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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. 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.

  3. 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.

  4. Linkage and Association Analysis of ADHD Endophenotypes in Extended and Multigenerational Pedigrees from a Genetic Isolate

    PubMed Central

    Martinez, Ariel F.; Lopera, Francisco; Velez, Jorge I.; Palacio, Juan D.; Patel, Hardip; Easteal, Simon; Acosta, Maria T.; Castellanos, F. Xavier

    2015-01-01

    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, e.g., 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

  5. Genetic associations of nonsynonymous exonic variants with psychophysiological endophenotypes.

    PubMed

    Vrieze, Scott I; Malone, Stephen M; Pankratz, Nathan; Vaidyanathan, Uma; Miller, Michael B; Kang, Hyun Min; McGue, Matt; Abecasis, Gonçalo; Iacono, William G

    2014-12-01

    We mapped ∼85,000 rare nonsynonymous exonic single nucleotide polymorphisms (SNPs) to 17 psychophysiological endophenotypes in 4,905 individuals, including antisaccade eye movements, resting EEG, P300 amplitude, electrodermal activity, affect-modulated startle eye blink. Nonsynonymous SNPs are predicted to directly change or disrupt proteins encoded by genes and are expected to have significant biological consequences. Most such variants are rare, and new technologies can efficiently assay them on a large scale. We assayed 247,870 mostly rare SNPs on an Illumina exome array. Approximately 85,000 of the SNPs were polymorphic, rare (MAF < .05), and nonsynonymous. Single variant association tests identified a SNP in the PARD3 gene associated with theta resting EEG power. The sequence kernel association test, a gene-based test, identified a gene PNPLA7 associated with pleasant difference startle, the difference in startle magnitude between pleasant and neutral images. No other single nonsynonymous variant, or gene-based group of variants, was strongly associated with any endophenotype. PMID:25387709

  6. Genetic associations of nonsynonymous exonic variants with psychophysiological endophenotypes

    PubMed Central

    Vrieze, Scott I.; Malone, Stephen M.; Pankratz, Nathan; Vaidyanathan, Uma; Miller, Michael B.; Kang, Hyun Min; McGue, Matt; Abecasis, Gonçalo; Iacono, William G.

    2014-01-01

    We mapped ~85,000 rare nonsynonymous exonic single nucleotide polymorphisms (SNPs) to 17 psychophysiological endophenotypes in 4,905 individuals, including antisaccade eye movements, resting EEG, P300 amplitude, electrodermal activity, affect-modulated startle eye blink. Nonsynonymous SNPs are predicted to directly change or disrupt proteins encoded by genes and are expected to have significant biological consequences. Most such variants are rare, and new technologies can efficiently assay them on a large scale. We assayed 247,870 mostly rare SNPs on an Illumina exome array. Approximately 85,000 of the SNPs were polymorphic, rare (MAF < .05), and nonsynonymous. Single variant association tests identified a SNP in the PARD3 gene associated with theta resting EEG power. The sequence kernel association test, a gene-based test, identified a gene PNPLA7 associated with pleasant difference startle, the difference in startle magnitude between pleasant and neutral images. No other single nonsynonymous variant, or gene-based group of variants, was strongly associated with any endophenotype. PMID:25387709

  7. 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.

  8. 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…

  9. Endophenotype Network Models: Common Core of Complex Diseases.

    PubMed

    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

    2016-01-01

    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. PMID:27278246

  10. Endophenotype Network Models: Common Core of Complex Diseases.

    PubMed

    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

    2016-06-09

    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.

  11. Endophenotype Network Models: Common Core of Complex Diseases

    PubMed Central

    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

    2016-01-01

    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. PMID:27278246

  12. 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

  13. 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. PMID:25798540

  14. 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.

  15. 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

  16. [The endophenotype concept in the neurophysiological studies of schizophrenia].

    PubMed

    Kirenskaia, A V; Storozheva, Z I; Miamlin, V V; Tkachenko, A A

    2013-01-01

    The endophenotype concept is considered as theoretical basis for the study of pathobiological mechanisms of schizophrenia and for the development of the complex of instrumental diagnostic methods. The contemporary state of the problem and the most significant results of the study of three neurophysiological schizophrenia endophenotypes are presented in the review: P50 auditory evoked potential suppression, prepulse inhibition of the startle reflex and antisaccade task. The current understanding of the underlying neurophysiological and neurochemical mechanisms is described for each measure. The results of the association studies of neurophysiological endophenotypes with the relevant to schizophrenia genes' polymorphisms are laid down. High degree of independence of the considered endophenotypes is demonstrated. Taking into account the data on relatively low specificity of each endophenotype to schizophrenia compared to other mental disturbances the authors pay special attention to the model of multivariate endophenotype as a scientific and diagnostic tool.

  17. Endophenotypes in Schizophrenia for the Perinatal Period: Criteria for Validation

    PubMed Central

    Ross, Randal G.; Freedman, Robert

    2015-01-01

    Endophenotypes are disease-associated phenotypes that are thought to reflect the neurobiological or other mechanisms that underlie the more overt symptoms of a psychiatric illness. Endophenotypes have been critical in understanding the genetics, neurobiology, and treatment of schizophrenia. Because psychiatric illnesses have multiple causes, including both genetic and nongenetic risk factors, an endophenotype linked to one of the mechanisms may be expressed more frequently than the disease itself. However, in schizophrenia research, endophenotypes have almost exclusively been studied in older adolescents or adults who have entered or passed through the age of risk for the disorder. Yet, schizophrenia is a neurodevelopmental disorder where prenatal development starts a cascade of brain changes across the lifespan. Endophenotypes have only minimally been utilized to explore the perinatal development of vulnerability. One major impediment to the development of perinatally-useful endophenotypes has been the established validity criteria. For example, the criterion that the endophenotype be more frequently present in those with disease than those without is difficult to demonstrate when there can be a decades-long period between endophenotype measurement and the age of greatest risk for onset of the disorder. This article proposes changes to the endophenotype validity criteria appropriate to perinatal research and reviews how application of these modified criteria helped identify a perinatally-usable phenotype of risk for schizophrenia, P50 sensory gating, which was then used to propose a novel perinatal primary prevention intervention. PMID:25943124

