension associated with poverty in affective reactions, lack of attachment to others, and a callous disregard for the feelings, rights, and welfare of others. Neuroscience research on the relation between empathy and psychopathy has predominately focused on the affective sharing and cognitive components of empathy in forensic populations, and much less on empathic concern. The current study used high-density electroencephalography in a community sample to examine the spatiotemporal neurodynamic responses when viewing people in physical distress under two subjective contexts: one evoking affective sharing, the other, empathic concern. Results indicate that early automatic (175-275 ms) and later controlled responses (LPP 400-1,000 ms) were differentially modulated by engagement in affective sharing or empathic concern. Importantly, the late event-related potentials (ERP) component was significantly impacted by dispositional empathy and psychopathy, but the early component was not. Individual differences in dispositional empathic concern directly predicted gamma coherence (25-40 Hz), whereas psychopathy was inversely modulatory. Interestingly, significant suppression in the mu/alpha band (8-13 Hz) when perceiving others in distress was positively associated with higher trait psychopathy, which argues against the assumption that sensorimotor resonance underpins empathy. Greater scores on trait psychopathy were inversely related to subjective ratings of both empathic concern and affective sharing. Overall, the study demonstrates that neural markers of affective sharing and empathic concern to the same cues of another's distress can be distinguished at an electrophysiological level, and that psychopathy alters later time-locked differentiations and spectral coherence associated with empathic concern. Copyright © 2015 the American Physiological Society.

Specific electrophysiological components disentangle affective sharing and empathic concern in psychopathy

PubMed Central

Lewis, Kimberly L.; Cowell, Jason M.

2015-01-01

Empathic impairment is one of the hallmarks of psychopathy, a personality dimension associated with poverty in affective reactions, lack of attachment to others, and a callous disregard for the feelings, rights, and welfare of others. Neuroscience research on the relation between empathy and psychopathy has predominately focused on the affective sharing and cognitive components of empathy in forensic populations, and much less on empathic concern. The current study used high-density electroencephalography in a community sample to examine the spatiotemporal neurodynamic responses when viewing people in physical distress under two subjective contexts: one evoking affective sharing, the other, empathic concern. Results indicate that early automatic (175–275 ms) and later controlled responses (LPP 400–1,000 ms) were differentially modulated by engagement in affective sharing or empathic concern. Importantly, the late event-related potentials (ERP) component was significantly impacted by dispositional empathy and psychopathy, but the early component was not. Individual differences in dispositional empathic concern directly predicted gamma coherence (25–40 Hz), whereas psychopathy was inversely modulatory. Interestingly, significant suppression in the mu/alpha band (8–13 Hz) when perceiving others in distress was positively associated with higher trait psychopathy, which argues against the assumption that sensorimotor resonance underpins empathy. Greater scores on trait psychopathy were inversely related to subjective ratings of both empathic concern and affective sharing. Overall, the study demonstrates that neural markers of affective sharing and empathic concern to the same cues of another's distress can be distinguished at an electrophysiological level, and that psychopathy alters later time-locked differentiations and spectral coherence associated with empathic concern. PMID:25948868

Shared prefetching to reduce execution skew in multi-threaded systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eichenberger, Alexandre E; Gunnels, John A

Mechanisms are provided for optimizing code to perform prefetching of data into a shared memory of a computing device that is shared by a plurality of threads that execute on the computing device. A memory stream of a portion of code that is shared by the plurality of threads is identified. A set of prefetch instructions is distributed across the plurality of threads. Prefetch instructions are inserted into the instruction sequences of the plurality of threads such that each instruction sequence has a separate sub-portion of the set of prefetch instructions, thereby generating optimized code. Executable code is generated basedmore » on the optimized code and stored in a storage device. The executable code, when executed, performs the prefetches associated with the distributed set of prefetch instructions in a shared manner across the plurality of threads.« less

Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening.

