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Sample records for association shared endophenotypes

  1. Comorbid Problems in ADHD: Degree of Association, Shared Endophenotypes, and Formation of Distinct Subtypes. Implications for a Future "DSM"

    ERIC Educational Resources Information Center

    Rommelse, Nanda N. J.; Altink, Marieke E.; Fliers, Ellen A.; Martin, Neilson C.; Buschgens, Cathelijne J. M.; Hartman, Catharina A.; Buitelaar, Jan K.; Faraone, Stephen V.; Sergeant, Joseph A.; Oosterlaan, Jaap

    2009-01-01

    We aimed to assess which comorbid problems (oppositional defiant behaviors, anxiety, autistic traits, motor coordination problems, and reading problems) were most associated with Attention-Deficit/Hyperactivity Disorder (ADHD); to determine whether these comorbid problems shared executive and motor problems on an endophenotype level with ADHD; and…

  2. A Neurocognitive Endophenotype Associated with Rolandic Epilepsy

    PubMed Central

    Smith, Anna B; Kavros, Peregrine M; Clarke, Tara; Dorta, Nelson J; Tremont, Geoffrey; Pal, Deb K

    2011-01-01

    Purpose Children with Rolandic Epilepsy (RE) experience difficulties in reading, language and attention. Their siblings are at high risk of dyslexia but are not otherwise known to have neurocognitive deficits. We therefore sought evidence for a RE-associated neurocognitive endophenotype. Methods Thirteen probands (male:female 9:4) and 11 epilepsy-free siblings (male:female 5:6) completed a neurocognitive evaluation within the domains of reading, language and attention. Frequencies of impairment were compared, and mean standardized scores of children with RE and their siblings were each compared against population means. Key findings Frequency of impairment in each domain was comparable for siblings and probands: 9% of siblings and 31% of probands were reading impaired; 36% of siblings and 54% of probands were language impaired; 70% of siblings and 67% of probands had attention impairments. Comparison of differences between sample and population means revealed evidence of a similar pattern of language deficits in both groups, specifically for picture naming and attention to competing words. For measures of attention, both groups made significantly higher omission errors and were impaired in their ability to sustain attention. Significance Children with RE and unaffected siblings demonstrate neurocognitive impairments in the domains of language and attention that are likely to remain undetected with general clinical protocols. Neurocognitively impaired probands and siblings showed a remarkably similar profile of deficits in language and attention that could explain poor academic performance. Early evaluation and intervention may benefit these children academically. PMID:22220688

  3. Distinct and Shared Endophenotypes of Neural Substrates in Bipolar and Major Depressive Disorders

    PubMed Central

    Matsuo, Koji; Harada, Kenichiro; Nakano, Masayuki; Nakashima, Mami; Watanuki, Toshio; Egashira, Kazuteru; Furukawa, Matakazu; Matsunaga, Naofumi; Watanabe, Yoshifumi

    2016-01-01

    Little is known about disorder-specific biomarkers of bipolar disorder (BD) and major depressive disorder (MDD). Our aim was to determine a neural substrate that could be used to distinguish BD from MDD. Our study included a BD group (10 patients with BD, 10 first-degree relatives (FDRs) of individuals with BD), MDD group (17 patients with MDD, 17 FDRs of individuals with MDD), and 27 healthy individuals. Structural and functional brain abnormalities were evaluated by voxel-based morphometry and a trail making test (TMT), respectively. The BD group showed a significant main effect of diagnosis in the gray matter (GM) volume of the anterior cingulate cortex (ACC; p = 0.01) and left insula (p < 0.01). FDRs of individuals with BD showed significantly smaller left ACC GM volume than healthy subjects (p < 0.01), and patients with BD showed significantly smaller ACC (p < 0.01) and left insular GM volume (p < 0.01) than healthy subjects. The MDD group showed a tendency toward a main effect of diagnosis in the right and left insular GM volume. The BD group showed a significantly inverse correlation between the left insular GM volume and TMT-A scores (p < 0.05). Our results suggest that the ACC volume could be a distinct endophenotype of BD, while the insular volume could be a shared BD and MDD endophenotype. Moreover, the insula could be associated with cognitive decline and poor outcome in BD. PMID:28030612

  4. Using endophenotypes to examine molecules related to candidate genes as novel therapeutics: The "endophenotype-associated surrogate endpoint (EASE)" concept.

    PubMed

    Yamasue, Hidenori

    2015-10-01

    In this article, a new concept of an "endophenotype-associated surrogate endpoint (EASE)" is proposed. To examine effect of a novel therapeutic molecule on a target phenotype of a genotype associated with the molecule, state-dependent aspect of an endophenotype can be used as a surrogate endpoint. Desired characteristics for EASE are (1) a close relationship to the endophenotype associated with therapeutics, (2) longitudinal changes in illness severity, while the original "endophenotype" is primarily state independent, (3) a physical sign or laboratory measurement that occurs in association with a pathological process and has putative diagnostic and/or prognostic utility, and (4) serves as a substitute for a clinically meaningful endpoint. Advantages are expected for both surrogate endpoints in drug development and endophenotypes in uncovering pathogenesis. EASE are closer to molecules than clinically meaningful endpoints and can respond to administration of the molecule in a more direct manner. Therefore, a statistically significant effect is likely to be observed in clinical trials with smaller sample sizes and shorter durations. As with endophenotypes, reduced heterogeneity might be expected especially in heterogeneous syndromes such as psychiatric disorders. Potential interactions (e.g., elucidating biological mechanisms underlying novel treatments) can be further expected.

  5. Linkage and association analysis of ADHD endophenotypes in extended and multigenerational pedigrees from a genetic isolate.

    PubMed

    Mastronardi, C A; Pillai, E; Pineda, D A; Martinez, A F; Lopera, F; Velez, J I; Palacio, J D; Patel, H; Easteal, S; Acosta, M T; Castellanos, F X; Muenke, M; Arcos-Burgos, M

    2016-10-01

    Attention-deficit/hyperactivity disorder (ADHD) is a heritable, chronic, neurodevelopmental disorder with serious long-term repercussions. Despite being one of the most common cognitive disorders, the clinical diagnosis of ADHD is based on subjective assessments of perceived behaviors. Endophenotypes (neurobiological markers that cosegregate and are associated with an illness) are thought to provide a more powerful and objective framework for revealing the underlying neurobiology than syndromic psychiatric classification. Here, we present the results of applying genetic linkage and association analyses to neuropsychological endophenotypes using microsatellite and single nucleotide polymorphisms. We found several new genetic regions linked and/or associated with these endophenotypes, and others previously associated to ADHD, for example, loci harbored in the LPHN3, FGF1, POLR2A, CHRNA4 and ANKFY1 genes. These findings, when compared with those linked and/or associated to ADHD, suggest that these endophenotypes lie on shared pathways. The genetic information provided by this study offers a novel and complementary method of assessing the genetic causes underpinning the susceptibility to behavioral conditions and may offer new insights on the neurobiology of the disorder.

  6. Linkage and association analysis of ADHD endophenotypes in extended and multigenerational pedigrees from a genetic isolate

    PubMed Central

    Mastronardi, C A; Pillai, E; Pineda, D A; Martinez, A F; Lopera, F; Velez, J I; Palacio, J D; Patel, H; Easteal, S; Acosta, M T; Castellanos, F X; Muenke, M; Arcos-Burgos, M

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a heritable, chronic, neurodevelopmental disorder with serious long-term repercussions. Despite being one of the most common cognitive disorders, the clinical diagnosis of ADHD is based on subjective assessments of perceived behaviors. Endophenotypes (neurobiological markers that cosegregate and are associated with an illness) are thought to provide a more powerful and objective framework for revealing the underlying neurobiology than syndromic psychiatric classification. Here, we present the results of applying genetic linkage and association analyses to neuropsychological endophenotypes using microsatellite and single nucleotide polymorphisms. We found several new genetic regions linked and/or associated with these endophenotypes, and others previously associated to ADHD, for example, loci harbored in the LPHN3, FGF1, POLR2A, CHRNA4 and ANKFY1 genes. These findings, when compared with those linked and/or associated to ADHD, suggest that these endophenotypes lie on shared pathways. The genetic information provided by this study offers a novel and complementary method of assessing the genetic causes underpinning the susceptibility to behavioral conditions and may offer new insights on the neurobiology of the disorder. PMID:26598068

  7. Association Analysis of 94 Candidate Genes and Schizophrenia-Related Endophenotypes

    PubMed Central

    Swerdlow, Neal R.; Radant, Allen D.; Braff, David L.

    2012-01-01

    While it is clear that schizophrenia is highly heritable, the genetic basis of this heritability is complex. Human genetic, brain imaging, and model organism studies have met with only modest gains. A complementary research tactic is to evaluate the genetic substrates of quantitative endophenotypes with demonstrated deficits in schizophrenia patients. We used an Illumina custom 1,536-SNP array to interrogate 94 functionally relevant candidate genes for schizophrenia and evaluate association with both the qualitative diagnosis of schizophrenia and quantitative endophenotypes for schizophrenia. Subjects included 219 schizophrenia patients and normal comparison subjects of European ancestry and 76 schizophrenia patients and normal comparison subjects of African ancestry, all ascertained by the UCSD Schizophrenia Research Program. Six neurophysiological and neurocognitive endophenotype test paradigms were assessed: prepulse inhibition (PPI), P50 suppression, the antisaccade oculomotor task, the Letter-Number Span Test, the California Verbal Learning Test-II, and the Wisconsin Card Sorting Test-64 Card Version. These endophenotype test paradigms yielded six primary endophenotypes with prior evidence of heritability and demonstrated schizophrenia-related impairments, as well as eight secondary measures investigated as candidate endophenotypes. Schizophrenia patients showed significant deficits on ten of the endophenotypic measures, replicating prior studies and facilitating genetic analyses of these phenotypes. A total of 38 genes were found to be associated with at least one endophenotypic measure or schizophrenia with an empirical p-value<0.01. Many of these genes have been shown to interact on a molecular level, and eleven genes displayed evidence for pleiotropy, revealing associations with three or more endophenotypic measures. Among these genes were ERBB4 and NRG1, providing further support for a role of these genes in schizophrenia susceptibility. The observation

  8. Association analysis of 94 candidate genes and schizophrenia-related endophenotypes.

    PubMed

    Greenwood, Tiffany A; Light, Gregory A; Swerdlow, Neal R; Radant, Allen D; Braff, David L

    2012-01-01

    While it is clear that schizophrenia is highly heritable, the genetic basis of this heritability is complex. Human genetic, brain imaging, and model organism studies have met with only modest gains. A complementary research tactic is to evaluate the genetic substrates of quantitative endophenotypes with demonstrated deficits in schizophrenia patients. We used an Illumina custom 1,536-SNP array to interrogate 94 functionally relevant candidate genes for schizophrenia and evaluate association with both the qualitative diagnosis of schizophrenia and quantitative endophenotypes for schizophrenia. Subjects included 219 schizophrenia patients and normal comparison subjects of European ancestry and 76 schizophrenia patients and normal comparison subjects of African ancestry, all ascertained by the UCSD Schizophrenia Research Program. Six neurophysiological and neurocognitive endophenotype test paradigms were assessed: prepulse inhibition (PPI), P50 suppression, the antisaccade oculomotor task, the Letter-Number Span Test, the California Verbal Learning Test-II, and the Wisconsin Card Sorting Test-64 Card Version. These endophenotype test paradigms yielded six primary endophenotypes with prior evidence of heritability and demonstrated schizophrenia-related impairments, as well as eight secondary measures investigated as candidate endophenotypes. Schizophrenia patients showed significant deficits on ten of the endophenotypic measures, replicating prior studies and facilitating genetic analyses of these phenotypes. A total of 38 genes were found to be associated with at least one endophenotypic measure or schizophrenia with an empirical p-value<0.01. Many of these genes have been shown to interact on a molecular level, and eleven genes displayed evidence for pleiotropy, revealing associations with three or more endophenotypic measures. Among these genes were ERBB4 and NRG1, providing further support for a role of these genes in schizophrenia susceptibility. The observation

  9. Electrophysiological Endophenotypes for Schizophrenia

    PubMed Central

    Owens, Emily; Bachman, Peter; Glahn, David C; Bearden, Carrie E

    2016-01-01

    Endophenotypes are quantitative, heritable traits that may help to elucidate the pathophysiologic mechanisms underlying complex disease syndromes, such as schizophrenia. They can be assessed at numerous levels of analysis; here, we review electrophysiological endophenotypes that have shown promise in helping us understand schizophrenia from a more mechanistic point of view. For each endophenotype, we describe typical experimental procedures, reliability, heritability, and reported gene and neurobiological associations. We discuss recent findings regarding the genetic architecture of specific electrophysiological endophenotypes, as well as converging evidence from EEG studies implicating disrupted balance of glutamatergic signaling and GABA-ergic inhibition in the pathophysiology of schizophrenia. We conclude that refining the measurement of electrophysiological endophenotypes, expanding genetic association studies, and integrating datasets are important next steps for understanding the mechanisms that connect identified genetic risk loci for schizophrenia to the disease phenotype. PMID:26954597

  10. Working-memory endophenotype and dyslexia-associated genetic variant predict dyslexia phenotype.

    PubMed

    Männel, Claudia; Meyer, Lars; Wilcke, Arndt; Boltze, Johannes; Kirsten, Holger; Friederici, Angela D

    2015-10-01

    Developmental dyslexia, a severe impairment of literacy acquisition, is known to have a neurological basis and a strong genetic background. However, effects of individual genetic variations on dyslexia-associated deficits are only moderate and call for the assessment of the genotype's impact on mediating neuro-endophenotypes by the imaging genetics approach. Using voxel-based morphometry (VBM) in German participants with and without dyslexia, we investigated gray matter changes and their association with impaired phonological processing, such as reduced verbal working memory. These endophenotypical alterations were, together with dyslexia-associated genetic variations, examined on their suitability as potential predictors of dyslexia. We identified two gray matter clusters in the left posterior temporal cortex related to verbal working memory capacity. Regional cluster differences correlated with genetic risk variants in TNFRSF1B. High-genetic-risk participants exhibit a structural predominance of auditory-association areas relative to auditory-sensory areas, which may partly compensate for deficient early auditory-sensory processing stages of verbal working memory. The reverse regional predominance observed in low-genetic-risk participants may in turn reflect reliance on these early auditory-sensory processing stages. Logistic regression analysis further supported that regional gray matter differences and genetic risk interact in the prediction of individuals' diagnostic status: With increasing genetic risk, the working-memory related structural predominance of auditory-association areas relative to auditory-sensory areas classifies participants with dyslexia versus control participants. Focusing on phonological deficits in dyslexia, our findings suggest endophenotypical changes in the left posterior temporal cortex could comprise novel pathomechanisms for verbal working memory-related processes translating TNFRSF1B genotype into the dyslexia phenotype.

  11. 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

  12. Cognitive Endophenotypes of Dyslexia

    ERIC Educational Resources Information Center

    Moll, Kristina; Loff, Ariana; Snowling, Margaret J.

    2013-01-01

    The study investigated cognitive deficits associated with dyslexia and familial risk of dyslexia (endophenotypes) by comparing children from families with and without a history of dyslexia. Eighty-eight school-aged children were assessed on measures of phonology, language and rapid automatized naming. A series of regression analyses with family…

  13. Variants in the 1q21 risk region are associated with a visual endophenotype of autism and schizophrenia.

    PubMed

    Goodbourn, P T; Bosten, J M; Bargary, G; Hogg, R E; Lawrance-Owen, A J; Mollon, J D

    2014-02-01

    Deficits in sensitivity to visual stimuli of low spatial frequency and high temporal frequency (so-called frequency-doubled gratings) have been demonstrated both in schizophrenia and in autism spectrum disorder (ASD). Such basic perceptual functions are ideal candidates for molecular genetic study, because the underlying neural mechanisms are well characterized; but they have sometimes been overlooked in favor of cognitive and neurophysiological endophenotypes, for which neural substrates are often unknown. Here, we report a genome-wide association study of a basic visual endophenotype associated with psychological disorder. Sensitivity to frequency-doubled gratings was measured in 1060 healthy young adults, and analyzed for association with genotype using linear regression at 642 758 single nucleotide polymorphism (SNP) markers. A significant association (P = 7.9 × 10(-9) ) was found with the SNP marker rs1797052, situated in the 5'-untranslated region of PDZK1; each additional copy of the minor allele was associated with an increase in sensitivity equivalent to more than half a standard deviation. A permutation procedure, which accounts for multiple testing, showed that the association was significant at the α = 0.005 level. The region on chromosome 1q21.1 surrounding PDZK1 is an established susceptibility locus both for schizophrenia and for ASD, mirroring the common association of the visual endophenotype with the two disorders. PDZK1 interacts with N-methyl-d-aspartate receptors and neuroligins, which have been implicated in the etiologies of schizophrenia and ASD. These findings suggest that perceptual abnormalities observed in two different disorders may be linked by common genetic elements.

  14. Endophenotype Network Models: Common Core of Complex Diseases

    NASA Astrophysics Data System (ADS)

    Ghiassian, Susan Dina; Menche, Jörg; Chasman, Daniel I.; Giulianini, Franco; Wang, Ruisheng; Ricchiuto, Piero; Aikawa, Masanori; Iwata, Hiroshi; Müller, Christian; Zeller, Tania; Sharma, Amitabh; Wild, Philipp; Lackner, Karl; Singh, Sasha; Ridker, Paul M.; Blankenberg, Stefan; Barabási, Albert-László; Loscalzo, Joseph

    2016-06-01

    Historically, human diseases have been differentiated and categorized based on the organ system in which they primarily manifest. Recently, an alternative view is emerging that emphasizes that different diseases often have common underlying mechanisms and shared intermediate pathophenotypes, or endo(pheno)types. Within this framework, a specific disease’s expression is a consequence of the interplay between the relevant endophenotypes and their local, organ-based environment. Important examples of such endophenotypes are inflammation, fibrosis, and thrombosis and their essential roles in many developing diseases. In this study, we construct endophenotype network models and explore their relation to different diseases in general and to cardiovascular diseases in particular. We identify the local neighborhoods (module) within the interconnected map of molecular components, i.e., the subnetworks of the human interactome that represent the inflammasome, thrombosome, and fibrosome. We find that these neighborhoods are highly overlapping and significantly enriched with disease-associated genes. In particular they are also enriched with differentially expressed genes linked to cardiovascular disease (risk). Finally, using proteomic data, we explore how macrophage activation contributes to our understanding of inflammatory processes and responses. The results of our analysis show that inflammatory responses initiate from within the cross-talk of the three identified endophenotypic modules.

  15. Mouse behavioral endophenotypes for schizophrenia.

    PubMed

    Amann, Laura C; Gandal, Michael J; Halene, Tobias B; Ehrlichman, Richard S; White, Samantha L; McCarren, Hilary S; Siegel, Steven J

    2010-09-30

    An endophenotype is a heritable trait that is generally considered to be more highly, associated with a gene-based neurological deficit than a disease phenotype itself. Such, endophenotypic deficits may therefore be observed in the non-affected relatives of disease patients. Once endophenotypes have been established for a given illness, such as schizophrenia, mechanisms of, action may then be established and treatment options developed in order to target such measures. The, current paper describes and assesses the merits and limitations of utilizing behavioral and, electrophysiological endophenotypes of schizophrenia in mice. Such endophenotypic deficits include: decreased auditory event related potential (ERP) amplitude and gating (specifically, that of the P20, N40, P80 and P120); impaired mismatch negativity (MMN); changes in theta and gamma frequency, analyses; decreased pre-pulse inhibition (PPI); impaired working and episodic memories (for instance, novel object recognition [NOR], contextual and cued fear conditioning, latent inhibition, Morris and, radial arm maze identification and nose poke); sociability; and locomotor activity. A variety of, pharmacological treatments, including ketamine, MK-801 and phencyclidine (PCP) can be used to, induce some of the deficits described above, and numerous transgenic mouse strains have been, developed to address the mechanisms responsible for such endophenotypic differences. We also, address the viability and validity of using such measures regarding their potential clinical implications, and suggest several practices that could increase the translatability of preclinical data.

  16. [Endophenotypes: the molecular biology point of view].

    PubMed

    Belzeaux, R; Ibrahim, E C; Cermolacce, M; Fakra, E; Azorin, J M

    2012-12-01

    Endophenotypes are proposed for a better understanding of the molecular substrate underlying psychiatric disorders vulnerability. In this review, we discuss key points of the definition of endophenotypes from the molecular biology point of view. First, we examine the concept of heritability of endophenotype, which does not directly explain the molecular mechanisms responsible for the studied disorder Indeed, we discuss the necessity to better decipher the functional role of polymorphisms associated to endophenotypes, especially if those endophenotypes would be assigned a clinical and biological value. The complexity of endophenotypes definition and use in psychiatric research is also illustrated by the complexity of the human genome organization and gene networks as well as by the gene x environment interactions and also the possible existence of phenocopies.

  17. Discovering endophenotypes for major depression.

    PubMed

    Hasler, Gregor; Drevets, Wayne C; Manji, Husseini K; Charney, Dennis S

    2004-10-01

    The limited success of genetic studies of major depression has raised questions concerning the definition of genetically relevant phenotypes. This paper presents strategies to improve the phenotypic definition of major depression by proposing endophenotypes at two levels: First, dissecting the depressive phenotype into key components results in narrow definitions of putative psychopathological endophenotypes: mood bias toward negative emotions, impaired reward function, impaired learning and memory, neurovegetative signs, impaired diurnal variation, impaired executive cognitive function, psychomotor change, and increased stress sensitivity. A review of the recent literature on neurobiological and genetic findings associated with these components is given. Second, the most consistent heritable biological markers of major depression are proposed as biological endophenotypes for genetic studies: REM sleep abnormalities, functional and structural brain abnormalities, dysfunctions in serotonergic, catecholaminergic, hypothalamic-pituitary-adrenocortical axis, and CRH systems, and intracellular signal transduction endophenotypes. The associations among the psychopathological and biological endophenotypes are discussed with respect to specificity, temporal stability, heritability, familiality, and clinical and biological plausibility. Finally, the case is made for the development of a new classification system in order to reduce the heterogeneity of depression representing a major impediment to elucidating the genetic and neurobiological basis of this common, severe, and often life-threatening illness.

  18. Endophenotypes for Alcohol Use Disorder: An Update on the Field

    PubMed Central

    Salvatore, Jessica E.; Gottesman, Irving I.; Dick, Danielle M.

    2015-01-01

    The endophenotype concept was first proposed as a strategy to use (purportedly) genetically simpler phenotypes in gene identification studies for psychiatric disorders, and is distinct from the closely related concept of intermediate phenotypes. In the area of alcohol use disorder (AUD) research, two candidate endophenotypes have produced replicable genetic associations: level of response to alcohol and neurophysiology markers (e.g., event-related oscillations and event-related potentials). Additional candidate endophenotypes from the cognitive, sensory, and neuroimaging literatures show promise, although more evidence is needed to fully evaluate their potential utility. Translational approaches to AUD endophenotypes have helped characterize the underlying neurobiology and genetics of AUD endophenotypes and identified relevant pharmacological interventions. Future research that capitalizes on the polygenic nature of endophenotypes and emphasizes endophenotypes that may change across development will enhance the usefulness of this concept to understand the genetically-influenced pathways toward AUD. PMID:26236574

  19. Differences in planning performance, a neurocognitive endophenotype, are associated with a functional variant in PER3 gene.

    PubMed

    González-Giraldo, Yeimy; González-Reyes, Rodrigo E; Mueller, Shane T; Piper, Brian J; Adan, Ana; Forero, Diego A

    2015-06-01

    Performance alterations in executive function have been studied as potential endophenotypes for several neuropsychiatric diseases. Planning is an important component of executive function and has been shown to be affected in diseases such as attention deficit hyperactivity disorder, schizophrenia, obsessive-compulsive disorder and Parkinson's disease. Several genes related to dopaminergic systems, such as COMT, have been explored as candidates for influencing planning performance. The circadian clock gene PERIOD3 (PER3) has been shown to be associated with several complex behaviors in humans and could be involved in different signaling mechanisms. In this study, we evaluated the possible association between a functional polymorphism in the PER3 gene (PER3-VNTR, rs57875989) and performance in a commonly used test of planning (Tower of London, TOL) in 229 healthy subjects from Bogotá, Colombia. PER3-VNTR genotyping was carried out with conventional PCR and all participants completed the TOL test using the computerized Psychology Experiment Building Language (PEBL) battery. A linear regression model was used for the analysis of association with the SNPStats program. We found that 4/4 genotype carriers showed a better performance and made fewer moves, in comparison to 4/5 and 5/5 genotype carriers (p = 0.003). These results appear to be independent from effects of this polymorphism on self-reported average hours of sleep during work days in our sample. This is the first evidence of an association between PER3-VNTR and planning performance in a sample of healthy subjects and our results are consistent from previous findings for alterations in other cognitive domains. Future studies examining additional genes could lead to the identification of novel molecular underpinnings of planning in healthy subjects and in patients with neuropsychiatric disorders.

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

    PubMed Central

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

    2016-01-01

    Background: 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. Methods: 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: 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

  1. Endophenotypes and serotonergic polymorphisms associated with treatment response in obsessive-compulsive disorder

    PubMed Central

    Corregiari, Fábio M; Bernik, Márcio; Cordeiro, Quirino; Vallada, Homero

    2012-01-01

    OBJECTIVES: Approximately 40-60% of obsessive-compulsive disorder patients are nonresponsive to serotonin reuptake inhibitors. Genetic markers associated with treatment response remain largely unknown. We aimed (1) to investigate a possible association of serotonergic polymorphisms in obsessive-compulsive disorder patients and therapeutic response to selective serotonin reuptake inhibitors and (2) to examine the relationship between these polymorphisms and endocrine response to intravenous citalopram challenge in responders and non-responders to serotonin reuptake inhibitors and in healthy volunteers. METHODS: Patients with obsessive-compulsive disorder were classified as either responders or non-responders after long-term treatment with serotonin reuptake inhibitors, and both groups were compared with a control group of healthy volunteers. The investigated genetic markers were the G861C polymorphism of the serotonin receptor 1Dβ gene and the T102C and C516T polymorphisms of the serotonin receptor subtype 2A gene. RESULTS: The T allele of the serotonin receptor subtype 2A T102C polymorphism was more frequent among obsessive-compulsive disorder patients (responders and non-responders) than in the controls (p<0.01). The CC genotype of the serotonin receptor subtype 2A C516T polymorphism was more frequent among the non-responders than in the responders (p<0.01). The CC genotype of the serotonin receptor subtype 1Dβ G681C polymorphism was associated with higher cortisol and prolactin responses to citalopram (p<0.01 and p<0.001, respectively) and with a higher platelet-rich plasma serotonin concentration among the controls (p<0.05). However, this pattern was not observed in the non-responders with the same CC genotype after chronic treatment with serotonin reuptake inhibitors. This CC homozygosity was not observed in the responders. PMID:22522758

  2. Electrophysiological endophenotypes in rodent models of schizophrenia and psychosis

    PubMed Central

    Rosen, Andrew M.; Spellman, Timothy; Gordon, Joshua A.

    2015-01-01

    Schizophrenia is caused by a diverse array of risk factors, and results in a similarly diverse set of symptoms. Electrophysiological endophenotypes lie between risks and symptoms, and have the potential to link the two. Electrophysiological studies in rodent models, described here, demonstrate that widely differing risk factors result in a similar set of core electrophysiological endophenotypes, suggesting the possibility of a shared neurobiological substrate. PMID:25910423

  3. Neurophysiological Endophenotypes of Schizophrenia: The Viability of Selected Candidate Measures

    PubMed Central

    Turetsky, Bruce I.; Calkins, Monica E.; Light, Gregory A.; Olincy, Ann; Radant, Allen D.; Swerdlow, Neal R.

    2007-01-01

    In an effort to reveal susceptibility genes, schizophrenia research has turned to the endophenotype strategy. Endophenotypes are characteristics that reflect the actions of genes predisposing an individual to a disorder, even in the absence of diagnosable pathology. Individual endophenotypes are presumably determined by fewer genes than the more complex phenotype of schizophrenia and would, therefore, reduce the complexity of genetic analyses. Unfortunately, despite there being rational criteria to define a viable endophenotype, the term is sometimes applied indiscriminately to characteristics that are deviant in affected individuals. Schizophrenia patients exhibit deficits in several neurophysiological measures of information processing that have been proposed as candidate endophenotypes. Successful processing of sensory inputs requires the ability to inhibit intrinsic responses to redundant stimuli and, reciprocally, to facilitate responses to less frequent salient stimuli. There is evidence to suggest that both these processes are “impaired” in schizophrenia. Measures of inhibitory failure include prepulse inhibition of the startle reflex, P50 auditory evoked potential suppression, and antisaccade eye movements. Measures of impaired deviance detection include mismatch negativity and the P300 event-related potential. The purpose of this review is to systematically evaluate the endophenotype candidacy of these key neurophysiological abilities. For each candidate, we describe typical experimental procedures, the current understanding of the underlying neurobiology, the nature of the abnormality in schizophrenia, the reliability, stability and heritability of the measure, and any reported gene associations. We conclude with a discussion of the few studies thus far that have employed a multivariate approach with these candidates. PMID:17135482

  4. Factors Associated With Infant Bed-Sharing

    PubMed Central

    Heere, Megan; Moughan, Beth; Alfonsi, Joseph; Rodriguez, Jennifer; Aronoff, Stephen

    2017-01-01

    Objective: Bed-sharing is associated with sudden infant death syndrome and accidental suffocation and strangulation in bed. The purpose of this study was to identify risk factors for newborn bed-sharing. Methods: Postpartum mothers from a university maternity service were contacted by phone to complete a survey. Demographic and environmental data were collected; newborn bed-sharing and sleep environment were self-reported. Results: A total of 1261 mothers completed surveys; bed-sharing was reported by 79 mothers (6.3%). Multivariate logistic regression identified referral to a nurse (odds ratio [OR] = 10; 95% confidence interval [CI] = 4.5-30) and sleep location “other” than a crib, bassinet, or Pack and Play (OR = 7.1; 95% CI = 1.9-25.9) as factors associated with an increased risk of bed-sharing; formula feeding (OR = 0.4; 95% CI = 0.20-0.77) and crib sleeping (OR = 0.49; 95% CI = 0.26-0.86) reduced this risk. Conclusion: Infants with no identifiable places to sleep, significant health issues, and who are breastfed are more likely to bed-share. Interventional studies should be directed at these factors. PMID:28229101

  5. 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.

  6. 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

  7. 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…

  8. 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

  9. Genetic Assessment of Additional Endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study

    PubMed Central

    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.

    2015-01-01

    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. PMID:26597662

  10. 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).…

  11. Sharing Assessment Data: An Example from a National Professional Association.

    ERIC Educational Resources Information Center

    Bradley, Jama L.; And Others

    Alexander Astin, a pioneer in assessment research, has argued persuasively for building national databases that would permit programs and institutions to share common data and thus compare themselves with peers (1987, 1991). Others have suggested that certain process and outcome data should be collected and shared by disciplinary associations and…

  12. Detecting local haplotype sharing and haplotype association

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel haplotype association method is presented, and its power is demonstrated. Relying on a statistical model for linkage disequilibrium (LD), the method first infers ancestral haplotypes and their loadings at each marker for each individual. The loadings are then used to quantify local haplotype...

  13. Genetic correlates of behavioral endophenotypes in Alzheimer disease: role of COMT, 5-HTTLPR and APOE polymorphisms.

    PubMed

    Borroni, B; Grassi, M; Agosti, C; Costanzi, C; Archetti, S; Franzoni, S; Caltagirone, C; Di Luca, M; Caimi, L; Padovani, A

    2006-11-01

    Several studies have been conducted to understand the genetic correlates of Alzheimer disease (AD)-related behavioral and psychological symptoms in dementia (BPSD). However, given that BPSD rarely occur in isolation, it has been suggested that targeting BPSD individually is too narrow of an approach if one wants to accurately define all the associated risk factors. To date, we know of no work on genetic polymorphisms related to behavioral endophenotypes in AD. The present study sought to evaluate the relationship between such behavioral endophenotypes in AD and genetic variations in dopamine- or serotonin-related genes, such as catechol-O-methyltransferase (COMT) or 5-HTT gene-linked promoter region (5-HTTLPR), and apolipoprotein E (APOE). Among 232 AD patients who underwent clinical and neuropsychological examination, a behavioral and psychiatric evaluation, and genotyping at COMT, 5-HTTPLR, and APOE; 66.4% showed more than one behavioral symptom. By Principal Component Analysis of Neuropsychiatric Inventory (NPI) symptoms four endophenotypes were identified, these were termed "psychosis", "moods", "apathy", and "frontal". Modeling NPI symptom-endophenotype-genotype relationships, and taking into account possible confounds (i.e. demographic characteristics, comorbidities, concomitant pharmacological treatments, and disease severity) by latent variable models, COMT and 5-HTTLPR genetic variations correlated with "frontal" and "psychosis" endophenotypes. APOE genotype did not correlate with any endophenotype. These findings suggest that the possibility of identifying distinct phenotypes on a genetic basis among AD patients exists, and suggest that clustering of BPSD into endophenotypes might provide a new strategy for guiding future research on this issue.

  14. Disruptions in the left frontoparietal network underlie resting state endophenotypic markers in schizophrenia.

    PubMed

    Chahine, George; Richter, Anja; Wolter, Sarah; Goya-Maldonado, Roberto; Gruber, Oliver

    2017-04-01

    Advances in functional brain imaging have improved the search for potential endophenotypic markers in schizophrenia. Here, we employed independent component analysis (ICA) and dynamic causal modeling (DCM) in resting state fMRI on a sample of 35 schizophrenia patients, 20 first-degree relatives and 35 control subjects. Analysis on ICA-derived networks revealed increased functional connectivity between the left frontoparietal network (FPN) and left temporal and parietal regions in schizophrenia patients (P < 0.001). First-degree relatives shared this hyperconnectivity, in particular in the supramarginal gyrus (SMG; P = 0.008). DCM analysis was employed to further explore underlying effective connectivity. Results showed increased inhibitory connections to the left angular gyrus (AG) in schizophrenia patients from all other nodes of the left FPN (P < 0.001), and in particular from the left SMG (P = 0.001). Relatives also showed a pattern of increased inhibitory connections to the left AG (P = 0.008). Furthermore, the patient group showed increased excitatory connectivity between the left fusiform gyrus and the left SMG (P = 0.002). This connection was negatively correlated to inhibitory afferents to the left AG (P = 0.005) and to the negative symptom score on the PANSS scale (P = 0.001, r = -0.51). Left frontoparietotemporal dysfunction in schizophrenia has been previously associated with a range of abnormalities, including formal thought disorder, working memory dysfunction and sensory hallucinations. Our analysis uncovered new potential endophenotypic markers of schizophrenia and shed light on the organization of the left FPN in patients and their first-degree relatives. Hum Brain Mapp 38:1741-1750, 2017. © 2017 Wiley Periodicals, Inc.

  15. 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

  16. [Psychotherapeutic and psychosocial interventions and endophenotypes in bipolar disorders].

    PubMed

    Correard, N; Elissalde, S N; Azorin, J-M; Fakra, E; Belzeaux, R

    2012-12-01

    Diseases with complex determinism, bipolar disorders, involve at the same time environmental and genetic factors of vulnerability. The characterization of these vulnerabilities would allow a better knowledge of their etiology and envisage the development of therapeutics, more specialized, even preventive. The research in genetic psychiatry allowed to highlight endophenotype candidates associated to bipolar disorders. They are endogenous clinical or biological features, biologically more elementary than phenotypes and more directly bound to the physiological consequences of genes and their polymorphisms. Targeting some of them with specific psychotherapy and psychosocial interventions could reduce the consequences of their expression and so have an action on the course of the disease and also preventive.

  17. Evaluation of behavioral impulsivity and aggression tasks as endophenotypes for borderline personality disorder

    PubMed Central

    McCloskey, Michael S.; New, Antonia S.; Siever, Larry J.; Goodman, Marianne; Koenigsberg, Harold W.; Flory, Janine D.; Coccaro, Emil F.

    2010-01-01

    Borderline personality disorder (BPD) is marked by aggression and impulsive, often self-destructive behavior. Despite the severe risks associated with BPD, relatively little is known about the disorder’s etiology. Identification of genetic correlates (endophenotypes) of BPD would improve the prospects of targeted interventions for more homogeneous subsets of borderline patients characterized by specific genetic vulnerabilities. The current study evaluated behavioral measures of aggression and impulsivity as potential endophenotypes for BPD. Subjects with BPD (N = 127), a non cluster B personality disorder (OPD N = 122), or healthy volunteers (HV N = 112) completed self report and behavioral measures of aggression, motor impulsivity and cognitive impulsivity. Results showed that BPD subjects demonstrated more aggression and motor impulsivity than HV (but not OPD) subjects on behavioral tasks. In contrast, BPD subjects self-reported more impulsivity and aggression than either comparison group. Subsequent analyses showed that among BPD subjects behavioral aggression was associated with self-reported aggression, while behavioral and self-report impulsivity measures were more modestly associated. Overall, the results provide partial support for the use of behavioral measures of aggression and motor impulsivity as endophenotypes for BPD, with stronger support for behavioral aggression measures as an endophenotype for aggression within BPD samples. PMID:19232640

  18. 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

  19. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

    PubMed Central

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N.; Nyholt, Dale R.; Morris, Andrew P.; Fasching, Peter A.; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W.; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Wicklund, Kristine G.; Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T.; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B.; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.; Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Cannioto, Rikki; Høgdall, Estrid; Jensen, Allan; Giles, Graham G.; Bruinsma, Fiona; Kjaer, Susanne K.; Hildebrandt, Michelle A.T.; Liang, Dong; Lu, Karen H.; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A.; Cramer, Daniel W.; Terry, Kathryn L.; Tworoger, Shelley S.; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B.; Kopperud, Reidun K.; Bischof, Katharina; Aben, Katja K.H.; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Brooks-Wilson, Angela; Olson, Sara H.; McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.; Cook, Linda S.; Le, Nhu D.; Gilks, C. Blake; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Gawełko, Jan; Song, Honglin; Tyrer, Jonathan P.; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; Mclaughlin, John R.; Narod, Steven A.; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J.; Wu, Anna H.; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M.; Fridley, Brooke L.; Winham, Stacey J.; Bandera, Elisa V.; Poole, Elizabeth M.; Morgan, Terry K.; Risch, Harvey A.; Goode, Ellen L.; Schildkraut, Joellen M.; Webb, Penelope M.; Pearce, Celeste L.; Berchuck, Andrew; Pharoah, Paul D.P.; Montgomery, Grant W.; Zondervan, Krina T.; Chenevix-Trench, Georgia; MacGregor, Stuart

    2015-01-01

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18–0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07–0.89 and 0.40, 95% CI = 0.05–0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11–0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci. PMID:26231222

  20. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer.

    PubMed

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N; Nyholt, Dale R; Morris, Andrew P; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Wicklund, Kristine G; Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle A T; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Gilks, C Blake; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Gawełko, Jan; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; Mclaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Risch, Harvey A; Goode, Ellen L; Schildkraut, Joellen M; Webb, Penelope M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul D P; Montgomery, Grant W; Zondervan, Krina T; Chenevix-Trench, Georgia; MacGregor, Stuart

    2015-10-15

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.

  1. 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.

  2. 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

  3. Estimating genetic effect sizes under joint disease-endophenotype models in presence of gene-environment interactions

    PubMed Central

    Bureau, Alexandre; Croteau, Jordie; Couture, Christian; Vohl, Marie-Claude; Bouchard, Claude; Pérusse, Louis

    2015-01-01

    Effects of genetic variants on the risk of complex diseases estimated from association studies are typically small. Nonetheless, variants may have important effects in presence of specific levels of environmental exposures, and when a trait related to the disease (endophenotype) is either normal or impaired. We propose polytomous and transition models to represent the relationship between disease, endophenotype, genotype and environmental exposure in family studies. Model coefficients were estimated using generalized estimating equations and were used to derive gene-environment interaction effects and genotype effects at specific levels of exposure. In a simulation study, estimates of the effect of a genetic variant were substantially higher when both an endophenotype and an environmental exposure modifying the variant effect were taken into account, particularly under transition models, compared to the alternative of ignoring the endophenotype. Illustration of the proposed modeling with the metabolic syndrome, abdominal obesity, physical activity and polymorphisms in the NOX3 gene in the Quebec Family Study revealed that the positive association of the A allele of rs1375713 with the metabolic syndrome at high levels of physical activity was only detectable in subjects without abdominal obesity, illustrating the importance of taking into account the abdominal obesity endophenotype in this analysis. PMID:26284107

  4. A Brain-Based Endophenotype for Major Depressive Disorder

    PubMed Central

    Peterson, Bradley S.; Weissman, Myrna M.

    2012-01-01

    We have identified a brain-based endophenotype for major depressive disorder (MDD) that includes thinning of the cortex of the lateral aspect of the right hemisphere and the medial aspect of the left, as well as bilateral hypoplasia of frontal and parietal white matter. The endophenotype status of these abnormalities is supported by their presence in a multi-generational cohort of persons who themselves do not have MDD but who are at increased familial risk for developing the illness. Those who have the endophenotype but who are not ill nevertheless still suffer from inattention and poor visual memory for social stimuli in direct proportion to the magnitude of cortical thinning and white matter hypoplasia within the endophenotype. Identification of this endophenotype and its cognitive correlates provides targets for devising new preventive and therapeutic interventions for MDD. PMID:21226617

  5. Immature Dentate Gyrus: An Endophenotype of Neuropsychiatric Disorders

    PubMed Central

    Walton, Noah M.; Matsumoto, Mitsuyuki; Miyakawa, Tsuyoshi

    2013-01-01

    Adequate maturation of neurons and their integration into the hippocampal circuit is crucial for normal cognitive function and emotional behavior, and disruption of this process could cause disturbances in mental health. Previous reports have shown that mice heterozygous for a null mutation in α-CaMKII, which encodes a key synaptic plasticity molecule, display abnormal behaviors related to schizophrenia and other psychiatric disorders. In these mutants, almost all neurons in the dentate gyrus are arrested at a pseudoimmature state at the molecular and electrophysiological levels, a phenomenon defined as “immature dentate gyrus (iDG).” To date, the iDG phenotype and shared behavioral abnormalities (including working memory deficit and hyperlocomotor activity) have been discovered in Schnurri-2 knockout, mutant SNAP-25 knock-in, and forebrain-specific calcineurin knockout mice. In addition, both chronic fluoxetine treatment and pilocarpine-induced seizures reverse the neuronal maturation, resulting in the iDG phenotype in wild-type mice. Importantly, an iDG-like phenomenon was observed in post-mortem analysis of brains from patients with schizophrenia/bipolar disorder. Based on these observations, we proposed that the iDG is a potential endophenotype shared by certain types of neuropsychiatric disorders. This review summarizes recent data describing this phenotype and discusses the data's potential implication in elucidating the pathophysiology of neuropsychiatric disorders. PMID:23840971

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

    PubMed

    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

    2015-03-31

    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.

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

    PubMed Central

    IACONO, WILLIAM. G.; MALONE, STEPHEN. M.; VAIDYANATHAN, UMA; VRIEZE, SCOTT I.

    2014-01-01

    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. PMID:25387703

  8. 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.

  9. The 5-HTTLPR polymorphism, early and recent life stress, and cognitive endophenotypes of depression.

    PubMed

    Kruijt, Anne-Wil; Putman, Peter; Van der Does, Willem

    2014-01-01

    Studies associating interactions of 5-HTTLPR and life adversities with depression have yielded equivocal results. Studying endophenotypes may constitute a more powerful approach. In the current study, it was assessed whether interactions of 5-HTTLPR with childhood emotional abuse (CEA) and recent negative life events (RNLE) affect possible cognitive endophenotypes of depression, namely, attention-allocation bias and the ability to recognise others' mind states in 215 young adults of North-West European descent. The ability to classify others' negative mind states was found to be increased with increasing RNLE in carriers of low-expressing Serotonin Transporter Linked Polymorphic Region (5-HTTLPR) alleles. Carriers of two low-expressing alleles also preferentially oriented attention towards negative information. Gene-environment interactions were not observed for attention allocation bias. No effects involving CEA were observed. These results suggest that low-expressing 5-HTTLPR alleles may confer increased risk for depression through enhanced recognition of negative facial expressions following RNLE.

  10. Integrating behavioral economics and behavioral genetics: delayed reward discounting as an endophenotype for addictive disorders.

    PubMed

    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.

  11. Satellite RNA associated with bamboo mosaic potexvirus shares similarity with satellites associated with sobemoviruses.

    PubMed

    Liu, J S; Lin, N S

    1995-01-01

    A putative nonstructural protein encoded by a satellite RNA associated with bamboo mosaic potexvirus shares 46% identity with the capsid protein of satellite virus of panicum mosaic sobemovirus. The sequence similarity among satellite plant viruses which have no apparent relationship implies a common origin.

  12. Genetic covariance between psychopathic traits and anticipatory skin conductance responses to threat: Evidence for a potential endophenotype

    PubMed Central

    WANG, PAN; GAO, YU; ISEN, JOSHUA; TUVBLAD, CATHERINE; RAINE, ADRIAN; BAKER, LAURA A.

    2015-01-01

    The genetic architecture of the association between psychopathic traits and reduced skin conductance responses (SCRs) is poorly understood. By using 752 twins aged 9–10 years, this study investigated the heritability of two SCR measures (anticipatory SCRs to impending aversive stimuli and unconditioned SCRs to the aversive stimuli themselves) in a countdown task. The study also investigated the genetic and environmental sources of the covariance between these SCR measures and two psychopathic personality traits: impulsive/disinhibited (reflecting impulsive–antisocial tendencies) and manipulative/deceitful (reflecting the affective–interpersonal features). For anticipatory SCRs, 27%, 14%, and 59% of the variation was due to genetic, shared environmental, and nonshared environmental effects, respectively, while the percentages for unconditioned SCRs were 44%, 2%, and 54%. The manipulative/deceitful (not impulsive/disinhibited) traits were negatively associated with both anticipatory SCRs (r = −.14, p < .05) and unconditioned SCRs (r = −.17, p < .05) in males only, with the former association significantly accounted for by genetic influences (rg = −.72). Reduced anticipatory SCRs represent a candidate endophenotype for the affective–interpersonal facets of psychopathic traits in males. PMID:26439076

  13. Behavioral endophenotypes of drug addiction: Etiological insights from neuroimaging studies.

    PubMed

    Jupp, Bianca; Dalley, Jeffrey W

    2014-01-01

    This article reviews recent advances in the elucidation of neurobehavioral endophenotypes associated with drug addiction made possible by the translational neuroimaging techniques magnetic resonance imaging (MRI) and positron emission tomography (PET). Increasingly, these non-invasive imaging approaches have been the catalyst for advancing our understanding of the etiology of drug addiction as a brain disorder involving complex interactions between pre-disposing behavioral traits, environmental influences and neural perturbations arising from the chronic abuse of licit and illicit drugs. In this article we discuss the causal role of trait markers associated with impulsivity and novelty-/sensation-seeking in speeding the development of compulsive drug administration and in facilitating relapse. We also discuss the striking convergence of imaging findings from these behavioural traits and addiction in rats, monkeys and humans with a focus on biomarkers of dopamine neurotransmission, and highlight areas where further research is needed to disambiguate underlying causal mechanisms. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

  14. [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

  15. Analysis of 94 Candidate Genes and Twelve Endophenotypes for Schizophrenia from the Consortium on the Genetics of Schizophrenia

    PubMed Central

    Greenwood, Tiffany A.; Lazzeroni, Laura C.; Murray, Sarah S.; Cadenhead, Kristin S.; Calkins, Monica E.; Dobie, Dorcas J.; Green, Michael F.; Gur, Raquel E.; Gur, Reuben C.; Hardiman, Gary; Kelsoe, John R.; Leonard, Sherry; Light, Gregory A.; Nuechterlein, Keith H.; Olincy, Ann; 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.; Freedman, Robert; Braff, David L.

    2013-01-01

    Objective We have used a custom 1,536-SNP array to interrogate 94 functionally relevant candidate genes for schizophrenia and identify associations with 12 heritable neurophysiological and neurocognitive endophenotypes collected as part of the Consortium on the Genetics of Schizophrenia (COGS). Method Variance-component association analyses of 534 genotyped subjects from 130 families were conducted using Merlin. A novel bootstrap Total Significance Test was also developed to overcome the limitations of existing genomic multiple testing methods and robustly demonstrate the presence of significant associations in the context of complex family data and possible population stratification effects. Results Associations were observed for 46 genes of potential functional significance with 3 SNPs at p<10−4, 27 SNPs at p<10−3, and 147 SNPs at p<0.01. The bootstrap analyses confirmed that the 47 SNP-endophenotype combinations with the strongest evidence of association significantly exceeded (p=0.001) that expected by chance alone with 93% of these findings expected to be true. Many of the genes interact on a molecular level, and eight genes displayed evidence for pleiotropy (e.g., NRG1 and ERBB4), revealing associations with four or more endophenotypes. Our results collectively support a strong role for genes related to glutamate signaling in mediating schizophrenia susceptibility. Conclusions This study supports the use of relevant endophenotypes and the bootstrap Total Significance Test for the identification of genetic variation underlying the etiology of schizophrenia. In addition, the observation of extensive pleiotropy for some genes and singular associations for others in our data suggests alternative, independent pathways mediating pathogenesis in the “group of schizophrenias”. PMID:21498463

  16. Affective value and associative processing share a cortical substrate.

    PubMed

    Shenhav, Amitai; Barrett, Lisa Feldman; Bar, Moshe

    2013-03-01

    The brain stores information in an associative manner so that contextually related entities are connected in memory. Such associative representations mediate the brain's ability to generate predictions about which other objects and events to expect in a given context. Likewise, the brain encodes and is able to rapidly retrieve the affective value of stimuli in our environment. That both contextual associations and affect serve as building blocks of numerous mental functions often makes interpretation of brain activation ambiguous. A critical brain region where such activation has often resulted in equivocal interpretation is the medial orbitofrontal cortex (mOFC), which has been implicated separately in both affective and associative processing. To characterize its role more unequivocally, we tested whether activity in the mOFC was most directly attributable to affective processing, associative processing, or a combination of both. Subjects performed an object recognition task while undergoing fMRI scans. Objects varied independently in their affective valence and in their degree of association with other objects (associativity). Analyses revealed an overlapping sensitivity whereby the left mOFC responded both to increasingly positive affective value and to stronger associativity. These two properties individually accounted for mOFC response, even after controlling for their interrelationship. The role of the mOFC is either general enough to encompass associations that link stimuli both with reinforcing outcomes and with other stimuli or abstract enough to use both valence and associativity in conjunction to inform downstream processes related to perception and action. These results may further point to a fundamental relationship between associativity and positive affect.