  18. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism

    PubMed Central

    James, S. Jill; Melnyk, Stepan; Jernigan, Stefanie; Cleves, Mario A.; Halsted, Charles H.; Wong, Donna H.; Cutler, Paul; Bock, Kenneth; Boris, Marvin; Bradstreet, J. Jeffrey; Baker, Sidney M.; Gaylor, David W.

    2008-01-01

    Autism is a behaviorally-defined neurodevelopmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal. Although both genetic and environmental factors are thought to be involved, none have been reproducibly identified. The metabolic phenotype of an individual reflects the influence of endogenous and exogenous factors on genotype. As such, it provides a window through which the interactive impact of genes and environment may be viewed and relevant susceptibility factors identified. Although abnormal methionine metabolism has been associated with other neurologic disorders, these pathways and related polymorphisms have not been evaluated in autistic children. Plasma levels of metabolites in methionine transmethylation and transsulfuration pathways were measured in 80 autistic and 73 control children. In addition, common polymorphic variants known to modulate these metabolic pathways were evaluated in 360 autistic children and 205 controls. The metabolic results indicated that plasma methionine and the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), an indicator of methylation capacity, were significantly decreased in the autistic children relative to age-matched controls. In addition, plasma levels of cysteine, glutathione, and the ratio of reduced to oxidized glutathione, an indication of antioxidant capacity and redox homeostasis, were significantly decreased. Differences in allele frequency and/or significant gene-gene interactions were found for relevant genes encoding the reduced folate carrier (RFC 80G>A), transcobalamin II (TCN2 776G>C), catechol-O-methyltransferase (COMT 472G>A), methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C), and GST M1. We propose that an increased vulnerability to oxidative stress (endogenous or environmental) may contribute to the development and clinical manifestations of autism. PMID

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

    PubMed Central

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

    2016-01-01

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

  20. 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

  1. Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample.

    PubMed

    Mobascher, A; Diaz-Lacava, A; Wagner, M; Gallinat, J; Wienker, T F; Drichel, D; Becker, T; Steffens, M; Dahmen, N; Gründer, G; Thürauf, N; Kiefer, F; Kornhuber, J; Toliat, M R; Thiele, H; Nürnberg, P; Steinlein, O; Winterer, G

    2016-01-01

    Variation in genes coding for nicotinic acetylcholine receptor (nAChR) subunits affect cognitive processes and may contribute to the genetic architecture of neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in the CHRNA4 gene that codes for the alpha4 subunit of alpha4/beta2-containing receptors have previously been implicated in aspects of (mostly visual) attention and smoking-related behavioral measures. Here we investigated the effects of six synonymous but functional CHRNA4 exon 5 SNPs on the N100 event-related potential (ERP), an electrophysiological endophenotype elicited by a standard auditory oddball. A total of N = 1,705 subjects randomly selected from the general population were studied with electroencephalography (EEG) as part of the German Multicenter Study on nicotine addiction. Two of the six variants, rs1044396 and neighboring rs1044397, were significantly associated with N100 amplitude. This effect was pronounced in females where we also observed an effect on reaction time. Sequencing of the complete exon 5 region in the population sample excluded the existence of additional/functional variants that may be responsible for the observed effects. This is the first large-scale population-based study investigation the effects of CHRNA4 SNPs on brain activity measures related to stimulus processing and attention. Our results provide further evidence that common synonymous CHRNA4 exon 5 SNPs affect cognitive processes and suggest that they also play a role in the auditory system. As N100 amplitude reduction is considered a schizophrenia-related endophenotype the SNPs studied here may also be associated with schizophrenia outcome measures. PMID:27054571

  2. Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample

    PubMed Central

    Mobascher, A.; Diaz-Lacava, A.; Wagner, M.; Gallinat, J.; Wienker, T. F.; Drichel, D.; Becker, T.; Steffens, M.; Dahmen, N.; Gründer, G.; Thürauf, N.; Kiefer, F.; Kornhuber, J.; Toliat, M. R.; Thiele, H.; Nürnberg, P.; Steinlein, O.; Winterer, G.

    2016-01-01

    Variation in genes coding for nicotinic acetylcholine receptor (nAChR) subunits affect cognitive processes and may contribute to the genetic architecture of neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in the CHRNA4 gene that codes for the alpha4 subunit of alpha4/beta2-containing receptors have previously been implicated in aspects of (mostly visual) attention and smoking-related behavioral measures. Here we investigated the effects of six synonymous but functional CHRNA4 exon 5 SNPs on the N100 event-related potential (ERP), an electrophysiological endophenotype elicited by a standard auditory oddball. A total of N = 1,705 subjects randomly selected from the general population were studied with electroencephalography (EEG) as part of the German Multicenter Study on nicotine addiction. Two of the six variants, rs1044396 and neighboring rs1044397, were significantly associated with N100 amplitude. This effect was pronounced in females where we also observed an effect on reaction time. Sequencing of the complete exon 5 region in the population sample excluded the existence of additional/functional variants that may be responsible for the observed effects. This is the first large-scale population-based study investigation the effects of CHRNA4 SNPs on brain activity measures related to stimulus processing and attention. Our results provide further evidence that common synonymous CHRNA4 exon 5 SNPs affect cognitive processes and suggest that they also play a role in the auditory system. As N100 amplitude reduction is considered a schizophrenia-related endophenotype the SNPs studied here may also be associated with schizophrenia outcome measures. PMID:27054571

  3. [Endophenotypes and autism spectrum disorders].