PubMed

Marchese, Maria; Conti, Valerio; Valvo, Giulia; Moro, Francesca; Muratori, Filippo; Tancredi, Raffaella; Santorelli, Filippo M; Guerrini, Renzo; Sicca, Federico

2014-02-27

With a complex and extremely high clinical and genetic heterogeneity, autism spectrum disorders (ASD) are better dissected if one takes into account specific endophenotypes. Comorbidity of ASD with epilepsy (or paroxysmal EEG) has long been described and seems to have strong genetic background. Macrocephaly also represents a well-known endophenotype in subgroups of ASD individuals, which suggests pathogenic mechanisms accelerating brain growth in early development and predisposing to the disorder. We attempted to estimate the association of gene variants with neurodevelopmental disorders in patients with autism-epilepsy phenotype (AEP) and cranial overgrowth, analyzing two genes previously reported to be associated with autism and macrocephaly. We analyzed the coding sequences and exon-intron boundaries of GLIALCAM, encoding an IgG-like cell adhesion protein, in 81 individuals with Autism Spectrum Disorders, either with or without comorbid epilepsy, paroxysmal EEG and/or macrocephaly, and the PTEN gene in the subsample with macrocephaly. Among 81 individuals with ASD, 31 had concurrent macrocephaly. Head circumference, moreover, was over the 99.7th percentile ("extreme" macrocephaly) in 6/31 (19%) patients. Whilst we detected in GLIALCAM several single nucleotide variants without clear pathogenic effects, we found a novel PTEN heterozygous frameshift mutation in one case with "extreme" macrocephaly, autism, intellectual disability and seizures. We did not find a clear association between GLIALCAM mutations and AEP-macrocephaly comorbidity. The identification of a novel frameshift variant of PTEN in a patient with "extreme" macrocephaly, autism, intellectual disability and seizures, confirms this gene as a major candidate in the ASD-macrocephaly endophenotype. The concurrence of epilepsy in the same patient also suggests that PTEN, and the downstream signaling pathway, might deserve to be investigated in autism-epilepsy comorbidity. Working on clinical

Impact of type 2 diabetes medication cost sharing on patient outcomes and health plan costs.

PubMed

Thornton Snider, Julia; Seabury, Seth; Lopez, Janice; McKenzie, Scott; Goldman, Dana P

2016-06-01

To study the association between cost sharing for diabetes medications, adherence, hospitalization rates, and healthcare costs, with relationship to patient risk. A retrospective claims analysis of data from 35 large, private, self-insured employers (2004 to 2012). We examined outcomes for 92,410 patients aged 18 to 64 years with a type 2 diabetes (T2D) diagnosis who filled at least 1 T2D prescription. First, we examined the relationship between adherence, measured as the proportion of days covered, and cost sharing, measured as the out-of-pocket cost to purchase a pre-specified bundle of T2D prescriptions. We then examined the association between adherence and hospital days. Simulations showed the effect of increased cost sharing on adherence and inpatient utilization. A $10 increase in out-of-pocket cost was associated with a 1.9% reduction in adherence (P < .01). In turn, a 10% reduction in adherence was associated with a 15% increase in per-patient hospital days (0.17 days; P < .01). For the average plan, switching from low to high cost sharing reduced per-patient medication costs by $242 and increased per-patient hospitalization costs by $342, for a net increase of $100 in plan costs. Increases in per-patient costs were greater for high-risk patients, such as those with heart failure ($1328). Increased cost sharing for T2D medication was associated with reductions in pharmacy costs, but higher total costs for patients with T2D. This problem is particularly acute for patients with 1 or more cardiovascular comorbidities. The results suggest that increased diabetes cost sharing may hamper efforts to lower the total cost of diabetes care.