  17. 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…

  18. Abnormal Vestibulo-Ocular Reflexes in Autism: A Potential Endophenotype

    DTIC Science & Technology

    2013-06-01

    assistants trained in administration of Autism Diagnostic Observation Schedule (ADOS), certification required, and other testing administration...and UF Center for Autism and Related Disorders (CARD). Administration of the following questionnaires to each set of parent (s)/guardian(s...0382 TITLE: Abnormal Vestibulo-Ocular Reflexes in Autism : A Potential Endophenotype PRINCIPAL INVESTIGATOR: Keith D. White, Ph.D

  19. 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

  20. 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

  1. HIV and HCV discordant injecting partners and their association to drug equipment sharing.

    PubMed

    De, Prithwish; Cox, Joseph; Boivin, Jean-Francois; Platt, Robert W; Jolly, Ann M; Alexander, Paul E

    2009-01-01

    Our objective was to examine the association between HIV and HCV discordant infection status and the sharing of drug equipment by injection drug users (IDUs). IDUs were recruited from syringe exchange and methadone treatment programmes in Montreal, Canada. Characteristics of participants and their injecting partners were elicited using a structured questionnaire. Among 159 participants and 245 injecting partners, sharing of syringes and drug preparation equipment did not differ between concordant or discordant partners, although HIV-positive subjects did not share with HIV-negative injectors. Sharing of syringes was positively associated with discordant HIV status (OR=1.85) and negatively with discordant HCV status (OR=0.65), but both results were not statistically significant. Sharing of drug preparation equipment was positively associated with both discordant HIV (OR=1.61) and HCV (OR=1.18) status, but both results were non-significant. Factors such as large injecting networks, frequent mutual injections, younger age, and male gender were stronger predictors of equipment sharing. In conclusion, IDUs do not appear to discriminate drug equipment sharing partners based at least on their HCV infection status. The results warrant greater screening to raise awareness of infection status, post-test counselling to promote status disclosure among partners, and skill-building to avoid equipment sharing between discordant partners.

  2. 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

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

    PubMed

    Arenas, M Carmen; 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.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Deconstructing Schizophrenia: An Overview of the Use of Endophenotypes in Order to Understand a Complex Disorder

    PubMed Central

    Braff, David L.; Freedman, Robert; Schork, Nicholas J.; Gottesman, Irving I.

    2007-01-01

    The genetics of schizophrenia has been approached utilizing a variety of methods. One emerging strategy is the use of endophenotypes in order to understand and identify the functional importance of genetically transmitted, brain-based deficits across schizophrenia kindreds. The endophenotype strategy is a topic of this issue of Schizophrenia Bulletin. Endophenotypes are quantitative, heritable, trait-related deficits typically assessed by laboratory-based methods rather than clinical observation. Endophenotypes are seen as closer to genetic variation than are clinical symptoms of schizophrenia, and are therefore closely linked to heritable risk factors. There has been a broad expansion of opportunities available to psychiatric neuroscientists who use the endophenotype strategy to understand the genetic basis of schizophrenia. In this context, genetic variation such as single nucleotide polymorphisms (SNPs) induces abnormalities in endophenotypic domains such as neurocognition, neurodevelopment, metabolism, and neurophysiology. This article discusses the challenges that abound in genetic research of schizophrenia, including issues in ascertainment, epistasis, ethnic diversity, and the potentially normalizing effects of second-generation antipsychotic medications on neurocognitive and neurophysiological measures. Robust strategies for meeting these challenges are discussed in this review and the subsequent articles in this issue. This article summarizes conceptual advances and progress in the measurement and use of endophenotypes in schizophrenia that form the basis of the multisite National Institute of Mental Health Consortium on the Genetics of Schizophrenia. The endophenotype strategy offers powerful and exciting opportunities to understand the genetically conferred neurobiological vulnerabilities and possible new strong inference and molecularly based treatments for schizophrenia. PMID:17088422

  11. 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…

  12. 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.

  13. The error-related negativity (ERN) and psychopathology: Toward an Endophenotype

    PubMed Central

    Olvet, Doreen M.; Hajcak, Greg

    2008-01-01

    The ERN is a negative deflection in the event-related potential that peaks approximately 50 ms after the commission of an error. The ERN is thought to reflect early error-processing activity of the anterior cingulate cortex (ACC). First, we review current functional, neurobiological, and developmental data on the ERN. Next, the ERN is discussed in terms of three psychiatric disorders characterized by abnormal response monitoring: anxiety disorders, depression, and substance abuse. These data indicate that increased and decreased error-related brain activity is associated with the internalizing and externalizing dimensions of psychopathology, respectively. Recent data further suggest that abnormal error-processing indexed by the ERN indexes trait- but not state-related symptoms, especially related to anxiety. Overall, these data point to utility of ERN in studying risk for psychiatric disorders, and are discussed in terms of the endophenotype construct. PMID:18694617

  14. 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

  15. 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

  16. 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

  17. 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.

  18. Monozygotic twin differences in non-shared environmental factors associated with chronotype.

    PubMed

    Barclay, Nicola L; Eley, Thalia C; Parsons, Michael J; Willis, Thomas A; Gregory, Alice M

    2013-02-01

    Twin studies have highlighted that a large proportion of variability in chronotype is accounted for by individual-specific environmental factors (non-shared environmental influences). However, little research has aimed to identify specific non-shared environmental influences on chronotype. Although epidemiological studies have shed light on possible environmental influences on chronotype, a substantial amount of research has highlighted the importance of genetic influences on exposure toward specific environments, a process termed gene-environment correlation. It is possible that associations between the environment and chronotype are in part determined by genetics, rather than being purely environmental in origin. One way of exploring the contribution of purely non-shared environmental components on associations between chronotype and the environment is to use the monozygotic twin differences design. This design allows us to tease apart the influences of genetics and the environment to identify purely environmental components. One hundred eighty-nine monozygotic twin pairs (mean age 19.81 years, SD = 1.26, range = 18-22 years, 66.1% female) completed the Horne and Östberg Morningness-Eveningness Questionnaire as a measure of chronotype and questionnaires assessing the following candidate non-shared environmental influences: dependent and independent negative life events, educational attainment, employment status, relationship status, deviant peers, affiliation with deviant peers, general health, smoking, drug use, and alcohol use. Linear regression analyses indicated the presence of gene-environment correlation for the majority of associations between chronotype and candidate environmental influences. When controlling for genetic and shared environmental effects, within monozygotic twin-pair differences in chronotype were associated with within monozygotic twin-pair differences in dependent negative life events (β = -0.27, p < 0.001), educational attainment (

  19. A Study of Faculty, Administrative, and Staff Perceptions of the Climate for Shared Governance at Appalachian College Association Member Institutions

    ERIC Educational Resources Information Center

    Easton, Tanya L.

    2014-01-01

    The purpose of this study was to investigate how faculty, administrators, and staff perceived the climate for shared governance at 36 member institutions of the Appalachian College Association (ACA), based on standards for sound shared governance in higher education as outlined by the American Association of University Professors (AAUP). Numerous…

  20. 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

  1. 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.

  2. Motor abnormalities as a putative endophenotype for Autism Spectrum Disorders

    PubMed Central

    Esposito, Gianluca; Paşca, Sergiu P.

    2013-01-01

    Autism Spectrum Disorders (ASDs) represent a complex group of behaviorally defined conditions with core deficits in social communication and the presence of repetitive and restrictive behaviors. To date, neuropathological studies have failed to identify pathognomonic cellular features for ASDs and there remains a fundamental disconnection between the complex clinical aspects of ASDs and the underlying neurobiology. Although not listed among the core diagnostic domains of impairment in ASDs, motor abnormalities have been consistently reported across the spectrum. In this perspective article, we summarize the evidence that supports the use of motor abnormalities as a putative endophenotype for ASDs. We argue that because these motor abnormalities do not directly depend on social or linguistic development, they may serve as an early disease indicator. Furthermore, we propose that stratifying patients based on motor development could be useful not only as an outcome predictor and in identifying more specific treatments for different ASDs categories, but also in exposing neurobiological mechanisms. PMID:23781177

  3. Sharing Data In The Global Alzheimer’s Association Interactive Network

    PubMed Central

    Neu, Scott C.; Crawford, Karen L.; Toga, Arthur W.

    2015-01-01

    The Global Alzheimer’s Association Interactive Network (GAAIN) aims to be a shared network of research data, analysis tools, and computational resources for studying the causes of Alzheimer’s disease. Central to its design are policies that honor data ownership, prevent unauthorized data distribution, and respect the boundaries of contributing institutions. The results of data queries are displayed in graphs and summary tables, which protects data ownership while providing sufficient information to view trends in aggregated data and discover new data sets. In this article we report on our progress in sharing data through the integration of geographically-separated and independently-operated Alzheimer’s disease research studies around the world. PMID:26049147

  4. 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

  5. P-value based analysis for shared controls design in genome-wide association studies.

    PubMed

    Zaykin, Dmitri V; Kozbur, Damian O

    2010-11-01

    An appealing genome-wide association study design compares one large control group against several disease samples. A pioneering study by the Wellcome Trust Case Control Consortium that employed such a design has identified multiple susceptibility regions, many of which have been independently replicated. While reusing a control sample provides effective utilization of data, it also creates correlation between association statistics across diseases. An observation of a large association statistic for one of the diseases may greatly increase chances of observing a spuriously large association for a different disease. Accounting for the correlation is also particularly important when screening for SNPs that might be involved in a set of diseases with overlapping etiology. We describe methods that correct association statistics for dependency due to shared controls, and we describe ways to obtain a measure of overall evidence and to combine association signals across multiple diseases. The methods we describe require no access to individual subject data, instead, they efficiently utilize information contained in P-values for association reported for individual diseases. P-value based combined tests for association are flexible and essentially as powerful as the approach based on aggregating the individual subject data.

  6. 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.

  7. Neuropsychiatric Symptoms, Endophenotypes, and Syndromes in Late-Onset Alzheimer's Disease: Focus on APOE Gene

    PubMed Central

    Panza, Francesco; Seripa, Davide; D'Onofrio, Grazia; Frisardi, Vincenza; Solfrizzi, Vincenzo; Mecocci, Patrizia; Pilotto, Alberto

    2011-01-01

    Neuropsychiatric symptoms, previously denominated as behavioural and psychological symptoms of dementia, are common features of Alzheimer's disease (AD) and are one of the major risk factors for institutionalization. At present, the role of the apolipoprotein E (APOE) gene in the development of neuropsychiatric symptoms in AD patients is unclear. In this paper, we summarized the findings of the studies of neuropsychiatric symptoms and neuropsychiatric syndromes/endophenotypes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between APOE and neuropsychiatric symptoms in late-onset AD, other studies reported a significant association between the APOE ε4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. Furthermore, some negative studies that focused on the distribution of APOE genotypes between AD patients with or without neuropsychiatric symptoms further emphasized the importance of subgrouping neuropsychiatric symptoms in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, and possible lack of statistical power to detect associations in the negative studies. PMID:21559196

  8. Endophenotypes of FOXP2: dysfunction within the human articulatory network.

    PubMed

    Liégeois, F; Morgan, A T; Connelly, A; Vargha-Khadem, F

    2011-07-01

    The identification of the first gene involved in a speech-language disorder was made possible through the study of a British multi-generational family (the "KE family") in whom half the members have an inherited speech-language disorder caused by a FOXP2 mutation. Neuroimaging investigations in the affected members of the KE family have revealed structural and functional abnormalities in a wide cortical-subcortical network. Functional imaging studies have confirmed dysfunction of this network by revealing abnormal activation in several areas including Broca's area and the putamen during language-related tasks, such as word repetition and generation. Repeating nonsense words is particularly challenging for the affected members of the family, as well as in other individuals suffering from idiopathic developmental specific language impairments; yet, thus far the neural correlates of the nonword repetition task have not been examined in individuals with developmental speech and language disorders. Here, four affected members of the KE family and four unrelated age-matched healthy participants repeated nonsense words aloud during functional MRI scanning. Relative to control participants, repetition in the affected members was severely impaired, and brain activation was significantly reduced in the premotor, supplementary and primary motor cortices, as well as in the cerebellum and basal ganglia. We suggest that nonword repetition is the optimal endophenotype for FOXP2 disruption in humans because this task recruits brain regions involved in the imitation and vocal learning of novel sequences of speech sounds.

  9. Testing for the mediating role of endophenotypes using molecular genetic data in a twin study of ADHD traits

    PubMed Central

    Pinto, Rebecca; Asherson, Philip; Ilott, Nicholas; Cheung, Celeste H. M.

    2016-01-01

    Family and twin studies have identified endophenotypes that capture familial and genetic risk in attention‐deficit/hyperactivity disorder (ADHD), but it remains unclear if they lie on the causal pathway. Here, we illustrate a stepwise approach to identifying intermediate phenotypes. First, we use previous quantitative genetic findings to delineate the expected pattern of genetically correlated phenotypes. Second, we identify overlapping genetic associations with ADHD‐related quantitative traits. Finally, we test for the mediating role of associated endophenotypes. We applied this approach to a sample of 1,312 twins aged 7–10. Based on previous twin model‐fitting analyses, we selected hyperactivity–impulsivity, inattention, reading difficulties (RD), reaction time variability (RTV) and commission errors (CE), and tested for association with selected ADHD risk alleles. For nominally significant associations with both a symptom and a cognitive variable, matching the expected pattern based on previous genetic correlations, we performed mediation analysis to distinguish pleiotropic from mediating effects. The strongest association was observed for the rs7984966 SNP in the serotonin receptor gene (HTR2A), and RTV (P = 0.007; unadjusted for multiple testing). Mediation analysis suggested that CE (38%) and RTV (44%) substantially mediated the association between inattention and the T‐allele of SNP rs3785157 in the norepinephrine transporter gene (SLC6A2) and the T‐allele of SNP rs7984966 in HTR2A, respectively. The SNPs tag risk‐haplotypes but are not thought to be functionally significant. While these exploratory findings are preliminary, requiring replication, this study demonstrates the value of this approach that can be adapted to the investigation of multiple genetic markers and polygenic risk scores. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:27230021

  10. Immunotherapeutic targeting of shared melanoma-associated antigens in a murine glioma model.

    PubMed

    Prins, Robert M; Odesa, Sylvia K; Liau, Linda M

    2003-12-01

    Immune-based treatments for central nervous system gliomas have traditionally lagged behind those of more immunogenic tumors such as melanoma. The relative paucity of defined glioma-associated antigens that can be targeted by the immune system may partially account for this situation. Antigens present on melanomas have been extensively characterized, both in humans and in murine preclinical models. Melanocytes and astrocytes are both derived embryologically from the neural ectoderm. Their neoplastic counterparts, malignant melanomas and gliomas, have been shown in humans to share common antigens at the RNA level. However, little is known concerning whether gliomas can be targeted by immune-based strategies that prime T cells to epitopes from melanoma-associated antigens (MAAs). In this study, we provide evidence that two common murine glioma cell lines (GL26 and GL261) express the melanoma antigens gp100 and tyrosinase-related protein 2 (TRP-2). To understand the immunogenicity of murine gliomas to CD8(+) T cells, we examined the ability of a MAA-specific CTL cell line to lyse the glioma cells, as well as the in vivo expansion of MAA-specific CD8(+) T cells in animals harboring gliomas. Both glioma cell lines were lysed by a human gp100-specific CTL cell line in vitro. Mice harboring s.c. GL26 gliomas possessed TRP-2-specific CD8(+) T cells, providing further evidence that these gliomas express the protein products in the context of MHC class I. Furthermore, MAA peptide-pulsed dendritic cells could prime T cells that specifically recognize GL26 glioma cells in vitro. Lastly, mice that were prevaccinated with human gp100 and TRP-2 peptide-pulsed dendritic cells had significantly extended survival when challenged with tumor cells in the brain, resulting in >50% long-term survival. These results suggest that shared MAAs on gliomas can be targeted immunotherapeutically, pointing the way to a new potential treatment option for patients with malignant gliomas.

  11. The Importance of Endophenotypes to Evaluate the Relationship between Genotype and External Phenotype.

    PubMed

    Te Pas, Marinus F W; Madsen, Ole; Calus, Mario P L; Smits, Mari A

    2017-02-22

    With the exception of a few Mendelian traits, almost all phenotypes (traits) in livestock science are quantitative or complex traits regulated by the expression of many genes. For most of the complex traits, differential expression of genes, rather than genomic variation in the gene coding sequences, is associated with the genotype of a trait. The expression profiles of the animal's transcriptome, proteome and metabolome represent endophenotypes that influence/regulate the externally-observed phenotype. These expression profiles are generated by interactions between the animal's genome and its environment that range from the cellular, up to the husbandry environment. Thus, understanding complex traits requires knowledge about not only genomic variation, but also environmental effects that affect genome expression. Gene products act together in physiological pathways and interaction networks (of pathways). Due to the lack of annotation of the functional genome and ontologies of genes, our knowledge about the various biological systems that contribute to the development of external phenotypes is sparse. Furthermore, interaction with the animals' microbiome, especially in the gut, greatly influences the external phenotype. We conclude that a detailed understanding of complex traits requires not only understanding of variation in the genome, but also its expression at all functional levels.

  12. The Importance of Endophenotypes to Evaluate the Relationship between Genotype and External Phenotype

    PubMed Central

    te Pas, Marinus F. W.; Madsen, Ole; Calus, Mario P. L.; Smits, Mari A.

    2017-01-01

    With the exception of a few Mendelian traits, almost all phenotypes (traits) in livestock science are quantitative or complex traits regulated by the expression of many genes. For most of the complex traits, differential expression of genes, rather than genomic variation in the gene coding sequences, is associated with the genotype of a trait. The expression profiles of the animal’s transcriptome, proteome and metabolome represent endophenotypes that influence/regulate the externally-observed phenotype. These expression profiles are generated by interactions between the animal’s genome and its environment that range from the cellular, up to the husbandry environment. Thus, understanding complex traits requires knowledge about not only genomic variation, but also environmental effects that affect genome expression. Gene products act together in physiological pathways and interaction networks (of pathways). Due to the lack of annotation of the functional genome and ontologies of genes, our knowledge about the various biological systems that contribute to the development of external phenotypes is sparse. Furthermore, interaction with the animals’ microbiome, especially in the gut, greatly influences the external phenotype. We conclude that a detailed understanding of complex traits requires not only understanding of variation in the genome, but also its expression at all functional levels. PMID:28241430

  13. Genome-wide association study of shared components of reading disability and language impairment.

    PubMed

    Eicher, J D; Powers, N R; Miller, L L; Akshoomoff, N; Amaral, D G; Bloss, C S; Libiger, O; Schork, N J; Darst, B F; Casey, B J; Chang, L; Ernst, T; Frazier, J; Kaufmann, W E; Keating, B; Kenet, T; Kennedy, D; Mostofsky, S; Murray, S S; Sowell, E R; Bartsch, H; Kuperman, J M; Brown, T T; Hagler, D J; Dale, A M; Jernigan, T L; St Pourcain, B; Davey Smith, G; Ring, S M; Gruen, J R

    2013-11-01

    Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.

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

    PubMed Central

    2012-01-01

    Background 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. Findings 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. Conclusions 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

  15. SHARE: an adaptive algorithm to select the most informative set of SNPs for candidate genetic association.

    PubMed

    Dai, James Y; Leblanc, Michael; Smith, Nicholas L; Psaty, Bruce; Kooperberg, Charles

    2009-10-01

    Association studies have been widely used to identify genetic liability variants for complex diseases. While scanning the chromosomal region 1 single nucleotide polymorphism (SNP) at a time may not fully explore linkage disequilibrium, haplotype analyses tend to require a fairly large number of parameters, thus potentially losing power. Clustering algorithms, such as the cladistic approach, have been proposed to reduce the dimensionality, yet they have important limitations. We propose a SNP-Haplotype Adaptive REgression (SHARE) algorithm that seeks the most informative set of SNPs for genetic association in a targeted candidate region by growing and shrinking haplotypes with 1 more or less SNP in a stepwise fashion, and comparing prediction errors of different models via cross-validation. Depending on the evolutionary history of the disease mutations and the markers, this set may contain a single SNP or several SNPs that lay a foundation for haplotype analyses. Haplotype phase ambiguity is effectively accounted for by treating haplotype reconstruction as a part of the learning procedure. Simulations and a data application show that our method has improved power over existing methodologies and that the results are informative in the search for disease-causal loci.

  16. 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.

  17. 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

  18. Resting frontal EEG asymmetry as an endophenotype for depression risk: sex-specific patterns of frontal brain asymmetry.

    PubMed

    Stewart, Jennifer L; Bismark, Andrew W; Towers, David N; Coan, James A; Allen, John J B

    2010-08-01

    Resting frontal electroencephalographic (EEG) asymmetry has been hypothesized as a marker of risk for major depressive disorder (MDD), but the extant literature is based predominately on female samples. Resting frontal asymmetry was assessed on 4 occasions within a 2-week period in 306 individuals aged 18-34 (31% male) with (n = 143) and without (n = 163) lifetime MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (American Psychiatric Association, 1994). Lifetime MDD was linked to relatively less left frontal activity for both sexes using a current source density (CSD) reference, findings that were not accounted for solely by current MDD status or current depression severity, suggesting that CSD-referenced EEG asymmetry is a possible endophenotype for depression. In contrast, results for average and linked mastoid references were less consistent but demonstrated a link between less left frontal activity and current depression severity in women.

  19. Cellulolytic Streptomyces Strains Associated with Herbivorous Insects Share a Phylogenetically Linked Capacity To Degrade Lignocellulose

    PubMed Central

    Book, Adam J.; Lewin, Gina R.; McDonald, Bradon R.; Takasuka, Taichi E.; Doering, Drew T.; Adams, Aaron S.; Blodgett, Joshua A. V.; Clardy, Jon; Raffa, Kenneth F.; Fox, Brian G.

    2014-01-01

    Actinobacteria in the genus Streptomyces are critical players in microbial communities that decompose complex carbohydrates in the soil, and these bacteria have recently been implicated in the deconstruction of plant polysaccharides for some herbivorous insects. Despite the importance of Streptomyces to carbon cycling, the extent of their plant biomass-degrading ability remains largely unknown. In this study, we compared four strains of Streptomyces isolated from insect herbivores that attack pine trees: DpondAA-B6 (SDPB6) from the mountain pine beetle, SPB74 from the southern pine beetle, and SirexAA-E (SACTE) and SirexAA-G from the woodwasp, Sirex noctilio. Biochemical analysis of secreted enzymes demonstrated that only two of these strains, SACTE and SDPB6, were efficient at degrading plant biomass. Genomic analyses indicated that SACTE and SDPB6 are closely related and that they share similar compositions of carbohydrate-active enzymes. Genome-wide proteomic and transcriptomic analyses revealed that the major exocellulases (GH6 and GH48), lytic polysaccharide monooxygenases (AA10), and mannanases (GH5) were conserved and secreted by both organisms, while the secreted endocellulases (GH5 and GH9 versus GH9 and GH12) were from diverged enzyme families. Together, these data identify two phylogenetically related insect-associated Streptomyces strains with high biomass-degrading activity and characterize key enzymatic similarities and differences used by these organisms to deconstruct plant biomass. PMID:24837391

  20. Does academic performance or personal growth share a stronger association with learning environment perception?

    PubMed Central

    Tackett, Sean; Wright, Scott M.; Shochet, Robert S.

    2016-01-01

    Objectives This study was conducted to characterize the relative strength of associations of learning environment perception with academic performance and with personal growth. Methods In 2012-2014 second and third year students at Johns Hopkins University School of Medicine completed a learning environment survey and personal growth scale. Hierarchical linear regression analysis was employed to determine if the proportion of variance in learning environment scores accounted for by personal growth was significantly larger than the proportion accounted for by academic performance (course/clerkship grades). Results The proportion of variance in learning environment scores accounted for by personal growth was larger than the proportion accounted for by academic performance in year 2 [R2Δ of 0.09, F(1,175) = 14.99,  p < .001] and year 3 [R2Δ of 0.28, F(1,169) = 76.80, p < .001]. Learning environment scores shared a small amount of variance with academic performance in years 2 and 3.  The amount of variance between learning environment scores and personal growth was small in year 2 and large in year 3. Conclusions Since supportive learning environments are essential for medical education, future work must determine if enhancing personal growth prior to and during the clerkship year will increase learning environment perception. PMID:27570912

  1. 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

  2. 31 CFR 50.36 - Allocation of premium income associated with entities that do share profits and losses with...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 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...

  3. 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...

  4. 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…

  5. 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.

  6. Stratification Based on Language-Related Endophenotypes in Autism: Attempt to Replicate Reported Linkage

    PubMed Central

    Spence, Sarah J.; Cantor, Rita M.; Chung, Lien; Kim, Sharon; Geschwind, Daniel H.; Alarcón, Maricela

    2013-01-01

    The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism-related susceptibility regions. To further explore the utility of using language related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage. A whole genome scan using a multipoint nonparametric linkage approach was performed in 133 families, stratifying the sample by phrase speech delay and word delay. None of the regions reached suggested genome-wide or replication significance thresholds. However, several loci on chromosomes 1, 2, 4, 6, 7, 8, 9, 10, 12, 15, and 19 yielded nominally higher linkage signals in the delayed groups. The results did not support reported linkage findings for loci on chromosomes 7 or 13 that were a result of stratification based on the language delay endophenotype. In addition, inclusion of information on parental history of language delay did not appreciably affect the linkage results. The nominal increase in NPL scores across several regions using language delay endophenotypes for stratification suggests that this strategy may be useful in attenuating heterogeneity. However, the inconsistencies in regions identified across studies highlight the importance of increasing sample sizes to provide adequate power to test replications in independent samples. PMID:16752361

  7. [Neurophysiological endophenotypes and schizophrenic disorder: emergence and evolution of a clinical concept].

    PubMed

    Micoulaud Franchi, J-A; Vion Dury, J; Cermolacce, M

    2012-12-01

    It is proposed an historical approach to concepts leading to the development of operational paradigms for measuring objectives neurophysiological endophenotypes. It is hypothesized that psychiatric interest for paradigms measuring Event-Related Potential (ERP) come from Bleuler (1911) and McGhie and Chapman (1961) phenomenological and clinical descriptions. They noted, first that patients with schizophrenia generally feel as if they are being flooded by an overwhelming mass of sensory input combined with a heightened sensory perception, second that they were distractible to irrelevant sensory stimuli. These subjective abnormalities may be related, first to inability to filter incongruent information measured in a double click paradigm by a deficit in P50 amplitude gating, and second to an inability to select a stimulus of interest measured in the oddball paradigm by a deficit in P300 amplitude. The analysis of these P50 and P300 ERP in cohorts of patients with schizophrenia found most of Gottesman endophenotype criteria. P50 and P300 ERP are therefore relevant neurophysiological endophenotypes. However, from a clinical point of view, these endophenotypes lack specificity. The hypothesis of this article leads us to formulate ways of research. It is shown the value of combining objective neurophysiological measures with subjective measures using self-administered questionnaires ("offline") or psychophysiological tests ("online") to develop rigorous neurophysiological experimental paradigms especially as clinical observations of their origins are not forgotten.

  8. 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

  9. The Shine-Through Masking Paradigm Is a Potential Endophenotype of Schizophrenia

    PubMed Central

    Chkonia, Eka; Roinishvili, Maya; Makhatadze, Natia; Tsverava, Lidia; Stroux, Andrea; Neumann, Konrad; Herzog, Michael H.; Brand, Andreas

    2010-01-01

    Background To understand the genetics of schizophrenia, a hunt for so-called intermediate phenotypes or endophenotypes is ongoing. Visual masking has been proposed to be such an endophenotype. However, no systematic study has been conducted yet to prove this claim. Here, we present the first study showing that masking meets the most important criteria for an endophenotype. Methodology/Principal Findings We tested 62 schizophrenic patients, 39 non-affected first-degree relatives, and 38 healthy controls in the shine-through masking paradigm and, in addition, in the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST). Most importantly, masking performance of relatives was significantly in between the one of patients and controls in the shine-through paradigm. Moreover, deficits were stable throughout one year. Using receiver operating characteristics (ROC) methods, we show that the shine-through paradigm distinguishes with high sensitivity and specificity between schizophrenic patients, first-order relatives and healthy controls. Conclusions/Significance The shine-through paradigm is a potential endophenotype. PMID:21151559

  10. 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…

  11. 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…

  12. A Novel Extracellular Metallopeptidase Domain Shared by Animal Host-Associated Mutualistic and Pathogenic Microbes

    PubMed Central

    Nakjang, Sirintra; Ndeh, Didier A.; Wipat, Anil; Bolam, David N.; Hirt, Robert P.

    2012-01-01

    The mucosal microbiota is recognised as an important factor for our health, with many disease states linked to imbalances in the normal community structure. Hence, there is considerable interest in identifying the molecular basis of human-microbe interactions. In this work we investigated the capacity of microbes to thrive on mucosal surfaces, either as mutualists, commensals or pathogens, using comparative genomics to identify co-occurring molecular traits. We identified a novel domain we named M60-like/PF13402 (new Pfam entry PF13402), which was detected mainly among proteins from animal host mucosa-associated prokaryotic and eukaryotic microbes ranging from mutualists to pathogens. Lateral gene transfers between distantly related microbes explained their shared M60-like/PF13402 domain. The novel domain is characterised by a zinc-metallopeptidase-like motif and is distantly related to known viral enhancin zinc-metallopeptidases. Signal peptides and/or cell surface anchoring features were detected in most microbial M60-like/PF13402 domain-containing proteins, indicating that these proteins target an extracellular substrate. A significant subset of these putative peptidases was further characterised by the presence of associated domains belonging to carbohydrate-binding module family 5/12, 32 and 51 and other glycan-binding domains, suggesting that these novel proteases are targeted to complex glycoproteins such as mucins. An in vitro mucinase assay demonstrated degradation of mammalian mucins by a recombinant form of an M60-like/PF13402-containing protein from the gut mutualist Bacteroides thetaiotaomicron. This study reveals that M60-like domains are peptidases targeting host glycoproteins. These peptidases likely play an important role in successful colonisation of both vertebrate mucosal surfaces and the invertebrate digestive tract by both mutualistic and pathogenic microbes. Moreover, 141 entries across various peptidase families described in the MEROPS

  13. PTSD in Court II: Risk factors, endophenotypes, and biological underpinnings in PTSD.

    PubMed

    Young, Gerald

    The second article in the series of three for the journal on "PTSD in Court" especially concerns the biological bases that have been found to be associated with PTSD (posttraumatic stress disorder). The cohering concepts in this section relate to risk factors; candidate genes; polygenetics; "gene×environment" interactions; epigenetics; endophenotypes; biomarkers; and connective networks both structurally and functionally (in terms of intrinsic connectivity networks, ICNs, including the DMN, SN, and CEN; that is, default mode, salience, and central executive networks, respectively). Risk factors related to PTSD include pre-event, event- and post-event ones. Some of the genes related to PTSD include: FKBP5, 5-HTTLPR, and COMT (which are, respectively, FK506-binding protein 5 gene, serotonin-transporter linked polymorphic region, catechol-O-methyl-transferase). These genetic findings give an estimate of 30% for the genetic influence on PTSD. The typical brain regions involved in PTSD include the amygdala, hippocampus, and prefrontal cortex, along with the insula. Causal models of behavior are multifactorial and biopsychosocial, and these types of models apply to PTSD, as well. The paper presents a multilevel systems model of psychopathology, including PTSD, which involves three levels - a top-down psychological construct one, a bottom-up symptom connection one, and a middle one involving symptom appraisal. Legally, causality refers to the event at issue needing to meet the bar of being materially contributory to the outcome. Finally, this section of the article reviews empirically-supported therapies for PTSD and the dangers of not receiving treatment for it.

  14. 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.

  15. 13 CFR 120.222 - Fees which the Lender or Associate may not collect from the Borrower or share with third parties.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Fees which the Lender or Associate may not collect from the Borrower or share with third parties. 120.222 Section 120.222 Business Credit... Guaranteed Loans § 120.222 Fees which the Lender or Associate may not collect from the Borrower or share...

  16. Phenylthiocarbamide (PTC) perception in ultra-high risk for psychosis participants who develop schizophrenia: testing the evidence for an endophenotypic marker.

    PubMed

    Brewer, Warrick J; Lin, Ashleigh; Moberg, Paul J; Smutzer, Gregory; Nelson, Barnaby; Yung, Alison R; Pantelis, Christos; McGorry, Patrick D; Turetsky, Bruce I; Wood, Stephen J

    2012-08-30

    Reports suggesting that schizophrenia participants are more likely to be phenylthiocarbamide (PTC) non-tasters when compared to controls have recently been controversial. If supported, a genetic-based phenotypic variation in PTC taster status is implicated, suggesting a greater illness risk for those participants with recessive alleles for the TAS2R38 receptor. Should PTC insensitivity be a schizophrenia endophenotype, then it would be expected in follow-up of ultra high-risk for psychosis participants who later develop schizophrenia (UHR-S). UHR-S was hypothesised to show reduced PTC sensitivity compared to those who were previously at risk, but did not transition (UHR-NP). PTC perception was assessed in 219 UHR participants at long-term follow-up, of whom 53 had transitioned to psychosis (UHR-P) during the follow-up period. Fifteen of the 219 participants were diagnosed with schizophrenia. Seventy-eight had a family history of psychotic disorder. No differences in PTC taster status were found in UHR participants based upon transition to psychosis status, schizophrenia diagnosis, or family history of schizophrenia. This report indicates that schizophrenia development among UHR participants is not associated with PTC tasting deficits and fails to support previous findings that inability to detect the bitter taste of PTC is a schizophrenia endophenotype.

  17. Neuropsychological, electrophysiological and neurological impairments in patients with obsessive compulsive disorder, their healthy siblings and healthy controls: Identifying potential endophenotype(s).

    PubMed

    Ozcan, Halil; Ozer, Suzan; Yagcioglu, Suha

    2016-06-30

    The etiology of obsessive-compulsive disorder (OCD) has not been clarified. This study aimed to investigate the cognitive, neurological, electrophysiological functions which are reflected in executive functions, memory, visuospatial integration; neurological examination and auditory event related potentials (AERP) (N100, N200, P200 and P300) in patients with OCD, their siblings, and control subjects and to determine potential endophenotypic markers. Thirty-three patients with OCD, 18 siblings and 21 controls; matched for age, gender and years of education were included. Yale Brown Obsessive Compulsive Symptoms Checklist Scale, Hamilton Depression-Rating Scale, an exhaustive neuropscyhological test battery and Neurological Evaluation Scale were administered. Their AERP recordings were obtained. Executive functions and visuospatial integration were highly impaired in patients and slightly in their siblings compared to controls. P200 amplitude was sorted as siblings>patients>controls. P300 amplitude was sorted as patientsendophenotypes of OCD.

  18. 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

  19. An Indian experience of neurocognitive endophenotypic markers in unaffected first-degree relatives of schizophrenia patients

    PubMed Central

    Solanki, Ram Kumar; Kumar, Ashok; Satija, Yogesh; Gupta, Suresh; Singh, Paramjeet

    2016-01-01

    Context: Multiple vulnerability genes interact with environmental factors to develop a range of phenotypes in the schizophrenia spectrum. Endophenotypes can help characterize the impact of risk genes by providing genetically relevant traits that are more complaisant than the behavioral symptoms that classify mental illness. Aims: We aimed to investigate the neurocognitive endophenotypic markers for schizophrenia in Indian population. Settings and Design: In a cross-sectional study, we assessed neurocognitive functioning in 40 unaffected first-degree relatives (FDR) of schizophrenia patients with an equal number of healthy controls. Materials and Methods: FDR schizophrenia group was compared with the control group on measures of short-term memory, verbal working memory, auditory verbal memory on indices of immediate recall and recognition, visuospatial working memory, visual attention, and executive functions. Results: The study found that FDR schizophrenia scored poorly on all tested measures of neurocognition except visual attention. On calculating composite score, we found that composite neurocognitive score better discriminated the FDR schizophrenia from the control group. Conclusions: Neurocognitive measures of short-term memory, verbal working memory, auditory verbal memory, visuospatial working memory, and executive functions significantly differentiate FDR of patients with schizophrenia from controls and can be considered as endophenotypic markers of schizophrenia in non-Caucasian population. The exactitude of this approach can be increased by calculating a composite neurocognitive score which combines various neurocognitive measures. PMID:26985100

  20. Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia.

    PubMed

    Costas, J; Carrera, N; Alonso, P; Gurriarán, X; Segalàs, C; Real, E; López-Solà, C; Mas, S; Gassó, P; Domènech, L; Morell, M; Quintela, I; Lázaro, L; Menchón, J M; Estivill, X; Carracedo, Á

    2016-03-29

    Common single-nucleotide polymorphisms (SNPs) account for a large proportion of the heritability of obsessive-compulsive disorder (OCD). Co-ocurrence of OCD and schizophrenia is commoner than expected based on their respective prevalences, complicating the clinical management of patients. This study addresses two main objectives: to identify particular genes associated with OCD by SNP-based and gene-based tests; and to test the existence of a polygenic risk shared with schizophrenia. The primary analysis was an exon-focused genome-wide association study of 370 OCD cases and 443 controls from Spain. A polygenic risk model based on the Psychiatric Genetics Consortium schizophrenia data set (PGC-SCZ2) was tested in our OCD data. A polygenic risk model based on our OCD data was tested on previous data of schizophrenia from our group. The most significant association at the gene-based test was found at DNM3 (P=7.9 × 10(-5)), a gene involved in synaptic vesicle endocytosis. The polygenic risk model from PGC-SCZ2 data was strongly associated with disease status in our OCD sample, reaching its most significant value after removal of the major histocompatibility complex region (lowest P=2.3 × 10(-6), explaining 3.7% of the variance). The shared polygenic risk was confirmed in our schizophrenia data. In conclusion, DNM3 may be involved in risk to OCD. The shared polygenic risk between schizophrenia and OCD may be partially responsible for the frequent comorbidity of both disorders, explaining epidemiological data on cross-disorder risk. This common etiology may have clinical implications.

  1. Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia

    PubMed Central

    Costas, J; Carrera, N; Alonso, P; Gurriarán, X; Segalàs, C; Real, E; López-Solà, C; Mas, S; Gassó, P; Domènech, L; Morell, M; Quintela, I; Lázaro, L; Menchón, J M; Estivill, X; Carracedo, Á

    2016-01-01

    Common single-nucleotide polymorphisms (SNPs) account for a large proportion of the heritability of obsessive-compulsive disorder (OCD). Co-ocurrence of OCD and schizophrenia is commoner than expected based on their respective prevalences, complicating the clinical management of patients. This study addresses two main objectives: to identify particular genes associated with OCD by SNP-based and gene-based tests; and to test the existence of a polygenic risk shared with schizophrenia. The primary analysis was an exon-focused genome-wide association study of 370 OCD cases and 443 controls from Spain. A polygenic risk model based on the Psychiatric Genetics Consortium schizophrenia data set (PGC-SCZ2) was tested in our OCD data. A polygenic risk model based on our OCD data was tested on previous data of schizophrenia from our group. The most significant association at the gene-based test was found at DNM3 (P=7.9 × 10−5), a gene involved in synaptic vesicle endocytosis. The polygenic risk model from PGC-SCZ2 data was strongly associated with disease status in our OCD sample, reaching its most significant value after removal of the major histocompatibility complex region (lowest P=2.3 × 10−6, explaining 3.7% of the variance). The shared polygenic risk was confirmed in our schizophrenia data. In conclusion, DNM3 may be involved in risk to OCD. The shared polygenic risk between schizophrenia and OCD may be partially responsible for the frequent comorbidity of both disorders, explaining epidemiological data on cross-disorder risk. This common etiology may have clinical implications. PMID:27023174

  2. 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

  3. Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects

    PubMed Central

    Zhou, Yang; Kaiser, Tobias; Monteiro, Patrícia; Zhang, Xiangyu; Van der Goes, Marie. S.; Wang, Dongqing; Barak, Boaz; Zeng, Menglong; Li, Chenchen; Lu, Congyi; Wells, Michael; Amaya, Aldo; Nguyen, Shannon; Lewis, Michael; Sanjana, Neville; Zhou, Yongdi; Zhang, Mingjie; Zhang, Feng; Fu, Zhanyan; Feng, Guoping

    2016-01-01

    SUMMARY Genetic studies have revealed significant overlaps of risk genes among psychiatric disorders. However, it is not clear how different mutations of the same gene contribute to different disorders. We characterized two lines of mutant mice with Shank3 mutations linked to ASD and schizophrenia. We found both shared and distinct synaptic and behavioral phenotypes. Mice with the ASD-linked InsG3680 mutation manifest striatal synaptic transmission defects before weaning age and impaired juvenile social interaction, coinciding with the early onset of ASD symptoms. On the other hand, adult mice carrying the schizophrenia-linked R1117X mutation show profound synaptic defects in prefrontal cortex and social dominance behavior. Furthermore, we found differential Shank3 mRNA stability and SHANK1/2 upregulation in these two lines. These data demonstrate that different alleles of the same gene may have distinct phenotypes at molecular, synaptic, and circuit levels in mice, which may inform exploration of these relationships in human patients. PMID:26687841

  4. Genome-wide association uncovers shared genetic effects among personality traits and mood states

    PubMed Central

    Luciano, Michelle; Huffman, Jennifer E; Arias-Vásquez, Alejandro; Vinkhuyzen, Anna AE; Middeldorp, Christel M; Giegling, Ina; Payton, Antony; Davies, Gail; Zgaga, Lina; Janzing, Joost; Ke, Xiayi; Galesloot, Tessel; Hartmann, Annette M; Ollier, William; Tenesa, Albert; Hayward, Caroline; Verhagen, Maaike; Montgomery, Grant W; Hottenga, Jouke-Jan; Konte, Bettina; Starr, John M; Vitart, Veronique; Vos, Pieter E; Madden, Pamela AF; Willemsen, Gonneke; Konnerth, Heike; Horan, Michael A; Porteous, David J; Campbell, Harry; Vermeulen, Sita H; Heath, Andrew C; Wright, Alan; Polasek, Ozren; Kovacevic, Sanja B; Hastie, Nicholas D; Franke, Barbara; Boomsma, Dorret I; Martin, Nicholas G; Rujescu, Dan; Wilson, James F; Buitelaar, Jan; Pendleton, Neil; Rudan, Igor; Deary, Ian J

    2013-01-01

    Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP (~2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546 to 1 338; maximum total n=6 268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n=527 to 6 032). Suggestive association (P=8×10−8) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P<6.09×10−6) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P<0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits. PMID:22628180

  5. The association between kinematic risky driving among parents and their teenage children: moderation by shared personality characteristics.

    PubMed

    Ehsani, Johnathon P; Simons-Morton, Bruce; Xie, Yunlong; Klauer, Sheila G; Albert, Paul S

    2014-08-01

    This study examined the driving behavior of 42 parent-teenager dyads for 18 months, under naturalistic driving conditions. At baseline participants' personality characteristics were assessed. Objective risky driving measures (kinematic risky driving) were captured by accelerometers for the duration of the study. To estimate teenage and parent correlations in kinematic risky driving, separate Poisson regression models were fit for teenagers and parents. Standardized residuals were computed for each trip for each individual. Correlations were obtained by estimating the Spearman rank correlations of the individual average residuals across teenagers and parents. The bootstrap technique was used to estimate the standard errors associated with the parent-teenager correlations. The overall correlation between teenage and parent kinematic risky driving for the 18-month study period was positive, but weak (r=0.18). When the association between parent and teenagers' risky driving was adjusted for shared personality characteristics, the correlation reduced to 0.09. Although interesting, the 95% confidence intervals on the difference between these two estimates overlapped zero. We conclude that the weak similarity in parent-teen kinematic risky driving was partly explained by shared personality characteristics.

  6. 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

  7. SHARE and Share Alike

    ERIC Educational Resources Information Center

    Baird, Jeffrey Marshall

    2006-01-01

    This article describes a reading comprehension program adopted at J. E. Cosgriff Memorial Catholic School in Salt Lake City, Utah. The program is called SHARE: Students Helping Achieve Reading Excellence, and involves seventh and eighth grade students teaching first and second graders reading comprehension strategies learned in middle school…

  8. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes.

    PubMed

    Sepúlveda, Maria; Armangue, Thaís; Martinez-Hernandez, Eugenia; Arrambide, Georgina; Sola-Valls, Nuria; Sabater, Lidia; Téllez, Nieves; Midaglia, Luciana; Ariño, Helena; Peschl, Patrick; Reindl, Markus; Rovira, Alex; Montalban, Xavier; Blanco, Yolanda; Dalmau, Josep; Graus, Francesc; Saiz, Albert

    2016-07-01

    The aim of this study was to report the clinical spectrum associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) in adult patients, and to assess whether phenotypic variants are dependent on recognition of rodent MOG epitopes. We retrospectively analyzed the features, course and outcome of 56 patients whose samples were investigated by brain tissue immunohistochemistry and cell-based assays using human and rodent MOG. The median age at symptom onset was 37 years (range 18-70); 35 patients (63 %) were female. After a median follow-up of 43 months (range 4-554), only 14 patients (25 %) developed a neuromyelitis optica spectrum disorder (NMOSD), 27 patients (47 %) retained the initial diagnosis of isolated optic neuritis, 7 (12 %) of longitudinally extensive transverse myelitis, and 2 (4 %) of acute disseminated encephalomyelitis; 6 patients (11 %) developed atypical demyelinating syndromes (4 had relapsing episodes of short myelitis lesions which in one occurred with optic neuritis; 1 had relapsing brainstem symptoms, and 1 relapsing demyelinating encephalomyelitis). The course was frequently associated with relapses (71 %) and good outcome. Twenty-seven patients (49 %) had antibodies that recognized rodent MOG epitopes, and 9 of them (16 %) showed a myelin staining pattern in rodent tissue. Only the myelin staining pattern was linked to NMOSD (p = 0.005). In conclusion, MOG autoimmunity in adult patients associates with a clinical spectrum wider than the one expected for patients with suspected NMOSD and overall good outcome. Antibodies to rodent MOG epitopes do not associate with any phenotypic variant.

  9. 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

  10. Human telomerase and Cajal body ribonucleoproteins share a unique specificity of Sm protein association.

    PubMed

    Fu, Dragony; Collins, Kathleen

    2006-03-01

    Cajal bodies are nuclear structures that host RNA modification and assembly reactions. Some RNAs transit Cajal bodies, while others must concentrate in Cajal bodies to function. Here we report that at least a subfraction of human telomerase RNA and individual resident Cajal body RNAs is associated with Sm proteins. Surprisingly, of seven Sm proteins assembled into a heteroheptameric ring, only a subset copurifies telomerase and Cajal body ribonucleoproteins. We show that a Cajal body RNA localization motif determines this specificity. These discoveries expand the cellular repertoire of Sm protein assemblies and their involvement in ribonucleoprotein localization and function.

  11. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.

    PubMed

    2007-06-07

    There is increasing evidence that genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study (using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined approximately 2,000 individuals for each of 7 major diseases and a shared set of approximately 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 x 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals (including 58 loci with single-point P values between 10(-5) and 5 x 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a

  12. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

    PubMed Central

    2009-01-01

    There is increasing evidence that genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study (using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined ~2,000 individuals for each of 7 major diseases and a shared set of ~3,000 controls. Case-control comparisons identified 24 independent association signals at P<5×10-7: 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn’s disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals (including 58 loci with single-point P values between 10-5 and 5×10-7) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics

  13. Type VI secretion apparatus and phage tail-associated protein complexes share a common evolutionary origin

    SciTech Connect

    Leiman, Petr G.; Basler, Marek; Ramagopal, Udupi A.; Bonanno, Jeffrey B.; Sauder, J. Michael; Pukatzki, Stefan; Burley, Stephen K.; Almo, Steven C.; Mekalanos, John J.

    2009-04-22

    Protein secretion is a common property of pathogenic microbes. Gram-negative bacterial pathogens use at least 6 distinct extracellular protein secretion systems to export proteins through their multilayered cell envelope and in some cases into host cells. Among the most widespread is the newly recognized Type VI secretion system (T6SS) which is composed of 15--20 proteins whose biochemical functions are not well understood. Using crystallographic, biochemical, and bioinformatic analyses, we identified 3 T6SS components, which are homologous to bacteriophage tail proteins. These include the tail tube protein; the membrane-penetrating needle, situated at the distal end of the tube; and another protein associated with the needle and tube. We propose that T6SS is a multicomponent structure whose extracellular part resembles both structurally and functionally a bacteriophage tail, an efficient machine that translocates proteins and DNA across lipid membranes into cells.