    PubMed

    Sokolowsky, M; Fakra, E; Azorin, J-M

    2012-12-01

    Genetic factors of ASD stay unknown after 30 years of research. The concept of "endophenotype" seems an interesting approach toward these factors. "Enlarged phenotypes" in families of ASD persons could lead to the definition of ASD endophenotypes. "Enlarged phenotypes" include clinical symptoms, morphological and functional brain anomalies enlightening ASD physiopathology and brain physiology. Knowledge of endophenotypes will lead to ASD genetic risk factors. This knowledge will open ethical questions about prenatal diagnosis.

  4. [Neurological soft signs as a candidate for endophenotype of schizophrenia].

    PubMed

    Kałuzyńska, Olga; Rabe-Jabłońska, Jolanta

    2014-01-01

    A concept of an endophenotype, also termed as an internal endophenotype, is used in genetic studies on psychiatric disorders. Neurological soft signs are also considered candidates for endophenotypes of schizophrenia. Neurological soft signs are, objectively measured, non-localizing abnormalities, not related to impairment of a specific brain region, reflecting improper cortical-subcorical and intercortical connections. This paper presents the main domains of NSS, methods of measurement of NSS, their neuroanatomical substrate, association of NSS with schizophrenia symptoms the and analysis of the literature in order to check whether NSS meet the criteria of the phenotype. A marker can be considered a phenotype if it meets the following criteria: 1) association with a disease in a population, 2) heritability, 3) state-independence, 4) familial association (the endophenotype is more prevalent in the affected individuals, their affected and non-affected family members in comparison to the normal population), 5) co-segregation (the endophenotype is more prevalent among ill family members of ill probands compared with healthy relatives). Currently, there is an ample evidence that the NSS, especially these representing impaired motor coordination, meet certain criteria of an endophenotype. However, there are still several unresolved questions concerning NSS: studies on relatives of schizophrenic patients included small groups of subjects, many of the studies included individuals with schizophrenia, as well as schizophrenia spectrum disorders, the available date-base of twins (schizophrenia-concordant and schizophrenia non -concordant) is not sufficiently large, there are too few studies evaluating the relationship of NSS and individual genes, there are no objective and quantitative methods of measurement of NSS. Therefore, NSS still represent only candidates for an endophenotype of schizophrenia. Finding correlations of selected NSS with other endophenotypes and their

  5. Endophenotypes in Schizophrenia: A Selective Review

    PubMed Central

    Allen, Allyssa J.; Griss, Mélina E.; Folley, Bradley S.; Hawkins, Keith A.; Pearlson, Godfrey D.

    2009-01-01

    Background Given the wealth of data in the literature on schizophrenia endophenotypes, it is useful to have one source to reference their frequency data. We reviewed the literature on disease-liability associated variants in structural and functional magnetic resonance images (MRI), sensory processing measures, neuromotor abilities, neuropsychological measures, and physical characteristics in schizophrenia patients (SCZ), their first-degree relatives (REL), and healthy controls (HC). The purpose of this review was to provide a summary of the existing data on the most extensively published endophenotypes for schizophrenia. Methods We searched PubMed and MedLine for all studies on schizophrenia endophenotypes comparing SCZ to HC and/or REL to HC groups. Percent abnormal values, generally defined as > 2 SD from the mean (in the direction of abnormality) and/or associated effect sizes (Cohen’s d) were calculated foreach study. Results Combined, the articles reported an average 39.4% (SD=20.7%; range=2.2-100%) of abnormal values in SCZ, 28.1% (SD=16.6%; range=1.6-67.0%) abnormal values in REL, and 10.2% (SD=6.7%; range=0.0-34.6%) in HC groups. Conclusions These findings are reviewed in the context of emerging hypotheses on schizophrenia endophenotypes, as well as a discussion of clustering trends among the various intermediate phenotypes. In addition, programs for future research are discussed, as instantiated in a few recent large-scale studies on multiple endophenotypes across patients, relatives, and healthy controls. PMID:19223268

  6. 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

  7. Endophenotypes in the personality disorders

    PubMed Central

    Siever, Larry J.

    2005-01-01

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

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

    PubMed Central

    Rangaswamy, Madhavi; Porjesz, Bernice

    2010-01-01

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

  9. 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.

  10. Association of polymorphisms in the dopamine D4 receptor gene and the activity-impulsivity endophenotype in dogs.

    PubMed

    Hejjas, K; Vas, J; Topal, J; Szantai, E; Ronai, Z; Szekely, A; Kubinyi, E; Horvath, Z; Sasvari-Szekely, M; Miklosi, A