Shared clinical decision making

PubMed Central

AlHaqwi, Ali I.; AlDrees, Turki M.; AlRumayyan, Ahmad; AlFarhan, Ali I.; Alotaibi, Sultan S.; AlKhashan, Hesham I.; Badri, Motasim

2015-01-01

Objectives: To determine preferences of patients regarding their involvement in the clinical decision making process and the related factors in Saudi Arabia. Methods: This cross-sectional study was conducted in a major family practice center in King Abdulaziz Medical City, Riyadh, Saudi Arabia, between March and May 2012. Multivariate multinomial regression models were fitted to identify factors associated with patients preferences. Results: The study included 236 participants. The most preferred decision-making style was shared decision-making (57%), followed by paternalistic (28%), and informed consumerism (14%). The preference for shared clinical decision making was significantly higher among male patients and those with higher level of education, whereas paternalism was significantly higher among older patients and those with chronic health conditions, and consumerism was significantly higher in younger age groups. In multivariate multinomial regression analysis, compared with the shared group, the consumerism group were more likely to be female [adjusted odds ratio (AOR) =2.87, 95% confidence interval [CI] 1.31-6.27, p=0.008] and non-dyslipidemic (AOR=2.90, 95% CI: 1.03-8.09, p=0.04), and the paternalism group were more likely to be older (AOR=1.03, 95% CI: 1.01-1.05, p=0.04), and female (AOR=2.47, 95% CI: 1.32-4.06, p=0.008). Conclusion: Preferences of patients for involvement in the clinical decision-making varied considerably. In our setting, underlying factors that influence these preferences identified in this study should be considered and tailored individually to achieve optimal treatment outcomes. PMID:26620990

Ad spending: maintaining market share.

PubMed

Jones, J P

1990-01-01

Accuracy in manufacturers' advertising budgeting is hampered by reliance on the case rate system, which ties budgets to sales. A better measure is a brand's market share compared with its share of voice (the brand's share of the total value of the main media exposure in that product category). New brands are often "investing" in the market: speaking in a louder voice than their market shares would justify. Popular brands are often "profit taking"--keeping their voices low but enjoying a disproportionately large market share. The interrelationship between market share and share of voice, with either "investing" or "profit taking" the desired result, is not usually considered when determining ad budgets. But as advertisers realize how market share can respond to advertising pressure through switches in the share of voice, this method of market testing should gain in importance.

Breaking the Myths of Rewards: An Exploratory Study of Attitudes about Knowledge Sharing.

ERIC Educational Resources Information Center

Bock, Gee-Woo; Kim, Young-Gul

2002-01-01

Discussion of organizational knowledge sharing focuses on a study of Korean public organizations that investigated factors affecting the individual's knowledge sharing behavior. Highlights include social exchange theory; self-efficacy; theory of reasoned action; and hypothesis testing that showed expected associations and contribution, rather than…

Spontaneous mental associations with the words "side effect": Implications for informed and shared decision making.

PubMed

Izadi, Sonya; Pachur, Thorsten; Wheeler, Courtney; McGuire, Jaclyn; Waters, Erika A

2017-10-01

To gain insight into patients' medical decisions by exploring the content of laypeople's spontaneous mental associations with the term "side effect." An online cross-sectional survey asked 144 women aged 40-74, "What are the first three things you think of when you hear the words 'side effect?"' Data were analyzed using content analysis, chi-square, and Fisher's exact tests. 17 codes emerged and were grouped into 4 themes and a Miscellaneous category: Health Problems (70.8% of participants), Decision-Relevant Evaluations (52.8%), Negative Affect (30.6%), Practical Considerations (18.1%) and Miscellaneous (9.7%). The 4 most frequently identified codes were: Risk (36.1%), Health Problems-Specific Symptoms (35.4%), Health Problems-General Terms (32.6%), and Negative Affect-Strong (19.4%). Code and theme frequencies were generally similar across demographic groups (ps>0.05). The term "side effect" spontaneously elicited comments related to identifying health problems and expressing negative emotions. This might explain why the mere possibility of side effects triggers negative affect for people making medical decisions. Some respondents also mentioned decision-relevant evaluations and practical considerations in response to side effects. Addressing commonly-held associations and acknowledging negative affects provoked by side effects are first steps healthcare providers can take towards improving informed and shared patient decision making. Copyright © 2017 Elsevier B.V. All rights reserved.

Syringe Sharing in Drug Injecting Dyads: A Cross-Classified Multilevel Analysis of Social Networks.