  14. Scalable privacy-preserving data sharing methodology for genome-wide association studies.

    PubMed

    Yu, Fei; Fienberg, Stephen E; Slavković, Aleksandra B; Uhler, Caroline

    2014-08-01

    The protection of privacy of individual-level information in genome-wide association study (GWAS) databases has been a major concern of researchers following the publication of "an attack" on GWAS data by Homer et al. (2008). Traditional statistical methods for confidentiality and privacy protection of statistical databases do not scale well to deal with GWAS data, especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach that provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information, although the guarantees may come at a serious price in terms of data utility. Building on such notions, Uhler et al. (2013) proposed new methods to release aggregate GWAS data without compromising an individual's privacy. We extend the methods developed in Uhler et al. (2013) for releasing differentially-private χ(2)-statistics by allowing for arbitrary number of cases and controls, and for releasing differentially-private allelic test statistics. We also provide a new interpretation by assuming the controls' data are known, which is a realistic assumption because some GWAS use publicly available data as controls. We assess the performance of the proposed methods through a risk-utility analysis on a real data set consisting of DNA samples collected by the Wellcome Trust Case Control Consortium and compare the methods with the differentially-private release mechanism proposed by Johnson and Shmatikov (2013).

  15. Clonogenic Multiple Myeloma Cells have Shared stemness Signature Associated with Patient Survival

    PubMed Central

    Reghunathan, Renji; Bi, Chonglei; Liu, Shaw Cheng; Loong, Koh Tze; Chung, Tae-Hoon; Huang, Gaofeng; Chng, Wee Joo

    2013-01-01

    Multiple myeloma is the abnormal clonal expansion of post germinal B cells in the bone marrow. It was previously reported that clonogenic myeloma cells are CD138−. Human MM cell lines RPMI8226 and NCI H929 contained 2-5% of CD138− population. In this study, we showed that CD138− cells have increased ALDH1 activity, a hallmark of normal and neoplastic stem cells. CD138−ALDH+ cells were more clonogenic than CD138+ALDH− cells and only CD138− cells differentiated into CD138+ population. In vivo tumor initiation and clonogenic potentials of the CD138− population was confirmed using NOG mice. We derived a gene expression signature from functionally validated and enriched CD138− clonogenic population from MM cell lines and validated these in patient samples. This data showed that CD138− cells had an enriched expression of genes that are expressed in normal and malignant stem cells. Differentially expressed genes included components of the polycomb repressor complex (PRC) and their targets. Inhibition of PRC by DZNep showed differential effect on CD138− and CD138+ populations. The ‘stemness’ signature derived from clonogenic CD138− cells overlap significantly with signatures of common progenitor cells, hematopoietic stem cells, and Leukemic stem cells and is associated with poorer survival in different clinical datasets. PMID:23985559

  16. A Narrative Review of Binge Eating and Addictive Behaviors: Shared Associations with Seasonality and Personality Factors

    PubMed Central

    Davis, Caroline

    2013-01-01

    Binge-eating disorder and seasonal affective disorder were first described as clinically relevant conditions in very close temporal proximity a few decades ago. Both disorders have a higher prevalence rate in woman than in men, are characterized by a high proneness-to-stress and manifest heightened responsiveness to high-calorie, hyper-palatable foods. In recent years, a compelling body of evidence suggests that foods high in sugar and fat have the potential to alter brain reward circuitry in a manner similar to that seen when addictive drugs like alcohol and heroin are consumed in excess. These findings have led to suggestions that some cases of compulsive overeating may be understood as an addiction to sweet, fatty, and salty foods. In this paper, it is proposed that high seasonality is a risk factor for binge eating, especially in those characterized by anxious and impulsive personality traits – associations that could only occur in an environment with a superfluity of, and easy access to, rich and tasty foods. Given the well-established links between binge eating and addiction disorders [Ref. (1–3) for reviews], it is also suggested that seasonality, together with the same high-risk psychological profile, exacerbates the likelihood of engaging in a broad range of addictive behaviors. Data from a community sample (n = 412) of adults tested these models using linear regression procedures. Results confirmed that symptoms of binge eating and other addictive behaviors were significantly inter-correlated, and that seasonality, gender, and addictive personality traits were strong statistical predictors of the variance in binge-eating scores. Seasonality and addictive personality traits also accounted for a significant proportion of the variance in the measure of addictive behaviors. Conclusions are discussed in the context of brain reward mechanisms, motivational alternations in response to chronic over-consumption, and their relevance for the treatment of

  17. A narrative review of binge eating and addictive behaviors: shared associations with seasonality and personality factors.

    PubMed

    Davis, Caroline

    2013-12-27

    Binge-eating disorder and seasonal affective disorder were first described as clinically relevant conditions in very close temporal proximity a few decades ago. Both disorders have a higher prevalence rate in woman than in men, are characterized by a high proneness-to-stress and manifest heightened responsiveness to high-calorie, hyper-palatable foods. In recent years, a compelling body of evidence suggests that foods high in sugar and fat have the potential to alter brain reward circuitry in a manner similar to that seen when addictive drugs like alcohol and heroin are consumed in excess. These findings have led to suggestions that some cases of compulsive overeating may be understood as an addiction to sweet, fatty, and salty foods. In this paper, it is proposed that high seasonality is a risk factor for binge eating, especially in those characterized by anxious and impulsive personality traits - associations that could only occur in an environment with a superfluity of, and easy access to, rich and tasty foods. Given the well-established links between binge eating and addiction disorders [Ref. (1-3) for reviews], it is also suggested that seasonality, together with the same high-risk psychological profile, exacerbates the likelihood of engaging in a broad range of addictive behaviors. Data from a community sample (n = 412) of adults tested these models using linear regression procedures. Results confirmed that symptoms of binge eating and other addictive behaviors were significantly inter-correlated, and that seasonality, gender, and addictive personality traits were strong statistical predictors of the variance in binge-eating scores. Seasonality and addictive personality traits also accounted for a significant proportion of the variance in the measure of addictive behaviors. Conclusions are discussed in the context of brain reward mechanisms, motivational alternations in response to chronic over-consumption, and their relevance for the treatment of

  18. Comprehensive Neurocognitive Endophenotyping Strategies for Mouse Models of Genetic Disorders

    PubMed Central

    Hunsaker, Michael R.

    2012-01-01

    There is a need for refinement of the current behavioral phenotyping methods for mouse models of genetic disorders. The current approach is to perform a behavioral screen using standardized tasks to define a broad phenotype of the model. This phenotype is then compared to what is known concerning the disorder being modeled. The weakness inherent in this approach is twofold: First, the tasks that make up these standard behavioral screens do not model specific behaviors associated with a given genetic mutation but rather phenotypes affected in various genetic disorders; secondly, these behavioral tasks are insufficiently sensitive to identify subtle phenotypes. An alternate phenotyping strategy is to determine the core behavioral phenotypes of the genetic disorder being studied and develop behavioral tasks to evaluate specific hypotheses concerning the behavioral consequences of the genetic mutation. This approach emphasizes direct comparisons between the mouse and human that facilitate the development of neurobehavioral biomarkers or quantitative outcome measures for studies of genetic disorders across species. PMID:22266125

  19. New parasitoid-predator associations: female parasitoids do not avoid competition with generalist predators when sharing invasive prey

    NASA Astrophysics Data System (ADS)

    Chailleux, Anaïs; Wajnberg, Eric; Zhou, Yuxiang; Amiens-Desneux, Edwige; Desneux, Nicolas

    2014-12-01

    Optimal habitat selection is essential for species survival in ecosystems, and interspecific competition is a key ecological mechanism for many observed species association patterns. Specialized animal species are commonly affected by resource and interference competition with generalist and/or omnivorous competitors, so avoidance behavior could be expected. We hypothesize that specialist species may exploit broad range cues from such potential resource competitors (i.e., cues possibly common to various generalist and/or omnivorous predators) to avoid costly competition regarding food or reproduction, even in new species associations. We tested this hypothesis by studying short-term interactions between a native larval parasitoid and a native generalist omnivorous predator recently sharing the same invasive host/prey, the leaf miner Tuta absoluta. We observed a strong negative effect of kleptoparasitism (food resource stealing) instead of classical intraguild predation on immature parasitoids. There was no evidence that parasitoid females avoided the omnivorous predator when searching for oviposition sites, although we studied both long- and short-range known detection mechanisms. Therefore, we conclude that broad range cue avoidance may not exist in our biological system, probably because it would lead to too much oviposition site avoidance which would not be an efficient and, thus, beneficial strategy. If confirmed in other parasitoids or specialist predators, our findings may have implications for population dynamics, especially in the current context of increasing invasive species and the resulting creation of many new species associations.

  20. Collaboratively Sharing Scientific Data

    NASA Astrophysics Data System (ADS)

    Wang, Fusheng; Vergara-Niedermayr, Cristobal

    Scientific research becomes increasingly reliant on multi-disciplinary, multi-institutional collaboration through sharing experimental data. Indeed, data sharing is mandatory by government research agencies such as NIH. The major hurdles for data sharing come from: i) the lack of data sharing infrastructure to make data sharing convenient for users; ii) users’ fear of losing control of their data; iii) difficulty on sharing schemas and incompatible data from sharing partners; and iv) inconsistent data under schema evolution. In this paper, we develop a collaborative data sharing system SciPort, to support consistency preserved data sharing among multiple distributed organizations. The system first provides Central Server based lightweight data integration architecture, so data and schemas can be conveniently shared across multiple organizations. Through distributed schema management, schema sharing and evolution is made possible, while data consistency is maintained and data compatibility is enforced. With this data sharing system, distributed sites can now consistently share their research data and their associated schemas with much convenience and flexibility. SciPort has been successfully used for data sharing in biomedical research, clinical trials and large scale research collaboration.

  1. Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

    PubMed Central

    Cheng, Ching-Yu; Schache, Maria; Ikram, M. Kamran; Young, Terri L.; Guggenheim, Jeremy A.; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J.M.; Barathi, Veluchamy A.; Liao, Jiemin; Hysi, Pirro G.; Bailey-Wilson, Joan E.; St. Pourcain, Beate; Kemp, John P.; McMahon, George; Timpson, Nicholas J.; Evans, David M.; Montgomery, Grant W.; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F.; Amin, Najaf; van Leeuwen, Elisabeth M.; Wilson, James F.; Pennell, Craig E.; van Duijn, Cornelia M.; de Jong, Paulus T.V.M.; Vingerling, Johannes R.; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Rahi, Jugnoo S.; Hysi, Pirro G.; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Delcourt, Cécile; Maubaret, Cecilia; Williams, Cathy; Guggenheim, Jeremy A.; Northstone, Kate; Ring, Susan M.; Davey-Smith, George; Craig, Jamie E.; Burdon, Kathryn P.; Fogarty, Rhys D.; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Stambolian, Dwight; Wilson, Joan E. Bailey; MacGregor, Stuart; Lu, Yi; Jonas, Jost B.; Xu, Liang; Saw, Seang-Mei; Baird, Paul N.; Rochtchina, Elena; Mitchell, Paul; Wang, Jie Jin; Jonas, Jost B.; Nangia, Vinay; Hayward, Caroline; Wright, Alan F.; Vitart, Veronique; Polasek, Ozren; Campbell, Harry; Vitart, Veronique; Rudan, Igor; Vatavuk, Zoran; Vitart, Veronique; Paterson, Andrew D.; Hosseini, S. Mohsen; Iyengar, Sudha K.; Igo, Robert P.; Fondran, Jeremy R.; Young, Terri L.; Feng, Sheng; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Metspalu, Andres; Haller, Toomas; Mihailov, Evelin; Pärssinen, Olavi; Wedenoja, Juho; Wilson, Joan E. Bailey; Wojciechowski, Robert; Baird, Paul N.; Schache, Maria; Pfeiffer, Norbert; Höhn, René; Pang, Chi Pui; Chen, Peng; Meitinger, Thomas; Oexle, Konrad; Wegner, Aharon; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Pärssinen, Olavi; Yip, Shea Ping; Ho, Daniel W.H.; Pirastu, Mario; Murgia, Federico; Portas, Laura; Biino, Genevra; Wilson, James F.; Fleck, Brian; Vitart, Veronique; Stambolian, Dwight; Wilson, Joan E. Bailey; Hewitt, Alex W.; Ang, Wei; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Tai, E-Shyong; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Mackey, David A.; MacGregor, Stuart; Hammond, Christopher J.; Hysi, Pirro G.; Deangelis, Margaret M.; Morrison, Margaux; Zhou, Xiangtian; Chen, Wei; Paterson, Andrew D.; Hosseini, S. Mohsen; Mizuki, Nobuhisa; Meguro, Akira; Lehtimäki, Terho; Mäkelä, Kari-Matti; Raitakari, Olli; Kähönen, Mika; Burdon, Kathryn P.; Craig, Jamie E.; Iyengar, Sudha K.; Igo, Robert P.; Lass, Jonathan H.; Reinhart, William; Belin, Michael W.; Schultze, Robert L.; Morason, Todd; Sugar, Alan; Mian, Shahzad; Soong, Hunson Kaz; Colby, Kathryn; Jurkunas, Ula; Yee, Richard; Vital, Mark; Alfonso, Eduardo; Karp, Carol; Lee, Yunhee; Yoo, Sonia; Hammersmith, Kristin; Cohen, Elisabeth; Laibson, Peter; Rapuano, Christopher; Ayres, Brandon; Croasdale, Christopher; Caudill, James; Patel, Sanjay; Baratz, Keith; Bourne, William; Maguire, Leo; Sugar, Joel; Tu, Elmer; Djalilian, Ali; Mootha, Vinod; McCulley, James; Bowman, Wayne; Cavanaugh, H. Dwight; Verity, Steven; Verdier, David; Renucci, Ann; Oliva, Matt; Rotkis, Walter; Hardten, David R.; Fahmy, Ahmad; Brown, Marlene; Reeves, Sherman; Davis, Elizabeth A.; Lindstrom, Richard; Hauswirth, Scott; Hamilton, Stephen; Lee, W. Barry; Price, Francis; Price, Marianne; Kelly, Kathleen; Peters, Faye; Shaughnessy, Michael; Steinemann, Thomas; Dupps, B.J.; Meisler, David M.; Mifflin, Mark; Olson, Randal; Aldave, Anthony; Holland, Gary; Mondino, Bartly J.; Rosenwasser, George; Gorovoy, Mark; Dunn, Steven P.; Heidemann, David G.; Terry, Mark; Shamie, Neda; Rosenfeld, Steven I.; Suedekum, Brandon; Hwang, David; Stone, Donald; Chodosh, James; Galentine, Paul G.; Bardenstein, David; Goddard, Katrina; Chin, Hemin; Mannis, Mark; Varma, Rohit; Borecki, Ingrid; Chew, Emily Y.; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L.; Wojciechowski, Robert; Höhn, René; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J.; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N.A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C.A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G.; Blackwell, Jenefer M.; Brown, Matthew A.; Corvin, Aiden; Spencer, Chris C.A.; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M.; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E.; Hosseini, S. Mohsen; Paterson, Andrew D.; Genuth, S.; Nathan, D.M.; Zinman, B.; Crofford, O.; Crandall, J.; Reid, M.; Brown-Friday, J.; Engel, S.; Sheindlin, J.; Martinez, H.; Shamoon, H.; Engel, H.; Phillips, M.; Gubitosi-Klug, R.; Mayer, L.; Pendegast, S.; Zegarra, H.; Miller, D.; Singerman, L.; Smith-Brewer, S.; Novak, M.; Quin, J.; Dahms, W.; Genuth, Saul; Palmert, M.; Brillon, D.; Lackaye, M.E.; Kiss, S.; Chan, R.; Reppucci, V.; Lee, T.; Heinemann, M.; Whitehouse, F.; Kruger, D.; Jones, J.K.; McLellan, M.; Carey, J.D.; Angus, E.; Thomas, A.; Galprin, A.; Bergenstal, R.; Johnson, M.; Spencer, M.; Morgan, K.; Etzwiler, D.; Kendall, D.; Aiello, Lloyd Paul; Golden, E.; Jacobson, A.; Beaser, R.; Ganda, O.; Hamdy, O.; Wolpert, H.; Sharuk, G.; Arrigg, P.; Schlossman, D.; Rosenzwieg, J.; Rand, L.; Nathan, D.M.; Larkin, M.; Ong, M.; Godine, J.; Cagliero, E.; Lou, P.; Folino, K.; Fritz, S.; Crowell, S.; Hansen, K.; Gauthier-Kelly, C.; Service, J.; Ziegler, G.; Luttrell, L.; Caulder, S.; Lopes-Virella, M.; Colwell, J.; Soule, J.; Fernandes, J.; Hermayer, K.; Kwon, S.; Brabham, M.; Blevins, A.; Parker, J.; Lee, D.; Patel, N.; Pittman, C.; Lindsey, P.; Bracey, M.; Lee, K.; Nutaitis, M.; Farr, A.; Elsing, S.; Thompson, T.; Selby, J.; Lyons, T.; Yacoub-Wasef, S.; Szpiech, M.; Wood, D.; Mayfield, R.; Molitch, M.; Schaefer, B.; Jampol, L.; Lyon, A.; Gill, M.; Strugula, Z.; Kaminski, L.; Mirza, R.; Simjanoski, E.; Ryan, D.; Kolterman, O.; Lorenzi, G.; Goldbaum, M.; Sivitz, W.; Bayless, M.; Counts, D.; Johnsonbaugh, S.; Hebdon, M.; Salemi, P.; Liss, R.; Donner, T.; Gordon, J.; Hemady, R.; Kowarski, A.; Ostrowski, D.; Steidl, S.; Jones, B.; Herman, W.H.; Martin, C.L.; Pop-Busui, R.; Sarma, A.; Albers, J.; Feldman, E.; Kim, K.; Elner, S.; Comer, G.; Gardner, T.; Hackel, R.; Prusak, R.; Goings, L.; Smith, A.; Gothrup, J.; Titus, P.; Lee, J.; Brandle, M.; Prosser, L.; Greene, D.A.; Stevens, M.J.; Vine, A.K.; Bantle, J.; Wimmergren, N.; Cochrane, A.; Olsen, T.; Steuer, E.; Rath, P.; Rogness, B.; Hainsworth, D.; Goldstein, D.; Hitt, S.; Giangiacomo, J.; Schade, D.S.; Canady, J.L.; Chapin, J.E.; Ketai, L.H.; Braunstein, C.S.; Bourne, P.A.; Schwartz, S.; Brucker, A.; Maschak-Carey, B.J.; Baker, L.; Orchard, T.; Silvers, N.; Ryan, C.; Songer, T.; Doft, B.; Olson, S.; Bergren, R.L.; Lobes, L.; Rath, P. Paczan; Becker, D.; Rubinstein, D.; Conrad, P.W.; Yalamanchi, S.; Drash, A.; Morrison, A.; Bernal, M.L.; Vaccaro-Kish, J.; Malone, J.; Pavan, P.R.; Grove, N.; Iyer, M.N.; Burrows, A.F.; Tanaka, E.A.; Gstalder, R.; Dagogo-Jack, S.; Wigley, C.; Ricks, H.; Kitabchi, A.; Murphy, M.B.; Moser, S.; Meyer, D.; Iannacone, A.; Chaum, E.; Yoser, S.; Bryer-Ash, M.; Schussler, S.; Lambeth, H.; Raskin, P.; Strowig, S.; Zinman, B.; Barnie, A.; Devenyi, R.; Mandelcorn, M.; Brent, M.; Rogers, S.; Gordon, A.; Palmer, J.; Catton, S.; Brunzell, J.; Wessells, H.; de Boer, I.H.; Hokanson, J.; Purnell, J.; Ginsberg, J.; Kinyoun, J.; Deeb, S.; Weiss, M.; Meekins, G.; Distad, J.; Van Ottingham, L.; Dupre, J.; Harth, J.; Nicolle, D.; Driscoll, M.; Mahon, J.; Canny, C.; May, M.; Lipps, J.; Agarwal, A.; Adkins, T.; Survant, L.; Pate, R.L.; Munn, G.E.; Lorenz, R.; Feman, S.; White, N.; Levandoski, L.; Boniuk, I.; Grand, G.; Thomas, M.; Joseph, D.D.; Blinder, K.; Shah, G.; Boniuk; Burgess; Santiago, J.; Tamborlane, W.; Gatcomb, P.; Stoessel, K.; Taylor, K.; Goldstein, J.; Novella, S.; Mojibian, H.; Cornfeld, D.; Lima, J.; Bluemke, D.; Turkbey, E.; van der Geest, R.J.; Liu, C.; Malayeri, A.; Jain, A.; Miao, C.; Chahal, H.; Jarboe, R.; Maynard, J.; Gubitosi-Klug, R.; Quin, J.; Gaston, P.; Palmert, M.; Trail, R.; Dahms, W.; Lachin, J.; Cleary, P.; Backlund, J.; Sun, W.; Braffett, B.; Klumpp, K.; Chan, K.; Diminick, L.; Rosenberg, D.; Petty, B.; Determan, A.; Kenny, D.; Rutledge, B.; Younes, Naji; Dews, L.; Hawkins, M.; Cowie, C.; Fradkin, J.; Siebert, C.; Eastman, R.; Danis, R.; Gangaputra, S.; Neill, S.; Davis, M.; Hubbard, L.; Wabers, H.; Burger, M.; Dingledine, J.; Gama, V.; Sussman, R.; Steffes, M.; Bucksa, J.; Nowicki, M.; Chavers, B.; O’Leary, D.; Polak, J.; Harrington, A.; Funk, L.; Crow, R.; Gloeb, B.; Thomas, S.; O’Donnell, C.; Soliman, E.; Zhang, Z.M.; Prineas, R.; Campbell, C.; Ryan, C.; Sandstrom, D.; Williams, T.; Geckle, M.; Cupelli, E.; Thoma, F.; Burzuk, B.; Woodfill, T.; Low, P.; Sommer, C.; Nickander, K.; Budoff, M.; Detrano, R.; Wong, N.; Fox, M.; Kim, L.; Oudiz, R.; Weir, G.; Espeland, M.; Manolio, T.; Rand, L.; Singer, D.; Stern, M.; Boulton, A.E.; Clark, C.; D’Agostino, R.; Lopes-Virella, M.; Garvey, W.T.; Lyons, T.J.; Jenkins, A.; Virella, G.; Jaffa, A.; Carter, Rickey; Lackland, D.; Brabham, M.; McGee, D.; Zheng, D.; Mayfield, R.K.; Boright, A.; Bull, S.; Sun, L.; Scherer, S.; Zinman, B.; Natarajan, R.; Miao, F.; Zhang, L.; Chen;, Z.; Nathan, D.M.; Makela, Kari-Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K.H.; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J.; Zhao, Jing Hua; Vithana, Eranga; Tai, E-Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G.; Bencic, Goran; Khor, Chiea-Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W.; Williams, Cathy; Oostra, Ben A.; Teo, Yik-Ying; Hammond, Christopher J.; Stambolian, Dwight; Mackey, David A.; Klaver, Caroline C.W.; Wong, Tien-Yin; Saw, Seang-Mei; Baird, Paul N.

    2013-01-01

    Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways. PMID:24144296

  2. Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

    PubMed

    Cheng, Ching-Yu; Schache, Maria; Ikram, M Kamran; Young, Terri L; Guggenheim, Jeremy A; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J M; Barathi, Veluchamy A; Liao, Jiemin; Hysi, Pirro G; Bailey-Wilson, Joan E; St Pourcain, Beate; Kemp, John P; McMahon, George; Timpson, Nicholas J; Evans, David M; Montgomery, Grant W; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F; Amin, Najaf; van Leeuwen, Elisabeth M; Wilson, James F; Pennell, Craig E; van Duijn, Cornelia M; de Jong, Paulus T V M; Vingerling, Johannes R; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Burdon, Kathryn P; Craig, Jamie E; Iyengar, Sudha K; Igo, Robert P; Lass, Jonathan H; Chew, Emily Y; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L; Wojciechowski, Robert; Höhn, René; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E; Hosseini, S Mohsen; Paterson, Andrew D; Makela, Kari-Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K H; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J; Zhao, Jing Hua; Vithana, Eranga; Tai, E-Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G; Bencic, Goran; Khor, Chiea-Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W; Williams, Cathy; Oostra, Ben A; Teo, Yik-Ying; Hammond, Christopher J; Stambolian, Dwight; Mackey, David A; Klaver, Caroline C W; Wong, Tien-Yin; Saw, Seang-Mei; Baird, Paul N

    2013-08-08

    Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.

  3. S-SCAM, A Rare Copy Number Variation Gene, Induces Schizophrenia-Related Endophenotypes in Transgenic Mouse Model

    PubMed Central

    Zhang, Nanyan; Zhong, Peng; Shin, Seung Min; Metallo, Jacob; Danielson, Eric; Olsen, Christopher M.; Liu, Qing-song

    2015-01-01

    Accumulating genetic evidence suggests that schizophrenia (SZ) is associated with individually rare copy number variations (CNVs) of diverse genes, often specific to single cases. However, the causality of these rare mutations remains unknown. One of the rare CNVs found in SZ cohorts is the duplication of Synaptic Scaffolding Molecule (S-SCAM, also called MAGI-2), which encodes a postsynaptic scaffolding protein controlling synaptic AMPA receptor levels, and thus the strength of excitatory synaptic transmission. Here we report that, in a transgenic mouse model simulating the duplication conditions, elevation of S-SCAM levels in excitatory neurons of the forebrain was sufficient to induce multiple SZ-related endophenotypes. S-SCAM transgenic mice showed an increased number of lateral ventricles and a reduced number of parvalbumin-stained neurons. In addition, the mice exhibited SZ-like behavioral abnormalities, including hyperlocomotor activity, deficits in prepulse inhibition, increased anxiety, impaired social interaction, and working memory deficit. Notably, the S-SCAM transgenic mice showed a unique sex difference in showing these behavioral symptoms, which is reminiscent of human conditions. These behavioral abnormalities were accompanied by hyperglutamatergic function associated with increased synaptic AMPA receptor levels and impaired long-term potentiation. Importantly, reducing glutamate release by the group 2 metabotropic glutamate receptor agonist LY379268 ameliorated the working memory deficits in the transgenic mice, suggesting that hyperglutamatergic function underlies the cognitive functional deficits. Together, these results contribute to validate a causal relationship of the rare S-SCAM CNV and provide supporting evidence for the rare CNV hypothesis in SZ pathogenesis. Furthermore, the S-SCAM transgenic mice provide a valuable new animal model for studying SZ pathogenesis. PMID:25653350

  4. 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.

  5. 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

  6. 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…

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

    PubMed Central

    Markotic, Filipa; Puljak, Livia

    2016-01-01

    Background 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. Methods This qualitative study was conducted by semi-structured interviews among PMPs employed in Croatian pain clinics. The study involved two researchers and 15 PMPs. Results 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. Conclusion 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. PMID:27942233

  8. Neurological soft signs might be endophenotype candidates for patients with deficit syndrome schizophrenia

    PubMed Central

    Albayrak, Yakup; Akyol, Esra Soydaş; Beyazyüz, Murat; Baykal, Saliha; Kuloglu, Murat

    2015-01-01

    Background Schizophrenia is a chronic, disabling, disorder that affects approximately 1% of the population. The nature of schizophrenia is heterogeneous, and unsuccessful efforts to subtype this disorder have been made. Deficit syndrome schizophrenia (DS) is a clinical diagnosis that has not been placed in main diagnostic manuals. In this study, we aimed to investigate and compare neurological soft signs (NSS) in DS patients, non-deficit schizophrenia (NDS) patients, and healthy controls (HCs). We suggest that NSS might be an endophenotype candidate for DS patients. Methods Sixty-six patients with schizophrenia and 30 HCs were enrolled in accordance with our inclusion and exclusion criteria. The patients were sub-typed as DS (n=24) and NDS (n=42) according to the Schedule for the Deficit Syndrome. The three groups were compared in terms of sociodemographic and clinical variables and total scores and subscores on the Physical and Neurological Examination for Soft Signs (PANESS). Following the comparison, a regression analysis was performed for predictability of total PANESS score and its subscales in the diagnosis of DS and NDS. Results The groups were similar in terms of age, sex, and smoking status. The results of our study indicated that the total PANESS score was significantly higher in the DS group compared to the NDS and HC groups, and all PANESS subscales were significantly higher in the DS group than in the HC group. The diagnosis of DS was predicted significantly by total PANESS score (P<0.001, odds ratio =9.48, 95% confidence interval: 0.00–4.56); the synergy, graphesthesia, stereognosis, motor tasks, and ability to maintain posture subscales were found to be significant predictors. Conclusion This study confirms that NSS were higher in patients with DS. In addition, we suggest that our results might support the notion of DS as a different and distinct type of schizophrenia. NSS might also be a promising candidate as an endophenotype for DS. However

  9. A Transient Receptor Potential Ion Channel in Chlamydomonas Shares Key Features with Sensory Transduction-Associated TRP Channels in Mammals

    PubMed Central

    Arias-Darraz, Luis; Cabezas, Deny; Colenso, Charlotte K.; Alegría-Arcos, Melissa; Bravo-Moraga, Felipe; Varas-Concha, Ignacio; Almonacid, Daniel E.; Madrid, Rodolfo; Brauchi, Sebastian

    2015-01-01

    Sensory modalities are essential for navigating through an ever-changing environment. From insects to mammals, transient receptor potential (TRP) channels are known mediators for cellular sensing. Chlamydomonas reinhardtii is a motile single-celled freshwater green alga that is guided by photosensory, mechanosensory, and chemosensory cues. In this type of alga, sensory input is first detected by membrane receptors located in the cell body and then transduced to the beating cilia by membrane depolarization. Although TRP channels seem to be absent in plants, C. reinhardtii possesses genomic sequences encoding TRP proteins. Here, we describe the cloning and characterization of a C. reinhardtii version of a TRP channel sharing key features present in mammalian TRP channels associated with sensory transduction. In silico sequence-structure analysis unveiled the modular design of TRP channels, and electrophysiological experiments conducted on Human Embryonic Kidney-293T cells expressing the Cr-TRP1 clone showed that many of the core functional features of metazoan TRP channels are present in Cr-TRP1, suggesting that basic TRP channel gating characteristics evolved early in the history of eukaryotes. PMID:25595824

  10. Understanding Neuropsychiatric Diseases, Analyzing the Peptide Sharing between Infectious Agents and the Language-Associated NMDA 2A Protein

    PubMed Central

    Lucchese, Guglielmo

    2016-01-01

    Language disorders and infections may occur together and often concur, to a different extent and via different modalities, in characterizing brain pathologies, such as schizophrenia, autism, epilepsies, bipolar disorders, frontotemporal neurodegeneration, and encephalitis, inter alia. The biological mechanism(s) that might channel language dysfunctions and infections into etiological pathways connected to neuropathologic sequelae are unclear. Searching for molecular link(s) between language disorders and infections, the present study explores the language-associated NMDA 2A subunit for peptide sharing with pathogens that have been described in concomitance with neuropsychiatric diseases. It was found that a vast peptide commonality links the human glutamate ionotropic receptor NMDA 2A subunit to infectious agents. Such a link expands to and interfaces with neuropsychiatric disorders in light of the specific allocation of NMDA 2A gene expression in brain areas related to language functions. The data hint at a possible pathologic scenario based on anti-pathogen immune responses cross-reacting with NMDA 2A in the brain. PMID:27148089

  11. The Autism-Spectrum Quotient and Visual Search: Shallow and Deep Autistic Endophenotypes.

    PubMed

    Gregory, B L; Plaisted-Grant, K C

    2016-05-01

    A high Autism-Spectrum Quotient (AQ) score (Baron-Cohen et al. in J Autism Dev Disord 31(1):5-17, 2001) is increasingly used as a proxy in empirical studies of perceptual mechanisms in autism. Several investigations have assessed perception in non-autistic people measured for AQ, claiming the same relationship exists between performance on perceptual tasks in high-AQ individuals as observed in autism. We question whether the similarity in performance by high-AQ individuals and autistics reflects the same underlying perceptual cause in the context of two visual search tasks administered to a large sample of typical individuals assessed for AQ. Our results indicate otherwise and that deploying the AQ as a proxy for autism introduces unsubstantiated assumptions about high-AQ individuals, the endophenotypes they express, and their relationship to Autistic Spectrum Conditions (ASC) individuals.

  12. L-type Ca(2+) 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 Cav 1.2 and Cav 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 Cav 1.2 and Cav 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.

  13. [A case of shared psychotic disorder (folie à deux) with original aspects associated with cross-cultural elements].

    PubMed

    Cuoco, Valentina; Colletti, Chiara; Anastasia, Annalisa; Weisz, Filippo; Bersani, Giuseppe

    2015-01-01

    Shared psychotic disorder (folie à deux) is a rare condition characterized by the transmission of delusional aspects from a patient (the "dominant partner") to another (the "submissive partner") linked to the first by a close relationship. We report the case of two Moroccan sisters who have experienced a combined delusional episode diagnosed as shared psychotic disorder. In these circumstances, assessment of symptoms from a cross-cultural perspective is a key factor for proper diagnostic evaluation.

  14. A neurotropic herpesvirus infecting the gastropod, abalone, shares ancestry with oyster herpesvirus and a herpesvirus associated with the amphioxus genome

    PubMed Central

    2010-01-01

    Background With the exception of the oyster herpesvirus OsHV-1, all herpesviruses characterized thus far infect only vertebrates. Some cause neurological disease in their hosts, while others replicate or become latent in neurological tissues. Recently a new herpesvirus causing ganglioneuritis in abalone, a gastropod, was discovered. Molecular analysis of new herpesviruses, such as this one and others, still to be discovered in invertebrates, will provide insight into the evolution of herpesviruses. Results We sequenced the genome of a neurotropic virus linked to a fatal ganglioneuritis devastating parts of a valuable wild abalone fishery in Australia. We show that the newly identified virus forms part of an ancient clade with its nearest relatives being a herpesvirus infecting bivalves (oyster) and, unexpectedly, one we identified, from published data, apparently integrated within the genome of amphioxus, an invertebrate chordate. Predicted protein sequences from the abalone virus genome have significant similarity to several herpesvirus proteins including the DNA packaging ATPase subunit of (putative) terminase and DNA polymerase. Conservation of amino acid sequences in the terminase across all herpesviruses and phylogenetic analysis using the DNA polymerase and terminase proteins demonstrate that the herpesviruses infecting the molluscs, oyster and abalone, are distantly related. The terminase and polymerase protein sequences from the putative amphioxus herpesvirus share more sequence similarity with those of the mollusc viruses than with sequences from any of the vertebrate herpesviruses analysed. Conclusions A family of mollusc herpesviruses, Malacoherpesviridae, that was based on a single virus infecting oyster can now be further established by including a distantly related herpesvirus infecting abalone, which, like many vertebrate viruses is neurotropic. The genome of Branchiostoma floridae (amphioxus) provides evidence for the existence of a herpesvirus

  15. Association between Dietary Share of Ultra-Processed Foods and Urinary Concentrations of Phytoestrogens in the US

    PubMed Central

    Martínez Steele, Eurídice; Monteiro, Carlos A.

    2017-01-01

    The aim of this study was to examine the relationship between dietary contribution of ultra-processed foods and urinary phytoestrogen concentrations in the US. Participants from cross-sectional 2009–2010 National Health and Nutrition Examination Survey aged 6+ years, selected to measure urinary phytoestrogens and with one 24-h dietary recall were evaluated (2692 participants). Food items were classified according to NOVA (a name, not an acronym), a four-group food classification based on the extent and purpose of industrial food processing. Ultra-processed foods are formulations manufactured using several ingredients and a series of processes (hence “ultra-processed”). Most of their ingredients are lower-cost industrial sources of dietary energy and nutrients, with additives used for the purpose of imitating sensorial qualities of minimally processed foods or of culinary preparations of these foods. Studied phytoestrogens included lignans (enterolactone and enterodiol) and isoflavones (genistein, daidzein, O-desmethylangolensin and equol). Gaussian regression was used to compare average urinary phytoestrogen concentrations (normalized by creatinine) across quintiles of energy share of ultra-processed foods. Models incorporated survey sample weights and were adjusted for age, sex, race/ethnicity, family income, and education, among other factors. Adjusted enterodiol geometric means decreased monotonically from 60.6 in the lowest quintile to 35.1 µg/g creatinine in the highest, while adjusted enterolactone geometric means dropped from 281.1 to 200.1 across the same quintiles, respectively. No significant linear trend was observed in the association between these quintiles and isoflavone concentrations. This finding reinforces the existing evidence regarding the negative impact of ultra-processed food consumption on the overall quality of the diet and expands it to include non-nutrients such as lignans. PMID:28264475

  16. Association between Dietary Share of Ultra-Processed Foods and Urinary Concentrations of Phytoestrogens in the US.

    PubMed

    Martínez Steele, Eurídice; Monteiro, Carlos A

    2017-02-28

    The aim of this study was to examine the relationship between dietary contribution of ultra-processed foods and urinary phytoestrogen concentrations in the US. Participants from cross-sectional 2009-2010 National Health and Nutrition Examination Survey aged 6+ years, selected to measure urinary phytoestrogens and with one 24-h dietary recall were evaluated (2692 participants). Food items were classified according to NOVA (a name, not an acronym), a four-group food classification based on the extent and purpose of industrial food processing. Ultra-processed foods are formulations manufactured using several ingredients and a series of processes (hence "ultra-processed"). Most of their ingredients are lower-cost industrial sources of dietary energy and nutrients, with additives used for the purpose of imitating sensorial qualities of minimally processed foods or of culinary preparations of these foods. Studied phytoestrogens included lignans (enterolactone and enterodiol) and isoflavones (genistein, daidzein, O-desmethylangolensin and equol). Gaussian regression was used to compare average urinary phytoestrogen concentrations (normalized by creatinine) across quintiles of energy share of ultra-processed foods. Models incorporated survey sample weights and were adjusted for age, sex, race/ethnicity, family income, and education, among other factors. Adjusted enterodiol geometric means decreased monotonically from 60.6 in the lowest quintile to 35.1 µg/g creatinine in the highest, while adjusted enterolactone geometric means dropped from 281.1 to 200.1 across the same quintiles, respectively. No significant linear trend was observed in the association between these quintiles and isoflavone concentrations. This finding reinforces the existing evidence regarding the negative impact of ultra-processed food consumption on the overall quality of the diet and expands it to include non-nutrients such as lignans.

  17. Association of implementation of a public bicycle share program with intention and self-efficacy: The moderating role of socioeconomic status.

    PubMed

    Bélanger-Gravel, Ariane; Gauvin, Lise; Fuller, Daniel; Drouin, Louis

    2016-06-01

    This natural experiment examines the effect of a public bicycle share program on cognitions and investigates the moderating influence of socioeconomic status on this effect. Two cross-sectional population-based surveys were conducted. Intention and self-efficacy to use the public bicycle share program were assessed by questionnaire. A difference-in-differences approach was adopted using logistic regression analyses. A significant effect of the public bicycle share program was observed on intention (exposure × time; odds ratio = 3.41; 95% confidence interval: 1.50-7.73) and self-efficacy (exposure; odds ratio = 1.61; 95% confidence interval: 1.28-2.01). A positive effect on intention was observed among individuals with low income (exposure × time; odds ratio = 27.85; 95% confidence interval: 2.51-309.25). Implementing a public bicycle share program is associated with increases in intention and self-efficacy for public bicycle share use, although some social inequalities persist.

  18. Sharing code.

    PubMed

    Kubilius, Jonas

    2014-01-01

    Sharing code is becoming increasingly important in the wake of Open Science. In this review I describe and compare two popular code-sharing utilities, GitHub and Open Science Framework (OSF). GitHub is a mature, industry-standard tool but lacks focus towards researchers. In comparison, OSF offers a one-stop solution for researchers but a lot of functionality is still under development. I conclude by listing alternative lesser-known tools for code and materials sharing.

  19. Endophenotypes of Dementia Associated with Traumatic Brain Injury in Retired Military Personnel

    DTIC Science & Technology

    2013-10-01

    condition (such as epilepsy, multiple sclerosis , cortical stroke, hypoxic-ischemic encephalopathy, encephalitis or schizophrenia) o Lack of competence... multiple sclerosis , cortical stroke, hypoxic-ischemic encephalopathy, encephalitis or schizophrenia) o Lack of competence to provide consent to...hospitalization. Compared to those without  TBI, those with TBI had higher levels of  depression  (61.3% for hospitalization group vs. 55.3% for head

  20. Endophenotypes of Dementia Associated with Traumatic Brain Injury in Retired Military Personnel

    DTIC Science & Technology

    2015-06-01

    neuropsychological results, is in preparation. The results of this study show that older veterans with past TBI have a specific clinical and... neuropsychological phenotype, which has relevance for future treatment. 15. SUBJECT TERMS Traumatic brain injury (TBI), dementia, chronic traumatic...Kramer trained all study personnel on the administration of the neuropsychological tests; Dr. Kramer traveled to HJF and select HJF study staff

  1. Endophenotypes of Dementia Associated with Traumatic Brain Injury in Retired Military Personnel

    DTIC Science & Technology

    2014-10-01

    ischemic encephalopathy, encephalitis or schizophrenia ) o Lack of competence to provide consent to participate in research o No verbal and oral fluency... schizophrenia ) o Lack of competence to provide consent to participate in research o No verbal and oral fluency English o Non‐correctable vision or hearing impairments (severe enough to impair testing)

  2. You Say Potato, I Say Potato: Problems Associated with the Lack of Shared Meaning in Instruction and Learning.

    ERIC Educational Resources Information Center

    Stork, Steve; Sanders, Stephen W.

    2000-01-01

    Physical educators and their students often perceive physical education differently. Lack of shared meaning can negatively affect instruction, participation, and learning. Teachers often incorrectly assume that differing responses to instruction reflect off-task behavior. The paper examines the issue, presents implications for teaching and teacher…

  3. Executive Cognitive Dysfunction and ADHD in Cocaine Dependence: Searching for a Common Cognitive Endophenotype for Addictive Disorders

    PubMed Central

    Cunha, Paulo Jannuzzi; Gonçalves, Priscila Dib; Ometto, Mariella; dos Santos, Bernardo; Nicastri, Sergio; Busatto, Geraldo F.; de Andrade, Arthur Guerra

    2013-01-01

    Background: Cocaine-dependent individuals (CDI) present executive cognitive function (ECF) deficits, but the impact of psychiatric comorbidities such as Attention-Deficit Hyperactivity Disorder (ADHD) on neuropsychological functioning is still poorly understood. The aim of this study was to investigate if CDI with ADHD (CDI + ADHD) would have a distinct pattern of executive functioning when compared with CDI without ADHD (CDI). Methods: We evaluated 101 adults, including 69 cocaine-dependent subjects (divided in CDI and CDI + ADHD) and 32 controls. ECF domains were assessed with Digits Forward (DF), Digits Backward (DB), Stroop Color Word Test (SCWT), the Wisconsin Card Sorting Test (WCST), and the Frontal Assessment Battery (FAB). DSM-IV criteria for ADHD were used for diagnosis and previous ADHD symptoms (in the childhood) were retrospectively assessed by the Wender-Utah Rating Scale (WURS). Results: There were no significant differences between CDI + ADHD, CDI, and controls in estimated intellectual quotient (IQ), socioeconomic background, education (in years), and pre-morbid IQ (p > 0.05). SCWT and WCST scores did not differ across groups (p > 0.05). Nevertheless, CDI and CDI + ADHD performed more poorly than controls in total score of the FAB (p < 0.05). Also, CDI + ADHD did worse than CDI on DF (F = 4.756, p = 0.011), DB (F = 8.037, p = 0.001), Conceptualization/FAB (F = 4.635, p = 0.012), and Mental flexibility/FAB (F = 3.678, p = 0.029). We did not find correlations between cocaine-use variables and neuropsychological functioning, but previous ADHD symptoms assessed by WURS were negatively associated with DF (p = 0.016) and with the total score of the FAB (p = 0.017). Conclusion: CDI + ADHD presented more pronounced executive alterations than CDI and CDI exhibited poorer cognitive functioning than controls. Pre-existing ADHD symptoms may have a significant negative impact on

  4. The Broad Autism (Endo)Phenotype: Neurostructural and Neurofunctional Correlates in Parents of Individuals with Autism Spectrum Disorders

    PubMed Central

    Billeci, Lucia; Calderoni, Sara; Conti, Eugenia; Gesi, Camilla; Carmassi, Claudia; Dell'Osso, Liliana; Cioni, Giovanni; Muratori, Filippo; Guzzetta, Andrea

    2016-01-01

    Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with an early-onset and a strong genetic component in their pathogenesis. According to genetic and epidemiological data, ASD relatives present personality traits similar to, but not as severe as the defining features of ASD, which have been indicated as the “Broader Autism Phenotype” (BAP). BAP features seem to be more prevalent in first-degree relatives of individuals with ASD than in the general population. Characterizing brain profiles of relatives of autistic probands may help to understand ASD endophenotype. The aim of this review was to provide an up-to-date overview of research findings on the neurostructural and neurofunctional substrates in parents of individuals with ASD (pASD). The primary hypothesis was that, like for the behavioral profile, the pASD express an intermediate neurobiological pattern between ASD individuals and healthy controls. The 13 reviewed studies evaluated structural magnetic resonance imaging (MRI) brain volumes, chemical signals using magnetic resonance spectroscopy (MRS), task-related functional activation by functional magnetic resonance imaging (fMRI), electroencephalography (EEG), or magnetoencephalography (MEG) in pASD.The studies showed that pASD are generally different from healthy controls at a structural and functional level despite often not behaviorally impaired. More atypicalities in neural patterns of pASD seem to be associated with higher scores at BAP assessment. Some of the observed atypicalities are the same of the ASD probands. In addition, the pattern of neural correlates in pASD resembles that of adult individuals with ASD, or it is specific, possibly due to a compensatory mechanism. Future studies should ideally include a group of pASD and HC with their ASD and non-ASD probands respectively. They should subgrouping the pASD according to the BAP scores, considering gender as a possible confounding factor, and correlating these scores

  5. 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

  6. Clinical phenotypes and endophenotypes of atopic dermatitis: Where are we, and where should we go?

    PubMed

    Bieber, Thomas; D'Erme, Angelo M; Akdis, Cezmi A; Traidl-Hoffmann, Claudia; Lauener, Roger; Schäppi, Georg; Schmid-Grendelmeier, Peter

    2017-04-01

    Atopic dermatitis (AD) is a paradigmatic chronic inflammatory skin disease characterized by a complex pathophysiology and a wide spectrum of the clinical phenotype. Despite this high degree of heterogeneity, AD is still considered a single disease and usually treated according to the "one-size-fits-all" approach. Thus more tailored prevention and therapeutic strategies are still lacking. As for other disciplines, such as oncology or rheumatology, we have to approach AD in a more differentiated way (ie, to dissect and stratify the complex clinical phenotype into more homogeneous subgroups based on the endophenotype [panel of biomarkers]) with the aim to refine the management of this condition. Because we are now entering the era of personalized medicine, a systems biology approach merging the numerous clinical phenotypes with robust (ie, relevant and validated) biomarkers will be needed to best exploit their potential significance for the future molecular taxonomy of AD. This approach will not only allow an optimized prevention and treatment with the available drugs but also hopefully help assign newly developed medicinal products to those patients who will have the best benefit/risk ratio.

  7. 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

  8. Shared Attention.

    PubMed

    Shteynberg, Garriy

    2015-09-01

    Shared attention is extremely common. In stadiums, public squares, and private living rooms, people attend to the world with others. Humans do so across all sensory modalities-sharing the sights, sounds, tastes, smells, and textures of everyday life with one another. The potential for attending with others has grown considerably with the emergence of mass media technologies, which allow for the sharing of attention in the absence of physical co-presence. In the last several years, studies have begun to outline the conditions under which attending together is consequential for human memory, motivation, judgment, emotion, and behavior. Here, I advance a psychological theory of shared attention, defining its properties as a mental state and outlining its cognitive, affective, and behavioral consequences. I review empirical findings that are uniquely predicted by shared-attention theory and discuss the possibility of integrating shared-attention, social-facilitation, and social-loafing perspectives. Finally, I reflect on what shared-attention theory implies for living in the digital world.

  9. Sharing code

    PubMed Central

    Kubilius, Jonas

    2014-01-01

    Sharing code is becoming increasingly important in the wake of Open Science. In this review I describe and compare two popular code-sharing utilities, GitHub and Open Science Framework (OSF). GitHub is a mature, industry-standard tool but lacks focus towards researchers. In comparison, OSF offers a one-stop solution for researchers but a lot of functionality is still under development. I conclude by listing alternative lesser-known tools for code and materials sharing. PMID:25165519

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

    PubMed

    Ellinghaus, David; Jostins, Luke; Spain, Sarah L; Cortes, Adrian; Bethune, Jörn; Han, Buhm; Park, Yu Rang; Raychaudhuri, Soumya; Pouget, Jennie G; Hübenthal, Matthias; Folseraas, Trine; Wang, Yunpeng; Esko, Tonu; Metspalu, Andres; Westra, Harm-Jan; Franke, Lude; Pers, Tune H; Weersma, Rinse K; Collij, Valerie; D'Amato, Mauro; Halfvarson, Jonas; Jensen, Anders Boeck; Lieb, Wolfgang; Degenhardt, Franziska; Forstner, Andreas J; Hofmann, Andrea; Schreiber, Stefan; Mrowietz, Ulrich; Juran, Brian D; Lazaridis, Konstantinos N; Brunak, Søren; Dale, Anders M; Trembath, Richard C; Weidinger, Stephan; Weichenthal, Michael; Ellinghaus, Eva; Elder, James T; Barker, Jonathan N W N; Andreassen, Ole A; McGovern, Dermot P; Karlsen, Tom H; Barrett, Jeffrey C; Parkes, Miles; Brown, Matthew A; Franke, Andre

    2016-05-01

    We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.