    2007-12-01

    A variable number of tandem repeats (VNTR) polymorphism in exon 3 of the human dopamine D4 receptor gene (DRD4) has been associated with attention deficit hyperactivity disorder (ADHD). Rodents possess no analogous repeat sequence, whereas a similar tandem repeat polymorphism of the DRD4 gene was identified in dogs, horses and chimpanzees. Here, we present a genetic association study of the DRD4 VNTR and the activity-impulsivity dimension of the recently validated dog-ADHD Rating Scale. To avoid false positives arising from population stratification, a single breed of dogs (German shepherd) was studied. Two DRD4 alleles (referred to as 2 and 3a) were detected in this breed, and genotype frequencies were in Hardy-Weinberg equilibrium. For modelling distinct environmental conditions, 'pet' and 'police' German shepherds were characterized. Police German shepherds possessing at least one 3a allele showed significantly higher scores in the activity-impulsivity dimension of the dog-ADHD Rating Scale than dogs without this allele (P = 0.0180). This difference was not significant in pet German shepherds. To the best of our knowledge, this is the first report of an association between a candidate gene and a behaviour trait in dogs, and it reinforces the functional role of DRD4 exon 3 polymorphism. PMID:17986156

  11. Association of polymorphisms in the dopamine D4 receptor gene and the activity-impulsivity endophenotype in dogs.

    PubMed

    Hejjas, K; Vas, J; Topal, J; Szantai, E; Ronai, Z; Szekely, A; Kubinyi, E; Horvath, Z; Sasvari-Szekely, M; Miklosi, A

    2007-12-01

    A variable number of tandem repeats (VNTR) polymorphism in exon 3 of the human dopamine D4 receptor gene (DRD4) has been associated with attention deficit hyperactivity disorder (ADHD). Rodents possess no analogous repeat sequence, whereas a similar tandem repeat polymorphism of the DRD4 gene was identified in dogs, horses and chimpanzees. Here, we present a genetic association study of the DRD4 VNTR and the activity-impulsivity dimension of the recently validated dog-ADHD Rating Scale. To avoid false positives arising from population stratification, a single breed of dogs (German shepherd) was studied. Two DRD4 alleles (referred to as 2 and 3a) were detected in this breed, and genotype frequencies were in Hardy-Weinberg equilibrium. For modelling distinct environmental conditions, 'pet' and 'police' German shepherds were characterized. Police German shepherds possessing at least one 3a allele showed significantly higher scores in the activity-impulsivity dimension of the dog-ADHD Rating Scale than dogs without this allele (P = 0.0180). This difference was not significant in pet German shepherds. To the best of our knowledge, this is the first report of an association between a candidate gene and a behaviour trait in dogs, and it reinforces the functional role of DRD4 exon 3 polymorphism.

  12. 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…

  13. 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

  14. Endophenotypes for Intelligence in Children and Adolescents

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    PubMed

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

    2016-01-01

    The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) has previously reported our efforts to characterize the genetic architecture of 12 primary endophenotypes for schizophrenia. We now report the characterization of 13 additional measures derived from the same endophenotype test paradigms in the COGS-1 families. Nine of the measures were found to discriminate between schizophrenia patients and controls, were significantly heritable (31 to 62%), and were sufficiently independent of previously assessed endophenotypes, demonstrating utility as additional endophenotypes. Genotyping via a custom array of 1536 SNPs from 94 candidate genes identified associations for CTNNA2, ERBB4, GRID1, GRID2, GRIK3, GRIK4, GRIN2B, NOS1AP, NRG1, and RELN across multiple endophenotypes. An experiment-wide p value of 0.003 suggested that the associations across all SNPs and endophenotypes collectively exceeded chance. Linkage analyses performed using a genome-wide SNP array further identified significant or suggestive linkage for six of the candidate endophenotypes, with several genes of interest located beneath the linkage peaks (e.g., CSMD1, DISC1, DLGAP2, GRIK2, GRIN3A, and SLC6A3). While the partial convergence of the association and linkage likely reflects differences in density of gene coverage provided by the distinct genotyping platforms, it is also likely an indication of the differential contribution of rare and common variants for some genes and methodological differences in detection ability. Still, many of the genes implicated by COGS through endophenotypes have been identified by independent studies of common, rare, and de novo variation in schizophrenia, all converging on a functional genetic network related to glutamatergic neurotransmission that warrants further investigation. PMID:26597662

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

    PubMed

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

    2016-01-01

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

  17. Knowns and unknowns for psychophysiological endophenotypes: Integration and response to commentaries

    PubMed Central

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

    2014-01-01

    We review and summarize seven molecular genetic studies of 17 psychophysiological endophenotypes that comprise this special issue of Psychophysiology, address criticisms raised in accompanying Perspective and Commentary pieces, and offer suggestions for future research. Endophenotypes are polygenic, and possibly influenced by rare genetic variants. Because they are not simpler genetically than clinical phenotypes, they are unlikely to assist gene discovery for psychiatric disorder. Once genetic variants for clinical phenotypes are identified, associated endophenotypes are likely to provide valuable insights into the psychological and neural mechanisms important to disorder pathology. This special issue provides a foundation for informed future steps in endophenotype genetics, including the formation of large sample consortia capable of fleshing out the many genetic variants contributing to individual differences in psychophysiological measures. PMID:25387720

  18. 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).…

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

    PubMed

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

    2016-07-01

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

  20. 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...