PubMed

Shahesmaeili, Armita; Mirzazadeh, Ali; McFarland, Willi; Sharifi, Hamid; Haghdoost, Ali Akbar; Soori, Hamid

2018-05-15

We examined the association of dyadic-level factors with syringe sharing among people who inject drugs (PWID) in Kerman, Iran. In a cross-sectional study, we collected data on 329 drug-injecting dyads by individual face-to-face interviews. An injecting dyad was defined as 2 PWID who knew each other and injected drugs together during the last 6 months. If they reported at least 1 occasion of syringe sharing, the dyad was considered high-risk. Dyadic-level factors associated with syringe sharing were assessed using cross-classified multilevel logistic regression. The rate of syringe sharing was significantly higher for dyads who were more intimate (adjusted odds ratio [AOR] 4.5, CI 95%, 2.3-8.6), who had instrumental support (AOR 2.1, 95% CI 1.1-4.5), and who pooled money for drugs (AOR 4.1, 95% CI 2.0-8.3). The rate was lower in same-sex dyads (AOR 0.4, 95% CI 0.2-0.9) and in dyads who shared health information (AOR 0.5, 95% CI 0.2-0.9). Findings highlight close-peer influences on syringe-sharing behavior.

Quantifying the conservation gains from shared access to linear infrastructure.

PubMed

Runge, Claire A; Tulloch, Ayesha I T; Gordon, Ascelin; Rhodes, Jonathan R

2017-12-01

The proliferation of linear infrastructure such as roads and railways is a major global driver of cumulative biodiversity loss. One strategy for reducing habitat loss associated with development is to encourage linear infrastructure providers and users to share infrastructure networks. We quantified the reductions in biodiversity impact and capital costs under linear infrastructure sharing of a range of potential mine to port transportation links for 47 mine locations operated by 28 separate companies in the Upper Spencer Gulf Region of South Australia. We mapped transport links based on least-cost pathways for different levels of linear-infrastructure sharing and used expert-elicited impacts of linear infrastructure to estimate the consequences for biodiversity. Capital costs were calculated based on estimates of construction costs, compensation payments, and transaction costs. We evaluated proposed mine-port links by comparing biodiversity impacts and capital costs across 3 scenarios: an independent scenario, where no infrastructure is shared; a restricted-access scenario, where the largest mining companies share infrastructure but exclude smaller mining companies from sharing; and a shared scenario where all mining companies share linear infrastructure. Fully shared development of linear infrastructure reduced overall biodiversity impacts by 76% and reduced capital costs by 64% compared with the independent scenario. However, there was considerable variation among companies. Our restricted-access scenario showed only modest biodiversity benefits relative to the independent scenario, indicating that reductions are likely to be limited if the dominant mining companies restrict access to infrastructure, which often occurs without policies that promote sharing of infrastructure. Our research helps illuminate the circumstances under which infrastructure sharing can minimize the biodiversity impacts of development. © 2017 The Authors. Conservation Biology published

Barriers to Shared Use of Indoor and Outdoor Facilities at US Elementary Schools

ERIC Educational Resources Information Center

Turner, Lindsey; Calvert, Hannah G.; Chaloupka, Frank J.

2018-01-01

Background: School policies and practices, such as the sharing of school facilities with the surrounding community, support physical activity among students and community members, but are often underutilized. This study examined variations in shared use practices, and associations with perceived barriers. Methods: Surveys were completed by a…

12 CFR Part 745 - SHARE INSURANCE AND APPENDIX

Code of Federal Regulations, 2010 CFR

2010-01-01

...—SHARE INSURANCE AND APPENDIX Subpart A—Clarification and Definition of Account Insurance Coverage Sec... accounts. 745.3 Single ownership accounts. 745.4 Revocable trust accounts. 745.5 Accounts held by executors or administrators. 745.6 Accounts held by a corporation, partnership, or unincorporated association...