  16. Dissociation of decision making under ambiguity and decision making under risk: a neurocognitive endophenotype candidate for obsessive-compulsive disorder.

    PubMed

    Zhang, Long; Dong, Yi; Ji, Yifu; Zhu, Chunyan; Yu, Fengqiong; Ma, Huijuan; Chen, Xingui; Wang, Kai

    2015-03-03

    Evidence in the literature suggests that executive dysfunction is regarded as an endophenotype candidate for obsessive-compulsive disorder (OCD). Decision making is an important domain of executive function. However, few studies that have investigated whether decision making is a potential endophenotype for OCD have produced inconsistent results. Differences in the findings across these studies may be attributed to several factors: different study materials, comorbidity, medication, etc. There are at least two types of decision making that differ mainly in the degree of uncertainty and how much useful information about consequences and their probabilities are provided to the decision maker: decision making under ambiguity and decision making under risk. The aim of the present study was to simultaneously examine decision making under ambiguity as assessed by the Iowa Gambling Task (IGT) and decision making under risk as measured by the Game of Dice Task (GDT) in OCD patients and their unaffected first-degree relative (UFDR) for the first time. The study analyzed 55 medication-naïve, non-depressed OCD patient probands, 55 UFDRs of the OCD patients and 55 healthy matched comparison subjects (CS) without a family history of OCD with the IGT, the GDT and a neuropsychological test battery. While the OCD patients and the UFDRs performed worse than the CS on the IGT, they were unimpaired on the GDT. Our study supports the claim that decision making under ambiguity differs from decision making under risk and suggests that dissociation of decision making under ambiguity and decision making under risk may qualify to be a neurocognitive endophenotypes for OCD.

  17. 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

  18. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci

    PubMed Central

    Ellinghaus, David; Jostins, Luke; Spain, Sarah L; Cortes, Adrian; Bethune, Jörn; Han, Buhm; Park, Yu Rang; Raychaudhuri, Soumya; Pouget, Jennie G; Hübenthal, Matthias; Folseraas, Trine; Wang, Yunpeng; Esko, Tonu; Metspalu, Andres; Westra, Harm-Jan; Franke, Lude; Pers, Tune H; Weersma, Rinse K; Collij, Valerie; D'Amato, Mauro; Halfvarson, Jonas; Jensen, Anders Boeck; Lieb, Wolfgang; Degenhardt, Franziska; Forstner, Andreas J; Hofmann, Andrea; Schreiber, Stefan; Mrowietz, Ulrich; Juran, Brian D; Lazaridis, Konstantinos N; Brunak, Søren; Dale, Anders M; Trembath, Richard C; Weidinger, Stephan; Weichenthal, Michael; Ellinghaus, Eva; Elder, James T; Barker, Jonathan NWN; Andreassen, Ole A; McGovern, Dermot P; Karlsen, Tom H; Barrett, Jeffrey C; Parkes, Miles; Brown, Matthew A; Franke, Andre

    2016-01-01

    We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European-ancestry we identified 244 independent multi-disease signals including 27 novel genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multi-disease signals with expression data sets from human, rat and mouse, and epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases that is genetically identical to another disease, possibly due to diagnostic misclassification, molecular subtypes, or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes. PMID:26974007

  19. Metabolomics of trauma-associated death: shared and fluid-specific features of human plasma vs lymph

    PubMed Central

    D’Alessandro, Angelo; Nemkov, Travis; Moore, Hunter B.; Moore, Ernest E.; Wither, Matthew; Nydam, Trevor; Slaughter, Annie; Silliman, Christopher C.; Banerjee, Anirban; Hansen, Kirk C.

    2016-01-01

    Background Water-soluble components in mesenteric lymph have been implicated in the pathophysiology of acute lung injury and distal organ failure following trauma and haemorrhagic shock. Proteomics analyses have recently shown similarities and specificities of post-trauma/haemorrhagic shock lymph and plasma. We hypothesise that the metabolic phenotype of post-trauma/haemorrhagic shock mesenteric lymph and plasma share common metabolites, but are also characterised by unique features that differentiate these two fluids. Materials and methods Matched samples were collected from 5 brain-dead organ donors who had suffered extreme trauma/haemorrhagic shock. Metabolomics analyses were performed through ultra-high performance liquid chromatography mass spectrometry. Results Overall, 269 metabolites were identified in either fluid. Despite significant overlapping, metabolic phenotypes of matched lymph or plasma from the same patients could be used to discriminate sample fluid or biological patient/traumatic-injury origin. Metabolites showing relatively high levels in both fluids included markers of haemolysis and cell lysis secondary to tissue injury. Discussion High positive correlations were observed between the quantitative levels of markers of systemic metabolic derangement following traumatic/haemorrhagic hypoxaemia, such as succinate, oxoproline, urate and fatty acids. These metabolites might contribute to coagulopathies of trauma and neutrophil priming driving acute lung injury. Future studies will investigate whether the observed compositional specificities mirror functional or pathological adaptations after trauma and haemorrhage. PMID:27177401

  20. The association between lower educational attainment and depression owing to shared genetic effects? Results in ~25,000 subjects.

    PubMed

    Peyrot, W J; Lee, S H; Milaneschi, Y; Abdellaoui, A; Byrne, E M; Esko, T; de Geus, E J C; Hemani, G; Hottenga, J J; Kloiber, S; Levinson, D F; Lucae, S; Martin, N G; Medland, S E; Metspalu, A; Milani, L; Noethen, M M; Potash, J B; Rietschel, M; Rietveld, C A; Ripke, S; Shi, J; Willemsen, G; Zhu, Z; Boomsma, D I; Wray, N R; Penninx, B W J H

    2015-06-01

    An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14,949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15,138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884,105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ~120,000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

  1. Shared genes related to aggression, rather than chemical communication, are associated with reproductive dominance in paper wasps (Polistes metricus)

    PubMed Central

    2014-01-01

    Background In social groups, dominant individuals may socially inhibit reproduction of subordinates using aggressive interactions or, in the case of highly eusocial insects, pheromonal communication. It has been hypothesized these two modes of reproductive inhibition utilize conserved pathways. Here, we use a comparative framework to investigate the chemical and genomic underpinnings of reproductive dominance in the primitively eusocial wasp Polistes metricus. Our goals were to first characterize transcriptomic and chemical correlates of reproductive dominance and second, to test whether dominance-associated mechanisms in paper wasps overlapped with aggression or pheromone-related gene expression patterns in other species. To explore whether conserved molecular pathways relate to dominance, we compared wasp transcriptomic data to previous studies of gene expression associated with pheromonal communication and queen-worker differences in honey bees, and aggressive behavior in bees, Drosophila, and mice. Results By examining dominant and subordinate females from queen and worker castes in early and late season colonies, we found that cuticular hydrocarbon profiles and genome-wide patterns of brain gene expression were primarily associated with season/social environment rather than dominance status. In contrast, gene expression patterns in the ovaries were associated primarily with caste and ovary activation. Comparative analyses suggest genes identified as differentially expressed in wasp brains are not related to queen pheromonal communication or caste in bees, but were significantly more likely to be associated with aggression in other insects (bees, flies), and even a mammal (mice). Conclusions This study provides the first comprehensive chemical and molecular analysis of reproductive dominance in paper wasps. We found little evidence for a chemical basis for reproductive dominance in P. metricus, and our transcriptomic analyses suggest that different pathways

  2. "Not Just Right Experiences" as a psychological endophenotype for obsessive-compulsive disorder: Evidence from an Italian family study.

    PubMed

    Sica, Claudio; Bottesi, Gioia; Caudek, Corrado; Orsucci, Antonella; Ghisi, Marta

    2016-11-30

    The heart of the obsessional process may be considered the subject's underlying impression that "something is wrong" or "that something is not just as it should be". This phenomenon, labeled "not just right experiences" (NJREs), has increasingly been receiving attention as a possible marker of obsessive-compulsive disorder (OCD). The present study sought to add to the evidence that NJREs may be a putative endophenotype of obsessional symptoms. To this aim, measures of NJREs, obsessive-compulsive (OC) symptoms and psychological distress were compared in offspring of parents with and without OC symptoms. The offspring of parents with OC symptoms (N=120) reported higher frequency and severity of NJREs compared to offspring of parents without OC symptoms (N=106). Such differences remained significant for NJREs frequency and close to significance for NJREs severity, when general distress (i.e., anxiety and depression) was controlled. The possible role of NJREs as an endophenotype for OCD is discussed in reference to Gottesman and Gould criteria and the National Institute of Mental Health RDoC initiative.

  3. Sharing the slope: depth partitioning of agariciid corals and associated Symbiodinium across shallow and mesophotic habitats (2-60 m) on a Caribbean reef

    PubMed Central

    2013-01-01

    Background Scleractinian corals and their algal endosymbionts (genus Symbiodinium) exhibit distinct bathymetric distributions on coral reefs. Yet, few studies have assessed the evolutionary context of these ecological distributions by exploring the genetic diversity of closely related coral species and their associated Symbiodinium over large depth ranges. Here we assess the distribution and genetic diversity of five agariciid coral species (Agaricia humilis, A. agaricites, A. lamarcki, A. grahamae, and Helioseris cucullata) and their algal endosymbionts (Symbiodinium) across a large depth gradient (2-60 m) covering shallow to mesophotic depths on a Caribbean reef. Results The five agariciid species exhibited distinct depth distributions, and dominant Symbiodinium associations were found to be species-specific, with each of the agariciid species harbouring a distinct ITS2-DGGE profile (except for a shared profile between A. lamarcki and A. grahamae). Only A. lamarcki harboured different Symbiodinium types across its depth distribution (i.e. exhibited symbiont zonation). Phylogenetic analysis (atp6) of the coral hosts demonstrated a division of the Agaricia genus into two major lineages that correspond to their bathymetric distribution (“shallow”: A. humilis / A. agaricites and “deep”: A. lamarcki / A. grahamae), highlighting the role of depth-related factors in the diversification of these congeneric agariciid species. The divergence between “shallow” and “deep” host species was reflected in the relatedness of the associated Symbiodinium (with A. lamarcki and A. grahamae sharing an identical Symbiodinium profile, and A. humilis and A. agaricites harbouring a related ITS2 sequence in their Symbiodinium profiles), corroborating the notion that brooding corals and their Symbiodinium are engaged in coevolutionary processes. Conclusions Our findings support the hypothesis that the depth-related environmental gradient on reefs has played an important

  4. Satellite NG2 progenitor cells share common glutamatergic inputs with associated interneurons in the mouse dentate gyrus.

    PubMed

    Mangin, Jean-Marie; Kunze, Albrecht; Chittajallu, Ramesh; Gallo, Vittorio

    2008-07-23

    Several studies have provided evidence that NG2-expressing (NG2(+)) progenitor cells are anatomically associated to neurons in gray matter areas. By analyzing the spatial distribution of NG2(+) cells in the hilus of the mouse dentate gyrus, we demonstrate that NG2(+) cells are indeed closely associated to interneurons. To define whether this anatomical proximity reflected a specific physiological interaction, we performed patch-clamp recordings on hilar NG2(+) cells and interneurons between 3 and 21 postnatal days. We first observed that hilar NG2(+) cells exhibit spontaneous glutamatergic EPSCs (sEPSCs) whose frequency and amplitude increase during the first 3 postnatal weeks. At the same time, the rise time and decay time of sEPSCs significantly decreased, suggesting that glutamatergic synapses in NG2(+) cells undergo a maturation process that is reminiscent of what has been reported in neurons during the same time period. We also observed that hilar interneurons and associated NG2(+) cells are similarly integrated into the local network, receiving excitatory inputs from both granule cells and CA3 pyramidal neurons. By performing pair recordings, we found that bursts of activity induced by GABAergic antagonists were strongly synchronized between both cell types and that the amplitude of these bursts was positively correlated. Finally, by applying carbachol to increase EPSC activity, we observed that closely apposed cells were more likely to exhibit synchronized EPSCs than cells separated by >200 microm. The finding that NG2(+) cells are sensing patterns of activity arising in closely associated neurons suggests that NG2(+) cell function is finely regulated by the local network.

  5. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.

    PubMed

    Liu, Jimmy Z; van Sommeren, Suzanne; Huang, Hailiang; Ng, Siew C; Alberts, Rudi; Takahashi, Atsushi; Ripke, Stephan; Lee, James C; Jostins, Luke; Shah, Tejas; Abedian, Shifteh; Cheon, Jae Hee; Cho, Judy; Daryani, Naser E; Franke, Lude; Fuyuno, Yuta; Hart, Ailsa; Juyal, Ramesh C; Juyal, Garima; Kim, Won Ho; Morris, Andrew P; Poustchi, Hossein; Newman, William G; Midha, Vandana; Orchard, Timothy R; Vahedi, Homayon; Sood, Ajit; Sung, Joseph J Y; Malekzadeh, Reza; Westra, Harm-Jan; Yamazaki, Keiko; Yang, Suk-Kyun; Barrett, Jeffrey C; Franke, Andre; Alizadeh, Behrooz Z; Parkes, Miles; B K, Thelma; Daly, Mark J; Kubo, Michiaki; Anderson, Carl A; Weersma, Rinse K

    2015-09-01

    Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.

  6. Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.

    PubMed

    Kapeli, Katannya; Pratt, Gabriel A; Vu, Anthony Q; Hutt, Kasey R; Martinez, Fernando J; Sundararaman, Balaji; Batra, Ranjan; Freese, Peter; Lambert, Nicole J; Huelga, Stephanie C; Chun, Seung J; Liang, Tiffany Y; Chang, Jeremy; Donohue, John P; Shiue, Lily; Zhang, Jiayu; Zhu, Haining; Cambi, Franca; Kasarskis, Edward; Hoon, Shawn; Ares, Manuel; Burge, Christopher B; Ravits, John; Rigo, Frank; Yeo, Gene W

    2016-07-05

    The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3' untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism.

  7. Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses

    PubMed Central

    Kapeli, Katannya; Pratt, Gabriel A.; Vu, Anthony Q.; Hutt, Kasey R.; Martinez, Fernando J.; Sundararaman, Balaji; Batra, Ranjan; Freese, Peter; Lambert, Nicole J.; Huelga, Stephanie C.; Chun, Seung J.; Liang, Tiffany Y.; Chang, Jeremy; Donohue, John P.; Shiue, Lily; Zhang, Jiayu; Zhu, Haining; Cambi, Franca; Kasarskis, Edward; Hoon, Shawn; Ares Jr., Manuel; Burge, Christopher B.; Ravits, John; Rigo, Frank; Yeo, Gene W.

    2016-01-01

    The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3′ untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism. PMID:27378374

  8. Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis

    PubMed Central

    Gan, Ryan W; Demoruelle, M Kristen; Deane, Kevin D; Weisman, Michael H; Buckner, Jane H; Gregersen, Peter K; Mikuls, Ted R; O’Dell, James R; Keating, Richard M; Fingerlin, Tasha E; Zerbe, Gary O; Clare-Salzler, Michael J; Holers, V Michael; Norris, Jill M

    2017-01-01

    Objectives Previously, we found that omega-3 fatty acids (n-3 FAs) were inversely associated with anti-cyclic citrullinated peptide (anti-CCP) positivity in participants at risk for future rheumatoid arthritis (RA). We investigated whether n-3 FAs were also associated with rheumatoid factor (RF) positivity and whether these associations were modified by shared epitope (SE) positivity. Methods The Studies of the Etiology of RA (SERA) cohort includes RA-free participants who are at increased risk for RA. We conducted a nested case–control study (n=136) to determine the association between RF and anti-CCP2 positivity and n-3 FA percentage in erythrocyte membranes (n-3 FA% in red blood cells (RBCs)). Additionally, in the baseline visit of the SERA cohort (n=2166), we evaluated the association between reported n-3 FA supplement use and prevalence of RF and anti-CCP2. We assessed SE positivity as an effect modifier. Results In the case–control study, increasing n-3 FA% in RBCs was inversely associated with RF positivity in SE-positive participants (OR 0.27, 95% CI 0.10 to 0.79), but not SE-negative participants. Similar associations were seen with anti-CCP positivity in SE-positive participants (OR 0.42, 95% CI 0.20 to 0.89), but not SE-negative participants. In the SERA cohort at baseline, n-3 FA supplement use was associated with a lower prevalence of RF positivity in SE-positive participants (OR 0.32, 95% CI 0.12 to 0.82), but not SE-negative participants; similar but non-significant trends were observed with anti-CCP2. Conclusions The potential protective effect of n-3 FAs on RA-related autoimmunity may be most pronounced in those who exhibit HLA class II genetic susceptibility to RA. PMID:27190099

  9. The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.

    PubMed

    Kottyan, Leah C; Zoller, Erin E; Bene, Jessica; Lu, Xiaoming; Kelly, Jennifer A; Rupert, Andrew M; Lessard, Christopher J; Vaughn, Samuel E; Marion, Miranda; Weirauch, Matthew T; Namjou, Bahram; Adler, Adam; Rasmussen, Astrid; Glenn, Stuart; Montgomery, Courtney G; Hirschfield, Gideon M; Xie, Gang; Coltescu, Catalina; Amos, Chris; Li, He; Ice, John A; Nath, Swapan K; Mariette, Xavier; Bowman, Simon; Rischmueller, Maureen; Lester, Sue; Brun, Johan G; Gøransson, Lasse G; Harboe, Erna; Omdal, Roald; Cunninghame-Graham, Deborah S; Vyse, Tim; Miceli-Richard, Corinne; Brennan, Michael T; Lessard, James A; Wahren-Herlenius, Marie; Kvarnström, Marika; Illei, Gabor G; Witte, Torsten; Jonsson, Roland; Eriksson, Per; Nordmark, Gunnel; Ng, Wan-Fai; Anaya, Juan-Manuel; Rhodus, Nelson L; Segal, Barbara M; Merrill, Joan T; James, Judith A; Guthridge, Joel M; Scofield, R Hal; Alarcon-Riquelme, Marta; Bae, Sang-Cheol; Boackle, Susan A; Criswell, Lindsey A; Gilkeson, Gary; Kamen, Diane L; Jacob, Chaim O; Kimberly, Robert; Brown, Elizabeth; Edberg, Jeffrey; Alarcón, Graciela S; Reveille, John D; Vilá, Luis M; Petri, Michelle; Ramsey-Goldman, Rosalind; Freedman, Barry I; Niewold, Timothy; Stevens, Anne M; Tsao, Betty P; Ying, Jun; Mayes, Maureen D; Gorlova, Olga Y; Wakeland, Ward; Radstake, Timothy; Martin, Ezequiel; Martin, Javier; Siminovitch, Katherine; Moser Sivils, Kathy L; Gaffney, Patrick M; Langefeld, Carl D; Harley, John B; Kaufman, Kenneth M

    2015-01-15

    Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.

  10. 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.…

  11. Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types

    PubMed Central

    Kar, Siddhartha P.; Beesley, Jonathan; Al Olama, Ali Amin; Michailidou, Kyriaki; Tyrer, Jonathan; Kote-Jarai, ZSofia; Lawrenson, Kate; Lindstrom, Sara; Ramus, Susan J.; Thompson, Deborah J.; Kibel, Adam S.; Dansonka-Mieszkowska, Agnieszka; Michael, Agnieszka; Dieffenbach, Aida K.; Gentry-Maharaj, Aleksandra; Whittemore, Alice S.; Wolk, Alicja; Monteiro, Alvaro; Peixoto, Ana; Kierzek, Andrzej; Cox, Angela; Rudolph, Anja; Gonzalez-Neira, Anna; Wu, Anna H.; Lindblom, Annika; Swerdlow, Anthony; Ziogas, Argyrios; Ekici, Arif B.; Burwinkel, Barbara; Karlan, Beth Y.; Nordestgaard, Børge G.; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B.; Høgdall, Claus K.; Teerlink, Craig C.; Kang, Daehee; Tessier, Daniel C.; Schaid, Daniel J.; Stram, Daniel O.; Cramer, Daniel W.; Neal, David E.; Eccles, Diana; Flesch-Janys, Dieter; Velez Edwards, Digna R.; Wokozorczyk, Dominika; Levine, Douglas A.; Yannoukakos, Drakoulis; Sawyer, Elinor J.; Bandera, Elisa V.; Poole, Elizabeth M.; Goode, Ellen L.; Khusnutdinova, Elza; Høgdall, Estrid; Song, Fengju; Bruinsma, Fiona; Heitz, Florian; Modugno, Francesmary; Hamdy, Freddie C.; Wiklund, Fredrik; Giles, Graham G.; Olsson, Håkan; Wildiers, Hans; Ulmer, Hans-Ulrich; Pandha, Hardev; Risch, Harvey A.; Darabi, Hatef; Salvesen, Helga B.; Nevanlinna, Heli; Gronberg, Henrik; Brenner, Hermann; Brauch, Hiltrud; Anton-Culver, Hoda; Song, Honglin; Lim, Hui-Yi; McNeish, Iain; Campbell, Ian; Vergote, Ignace; Gronwald, Jacek; Lubiński, Jan; Stanford, Janet L.; Benítez, Javier; Doherty, Jennifer A.; Permuth, Jennifer B.; Chang-Claude, Jenny; Donovan, Jenny L.; Dennis, Joe; Schildkraut, Joellen M.; Schleutker, Johanna; Hopper, John L.; Kupryjanczyk, Jolanta; Park, Jong Y.; Figueroa, Jonine; Clements, Judith A.; Knight, Julia A.; Peto, Julian; Cunningham, Julie M.; Pow-Sang, Julio; Batra, Jyotsna; Czene, Kamila; Lu, Karen H.; Herkommer, Kathleen; Khaw, Kay-Tee; Matsuo, Keitaro; Muir, Kenneth; Offitt, Kenneth; Chen, Kexin; Moysich, Kirsten B.; Aittomäki, Kristiina; Odunsi, Kunle; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Fitzgerald, Liesel M.; Cook, Linda S.; Cannon-Albright, Lisa; Hooning, Maartje J.; Pike, Malcolm C.; Bolla, Manjeet K.; Luedeke, Manuel; Teixeira, Manuel R.; Goodman, Marc T.; Schmidt, Marjanka K.; Riggan, Marjorie; Aly, Markus; Rossing, Mary Anne; Beckmann, Matthias W.; Moisse, Matthieu; Sanderson, Maureen; Southey, Melissa C.; Jones, Michael; Lush, Michael; Hildebrandt, Michelle A. T.; Hou, Ming-Feng; Schoemaker, Minouk J.; Garcia-Closas, Montserrat; Bogdanova, Natalia; Rahman, Nazneen; Le, Nhu D.; Orr, Nick; Wentzensen, Nicolas; Pashayan, Nora; Peterlongo, Paolo; Guénel, Pascal; Brennan, Paul; Paulo, Paula; Webb, Penelope M.; Broberg, Per; Fasching, Peter A.; Devilee, Peter; Wang, Qin; Cai, Qiuyin; Li, Qiyuan; Kaneva, Radka; Butzow, Ralf; Kopperud, Reidun Kristin; Schmutzler, Rita K.; Stephenson, Robert A.; MacInnis, Robert J.; Hoover, Robert N.; Winqvist, Robert; Ness, Roberta; Milne, Roger L.; Travis, Ruth C.; Benlloch, Sara; Olson, Sara H.; McDonnell, Shannon K.; Tworoger, Shelley S.; Maia, Sofia; Berndt, Sonja; Lee, Soo Chin; Teo, Soo-Hwang; Thibodeau, Stephen N.; Bojesen, Stig E.; Gapstur, Susan M.; Kjær, Susanne Krüger; Pejovic, Tanja; Tammela, Teuvo L.J.; Dörk, Thilo; Brüning, Thomas; Wahlfors, Tiina; Key, Tim J.; Edwards, Todd L.; Menon, Usha; Hamann, Ute; Mitev, Vanio; Kosma, Veli-Matti; Setiawan, Veronica Wendy; Kristensen, Vessela; Arndt, Volker; Vogel, Walther; Zheng, Wei; Sieh, Weiva; Blot, William J.; Kluzniak, Wojciech; Shu, Xiao-Ou; Gao, Yu-Tang; Schumacher, Fredrick; Freedman, Matthew L.; Berchuck, Andrew; Dunning, Alison M.; Simard, Jacques; Haiman, Christopher A.; Spurdle, Amanda; Sellers, Thomas A.; Hunter, David J.; Henderson, Brian E.; Kraft, Peter; Chanock, Stephen J.; Couch, Fergus J.; Hall, Per; Gayther, Simon A.; Easton, Douglas F.; Chenevix-Trench, Georgia; Eeles, Rosalind; Pharoah, Paul D.P.; Lambrechts, Diether

    2016-01-01

    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis. PMID:27432226

  12. Distinct and Shared Transcriptomes Are Regulated by Microphthalmia-Associated Transcription Factor Isoforms in Mast Cells1

    PubMed Central

    Shahlaee, Amir H.; Brandal, Stephanie; Lee, Youl-Nam; Jie, Chunfa; Takemoto, Clifford M.

    2008-01-01

    The Microphthalmia-associated transcription factor (Mitf) is an essential basic helix-loop-helix leucine zipper transcription factor for mast cell development. Mice deficient in Mitf harbor a severe mast cell deficiency, and Mitf-mutant mast cells cultured ex vivo display a number of functional defects. Therefore, an understanding of the genetic program regulated by Mitf may provide important insights into mast cell differentiation. Multiple, distinct isoforms of Mitf have been identified in a variety of cell types; we found that Mitf-a, Mitf-e, and Mitf-mc were the major isoforms expressed in mast cells. To determine the physiologic function of Mitf in mast cells, we restored expression of these isoforms in primary mast cells from Mitf−/−mice. We found that these isoforms restored granular morphology and integrin-mediated migration. By microarray analysis, proteases, signaling molecules, cell surface receptor, and transporters comprised the largest groups of genes up-regulated by all isoforms. Furthermore, we found that isoforms also regulated distinct genes sets, suggesting separable biological activities. This work defines the transcriptome regulated by Mitf in mast cells and supports its role as master regulator of mast cell differentiation. Expression of multiple isoforms of this transcription factor may provide for redundancy of biological activities while also allowing diversity of function. PMID:17182576

  13. Scalable privacy-preserving data sharing methodology for genome-wide association studies: an application to iDASH healthcare privacy protection challenge.

    PubMed

    Yu, Fei; Ji, Zhanglong

    2014-01-01

    In response to the growing interest in genome-wide association study (GWAS) data privacy, the Integrating Data for Analysis, Anonymization and SHaring (iDASH) center organized the iDASH Healthcare Privacy Protection Challenge, with the aim of investigating the effectiveness of applying privacy-preserving methodologies to human genetic data. This paper is based on a submission to the iDASH Healthcare Privacy Protection Challenge. We apply privacy-preserving methods that are adapted from Uhler et al. 2013 and Yu et al. 2014 to the challenge's data and analyze the data utility after the data are perturbed by the privacy-preserving methods. Major contributions of this paper include new interpretation of the χ2 statistic in a GWAS setting and new results about the Hamming distance score, a key component for one of the privacy-preserving methods.

  14. Genome-wide association study SNPs in the human genome diversity project populations: does selection affect unlinked SNPs with shared trait associations?

    PubMed

    Casto, Amanda M; Feldman, Marcus W

    2011-01-06

    Genome-wide association studies (GWAS) have identified more than 2,000 trait-SNP associations, and the number continues to increase. GWAS have focused on traits with potential consequences for human fitness, including many immunological, metabolic, cardiovascular, and behavioral phenotypes. Given the polygenic nature of complex traits, selection may exert its influence on them by altering allele frequencies at many associated loci, a possibility which has yet to be explored empirically. Here we use 38 different measures of allele frequency variation and 8 iHS scores to characterize over 1,300 GWAS SNPs in 53 globally distributed human populations. We apply these same techniques to evaluate SNPs grouped by trait association. We find that groups of SNPs associated with pigmentation, blood pressure, infectious disease, and autoimmune disease traits exhibit unusual allele frequency patterns and elevated iHS scores in certain geographical locations. We also find that GWAS SNPs have generally elevated scores for measures of allele frequency variation and for iHS in Eurasia and East Asia. Overall, we believe that our results provide evidence for selection on several complex traits that has caused changes in allele frequencies and/or elevated iHS scores at a number of associated loci. Since GWAS SNPs collectively exhibit elevated allele frequency measures and iHS scores, selection on complex traits may be quite widespread. Our findings are most consistent with this selection being either positive or negative, although the relative contributions of the two are difficult to discern. Our results also suggest that trait-SNP associations identified in Eurasian samples may not be present in Africa, Oceania, and the Americas, possibly due to differences in linkage disequilibrium patterns. This observation suggests that non-Eurasian and non-East Asian sample populations should be included in future GWAS.

  15. Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases.

    PubMed

    Marzano, Angelo V; Ceccherini, Isabella; Gattorno, Marco; Fanoni, Daniele; Caroli, Francesco; Rusmini, Marta; Grossi, Alice; De Simone, Clara; Borghi, Orietta M; Meroni, Pier Luigi; Crosti, Carlo; Cugno, Massimo

    2014-12-01

    The association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T-cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (AIDs), and cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of interleukin (IL)-1β and its receptors I and II were significantly higher in PASH (P = 0.028, 0.047, and 0.050, respectively) than in controls. In PASH patients, chemokines such as IL-8 (P = 0.004), C-X-C motif ligand (CXCL) 1/2/3 (P = 0.028), CXCL 16 (P = 0.008), and regulated on activation, normal T cell expressed and secreted (RANTES) (P = 0.005) were overexpressed. Fas/Fas ligand and cluster of differentiation (CD)40/CD40 ligand systems were also overexpressed (P = 0.016 for Fas, P = 0.006 for Fas ligand, P = 0.005 for CD40, and P = 0.004 for CD40 ligand), contributing to tissue damage and inflammation. In peripheral blood, serum levels of the main proinflammatory cytokines, that is, IL-1β, tumor necrosis factor-α, and IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical of well-known AIDs, including inflammatory bowel diseases, and the only patient lacking genetic changes had clinically evident Crohn disease. In conclusion, overexpression of cytokines/chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin.

  16. Reciprocal Relationship between Head Size, an Autism Endophenotype, and Gene Dosage at 19p13.12 Points to AKAP8 and AKAP8L.

    PubMed

    Nebel, Rebecca A; Kirschen, Jill; Cai, Jinlu; Woo, Young Jae; Cherian, Koshi; Abrahams, Brett S

    2015-01-01

    Microcephaly and macrocephaly are overrepresented in individuals with autism and are thought to be disease-related risk factors or endophenotypes. Analysis of DNA microarray results from a family with a low functioning autistic child determined that the proband and two additional unaffected family members who carry a rare inherited 760 kb duplication of unknown clinical significance at 19p13.12 are macrocephalic. Consideration alongside overlapping deletion and duplication events in the literature provides support for a strong relationship between gene dosage at this locus and head size, with losses and gains associated with microcephaly (p=1.11x10(-11)) and macrocephaly (p=2.47x10(-11)), respectively. Data support A kinase anchor protein 8 and 8-like (AKAP8 and AKAP8L) as candidate genes involved in regulation of head growth, an interesting finding given previous work implicating the AKAP gene family in autism. Towards determination of which of AKAP8 and AKAP8L may be involved in the modulation of head size and risk for disease, we analyzed exome sequencing data for 693 autism families (2591 individuals) where head circumference data were available. No predicted loss of function variants were observed, precluding insights into relationship to head size, but highlighting strong evolutionary conservation. Taken together, findings support the idea that gene dosage at 19p13.12, and AKAP8 and/or AKAP8L in particular, play an important role in modulation of head size and may contribute to autism risk. Exome sequencing of the family also identified a rare inherited variant predicted to disrupt splicing of TPTE / PTEN2, a PTEN homologue, which may likewise contribute to both macrocephaly and autism risk.

  17. Reciprocal Relationship between Head Size, an Autism Endophenotype, and Gene Dosage at 19p13.12 Points to AKAP8 and AKAP8L

    PubMed Central

    Nebel, Rebecca A.; Kirschen, Jill; Cai, Jinlu; Woo, Young Jae; Cherian, Koshi; Abrahams, Brett S.

    2015-01-01

    Microcephaly and macrocephaly are overrepresented in individuals with autism and are thought to be disease-related risk factors or endophenotypes. Analysis of DNA microarray results from a family with a low functioning autistic child determined that the proband and two additional unaffected family members who carry a rare inherited 760 kb duplication of unknown clinical significance at 19p13.12 are macrocephalic. Consideration alongside overlapping deletion and duplication events in the literature provides support for a strong relationship between gene dosage at this locus and head size, with losses and gains associated with microcephaly (p=1.11x10-11) and macrocephaly (p=2.47x10-11), respectively. Data support A kinase anchor protein 8 and 8-like (AKAP8 and AKAP8L) as candidate genes involved in regulation of head growth, an interesting finding given previous work implicating the AKAP gene family in autism. Towards determination of which of AKAP8 and AKAP8L may be involved in the modulation of head size and risk for disease, we analyzed exome sequencing data for 693 autism families (2591 individuals) where head circumference data were available. No predicted loss of function variants were observed, precluding insights into relationship to head size, but highlighting strong evolutionary conservation. Taken together, findings support the idea that gene dosage at 19p13.12, and AKAP8 and/or AKAP8L in particular, play an important role in modulation of head size and may contribute to autism risk. Exome sequencing of the family also identified a rare inherited variant predicted to disrupt splicing of TPTE / PTEN2, a PTEN homologue, which may likewise contribute to both macrocephaly and autism risk. PMID:26076356

  18. Association of Pyoderma Gangrenosum, Acne, and Suppurative Hidradenitis (PASH) Shares Genetic and Cytokine Profiles With Other Autoinflammatory Diseases

    PubMed Central

    Marzano, Angelo V.; Ceccherini, Isabella; Gattorno, Marco; Fanoni, Daniele; Caroli, Francesco; Rusmini, Marta; Grossi, Alice; De Simone, Clara; Borghi, Orietta M.; Meroni, Pier Luigi; Crosti, Carlo; Cugno, Massimo

    2014-01-01

    Abstract The association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T-cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (AIDs), and cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of interleukin (IL)-1β and its receptors I and II were significantly higher in PASH (P = 0.028, 0.047, and 0.050, respectively) than in controls. In PASH patients, chemokines such as IL-8 (P = 0.004), C-X-C motif ligand (CXCL) 1/2/3 (P = 0.028), CXCL 16 (P = 0.008), and regulated on activation, normal T cell expressed and secreted (RANTES) (P = 0.005) were overexpressed. Fas/Fas ligand and cluster of differentiation (CD)40/CD40 ligand systems were also overexpressed (P = 0.016 for Fas, P = 0.006 for Fas ligand, P = 0.005 for CD40, and P = 0.004 for CD40 ligand), contributing to tissue damage and inflammation. In peripheral blood, serum levels of the main proinflammatory cytokines, that is, IL-1β, tumor necrosis factor-α, and IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical of well-known AIDs, including inflammatory bowel diseases, and the only patient lacking genetic changes had clinically evident Crohn disease. In conclusion, overexpression of cytokines/chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin. PMID:25501066

  19. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types

    PubMed Central

    Wheeler, William A.; Yeager, Meredith; Panagiotou, Orestis; Wang, Zhaoming; Berndt, Sonja I.; Lan, Qing; Abnet, Christian C.; Amundadottir, Laufey T.; Figueroa, Jonine D.; Landi, Maria Teresa; Mirabello, Lisa; Savage, Sharon A.; Taylor, Philip R.; Vivo, Immaculata De; McGlynn, Katherine A.; Purdue, Mark P.; Rajaraman, Preetha; Adami, Hans-Olov; Ahlbom, Anders; Albanes, Demetrius; Amary, Maria Fernanda; An, She-Juan; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L.; Angelucci, Emanuele; Ansell, Stephen M.; Arici, Cecilia; Armstrong, Bruce K.; Arslan, Alan A.; Austin, Melissa A.; Baris, Dalsu; Barkauskas, Donald A.; Bassig, Bryan A.; Becker, Nikolaus; Benavente, Yolanda; Benhamou, Simone; Berg, Christine; Van Den Berg, David; Bernstein, Leslie; Bertrand, Kimberly A.; Birmann, Brenda M.; Black, Amanda; Boeing, Heiner; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Brinton, Louise; Brooks-Wilson, Angela R.; Bueno-de-Mesquita, H. Bas; Burdett, Laurie; Buring, Julie; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chan, John K. C.; Chang, Ellen T.; Chang, Gee-Chen; Chang, I-Shou; Chang, Jiang; Chang-Claude, Jenny; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chu; Chen, Chung-Hsing; Chen, Constance; Chen, Hongyan; Chen, Kexin; Chen, Kuan-Yu; Chen, Kun-Chieh; Chen, Ying; Chen, Ying-Hsiang; Chen, Yi-Song; Chen, Yuh-Min; Chien, Li-Hsin; Chirlaque, María-Dolores; Choi, Jin Eun; Choi, Yi Young; Chow, Wong-Ho; Chung, Charles C.; Clavel, Jacqueline; Clavel-Chapelon, Françoise; Cocco, Pierluigi; Colt, Joanne S.; Comperat, Eva; Conde, Lucia; Connors, Joseph M.; Conti, David; Cortessis, Victoria K.; Cotterchio, Michelle; Cozen, Wendy; Crouch, Simon; Crous-Bou, Marta; Cussenot, Olivier; Davis, Faith G.; Ding, Ti; Diver, W. Ryan; Dorronsoro, Miren; Dossus, Laure; Duell, Eric J.; Ennas, Maria Grazia; Erickson, Ralph L.; Feychting, Maria; Flanagan, Adrienne M.; Foretova, Lenka; Fraumeni, Joseph F.; Freedman, Neal D.; Beane Freeman, Laura E.; Fuchs, Charles; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; García-Closas, Reina; Gascoyne, Randy D.; Gastier-Foster, Julie; Gaudet, Mia M.; Gaziano, J. Michael; Giffen, Carol; Giles, Graham G.; Giovannucci, Edward; Glimelius, Bengt; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M.; Gorlick, Richard; Gross, Myron; Grubb, Robert; Gu, Jian; Guan, Peng; Gunter, Marc; Guo, Huan; Habermann, Thomas M.; Haiman, Christopher A.; Halai, Dina; Hallmans, Goran; Hassan, Manal; Hattinger, Claudia; He, Qincheng; He, Xingzhou; Helzlsouer, Kathy; Henderson, Brian; Henriksson, Roger; Hjalgrim, Henrik; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holford, Theodore R.; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Horn-Ross, Pamela L.; Hosain, G. M. Monawar; Hosgood, H. Dean; Hsiao, Chin-Fu; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Huerta, Jose-Maria; Hung, Jen-Yu; Hutchinson, Amy; Inskip, Peter D.; Jackson, Rebecca D.; Jacobs, Eric J.; Jenab, Mazda; Jeon, Hyo-Sung; Ji, Bu-Tian; Jin, Guangfu; Jin, Li; Johansen, Christoffer; Johnson, Alison; Jung, Yoo Jin; Kaaks, Rudolph; Kamineni, Aruna; Kane, Eleanor; Kang, Chang Hyun; Karagas, Margaret R.; Kelly, Rachel S.; Khaw, Kay-Tee; Kim, Christopher; Kim, Hee Nam; Kim, Jin Hee; Kim, Jun Suk; Kim, Yeul Hong; Kim, Young Tae; Kim, Young-Chul; Kitahara, Cari M.; Klein, Alison P.; Klein, Robert J.; Kogevinas, Manolis; Kohno, Takashi; Kolonel, Laurence N.; Kooperberg, Charles; Kricker, Anne; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C.; Kweon, Sun-Seog; LaCroix, Andrea; Lawrence, Charles; Lecanda, Fernando; Lee, Victor Ho Fun; Li, Donghui; Li, Haixin; Li, Jihua; Li, Yao-Jen; Li, Yuqing; Liao, Linda M.; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S.; Link, Brian K.; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Börje; Lloreta, Josep; Lollo, Simonetta Di; Lu, Daru; Lund, Eiluv; Malats, Nuria; Mannisto, Satu; Marchand, Loic Le; Marina, Neyssa; Masala, Giovanna; Mastrangelo, Giuseppe; Matsuo, Keitaro; Maynadie, Marc; McKay, James; McKean-Cowdin, Roberta; Melbye, Mads; Melin, Beatrice S.; Michaud, Dominique S.; Mitsudomi, Tetsuya; Monnereau, Alain; Montalvan, Rebecca; Moore, Lee E.; Mortensen, Lotte Maxild; Nieters, Alexandra; North, Kari E.; Novak, Anne J.; Oberg, Ann L.; Offit, Kenneth; Oh, In-Jae; Olson, Sara H.; Palli, Domenico; Pao, William; Park, In Kyu; Park, Jae Yong; Park, Kyong Hwa; Patiño-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H. M.; Perng, Reury-Perng; Peters, Ulrike; Petersen, Gloria M.; Picci, Piero; Pike, Malcolm C.; Porru, Stefano; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Qian, Biyun; Qiao, You-Lin; Rais, Marco; Riboli, Elio; Riby, Jacques; Risch, Harvey A.; Rizzato, Cosmeri; Rodabough, Rebecca; Roman, Eve; Roupret, Morgan; Ruder, Avima M.; de Sanjose, Silvia; Scelo, Ghislaine; Schned, Alan; Schumacher, Fredrick; Schwartz, Kendra; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D.; Setiawan, Veronica Wendy; Severi, Gianluca; Severson, Richard K.; Shanafelt, Tait D.; Shen, Hongbing; Shen, Wei; Shin, Min-Ho; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesúmaga, Luis; Sihoe, Alan Dart Loon; Skibola, Christine F.; Smith, Alex; Smith, Martyn T.; Southey, Melissa C.; Spinelli, John J.; Staines, Anthony; Stampfer, Meir; Stern, Marianna C.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael S.; Su, Jian; Su, Wu-Chou; Sund, Malin; Sung, Jae Sook; Sung, Sook Whan; Tan, Wen; Tang, Wei; Tardón, Adonina; Thomas, David; Thompson, Carrie A.; Tinker, Lesley F.; Tirabosco, Roberto; Tjønneland, Anne; Travis, Ruth C.; Trichopoulos, Dimitrios; Tsai, Fang-Yu; Tsai, Ying-Huang; Tucker, Margaret; Turner, Jenny; Vajdic, Claire M.; Vermeulen, Roel C. H.; Villano, Danylo J.; Vineis, Paolo; Virtamo, Jarmo; Visvanathan, Kala; Wactawski-Wende, Jean; Wang, Chaoyu; Wang, Chih-Liang; Wang, Jiu-Cun; Wang, Junwen; Wei, Fusheng; Weiderpass, Elisabete; Weiner, George J.; Weinstein, Stephanie; Wentzensen, Nicolas; White, Emily; Witzig, Thomas E.; Wolpin, Brian M.; Wong, Maria Pik; Wu, Chen; Wu, Guoping; Wu, Junjie; Wu, Tangchun; Wu, Wei; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xiang, Yong-Bing; Xu, Jun; Xu, Ping; Yang, Pan-Chyr; Yang, Tsung-Ying; Ye, Yuanqing; Yin, Zhihua; Yokota, Jun; Yoon, Ho-Il; Yu, Chong-Jen; Yu, Herbert; Yu, Kai; Yuan, Jian-Min; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Xu-Chao; Zhang, Yawei; Zhao, Xueying; Zhao, Zhenhong; Zheng, Hong; Zheng, Tongzhang; Zheng, Wei; Zhou, Baosen; Zhu, Meng; Zucca, Mariagrazia; Boca, Simina M.; Cerhan, James R.; Ferri, Giovanni M.; Hartge, Patricia; Hsiung, Chao Agnes; Magnani, Corrado; Miligi, Lucia; Morton, Lindsay M.; Smedby, Karin E.; Teras, Lauren R.; Vijai, Joseph; Wang, Sophia S.; Brennan, Paul; Caporaso, Neil E.; Hunter, David J.; Kraft, Peter; Rothman, Nathaniel; Silverman, Debra T.; Slager, Susan L.; Chanock, Stephen J.; Chatterjee, Nilanjan

    2015-01-01

    Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl 2, on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our

  20. 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

  1. Labia Majora Share

    PubMed Central

    Lee, Hanjing; Yap, Yan Lin; Low, Jeffrey Jen Hui

    2017-01-01

    Defects involving specialised areas with characteristic anatomical features, such as the nipple, upper eyelid, and lip, benefit greatly from the use of sharing procedures. The vulva, a complex 3-dimensional structure, can also be reconstructed through a sharing procedure drawing upon the contralateral vulva. In this report, we present the interesting case of a patient with chronic, massive, localised lymphedema of her left labia majora that was resected in 2011. Five years later, she presented with squamous cell carcinoma over the left vulva region, which is rarely associated with chronic lymphedema. To the best of our knowledge, our management of the radical vulvectomy defect with a labia majora sharing procedure is novel and has not been previously described. The labia major flap presented in this report is a shared flap; that is, a transposition flap based on the dorsal clitoral artery, which has consistent vascular anatomy, making this flap durable and reliable. This procedure epitomises the principle of replacing like with like, does not interfere with leg movement or patient positioning, has minimal donor site morbidity, and preserves other locoregional flap options for future reconstruction. One limitation is the need for a lax contralateral vulva. This labia majora sharing procedure is a viable option in carefully selected patients. PMID:28194353

  2. Sharing values, sharing a vision

    SciTech Connect

    Not Available

    1993-12-31

    Teamwork, partnership and shared values emerged as recurring themes at the Third Technology Transfer/Communications Conference. The program drew about 100 participants who sat through a packed two days to find ways for their laboratories and facilities to better help American business and the economy. Co-hosts were the Lawrence Livermore National Laboratory and the Lawrence Berkeley Laboratory, where most meetings took place. The conference followed traditions established at the First Technology Transfer/Communications Conference, conceived of and hosted by the Pacific Northwest Laboratory in May 1992 in Richmond, Washington, and the second conference, hosted by the National Renewable Energy Laboratory in January 1993 in Golden, Colorado. As at the other conferences, participants at the third session represented the fields of technology transfer, public affairs and communications. They came from Department of Energy headquarters and DOE offices, laboratories and production facilities. Continued in this report are keynote address; panel discussion; workshops; and presentations in technology transfer.

  3. Resource Sharing. SPEC Kit 42.

    ERIC Educational Resources Information Center

    Association of Research Libraries, Washington, DC. Office of Management Studies.

    A 1977 Association of Research Libraries (ARL) survey indicated that nearly all respondents viewed enhanced access to needed information and service capabilities as the primary benefit of resource sharing. Most responding libraries participated in more than one type of resource sharing activity, ranging from informal understandings among a few…

  4. Epileptic Electroencephalography Profile Associates with Attention Problems in Children with Fragile X Syndrome: Review and Case Series

    PubMed Central

    Cowley, Benjamin; Kirjanen, Svetlana; Partanen, Juhani; Castrén, Maija L.

    2016-01-01

    Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and a variant of autism spectrum disorder (ASD). The FXS population is quite heterogeneous with respect to comorbidities, which implies the need for a personalized medicine approach, relying on biomarkers or endophenotypes to guide treatment. There is evidence that quantitative electroencephalography (EEG) endophenotype-guided treatments can support increased clinical benefit by considering the patient's neurophysiological profile. We describe a case series of 11 children diagnosed with FXS, aged one to 14 years, mean 4.6 years. Case data are based on longitudinal clinically-observed reports by attending physicians for comorbid symptoms including awake and asleep EEG profiles. We tabulate the comorbid EEG symptoms in this case series, and relate them to the literature on EEG endophenotypes and associated treatment options. The two most common endophenotypes in the data were diffuse slow oscillations and epileptiform EEG, which have been associated with attention and epilepsy respectively. This observation agrees with reported prevalence of comorbid behavioral symptoms for FXS. In this sample of FXS children, attention problems were found in 37% (4 of 11), and epileptic seizures in 45% (5 of 11). Attention problems were found to associate with the epilepsy endophenotype. From the synthesis of this case series and literature review, we argue that the evidence-based personalized treatment approach, exemplified by neurofeedback, could benefit FXS children by focusing on observable, specific characteristics of comorbid disease symptoms. PMID:27462212

  5. Identification of shared and unique susceptibility pathways among cancers of the lung, breast, and prostate from genome-wide association studies and tissue-specific protein interactions

    PubMed Central

    Qian, David C.; Byun, Jinyoung; Han, Younghun; Greene, Casey S.; Field, John K.; Hung, Rayjean J.; Brhane, Yonathan; Mclaughlin, John R.; Fehringer, Gordon; Landi, Maria Teresa; Rosenberger, Albert; Bickeböller, Heike; Malhotra, Jyoti; Risch, Angela; Heinrich, Joachim; Hunter, David J.; Henderson, Brian E.; Haiman, Christopher A.; Schumacher, Fredrick R.; Eeles, Rosalind A.; Easton, Douglas F.; Seminara, Daniela; Amos, Christopher I.