  1. 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

  2. An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7.

    PubMed

    Gass, Natalia; Weber-Fahr, Wolfgang; Sartorius, Alexander; Becker, Robert; Didriksen, Michael; Stensbøl, Tine Bryan; Bastlund, Jesper Frank; Meyer-Lindenberg, Andreas; Schwarz, Adam J

    2016-07-01

    The 15q13.3 microdeletion copy number variation is strongly associated with schizophrenia and epilepsy. The CHRNA7 gene, encoding nicotinic acetylcholine alpha 7 receptors (nAChA7Rs), is hypothesized to be one of the main genes in this deletion causing the neuropsychiatric phenotype. Here we used a recently developed 15q13.3 microdeletion mouse model to explore whether an established schizophrenia-associated connectivity phenotype is replicated in a murine model, and whether positive modulation of nAChA7 receptor might pharmacologically normalize the connectivity patterns. Resting-state fMRI data were acquired from male mice carrying a hemizygous 15q13.3 microdeletion (N=9) and from wild-type mice (N=9). To study the connectivity profile of 15q13.3 mice and test the effect of nAChA7 positive allosteric modulation, the 15q13.3 mice underwent two imaging sessions, one week apart, receiving a single intraperitoneal injection of either 15mg/kg Lu AF58801 or saline. The control group comprised wild-type mice treated with saline. We performed seed-based functional connectivity analysis to delineate aberrant connectivity patterns associated with the deletion (15q13.3 mice (saline treatment) versus wild-type mice (saline treatment)) and their modulation by Lu AF58801 (15q13.3 mice (Lu AF58801 treatment) versus 15q13.3 mice (saline treatment)). Compared to wild-type mice, 15q13.3 mice evidenced a predominant hyperconnectivity pattern. The main effect of Lu AF58801 was a normalization of elevated functional connectivity between prefrontal and frontal, hippocampal, striatal, thalamic and auditory regions. The strongest effects were observed in brain regions expressing nAChA7Rs, namely hippocampus, cerebral cortex and thalamus. These effects may underlie the antiepileptic, pro-cognitive and auditory gating deficit-reversal effects of nAChA7R stimulation. PMID:27061851

  3. 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

  4. Measuring the Corticosteroid Responsiveness Endophenotype in Asthma

    PubMed Central

    Clemmer, George L.; Wu, Ann Chen; Rosner, Bernard; McGeachie, Michael J.; Litonjua, Augusto A.; Tantisira, Kelan G.; Weiss, Scott T.

    2015-01-01

    Background Inhaled corticosteroids are the most commonly used controller therapies for asthma, producing treatment responses in six clinical phenotypes; lung function, bronchodilator response, airway responsiveness, symptoms, need for oral steroids and frequency of emergency department visits and hospitalizations. We hypothesize that treatment response in all of these phenotypes is modulated by a single, quantative corticosteroid responsiveness endophenotype. Objective To develop a composite phenotype that combines multiple clinical phenotypes to measure corticosteroid responsiveness with high accuracy, high stability across populations, and high robustness to missing data. Methods We employed principal component analysis (PCA) to determine a composite corticosteroid responsiveness phenotype that we tested in four replication populations. We evaluated the relative accuracy with which the composite and clinical phenotypes measure the endophenotype using treatment effect area under the receiver operating characteristic curve (AUC). Results In the study population, the composite phenotype measured the endophenotype with an AUC of 0.74, significantly exceeding the AUCs of the six individual clinical phenotypes, which ranged from 0.56 (p-value <.001) to 0.67 (p-value 0.015). In four replication populations with a total of 22 clinical phenotypes available, the composite phenotype AUC ranged from 0.69 to 0.73, significantly exceeded the AUCs of 14 phenotypes, and was not significantly exceeded by any single phenotype. Conclusion The composite phenotype measured the endophenotype with higher accuracy, higher stability across populations, and higher robustness to missing data than any clinical phenotype. This should provide the capability to model corticosteroid pharmacologic response and resistance with increased accuracy and reproducibility. PMID:25951964

  5. In search of rare variants: preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes.

    PubMed

    Vrieze, Scott I; Malone, Stephen M; Vaidyanathan, Uma; Kwong, Alan; Kang, Hyun Min; Zhan, Xiaowei; Flickinger, Matthew; Irons, Daniel; Jun, Goo; Locke, Adam E; Pistis, Giorgio; Porcu, Eleonora; Levy, Shawn; Myers, Richard M; Oetting, William; McGue, Matt; Abecasis, Goncalo; Iacono, William G

    2014-12-01

    Whole genome sequencing was completed on 1,325 individuals from 602 families, identifying 27 million autosomal variants. Genetic association tests were conducted for those individuals who had been assessed for one or more of 17 endophenotypes (N range = 802-1,185). No significant associations were found. These 27 million variants were then imputed into the full sample of individuals with psychophysiological data (N range = 3,088-4,469) and again tested for associations with the 17 endophenotypes. No association was significant. Using a gene-based variable threshold burden test of nonsynonymous variants, we obtained five significant associations. These findings are preliminary and call for additional analysis of this rich sample. We argue that larger samples, alternative study designs, and additional bioinformatics approaches will be necessary to discover associations between these endophenotypes and genomic variation. PMID:25387710

  6. In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes

    PubMed Central

    VRIEZE, SCOTT I.; MALONE, STEPHEN M.; VAIDYANATHAN, UMA; KWONG, ALAN; KANG, HYUN MIN; ZHAN, XIAOWEI; FLICKINGER, MATTHEW; IRONS, DANIEL; JUN, GOO; LOCKE, ADAM E.; PISTIS, GIORGIO; PORCU, ELEONORA; LEVY, SHAWN; MYERS, RICHARD M.; OETTING, WILLIAM; MCGUE, MATT; ABECASIS, GONCALO; IACONO, WILLIAM G.

    2014-01-01

    Whole genome sequencing was completed on 1,325 individuals from 602 families, identifying 27 million autosomal variants. Genetic association tests were conducted for those individuals who had been assessed for one or more of 17 endophenotypes (N range = 802–1,185). No significant associations were found. These 27 million variants were then imputed into the full sample of individuals with psychophysiological data (N range = 3,088–4,469) and again tested for associations with the 17 endophenotypes. No association was significant. Using a gene-based variable threshold burden test of nonsynonymous variants, we obtained five significant associations. These findings are preliminary and call for additional analysis of this rich sample. We argue that larger samples, alternative study designs, and additional bioinformatics approaches will be necessary to discover associations between these endophenotypes and genomic variation. PMID:25387710

  7. 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

  8. 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

  9. 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.