Dominant Groups of Potentially Active Bacteria Shared by Barley Seeds become Less Abundant in Root Associated Microbiome

PubMed Central

Yang, Luhua; Danzberger, Jasmin; Schöler, Anne; Schröder, Peter; Schloter, Michael; Radl, Viviane

2017-01-01

Endophytes are microorganisms colonizing plant internal tissues. They are ubiquitously associated with plants and play an important role in plant growth and health. In this work, we grew five modern cultivars of barley in axenic systems using sterile sand mixture as well as in greenhouse with natural soil. We characterized the potentially active microbial communities associated with seeds and roots using rRNA based amplicon sequencing. The seeds of the different cultivars share a great part of their microbiome, as we observed a predominance of a few bacterial OTUs assigned to Phyllobacterium, Paenibacillus, and Trabusiella. Seed endophytes, particularly members of the Enterobacteriacea and Paenibacillaceae, were important members of root endophytes in axenic systems, where there were no external microbes. However, when plants were grown in soil, seed endophytes became less abundant in root associated microbiome. We observed a clear enrichment of Actinobacteriacea and Rhizobiaceae, indicating a strong influence of the soil bacterial communities on the composition of the root microbiome. Two OTUs assigned to Phyllobacteriaceae were found in all seeds and root samples growing in soil, indicating a relationship between seed-borne and root associated microbiome in barley. Even though the role of endophytic bacteria remains to be clarified, it is known that many members of the genera detected in our study produce phytohormones, shape seedling exudate profile and may play an important role in germination and establishment of the seedlings. PMID:28663753

Open innovation: Towards sharing of data, models and workflows.

PubMed

Conrado, Daniela J; Karlsson, Mats O; Romero, Klaus; Sarr, Céline; Wilkins, Justin J

2017-11-15

Sharing of resources across organisations to support open innovation is an old idea, but which is being taken up by the scientific community at increasing speed, concerning public sharing in particular. The ability to address new questions or provide more precise answers to old questions through merged information is among the attractive features of sharing. Increased efficiency through reuse, and increased reliability of scientific findings through enhanced transparency, are expected outcomes from sharing. In the field of pharmacometrics, efforts to publicly share data, models and workflow have recently started. Sharing of individual-level longitudinal data for modelling requires solving legal, ethical and proprietary issues similar to many other fields, but there are also pharmacometric-specific aspects regarding data formats, exchange standards, and database properties. Several organisations (CDISC, C-Path, IMI, ISoP) are working to solve these issues and propose standards. There are also a number of initiatives aimed at collecting disease-specific databases - Alzheimer's Disease (ADNI, CAMD), malaria (WWARN), oncology (PDS), Parkinson's Disease (PPMI), tuberculosis (CPTR, TB-PACTS, ReSeqTB) - suitable for drug-disease modelling. Organized sharing of pharmacometric executable model code and associated information has in the past been sparse, but a model repository (DDMoRe Model Repository) intended for the purpose has recently been launched. In addition several other services can facilitate model sharing more generally. Pharmacometric workflows have matured over the last decades and initiatives to more fully capture those applied to analyses are ongoing. In order to maximize both the impact of pharmacometrics and the knowledge extracted from clinical data, the scientific community needs to take ownership of and create opportunities for open innovation. Copyright © 2017 Elsevier B.V. All rights reserved.

Policy enabled information sharing system

DOEpatents

Jorgensen, Craig R.; Nelson, Brian D.; Ratheal, Steve W.

2014-09-02

A technique for dynamically sharing information includes executing a sharing policy indicating when to share a data object responsive to the occurrence of an event. The data object is created by formatting a data file to be shared with a receiving entity. The data object includes a file data portion and a sharing metadata portion. The data object is encrypted and then automatically transmitted to the receiving entity upon occurrence of the event. The sharing metadata portion includes metadata characterizing the data file and referenced in connection with the sharing policy to determine when to automatically transmit the data object to the receiving entity.

Identification of genetic loci shared between schizophrenia and the Big Five personality traits.