    2015-01-01

    Results from genome-wide association studies (GWAS) have indicated that strong single-gene effects are the exception, not the rule, for most diseases. We assessed the joint effects of germline genetic variations through a pathway-based approach that considers the tissue-specific contexts of GWAS findings. From GWAS meta-analyses of lung cancer (12 160 cases/16 838 controls), breast cancer (15 748 cases/18 084 controls) and prostate cancer (14 160 cases/12 724 controls) in individuals of European ancestry, we determined the tissue-specific interaction networks of proteins expressed from genes that are likely to be affected by disease-associated variants. Reactome pathways exhibiting enrichment of proteins from each network were compared across the cancers. Our results show that pathways associated with all three cancers tend to be broad cellular processes required for growth and survival. Significant examples include the nerve growth factor (P = 7.86 × 10−33), epidermal growth factor (P = 1.18 × 10−31) and fibroblast growth factor (P = 2.47 × 10−31) signaling pathways. However, within these shared pathways, the genes that influence risk largely differ by cancer. Pathways found to be unique for a single cancer focus on more specific cellular functions, such as interleukin signaling in lung cancer (P = 1.69 × 10−15), apoptosis initiation by Bad in breast cancer (P = 3.14 × 10−9) and cellular responses to hypoxia in prostate cancer (P = 2.14 × 10−9). We present the largest comparative cross-cancer pathway analysis of GWAS to date. Our approach can also be applied to the study of inherited mechanisms underlying risk across multiple diseases in general. PMID:26483192

  6. Understanding the Effects of Team Cognition Associated with Complex Engineering Tasks: Dynamics of Shared Mental Models, Task-SMM, and Team-SMM

    ERIC Educational Resources Information Center

    Lee, Miyoung; Johnson, Tristan E.

    2008-01-01

    This study investigates how shared mental models (SMMs) change over time in teams of students in a manufacturing engineering course. A complex ill-structured project was given to each team. The objective of the team project was to analyze, test, and propose ways to improve their given manufactured product. Shared mental models were measured in…

  7. 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

  8. Multiple paternity is a shared reproductive strategy in the live-bearing surfperches (Embiotocidae) that may be associated with female fitness

    PubMed Central

    LaBrecque, John R; Alva-Campbell, Yvette R; Archambeault, Sophie; Crow, Karen D

    2014-01-01

    According to Bateman's principle, female fecundity is limited relative to males, setting the expectation that males should be promiscuous, while females should be choosy and select fewer mates. However, several surfperches (Embiotocidae) exhibit multiple paternity within broods indicating that females mate with multiple males throughout the mating season. Previous studies found no correlation between mating success and reproductive success (i.e., a Bateman gradient). However, by including samples from a broader range of reproductive size classes, we found evidence of a Bateman gradient in two surfperch species from distinct embiotocid clades. Using microsatellite analyses, we found that 100% of the spotfin surfperch families sampled exhibit multiple paternity (Hyperprosopon anale, the basal taxon from the only clade that has not previously been investigated) indicating that this tactic is a shared reproductive strategy among surfperches. Further, we detected evidence for a Bateman gradient in H. anale; however, this result was not significant after correction for biases. Similarly, we found evidence for multiple paternity in 83% of the shiner surfperch families (Cymatogaster aggregata) sampled. When we combine these data with a previous study on the same species, representing a larger range of reproductive size classes and associated brood sizes, we detect a Bateman gradient in shiner surfperch for the first time that remains significant after several conservative tests for bias correction. These results indicate that sexual selection is likely complex in this system, with the potential for conflicting optima between sexes, and imply a positive shift in fertility (i.e., increasing number) and reproductive tactic with respect to the mating system and number of sires throughout the reproductive life history of females. We argue that the complex reproductive natural history of surfperches is characterized by several traits that may be associated with cryptic female

  9. 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

    Festen, Eleonora A M; Goyette, Philippe; Green, Todd; 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

    2011-01-27

    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 x 10⁻⁵ in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value < 1 x 10⁻² in CelD and < 1 x 10⁻³ in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37 x 10⁻⁸ and 6.39 x 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 x 10⁻¹⁰ and 1.38 x 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

  10. A genome wide association study identifies a lncRna as risk factor for pathological inflammatory responses in leprosy

    PubMed Central

    Orlova, Marianna; Van Thuc, Nguyen; Moraes, Milton O.; Sales-Marques, Carolinne; Latini, Ana Carla P.; Belone, Andrea F.; Thai, Vu Hong; Abel, Laurent; Alcaïs, Alexandre; Schurr, Erwin

    2017-01-01

    Leprosy Type-1 Reactions (T1Rs) are pathological inflammatory responses that afflict a sub-group of leprosy patients and result in peripheral nerve damage. Here, we employed a family-based GWAS in 221 families with 229 T1R-affect offspring with stepwise replication to identify risk factors for T1R. We discovered, replicated and validated T1R-specific associations with SNPs located in chromosome region 10p21.2. Combined analysis across the three independent samples resulted in strong evidence of association of rs1875147 with T1R (p = 4.5x10-8; OR = 1.54, 95% CI = 1.32–1.80). The T1R-risk locus was restricted to a lncRNA-encoding genomic interval with rs1875147 being an eQTL for the lncRNA. Since a genetic overlap between leprosy and inflammatory bowel disease (IBD) has been detected, we evaluated if the shared genetic control could be traced to the T1R endophenotype. Employing the results of a recent IBD GWAS meta-analysis we found that 10.6% of IBD SNPs available in our dataset shared a common risk-allele with T1R (p = 2.4x10-4). This finding points to a substantial overlap in the genetic control of clinically diverse inflammatory disorders. PMID:28222097

  11. [Searching for psychosocial endophenotypes in schizophrenia: the innovative role of brain imaging].

    PubMed

    Dusi, Nicola; Perlini, Cinzia; Bellani, Marcella; Brambilla, Paolo

    2012-01-01

    Schizophrenia is a disease with heterogeneous features and often a disabling longitudinal outcome. In order to achieve a better understanding of the disease, a detailed characterization and definition of symptomatology, social functioning and cognitive performance of patients is required. Imaging techniques may allow to identify measurable markers of different subgroups of patients, who share common clinical course and, probably, a similar hereditary pathway. The review offers a description of cross-sectional, predictive and longitudinal studies on the relationship between biological, clinical and psychosocial features of patients with schizophrenia. Patients with a more severe and disabling course of illness present larger ventricles, smaller prefrontal, temporal and occipital cortices and smaller subcortical regions such as basal ganglia, the thalamus and limbic areas. These alterations are predictive of a worse prognosis, as observed in predictive and longitudinal studies, both on chronic and first episode patients. The detection of more homogenous groups of patients with schizophrenia will help neurobiological research progress in this field. Furthermore, patients with similar clinical and biological features could undergo more tailored therapeutic and rehabilitative strategies.

  12. 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…

  13. 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.

  14. Heavy cannabis use prior psychosis in schizophrenia: clinical, cognitive and neurological evidences for a new endophenotype?

    PubMed

    Mallet, Jasmina; Ramoz, Nicolas; Le Strat, Yann; Gorwood, Philip; Dubertret, Caroline

    2017-02-11

    Cannabis use is associated with an increased risk of schizophrenia, and is considered to impact late neurodevelopment. Neurological soft signs (NSS) associated with schizophrenia are considered as markers of early neurodevelopmental impairment. Our study examines the association between heavy cannabis use before the onset of psychosis and clinical, neuropsychological and neurological symptoms, including NSS. In a cross-sectional study, we consecutively included 61 patients with schizophrenia (34 reporting heavy cannabis use before the onset of psychosis and 27 not reporting such use), in the setting of a University Hospital and a Medical Center. Symptoms assessment and substance use disorder were evaluated with the Diagnostic Interview for Genetic Studies. NSS were assessed with the Neurological Evaluation Scale. Psychopathology was assessed with the Positive and Negative Symptom Scale. All patients underwent a battery of neurocognitive tests evaluating attention, memory and executive functions domains. Patients with heavy cannabis use before the onset of psychosis showed significantly less NSS (p < 0.05), less negative symptoms (p < 10(-3)) and a better cognitive functioning in different domains [median reaction time (p = 0.03), episodic memory (p = 0.04), visuoconstructive praxs (p = 0.03) than their non-heavy user counterparts]. Confounding effects of alcohol and tobacco were taken into account. Age and gender were not statistically different between the two groups (p = 0.70 and p = 0.16, respectively). Our study supports the clinical, neuropsychological and neurological specificity associated with the heavy use of cannabis before the onset of schizophrenia. Patients with heavy cannabis use before the onset of schizophrenia may exhibit later neurodevelopmental impairment than those who do not report such use. Schizophrenia associated with heavy cannabis use could represent a specific phenotype.

  15. Reversal learning in patients with obsessive-compulsive disorder (OCD) and their unaffected relatives: Is orbitofrontal dysfunction an endophenotype of OCD?

    PubMed

    Tezcan, Didem; Tumkaya, Selim; Bora, Emre

    2017-03-06

    It has been suggested that reversal learning deficits might be an endophenotype of OCD. To investigate this hypothesis, we administered a probabilistic reversal learning task (ProbRev) to OCD patients, their unaffected first-degree relatives, and healthy controls. Although the relatives had a performance in between OCDs and controls at the early phase of the ProbRev, their performance was similar to controls and was significantly better than OCD patients at the later stages of the test. Our findings imply that reversal learning impairment might be partly a trait-related feature of OCD but state-related factors can also contribute to observed deficits.

  16. Mood and metabolic consequences of sleep deprivation as a potential endophenotype' in bipolar disorder.

    PubMed

    Aydin, Adem; Selvi, Yavuz; Besiroglu, Lutfullah; Boysan, Murat; Atli, Abdullah; Ozdemir, Osman; Kilic, Sultan; Balaharoglu, Ragıp

    2013-09-05

    It has been commonly recognized that circadian rhythm and sleep/wake cycle are causally involved in bipolar disorder. There has been a paucity of systematic research considering the relations between sleep and mood states in bipolar disorder. The current study examines the possible influences of sleep deprivation on mood states and endocrine functions among first-degree relatives of patients with bipolar disorder and healthy controls. Blood samples were taken at two time points in the consecutive mornings at predeprivation and postdeprivation periods. Participants simultaneously completed the Profiles of Mood States at two time points after giving blood samples. Plasma T3 and TSH levels increased after total sleep deprivation in both groups. Sleep deprivation induced TSH levels were reversely associated with depression-dejection among healthy controls. A paradoxical effect was detected for only the first-degree relatives of the patients that changes in plasma cortisol levels negatively linked to depression-dejection and anger-hostility scores after total sleep deprivation. Plasma DHEA levels became correlated with vigor-activity scores after sleep deprivation among first-degree relatives of bipolar patients. On the contrary, significant associations of depression-dejection, anger-hostility, and confusion-bewilderment with the baseline plasma DHEA levels became statistically trivial in the postdeprivation period. Findings suggested that first-degree relatives of patients with bipolar disorder had completely distinct characteristics with respect to sleep deprivation induced responses in terms of associations between endocrine functions and mood states as compared to individuals whose relatives had no psychiatric problems. Considering the relationships between endocrine functions and mood states among relatives of the patients, it appears like sleep deprivation changes the receptor sensitivity which probably plays a pivotal role on mood outcomes among the first

  17. Targeting Neural Endophenotypes of Eating Disorders with Non-invasive Brain Stimulation

    PubMed Central

    Dunlop, Katharine A.; Woodside, Blake; Downar, Jonathan

    2016-01-01

    The term “eating disorders” (ED) encompasses a wide variety of disordered eating and compensatory behaviors, and so the term is associated with considerable clinical and phenotypic heterogeneity. This heterogeneity makes optimizing treatment techniques difficult. One class of treatments is non-invasive brain stimulation (NIBS). NIBS, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), are accessible forms of neuromodulation that alter the cortical excitability of a target brain region. It is crucial for NIBS to be successful that the target is well selected for the patient population in question. Targets may best be selected by stepping back from conventional DSM-5 diagnostic criteria to identify neural substrates of more basic phenotypes, including behavior related to rewards and punishment, cognitive control, and social processes. These phenotypic dimensions have been recently laid out by the Research Domain Criteria (RDoC) initiative. Consequently, this review is intended to identify potential dimensions as outlined by the RDoC and the underlying behavioral and neurobiological targets associated with ED. This review will also identify candidate targets for NIBS based on these dimensions and review the available literature on rTMS and tDCS in ED. This review systematically reviews abnormal neural circuitry in ED within the RDoC framework, and also systematically reviews the available literature investigating NIBS as a treatment for ED. PMID:26909013

  18. Mild neurological impairment may indicate a psychomotor endophenotype in patients with borderline personality disorder.

    PubMed

    Arbabi, Mohammad; Paast, Negin; Karim, Hamid Reza; Faghfori, Sara; Memari, Amir Hossein

    2016-11-30

    The aim of the present study was to determine whether patients with borderline personality disorder (BPD) show any neurological soft signs compared to healthy controls. Furthermore we sought to examine the role of common symptoms related to BPD, such as depression, anxiety or impulsivity, in association with neurological soft signs. Thirty patients with borderline personality disorder and thirty hospital-based controls were examined for neurological soft signs. The total score of neurological soft signs in BPD was significantly higher than controls. In terms of subscales, patients had higher scores in Sensory Integration and Motor Coordination and other neurological soft signs compared to control group. Multiple regression analysis showed that the impulsivity score was the best significant predictor of neurological soft signs in BPD. The increase of neurological soft signs in patients with BPD may address a non-focal neurological dysfunction in borderline personality disorder.

  19. Generalized quantum secret sharing

    SciTech Connect

    Singh, Sudhir Kumar; Srikanth, R.

    2005-01-01

    We explore a generalization of quantum secret sharing (QSS) in which classical shares play a complementary role to quantum shares, exploring further consequences of an idea first studied by Nascimento, Mueller-Quade, and Imai [Phys. Rev. A 64, 042311 (2001)]. We examine three ways, termed inflation, compression, and twin thresholding, by which the proportion of classical shares can be augmented. This has the important application that it reduces quantum (information processing) players by replacing them with their classical counterparts, thereby making quantum secret sharing considerably easier and less expensive to implement in a practical setting. In compression, a QSS scheme is turned into an equivalent scheme with fewer quantum players, compensated for by suitable classical shares. In inflation, a QSS scheme is enlarged by adding only classical shares and players. In a twin-threshold scheme, we invoke two separate thresholds for classical and quantum shares based on the idea of information dilution.

  20. Investigation of the HLA component involved in rheumatoid arthritis (RA) by using the marker association-segregation [chi][sup 2] (MASC) method: Rejection of the unifying-shared-epitope hypothesis

    SciTech Connect

    Dizier, M.H.; Eliaou, J.F.; Babron, M.C.; Combe, B.; Sany, J.; Clot, J.; Clerget-Darpoux, F.

    1993-09-01

    In order to investigate the HLA component involved in rheumatoid arthritis (RA), the authors tested genetic models by the marker association-segregation [chi][sup 2] (MASC) method, using the HLA genotypic distribution observed in a sample of 97 RA patients. First they tested models assuming the involvement of a susceptibility gene linked to the DR locus. They showed that the present data are compatible with a simple model assuming the effect of a recessive allele of a biallelic locus linked to the DR locus and without any assumption of synergistic effect. Then they considered models assuming the direct involvement of the DR allele products, and tested the unifying-shared-epitope hypothesis, which has been proposed. Under this hypothesis the DR alleles are assumed to be directly involved in the susceptibility to the disease because of the presence of similar or identical amino acid sequences in position 70-74 of the third hypervariable region of the DRBI molecules, shared by the RA-associated DR alleles DR4Dw4, DR4Dw14, and DR1. This hypothesis was strongly rejected with the present data. In the case of the direct involvement of the DR alleles, hypotheses more complex that the unifying-shared-epitope hypothesis would have to be considered. 28 refs., 2 tabs.

  1. In Search of Neural Endophenotypes of Postpartum Psychopathology and Disrupted Maternal Caregiving

    PubMed Central

    Moses-Kolko, E. L.; Horner, M. S.; Phillips, M. L.; Hipwell, A. E.; Swain, J. E.

    2015-01-01

    This is a selective review that provides the context for the study of perinatal affective disorder mechanisms and outlines directions for future research. We integrate existing literature along neural networks of interest for affective disorders and maternal caregiving: (i) the salience/fear network; (ii) the executive network; (iii) the reward/social attachment network; and (iv) the default mode network. Extant salience/fear network research reveals disparate responses and corticolimbic coupling to various stimuli based upon a predominantly depressive versus anxious (post-traumatic stress disorder) clinical phenotype. Executive network and default mode connectivity abnormalities have been described in postpartum depression (PPD), although studies are very limited in these domains. Reward/social attachment studies confirm a robust ventral striatal response to infant stimuli, including cry and happy infant faces, which is diminished in depressed, insecurely attached and substance-using mothers. The adverse parenting experiences received and the attachment insecurity of current mothers are factors that are associated with a diminution in infant stimulus-related neural activity similar to that in PPD, and raise the need for additional studies that integrate mood and attachment concepts in larger study samples. Several studies examining functional connectivity in resting state and emotional activation functional magnetic resonance imaging paradigms have revealed attenuated corticolimbic connectivity, which remains an important outcome that requires dissection with increasing precision to better define neural treatment targets. Methodological progress is expected in the coming years in terms of refining clinical phenotypes of interest and experimental paradigms, as well as enlarging samples to facilitate the examination of multiple constructs. Functional imaging promises to determine neural mechanisms underlying maternal psychopathology and impaired caregiving, such

  2. 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.

  3. Proactive quantum secret sharing

    NASA Astrophysics Data System (ADS)

    Qin, Huawang; Dai, Yuewei

    2015-11-01

    A proactive quantum secret sharing scheme is proposed, in which the participants can update their key shares periodically. In an updating period, one participant randomly generates the EPR pairs, and the other participants update their key shares and perform the corresponding unitary operations on the particles of the EPR pairs. Then, the participant who generated the EPR pairs performs the Bell-state measurement and updates his key share according to the result of the Bell-state measurement. After an updating period, each participant can change his key share, but the secret is changeless, and the old key shares will be useless even if they have been stolen by the attacker. The proactive property of our scheme is very useful to resist the mobile attacker.

  4. Root-Associated Ectomycorrhizal Fungi Shared by Various Boreal Forest Seedlings Naturally Regenerating after a Fire in Interior Alaska and Correlation of Different Fungi with Host Growth Responses ▿

    PubMed Central

    Bent, Elizabeth; Kiekel, Preston; Brenton, Rebecca; Taylor, D. Lee

    2011-01-01

    The role of common mycorrhizal networks (CMNs) in postfire boreal forest successional trajectories is unknown. We investigated this issue by sampling a 50-m by 40-m area of naturally regenerating black spruce (Picea mariana), trembling aspen (Populus tremuloides), and paper birch (Betula papyrifera) seedlings at various distances from alder (Alnus viridis subsp. crispa), a nitrogen-fixing shrub, 5 years after wildfire in an Alaskan interior boreal forest. Shoot biomasses and stem diameters of 4-year-old seedlings were recorded, and the fungal community associated with ectomycorrhizal (ECM) root tips from each seedling was profiled using molecular techniques. We found distinct assemblages of fungi associated with alder compared with those associated with the other tree species, making the formation of CMNs between them unlikely. However, among the spruce, aspen, and birch seedlings, there were many shared fungi (including members of the Pezoloma ericae [Hymenoscyphus ericae] species aggregate, Thelephora terrestris, and Russula spp.), raising the possibility that these regenerating seedlings may form interspecies CMNs. Distance between samples did not influence how similar ECM root tip-associated fungal communities were, and of the fungal groups identified, only one of them was more likely to be shared between seedlings that were closer together, suggesting that the majority of fungi surveyed did not have a clumped distribution across the small scale of this study. The presence of some fungal ribotypes was associated with larger or smaller seedlings, suggesting that these fungi may play a role in the promotion or inhibition of seedling growth. The fungal ribotypes associated with larger seedlings were different between spruce, aspen, and birch, suggesting differential impacts of some host-fungus combinations. One may speculate that wildfire-induced shifts in a given soil fungal community could result in variation in the growth response of different plant species

  5. 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.

  6. Mitochondrial Haplotypes Associated with Biomarkers for Alzheimer’s Disease

    PubMed Central

    Ridge, Perry G.; Koop, Andre; Maxwell, Taylor J.; Bailey, Matthew H.; Swerdlow, Russell H.; Kauwe, John S. K.; Honea, Robyn A.

    2013-01-01

    Various studies have suggested that the mitochondrial genome plays a role in late-onset Alzheimer’s disease, although results are mixed. We used an endophenotype-based approach to further characterize mitochondrial genetic variation and its relationship to risk markers for Alzheimer’s disease. We analyzed longitudinal data from non-demented, mild cognitive impairment, and late-onset Alzheimer’s disease participants in the Alzheimer’s Disease Neuroimaging Initiative with genetic, brain imaging, and behavioral data. We assessed the relationship of structural MRI and cognitive biomarkers with mitochondrial genome variation using TreeScanning, a haplotype-based approach that concentrates statistical power by analyzing evolutionarily meaningful groups (or clades) of haplotypes together for association with a phenotype. Four clades were associated with three different endophenotypes: whole brain volume, percent change in temporal pole thickness, and left hippocampal atrophy over two years. This is the first study of its kind to identify mitochondrial variation associated with brain imaging endophenotypes of Alzheimer’s disease. Our results provide additional evidence that the mitochondrial genome plays a role in risk for Alzheimer’s disease. PMID:24040196

  7. Insight from the lamprey genome: glimpsing early vertebrate development via neuroendocrine-associated genes and shared synteny of gonadotropin-releasing hormone (GnRH).

    PubMed

    Decatur, Wayne A; Hall, Jeffrey A; Smith, Jeramiah J; Li, Weiming; Sower, Stacia A

    2013-10-01

    Study of the ancient lineage of jawless vertebrates is key to understanding the origins of vertebrate biology. The establishment of the neuroendocrine system with the hypothalamic-pituitary axis at its crux is of particular interest. Key neuroendocrine hormones in this system include the pivotal gonadotropin-releasing hormones (GnRHs) responsible for controlling reproduction via the pituitary. Previous data incorporating several lines of evidence showed all known vertebrate GnRHs were grouped into four paralogous lineages: GnRH1, 2, 3 and 4; with proposed evolutionary paths. Using the currently available lamprey genome assembly, we searched genes of the neuroendocrine system and summarize here the details representing the state of the current lamprey genome assembly. Additionally, we have analyzed in greater detail the evolutionary history of the GnRHs based on the information of the genomic neighborhood of the paralogs in lamprey as compared to other gnathostomes. Significantly, the current evidence suggests that two genome duplication events (both 1R and 2R) that generated the different fish and tetrapod paralogs took place before the divergence of the ancestral agnathans and gnathostome lineages. Syntenic analysis supports this evidence in that the previously-classified type IV GnRHs in lamprey (lGnRH-I and -III) share a common ancestry with GnRH2 and 3, and thus are no longer considered type IV GnRHs. Given the single amino acid difference between lGnRH-II and GnRH2 we propose that a GnRH2-like gene existed before the lamprey/gnathostome split giving rise to lGnRH-II and GnRH2. Furthermore, paralogous type 3 genes (lGnRH-I/III and GnRH3) evolved divergent structure/function in lamprey and gnathostome lineages.

  8. The search for neuroimaging and cognitive endophenotypes: A critical systematic review of studies involving unaffected first-degree relatives of individuals with bipolar disorder.

    PubMed

    Miskowiak, Kamilla W; Kjærstad, Hanne L; Meluken, Iselin; Petersen, Jeff Zarp; Maciel, Beatriz R; Köhler, Cristiano A; Vinberg, Maj; Kessing, Lars V; Carvalho, André F

    2017-02-01

    The phenomenology and underlying pathophysiology of bipolar disorder (BD) are heterogeneous. The identification of putative endophenotypes for BD can aid in the investigation of unique patho-etiological pathways, which may lead to the development of personalised preventative and therapeutic approaches for this multi-faceted disorder. We included original studies involving unaffected first-degree relatives of BD patients (URs) and a healthy control (HC) comparison group with no first-degree family history of mental disorders, investigating: 'cold' and 'hot' cognition and functional and structural neuroimaging. Seventy-seven cross-sectional studies met the inclusion criteria. The present review revealed that URs in comparison with HCs showed: (i) widespread deficits in verbal memory, sustained attention, and executive function; (ii) abnormalities in the reactivity to and regulation of emotional information along with aberrant reward processing, and heightened attentional interference by emotional stimuli; and (iii) less consistency in the findings regarding structural and resting state neuroimaging, and electrophysiological measures.

  9. Models, Norms and Sharing.

    ERIC Educational Resources Information Center

    Harris, Mary B.

    To investigate the effect of modeling on altruism, 156 third and fifth grade children were exposed to a model who either shared with them, gave to a charity, or refused to share. The test apparatus, identified as a game, consisted of a box with signal lights and a chute through which marbles were dispensed. Subjects and the model played the game…

  10. Shared Parenting Dysfunction.

    ERIC Educational Resources Information Center

    Turkat, Ira Daniel

    2002-01-01

    Joint custody of children is the most prevalent court ordered arrangement for families of divorce. A growing body of literature indicates that many parents engage in behaviors that are incompatible with shared parenting. This article provides specific criteria for a definition of the Shared Parenting Dysfunction. Clinical aspects of the phenomenon…

  11. Intelligence Sharing in Bosnia

    DTIC Science & Technology

    2007-11-02

    increases with the demands of near real time accurate intelligence for operational decision-making. Given this environment, intelligence-sharing...operating system providing actionable near-real- time intelligence to commanders for coalition synchronization and the requirement to protect national...real time accurate intelligence for operational decision-making. Given this environment, intelligence-sharing requirements across an ad hoc coalition

  12. Diminished error-related brain activity as a promising endophenotype for substance-use disorders: evidence from high-risk offspring.

    PubMed

    Euser, Anja S; Evans, Brittany E; Greaves-Lord, Kirstin; Huizink, Anja C; Franken, Ingmar H A

    2013-11-01

    One of the core features of individuals with a substance-use disorder (SUD) is the reduced ability to successfully process errors and monitor performance, as reflected by diminished error-related negativities (ERN). However, whether these error-related brain abnormalities are caused by chronic substance use or rather predates it remains unclear. The present study elucidated whether hypoactive performance monitoring represents an endophenotypic vulnerability marker for SUD by using a high-risk paradigm. We assessed the behavioral components of error-processing, as well as the amplitude of the ERN in the event-related brain potential (ERP) during performance of the Eriksen Flanker Task among high-risk adolescents of parents with a SUD (HR; n = 28) and normal-risk controls (NR; n = 40). Results revealed that HR offspring were characterized by a higher prevalence of internalizing symptoms and more frequent cannabis use, the latter having a significant influence on the ERN. Interestingly, risk group uniquely predicted the negativity amplitude in response to error trials above and beyond confounding variables. Moreover, we found evidence of smaller ERN amplitudes in (cannabis use-naïve) HR offspring, reflecting impaired early processing of error information and suboptimal performance monitoring, whereas no robust group differences were found for overall behavioral performance. This effect was independent of an overall reduction in brain activity. Taken together, although we cannot rule out alternative explanations, the results of our study may provide evidence for the idea that diminished error-processing represents a promising endophenotype for SUD that may indicate a vulnerability to the disorder.

  13. In Search of Shared and Nonshared Environmental Factors in Security of Attachment: A Behavior-Genetic Study of the Association between Sensitivity and Attachment Security

    ERIC Educational Resources Information Center

    Fearon, R. M. Pasco; Van IJzendoorn, Marinus H.; Fonagy, Peter; Bakermans-Kranenburg, Marian J.; Schuengel, Carlo; Bokhorst, Caroline L.

    2006-01-01

    The current article presents results from a twin study of genetic and environmental components of maternal sensitivity and infant attachment and their association. The sample consisted of 136 twin pairs from 2 sites: Leiden, the Netherlands, and London, UK. Maternal sensitivity was assessed in the home at 9-10 months, and infant attachment…

  14. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls.

    PubMed

    Craddock, Nick; Hurles, Matthew E; Cardin, Niall; Pearson, Richard D; Plagnol, Vincent; Robson, Samuel; Vukcevic, Damjan; Barnes, Chris; Conrad, Donald F; Giannoulatou, Eleni; Holmes, Chris; Marchini, Jonathan L; Stirrups, Kathy; Tobin, Martin D; Wain, Louise V; Yau, Chris; Aerts, Jan; Ahmad, Tariq; Andrews, T Daniel; Arbury, Hazel; Attwood, Anthony; Auton, Adam; Ball, Stephen G; Balmforth, Anthony J; Barrett, Jeffrey C; Barroso, Inês; Barton, Anne; Bennett, Amanda J; Bhaskar, Sanjeev; Blaszczyk, Katarzyna; Bowes, John; Brand, Oliver J; Braund, Peter S; Bredin, Francesca; Breen, Gerome; Brown, Morris J; Bruce, Ian N; Bull, Jaswinder; Burren, Oliver S; Burton, John; Byrnes, Jake; Caesar, Sian; Clee, Chris M; Coffey, Alison J; Connell, John M C; Cooper, Jason D; Dominiczak, Anna F; Downes, Kate; Drummond, Hazel E; Dudakia, Darshna; Dunham, Andrew; Ebbs, Bernadette; Eccles, Diana; Edkins, Sarah; Edwards, Cathryn; Elliot, Anna; Emery, Paul; Evans, David M; Evans, Gareth; Eyre, Steve; Farmer, Anne; Ferrier, I Nicol; Feuk, Lars; Fitzgerald, Tomas; Flynn, Edward; Forbes, Alistair; Forty, Liz; Franklyn, Jayne A; Freathy, Rachel M; Gibbs, Polly; Gilbert, Paul; Gokumen, Omer; Gordon-Smith, Katherine; Gray, Emma; Green, Elaine; Groves, Chris J; Grozeva, Detelina; Gwilliam, Rhian; Hall, Anita; Hammond, Naomi; Hardy, Matt; Harrison, Pile; Hassanali, Neelam; Hebaishi, Husam; Hines, Sarah; Hinks, Anne; Hitman, Graham A; Hocking, Lynne; Howard, Eleanor; Howard, Philip; Howson, Joanna M M; Hughes, Debbie; Hunt, Sarah; Isaacs, John D; Jain, Mahim; Jewell, Derek P; Johnson, Toby; Jolley, Jennifer D; Jones, Ian R; Jones, Lisa A; Kirov, George; Langford, Cordelia F; Lango-Allen, Hana; Lathrop, G Mark; Lee, James; Lee, Kate L; Lees, Charlie; Lewis, Kevin; Lindgren, Cecilia M; Maisuria-Armer, Meeta; Maller, Julian; Mansfield, John; Martin, Paul; Massey, Dunecan C O; McArdle, Wendy L; McGuffin, Peter; McLay, Kirsten E; Mentzer, Alex; Mimmack, Michael L; Morgan, Ann E; Morris, Andrew P; Mowat, Craig; Myers, Simon; Newman, William; Nimmo, Elaine R; O'Donovan, Michael C; Onipinla, Abiodun; Onyiah, Ifejinelo; Ovington, Nigel R; Owen, Michael J; Palin, Kimmo; Parnell, Kirstie; Pernet, David; Perry, John R B; Phillips, Anne; Pinto, Dalila; Prescott, Natalie J; Prokopenko, Inga; Quail, Michael A; Rafelt, Suzanne; Rayner, Nigel W; Redon, Richard; Reid, David M; Renwick; Ring, Susan M; Robertson, Neil; Russell, Ellie; St Clair, David; Sambrook, Jennifer G; Sanderson, Jeremy D; Schuilenburg, Helen; Scott, Carol E; Scott, Richard; Seal, Sheila; Shaw-Hawkins, Sue; Shields, Beverley M; Simmonds, Matthew J; Smyth, Debbie J; Somaskantharajah, Elilan; Spanova, Katarina; Steer, Sophia; Stephens, Jonathan; Stevens, Helen E; Stone, Millicent A; Su, Zhan; Symmons, Deborah P M; Thompson, John R; Thomson, Wendy; Travers, Mary E; Turnbull, Clare; Valsesia, Armand; Walker, Mark; Walker, Neil M; Wallace, Chris; Warren-Perry, Margaret; Watkins, Nicholas A; Webster, John; Weedon, Michael N; Wilson, Anthony G; Woodburn, Matthew; Wordsworth, B Paul; Young, Allan H; Zeggini, Eleftheria; Carter, Nigel P; Frayling, Timothy M; Lee, Charles; McVean, Gil; Munroe, Patricia B; Palotie, Aarno; Sawcer, Stephen J; Scherer, Stephen W; Strachan, David P; Tyler-Smith, Chris; Brown, Matthew A; Burton, Paul R; Caulfield, Mark J; Compston, Alastair; Farrall, Martin; Gough, Stephen C L; Hall, Alistair S; Hattersley, Andrew T; Hill, Adrian V S; Mathew, Christopher G; Pembrey, Marcus; Satsangi, Jack; Stratton, Michael R; Worthington, Jane; Deloukas, Panos; Duncanson, Audrey; Kwiatkowski, Dominic P; McCarthy, Mark I; Ouwehand, Willem; Parkes, Miles; Rahman, Nazneen; Todd, John A; Samani, Nilesh J; Donnelly, Peter

    2010-04-01

    Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.

  15. Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits.

    PubMed

    Lane, Jacqueline M; Liang, Jingjing; Vlasac, Irma; Anderson, Simon G; Bechtold, David A; Bowden, Jack; Emsley, Richard; Gill, Shubhroz; Little, Max A; Luik, Annemarie I; Loudon, Andrew; Scheer, Frank A J L; Purcell, Shaun M; Kyle, Simon D; Lawlor, Deborah A; Zhu, Xiaofeng; Redline, Susan; Ray, David W; Rutter, Martin K; Saxena, Richa

    2017-02-01

    Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR-OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (rg = 0.29, P = 1.90 × 10(-13)) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): rg = 0.20, P = 3.12 × 10(-9); waist circumference: rg = 0.20, P = 2.12 × 10(-7)).

  16. 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.

  17. Two case reports of an unusual association between Klippel-Feil syndrome and amyotrophic lateral sclerosis: Do they share same genetic defect?

    PubMed

    Umamaheshwar, Koneru Lakshmi; Sehrawat, Amit; Parashar, Manoj K; Mavade, Kshitij

    2013-10-01

    Klippel-Feil syndrome (KFS) is an unusual skeletal disorder characterized by congenital fusion of two or more cervical vertebrae which can be sporadic or familial. KFS emerges to be a failure of the normal segmentation and fusion of the mesodermal somites during 3(rd) and 8(th) weeks of embryonic development. The triad of low posterior hairline, short neck, and restricted neck motion is present only in 50% and often associated with scoliosis, spina bifida, Sprengel's deformity, cervical ribs, deafness, cleft palate, renal anomalies, congenital heart defects, and so on because of heterogeneous nature of the disease. The significance of KFS lies in the secondary effects produced on the nervous system, which usually presents with features of progressive cord and brain stem compression with relatively minor trauma. We here report two cases of KFS presented in association with amyotrophic lateral sclerosis. Only two such cases have been described in the literature in 1954 and 1975.

  18. Share with thy neighbors

    NASA Astrophysics Data System (ADS)

    Chandra, Surendar; Yu, Xuwen

    2007-01-01

    Peer to peer (P2P) systems are traditionally designed to scale to a large number of nodes. However, we focus on scenarios where the sharing is effected only among neighbors. Localized sharing is particularly attractive in scenarios where wide area network connectivity is undesirable, expensive or unavailable. On the other hand, local neighbors may not offer the wide variety of objects possible in a much larger system. The goal of this paper is to investigate a P2P system that shares contents with its neighbors. We analyze the sharing behavior of Apple iTunes users in an University setting. iTunes restricts the sharing of audio and video objects to peers within the same LAN sub-network. We show that users are already making a significant amount of content available for local sharing. We show that these systems are not appropriate for applications that require access to a specific object. We argue that mechanisms that allow the user to specify classes of interesting objects are better suited for these systems. Mechanisms such as bloom filters can allow each peer to summarize the contents available in the neighborhood, reducing network search overhead. This research can form the basis for future storage systems that utilize the shared storage available in neighbors and build a probabilistic storage for local consumption.

  19. Improving customer satisfaction and quality: hospitals recognized by J.D. power and associates share insights on meeting patient and employee needs.

    PubMed

    2003-08-01

    For 35 years, J.D. Power and Associates has presented its much-coveted awards recognizing product and service quality and customer satisfaction in a variety of industries. This year, the company added a new category: hospitals. To better understand patients' reactions to their hospital experiences, the company looked at five key drivers of customer satisfaction: dignity and respect, speed and efficiency, comfort, information and communication, and emotional support. This issue looks at five hospitals recognized by the company for their service excellence and why they emphasize employee satisfaction as well as patient satisfaction.

  20. Association between heroin use, needle sharing and tattoos received in prison with hepatitis B and C positivity among street-recruited injecting drug users in New Mexico, USA.

    PubMed

    Samuel, M C; Doherty, P M; Bulterys, M; Jenison, S A

    2001-12-01

    This study aimed to assess the seroprevalence and risk factors for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV-1 infections among injecting drug users (IDU) in New Mexico. Serological and behavioural surveys were conducted in conjunction with street-based outreach, education and HIV counselling and testing. High rates of antibody positivity for HCV (82.2%) and HBV (61.1%), and a low rate for HIV (0.5%) were found. In multivariate analyses, both HBV and HCV infection were positively associated with increasing age, increasing years of injection and heroin use. Receipt of a tattoo in prison/jail was associated with HBV (odds ratio = 2.3, 95% confidence interval 1.4, 3.8) and HCV (OR = 3.4, 95% CI = 1.6, 7.5) infections. Prevention of bloodborne pathogens among IDUs should focus on young users, early in their drug use experience. Studies examining the relationship between tattooing and HBV and HCV infection are needed as are efforts to promote sterile tattooing, in prisons and elsewhere.

  1. Access and benefits sharing of genetic resources and associated traditional knowledge in northern Canada: understanding the legal environment and creating effective research agreements

    PubMed Central

    Geary, Janis; Jardine, Cynthia G.; Guebert, Jenilee; Bubela, Tania

    2013-01-01

    Background Research in northern Canada focused on Aboriginal peoples has historically benefited academia with little consideration for the people being researched or their traditional knowledge (TK). Although this attitude is changing, the complexity of TK makes it difficult to develop mechanisms to preserve and protect it. Protecting TK becomes even more important when outside groups become interested in using TK or materials with associated TK. In the latter category are genetic resources, which may have commercial value and are the focus of this article. Objective This article addresses access to and use of genetic resources and associated TK in the context of the historical power-imbalances in research relationships in Canadian north. Design Review. Results Research involving genetic resources and TK is becoming increasingly relevant in northern Canada. The legal framework related to genetic resources and the cultural shift of universities towards commercial goals in research influence the environment for negotiating research agreements. Current guidelines for research agreements do not offer appropriate guidelines to achieve mutual benefit, reflect unequal bargaining power or take the relationship between parties into account. Conclusions Relational contract theory may be a useful framework to address the social, cultural and legal hurdles inherent in creating research agreements. PMID:23986896

  2. Accelerating Spectrum Sharing Technologies

    SciTech Connect

    Juan D. Deaton; Lynda L. Brighton; Rangam Subramanian; Hussein Moradi; Jose Loera

    2013-09-01

    Spectrum sharing potentially holds the promise of solving the emerging spectrum crisis. However, technology innovators face the conundrum of developing spectrum sharing technologies without the ability to experiment and test with real incumbent systems. Interference with operational incumbents can prevent critical services, and the cost of deploying and operating an incumbent system can be prohibitive. Thus, the lack of incumbent systems and frequency authorization for technology incubation and demonstration has stymied spectrum sharing research. To this end, industry, academia, and regulators all require a test facility for validating hypotheses and demonstrating functionality without affecting operational incumbent systems. This article proposes a four-phase program supported by our spectrum accountability architecture. We propose that our comprehensive experimentation and testing approach for technology incubation and demonstration will accelerate the development of spectrum sharing technologies.

  3. A Sharing Proposition.

    ERIC Educational Resources Information Center

    Sturgeon, Julie

    2002-01-01

    Describes how the University of Vermont and St. Michael's College in Burlington, Vermont cooperated to share a single card access system. Discusses the planning, financial, and marketplace advantages of the cooperation. (EV)

  4. Ancestry of the Timorese: age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world

    PubMed Central

    Morrison, Margaux A.; Magalhaes, Tiago R.; Ramke, Jacqueline; Smith, Silvia E.; Ennis, Sean; Simpson, Claire L.; Portas, Laura; Murgia, Federico; Ahn, Jeeyun; Dardenne, Caitlin; Mayne, Katie; Robinson, Rosann; Morgan, Denise J.; Brian, Garry; Lee, Lucy; Woo, Se J.; Zacharaki, Fani; Tsironi, Evangelia E.; Miller, Joan W.; Kim, Ivana K.; Park, Kyu H.; Bailey-Wilson, Joan E.; Farrer, Lindsay A.; Stambolian, Dwight; DeAngelis, Margaret M.

    2015-01-01

    We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age > 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus. PMID:26217379

  5. Global data sharing in Alzheimer's disease research

    PubMed Central

    Toga, Arthur W.; Bhatt, Priya; Ashish, Naveen

    2015-01-01

    Many investigators recognize the importance of data sharing, however they lack the capability to share data. Research efforts could be vastly expanded if Alzheimer's disease data from around the world was linked by a global infrastructure that would enable scientists to access and utilize a secure network of data with thousands of study participants at risk for or already suffering from the disease. We discuss the benefits of data sharing, impediments today and solutions to achieving this on a global scale. We introduce the Global Alzheimer's Association Interactive Network (GAAIN), a novel approach to create a global network of Alzheimer's disease data, researchers, analytical tools and computational resources to better our understanding of this debilitating condition. GAAIN has addressed the key impediments to Alzheimer's disease data sharing with its model and approach. It presents practical, promising, yet data owner sensitive data sharing solutions. PMID:26523713

  6. Coordinating Shared Activities

    NASA Technical Reports Server (NTRS)

    Clement, Bradley

    2004-01-01

    Shared Activity Coordination (ShAC) is a computer program for planning and scheduling the activities of an autonomous team of interacting spacecraft and exploratory robots. ShAC could also be adapted to such terrestrial uses as helping multiple factory managers work toward competing goals while sharing such common resources as floor space, raw materials, and transports. ShAC iteratively invokes the Continuous Activity Scheduling Planning Execution and Replanning (CASPER) program to replan and propagate changes to other planning programs in an effort to resolve conflicts. A domain-expert specifies which activities and parameters thereof are shared and reports the expected conditions and effects of these activities on the environment. By specifying these conditions and effects differently for each planning program, the domain-expert subprogram defines roles that each spacecraft plays in a coordinated activity. The domain-expert subprogram also specifies which planning program has scheduling control over each shared activity. ShAC enables sharing of information, consensus over the scheduling of collaborative activities, and distributed conflict resolution. As the other planning programs incorporate new goals and alter their schedules in the changing environment, ShAC continually coordinates to respond to unexpected events.

  7. Shared care (comanagement).

    PubMed

    Montero Ruiz, E

    2016-01-01

    Surgical departments have increasing difficulties in caring for their hospitalised patients due to the patients' advanced age and comorbidity, the growing specialisation in medical training and the strong political-healthcare pressure that a healthcare organisation places on them, where surgical acts take precedence over other activities. The pressure exerted by these departments on the medical area and the deficient response by the interconsultation system have led to the development of a different healthcare organisation model: Shared care, which includes perioperative medicine. In this model, 2 different specialists share the responsibility and authority in caring for hospitalised surgical patients. Internal Medicine is the most appropriate specialty for shared care. Internists who exercise this responsibility should have certain characteristics and must overcome a number of concerns from the surgeon and anaesthesiologist.

  8. Collaborate, compete and share

    NASA Astrophysics Data System (ADS)

    Pugliese, Emanuele; Castellano, Claudio; Marsili, Matteo; Pietronero, Luciano

    2009-02-01

    We introduce and study a model of an interacting population of agents who collaborate in groups which compete for limited resources. Groups are formed by random matching agents and their worth is determined by the sum of the efforts deployed by agents in group formation. Agents, on their side, have to share their effort between contributing to their group’s chances to outcompete other groups and resource sharing among partners, when the group is successful. A simple implementation of this strategic interaction gives rise to static and evolutionary properties with a very rich phenomenology. A robust emerging feature is the separation of the population between agents who invest mainly in the success of their group and agents who concentrate in getting the largest share of their group’s profits.

  9. Multiparty quantum secret sharing

    SciTech Connect

    Zhang Zhanjun; Li Yong; Man Zhongxiao

    2005-04-01

    Based on a quantum secure direct communication (QSDC) protocol [Phys. Rev. A 69 052319 (2004)], we propose a (n,n)-threshold scheme of multiparty quantum secret sharing of classical messages (QSSCM) using only single photons. We take advantage of this multiparty QSSCM scheme to establish a scheme of multiparty secret sharing of quantum information (SSQI), in which only all quantum information receivers collaborate can the original qubit be reconstructed. A general idea is also proposed for constructing multiparty SSQI schemes from any QSSCM scheme.

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

    PubMed

    Nolin, David A

    2012-07-01

    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.

  11. 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

  12. The Sharing Tree: Preschool Children Learn to Share.

    ERIC Educational Resources Information Center

    Wolf, Arlene; Fine, Elaine

    1996-01-01

    This article describes a learning activity in which preschool children learn cooperative skills and metacognitive strategies as they master sharing strategies guided by leaves on a "sharing tree." Leaf colors (red, yellow, green) cue the child to stop, slow down and think about sharing and playing with others, and go ahead with a sharing activity.…

  13. Sharing Research Results

    ERIC Educational Resources Information Center

    Ashbrook, Peggy

    2011-01-01

    There are many ways to share a collection of data and students' thinking about that data. Explaining the results of science inquiry is important--working scientists and amateurs both contribute information to the body of scientific knowledge. Students can collect data about an activity that is already happening in a classroom (e.g., the qualities…

  14. Shared Governance of Schools.

    ERIC Educational Resources Information Center

    Thomas, M. Donald

    Shared decision-making can help schools keep sight of their true goals. In the educational sector the conflicts that arise in collective bargaining disputes can be destructive to the organization. Schools require more than the mere coexistence of labor and management. They require cooperation and strong, supportive relationships. To establish a…

  15. Learning to Share

    ERIC Educational Resources Information Center

    Raths, David

    2010-01-01

    In the tug-of-war between researchers and IT for supercomputing resources, a centralized approach can help both sides get more bang for their buck. As 2010 began, the University of Washington was preparing to launch its first shared high-performance computing cluster, a 1,500-node system called Hyak, dedicated to research activities. Like other…

  16. Shared decision making

    MedlinePlus

    ... communicate openly and build a relationship of trust. Alternative Names Patient-centered care References Agency for Healthcare Research and Quality. The SHARE Approach. Updated September 2016. www.ahrq.gov/professionals/education/curriculum-tools/shareddecisionmaking/index.html . Accessed October 19, ...

  17. Illegal File Sharing 101

    ERIC Educational Resources Information Center

    Wada, Kent

    2008-01-01

    Much of higher education's unease arises from the cost of dealing with illegal file sharing. Illinois State University, for example, calculated a cost of $76 to process a first claim of copyright infringement and $146 for a second. Responses range from simply passing along claims to elaborate programs architected with specific goals in mind.…

  18. Share the Power.

    ERIC Educational Resources Information Center

    Mitchell, James E.

    1990-01-01

    Site-based management cannot work without the school board's active involvement and determined support. Suggestions are offered from School District 12, Adams County, Colorado, which has been moving away from a centralized administrative system to shared decision-making. (MLF)

  19. Shared Decision Making.

    ERIC Educational Resources Information Center

    Lashway, Larry

    1997-01-01

    In shared decision making (SDM), principals collaborate with teachers and sometimes parents to take actions aimed at improving instruction and school climate. While research on SDM outcomes is still inconclusive, the literature shows that SDM brings both benefits and problems, and that the principal is a key figure. This brief offers a sampling of…

  20. A game theoretic analysis of research data sharing

    PubMed Central

    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. PMID:26401453

  1. 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.

  2. Elastomeric load sharing device

    NASA Technical Reports Server (NTRS)

    Isabelle, Charles J. (Inventor); Kish, Jules G. (Inventor); Stone, Robert A. (Inventor)

    1992-01-01

    An elastomeric load sharing device, interposed in combination between a driven gear and a central drive shaft to facilitate balanced torque distribution in split power transmission systems, includes a cylindrical elastomeric bearing and a plurality of elastomeric bearing pads. The elastomeric bearing and bearing pads comprise one or more layers, each layer including an elastomer having a metal backing strip secured thereto. The elastomeric bearing is configured to have a high radial stiffness and a low torsional stiffness and is operative to radially center the driven gear and to minimize torque transfer through the elastomeric bearing. The bearing pads are configured to have a low radial and torsional stiffness and a high axial stiffness and are operative to compressively transmit torque from the driven gear to the drive shaft. The elastomeric load sharing device has spring rates that compensate for mechanical deviations in the gear train assembly to provide balanced torque distribution between complementary load paths of split power transmission systems.

  3. Shared Health Governance

    PubMed Central

    Ruger, Jennifer Prah

    2014-01-01

    Health and Social Justice (Ruger 2009a) developed the “health capability paradigm,” a conception of justice and health in domestic societies. This idea undergirds an alternative framework of social cooperation called “shared health governance” (SHG). SHG puts forth a set of moral responsibilities, motivational aspirations, and institutional arrangements, and apportions roles for implementation in striving for health justice. This article develops further the SHG framework and explains its importance and implications for governing health domestically. PMID:21745082

  4. Sharing our knowledge.

    PubMed

    Griffiths, Matt

    2017-01-25

    There are more than 70,000 nurse prescribers in the UK, many of whom have years of experience that should be shared with trainee prescribers. In November, the General Pharmaceutical Council launched a consultation on whether pharmacist independent prescribers (PIPs) should be able to mentor trainee PIPs. This discussion, which closes on 1 February, should be expanded to our own and other professional groups, because we could all gain so much from each other.