  10. 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

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

    PubMed

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

    2012-11-01

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

  12. [Endophenotypes of the biorhythms and the sleep in depression].

    PubMed

    Pringuey, D; Fakra, E; Cherikh, F; Jover, F; Giordana, B; Clad, C; Kohl, F; Azorin, J M

    2012-12-01

    Chronobiological markers of depression display a biological desynchronization which participates in the pathogenesis of depression. Mood disorders and clock genes have shown significant associations suggesting a possible pathogenetic link between them, providing a privileged base for exploring biorhythmic endophenotypes. They would be useful indicators of vulnerability mechanisms, giving rise to new therapies and prevention programs. Two ways of research are of interest: the study of the genetic determinants of cholinergic hypersensitivity generating REM sleep pressure in depression, and the analysis of clinical response to sleep deprivation suggesting an exploration of links between genomic function of arousal and mood regulation. To date, the empirical principle of behavioral stimulus control reaches the level of the available eco-instrumental synchronization procedures.

  13. Scale-dependent neighborhood effects: shared doom and associational refuge.

    PubMed

    Emerson, Sara E; Brown, Joel S; Whelan, Christopher J; Schmidt, Kenneth A

    2012-03-01

    A resource's susceptibility to predation may be influenced by its own palatability and the palatability of its neighbors. We tested for effects of plant chemical defenses on seed survival by manipulating the frequency of palatable and less palatable sunflower seeds in food patches subject to harvest by fox squirrels (Sciurus niger) and gray squirrels (Sciurus carolinensis). We varied resource distributions at three scales: among stations (aggregates of patches ca. 50 m apart), among patches immediately adjacent to each other, and within patches. When food patches were segregated into high-palatability and low-palatability stations (Experiment 1), seeds suffered greater mortality at stations with high levels of palatable seeds. In the same experiment, within patches, squirrels selected strongly for palatable seeds over less palatable seeds. When high- and low-palatability food patches were placed together at the same stations (Experiment 2), increasing densities of co-occurring palatable seeds amplified the mortality of less palatable seeds, indicating "shared doom." When palatable and less palatable seeds were partitioned into micropatches (Experiment 3), associational effects disappeared, as predicted. Furthermore, selectivity in less palatable patches increased as the initial densities of palatable seeds increased, and selectivity in palatable patches decreased as the initial densities of less palatable seeds increased. Foraging theory predicts associational effects among prey that vary in palatability. Our results show how the type and magnitude of associational effects emerge from the interplay among the spatial scale of prey heterogeneity, the diet selection strategy, and the scale-dependent foraging responses of the consumer.

  14. Neurophysiological endophenotypes, CNS disinhibition, and risk for alcohol dependence and related disorders.

    PubMed

    Porjesz, Bernice; Rangaswamy, Madhavi

    2007-01-01

    Biological endophenotypes are more proximal to gene function than psychiatric diagnosis, 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. The Collaborative Study on the Genetics of Alcoholism (COGA) has employed 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 found significant linkage and association between brain oscillations and genes involved with inhibitory neural networks (e.g., GABRA2, CHRM2), including frontal networks that are deficient in individuals with alcohol dependence, impulsivity, and related disinhibitory disorders. We reported significant linkage and linkage disequilibrium for the beta frequency of the EEG and GABRA2, a GABAA receptor gene on chromosome 4, which we found is also associated with diagnosis of alcohol dependence and related disorders. More recently, we found significant linkage and association with GABRA2 and interhemispheric theta coherence. We also reported significant linkage and linkage disequilibrium between the theta and delta event-related oscillations underlying P3 to target stimuli and CHRM2, a cholinergic muscarinic receptor gene on chromosome 7, which we found is also associated with diagnosis of alcohol dependence and related disorders. Thus, the identification of genes important for the expression of the endophenotypes (brain oscillations) helps when identifying genes that increase the susceptibility for risk of alcohol dependence and related disorders. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of complex disorders. We will present our recent genetic findings related to

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

    PubMed

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

    2014-12-01

    This article provides an introductory overview of the investigative strategy employed to evaluate the genetic basis of 17 endophenotypes examined as part of a 20-year data collection effort from the Minnesota Center for Twin and Family Research. Included are characterization of the study samples, descriptive statistics for key properties of the psychophysiological measures, and rationale behind the steps taken in the molecular genetic study design. The statistical approach included (a) biometric analysis of twin and family data, (b) heritability analysis using 527,829 single nucleotide polymorphisms (SNPs), (c) genome-wide association analysis of these SNPs and 17,601 autosomal genes, (d) follow-up analyses of candidate SNPs and genes hypothesized to have an association with each endophenotype, (e) rare variant analysis of nonsynonymous SNPs in the exome, and (f) whole genome sequencing association analysis using 27 million genetic variants. These methods were used in the accompanying empirical articles comprising this special issue, Genome-Wide Scans of Genetic Variants for Psychophysiological Endophenotypes. PMID:25387703

  16. 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

  17. 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.

  18. 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.