PubMed

Smeland, Olav B; Wang, Yunpeng; Lo, Min-Tzu; Li, Wen; Frei, Oleksandr; Witoelar, Aree; Tesli, Martin; Hinds, David A; Tung, Joyce Y; Djurovic, Srdjan; Chen, Chi-Hua; Dale, Anders M; Andreassen, Ole A

2017-05-22

Schizophrenia is associated with differences in personality traits, and recent studies suggest that personality traits and schizophrenia share a genetic basis. Here we aimed to identify specific genetic loci shared between schizophrenia and the Big Five personality traits using a Bayesian statistical framework. Using summary statistics from genome-wide association studies (GWAS) on personality traits in the 23andMe cohort (n = 59,225) and schizophrenia in the Psychiatric Genomics Consortium cohort (n = 82,315), we evaluated overlap in common genetic variants. The Big Five personality traits neuroticism, extraversion, openness, agreeableness and conscientiousness were measured using a web implementation of the Big Five Inventory. Applying the conditional false discovery rate approach, we increased discovery of genetic loci and identified two loci shared between neuroticism and schizophrenia and six loci shared between openness and schizophrenia. The study provides new insights into the relationship between personality traits and schizophrenia by highlighting genetic loci involved in their common genetic etiology.

Job Sharing in Geography.

ERIC Educational Resources Information Center

Kay, Jeanne

1982-01-01

Job sharing is an employment alternative in which two qualified individuals manage the responsibilities of a single position. Discusses the barriers to and the potential, advantages, disadvantages, pitfalls, and challenges of job sharing. Focuses on job sharing in the geography profession. (Author/JN)

Representing Hydrologic Models as HydroShare Resources to Facilitate Model Sharing and Collaboration

NASA Astrophysics Data System (ADS)

Castronova, A. M.; Goodall, J. L.; Mbewe, P.

2013-12-01

The CUAHSI HydroShare project is a collaborative effort that aims to provide software for sharing data and models within the hydrologic science community. One of the early focuses of this work has been establishing metadata standards for describing models and model-related data as HydroShare resources. By leveraging this metadata definition, a prototype extension has been developed to create model resources that can be shared within the community using the HydroShare system. The extension uses a general model metadata definition to create resource objects, and was designed so that model-specific parsing routines can extract and populate metadata fields from model input and output files. The long term goal is to establish a library of supported models where, for each model, the system has the ability to extract key metadata fields automatically, thereby establishing standardized model metadata that will serve as the foundation for model sharing and collaboration within HydroShare. The Soil Water & Assessment Tool (SWAT) is used to demonstrate this concept through a case study application.

Shared Negative Experiences Lead to Identity Fusion via Personal Reflection.

PubMed

Jong, Jonathan; Whitehouse, Harvey; Kavanagh, Christopher; Lane, Justin

2015-01-01

Across three studies, we examined the role of shared negative experiences in the formation of strong social bonds--identity fusion--previously associated with individuals' willingness to self-sacrifice for the sake of their groups. Studies 1 and 2 were correlational studies conducted on two different populations. In Study 1, we found that the extent to which Northern Irish Republicans and Unionists experienced shared negative experiences was associated with levels of identity fusion, and that this relationship was mediated by their reflection on these experiences. In Study 2, we replicated this finding among Bostonians, looking at their experiences of the 2013 Boston Marathon Bombings. These correlational studies provide initial evidence for the plausibility of our causal model; however, an experiment was required for a more direct test. Thus, in Study 3, we experimentally manipulated the salience of the Boston Marathon Bombings, and found that this increased state levels of identity fusion among those who experienced it negatively. Taken together, these three studies provide evidence that shared negative experience leads to identity fusion, and that this process involves personal reflection.

Sharing Rare Attitudes Attracts.

PubMed

Alves, Hans

2018-04-01

People like others who share their attitudes. Online dating platforms as well as other social media platforms regularly rely on the social bonding power of their users' shared attitudes. However, little is known about moderating variables. In the present work, I argue that sharing rare compared with sharing common attitudes should evoke stronger interpersonal attraction among people. In five studies, I tested this prediction for the case of shared interests from different domains. I found converging evidence that people's rare compared with their common interests are especially potent to elicit interpersonal attraction. I discuss the current framework's theoretical implications for impression formation and impression management as well as its practical implications for improving online dating services.