  5. Intelligence Sharing in Counterproliferation

    DTIC Science & Technology

    2007-09-01

    Routledge, 2004), 75. 3 Dieter Mahncke, Wyn Rees , and Wayne C. Thompson, Redefining transatlantic security relations: The Challenge of Change...Redefining Transatlantic Security Relations, by Dieter Mahncke, Wyn Rees , and Wayne C. Thompson, it is argued that these differences coupled with...Regarding Weapons of Mass Destruction” by U.S. Senators Laurence Silbermann and Charles Robb, “the information sharing problem manifested itself in

  6. University Reactor Sharing Program

    SciTech Connect

    Dr. W.D. Reece

    1999-09-01

    The University Reactor Sharing Program provides funding for reactor experimentation to institutions that do not normally have access to a research reactor. Research projects supported by the program include items such as dating geological material to producing high current super conducting magnets. The funding also gives small colleges and universities the opportunity to use the facility for teaching courses in nuclear processes; specifically neutron activation analysis and gamma spectroscopy.

  7. Efficient quantum secret sharing

    NASA Astrophysics Data System (ADS)

    Qin, Huawang; Dai, Yuewei

    2016-05-01

    An efficient quantum secret sharing scheme is proposed, in which the dealer generates some single particles and then uses the operations of quantum-controlled-not and Hadamard gate to encode a determinate secret into these particles. The participants get their shadows by performing the single-particle measurements on their particles, and even the dealer cannot know their shadows. Compared to the existing schemes, our scheme is more practical within the present technologies.

  8. Toward worldwide data sharing

    NASA Astrophysics Data System (ADS)

    Walker, Raymond; Joy, Steven; King, Todd

    2012-07-01

    Over the past decade the nature of space science research has changed dramatically. Earlier investigators could carry out meaningful research by looking at observations from a single instrument on a single spacecraft. Today that is rapidly changing and researchers regularly use data from multiple instruments on multiple spacecraft as well as observations from ground observatories. Increasingly those observations come from missions flown by many countries. Recent advances in distributed data management have made it possible for researchers located around the world to access and use data from multiple nations. By using virtual observatory technology it no longer matters where data are housed they can be freely accessed wherever they reside. In this presentation we will discuss two initiatives designed to make space science data access worldwide. One is the International Planetary Data Alliance (IPDA) and the other is the Heliophysics Data and Model Consortium (HDMC). In both cases the key to worldwide data sharing is adopting common metadata standards. In this talk we will review how these two groups are addressing the worldwide data sharing and their progress in achieving their goals. IPDA and HDMC are two of several efforts to promote broad based data sharing. Talks in the remainder of the symposium will discuss this is more detail.

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

    PubMed Central

    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. PMID:27013998

  10. Shared cognition as a product of, and precursor to, shared identity in negotiations.

    PubMed

    Swaab, Roderick; Postmes, Tom; van Beest, Ilja; Spears, Russell

    2007-02-01

    Three studies examined the hypothesis that shared cognition and group identification can be each other's catalysts as well as driving forces behind multiparty negotiation outcomes that might not otherwise be realized. Experiment 1 demonstrates that clear links exist between communication, the development of shared cognition and group identification, and integrative outcomes. The subsequent experiments isolated the causal directions of these links. Experiment 2 showed that stronger group identification before interaction was associated with the development of shared cognition in a subsequent phase of negotiation, which then increased the attainment of integrative outcomes. Conversely, a direct manipulation of shared cognition in Experiment 3 resulted in stronger identification during negotiation, which then led to more integrative outcomes. Thus, we find support for the theoretical claim that group identification can be both the product of, and precursor to, the development of shared cognition, with communication functioning as the interface between the two.

  11. Fixed Access Network Sharing

    NASA Astrophysics Data System (ADS)

    Cornaglia, Bruno; Young, Gavin; Marchetta, Antonio

    2015-12-01

    Fixed broadband network deployments are moving inexorably to the use of Next Generation Access (NGA) technologies and architectures. These NGA deployments involve building fiber infrastructure increasingly closer to the customer in order to increase the proportion of fiber on the customer's access connection (Fibre-To-The-Home/Building/Door/Cabinet… i.e. FTTx). This increases the speed of services that can be sold and will be increasingly required to meet the demands of new generations of video services as we evolve from HDTV to "Ultra-HD TV" with 4k and 8k lines of video resolution. However, building fiber access networks is a costly endeavor. It requires significant capital in order to cover any significant geographic coverage. Hence many companies are forming partnerships and joint-ventures in order to share the NGA network construction costs. One form of such a partnership involves two companies agreeing to each build to cover a certain geographic area and then "cross-selling" NGA products to each other in order to access customers within their partner's footprint (NGA coverage area). This is tantamount to a bi-lateral wholesale partnership. The concept of Fixed Access Network Sharing (FANS) is to address the possibility of sharing infrastructure with a high degree of flexibility for all network operators involved. By providing greater configuration control over the NGA network infrastructure, the service provider has a greater ability to define the network and hence to define their product capabilities at the active layer. This gives the service provider partners greater product development autonomy plus the ability to differentiate from each other at the active network layer.

  12. Tripartite quantum state sharing.

    PubMed

    Lance, Andrew M; Symul, Thomas; Bowen, Warwick P; Sanders, Barry C; Lam, Ping Koy

    2004-04-30

    We demonstrate a multipartite protocol to securely distribute and reconstruct a quantum state. A secret quantum state is encoded into a tripartite entangled state and distributed to three players. By collaborating, any two of the three players can reconstruct the state, while individual players obtain nothing. We characterize this (2,3) threshold quantum state sharing scheme in terms of fidelity, signal transfer, and reconstruction noise. We demonstrate a fidelity averaged over all reconstruction permutations of 0.73+/-0.04, a level achievable only using quantum resources.

  13. Plasma protein biomarkers of Alzheimer's disease endophenotypes in asymptomatic older twins: early cognitive decline and regional brain volumes

    PubMed Central

    Kiddle, S J; Steves, C J; Mehta, M; Simmons, A; Xu, X; Newhouse, S; Sattlecker, M; Ashton, N J; Bazenet, C; Killick, R; Adnan, J; Westman, E; Nelson, S; Soininen, H; Kloszewska, I; Mecocci, P; Tsolaki, M; Vellas, B; Curtis, C; Breen, G; Williams, S C R; Lovestone, S; Spector, T D; Dobson, R J B

    2015-01-01

    There is great interest in blood-based markers of Alzheimer's disease (AD), especially in its pre-symptomatic stages. Therefore, we aimed to identify plasma proteins whose levels associate with potential markers of pre-symptomatic AD. We also aimed to characterise confounding by genetics and the effect of genetics on blood proteins in general. Panel-based proteomics was performed using SOMAscan on plasma samples from TwinsUK subjects who are asymptomatic for AD, measuring the level of 1129 proteins. Protein levels were compared with 10-year change in CANTAB-paired associates learning (PAL; n=195), and regional brain volumes (n=34). Replication of proteins associated with regional brain volumes was performed in 254 individuals from the AddNeuroMed cohort. Across all the proteins measured, genetic factors were found to explain ~26% of the variability in blood protein levels on average. The plasma level of the mitogen-activated protein kinase (MAPK) MAPKAPK5 protein was found to positively associate with the 10-year change in CANTAB-PAL in both the individual and twin difference context. The plasma level of protein MAP2K4 was found to suggestively associate negatively (Q<0.1) with the volume of the left entorhinal cortex. Future studies will be needed to assess the specificity of MAPKAPK5 and MAP2K4 to eventual conversion to AD. PMID:26080319

  14. Vaccines, our shared responsibility.

    PubMed

    Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar

    2015-05-05

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases.

  15. Twin Studies and Their Implications for Molecular Genetic Studies: Endophenotypes Integrate Quantitative and Molecular Genetics in ADHD Research

    ERIC Educational Resources Information Center

    Wood, Alexis C.; Neale, Michael C.

    2010-01-01

    Objective: To describe the utility of twin studies for attention-deficit/hyperactivity disorder (ADHD) research and demonstrate their potential for the identification of alternative phenotypes suitable for genomewide association, developmental risk assessment, treatment response, and intervention targets. Method: Brief descriptions of the classic…

  16. Model Sharing and Collaboration using HydroShare

    NASA Astrophysics Data System (ADS)

    Goodall, J. L.; Morsy, M. M.; Castronova, A. M.; Miles, B.; Merwade, V.; Tarboton, D. G.

    2015-12-01

    HydroShare is a web-based system funded by the National Science Foundation (NSF) for sharing hydrologic data and models as resources. Resources in HydroShare can either be assigned a generic type, meaning the resource only has Dublin Core metadata properties, or one of a growing number of specific resource types with enhanced metadata profiles defined by the HydroShare development team. Examples of specific resource types in the current release of HydroShare (http://www.hydroshare.org) include time series, geographic raster, Multidimensional (NetCDF), model program, and model instance. Here we describe research and development efforts in HydroShare project for model-related resources types. This work has included efforts to define metadata profiles for common modeling resources, execute models directly through the HydroShare user interface using Docker containers, and interoperate with the 3rd party application SWATShare for model execution and visualization. These examples demonstrate the benefit of HydroShare to support model sharing and address collaborative problems involving modeling. The presentation will conclude with plans for future modeling-related development in HydroShare including supporting the publication of workflow resources, enhanced metadata for additional hydrologic models, and linking model resources with other resources in HydroShare to capture model provenance.

  17. School Nurses Share a Job.

    ERIC Educational Resources Information Center

    Merwin, Elizabeth G.; Voss, Sondra

    1981-01-01

    Job sharing is a relatively new idea in which two or more people share the hours, the work, and the responsibilities of one job. Advantages and disadvantages to this situation are discussed in relation to the experiences of two nurses who shared a position as district nurse. (JN)

  18. Sharing Educational Services. PREP-13.

    ERIC Educational Resources Information Center

    Jongeward, Ray; Heesacker, Frank

    The focus of this report is on shared services in the rural setting. The kit contains three documents of useful information for any school planning a shared service activity to improve rural education. 13-A identifies 215 shared services in 50 states along with an indexing of each service by subject area and by state. 13-B is a series of 10…

  19. Fractions: How to Fair Share

    ERIC Educational Resources Information Center

    Wilson, P. Holt; Edgington, Cynthia P.; Nguyen, Kenny H.; Pescosolido, Ryan S.; Confrey, Jere

    2011-01-01

    Children learn from a very early age what it means to get their "fair share." Whether it is candy or birthday cake, many children successfully create equal-size groups or parts of a collection or whole but later struggle to create fair shares of multiple wholes, such as fairly sharing four pies among a family of seven. Recent research suggests…

  20. Shared Governance: Balancing the Euphoria.

    ERIC Educational Resources Information Center

    Guffey, J. Stephen; Rampp, Lary C.

    This paper presents an alternative view of shared governance within higher education institutions, examining the major problems encountered by institutions as they implement a shared governance model. Based on a review of the literature, it argues that shared governance, though increasingly popular in recent years, is an issue that should be…

  1. SHARED TECHNOLOGY TRANSFER PROGRAM

    SciTech Connect

    GRIFFIN, JOHN M. HAUT, RICHARD C.

    2008-03-07

    The program established a collaborative process with domestic industries for the purpose of sharing Navy-developed technology. Private sector businesses were educated so as to increase their awareness of the vast amount of technologies that are available, with an initial focus on technology applications that are related to the Hydrogen, Fuel Cells and Infrastructure Technologies (Hydrogen) Program of the U.S. Department of Energy. Specifically, the project worked to increase industry awareness of the vast technology resources available to them that have been developed with taxpayer funding. NAVSEA-Carderock and the Houston Advanced Research Center teamed with Nicholls State University to catalog NAVSEA-Carderock unclassified technologies, rated the level of readiness of the technologies and established a web based catalog of the technologies. In particular, the catalog contains technology descriptions, including testing summaries and overviews of related presentations.

  2. Sharing a disparate landscape

    NASA Astrophysics Data System (ADS)

    Ali-Khan, Carolyne

    2010-06-01

    Working across boundaries of power, identity, and political geography is fraught with difficulties and contradictions. In Tali Tal and Iris Alkaher's, " Collaborative environmental projects in a multicultural society: Working from within separate or mutual landscapes?" the authors describe their efforts to do this in the highly charged atmosphere of Israel. This forum article offers a response to their efforts. Writing from a framework of critical pedagogy, I use the concepts of space and time to anchor my analysis, as I examine the issue of power in this Jew/Arab collaborative environmental project. This response problematizes "sharing" in a landscape fraught with disparities. It also looks to further Tal and Alkaher's work by geographically and politically grounding it in the broader current conflict and by juxtaposing sustainability with equity.

  3. University Reactor Sharing Program

    SciTech Connect

    W.D. Reese

    2004-02-24

    Research projects supported by the program include items such as dating geological material and producing high current super conducting magnets. The funding continues to give small colleges and universities the valuable opportunity to use the NSC for teaching courses in nuclear processes; specifically neutron activation analysis and gamma spectroscopy. The Reactor Sharing Program has supported the construction of a Fast Neutron Flux Irradiator for users at New Mexico Institute of Mining and Technology and the University of Houston. This device has been characterized and has been found to have near optimum neutron fluxes for A39/Ar 40 dating. Institution final reports and publications resulting from the use of these funds are on file at the Nuclear Science Center.

  4. Dysbindin (DTNBP1, 6p22.3) is Associated with Childhood-Onset Psychosis and Endophenotypes Measured by the Premorbid Adjustment Scale (PAS)

    ERIC Educational Resources Information Center

    Gornick, M. C.; Addington, A. M.; Sporn, A.; Gogtay, N.; Greenstein, D.; Lenane, M.; Gochman, P.; Ordonez, A.; Balkissoon, R.; Vakkalanka, R.; Weinberger, D. R.; Rapoport, J. L.; Straub, R. E.

    2005-01-01

    Straub "et al." ("2002") recently identified the 6p22.3 gene dysbindin (DTNBP1) through positional cloning as a schizophrenia susceptibility gene. We studied a rare cohort of 102 children with onset of psychosis before age 13. Standardized ratings of early development, medication response, neuropsychological and cognitive performance, premorbid…

  5. Precompetitive Data Sharing as a Catalyst to Address Unmet Needs in Parkinson's Disease.

    PubMed

    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

    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.

  6. Making SharePoint® Chemically Aware™

    PubMed Central

    2012-01-01

    Background The use of SharePoint® collaboration software for content management has become a critical part of today's drug discovery process. SharePoint 2010 software has laid a foundation which enables researchers to collaborate and search on various contents. The amount of data generated during a transition of a single compound from preclinical discovery to commercialization can easily range in terabytes, thus there is a greater demand of a chemically aware search algorithm that supplements SharePoint which enables researchers to query for information in a more intuitive and effective way. Thus by supplementing SharePoint with Chemically Aware™ features provides a great value to the pharmaceutical and biotech companies and makes drug discovery more efficient. Using several tools we have integrated SharePoint with chemical, compound, and reaction databases, thereby improving the traditional search engine capability and enhancing the user experience. Results This paper describes the implementation of a Chemically Aware™ system to supplement SharePoint. A Chemically Aware SharePoint (CASP) allows users to tag documents by drawing a structure and associating it with the related content. It also allows the user to search SharePoint software content and internal/external databases by carrying out substructure, similarity, SMILES, and IUPAC name searches. Building on traditional search, CASP takes SharePoint one step further by providing a intuitive GUI to the researchers to base their search on their knowledge of chemistry than textual search. CASP also provides a way to integrate with other systems, for example a researcher can perform a sub-structure search on pdf documents with embedded molecular entities. Conclusion A Chemically Aware™ system supplementing SharePoint is a step towards making drug discovery process more efficient and also helps researchers to search for information in a more intuitive way. It also helps the researchers to find information

  7. Framework for Shared Drinking Water Risk Assessment.

    SciTech Connect

    Lowry, Thomas Stephen; Tidwell, Vincent C.; Peplinski, William John; Mitchell, Roger; Binning, David; Meszaros, Jenny

    2017-01-01

    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 three water utilities. Demonstration results were then compared to risk assessment results developed using a different risk assessment application by a different set of analysts.

  8. 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

  9. Prefrontal hypoactivity associated with impaired inhibition in stimulant-dependent individuals but evidence for hyperactivation in their unaffected siblings.

    PubMed

    Morein-Zamir, Sharon; Simon Jones, P; Bullmore, Edward T; Robbins, Trevor W; Ersche, Karen D

    2013-09-01

    A neurocognitive endophenotype has been proposed for stimulant dependence, based on behavioral measures of inhibitory response control associated with white matter changes in the frontal cortex. This study investigated the functional neuroimaging correlates of inhibitory response control, as functional activity serves as a more dynamic measure than brain structure, allowing refinement of the suggested endophenotype. Stimulant-dependent individuals (SDIs), their unaffected siblings (SIBs), and healthy controls (CTs) performed the stop-signal task, including stop-signal reaction time (SSRT) as a measure of response inhibition, while undergoing functional magnetic resonance imaging. SDIs had impaired response inhibition accompanied by hypoactivation in the ventrolateral prefrontal cortex (PFC). In addition, they demonstrated hypoactivation in the anterior cingulate when failing to stop. In contrast, no hypoactivations were noted in their unaffected SIBs. Rather, they exhibited increased activation in the dorsomedial PFC relative to controls, together with inhibitory performance that was intermediate between that of the stimulant group and the healthy CT group. Such hyperactivations within the neurocircuitry underlying response inhibition and control are suggestive of compensatory mechanisms that could be protective in nature or could reflect coping with a pre-existing vulnerability, thus expressing potential aspects of resilience. The functional activation associated with response inhibition and error monitoring showed differential patterns of results between SDIs and their unaffected first-degree relatives, suggesting that the proposed endophenotype does not generalize to functional brain activity.

  10. Prefrontal Hypoactivity Associated with Impaired Inhibition in Stimulant-Dependent Individuals but Evidence for Hyperactivation in their Unaffected Siblings

    PubMed Central

    Morein-Zamir, Sharon; Simon Jones, P; Bullmore, Edward T; Robbins, Trevor W; Ersche, Karen D

    2013-01-01

    A neurocognitive endophenotype has been proposed for stimulant dependence, based on behavioral measures of inhibitory response control associated with white matter changes in the frontal cortex. This study investigated the functional neuroimaging correlates of inhibitory response control, as functional activity serves as a more dynamic measure than brain structure, allowing refinement of the suggested endophenotype. Stimulant-dependent individuals (SDIs), their unaffected siblings (SIBs), and healthy controls (CTs) performed the stop-signal task, including stop-signal reaction time (SSRT) as a measure of response inhibition, while undergoing functional magnetic resonance imaging. SDIs had impaired response inhibition accompanied by hypoactivation in the ventrolateral prefrontal cortex (PFC). In addition, they demonstrated hypoactivation in the anterior cingulate when failing to stop. In contrast, no hypoactivations were noted in their unaffected SIBs. Rather, they exhibited increased activation in the dorsomedial PFC relative to controls, together with inhibitory performance that was intermediate between that of the stimulant group and the healthy CT group. Such hyperactivations within the neurocircuitry underlying response inhibition and control are suggestive of compensatory mechanisms that could be protective in nature or could reflect coping with a pre-existing vulnerability, thus expressing potential aspects of resilience. The functional activation associated with response inhibition and error monitoring showed differential patterns of results between SDIs and their unaffected first-degree relatives, suggesting that the proposed endophenotype does not generalize to functional brain activity. PMID:23609131

  11. Data sharing in neuroimaging research

    PubMed Central

    Poline, Jean-Baptiste; Breeze, Janis L.; Ghosh, Satrajit; Gorgolewski, Krzysztof; Halchenko, Yaroslav O.; Hanke, Michael; Haselgrove, Christian; Helmer, Karl G.; Keator, David B.; Marcus, Daniel S.; Poldrack, Russell A.; Schwartz, Yannick; Ashburner, John; Kennedy, David N.

    2012-01-01

    Significant resources around the world have been invested in neuroimaging studies of brain function and disease. Easier access to this large body of work should have profound impact on research in cognitive neuroscience and psychiatry, leading to advances in the diagnosis and treatment of psychiatric and neurological disease. A trend toward increased sharing of neuroimaging data has emerged in recent years. Nevertheless, a number of barriers continue to impede momentum. Many researchers and institutions remain uncertain about how to share data or lack the tools and expertise to participate in data sharing. The use of electronic data capture (EDC) methods for neuroimaging greatly simplifies the task of data collection and has the potential to help standardize many aspects of data sharing. We review here the motivations for sharing neuroimaging data, the current data sharing landscape, and the sociological or technical barriers that still need to be addressed. The INCF Task Force on Neuroimaging Datasharing, in conjunction with several collaborative groups around the world, has started work on several tools to ease and eventually automate the practice of data sharing. It is hoped that such tools will allow researchers to easily share raw, processed, and derived neuroimaging data, with appropriate metadata and provenance records, and will improve the reproducibility of neuroimaging studies. By providing seamless integration of data sharing and analysis tools within a commodity research environment, the Task Force seeks to identify and minimize barriers to data sharing in the field of neuroimaging. PMID:22493576

  12. Contexts as Shared Commitments

    PubMed Central

    García-Carpintero, Manuel

    2015-01-01

    Contemporary semantics assumes two influential notions of context: one coming from Kaplan (1989), on which contexts are sets of predetermined parameters, and another originating in Stalnaker (1978), on which contexts are sets of propositions that are “common ground.” The latter is deservedly more popular, given its flexibility in accounting for context-dependent aspects of language beyond manifest indexicals, such as epistemic modals, predicates of taste, and so on and so forth; in fact, properly dealing with demonstratives (perhaps ultimately all indexicals) requires that further flexibility. Even if we acknowledge Lewis (1980)'s point that, in a sense, Kaplanian contexts already include common ground contexts, it is better to be clear and explicit about what contexts constitutively are. Now, Stalnaker (1978, 2002, 2014) defines context-as-common-ground as a set of propositions, but recent work shows that this is not an accurate conception. The paper explains why, and provides an alternative. The main reason is that several phenomena (presuppositional treatments of pejoratives and predicates of taste, forces other than assertion) require that the common ground includes non-doxastic attitudes such as appraisals, emotions, etc. Hence the common ground should not be taken to include merely contents (propositions), but those together with attitudes concerning them: shared commitments, as I will defend. PMID:26733087

  13. Contexts as Shared Commitments.

    PubMed

    García-Carpintero, Manuel

    2015-01-01

    Contemporary semantics assumes two influential notions of context: one coming from Kaplan (1989), on which contexts are sets of predetermined parameters, and another originating in Stalnaker (1978), on which contexts are sets of propositions that are "common ground." The latter is deservedly more popular, given its flexibility in accounting for context-dependent aspects of language beyond manifest indexicals, such as epistemic modals, predicates of taste, and so on and so forth; in fact, properly dealing with demonstratives (perhaps ultimately all indexicals) requires that further flexibility. Even if we acknowledge Lewis (1980)'s point that, in a sense, Kaplanian contexts already include common ground contexts, it is better to be clear and explicit about what contexts constitutively are. Now, Stalnaker (1978, 2002, 2014) defines context-as-common-ground as a set of propositions, but recent work shows that this is not an accurate conception. The paper explains why, and provides an alternative. The main reason is that several phenomena (presuppositional treatments of pejoratives and predicates of taste, forces other than assertion) require that the common ground includes non-doxastic attitudes such as appraisals, emotions, etc. Hence the common ground should not be taken to include merely contents (propositions), but those together with attitudes concerning them: shared commitments, as I will defend.

  14. Sharing Lessons Learned

    SciTech Connect

    Mohler, Bryan L.

    2004-09-01

    Workplace safety is inextricably tied to the culture – the leadership, management and organization – of the entire company. Nor is a safety lesson fundamentally different from any other business lesson. With these points in mind, Pacific Northwest National Laboratory recast its lessons learned program in 2000. The laboratory retained elements of a traditional lessons learned program, such as tracking and trending safety metrics, and added a best practices element to increase staff involvement in creating a safer, healthier work environment. Today, the Lessons Learned/Best Practices program offers the latest business thinking summarized from current external publications and shares better ways PNNL staff have discovered for doing things. According to PNNL strategic planning director Marilyn Quadrel, the goal is to sharpen the business acumen, project management ability and leadership skills of all staff and to capture the benefits of practices that emerge from lessons learned. A key tool in the PNNL effort to accelerate learning from past mistakes is one that can be easily implemented by other firms and tailored to their specific needs. It is the weekly placement of Lessons Learned/Best Practices articles in the lab’s internal electronic newsletter. The program is equally applicable in highly regulated environments, such as the national laboratories, and in enterprises that may have fewer external requirements imposed on their operations. And it is cost effective, using less than the equivalent of one fulltime person to administer.

  15. Are Auditory-Evoked Frequency and Duration Mismatch Negativity (MMN) Deficits Endophenotypic for Schizophrenia? High-Density Electrical Mapping in Clinically Unaffected First-Degree Relatives, First-Episode and Chronic Schizophrenia

    PubMed Central

    Magno, Elena; Yeap, Sherlyn; Thakore, Jogin H.; Garavan, Hugh; De Sanctis, Pierfilippo; Javitt, Daniel C.; Foxe, John J.

    2008-01-01

    Background Mismatch negativity (MMN) is a negative-going event-related potential (ERP) component that occurs in response to intermittent changes in constant auditory backgrounds. A consistent finding across a large number of studies has been impaired MMN generation in schizophrenia, which has been interpreted as evidence for fundamental deficits in automatic auditory sensory processing. The aim of this study was to investigate the extent to which dysfunction in MMN generation might represent an endophenotypic marker for schizophrenia. Methods We measured MMN to deviants in duration (25 msec, 1000Hz) and deviants in pitch (50 msec, 1200Hz) relative to standard tones (50 msec, 1000Hz) in 45 chronic schizophrenia patients, 25 of their first-degree unaffected biological relatives, 12 first-episode patients, and 27 healthy control subjects. Results In line with previous work, MMN amplitudes to duration deviants (but not to pitch deviants) were significantly reduced in patients with chronic schizophrenia compared to control subjects. However, both duration and pitch MMNs were completely unaffected in the first-degree biological relatives and this was also the case for the first-episode patients. Furthermore, length of illness did not predict the extent of MMN deficit. Conclusions These findings suggest that the MMN deficit seen in schizophrenia patients is most likely a consequence of the disease and that MMN, at least to basic auditory feature deviants, is at best only weakly endophenotypic for schizophrenia. PMID:18472090

  16. 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…

  17. 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…

  18. 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…

  19. 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.

  20. Technology Mediated Information Sharing (Monitor Sharing) in Primary Care Encounters

    ERIC Educational Resources Information Center

    Asan, Onur

    2013-01-01

    The aim of this dissertation study was to identify and describe the use of electronic health records (EHRs) for information sharing between patients and clinicians in primary-care encounters and to understand work system factors influencing information sharing. Ultimately, this will promote better design of EHR technologies and effective training…

  1. 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.

  2. Collecting, Preserving & Sharing Information in Micronesia. Proceedings of the Annual Pacific Islands Association of Libraries and Archives Conference (3rd, Saipan, Northern Mariana Islands, October 13-15, 1993).

    ERIC Educational Resources Information Center

    Pacific Islands Association of Libraries and Archives, Guam.

    Participants from Washington, Hawaii, Majuro, Palau, Guam and other points in the Northern Mariana Islands came together to share information relating to the functions of libraries and archives as information banks and as preservers of the cultural heritage of Micronesia. Papers presented were: (1) "Reading Motivation in the Pacific"…

  3. The Evolution of "Association" as a Model for Lay/Religious Collaboration in Catholic Education, Part II: The Emergence of Shared Mission as a Ministry Paradigm, 1986-2000

    ERIC Educational Resources Information Center

    Tidd, Kevin M.

    2009-01-01

    In Part I of this two-part series (published in the March 2009 issue), the author traced the evolution of the Brothers of the Christian Schools' (Christian Brothers in the United States) understanding of how they related to the lay people with whom they increasingly shared their apostolate of Catholic education. From a stance of wary distance in…

  4. 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

  5. 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.

  6. Sharing Teaching Ideas.

    ERIC Educational Resources Information Center

    Mathematics Teacher, 1992

    1992-01-01

    Presents three teaching ideas involving (1) results of participation in the annual American Statistical Association's poster contest for students in grades K-12; (2) a variation on an annuity problem in which the contribution each year is increased by a given percentage; and (3) concrete activities to help students understand the meaning of radian…

  7. Sharing stories of discrimination with parents.

    PubMed

    Juang, Linda P; Syed, Moin

    2014-04-01

    In this study we examined whether experiences of discrimination during childhood and adolescence were told to parents, the reasons for not telling, and whether telling was associated with adolescent characteristics and aspects of the current parent-child relationship. The sample included 200 ethnically diverse college students. Results supported a transactional view of socialization whereby youth who had not shared their discrimination stories expected negative parental reactions or were concerned for their parents' well-being. The likelihood of telling was not directly associated with ethnicity, gender, or parent-child communication. Rather, those who rated the discrimination event as more important and reported greater current parental cultural and racial socialization were more likely to have disclosed their story of discrimination, depending on ethnicity. Understanding disclosure of discrimination experiences is important. When adolescents choose not to share experiences of discrimination with their parents, there may be lost opportunities for a greater understanding of these challenging experiences.

  8. Different Approaches to Shared Services.

    ERIC Educational Resources Information Center

    Hall, Calvin W.

    Divided into four major sections, this collection of articles addresses the sharing of services in California by school districts or by districts and other agencies. The section on advertising and recruitment makes a case for districts to share in the purchase of employment ads or in the hiring of a recruiter. A reprint of an article about a…

  9. Food Sharing: An Evolutionary Perspective.

    ERIC Educational Resources Information Center

    Feinman, Saul

    Food altruism and the consumption of food are examined from a sociological perspective which assumes that humans share food as inclusive fitness actors. Inclusive fitness implies the representation of an individual's genes in future generations through his own or others' offspring. The discussion includes characteristics of food sharing among kin…

  10. Transforming Institutions through Shared Governance

    ERIC Educational Resources Information Center

    Bornstein, Rita

    2012-01-01

    Shared governance is a basic tenet of higher education and is frequently referred to. For shared governance to be successful, board members, administrators, and faculty members must learn to have respect for and confidence in each other, acting inclusively, transparently, and responsibly. Boards need to be active and involved, participating in…

  11. Resource Sharing in Community Colleges.

    ERIC Educational Resources Information Center

    Meyer, Frank; Hines, Edward; Lupo, Anita; Ley, Connie

    1998-01-01

    Presents a study analyzing voluntary resource sharing practices in a state population of 49 community colleges. Asserts that while resource sharing has been used primarily to solve short-term needs, it should be integrated in strategic and long-term fiscal planning. (JDI)

  12. Successful Shared Governance Through Education.

    PubMed

    Brull, Stacey

    2015-01-01

    Shared governance is one way nurses can attain a healthy work environment. Having direct-care nurses involved in raising relevant clinical and operational issues and creating systematic approaches has been linked to greater levels of empowerment which is often transposed into shared governance. Nurse leaders at one hospital used a comprehensive educational strategy to implement shared governance in less than 2 years. An authoritative style of leadership and decision making does not meet the needs of today's complex health care environment; nor does it meet the needs of today's employees. The focus on a very deliberate and educational strategy for shared governance was successful in building the structures and processes needed to take a unit and division from traditional governance to shared governance in less than 2 years.

  13. Nonlinear Secret Image Sharing Scheme

    PubMed Central

    Shin, Sang-Ho; Yoo, Kee-Young

    2014-01-01

    Over the past decade, most of secret image sharing schemes have been proposed by using Shamir's technique. It is based on a linear combination polynomial arithmetic. Although Shamir's technique based secret image sharing schemes are efficient and scalable for various environments, there exists a security threat such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing technique based on nonlinear combination polynomial arithmetic in order to solve this threat. It is hard to apply to the secret image sharing. In this paper, we propose a (t, n)-threshold nonlinear secret image sharing scheme with steganography concept. In order to achieve a suitable and secure secret image sharing scheme, we adapt a modified LSB embedding technique with XOR Boolean algebra operation, define a new variable m, and change a range of prime p in sharing procedure. In order to evaluate efficiency and security of proposed scheme, we use the embedding capacity and PSNR. As a result of it, average value of PSNR and embedding capacity are 44.78 (dB) and 1.74t⌈log2⁡m⌉ bit-per-pixel (bpp), respectively. PMID:25140334

  14. Nonlinear secret image sharing scheme.

    PubMed

    Shin, Sang-Ho; Lee, Gil-Je; Yoo, Kee-Young

    2014-01-01

    Over the past decade, most of secret image sharing schemes have been proposed by using Shamir's technique. It is based on a linear combination polynomial arithmetic. Although Shamir's technique based secret image sharing schemes are efficient and scalable for various environments, there exists a security threat such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing technique based on nonlinear combination polynomial arithmetic in order to solve this threat. It is hard to apply to the secret image sharing. In this paper, we propose a (t, n)-threshold nonlinear secret image sharing scheme with steganography concept. In order to achieve a suitable and secure secret image sharing scheme, we adapt a modified LSB embedding technique with XOR Boolean algebra operation, define a new variable m, and change a range of prime p in sharing procedure. In order to evaluate efficiency and security of proposed scheme, we use the embedding capacity and PSNR. As a result of it, average value of PSNR and embedding capacity are 44.78 (dB) and 1.74t⌈log2 m⌉ bit-per-pixel (bpp), respectively.

  15. Expansible quantum secret sharing network

    NASA Astrophysics Data System (ADS)

    Sun, Ying; Xu, Sheng-Wei; Chen, Xiu-Bo; Niu, Xin-Xin; Yang, Yi-Xian

    2013-08-01

    In the practical applications, member expansion is a usual demand during the development of a secret sharing network. However, there are few consideration and discussion on network expansibility in the existing quantum secret sharing schemes. We propose an expansible quantum secret sharing scheme with relatively simple and economical quantum resources and show how to split and reconstruct the quantum secret among an expansible user group in our scheme. Its trait, no requirement of any agent's assistant during the process of member expansion, can help to prevent potential menaces of insider cheating. We also give a discussion on the security of this scheme from three aspects.

  16. 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.

  17. Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

    PubMed Central

    Meda, Shashwath A.; Ruaño, Gualberto; Windemuth, Andreas; O’Neil, Kasey; Berwise, Clifton; Dunn, Sabra M.; Boccaccio, Leah E.; Narayanan, Balaji; Kocherla, Mohan; Sprooten, Emma; Keshavan, Matcheri S.; Tamminga, Carol A.; Sweeney, John A.; Clementz, Brett A.; Calhoun, Vince D.; Pearlson, Godfrey D.

    2014-01-01

    The brain’s default mode network (DMN) is highly heritable and is compromised in a variety of psychiatric disorders. However, genetic control over the DMN in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is largely unknown. Study subjects (n = 1,305) underwent a resting-state functional MRI scan and were analyzed by a two-stage approach. The initial analysis used independent component analysis (ICA) in 324 healthy controls, 296 SZ probands, 300 PBP probands, 179 unaffected first-degree relatives of SZ probands (SZREL), and 206 unaffected first-degree relatives of PBP probands to identify DMNs and to test their biomarker and/or endophenotype status. A subset of controls and probands (n = 549) then was subjected to a parallel ICA (para-ICA) to identify imaging–genetic relationships. ICA identified three DMNs. Hypo-connectivity was observed in both patient groups in all DMNs. Similar patterns observed in SZREL were restricted to only one network. DMN connectivity also correlated with several symptom measures. Para-ICA identified five sub-DMNs that were significantly associated with five different genetic networks. Several top-ranking SNPs across these networks belonged to previously identified, well-known psychosis/mood disorder genes. Global enrichment analyses revealed processes including NMDA-related long-term potentiation, PKA, immune response signaling, axon guidance, and synaptogenesis that significantly influenced DMN modulation in psychoses. In summary, we observed both unique and shared impairments in functional connectivity across the SZ and PBP cohorts; these impairments were selectively familial only for SZREL. Genes regulating specific neurodevelopment/transmission processes primarily mediated DMN disconnectivity. The study thus identifies biological pathways related to a widely researched quantitative trait that might suggest novel, targeted drug treatments for these diseases. PMID:24778245

  18. Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia.

    PubMed

    Meda, Shashwath A; Ruaño, Gualberto; Windemuth, Andreas; O'Neil, Kasey; Berwise, Clifton; Dunn, Sabra M; Boccaccio, Leah E; Narayanan, Balaji; Kocherla, Mohan; Sprooten, Emma; Keshavan, Matcheri S; Tamminga, Carol A; Sweeney, John A; Clementz, Brett A; Calhoun, Vince D; Pearlson, Godfrey D

    2014-05-13

    The brain's default mode network (DMN) is highly heritable and is compromised in a variety of psychiatric disorders. However, genetic control over the DMN in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is largely unknown. Study subjects (n = 1,305) underwent a resting-state functional MRI scan and were analyzed by a two-stage approach. The initial analysis used independent component analysis (ICA) in 324 healthy controls, 296 SZ probands, 300 PBP probands, 179 unaffected first-degree relatives of SZ probands (SZREL), and 206 unaffected first-degree relatives of PBP probands to identify DMNs and to test their biomarker and/or endophenotype status. A subset of controls and probands (n = 549) then was subjected to a parallel ICA (para-ICA) to identify imaging-genetic relationships. ICA identified three DMNs. Hypo-connectivity was observed in both patient groups in all DMNs. Similar patterns observed in SZREL were restricted to only one network. DMN connectivity also correlated with several symptom measures. Para-ICA identified five sub-DMNs that were significantly associated with five different genetic networks. Several top-ranking SNPs across these networks belonged to previously identified, well-known psychosis/mood disorder genes. Global enrichment analyses revealed processes including NMDA-related long-term potentiation, PKA, immune response signaling, axon guidance, and synaptogenesis that significantly influenced DMN modulation in psychoses. In summary, we observed both unique and shared impairments in functional connectivity across the SZ and PBP cohorts; these impairments were selectively familial only for SZREL. Genes regulating specific neurodevelopment/transmission processes primarily mediated DMN disconnectivity. The study thus identifies biological pathways related to a widely researched quantitative trait that might suggest novel, targeted drug treatments for these diseases.

  19. Bilevel shared control for teleoperators

    NASA Technical Reports Server (NTRS)

    Hayati, Samad A. (Inventor); Venkataraman, Subramanian T. (Inventor)

    1992-01-01

    A shared system is disclosed for robot control including integration of the human and autonomous input modalities for an improved control. Autonomously planned motion trajectories are modified by a teleoperator to track unmodelled target motions, while nominal teleoperator motions are modified through compliance to accommodate geometric errors autonomously in the latter. A hierarchical shared system intelligently shares control over a remote robot between the autonomous and teleoperative portions of an overall control system. Architecture is hierarchical, and consists of two levels. The top level represents the task level, while the bottom, the execution level. In space applications, the performance of pure teleoperation systems depend significantly on the communication time delays between the local and the remote sites. Selection/mixing matrices are provided with entries which reflect how each input's signals modality is weighted. The shared control minimizes the detrimental effects caused by these time delays between earth and space.

  20. Information sharing promotes prosocial behaviour

    NASA Astrophysics Data System (ADS)

    Szolnoki, Attila; Perc, Matjaž

    2013-05-01

    More often than not, bad decisions are bad regardless of where and when they are made. Information sharing might thus be utilized to mitigate them. Here we show that sharing information about strategy choice between players residing on two different networks reinforces the evolution of cooperation. In evolutionary games, the strategy reflects the action of each individual that warrants the highest utility in a competitive setting. We therefore assume that identical strategies on the two networks reinforce themselves by lessening their propensity to change. Besides network reciprocity working in favour of cooperation on each individual network, we observe the spontaneous emergence of correlated behaviour between the two networks, which further deters defection. If information is shared not just between individuals but also between groups, the positive effect is even stronger, and this despite the fact that information sharing is implemented without any assumptions with regard to content.

  1. The value of shared services.

    PubMed

    Wallace, Beverly B

    2011-07-01

    A multisite shared services organization, combined with a robust business continuity plan, provides infrastructure and redundancies that mitigate risk for hospital CFOs. These structures can position providers to do the following: move essential operations out of a disaster impact zone, if necessary. Allow resources to focus on immediate patient care needs. Take advantage of economies of scale in temporary staffing. Leverage technology. Share in investments in disaster preparedness and business continuity solutions

  2. Split torque transmission load sharing

    NASA Technical Reports Server (NTRS)

    Krantz, T. L.; Rashidi, M.; Kish, J. G.

    1992-01-01

    Split torque transmissions are attractive alternatives to conventional planetary designs for helicopter transmissions. The split torque designs can offer lighter weight and fewer parts but have not been used extensively for lack of experience, especially with obtaining proper load sharing. Two split torque designs that use different load sharing methods have been studied. Precise indexing and alignment of the geartrain to produce acceptable load sharing has been demonstrated. An elastomeric torque splitter that has large torsional compliance and damping produces even better load sharing while reducing dynamic transmission error and noise. However, the elastomeric torque splitter as now configured is not capable over the full range of operating conditions of a fielded system. A thrust balancing load sharing device was evaluated. Friction forces that oppose the motion of the balance mechanism are significant. A static analysis suggests increasing the helix angle of the input pinion of the thrust balancing design. Also, dynamic analysis of this design predicts good load sharing and significant torsional response to accumulative pitch errors of the gears.

  3. Creativity and psychopathology: a shared vulnerability model.

    PubMed

    Carson, Shelley H

    2011-03-01

    Creativity is considered a positive personal trait. However, highly creative people have demonstrated elevated risk for certain forms of psychopathology, including mood disorders, schizophrenia spectrum disorders, and alcoholism. A model of shared vulnerability explains the relation between creativity and psychopathology. This model, supported by recent findings from neuroscience and molecular genetics, suggests that the biological determinants conferring risk for psychopathology interact with protective cognitive factors to enhance creative ideation. Elements of shared vulnerability include cognitive disinhibition (which allows more stimuli into conscious awareness), an attentional style driven by novelty salience, and neural hyperconnectivity that may increase associations among disparate stimuli. These vulnerabilities interact with superior meta-cognitive protective factors, such as high IQ, increased working memory capacity, and enhanced cognitive flexibility, to enlarge the range and depth of stimuli available in conscious awareness to be manipulated and combined to form novel and original ideas.

  4. Reciprocal food sharing in the vampire bat

    NASA Astrophysics Data System (ADS)

    Wilkinson, Gerald S.

    1984-03-01

    Behavioural reciprocity can be evolutionarily stable1-3. Initial increase in frequency depends, however, on reciprocal altruists interacting predominantly with other reciprocal altruists either by associating within kin groups or by having sufficient memory to recognize and not aid nonreciprocators. Theory thus suggests that reciprocity should evolve more easily among animals which live in kin groups. Data are available separating reciprocity from nepotism only for unrelated nonhuman animals4. Here, I show that food sharing by regurgitation of blood among wild vampire bats (Desmodus rotundus) depends equally and independently on degree of relatedness and an index of opportunity for recipro cation. That reciprocity operates within groups containing both kin and nonkin is supported further with data on the availability of blood-sharing occasions, estimates of the economics of shar ing blood, and experiments which show that unrelated bats will reciprocally exchange blood in captivity.

  5. 7 CFR 1980.391 - Equity sharing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... property. Shared equity will be the lesser of the interest assistance granted or the amount of value appreciation available for shared equity. Value appreciation available for shared equity means the market value... amount of shared equity. The RHS approval official will calculate shared equity when a borrower's...

  6. Display Sharing: An Alternative Paradigm

    NASA Technical Reports Server (NTRS)

    Brown, Michael A.

    2010-01-01

    The current Johnson Space Center (JSC) Mission Control Center (MCC) Video Transport System (VTS) provides flight controllers and management the ability to meld raw video from various sources with telemetry to improve situational awareness. However, maintaining a separate infrastructure for video delivery and integration of video content with data adds significant complexity and cost to the system. When considering alternative architectures for a VTS, the current system's ability to share specific computer displays in their entirety to other locations, such as large projector systems, flight control rooms, and back supporting rooms throughout the facilities and centers must be incorporated into any new architecture. Internet Protocol (IP)-based systems also support video delivery and integration. IP-based systems generally have an advantage in terms of cost and maintainability. Although IP-based systems are versatile, the task of sharing a computer display from one workstation to another can be time consuming for an end-user and inconvenient to administer at a system level. The objective of this paper is to present a prototype display sharing enterprise solution. Display sharing is a system which delivers image sharing across the LAN while simultaneously managing bandwidth, supporting encryption, enabling recovery and resynchronization following a loss of signal, and, minimizing latency. Additional critical elements will include image scaling support, multi -sharing, ease of initial integration and configuration, integration with desktop window managers, collaboration tools, host and recipient controls. This goal of this paper is to summarize the various elements of an IP-based display sharing system that can be used in today's control center environment.

  7. 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…

  8. Theory and ontology for sharing temporal knowledge

    NASA Technical Reports Server (NTRS)

    Loganantharaj, Rasiah

    1996-01-01

    Using current technology, the sharing or re-using of knowledge-bases is very difficult, if not impossible. ARPA has correctly recognized the problem and funded a knowledge sharing initiative. One of the outcomes of this project is a formal language called Knowledge Interchange Format (KIF) for representing knowledge that could be translated into other languages. Capturing and representing design knowledge and reasoning with them have become very important for NASA who is a pioneer of innovative design of unique products. For upgrading an existing design for changing technology, needs, or requirements, it is essential to understand the design rationale, design choices, options and other relevant information associated with the design. Capturing such information and presenting them in the appropriate form are part of the ongoing Design Knowledge Capture project of NASA. The behavior of an object and various other aspects related to time are captured by the appropriate temporal knowledge. The captured design knowledge will be represented in such a way that various groups of NASA who are interested in various aspects of the design cycle should be able to access and use the design knowledge effectively. To facilitate knowledge sharing among these groups, one has to develop a very well defined ontology. Ontology is a specification of conceptualization. In the literature several specific domains were studied and some well defined ontologies were developed for such domains. However, very little, or no work has been done in the area of representing temporal knowledge to facilitate sharing. During the ASEE summer program, I have investigated several temporal models and have proposed a theory for time that is flexible to accommodate the time elements, such as, points and intervals, and is capable of handling the qualitative and quantitative temporal constraints. I have also proposed a primitive temporal ontology using which other relevant temporal ontologies can be built. I

  9. Multiple aberrations in shared inflammatory and oxidative & nitrosative stress (IO&NS) pathways explain the co-association of depression and cardiovascular disorder (CVD), and the increased risk for CVD and due mortality in depressed patients.

    PubMed

    Maes, Michael; Ruckoanich, Piyanuj; Chang, Young Seun; Mahanonda, Nithi; Berk, Michael

    2011-04-29

    There is evidence that there is a bidirectional relationship between major depression and cardiovascular disorder (CVD): depressed patients are a population at risk for increased cardiac morbidity and mortality, and depression is more frequent in patients who suffer from CVD. There is also evidence that inflammatory and oxidative and nitrosative stress (IO&NS) pathways underpin the common pathophysiology of both CVD and major depression. Activation of these pathways may increase risk for both disorders and contribute to shared risk. The shared IO&NS pathways that may contribute to CVD and depression comprise the following: increased levels of pro-inflammatory cytokines, like interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α, and interferon-γ; T cell activation; increased acute phase proteins, like C-reactive protein, haptoglobin, fibrinogen and α1-antitrypsin; complement factors; increased LPS load through bacterial translocation and subsequent gut-derived inflammation; induction of indoleamine 2,3-dioxygenase with increased levels of tryptophan catabolites; decreased levels of antioxidants, like coenzyme Q10, zinc, vitamin E, glutathione and glutathione peroxidase; increased O&NS characterized by oxidative damage to low density lipoprotein (LDL) and phospholipid inositol, increased malondialdehyde, and damage to DNA and mitochondria; increased nitrosative stress; and decreased ω3 polyunsaturated fatty acids (PUFAs). The complex interplay between the abovementioned IO&NS pathways in depression results in pro-atherogenic effects and should be regarded as a risk factor to future clinical CVD and due mortality. We suggest that major depression should be added as a risk factor to the Charlson "comorbidity" index. It is advised that patients with (sub)chronic or recurrent major depression should routinely be assessed by serology tests to predict if they have an increased risk to cardiovascular disorders.

  10. Shared versus distributed memory multiprocessors

    NASA Technical Reports Server (NTRS)

    Jordan, Harry F.

    1991-01-01

    The question of whether multiprocessors should have shared or distributed memory has attracted a great deal of attention. Some researchers argue strongly for building distributed memory machines, while others argue just as strongly for programming shared memory multiprocessors. A great deal of research is underway on both types of parallel systems. Special emphasis is placed on systems with a very large number of processors for computation intensive tasks and considers research and implementation trends. It appears that the two types of systems will likely converge to a common form for large scale multiprocessors.

  11. 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…

  12. Shared Governance in the Salt Lake City Schools.

    ERIC Educational Resources Information Center

    Morgan, Stanley R.

    Facing declining enrollment, loss of state funds, and decreasing public confidence, the Salt Lake City Schools found several groups demanding a voice in the decision-making process. A plan for shared governance was implemented. Representatives of the teachers' association, the administrative association, and the classified employees' association…

  13. Endosymbiosis: bacteria sharing the load.

    PubMed

    Keeling, Patrick J

    2011-08-23

    A nested set of bacterial endosymbionts within mealybug cells collectively provides amino acids to their host, but their genomes show that some pathways are distributed between both endosymbionts, while other essential proteins are missing altogether. The possibility that additional functions are shared between partners warrants comparisons with organelles.