  19. 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. PMID:26545630

  20. Scale-dependent neighborhood effects: shared doom and associational refuge.

    PubMed

    Emerson, Sara E; Brown, Joel S; Whelan, Christopher J; Schmidt, Kenneth A

    2012-03-01

    A resource's susceptibility to predation may be influenced by its own palatability and the palatability of its neighbors. We tested for effects of plant chemical defenses on seed survival by manipulating the frequency of palatable and less palatable sunflower seeds in food patches subject to harvest by fox squirrels (Sciurus niger) and gray squirrels (Sciurus carolinensis). We varied resource distributions at three scales: among stations (aggregates of patches ca. 50 m apart), among patches immediately adjacent to each other, and within patches. When food patches were segregated into high-palatability and low-palatability stations (Experiment 1), seeds suffered greater mortality at stations with high levels of palatable seeds. In the same experiment, within patches, squirrels selected strongly for palatable seeds over less palatable seeds. When high- and low-palatability food patches were placed together at the same stations (Experiment 2), increasing densities of co-occurring palatable seeds amplified the mortality of less palatable seeds, indicating "shared doom." When palatable and less palatable seeds were partitioned into micropatches (Experiment 3), associational effects disappeared, as predicted. Furthermore, selectivity in less palatable patches increased as the initial densities of palatable seeds increased, and selectivity in palatable patches decreased as the initial densities of less palatable seeds increased. Foraging theory predicts associational effects among prey that vary in palatability. Our results show how the type and magnitude of associational effects emerge from the interplay among the spatial scale of prey heterogeneity, the diet selection strategy, and the scale-dependent foraging responses of the consumer. PMID:21987268

  1. 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.

  2. 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

  3. [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

  4. [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

  5. Increased Causal Connectivity Related to Anatomical Alterations as Potential Endophenotypes for Schizophrenia

    PubMed Central

    Guo, Wenbin; Liu, Feng; Xiao, Changqing; Yu, Miaoyu; Zhang, Zhikun; Liu, Jianrong; Zhang, Jian; Zhao, Jingping

    2015-01-01

    Abstract Anatomical and functional abnormalities in the cortico-cerebellar-thalamo-cortical circuit have been observed in schizophrenia patients and their unaffected siblings. However, it remains unclear to the relationship between anatomical and functional abnormalities within this circuit in schizophrenia patients and their unaffected siblings, which may serve as potential endophenotypes for schizophrenia. Anatomical and resting-state functional magnetic resonance imaging data were acquired from 49 first-episode, drug-naive schizophrenia patients, 46 unaffected siblings, and 46 healthy controls. Data were analyzed by using voxel-based morphometry and Granger causality analysis. The patients and the siblings shared anatomical deficits in the left middle temporal gyrus (MTG) and increased left MTG–left angular gyrus (AG) connectivity. Moreover, the left MTG–left AG connectivity negatively correlates to the duration of untreated psychosis in the patients. The findings indicate that anatomical deficits in the left MTG and its increased causal connectivity with the left AG may serve as potential endophenotypes for schizophrenia with clinical implications. PMID:26496253

  6. 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…

  7. 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

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

    ERIC Educational Resources Information Center

    Curenton, Stephanie M.; Craig, Michelle Jones

    2011-01-01

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

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

    PubMed

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

    2015-07-21

    Schizophrenia is increasingly conceived as a disorder of brain network organization or dysconnectivity syndrome. Functional MRI (fMRI) networks in schizophrenia have been characterized by abnormally random topology. We tested the hypothesis that network randomization is an endophenotype of schizophrenia and therefore evident also in nonpsychotic relatives of patients. Head movement-corrected, resting-state fMRI data were acquired from 25 patients with schizophrenia, 25 first-degree relatives of patients, and 29 healthy volunteers. Graphs were used to model functional connectivity as a set of edges between regional nodes. We estimated the topological efficiency, clustering, degree distribution, resilience, and connection distance (in millimeters) of each functional network. The schizophrenic group demonstrated significant randomization of global network metrics (reduced clustering, greater efficiency), a shift in the degree distribution to a more homogeneous form (fewer hubs), a shift in the distance distribution (proportionally more long-distance edges), and greater resilience to targeted attack on network hubs. The networks of the relatives also demonstrated abnormal randomization and resilience compared with healthy volunteers, but they were typically less topologically abnormal than the patients' networks and did not have abnormal connection distances. We conclude that schizophrenia is associated with replicable and convergent evidence for functional network randomization, and a similar topological profile was evident also in nonpsychotic relatives, suggesting that this is a systems-level endophenotype or marker of familial risk. We speculate that the greater resilience of brain networks may confer some fitness advantages on nonpsychotic relatives that could explain persistence of this endophenotype in the population. PMID:26150519

  10. 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. PMID:19172434

  11. 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

  12. Sustained attention deficits in relation to psychometrically identified schizotypy: evaluating a potential endophenotypic marker.

    PubMed

    Gooding, Diane C; Matts, Christie W; Rollmann, Elizabeth A

    2006-02-15

    Sustained attention deficits have been posited as a potential endophenotypic marker of vulnerability to schizophrenia. Prior studies have indicated that schizophrenia patients, their first-degree relatives, and psychosis-prone individuals, identified on the basis of measures of positive schizotypy, have demonstrated sustained attention deficits. To date, there have been no published reports of sustained attention deficits in individuals with negative schizotypy, as measured by the revised Social Anhedonia Scale. In this study, we examined sustained attention, measured with the CPT-Identical Pairs version, in 160 individuals with elevated scores on the Chapman Perceptual Aberration and/or Magical Ideation Scales, 96 individuals with elevated scales on the Social Anhedonia Scale, and 137 controls. Both psychosis-prone groups performed more poorly than the controls in terms of discrimination ability, as measured by d', though the groups did not differ in terms of either their reaction time or overall response criterion (lnbeta). These results provide evidence that both positive and negative aspects of schizotypy are associated with sustained attention deficits, as measured by the Continuous Performance Test. The findings add to the converging evidence indicating that sustained attention deficits are a potential endophenotypic indicator of a schizophrenia diathesis.