Secret Sharing and Shared Information

NASA Astrophysics Data System (ADS)

Rauh, Johannes

2017-11-01

Secret sharing is a cryptographic discipline in which the goal is to distribute information about a secret over a set of participants in such a way that only specific authorized combinations of participants together can reconstruct the secret. Thus, secret sharing schemes are systems of variables in which it is very clearly specified which subsets have information about the secret. As such, they provide perfect model systems for information decompositions. However, following this intuition too far leads to an information decomposition with negative partial information terms, which are difficult to interpret. One possible explanation is that the partial information lattice proposed by Williams and Beer is incomplete and has to be extended to incorporate terms corresponding to higher order redundancy. These results put bounds on information decompositions that follow the partial information framework, and they hint at where the partial information lattice needs to be improved.

Can power be shared?

PubMed

Ten Pas, William S

2013-01-01

Dental insurance began with a partnership between dental service organizations and state dental associations with a view toward expanding the number of Americans receiving oral health care and as a means for permitting firms and other organizations to offer employee benefits. The goals have been achieved, but the alliance between dentistry and insurance has become strained. A lack of dialogue has fostered mutual misconceptions, some of which are reviewed in this paper. It is possible that the public, the profession, and the dental insurance industry can all be strengthened, but only through power-sharing around the original common objective.

Microbiome sharing between children, livestock and household surfaces in western Kenya.

PubMed

Mosites, Emily; Sammons, Matt; Otiang, Elkanah; Eng, Alexander; Noecker, Cecilia; Manor, Ohad; Hilton, Sarah; Thumbi, Samuel M; Onyango, Clayton; Garland-Lewis, Gemina; Call, Douglas R; Njenga, M Kariuki; Wasserheit, Judith N; Zambriski, Jennifer A; Walson, Judd L; Palmer, Guy H; Montgomery, Joel; Borenstein, Elhanan; Omore, Richard; Rabinowitz, Peter M

2017-01-01

The gut microbiome community structure and development are associated with several health outcomes in young children. To determine the household influences of gut microbiome structure, we assessed microbial sharing within households in western Kenya by sequencing 16S rRNA libraries of fecal samples from children and cattle, cloacal swabs from chickens, and swabs of household surfaces. Among the 156 households studied, children within the same household significantly shared their gut microbiome with each other, although we did not find significant sharing of gut microbiome across host species or household surfaces. Higher gut microbiome diversity among children was associated with lower wealth status and involvement in livestock feeding chores. Although more research is necessary to identify further drivers of microbiota development, these results suggest that the household should be considered as a unit. Livestock activities, health and microbiome perturbations among an individual child may have implications for other children in the household.

Job-Sharing at the Greater Victoria Public Library.

ERIC Educational Resources Information Center

Miller, Don

1978-01-01

Describes the problems associated with the management of part-time library employees and some solutions afforded by a job sharing arrangement in use at the Greater Victoria Public Library. This is a voluntary work arrangement, changing formerly full-time positions into multiple part-time positions. (JVP)

Heritability and molecular-genetic basis of the P3 event-related brain potential: A genome-wide association study

PubMed Central

MALONE, STEPHEN M.; VAIDYANATHAN, UMA; BASU, SAONLI; MILLER, MICHAEL B.; MCGUE, MATT; IACONO, WILLIAM G.

2014-01-01

P3 amplitude is a candidate endophenotype for disinhibitory psychopathology, psychosis, and other disorders. The present study is a comprehensive analysis of the behavioral- and molecular-genetic basis of P3 amplitude and a P3 genetic factor score in a large community sample (N = 4,211) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric models indicated that as much as 65% of the variance in each measure was due to additive genes. All SNPs in aggregate accounted for approximately 40% to 50% of the heritable variance. However, analyses of individual SNPs did not yield any significant associations. Analyses of individual genes did not confirm previous associations between P3 amplitude and candidate genes but did yield a novel association with myelin expression factor 2 (MYEF2). Main effects of individual variants may be too small to be detected by GWAS without larger samples. PMID:25387705

Categorical and associative relations increase false memory relative to purely associative relations.