  14. IRIS: Integrate, Relate. Infer. Share.

    DTIC Science & Technology

    2005-01-01

    share many of the goals and requirements for IRIS: Java-based, ontology-driven, user centric. We negotiated, and CEO Nova Spivack agreed to join the...Department of Interior-National Business Center (DOI-NBC). We would like to thank Nova Spivack and Jim Wissner at Radar Networks for their

  15. Learning by Sharing Graded Papers.

    ERIC Educational Resources Information Center

    Reisin, Gail

    1990-01-01

    Discusses using students' graded papers as a "text" to be read and commented upon by other students. Notes that sharing students' papers (and the teacher's comments) (1) reassures the students that they are not the only ones making errors; (2) deepens their understanding of literature; and (3) increases their awareness of writing styles and…

  16. Secret sharing using biometric traits

    NASA Astrophysics Data System (ADS)

    Kholmatov, Alisher; Yanikoglu, Berrin; Savas, Erkay; Levi, Albert

    2006-04-01

    In biometric based authentication, biometric traits of a person are matched against his/her stored biometric profile and access is granted if there is sufficient match. However, there are other access scenarios, which require participation of multiple previously registered users for a successful authentication or to get an access grant for a certain entity. For instance, there are cryptographic constructs generally known as secret sharing schemes, where a secret is split into shares and distributed amongst participants in such a way that it is reconstructed/revealed only when the necessary number of share holders come together. The revealed secret can then be used for encryption or authentication (if the revealed key is verified against the previously registered value). In this work we propose a method for the biometric based secret sharing. Instead of splitting a secret amongst participants, as is done in cryptography, a single biometric construct is created using the biometric traits of the participants. During authentication, a valid cryptographic key is released out of the construct when the required number of genuine participants present their biometric traits.

  17. Building a Shared Information Network.

    ERIC Educational Resources Information Center

    Stanat, Ruth

    1991-01-01

    Discussion of information needs in a business environment focuses on how to build a shared information network. Highlights include the evolution of corporate intelligence systems; results of a survey that examined the information networking needs of large corporations; and a case study of the development of an information network at Citibank N.A.…

  18. Barriers to Cyber Information Sharing

    DTIC Science & Technology

    2014-12-01

    machines and continued to collect shoppers ’ information for three more days.39 On December 27, Target also acknowledged, contrary to early reports...cyber criminals it is difficult, costly and ineffective to fight online attacks alone. Having the ability to connect and share information about

  19. Simulation Analysis of Data Sharing in Shared Memory Multiprocessors

    DTIC Science & Technology

    2016-06-14

    Submitted in partial satisfaction of the requirements for the degree of DOCfOR OF PHILOSOPHY in COMPUTER SCIENCE in the GRADUATE DMSION of the...California at Berkeley,Department of Electrical Engineering and Computer Sciences ,Berkeley,CA,94720 8. PERFORMING ORGANIZATION REPORT NUMBER 9...Susan J. Eggers Computer Science Division University of California Berkeley CA 94720 ABSTRACT This dissertation examines shared memory reference

  20. 50 CFR 85.40 - Cost sharing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Cost sharing. 85.40 Section 85.40 Wildlife... Use/Acceptance of Funds § 85.40 Cost sharing. (a) The Federal share shall not exceed 75% of total costs approved in the grant agreement. (b) The provisions of 43 CFR 12.64 apply to cost sharing...

  1. A Resilient Quantum Secret Sharing Scheme

    NASA Astrophysics Data System (ADS)

    Maitra, Arpita; Paul, Goutam

    2015-02-01

    A resilient secret sharing scheme is supposed to generate the secret correctly even after some shares are damaged. In this paper, we show how quantum error correcting codes can be exploited to design a resilient quantum secret sharing scheme, where a quantum state is shared among more than one parties.

  2. How to share underground reservoirs

    PubMed Central

    Schrenk, K. J.; Araújo, N. A. M.; Herrmann, H. J.

    2012-01-01

    Many resources, such as oil, gas, or water, are extracted from porous soils and their exploration is often shared among different companies or nations. We show that the effective shares can be obtained by invading the porous medium simultaneously with various fluids. Partitioning a volume in two parts requires one division surface while the simultaneous boundary between three parts consists of lines. We identify and characterize these lines, showing that they form a fractal set consisting of a single thread spanning the medium and a surrounding cloud of loops. While the spanning thread has fractal dimension 1.55 ± 0.03, the set of all lines has dimension 1.69 ± 0.02. The size distribution of the loops follows a power law and the evolution of the set of lines exhibits a tricritical point described by a crossover with a negative dimension at criticality. PMID:23087816

  3. Argumentation for coordinating shared activities

    NASA Technical Reports Server (NTRS)

    Clement, Bradley J.; Barrett, Anthony C.; Schaffer, Steven R.

    2004-01-01

    an increasing need for space missions to be able to collaboratively (and competitively) develop plans both within and across missions. In addition, interacting spacecraft that interleave onboard planning and execution must reach consensus on their commitments to each other prior to execution. In domains where missions have varying degrees of interaction and different constraints on communication and computation, the missions will require different coordination protocols in order to efficiently reach consensus with in their imposed deadlines. We describe a Shared Activity Coordination (SHAC) framework that provides a decentralized algorithm for negotiating the scheduling of shared activities over the lifetimes of multiple agents and a foundation for customizing protocols for negotiating planner interactions. We investigate variations of a few simple protocols based on argumentation and distributed constraints satisfaction techniques and evaluate their abilities to reach consistent solutions according to computation, time, and communication costs in an abstract domain where spacecraft propose joint measurements.

  4. How to share underground reservoirs

    NASA Astrophysics Data System (ADS)

    Schrenk, K. J.; Araújo, N. A. M.; Herrmann, H. J.

    2012-10-01

    Many resources, such as oil, gas, or water, are extracted from porous soils and their exploration is often shared among different companies or nations. We show that the effective shares can be obtained by invading the porous medium simultaneously with various fluids. Partitioning a volume in two parts requires one division surface while the simultaneous boundary between three parts consists of lines. We identify and characterize these lines, showing that they form a fractal set consisting of a single thread spanning the medium and a surrounding cloud of loops. While the spanning thread has fractal dimension 1.55 +/- 0.03, the set of all lines has dimension 1.69 +/- 0.02. The size distribution of the loops follows a power law and the evolution of the set of lines exhibits a tricritical point described by a crossover with a negative dimension at criticality.

  5. Our Second Quarter Century of Resource Sharing. Proceedings of the Association Supporting Computer Users in Education (ASCUE) Annual Conference (49th, Myrtle Beach, South Carolina, June 12-16, 2016)

    ERIC Educational Resources Information Center

    Association Supporting Computer Users in Education, 2016

    2016-01-01

    The Association Supporting Computer Users in Education (ASCUE) initiated a refereed track for paper submissions to the conference in 2008. In fact, at the 2008 business meeting, the membership approved three different presentation tracks: refereed with 3 blind reviews for each paper, session with paper where the author submits a paper but it is…

  6. Sharing Todays Resources--Meeting Tomorrows Needs. Papers, Workshop Reports and Associated Material Presented at the Seminar on Resources Coordination and Librarians' Groups: An Information Exchange Day (Sydney, Australia, July 26, 1980).

    ERIC Educational Resources Information Center

    Broadbent, Marianne, Ed.

    This booklet brings together papers, reports, and associated material from the seminar on school library resource coordination and librarians' groups in New South Wales held at Summer Hill Public School in Sydney. The collection includes a general introduction to the scope and goals of the seminar; a list of seminar speakers; papers on cooperative…

  7. Discover the Hidden Jewels in Your Library and Sharing the Wealth through Collaboration. Selected Papers from PIALA 2011, Pacific Islands Association of Libraries, Archives, and Museums Annual Conference (21st, Kosrae, Federated States of Micronesia, November 14-17, 2011)

    ERIC Educational Resources Information Center

    Drake, Paul B., Ed.

    2012-01-01

    This publication follows the tradition of publishing selected papers from Pacific Islands Association of Libraries, Archives and Museums (PIALA) annual conferences. This 21st annual conference was held in Kosrae, Federated States of Micronesia, November 14-17, 2011. The volume begins with a listing of the members of the PIALA 2011 Planning…

  8. So This is Knowledge Sharing

    NASA Technical Reports Server (NTRS)

    Motil, Susan

    2003-01-01

    People within large organizations have probably already dealt with problems similar to the problems that you face; you can save time and money by taking advantage of that experience and knowledge. Knowledge sharing by mentors can empower less experienced managers who would otherwise not challenge the status quo. Reviews should encourage joint problem solving rather than just reporting. To accomplish this, ensure that the review process is viewed as feedback from independent and supportive experts.

  9. What Drives Academic Data Sharing?

    PubMed Central

    Fecher, Benedikt; Friesike, Sascha; Hebing, Marcel

    2015-01-01

    Despite widespread support from policy makers, funding agencies, and scientific journals, academic researchers rarely make their research data available to others. At the same time, data sharing in research is attributed a vast potential for scientific progress. It allows the reproducibility of study results and the reuse of old data for new research questions. Based on a systematic review of 98 scholarly papers and an empirical survey among 603 secondary data users, we develop a conceptual framework that explains the process of data sharing from the primary researcher’s point of view. We show that this process can be divided into six descriptive categories: Data donor, research organization, research community, norms, data infrastructure, and data recipients. Drawing from our findings, we discuss theoretical implications regarding knowledge creation and dissemination as well as research policy measures to foster academic collaboration. We conclude that research data cannot be regarded as knowledge commons, but research policies that better incentivise data sharing are needed to improve the quality of research results and foster scientific progress. PMID:25714752

  10. Culture as shared cognitive representations.

    PubMed Central

    Romney, A K; Boyd, J P; Moore, C C; Batchelder, W H; Brazill, T J

    1996-01-01

    Culture consists of shared cognitive representations in the minds of individuals. This paper investigates the extent to which English speakers share the "same" semantic structure of English kinship terms. The semantic structure is defined as the arrangement of the terms relative to each other as represented in a metric space in which items judged more similar are placed closer to each other than items judged as less similar. The cognitive representation of the semantic structure, residing in the mind of an individual, is measured by judged similarity tasks involving comparisons among terms. Using six independent measurements, from each of 122 individuals, correspondence analysis represents the data in a common multidimensional spatial representation. Judged by a variety of statistical procedures, the individuals in our sample share virtually identical cognitive representations of the semantic structure of kinship terms. This model of culture accounts for 70-90% of the total variability in these data. We argue that our findings on kinship should generalize to all semantic domains--e.g., animals, emotions, etc. The investigation of semantic domains is important because they may reside in localized functional units in the brain, because they relate to a variety of cognitive processes, and because they have the potential to provide methods for diagnosing individual breakdowns in the structure of cognitive representations typical of such ailments as Alzheimer disease. PMID:11607678

  11. RACE pulls for shared control

    NASA Technical Reports Server (NTRS)

    Leahy, M. B., Jr.; Cassiday, B. K.

    1993-01-01

    Maintaining and supporting an aircraft fleet, in a climate of reduced manpower and financial resources, dictates effective utilization of robotics and automation technologies. To help develop a winning robotics and automation program the Air Force Logistics Command created the Robotics and Automation Center of Excellence (RACE). RACE is a command wide focal point. Race is an organic source of expertise to assist the Air Logistic Center (ALC) product directorates in improving process productivity through the judicious insertion of robotics and automation technologies. RACE is a champion for pulling emerging technologies into the aircraft logistic centers. One of those technology pulls is shared control. Small batch sizes, feature uncertainty, and varying work load conspire to make classic industrial robotic solutions impractical. One can view ALC process problems in the context of space robotics without the time delay. The ALC's will benefit greatly from the implementation of a common architecture that supports a range of control actions from fully autonomous to teleoperated. Working with national laboratories and private industry, we hope to transition shared control technology to the depot floor. This paper provides an overview of the RACE internal initiatives and customer support, with particular emphasis on production processes that will benefit from shared control technology.

  12. 76 FR 42127 - Change in Bank Control Notices; Acquisitions of Shares of a Bank or Bank Holding Company

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-18

    ... Hale Family Group, and to acquire voting shares of Sunflower Financial, Inc., and thereby indirectly acquire voting shares of Sunflower Bank, National Association, both in Salina, Kansas. Board of...

  13. Shared genetic factors in migraine and depression

    PubMed Central

    Stam, A H.; de Vries, B; Janssens, A C.J.W.; Vanmolkot, K R.J.; Aulchenko, Y S.; Henneman, P; Oostra, B A.; Frants, R R.; van den Maagdenberg, A M.J.M.; Ferrari, M D.; van Duijn, C M.; Terwindt, G M.

    2010-01-01

    Objective: To investigate the co-occurrence of migraine and depression and assess whether shared genetic factors may underlie both diseases. Methods: Subjects were 2,652 participants of the Erasmus Rucphen Family genetic isolate study. Migraine was diagnosed using a validated 3-stage screening method that included a telephone interview. Symptoms of depression were assessed using the Center for Epidemiologic Studies Depression scale and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). The contribution of shared genetic factors in migraine and depression was investigated by comparing heritability estimates for migraine with and without adjustment for symptoms of depression, and by comparing the heritability scores of depression between migraineurs and controls. Results: We identified 360 migraine cases: 209 had migraine without aura (MO) and 151 had migraine with aura (MA). Odds ratios for depression in patients with migraine were 1.29 (95% confidence interval [CI] 0.98–1.70) for MO and 1.70 (95% CI 1.28–2.24) for MA. Heritability estimates were significant for all migraine (0.56), MO (0.77), and MA (0.96), and decreased after adjustment for symptoms of depression or use of antidepressant medication, in particular for MA. Comparison of the heritability scores for depression between patients with migraine and controls showed a genetic correlation between HADS-D score and MA. Conclusions: There is a bidirectional association between depression and migraine, in particular migraine with aura, which can be explained, at least partly, by shared genetic factors. GLOSSARY CES-D = Center for Epidemiologic Studies Depression Scale; CI = confidence interval; ERF = Erasmus Rucphen Family; HADS-D = Hospital Anxiety and Depression Scale; IHS = International Headache Society; MA = migraine with aura; MO = migraine without aura; OR = odds ratio. PMID:20071666

  14. Data Sharing in P2P Systems

    NASA Astrophysics Data System (ADS)

    Hayek, Rabab; Raschia, Guillaume; Valduriez, Patrick; Mouaddib, Noureddine

    In this chapter, we survey P2P data sharing systems. All along, we focus on the evolution from simple file-sharing systems, with limited functionalities, to Peer Data Management Systems (PDMS) that support advanced applications with more sophisticated data management techniques. Advanced P2P applications are dealing with semantically rich data (e.g., XML documents, relational tables), using a high-level SQL-like query language. We start our survey with an overview over the existing P2P network architectures, and the associated routing protocols. Then, we discuss data indexing techniques based on their distribution degree and the semantics they can capture from the underlying data. We also discuss schema management techniques which allow integrating heterogeneous data. We conclude by discussing the techniques proposed for processing complex queries (e.g., range and join queries). Complex query facilities are necessary for advanced applications which require a high level of search expressiveness. This last part shows the lack of querying techniques that allow for an approximate query answering.

  15. Towards Information Enrichment through Recommendation Sharing

    NASA Astrophysics Data System (ADS)

    Weng, Li-Tung; Xu, Yue; Li, Yuefeng; Nayak, Richi

    Nowadays most existing recommender systems operate in a single organisational basis, i.e. a recommender system recommends items to customers of one organisation based on the organisation's datasets only. Very often the datasets of a single organisation do not have sufficient resources to be used to generate quality recommendations. Therefore, it would be beneficial if recommender systems of different organisations with similar nature can cooperate together to share their resources and recommendations. In this chapter, we present an Ecommerce-oriented Distributed Recommender System (EDRS) that consists of multiple recommender systems from different organisations. By sharing resources and recommendations with each other, these recommenders in the distributed recommendation system can provide better recommendation service to their users. As for most of the distributed systems, peer selection is often an important aspect. This chapter also presents a recommender selection technique for the proposed EDRS, and it selects and profiles recommenders based on their stability, average performance and selection frequency. Based on our experiments, it is shown that recommenders' recommendation quality can be effectively improved by adopting the proposed EDRS and the associated peer selection technique.

  16. 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

  17. 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…

  18. Shopping for a Time-sharing Service

    ERIC Educational Resources Information Center

    Elkholy, Hussein

    1970-01-01

    Offers the potential user of digital computers information and suggestions for acquiring a time-sharing system. The results of a survey of the equipment, cost, and services offered by a sample of time-sharing firms are presented. (LC)

  19. Quantum strongly secure ramp secret sharing

    NASA Astrophysics Data System (ADS)

    Zhang, Paul; Matsumoto, Ryutaroh

    2015-02-01

    Quantum secret sharing is a scheme for encoding a quantum state (the secret) into multiple shares and distributing them among several participants. If a sufficient number of shares are put together, then the secret can be fully reconstructed. If an insufficient number of shares are put together however, no information about the secret can be revealed. In quantum ramp secret sharing, partial information about the secret is allowed to leak to a set of participants, called an unqualified set, that cannot fully reconstruct the secret. By allowing this, the size of a share can be drastically reduced. This paper introduces a quantum analog of classical strong security in ramp secret sharing schemes. While the ramp secret sharing scheme still leaks partial information about the secret to unqualified sets of participants, the strong security condition ensures that qudits with critical information can no longer be leaked.

  20. Sharing a quota on cumulative carbon emissions

    NASA Astrophysics Data System (ADS)

    Raupach, Michael R.; Davis, Steven J.; Peters, Glen P.; Andrew, Robbie M.; Canadell, Josep G.; Ciais, Philippe; Friedlingstein, Pierre; Jotzo, Frank; van Vuuren, Detlef P.; Le Quéré, Corinne

    2014-10-01

    Any limit on future global warming is associated with a quota on cumulative global CO2 emissions. We translate this global carbon quota to regional and national scales, on a spectrum of sharing principles that extends from continuation of the present distribution of emissions to an equal per-capita distribution of cumulative emissions. A blend of these endpoints emerges as the most viable option. For a carbon quota consistent with a 2 °C warming limit (relative to pre-industrial levels), the necessary long-term mitigation rates are very challenging (typically over 5% per year), both because of strong limits on future emissions from the global carbon quota and also the likely short-term persistence in emissions growth in many regions.

  1. Shared decision making: improving care for children with autism.

    PubMed

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

    2012-08-01

    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 navigating the multitude of treatment options. Surveys assessing primary medical care and decision-making processes were developed on the basis of the U.S. Department of Health and Human Service's Consumer Assessment of Healthcare Providers and Systems survey. In May 2009, after pilot testing, we sent surveys to 203 parents of children from ages 3 to 18 with International Classification of Diseases-9 and parent-confirmed autism spectrum disorder diagnoses. The response rate was 64%. Controlling for key demographic variables, parents of children with autism spectrum disorder reporting higher levels of shared decision making reported significantly greater satisfaction with the overall quality of their child's health care (p ≤ .0001). Parents reporting higher levels of shared decision making were also significantly more likely to report receiving guidance on the many treatment options (p  =  .0002) and controversial issues related to autism spectrum disorder (p  =  .0322). In this study, shared decision making was associated with higher parent satisfaction and improved guidance regarding treatments and controversial issues within primary care for children with autism spectrum disorder.

  2. 42 CFR 438.108 - Cost sharing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Cost sharing. 438.108 Section 438.108 Public Health... ASSISTANCE PROGRAMS MANAGED CARE Enrollee Rights and Protections § 438.108 Cost sharing. The contract must provide that any cost sharing imposed on Medicaid enrollees is in accordance with §§ 447.50 through...

  3. 10 CFR 602.12 - Cost sharing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Cost sharing. 602.12 Section 602.12 Energy DEPARTMENT OF... PROGRAM § 602.12 Cost sharing. Cost sharing is not required, nor will it be considered, as a criterion in the evaluation and selection process unless otherwise provided under § 602.9(d)(5)....

  4. 10 CFR 605.13 - Cost sharing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Cost sharing. 605.13 Section 605.13 Energy DEPARTMENT OF... § 605.13 Cost sharing. Cost sharing is not required nor will it be considered as a criterion in the evaluation and selection process unless otherwise provided under § 605.10(d)(5)....

  5. Team Learning: Building Shared Mental Models

    ERIC Educational Resources Information Center

    Van den Bossche, Piet; Gijselaers, Wim; Segers, Mien; Woltjer, Geert; Kirschner, Paul

    2011-01-01

    To gain insight in the social processes that underlie knowledge sharing in teams, this article questions which team learning behaviors lead to the construction of a shared mental model. Additionally, it explores how the development of shared mental models mediates the relation between team learning behaviors and team effectiveness. Analyses were…

  6. 77 FR 4277 - Proposed Data Sharing Activity

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... Bureau of the Census Proposed Data Sharing Activity AGENCY: Bureau of the Census, Department of Commerce... the Department of Commerce proposes to share business data for statistical purposes. More specifically, the Census Bureau will share selected business data of multi-location businesses with the U.S....

  7. 38 CFR 17.274 - Cost sharing.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the beneficiary cost share. (b) In addition to the beneficiary cost share, an annual (calendar year... illness or injury, a calendar year cost limit or “catastrophic cap” has been placed on the beneficiary... cap computation. After a family has paid the maximum cost-share and deductible amounts for a...

  8. 38 CFR 17.274 - Cost sharing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the beneficiary cost share. (b) In addition to the beneficiary cost share, an annual (calendar year... illness or injury, a calendar year cost limit or “catastrophic cap” has been placed on the beneficiary... cap computation. After a family has paid the maximum cost-share and deductible amounts for a...

  9. 10 CFR 602.12 - Cost sharing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Cost sharing. 602.12 Section 602.12 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS EPIDEMIOLOGY AND OTHER HEALTH STUDIES FINANCIAL ASSISTANCE PROGRAM § 602.12 Cost sharing. Cost sharing is not required, nor will it be considered, as a criterion...

  10. Shared Services for Rural and Small Schools.

    ERIC Educational Resources Information Center

    Hanuske, Sarah

    As school populations decline and costs rise due to inflation, rural and small schools are turning to shared services in order to keep community schools open, meet federal mandates, and improve educational opportunities. Sharing ventures may be for limited purposes, such as sharing a physics teacher or having a joint drama production, or for more…

  11. Fair Shares, Matey, or Walk the Plank

    ERIC Educational Resources Information Center

    Wilson, P. Holt; Myers, Marrielle; Edgington, Cyndi; Confrey, Jere

    2012-01-01

    Whether sharing a collection of toys among friends or a pie for dessert, children as young as kindergarten age are keen on making sure that everyone gets their "fair share." In the classroom, fair-sharing activities call for creating equal-size groups from a collection of objects or creating equal-size parts of a whole and are generally used by…

  12. Quantum secret sharing with qudit graph states

    SciTech Connect

    Keet, Adrian; Fortescue, Ben; Sanders, Barry C.; Markham, Damian

    2010-12-15

    We present a unified formalism for threshold quantum secret sharing using graph states of systems with prime dimension. We construct protocols for three varieties of secret sharing: with classical and quantum secrets shared between parties over both classical and quantum channels.

  13. 47 CFR 73.1715 - Share time.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false Share time. 73.1715 Section 73.1715... Rules Applicable to All Broadcast Stations § 73.1715 Share time. Operation is permitted by two or more... considered part of their licenses. (a) If the licenses of stations authorized to share time do not...

  14. 47 CFR 73.1715 - Share time.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Share time. 73.1715 Section 73.1715... Rules Applicable to All Broadcast Stations § 73.1715 Share time. Operation is permitted by two or more... considered part of their licenses. (a) If the licenses of stations authorized to share time do not...

  15. 47 CFR 73.1715 - Share time.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false Share time. 73.1715 Section 73.1715... Rules Applicable to All Broadcast Stations § 73.1715 Share time. Operation is permitted by two or more... considered part of their licenses. (a) If the licenses of stations authorized to share time do not...

  16. 47 CFR 73.1715 - Share time.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 4 2014-10-01 2014-10-01 false Share time. 73.1715 Section 73.1715... Rules Applicable to All Broadcast Stations § 73.1715 Share time. Operation is permitted by two or more... considered part of their licenses. (a) If the licenses of stations authorized to share time do not...

  17. 44 CFR 204.61 - Cost share.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SECURITY DISASTER ASSISTANCE FIRE MANAGEMENT ASSISTANCE GRANT PROGRAM Grant Administration § 204.61 Cost share. (a) All fire management assistance grants are subject to a cost share. The Federal cost share for fire management assistance grants is seventy-five percent (75%). (b) As stated in § 204.25, the...

  18. Job Sharing in the Public Sector.

    ERIC Educational Resources Information Center

    Olmsted, Barney; And Others

    Job sharing is defined as "two people sharing the responsibilities of one full-time position with salary and benefits prorated"; the concept focuses on positions usually offered only as full-time jobs, often in professional and managerial categories. This book presents an overview of current job sharing and permanent part-time employment…

  19. Shared services centers can drive significant savings.

    PubMed

    McDowell, Jim

    2011-06-01

    A study of more than 30 U.S. integrated delivery systems (IDSs) found that implementing effective shared services centers can drive significant cost savings in human resources, accounts payable, and procurement. Many IDSs have not adopted effective shared services strategies. Implementing administrative shared services involves low risk and a relatively low start-up investment.

  20. 14 CFR 1260.54 - Cost sharing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Special Conditions § 1260.54 Cost sharing. Cost Sharing October 2000 (a) NASA and the Recipient will share in providing the resources necessary to perform the agreement. NASA funding and non-cash...-cash contribution will be on a___ percent NASA; ___ percent Recipient basis. (b) The funding and...

  1. 14 CFR 1260.54 - Cost sharing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Special Conditions § 1260.54 Cost sharing. Cost Sharing October 2000 (a) NASA and the Recipient will share in providing the resources necessary to perform the agreement. NASA funding and non-cash...-cash contribution will be on a___ percent NASA; ___ percent Recipient basis. (b) The funding and...

  2. 14 CFR 1260.54 - Cost sharing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Special Conditions § 1260.54 Cost sharing. Cost Sharing October 2000 (a) NASA and the Recipient will share in providing the resources necessary to perform the agreement. NASA funding and non-cash...-cash contribution will be on a___ percent NASA; ___ percent Recipient basis. (b) The funding and...

  3. 14 CFR 1260.54 - Cost sharing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Special Conditions § 1260.54 Cost sharing. Cost Sharing October 2000 (a) NASA and the Recipient will share in providing the resources necessary to perform the agreement. NASA funding and non-cash...-cash contribution will be on a___ percent NASA; ___ percent Recipient basis. (b) The funding and...

  4. 2q37.3 Deletion Syndrome: Two Cases with Highly Distinctive Facial Phenotype, Discordant Association with Schizophrenic Psychosis, and Shared Deletion Breakpoint Region on 2q37.3.

    PubMed

    Mehraein, Yasmin; Pfob, Martina; Steinlein, Ortrud; Aichinger, Eric; Eggert, Marlene; Bubendorff, Valerie; Mannhart, Adelina; Müller, Stefan

    2015-01-01

    2q37.3 deletion syndrome belongs to the chromosomal 2q37 deletion spectrum which clinically resembles Albright hereditary osteodystrophy (AHO) syndrome. It is is mainly characterized by short stature, obesity, round face, brachydactyly type E, intellectual disability, behavioral problems, and variable intellectual deficits. Different from classical AHO syndrome, patients with 2q37 deletion syndrome lack renal parathyroid hormone resistance (pseudohypoparathyroidism) and soft tissue ossification. So far, deletion mapping or molecular breakpoint analyses of 2q37 have been performed in only few patients. Here, we report on 2 patients with 2q37.3 deletion syndrome. In both patients the breakpoint of the 5.5-Mb terminal microdeletion could be narrowed down to the same ∼ 200-kb interval on 2q37.3 by BAC-FISH and/or array-CGH. Flanking low-copy repeats may indicate a classical microdeletion syndrome genesis for the 2q37.3 microdeletion subgroup. Clinical evaluation revealed intellectual deficits and type E brachydactyly typical for classical AHO syndrome together with distinctive facial dysmorphisms not present in the former. Furthermore, one patient presented with schizophrenic psychosis, an observation that would be in accordance with previous reports about an association between schizophrenia susceptibility and an unknown gene within the chromosomal region 2q37.

  5. Tamper-proof secret image-sharing scheme for identifying cheated secret keys and shared images

    NASA Astrophysics Data System (ADS)

    Chen, Chien-Chang; Liu, Chong-An

    2013-01-01

    A (t,n) secret image-sharing scheme shares a secret image to n participants, and the t users recover the image. During the recovery procedure of a conventional secret image-sharing scheme, cheaters may use counterfeit secret keys or modified shared images to cheat other users' secret keys and shared images. A cheated secret key or shared image leads to an incorrect secret image. Unfortunately, the cheater cannot be identified. We present an exponent and modulus-based scheme to provide a tamper-proof secret image-sharing scheme for identifying cheaters on secret keys or shared images. The proposed scheme allows users to securely select their secret key. This assignment can be performed over networks. Modulus results of each shared image is calculated to recognize cheaters of a shared image. Experimental results indicate that the proposed scheme is excellent at identifying cheated secret keys and shared images.

  6. How are important life events disclosed on facebook? Relationships with likelihood of sharing and privacy.

    PubMed

    Bevan, Jennifer L; Cummings, Megan B; Kubiniec, Ashley; Mogannam, Megan; Price, Madison; Todd, Rachel

    2015-01-01

    This study examined an aspect of Facebook disclosure that has as yet gone unexplored: whether a user prefers to share information directly, for example, through status updates, or indirectly, via photos with no caption or relationship status changes without context or explanation. The focus was on the sharing of important positive and negative life events related to romantic relationships, health, and work/school in relation to likelihood of sharing this type of information on Facebook and general attitudes toward privacy. An online survey of 599 adult Facebook users found that when positive life events were shared, users preferred to do so indirectly, whereas negative life events were more likely to be disclosed directly. Privacy shared little association with how information was shared. Implications for understanding the finer nuances of how news is shared on Facebook are discussed.

  7. 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

  8. Flowers and Wild Megachilid Bees Share Microbes.

    PubMed

    McFrederick, Quinn S; Thomas, Jason M; Neff, John L; Vuong, Hoang Q; Russell, Kaleigh A; Hale, Amanda R; Mueller, Ulrich G

    2017-01-01

    Transmission pathways have fundamental influence on microbial symbiont persistence and evolution. For example, the core gut microbiome of honey bees is transmitted socially and via hive surfaces, but some non-core bacteria associated with honey bees are also found on flowers, and these bacteria may therefore be transmitted indirectly between bees via flowers. Here, we test whether multiple flower and wild megachilid bee species share microbes, which would suggest that flowers may act as hubs of microbial transmission. We sampled the microbiomes of flowers (either bagged to exclude bees or open to allow bee visitation), adults, and larvae of seven megachilid bee species and their pollen provisions. We found a Lactobacillus operational taxonomic unit (OTU) in all samples but in the highest relative and absolute abundances in adult and larval bee guts and pollen provisions. The presence of the same bacterial types in open and bagged flowers, pollen provisions, and bees supports the hypothesis that flowers act as hubs of transmission of these bacteria between bees. The presence of bee-associated bacteria in flowers that have not been visited by bees suggests that these bacteria may also be transmitted to flowers via plant surfaces, the air, or minute insect vectors such as thrips. Phylogenetic analyses of nearly full-length 16S rRNA gene sequences indicated that the Lactobacillus OTU dominating in flower- and megachilid-associated microbiomes is monophyletic, and we propose the name Lactobacillus micheneri sp. nov. for this bacterium.

  9. Sharing a bowl of tea.

    PubMed

    Sen, S

    1993-06-01

    Soshitsu Sen's keynote speech before a symposium on population and the environment is summarized unofficially by the editorial staff. The instability of human thinking is given as the cause for the present destruction of the environment. In a visit to the His Majesty King of Sweden, Sen remarked that stabilizing human minds can be achieved within the tea ceremony through "serving tea heartily, receiving it with gratitude, and offering it to another." In this way, the spirit of concern for others can be practiced in everyday life and tranquility of mind reached. News broadcasts of starving parents and children as victims of civil war are disheartening. The Japanese people are not suffering such hunger, even though the economy has not been as robust as desired. The analogy is provided in the story by Chuang Chou about King Hun Dun and King Xiu and man's good intentions, which nonetheless destroy the earth. Japan has experienced forest and environmental destruction on the road to economic prosperity and satisfaction of self-interests. The advice on living in accord with nature is to appreciate each season for its own changes. For example, when it is the winter season, the complaint is about the cold and the desire is for spring; but when spring comes, the desire is for the cooler weather of fall. the ordinary way is to appreciate all seasons and is the best way of sustaining a healthy environment. In the garden of the tea hut, humans enter without their worldly title, position, and means; at the water basin, hands and mouth are cleansed, and entrance is made through a small hole into the hut much the same as emerging from the womb. Worldly matters are dispensed with and purity of thought is shared in the sharing of the bowl of green tea, saying "after you" to one another. Christianity and the Way of Tea share the same symbols of purification. The black tea bowl is in harmony with the green tea. Fatigue is relieved when gazing upon the color green; examples are given

  10. Recurrent Major Depression and Right Hippocampal Volume: A Bivariate Linkage and Association Study

    PubMed Central

    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 (χ2 = 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. PMID:26485182

  11. Bacteria like sharing their sweets.

    PubMed

    Cuccui, Jon; Wren, Brendan W

    2013-09-01

    Protein glycosylation and capsular polysaccharide formation are increasingly recognized as playing central roles in the survival and virulence of bacterial pathogens. In this issue of Molecular Microbiology, structural analysis in Acinetobacter baumannii 17978 revealed that a pentasaccharide that decorates glycoproteins is formed of the same building blocks used for capsule biosynthesis demonstrating split roles for this glycan. Disruption of PglC, the initiating glycosyltransferase responsible for attachment of the first sugar to undecaprenylphosphate abolished glycoprotein production and capsule biosynthesis. Both pathways are demonstrated to be important in biofilm formation and pathogenesis, and disabling their synthesis should provide a useful route for antimicrobial design. Shared polysaccharide usage reduces the genetic and metabolic burden in a bacterial cell and is an emerging theme among bacterial pathogens that need to be energy efficient for their streamlined lifestyle.

  12. Some thoughts on sharing science

    NASA Astrophysics Data System (ADS)

    Brady, Ivan; Kumar, Alok

    2000-07-01

    Sustaining and upgrading the national interest in science requires breaking through some of the barriers that separate science from the academy's other disciplines and interests, and from society as a whole. This article reviews some of the difficulties and prospects of sharing science within the academy and the ripple effect that such activities may have on the larger social context of attitudes toward science. We recognize that crossing into other disciplines for any purpose raises special communication problems. We also argue that much of the apprehension concerning such discourse rests on a fallacy. Some relief is anticipated through an ongoing critical and reflexive examination of ourselves and our activities with respect to the ways science touches our collective lives, and by conscientiously developing new relationships for teaching scientific thinking and values on the premise that science is inherently a form of public knowledge that relies heavily on cultural values and society.

  13. Sharing Space Situational Awareness Data

    NASA Astrophysics Data System (ADS)

    Bird, D.

    2010-09-01

    The Commander, United States Strategic Command (CDRUSSTRATCOM) accepted responsibility for sharing space situational awareness (SSA) information/services with commercial & foreign entities from the US Air Force on 22 Dec 09 (formerly the Commercial & Foreign Entities Pilot Program). The requirement to share SSA services with non-US Government (USG) entities is derived from Title 10, United States Code, Section 2274 (2010) and is consistent with the new National Space Policy. US Strategic Command’s (USSTRATCOM’s) sharing of SSA services consists of basic services (Two-Line Elements, decay data and satellite catalog details) available on www.space-track.org and advanced services (conjunction assessment, launch support, etc) available with a signed agreement. USSTRATCOM has requested USG permission to enter into international agreements to enable SSA data exchange with our foreign partners. USSTRATCOM recently authorized Joint Functional Component Command for Space (JFCC SPACE) to share Conjunction Summary Messages (CSMs) with satellite owner/operators whose satellites have been identified as closely approaching another space object. CSMs contain vector and covariance data computed using Special Perturbations theory. To facilitate the utility of the CSMs, USSTRATCOM has and is hosting CSM Workshops to ensure satellite operators fully understand the data contained in the CSM in order to provide an informed recommendation to their leadership. As JFCC SPACE matures its ability to accept ephemeris data from a satellite operator, it will be necessary to automatically transfer that data from one security level to another. USSTRATCOM and Air Force Space Command are coordinating the integration of a cross domain solution that will allow JFCC SPACE to do just that. Finally, USSTRATCOM is also working with commercial and governmental organizations to develop an internationally-accepted conjunction assessment message. The United States Government (USG), specifically the

  14. Hadron therapy information sharing prototype

    PubMed Central

    Roman, Faustin Laurentiu; Abler, Daniel; Kanellopoulos, Vassiliki; Amoros, Gabriel; Davies, Jim; Dosanjh, Manjit; Jena, Raj; Kirkby, Norman; Peach, Ken; Salt, Jose

    2013-01-01

    The European PARTNER project developed a prototypical system for sharing hadron therapy data. This system allows doctors and patients to record and report treatment-related events during and after hadron therapy. It presents doctors and statisticians with an integrated view of adverse events across institutions, using open-source components for data federation, semantics, and analysis. There is a particular emphasis upon semantic consistency, achieved through intelligent, annotated form designs. The system as presented is ready for use in a clinical setting, and amenable to further customization. The essential contribution of the work reported here lies in the novel data integration and reporting methods, as well as the approach to software sustainability achieved through the use of community-supported open-source components. PMID:23824127

  15. Financial Assets [share, bonds] & Ancylia

    NASA Astrophysics Data System (ADS)

    Maksoed, Wh-

    2016-11-01

    Instead Elaine Scarry: "Thermonuclear monarchy" reinvent Carry Nation since Aug 17, 1965 the Republic of Indonesia's President speech: "Reach to the Star", for "cancellation" usually found in External Debt herewith retrieved from "the Window of theWorld": Ancylia, feast in March, a month named after Mars, the god of war. "On March 19 they used to put on their biggest performance of gymnastics in order to "bribe" their god for another good year", further we have vacancy & "vacuum tube"- Bulat Air karena Pembuluh, Bulat Kata karena Mufakat" proverb from Minangkabau, West Sumatra. Follows March 19, 1984 are first prototype flight of IAI Astra Jet as well as March 19, 2012 invoice accompanies Electric car Kujang-193, Fainancial Assets [share, bonds] are the answer for "infrastructure" & state owned enterprises assets to be hedged first initial debt per capita accordances. Heartfelt gratitudes to HE. Mr. Ir. Sarwono Kusumaatmadja/PT. Smartfren INDONESIA.

  16. SHARE: Statistical hadronization with resonances

    NASA Astrophysics Data System (ADS)

    Torrieri, G.; Steinke, S.; Broniowski, W.; Florkowski, W.; Letessier, J.; Rafelski, J.

    2005-05-01

    SHARE is a collection of programs designed for the statistical analysis of particle production in relativistic heavy-ion collisions. With the physical input of intensive statistical parameters, it generates the ratios of particle abundances. The program includes cascade decays of all confirmed resonances from the Particle Data Tables. The complete treatment of these resonances has been known to be a crucial factor behind the success of the statistical approach. An optional feature implemented is the Breit-Wigner distribution for strong resonances. An interface for fitting the parameters of the model to the experimental data is provided. Program summaryTitle of the program:SHARE, October 2004, version 1.2 Catalogue identifier: ADVD Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADVD Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Computer: PC, Pentium III, 512 MB RAM (not hardware dependent) Operating system: Linux: RedHat 6.1, 7.2, FEDORA, etc. (not system dependent) Programming language:FORTRAN77: g77, f77 as well as Mathematica, ver. 4 or 5, for the case of full chemical equilibrium and particle widths set to zero Size of the package: 645 KB directory including example programs (87 KB compressed distribution archive) External routines: KERNLIB, MATHLIB and PACKLIB from the CERN Program Library (see http://cernlib.web.cern.ch for download and installation instructions) Distribution format: tar.gz Number of lines in distributed program, including test data, etc.: 15 277 Number of bytes in distributed program, including test data, etc.: 88 522 Computer: Any computer with an f77 compiler Nature of the physical problem: Statistical analysis of particle production in relativistic heavy-ion collisions involves the formation and the subsequent decays of a large number of resonances. With the physical input of thermal parameters, such as the temperature and fugacities, and considering cascading decays, along with weak

  17. Hepadnaviruses and retroviruses share genome homology and features of replication.

    PubMed

    Robinson, W S; Miller, R H; Marion, P L

    1987-01-01

    The hepadnavirus family includes hepatitis B virus (HBV), woodchuck hepatitis virus (WHV), ground squirrel hepatitis virus (GSHV) and duck hepatitis B virus (DHBV). These viruses share unique ultrastructural, molecular and biological features. HBV has great medical importance in many parts of the world. More important numerically than acute hepatitis B in high prevalence geographic regions is the liver disease associated with chronic infection. There appear to be more than 200 million chronically infected humans in the world, and these HBV infections appear to be the single most common cause of chronic liver disease and liver cancer in man. All hepadnaviruses share the propensity for silent infection in early life leading to persistence of the virus, and hepatocellular carcinoma (HCC) is clearly associated with long-standing persistent infection in man, woodchucks and ground squirrels. Although the viral DNA has been found to be integrated in cellular DNA of many HCC in man, woodchucks and ground squirrels, the precise role of the virus in tumor formation has not been defined. Hepadna viruses have an interesting molecular structure and mechanisms of replication, and they appear to share certain important features with retroviruses as reviewed here. It is of interest to define similarities and differences between hepadnaviruses and retroviruses in order to understand their evolutionary relationship and to determine whether they share a common oncogenic mechanism, since infection with members of both virus families is associated with neoplastic disease.

  18. The Development of Recipient-Dependent Sharing Behavior and Sharing Expectations in Preschool Children

    ERIC Educational Resources Information Center

    Paulus, Markus; Moore, Chris

    2014-01-01

    This study investigated the development of sharing expectations and sharing behavior in 3 groups of 3-, 4-, and 5-year-old children. We examined (a) whether preschool children expect a person to share more with a friend than with a disliked peer and (b) whether their expectation about others' sharing behavior depends on whether there is a cost or…

  19. HLA sharing and history of miscarriage among women with rheumatoid arthritis

    SciTech Connect

    Brennan, P.

    1997-03-01

    An increased frequency of recurrent spontaneous abortions (RSA), defined as three or more pregnancy losses without an identifiable cause, has been reported among women who share HLA alleles with their partner. A similar association has also been reported for women who have decreased fecundity. No specific HLA alleles have been identified as being the important etiological factor, raising the possibility that the observed sharing may represent a marker for sharing of other closely linked susceptibility genes. 12 refs., 1 tab.

  20. Sharing Clouds: Showing, Distributing, and Sharing Large Point Datasets

    NASA Astrophysics Data System (ADS)

    Grigsby, S.

    2012-12-01

    Sharing large data sets with colleagues and the general public presents a unique technological challenge for scientists. In addition to large data volumes, there are significant challenges in representing data that is often irregular, multidimensional and spatial in nature. For derived data products, additional challenges exist in displaying and providing provenance data. For this presentation, several open source technologies are demonstrated for the remote display and access of large irregular point data sets. These technologies and techniques include the remote viewing of point data using HTML5 and OpenGL, which provides a highly accessible preview of the data sets for a range of audiences. Intermediate levels of accessibility and high levels of interactivity are accomplished with technologies such as wevDAV, which allows collaborators to run analysis on local clients, using data stored and administered on remote servers. Remote processing and analysis, including provenance tracking, will be discussed at the workgroup level. The data sets used for this presentation include data acquired from the NSF funded National Center for Airborne Laser Mapping (NCALM), and data acquired for research and instructional use in NASA's Student Airborne Research Program (SARP). These datasets include Light Ranging And Detection (LiDAR) point clouds ranging in size from several hundred thousand to several hundred million data points; the techniques and technologies discussed are applicable to other forms of irregular point data.

  1. Understanding Palliative Cancer Chemotherapy: About Shared Decisions and Shared Trajectories

    PubMed Central

    Pols, Jeannette; Richel, Dick J.; Koedoot, Nelleke; Willems, Dick L.

    2009-01-01

    Most models of patient-physician communication take decision-making as a central concept. However, we found that often the treatment course of metastatic cancer patients is not easy to describe in straightforward terms used in decision-making models but is instead frequently more erratic. Our aim was to analyse these processes as trajectories. We used a longitudinal case study of 13 patients with metastatic colorectal and pancreatic cancer for whom palliative chemotherapy was a treatment option, and analysed 65 semi-structured interviews. We analysed three characteristics of the treatment course that contributed to the ‘erraticness’ of the course: (1) The treatment (with or without chemotherapy) contained many options; (2) these options were not stable entities to be decided upon, but changed identity over the course of treatment, and (3) contrary to the closure (option X means no option Y, Z, etc.) a decision implies, the treatment course was a continuous process in which options instead remained open. When the treatment course is characterised by these many and changeable options that do not result in closure, the shared decision-making model should take these into account. More attention needs to be paid to the erratic character of the process in which the doctor has to provide continuous information that is related to the changing situation of the patient; also, flexibility in dealing with protocols is warranted, as is vigilance about the overall direction of the process. PMID:19418228

  2. Interhousehold meat sharing among Mayangna and Miskito horticulturalists in Nicaragua.

    PubMed

    Koster, Jeremy

    2011-12-01

    Recent analyses of food sharing in small-scale societies indicate that reciprocal altruism maintains interhousehold food transfers, even among close kin. In this study, matrix-based regression methods are used to test the explanatory power of reciprocal altruism, kin selection, and tolerated scrounging. In a network of 35 households in Nicaragua's Bosawas Reserve, the significant predictors of food sharing include kinship, interhousehold distance, and reciprocity. In particular, resources tend to flow from households with relatively more meat to closely related households with little, as predicted by kin selection. This generalization is especially true of household dyads with mother-offspring relationships, which suggests that studies of food sharing may benefit from distinctions between lineal and collateral kin. Overall, this analysis suggests that exchanges among kin are primarily associated with differences in need, not reciprocity. Finally, although large game is distributed widely, qualitative observations indicate that hunters typically do not relinquish control of the distribution in ways predicted by costly signaling theory.

  3. 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.

  4. Expected size of shared haplotypes surrounding a common disease gene

    SciTech Connect

    Meerman, G.J. te; Meulen, M.A. van der; Sandkuijl, L.A.

    1994-09-01

    If two persons in a founder population share a rare disease, they may share genes involved in that disease Identical By Descent. We have calculated the probability of the size of the region IBD on either side of a shared common gene. Probabilities are plotted for various values of the meiotic count: the number of independent meioses connecting the persons. Even if this number is quite large, the shared area will, given the present density of markers, contain several markers. To be 95% certain that the area surrounding a gene can be delimited to less than 1 cM, approximately 500 meioses need to be observed. The many generations that are required before a gene is separated from its surrounding polymorphisms indicate that association between disease and marker alleles can be explained as IBD around a common gene. In founder populations apparantly unrelated affected persons will likely share disease genes introduced or mutated between 10 and 40 generations ago. Analyzing the overlap of haplotypes gives excellent opportunities to observe implicitly the many meioses required for genetic fine mapping.

  5. The OSG open facility: A sharing ecosystem

    DOE PAGES

    Jayatilaka, B.; Levshina, T.; Rynge, M.; ...

    2015-12-23

    The Open Science Grid (OSG) ties together individual experiments’ computing power, connecting their resources to create a large, robust computing grid, this computing infrastructure started primarily as a collection of sites associated with large HEP experiments such as ATLAS, CDF, CMS, and DZero. In the years since, the OSG has broadened its focus to also address the needs of other US researchers and increased delivery of Distributed High Through-put Computing (DHTC) to users from a wide variety of disciplines via the OSG Open Facility. Presently, the Open Facility delivers about 100 million computing wall hours per year to researchers whomore » are not already associated with the owners of the computing sites, this is primarily accomplished by harvesting and organizing the temporarily unused capacity (i.e. opportunistic cycles) from the sites in the OSG. Using these methods, OSG resource providers and scientists share computing hours with researchers in many other fields to enable their science, striving to make sure that these computing power used with maximal efficiency. Furthermore, we believe that expanded access to DHTC is an essential tool for scientific innovation and work continues in expanding this service.« less

  6. The OSG open facility: A sharing ecosystem

    SciTech Connect

    Jayatilaka, B.; Levshina, T.; Rynge, M.; Sehgal, C.; Slyz, M.

    2015-12-23

    The Open Science Grid (OSG) ties together individual experiments’ computing power, connecting their resources to create a large, robust computing grid, this computing infrastructure started primarily as a collection of sites associated with large HEP experiments such as ATLAS, CDF, CMS, and DZero. In the years since, the OSG has broadened its focus to also address the needs of other US researchers and increased delivery of Distributed High Through-put Computing (DHTC) to users from a wide variety of disciplines via the OSG Open Facility. Presently, the Open Facility delivers about 100 million computing wall hours per year to researchers who are not already associated with the owners of the computing sites, this is primarily accomplished by harvesting and organizing the temporarily unused capacity (i.e. opportunistic cycles) from the sites in the OSG. Using these methods, OSG resource providers and scientists share computing hours with researchers in many other fields to enable their science, striving to make sure that these computing power used with maximal efficiency. Furthermore, we believe that expanded access to DHTC is an essential tool for scientific innovation and work continues in expanding this service.

  7. The OSG open facility: A sharing ecosystem

    NASA Astrophysics Data System (ADS)

    Jayatilaka, B.; Levshina, T.; Rynge, M.; Sehgal, C.; Slyz, M.