PubMed

Coane, Jennifer H; McBride, Dawn M; Termonen, Miia-Liisa; Cutting, J Cooper

2016-01-01

The goal of the present study was to examine the contributions of associative strength and similarity in terms of shared features to the production of false memories in the Deese/Roediger-McDermott list-learning paradigm. Whereas the activation/monitoring account suggests that false memories are driven by automatic associative activation from list items to nonpresented lures, combined with errors in source monitoring, other accounts (e.g., fuzzy trace theory, global-matching models) emphasize the importance of semantic-level similarity, and thus predict that shared features between list and lure items will increase false memory. Participants studied lists of nine items related to a nonpresented lure. Half of the lists consisted of items that were associated but did not share features with the lure, and the other half included items that were equally associated but also shared features with the lure (in many cases, these were taxonomically related items). The two types of lists were carefully matched in terms of a variety of lexical and semantic factors, and the same lures were used across list types. In two experiments, false recognition of the critical lures was greater following the study of lists that shared features with the critical lure, suggesting that similarity at a categorical or taxonomic level contributes to false memory above and beyond associative strength. We refer to this phenomenon as a "feature boost" that reflects additive effects of shared meaning and association strength and is generally consistent with accounts of false memory that have emphasized thematic or feature-level similarity among studied and nonstudied representations.

Highly impulsive rats: modelling an endophenotype to determine the neurobiological, genetic and environmental mechanisms of addiction

PubMed Central

Jupp, Bianca; Caprioli, Daniele; Dalley, Jeffrey W.

2013-01-01

Impulsivity describes the tendency of an individual to act prematurely without foresight and is associated with a number of neuropsychiatric co-morbidities, including drug addiction. As such, there is increasing interest in the neurobiological mechanisms of impulsivity, as well as the genetic and environmental influences that govern the expression of this behaviour. Tests used on rodent models of impulsivity share strong parallels with tasks used to assess this trait in humans, and studies in both suggest a crucial role of monoaminergic corticostriatal systems in the expression of this behavioural trait. Furthermore, rodent models have enabled investigation of the causal relationship between drug abuse and impulsivity. Here, we review the use of rodent models of impulsivity for investigating the mechanisms involved in this trait, and how these mechanisms could contribute to the pathogenesis of addiction. PMID:23355644

A test of multiple hypotheses for the function of call sharing in female budgerigars, Melopsittacus undulatus

PubMed Central

Young, Anna M.; Cordier, Breanne; Mundry, Roger; Wright, Timothy F.

2014-01-01

In many social species group, members share acoustically similar calls. Functional hypotheses have been proposed for call sharing, but previous studies have been limited by an inability to distinguish among these hypotheses. We examined the function of vocal sharing in female budgerigars with a two-part experimental design that allowed us to distinguish between two functional hypotheses. The social association hypothesis proposes that shared calls help animals mediate affiliative and aggressive interactions, while the password hypothesis proposes that shared calls allow animals to distinguish group identity and exclude nonmembers. We also tested the labeling hypothesis, a mechanistic explanation which proposes that shared calls are used to address specific individuals within the sender–receiver relationship. We tested the social association hypothesis by creating four–member flocks of unfamiliar female budgerigars (Melopsittacus undulatus) and then monitoring the birds’ calls, social behaviors, and stress levels via fecal glucocorticoid metabolites. We tested the password hypothesis by moving immigrants into established social groups. To test the labeling hypothesis, we conducted additional recording sessions in which individuals were paired with different group members. The social association hypothesis was supported by the development of multiple shared call types in each cage and a correlation between the number of shared call types and the number of aggressive interactions between pairs of birds. We also found support for calls serving as a labeling mechanism using discriminant function analysis with a permutation procedure. Our results did not support the password hypothesis, as there was no difference in stress or directed behaviors between immigrant and control birds. PMID:24860236

User Perceptions of Shared Sanitation among Rural Households in Indonesia and Bangladesh