    2015-12-01

    The Open Science Grid (OSG) ties together individual experiments’ computing power, connecting their resources to create a large, robust computing grid; this computing infrastructure started primarily as a collection of sites associated with large HEP experiments such as ATLAS, CDF, CMS, and DZero. In the years since, the OSG has broadened its focus to also address the needs of other US researchers and increased delivery of Distributed High Through-put Computing (DHTC) to users from a wide variety of disciplines via the OSG Open Facility. Presently, the Open Facility delivers about 100 million computing wall hours per year to researchers who are not already associated with the owners of the computing sites; this is primarily accomplished by harvesting and organizing the temporarily unused capacity (i.e. opportunistic cycles) from the sites in the OSG. Using these methods, OSG resource providers and scientists share computing hours with researchers in many other fields to enable their science, striving to make sure that these computing power used with maximal efficiency. We believe that expanded access to DHTC is an essential tool for scientific innovation and work continues in expanding this service.

  8. 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

  9. 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

  10. Variants near CCK receptors are associated with electrophysiological responses to prepulse startle stimuli in a Mexican American cohort

    PubMed Central

    Norden-Krichmar, Trina M.; Gizer, Ian R.; Phillips, Evelyn; Wilhelmsen, Kirk C.; Schork, Nicholas J.; Ehlers, Cindy L.

    2016-01-01

    Neurophysiological measurements of the response to prepulse and startle stimuli have been suggested to represent an important endophenotype for both substance dependence and other select psychiatric disorders. We have previously shown, in young adult Mexican Americans (MA), that presentation of a short delay acoustic prepulse, prior to the startle stimuli can elicit a late negative component at about 400 msec (N4S), in the event-related potential (ERP), recorded from frontal cortical areas. In the present study we investigated whether genetic factors associated with this endophenotype could be identified. The study included 420 (age 18 – 30 years) MA men (n=170) and women (n=250). DNA was genotyped using an Affymetrix Axiom Exome1A chip. An association analysis revealed that the CCKAR and CCKBR (cholecystokinin A and B receptor) genes each had a nearby variant that showed suggestive significance with the amplitude of the N4S component to prepulse stimuli. The neurotransmitter cholecystokinin (CCK), along with its receptors, CCKAR and CCKBR, have been previously associated with psychiatric disorders, suggesting that variants near these genes may play a role in the prepulse/startle response in this cohort. PMID:26608796

  11. The SHARE 2012 data campaign

    NASA Astrophysics Data System (ADS)

    Giannandrea, AnneMarie; Raqueno, Nina; Messinger, David W.; Faulring, Jason; Kerekes, John P.; van Aardt, Jan; Canham, Kelly; Hagstrom, Shea; Ontiveros, Erin; Gerace, Aaron; Kaufman, Jason; Vongsy, Karmon M.; Griffith, Heather; Bartlett, Brent D.; Ientilucci, Emmett; Meola, Joseph; Scarff, Lauwrence; Daniel, Brian

    2013-05-01

    A multi-modal (hyperspectral, multispectral, and LIDAR) imaging data collection campaign was conducted just south of Rochester New York in Avon, NY on September 20, 2012 by the Rochester Institute of Technology (RIT) in conjunction with SpecTIR, LLC, the Air Force Research Lab (AFRL), the Naval Research Lab (NRL), United Technologies Aerospace Systems (UTAS) and MITRE. The campaign was a follow on from the SpecTIR Hyperspectral Airborne Rochester Experiment (SHARE) from 2010. Data was collected in support of the eleven simultaneous experiments described here. The airborne imagery was collected over four different sites with hyperspectral, multispectral, and LIDAR sensors. The sites for data collection included Avon, NY, Conesus Lake, Hemlock Lake and forest, and a nearby quarry. Experiments included topics such as target unmixing, subpixel detection, material identification, impacts of illumination on materials, forest health, and in-water target detection. An extensive ground truthing effort was conducted in addition to collection of the airborne imagery. The ultimate goal of the data collection campaign is to provide the remote sensing community with a shareable resource to support future research. This paper details the experiments conducted and the data that was collected during this campaign.

  12. 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…

  13. Mental Health Status, Drug Treatment Use, and Needle Sharing among Injection Drug Users

    ERIC Educational Resources Information Center

    Lundgren, Lena M.; Amodeo, Maryann; Chassler, Deborah

    2005-01-01

    This study examined the relationship among mental health symptoms, drug treatment use, and needle sharing in a sample of 507 injection drug users (IDUs). Mental health symptoms were measured through the ASI psychiatric scale. A logistic regression model identified that some of the ASI items were associated with needle sharing in an opposing…

  14. 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…

  15. NCSU Reactor Sharing Program. Final technical report, [September 1, 1980--August 29, 1992

    SciTech Connect

    Perez, P.B.

    1993-11-10

    The Nuclear Reactor Program at North Carolina State University provides the PULSTAR Research Reactor and associated facilities to eligible institutions with support, in part, from the Department of Energy Reactor Sharing Program. Participation in the NCSU Reactor Sharing Program continues to increase steadily with visitors ranging from advance high school physics and chemistry students to Ph.D. level research from neighboring universities.

  16. Perception and Management of Risk in Internet-Based Peer-to-Peer Milk-Sharing

    ERIC Educational Resources Information Center

    Gribble, Karleen D.

    2014-01-01

    The perception and management of the risks of peer-to-peer milk sharing was explored via a written questionnaire administered to 97 peer milk donors and 41 peer milk recipients who were recruited via Facebook. All recipients' respondents were aware that there were risks associated with using peer-shared milk and took action to mitigate these…

  17. Polynomial-style region incremental multisecret image sharing

    NASA Astrophysics Data System (ADS)

    Wang, Ran-Zan; Lin, Yung-Yi

    2011-03-01

    This paper proposes a polynomial-style region incremental multisecret image sharing (PBRIMSIS), for sharing multiple secrets in an image among n participants. The method enables the dealer to distribute the content of an image S to multiple regions, where each region is associated with a certain level of secrecy. In the proposed n-level PBRIMSIS scheme, input image S is encoded to n+1 shadow images that exhibit the following features: a. each shadow image cannot reveal any region in S, b. any t (2 <= t <= n + 1) shadow images can be used to reveal these regions associated with up to t - 1 secret levels, and c. S can be completely reconstructed when all of the n+1 shadow images are available. A discrete cosine transform-based PBRIMSIS with a smaller shadow image scheme is designed to improve the transmission and storage of the generated shadow images. The property of incremental disclosure to the region-based secrets in an image is applicable to image sharing in diverse applications that require the sharing of multiple secrets with different secrecy priorities, such as in cooperative working or in military secrets.

  18. Efficient multiparty quantum-secret-sharing schemes

    SciTech Connect

    Xiao Li; Deng Fuguo; Long Guilu; Pan Jianwei

    2004-05-01

    In this work, we generalize the quantum-secret-sharing scheme of Hillery, Buzek, and Berthiaume [Phys. Rev. A 59, 1829 (1999)] into arbitrary multiparties. Explicit expressions for the shared secret bit is given. It is shown that in the Hillery-Buzek-Berthiaume quantum-secret-sharing scheme the secret information is shared in the parity of binary strings formed by the measured outcomes of the participants. In addition, we have increased the efficiency of the quantum-secret-sharing scheme by generalizing two techniques from quantum key distribution. The favored-measuring-basis quantum-secret-sharing scheme is developed from the Lo-Chau-Ardehali technique [H. K. Lo, H. F. Chau, and M. Ardehali, e-print quant-ph/0011056] where all the participants choose their measuring-basis asymmetrically, and the measuring-basis-encrypted quantum-secret-sharing scheme is developed from the Hwang-Koh-Han technique [W. Y. Hwang, I. G. Koh, and Y. D. Han, Phys. Lett. A 244, 489 (1998)] where all participants choose their measuring basis according to a control key. Both schemes are asymptotically 100% in efficiency, hence nearly all the Greenberger-Horne-Zeilinger states in a quantum-secret-sharing process are used to generate shared secret information.

  19. Sharing in covalent and hydrogen bonds

    NASA Astrophysics Data System (ADS)

    Perhacs, Pablo

    1998-11-01

    The sharing of a single electron between two spatial and spin coordinates ζ and ζsp/prime in a many electron system is discussed in terms of the single particle sharing amplitude, sharing index, I(/zeta;/zeta/sp/prime) /equiv /langle/zeta;/zeta/sp/prime/rangle/ /langle/zeta/sp/prime;/zeta/rangle. The sharing amplitude serves as a single electron wave function within the context of the wave function for the entire system. The sharing index is a measure of the extent to which an electron is shared between ζ and ζsp/prime. The sharing of an electron between atoms in molecules is quantitatively interpreted through the sharing indices and graphically displayed in the fixed point sharing amplitude,

  20. Teaching behaviorally handicapped preschool children to share.

    PubMed Central

    Bryant, L E; Budd, K S

    1984-01-01

    We examined the effectiveness of Barton and Ascione 's (1979) package for training sharing in a classroom setting with six behaviorally handicapped preschool children, four of whom were also developmentally delayed. Individual responses in sharing and not sharing were examined. Training consisted of initial instructions, modeling, and behavioral rehearsal, followed by teacher prompts and praise regarding sharing directly in a classroom free play period. Introduction of training in a multiple-baseline design across three pairs of children resulted in substantial increases in sharing for five of the six children. Results for negative interactions were less clear but suggested that concomitant decreases occurred for the same five children. The response analysis indicated that (a) individual components of sharing (offers, requests, and acceptances ) all increased with training; (b) most children were more likely to initiate sharing through requests than through offers; (c) the proportion of sharing initiatives accepted by peers increased with training despite a much greater absolute number of initiatives; and (d) of the three negative behaviors (opposing play, taking without asking, and aggression) examined as incompatible with sharing, the most prevalent response was opposing other children's play. Individual differences in initial social repertoires and responsiveness to training were examined with respect to their implications for research and practice. Overall, the findings provide an encouraging indication of an intervention program for children with behavioral, social, and developmental handicaps. PMID:6725169

  1. Proposal for quantum rational secret sharing

    NASA Astrophysics Data System (ADS)

    Maitra, Arpita; De, Sourya Joyee; Paul, Goutam; Pal, Asim K.

    2015-08-01

    A rational secret sharing scheme is a game in which each party responsible for reconstructing a secret tries to maximize his or her utility by obtaining the secret alone. Quantum secret sharing schemes, derived either from quantum teleportation or from quantum error correcting code, do not succeed when we assume rational participants. This is because all existing quantum secret sharing schemes consider that the secret is reconstructed by a party chosen by the dealer. In this paper, for the first time, we propose a quantum secret sharing scheme which is resistant to rational parties. The proposed scheme is fair (everyone gets the secret), is correct, and achieves strict Nash equilibrium.

  2. 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.

  3. Timetabling: A Shared Services Model

    ERIC Educational Resources Information Center

    O'Regan, Carmel

    2012-01-01

    This paper identifies common timetabling issues and options as experienced in Australian universities, and develops a rationale to inform management decisions on a suitable system and the associated policies, procedures, management structure and resources at the University of Newcastle, to enable more effective timetabling in line with the needs…

  4. Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families.

    PubMed

    Wedenoja, J; Loukola, A; Tuulio-Henriksson, A; Paunio, T; Ekelund, J; Silander, K; Varilo, T; Heikkilä, K; Suvisaari, J; Partonen, T; Lönnqvist, J; Peltonen, L

    2008-07-01

    Schizophrenia is a common and complex mental disorder. Hereditary factors are important for its etiology, but despite linkage signals reported to several chromosomal regions in different populations, final identification of predisposing genes has remained a challenge. Utilizing a large family-based schizophrenia study sample from Finland, we have identified several linked loci: 1q32.2-q42, 2q, 4q31, 5q and 7q22. In this study, an independent sample of 352 nuclear schizophrenia families (n=1626) allowed replication of linkage on 7q21-32. In a sample of 245 nuclear families (n=1074) originating from the same geographical region as the families revealing the linkage, SNP and microsatellite association analyses of the four regional candidate genes, GRM3, RELN, SEMA3A and VGF, revealed no significant association to the clinical diagnosis of schizophrenia. Instead, quantifiable trait component analyses with neuropsychological endophenotypes available from 186 nuclear families (n=861) of the sample showed significant association to RELN variants for traits related to verbal (P=0.000003) and visual working memory (P=0.002), memory (P=0.002) and executive functioning (P=0.002). Trait-associated allele-positive subjects scored lower in the tests measuring working memory (P=0.0004-0.0000000004), memory (P=0.02-0.0001) and executive functioning (P=0.001). Our findings suggest that allelic variants of RELN contribute to the endophenotypes of schizophrenia.

  5. 48 CFR 48.104 - Sharing arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Sharing arrangements. 48.104 Section 48.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT VALUE ENGINEERING Policies and Procedures 48.104 Sharing arrangements....

  6. 47 CFR 73.3700 - Channel sharing.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... conjunction with the reverse auction. (2) The party relinquishing spectrum pursuant to a channel sharing... channel sharing licensee shall retain spectrum usage rights adequate to ensure a sufficient amount of the... carriage rights. A broadcast television station that voluntarily relinquishes spectrum usage rights...

  7. 45 CFR 63.22 - Cost sharing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Cost sharing. 63.22 Section 63.22 Public Welfare... THE ASSISTANT SECRETARY FOR PLANNING AND EVALUATION Financial Provisions § 63.22 Cost sharing. Policy... amount equal to as much as the entire cost of the project....

  8. 10 CFR 603.415 - Cost sharing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Cost sharing. To help ensure a competitive process that is fair and equitable to all potential... 10 Energy 4 2011-01-01 2011-01-01 false Cost sharing. 603.415 Section 603.415 Energy DEPARTMENT OF...-Federal parties carrying out a RD&D project under a TIA are to provide at least half of the costs of...

  9. Sharing Services and Facilities: Making It Work.

    ERIC Educational Resources Information Center

    Ritchey, David

    2002-01-01

    Describes several examples of cooperative efforts between school districts and municipalities to share facilities and other resources: Loveland, Colorado; Vaughan, Ontario; Yankton, South Dakota; Bangor, Maine; Mt. Pleasant, Iowa; Pamlico County, North Carolina. Also includes two examples of school districts sharing facilities and resources with…

  10. Data Sharing from a Policy Perspective

    ERIC Educational Resources Information Center

    Cheville, R. Alan

    2016-01-01

    This paper addresses questions of data sharing from the perspective of a former NSF program officer. A brief comparison of policy and research perspectives is made to highlight different values in these two communities. Data sharing is framed as one means to support dialog between researchers and those involved in policy. Other uses of data…

  11. 12 CFR 741.212 - Share insurance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Share insurance. 741.212 Section 741.212 Banks... INSURANCE Regulations Codified Elsewhere in NCUA's Regulations as Applying to Federal Credit Unions That Also Apply to Federally Insured State-Chartered Credit Unions § 741.212 Share insurance. (a)...

  12. 24 CFR 206.23 - Shared appreciation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Shared appreciation. 206.23 Section... CONVERSION MORTGAGE INSURANCE Eligibility; Endorsement Eligible Mortgages § 206.23 Shared appreciation. (a) Additional interest based on net appreciated value. Any mortgage for which the mortgagee has chosen...

  13. Matroids and quantum-secret-sharing schemes

    SciTech Connect

    Sarvepalli, Pradeep; Raussendorf, Robert

    2010-05-15

    A secret-sharing scheme is a cryptographic protocol to distribute a secret state in an encoded form among a group of players such that only authorized subsets of the players can reconstruct the secret. Classically, efficient secret-sharing schemes have been shown to be induced by matroids. Furthermore, access structures of such schemes can be characterized by an excluded minor relation. No such relations are known for quantum secret-sharing schemes. In this paper we take the first steps toward a matroidal characterization of quantum-secret-sharing schemes. In addition to providing a new perspective on quantum-secret-sharing schemes, this characterization has important benefits. While previous work has shown how to construct quantum-secret-sharing schemes for general access structures, these schemes are not claimed to be efficient. In this context the present results prove to be useful; they enable us to construct efficient quantum-secret-sharing schemes for many general access structures. More precisely, we show that an identically self-dual matroid that is representable over a finite field induces a pure-state quantum-secret-sharing scheme with information rate 1.

  14. 42 CFR 447.52 - Cost sharing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Services (physician visit, physical therapy, etc.) $4 10% of cost the agency pays 20% of cost the agency... paragraph (d)(2) of this section, the agency may target cost sharing to specified groups of individuals with... agency may target cost sharing to specified groups of individuals regardless of income. (e) Denial...

  15. Information Sharing for IT Security Professionals

    ERIC Educational Resources Information Center

    Petersen, Rodney J.

    2008-01-01

    Information sharing is a core value for information technology (IT) security professionals. It is also a familiar concept for those who work at institutions of higher education because of their long history of collaboration and openness. Information sharing has become part of the national fabric as IT security professionals attempt to secure cyber…

  16. 13 CFR 314.5 - Federal Share.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Federal Share. 314.5 Section 314.5 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE PROPERTY General § 314.5 Federal Share. (a) For purposes of this part, “Federal Share” means that portion of the...

  17. Planning a Shared-Schedule Residency.

    ERIC Educational Resources Information Center

    Chamberlin, Patricia A.; Jones, Mary D.

    1980-01-01

    The details of a shared-schedule residency program in the Department of Pediatrics of the University of Texas Medical Branch at Galveston are reviewed. Problems encountered are presented along with suggestions for their alleviation and the benefits of the job-sharing are discussed. Guidelines for planning such a program are offered. (Author/JMD)

  18. Revenue Sharing and the Spanish Speaking.

    ERIC Educational Resources Information Center

    Cabinet Committee on Opportunities for Spanish Speaking People, Washington, DC.

    Information of interest to Spanish speaking people on revenue sharing was presented in this booklet. Major topics were the utilization of General Revenue Sharing Funds, fund distribution, community action, reports on planned and actual use of funds, assurances to the Secretary of the Treasury, and civil rights provisions. Additional information on…

  19. 12 CFR 741.212 - Share insurance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 7 2014-01-01 2014-01-01 false Share insurance. 741.212 Section 741.212 Banks... INSURANCE Regulations Codified Elsewhere in NCUA's Regulations as Applying to Federal Credit Unions That Also Apply to Federally Insured State-Chartered Credit Unions § 741.212 Share insurance. (a)...

  20. 12 CFR 741.212 - Share insurance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Share insurance. 741.212 Section 741.212 Banks... INSURANCE Regulations Codified Elsewhere in NCUA's Regulations as Applying to Federal Credit Unions That Also Apply to Federally Insured State-Chartered Credit Unions § 741.212 Share insurance. (a)...

  1. 42 CFR 438.108 - Cost sharing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Cost sharing. 438.108 Section 438.108 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS MANAGED CARE Enrollee Rights and Protections § 438.108 Cost sharing. The contract...

  2. Learning to Share: How Literature Can Help.

    ERIC Educational Resources Information Center

    Krogh, Suzanne Lowell; Lamme, Linda Leonard

    1983-01-01

    Discusses elements of developmental theory needed in selecting literature for children, synthesizing Damon's (1977) and Selman's (1976) primary school stages. Criteria for choosing books about sharing are suggested, and an annotated list of books about sharing is offered along with suggestions for using the books. (RH)

  3. Shared Reading Goes High-Tech

    ERIC Educational Resources Information Center

    Gill, Sharon Ruth; Islam, Chhanda

    2011-01-01

    Shared Reading is a powerful teaching technique for teaching beginning reading. Technologies such as Interactive Whiteboards now make Shared Reading much easier to do. Large texts are projected on the whiteboard for Choral reading, and interactive features allow students to learn about letter-sound correspondences, spelling patterns, punctuation,…

  4. 33 CFR 239.8 - Cost sharing.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Cost sharing. 239.8 Section 239.8 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE WATER... for recreation facilities at local protection projects. Cost-sharing policies for project...

  5. 33 CFR 239.8 - Cost sharing.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Cost sharing. 239.8 Section 239.8 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE WATER... for recreation facilities at local protection projects. Cost-sharing policies for project...

  6. 33 CFR 239.8 - Cost sharing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Cost sharing. 239.8 Section 239.8 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE WATER... for recreation facilities at local protection projects. Cost-sharing policies for project...

  7. 47 CFR 95.7 - Channel sharing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Channel sharing. 95.7 Section 95.7... SERVICES General Mobile Radio Service (GMRS) § 95.7 Channel sharing. (a) Channels or channel pairs (one 462... and use of channels to reduce interference and to make the most effective use of the facilities....

  8. 47 CFR 95.7 - Channel sharing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Channel sharing. 95.7 Section 95.7... SERVICES General Mobile Radio Service (GMRS) § 95.7 Channel sharing. (a) Channels or channel pairs (one 462... and use of channels to reduce interference and to make the most effective use of the facilities....

  9. The Indiana Library Resource Sharing Manual.

    ERIC Educational Resources Information Center

    Indiana State Library, Indianapolis.

    Intended to encourage the appropriate and informed use of resource sharing mechanisms and services through the establishment of common policies and procedures throughout Indiana, this manual brings together in one document a description of current resource sharing activities in the state, codifies general practices, and provides guidelines based…

  10. Sharing the "Current Events" in Children's Lives

    ERIC Educational Resources Information Center

    Passe, Jeff

    2006-01-01

    In this article, the author talks about two elementary classroom activities used as teaching tools, namely "Show and Tell" and "Sharing Time." As a teaching tool, Sharing Time has several advantages over Show and Tell. It avoids children bringing valuable items to school, reduces emphasis on materialism, allows opportunities for extended oral…

  11. Tourism Skills Delivery: Sharing Tourism Knowledge Online

    ERIC Educational Resources Information Center

    Braun, Patrice; Hollick, Mary

    2006-01-01

    Purpose: The purpose of this paper is to share the authors' initial insights into tourism industry capacity building via flexibly delivered online skilling and knowledge sharing. Design/methodology/approach: An online research survey approach was employed, involving a sample of 64 micro tourism operators. Findings: The paper finds that the major…

  12. Another Kind of Diplomacy: International Resource Sharing

    ERIC Educational Resources Information Center

    Arlitsch, Kenning; Lombardo, Nancy T.; Gregory, Joan M.

    2005-01-01

    Over the past six years, the University of Utah libraries have developed an extensive international presence through digital resource sharing. Services include instruction, electronic document delivery, shared catalogs, and full-text databases. This paper will describe the process of establishing, extending, and improving these services through…

  13. Win-win data sharing in neuroscience.

    PubMed

    Ascoli, Giorgio A; Maraver, Patricia; Nanda, Sumit; Polavaram, Sridevi; Armañanzas, Rubén

    2017-01-31

    Most neuroscientists have yet to embrace a culture of data sharing. Using our decade-long experience at NeuroMorpho.Org as an example, we discuss how publicly available repositories may benefit data producers and end-users alike. We outline practical recipes for resource developers to maximize the research impact of data sharing platforms for both contributors and users.

  14. Shared Decisions & Technology-Assisted Learning

    ERIC Educational Resources Information Center

    Jacobs, Mary

    2005-01-01

    In this short article, the author discusses how Henderson Middle School in Jackson, Georgia used shared decision making to improve student achievement through the use of laptop computers. With effective use of technology and shared decision making, administrators at Henderson believe that they can continue to achieve Adequate Yearly Progress under…

  15. 10 CFR 603.415 - Cost sharing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Cost sharing. 603.415 Section 603.415 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Competition Phase § 603.415 Cost sharing. To help ensure a competitive process that is fair and equitable to all...

  16. 10 CFR 603.415 - Cost sharing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Cost sharing. 603.415 Section 603.415 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Competition Phase § 603.415 Cost sharing. To help ensure a competitive process that is fair and equitable to all...

  17. 10 CFR 603.415 - Cost sharing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Cost sharing. 603.415 Section 603.415 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Competition Phase § 603.415 Cost sharing. To help ensure a competitive process that is fair and equitable to all...

  18. Challenges to complete and useful data sharing.

    PubMed

    Mbuagbaw, Lawrence; Foster, Gary; Cheng, Ji; Thabane, Lehana

    2017-02-14

    Data sharing from clinical trials is one way of promoting fair and transparent conduct of clinical trials. It would maximise the use of data and permit the exploration of additional hypotheses. On the other hand, the quality of secondary analyses cannot always be ascertained, and it may be unfair to investigators who have expended resources to collect data to bear the additional burden of sharing. As the discussion on the best modalities of sharing data evolves, some of the practical issues that may arise need to be addressed. In this paper, we discuss issues which impede the use of data even when sharing should be possible: (1) multicentre studies requiring consent from all the investigators in each centre; (2) remote access platforms with software limitations and Internet requirements; (3) on-site data analysis when data cannot be moved; (4) governing bodies for data generated in one jurisdiction and analysed in another; (5) using programmatic data collected as part of routine care; (6) data collected in multiple languages; (7) poor data quality. We believe these issues apply to all primary data and cause undue difficulties in conducting analysis even when there is some willingness to share. They can be avoided by anticipating the possibility of sharing any clinical data and pre-emptively removing or addressing restrictions that limit complete sharing. These issues should be part of the data sharing discussion.

  19. 75 FR 9246 - Cooperative Share Loan Insurance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... URBAN DEVELOPMENT Cooperative Share Loan Insurance AGENCY: Office of the Chief Information Officer, HUD... cooperative housing loan insurance will be published to update existing policies, and better enable mortgagees to submit cooperative share loans for FHA insurance. This new publication will provide...

  20. 12 CFR 741.212 - Share insurance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Share insurance. 741.212 Section 741.212 Banks... INSURANCE Regulations Codified Elsewhere in NCUA's Regulations as Applying to Federal Credit Unions That Also Apply to Federally Insured State-Chartered Credit Unions § 741.212 Share insurance. (a)...

  1. 12 CFR 741.212 - Share insurance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Share insurance. 741.212 Section 741.212 Banks... INSURANCE Regulations Codified Elsewhere in NCUA's Regulations as Applying to Federal Credit Unions That Also Apply to Federally Insured State-Chartered Credit Unions § 741.212 Share insurance. (a)...

  2. Shared Leadership: Can It Work in Schools?

    ERIC Educational Resources Information Center

    Lindahl, Ronald

    2008-01-01

    Over the past couple of decades, K-12 schools have courageously struggled with the concept of shared, or distributed, leadership; however, the basic landscape of K-12 school leadership remains heavily hierarchical. Nonetheless, teachers can share leadership. This article explores productive forms of teacher leadership that are models of…

  3. 48 CFR 48.104 - Sharing arrangements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Sharing arrangements. 48.104 Section 48.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT VALUE ENGINEERING Policies and Procedures 48.104 Sharing arrangements....

  4. 48 CFR 48.104 - Sharing arrangements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Sharing arrangements. 48.104 Section 48.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT VALUE ENGINEERING Policies and Procedures 48.104 Sharing arrangements....

  5. 48 CFR 48.104 - Sharing arrangements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Sharing arrangements. 48.104 Section 48.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT VALUE ENGINEERING Policies and Procedures 48.104 Sharing arrangements....

  6. 48 CFR 48.104 - Sharing arrangements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Sharing arrangements. 48.104 Section 48.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT VALUE ENGINEERING Policies and Procedures 48.104 Sharing arrangements....

  7. 42 CFR 438.108 - Cost sharing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Cost sharing. 438.108 Section 438.108 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS MANAGED CARE Enrollee Rights and Protections § 438.108 Cost sharing. The contract...

  8. 42 CFR 438.108 - Cost sharing.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Cost sharing. 438.108 Section 438.108 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS MANAGED CARE Enrollee Rights and Protections § 438.108 Cost sharing. The contract...

  9. Intelligence Sharing, Fusion Centers, and Homeland Security

    DTIC Science & Technology

    2008-06-01

    33  VI. INTELIGENCE SHARING-LAW ENFORCEMENT...more competitive . Again, specifics on the results are scarce sense the public report is not available yet and because participants had to sign a...and local law enforcement. 36 VI. INTELIGENCE SHARING-LAW ENFORCEMENT Intelligence-led policing Intelligence-led policing is defined as

  10. How Do Children Share Information in Groups?

    ERIC Educational Resources Information Center

    Gummerum, Michaela; Leman, Patrick J.; Hollins, Tara S.

    2014-01-01

    Group decision making should be particularly beneficial when group members share unique information, because then a group can make a better decision than each group member alone. This study examined how elementary-school children share unique information during group decision making. Seventy-nine groups of 3 same-sex and same-age 7- and 9-year-old…

  11. Job Sharing: Is It for You?

    ERIC Educational Resources Information Center

    Schumann, Linda

    1994-01-01

    A teacher of deaf children describes her experience with job sharing at both the intermediate grade and preschool levels. The important role played by the full-time teacher's aide in providing continuity as well as the importance of communication are emphasized. Guidelines and answers to common questions regarding job sharing are offered. (DB)

  12. Liver sharing and organ procurement organization performance.

    PubMed

    Gentry, Sommer E; Chow, Eric K H; Massie, Allan; Luo, Xun; Zaun, David; Snyder, Jon J; Israni, Ajay K; Kasiske, Bert; Segev, Dorry L

    2015-03-01

    Whether the liver allocation system shifts organs from better performing organ procurement organizations (OPOs) to poorer performing OPOs has been debated for many years. Models of OPO performance from the Scientific Registry of Transplant Recipients make it possible to study this question in a data-driven manner. We investigated whether each OPO's net liver import was correlated with 2 performance metrics [observed to expected (O:E) liver yield and liver donor conversion ratio] as well as 2 alternative explanations [eligible deaths and incident listings above a Model for End-Stage Liver Disease (MELD) score of 15]. We found no evidence to support the hypothesis that the allocation system transfers livers from better performing OPOs to centers with poorer performing OPOs. Also, having fewer eligible deaths was not associated with a net import. However, having more incident listings was strongly correlated with the net import, both before and after Share 35. Most importantly, the magnitude of the variation in OPO performance was much lower than the variation in demand: although the poorest performing OPOs differed from the best ones by less than 2-fold in the O:E liver yield, incident listings above a MELD score of 15 varied nearly 14-fold. Although it is imperative that all OPOs achieve the best possible results, the flow of livers is not explained by OPO performance metrics, and instead, it appears to be strongly related to differences in demand.

  13. Performing an allreduce operation using shared memory

    DOEpatents

    Archer, Charles J; Dozsa, Gabor; Ratterman, Joseph D; Smith, Brian E

    2014-06-10

    Methods, apparatus, and products are disclosed for performing an allreduce operation using shared memory that include: receiving, by at least one of a plurality of processing cores on a compute node, an instruction to perform an allreduce operation; establishing, by the core that received the instruction, a job status object for specifying a plurality of shared memory allreduce work units, the plurality of shared memory allreduce work units together performing the allreduce operation on the compute node; determining, by an available core on the compute node, a next shared memory allreduce work unit in the job status object; and performing, by that available core on the compute node, that next shared memory allreduce work unit.

  14. Trust, vulnerable populations, and genetic data sharing

    PubMed Central

    Arias, Jalayne J.; Pham-Kanter, Genevieve; Gonzalez, Rosa; Campbell, Eric G.

    2015-01-01

    Recent policies and proposed regulations, including the Notice of Proposed Rulemaking for the Common Rule and the 2014 NIH Genetic Data Sharing Policy, seek to improve research subject protections. Protections for subjects whose genetic data is shared are critical to reduce risks such as loss of confidentiality, stigma, and discrimination. In the article ‘It depends whose data are being shared: considerations for genomic data sharing policies’, Robinson et al. provide a response to our article, ‘The Growth and Gaps of Genetic Data Sharing Policies’. Robinson et al. highlight the importance of individual and group preferences. In this article, we extend the conversation on models for improving protections which will mitigate consequences for individuals and groups that are vulnerable to stigma and discrimination. PMID:27774227

  15. Semiquantum secret sharing using entangled states

    SciTech Connect

    Li Qin; Chan, W. H.; Long Dongyang

    2010-08-15

    Secret sharing is a procedure for sharing a secret among a number of participants such that only the qualified subsets of participants have the ability to reconstruct the secret. Even in the presence of eavesdropping, secret sharing can be achieved when all the members are quantum. So what happens if not all the members are quantum? In this paper, we propose two semiquantum secret sharing protocols by using maximally entangled Greenberger-Horne-Zeilinger-type states in which quantum Alice shares a secret with two classical parties, Bob and Charlie, in a way that both parties are sufficient to obtain the secret, but one of them cannot. The presented protocols are also shown to be secure against eavesdropping.

  16. Performing an allreduce operation using shared memory

    DOEpatents

    Archer, Charles J [Rochester, MN; Dozsa, Gabor [Ardsley, NY; Ratterman, Joseph D [Rochester, MN; Smith, Brian E [Rochester, MN

    2012-04-17

    Methods, apparatus, and products are disclosed for performing an allreduce operation using shared memory that include: receiving, by at least one of a plurality of processing cores on a compute node, an instruction to perform an allreduce operation; establishing, by the core that received the instruction, a job status object for specifying a plurality of shared memory allreduce work units, the plurality of shared memory allreduce work units together performing the allreduce operation on the compute node; determining, by an available core on the compute node, a next shared memory allreduce work unit in the job status object; and performing, by that available core on the compute node, that next shared memory allreduce work unit.

  17. The Open Faculty: To Share or Not to Share--Is That the Question?

    ERIC Educational Resources Information Center

    Andersen, Maria H.

    2010-01-01

    In this article, the author shares her view of "open faculty." To truly understand "open faculty," one needs to step back to a time before the Internet, before it was so easy and inexpensive to share anything and everything. In the pre-Internet era, faculty fell on the same continuum between those who freely share ideas and resources and those who…

  18. 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

  19. Bayesian inference of shared recombination hotspots between humans and chimpanzees.

    PubMed

    Wang, Ying; Rannala, Bruce

    2014-12-01

    Recombination generates variation and facilitates evolution. Recombination (or lack thereof) also contributes to human genetic disease. Methods for mapping genes influencing complex genetic diseases via association rely on linkage disequilibrium (LD) in human populations, which is influenced by rates of recombination across the genome. Comparative population genomic analyses of recombination using related primate species can identify factors influencing rates of recombination in humans. Such studies can indicate how variable hotspots for recombination may be both among individuals (or populations) and over evolutionary timescales. Previous studies have suggested that locations of recombination hotspots are not conserved between humans and chimpanzees. We made use of the data sets from recent resequencing projects and applied a Bayesian method for identifying hotspots and estimating recombination rates. We also reanalyzed SNP data sets for regions with known hotspots in humans using samples from the human and chimpanzee. The Bayes factors (BF) of shared recombination hotspots between human and chimpanzee across regions were obtained. Based on the analysis of the aligned regions of human chromosome 21, locations where the two species show evidence of shared recombination hotspots (with high BFs) were identified. Interestingly, previous comparative studies of human and chimpanzee that focused on the known human recombination hotspots within the β-globin and HLA regions did not find overlapping of hotspots. Our results show high BFs of shared hotspots at locations within both regions, and the estimated locations of shared hotspots overlap with the locations of human recombination hotspots obtained from sperm-typing studies.

  20. Genomic Research and Wide Data Sharing: Views of Prospective Participants

    PubMed Central

    Trinidad, Susan Brown; Fullerton, Stephanie M.; Bares, Julie M.; Jarvik, Gail P.; Larson, Eric B.; Burke, Wylie

    2011-01-01

    Purpose Sharing study data within the research community generates tension between two important goods: promoting scientific goals and protecting the privacy interests of study participants. The present study was designed to explore the perceptions, beliefs, and attitudes of research participants and possible future participants regarding genome-wide association studies (GWAS) and repository-based research. Methods Focus group sessions with (1) current research participants, (2) surrogate decision-makers, and (3) three age-defined cohorts (18–34 years, 35–50, >50). Results Participants expressed a variety of opinions about the acceptability of wide sharing of genetic and phenotypic information for research purposes through large, publicly accessible data repositories. Most believed that making de-identified study data available to the research community is a social good that should be pursued. Privacy and confidentiality concerns were common, though they would not necessarily preclude participation. Many participants voiced reservations about sharing data with for-profit organizations. Conclusions Trust is central in participants’ views regarding GWAS data sharing. Further research is needed to develop governance models that enact the values of stewardship. PMID:20535021

  1. Shared governance in a clinic system.

    PubMed

    Meyers, Michelle M; Costanzo, Cindy

    2015-01-01

    Shared governance in health care empowers nurses to share in the decision-making process, which results in decentralized management and collective accountability. Share governance practices have been present in hospitals since the late 1970s. However, shared governance in ambulatory care clinics has not been well established. The subjects of this quality project included staff and administrative nurses in a clinic system. The stakeholder committee chose what model of shared governance to implement and educated clinic staff. The Index of Professional Nursing Governance measured a shared governance score pre- and postimplementation of the Clinic Nursing Council. The Clinic Nursing Council met bimonthly for 3 months during this project to discuss issues and make decisions related to nursing staff. The Index of Professional Nursing Governance scores indicated traditional governance pre- and postimplementation of the Clinic Nursing Council, which is to be expected. The stakeholder committee was beneficial to the initial implementation process and facilitated staff nurse involvement. Shared governance is an evolutionary process that develops empowered nurses and nurse leaders.

  2. Secret Sharing of a Quantum State.

    PubMed

    Lu, He; Zhang, Zhen; Chen, Luo-Kan; Li, Zheng-Da; Liu, Chang; Li, Li; Liu, Nai-Le; Ma, Xiongfeng; Chen, Yu-Ao; Pan, Jian-Wei

    2016-07-15

    Secret sharing of a quantum state, or quantum secret sharing, in which a dealer wants to share a certain amount of quantum information with a few players, has wide applications in quantum information. The critical criterion in a threshold secret sharing scheme is confidentiality: with less than the designated number of players, no information can be recovered. Furthermore, in a quantum scenario, one additional critical criterion exists: the capability of sharing entangled and unknown quantum information. Here, by employing a six-photon entangled state, we demonstrate a quantum threshold scheme, where the shared quantum secrecy can be efficiently reconstructed with a state fidelity as high as 93%. By observing that any one or two parties cannot recover the secrecy, we show that our scheme meets the confidentiality criterion. Meanwhile, we also demonstrate that entangled quantum information can be shared and recovered via our setting, which shows that our implemented scheme is fully quantum. Moreover, our experimental setup can be treated as a decoding circuit of the five-qubit quantum error-correcting code with two erasure errors.

  3. Secret Sharing of a Quantum State

    NASA Astrophysics Data System (ADS)

    Lu, He; Zhang, Zhen; Chen, Luo-Kan; Li, Zheng-Da; Liu, Chang; Li, Li; Liu, Nai-Le; Ma, Xiongfeng; Chen, Yu-Ao; Pan, Jian-Wei

    2016-07-01

    Secret sharing of a quantum state, or quantum secret sharing, in which a dealer wants to share a certain amount of quantum information with a few players, has wide applications in quantum information. The critical criterion in a threshold secret sharing scheme is confidentiality: with less than the designated number of players, no information can be recovered. Furthermore, in a quantum scenario, one additional critical criterion exists: the capability of sharing entangled and unknown quantum information. Here, by employing a six-photon entangled state, we demonstrate a quantum threshold scheme, where the shared quantum secrecy can be efficiently reconstructed with a state fidelity as high as 93%. By observing that any one or two parties cannot recover the secrecy, we show that our scheme meets the confidentiality criterion. Meanwhile, we also demonstrate that entangled quantum information can be shared and recovered via our setting, which shows that our implemented scheme is fully quantum. Moreover, our experimental setup can be treated as a decoding circuit of the five-qubit quantum error-correcting code with two erasure errors.

  4. Platelet associated antibodies

    MedlinePlus

    ... medlineplus.gov/ency/article/003552.htm Platelet-associated antibodies blood test To use the sharing features on ... JavaScript. This blood test shows if you have antibodies against platelets in your blood. Platelets are a ...

  5. American Behcet's Disease Association

    MedlinePlus

    ... Awareness Day May 20th is Behcet's Awareness Day Behcet's Disease Awareness Share your story and educate others about ... org/en/community/behcet-s-syndrome Upcoming Events American Behcet's Disease Association PO BOX 80576 Rochester, MI 48308 Contact ...

  6. Shaping future nurse leaders through shared governance.

    PubMed

    Beglinger, Joan Ellis; Hauge, Barbara; Krause, Sheryl; Ziebarth, Laura

    2011-03-01

    The progression of five professional nurses from shared governance council chairs to unit director positions and the progression of three nurses from shared governance council chairs to clinical nurse specialist roles in an 18-year period provide compelling evidence of the impact shared governance has provided in the development of future nurse leaders in our organization. The collective wisdom of those who have lived this experience suggests that the opportunities inherent in these clinical nurse leadership roles make this a logical progression, including getting noticed and nudged, developing an understanding of the big picture, developing a results orientation, and substantial skill acquisition.

  7. Can catch shares prevent fisheries collapse?

    PubMed

    Costello, Christopher; Gaines, Steven D; Lynham, John

    2008-09-19

    Recent reports suggest that most of the world's commercial fisheries could collapse within decades. Although poor fisheries governance is often implicated, evaluation of solutions remains rare. Bioeconomic theory and case studies suggest that rights-based catch shares can provide individual incentives for sustainable harvest that is less prone to collapse. To test whether catch-share fishery reforms achieve these hypothetical benefits, we have compiled a global database of fisheries institutions and catch statistics in 11,135 fisheries from 1950 to 2003. Implementation of catch shares halts, and even reverses, the global trend toward widespread collapse. Institutional change has the potential for greatly altering the future of global fisheries.

  8. Shared address collectives using counter mechanisms

    DOEpatents

    Blocksome, Michael; Dozsa, Gabor; Gooding, Thomas M; Heidelberger, Philip; Kumar, Sameer; Mamidala, Amith R; Miller, Douglas

    2014-02-18

    A shared address space on a compute node stores data received from a network and data to transmit to the network. The shared address space includes an application buffer that can be directly operated upon by a plurality of processes, for instance, running on different cores on the compute node. A shared counter is used for one or more of signaling arrival of the data across the plurality of processes running on the compute node, signaling completion of an operation performed by one or more of the plurality of processes, obtaining reservation slots by one or more of the plurality of processes, or combinations thereof.

  9. Shared-memory parallel programming in C++

    SciTech Connect

    Beck, B. )

    1990-07-01

    This paper discusses how researchers have produced a set of portable parallel-programming constructs for C, implemented in M4 macros. These parallel-programming macros are available under the name Parmacs. The Parmacs macros let one write parallel C programs for shared-memory, distributed-memory, and mixed-memory (shared and distributed) systems. They have been implemented on several machines. Because Parmacs offers useful parallel-programming features, the author has considered how these problems might be overcome or avoided. The author thought that using C++, rather than C, would address these problems adequately, and describes the C++ features exploited. The work described addresses shared-memory constructs.

  10. Sharing Your Knowledge: Getting Your Idea Published.

    PubMed

    Milner, Kerry A

    2016-01-01

    Nurses have a professional and ethical obligation to share best practices to advance nursing knowledge and create better outcomes for patients. Practice-based evidence is as important to advancing evidence-based practice as original research. Infusion nurses are in an excellent position to share local best practices more broadly. Writing for publication is a mechanism for disseminating practice-based evidence. This article reviews the importance of sharing best practices and describes not only how to prepare a manuscript for publication but also resources that will help nurses in this important endeavor.

  11. Sensorpedia: Information Sharing Across Autonomous Sensor Systems

    SciTech Connect

    Gorman, Bryan L; Resseguie, David R; Tomkins-Tinch, Christopher H

    2009-01-01

    The concept of adapting social media technologies is introduced as a means of achieving information sharing across autonomous sensor systems. Historical examples of interoperability as an underlying principle in loosely-coupled systems is compared and contrasted with corresponding tightly-coupled, integrated systems. Examples of ad hoc information sharing solutions based on Web 2.0 social networks, mashups, blogs, wikis, and data tags are presented and discussed. The underlying technologies of these solutions are isolated and defined, and Sensorpedia is presented as a formalized application for implementing sensor information sharing across large-scale enterprises with incompatible autonomous sensor systems.

  12. Describing functional requirements for knowledge sharing communities

    NASA Technical Reports Server (NTRS)

    Garrett, Sandra; Caldwell, Barrett

    2002-01-01

    Human collaboration in distributed knowledge sharing groups depends on the functionality of information and communication technologies (ICT) to support performance. Since many of these dynamic environments are constrained by time limits, knowledge must be shared efficiently by adapting the level of information detail to the specific situation. This paper focuses on the process of knowledge and context sharing with and without mediation by ICT, as well as issues to be resolved when determining appropriate ICT channels. Both technology-rich and non-technology examples are discussed.

  13. Shared governance in the endoscopy department.

    PubMed

    Metcalf, R; Tate, R

    1995-01-01

    Studies have indicated that active participation by employees improves job satisfaction and performance. There is a sense of pride and accountability that is demonstrated in the work environment when staff are involved in the decision-making process. Recent emergence of a relatively new philosophy for management that promotes employee ownership is shared governance. This type of leadership allows individuals who are at the center of the work place to participate in the decisions that actively reflect their needs. In this article, the authors describe the process of implementing shared governance in an Endoscopy Department. The effectiveness of shared governance is evidenced by the renewed enthusiasm and energy demonstrated by the staff.

  14. Cortical and trabecular load sharing in the human femoral neck.

    PubMed

    Nawathe, Shashank; Nguyen, Bich Phuong; Barzanian, Nasim; Akhlaghpour, Hosna; Bouxsein, Mary L; Keaveny, Tony M

    2015-03-18

    The relative role of the cortical vs trabecular bone in the load-carrying capacity of the proximal femur-a fundamental issue in both basic-science and clinical biomechanics-remains unclear. To gain insight into this issue, we performed micro-CT-based, linear elastic finite element analysis (61.5-micron-sized elements; ~280 million elements per model) on 18 proximal femurs (5M, 13F, ages 61-93 years) to quantify the fraction of frontal-plane bending moment shared by the cortical vs trabecular bone in the femoral neck, as well as the associated spatial distributions of stress. Analyses were performed separately for a sideways fall and stance loading. For both loading modes and across all 18 bones, we found consistent patterns of load-sharing in the neck: most proximally, the trabecular bone took most of the load; moving distally, the cortical bone took increasingly more of the load; and more distally, there was a region of uniform load-sharing, the cortical bone taking the majority of the load. This distal region of uniform load-sharing extended more for fall than stance loading (77 ± 8% vs 51 ± 6% of the neck length for fall vs. stance; mean ± SD) but the fraction of total load taken by the cortical bone in that region was greater for stance loading (88 ± 5% vs. 64 ± 9% for stance vs. fall). Locally, maximum stress levels occurred in the cortical bone distally, but in the trabecular bone proximally. Although the distal cortex showed qualitative stress distributions consistent with the behavior of an Euler-type beam, quantitatively beam theory did not apply. We conclude that consistent and well-delineated regions of uniform load-sharing and load-transfer between the cortical and trabecular bone exist within the femoral neck, the details of which depend on the external loading conditions.

  15. Shared Negative Experiences Lead to Identity Fusion via Personal Reflection

    PubMed Central

    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. PMID:26699364

  16. Catch shares slow the race to fish.

    PubMed

    Birkenbach, Anna M; Kaczan, David J; Smith, Martin D

    2017-04-05

    In fisheries, the tragedy of the commons manifests as a competitive race to fish that compresses fishing seasons, resulting in ecological damage, economic waste, and occupational hazards. Catch shares are hypothesized to halt the race by securing each individual's right to a portion of the total catch, but there is evidence for this from selected examples only. Here we systematically analyse natural experiments to test whether catch shares reduce racing in 39 US fisheries. We compare each fishery treated with catch shares to an individually matched control before and after the policy change. We estimate an average policy treatment effect in a pooled model and in a meta-analysis that combines separate estimates for each treatment-control pair. Consistent with the theory that market-based management ends the race to fish, we find strong evidence that catch shares extend fishing seasons. This evidence informs the current debate over expanding the use of market-based regulation to other fisheries.

  17. Benefit sharing: it's time for a definition.

    PubMed

    Schroeder, D

    2007-04-01

    Benefit sharing has been a recurrent theme in international debates for the past two decades. However, despite its prominence in law, medical ethics and political philosophy, the concept has never been satisfactorily defined. In this conceptual paper, a definition that combines current legal guidelines with input from ethics debates is developed. Philosophers like boxes; protective casings into which they can put concisely-defined concepts. Autonomy is the human capacity for self-determination; beneficence denotes the virtue of good deeds, coercion is the intentional threat of harm and so on. What about benefit sharing? Does the concept have a box and are the contents clearly defined? The answer to this question has to be no. The concept of benefit sharing is almost unique in that various disciplines use it regularly without precise definitions. In this article, a definition for benefit sharing is provided, to eliminate unnecessary ambiguity.

  18. Biotech Information-Sharing Memorandum of Understanding

    EPA Pesticide Factsheets

    EPA, FDA, and the U.S. Department of Agriculture's Animal and Plant Health Inspection Service/Biotechnology Regulatory Services share the regulatory oversight over genetically engineered plants and the foods derived from such plants.Learn how this works.

  19. Sharing Fiscal Information: A Legislative Branch View.

    ERIC Educational Resources Information Center

    Rivlin, Alice M.

    1978-01-01

    Decisions regarding budget matters are complex; therefore, information sharing between the executive and legislative branches is helpful and necessary. Budget reforms have been initiated, but future trends indicate the need for flexibility and revision of information pathways. (MBR)

  20. 32 CFR 37.1265 - Cost sharing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in This Part § 37.1265 Cost sharing. A portion of project costs that are borne by the recipient or non-Federal third parties on behalf of the...