  13. Performance variability, impulsivity errors and the impact of incentives as gender-independent endophenotypes for ADHD

    PubMed Central

    Uebel, Henrik; Albrecht, Björn; Asherson, Philip; Börger, Norbert A.; Butler, Louise; Chen, Wai; Christiansen, Hanna; Heise, Alexander; Kuntsi, Jonna; Schäfer, Ulrike; Andreou, Penny; Manor, Iris; Marco, Rafaela; Meidad, Sheera; Miranda, Ana; Mulligan, Aisling; Oades, Robert D.; van der Meere, Jaap; Faraone, Stephen V.; Rothenberger, Aribert; Banaschewski, Tobias

    2010-01-01

    Background Attention-deficit hyperactivity disorder (ADHD) is one of the most common and highly heritable child psychiatric disorders. There is strong evidence that children with ADHD show slower and more variable responses in tasks such as Go/Nogo tapping aspects of executive functions like sustained attention and response control which may be modulated by motivational factors and/or state-regulation processes. The aim of this study was (1) to determine if these executive functions may constitute an endophenotype for ADHD; (2) to investigate for the first time whether known modulators of these executive functions may also be familial and (3) to explore whether gender has an impact on these measures. Methods Two hundred and five children with ADHD combined type, 173 nonaffected biological siblings and 53 controls with no known family history of ADHD were examined using a Go/Nogo-Task in the framework of a multi-centre study. Performance-measures and modulating effects of event-rate and incentives were examined. Shared familial effects on these measures were assessed, and the influence of gender was tested. Results Children with ADHD responded more slowly and variably than nonaffected siblings or controls. Nonaffected siblings showed intermediate scores for reaction-time variability, false alarms and omission errors under fast and slow event rates. A slower event-rate did not led to reduced performance specific for ADHD. In the incentive condition, mean reaction times speeded-up and became less variable only in children with ADHD and their nonaffected siblings, while accuracy was improved in all groups. Males responded faster, but also committed more false alarms. There were no interactions of group by gender. Conclusions Reaction-time variability and accuracy parameters could be useful neuropsychological endophenotypes for ADHD. Performance modulating effects of incentives suggested a familially-driven motivational dysfunction which may play an important role on

  14. Prefrontal deviations in function but not volume are putative endophenotypes for schizophrenia.

    PubMed

    Owens, Sheena F; Picchioni, Marco M; Ettinger, Ulrich; McDonald, Colm; Walshe, Muriel; Schmechtig, Anne; Murray, Robin M; Rijsdijk, Fruhling; Toulopoulou, Timothea

    2012-07-01

    This study sought to systematically investigate whether prefrontal cortex grey matter volume reductions are valid endophenotypes for schizophrenia, specifically investigating their presence in unaffected relatives, heritability, genetic overlap with the disorder itself and finally to contrast their performance on these criteria with putative neuropsychological indices of prefrontal functioning. We used a combined twin and family design and examined four prefrontal cortical regions of interest. Superior and inferior regions were significantly smaller in patients. However, the volumes of these same regions were normal in unaffected relatives and therefore, we could confirm that such deficits were not due to familial effects. Volumes of the prefrontal and orbital cortices were, however, moderately heritable, but neither shared a genetic overlap with schizophrenia. Total prefrontal cortical volume reductions shared a significant unique environmental overlap with the disorder, suggesting that the reductions were not familial. In contrast, prefrontal (executive) functioning deficits were present in the unaffected relatives, were moderately heritable and shared a substantial genetic overlap with liability to schizophrenia. These results suggest that the well recognized prefrontal volume reductions are not related to the same familial influences that increase schizophrenia liability and instead may be attributable to illness related biological changes or indeed confounded by illness trajectory, chronicity, medication or substance abuse, or in fact a combination of some or all of them.

  15. 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.

  16. Oxytocin and vasopressin hormone genes in children's externalizing problems: A cognitive endophenotype approach.

    PubMed

    Wade, Mark; Hoffmann, Thomas J; Knafo-Noam, Ariel; O'Connor, Thomas G; Jenkins, Jennifer M

    2016-06-01

    Externalizing problems are among the most common mental health problems of children. Research suggests that these problems are heritable, yet little is known about the specific genes involved in their pathophysiology. The current study examined a genotype-endophenotype-phenotype model of externalizing problems in 320 preschool-aged children. Markers of the oxytocin (OXT) and arginine vasopressin (AVP) hormone genes were selected as candidates owing to their known association with psychopathology in other domains. We tested whether OXT and AVP variants were related to children's externalizing problems, as well as two cognitive endophenotypes presumed to underlie these problems: theory of mind (ToM) and executive functioning (EF). Externalizing problems were assessed at age 4.5 using a previously-validated rating scale. ToM and EF were measured with age-appropriate tasks. Using a family-based association design and controlling for non-genomic confounds, support was found for an association between a two-marker OXT haplotype (rs2740210-rs2770378) and a two-marker AVP haplotype (rs1887854-rs3761249) and externalizing problems. Specific associations of these haplotypes with ToM and EF were also observed. Further, ToM and EF were shown to independently and jointly predict externalizing problems, and to partially mediate the effects of OXT and AVP on externalizing problems. This study provides the first evidence that genetic variation in OXT and AVP may contribute to individual differences in childhood externalizing problems, and that these effects may operate through emerging neurocognitive abilities in the preschool period. PMID:27155104

  17. 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

  18. 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…

  19. Who Shares? Who Doesn't? Factors Associated with Openly Archiving Raw Research Data

    PubMed Central

    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. PMID:21765886

  20. 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

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

    PubMed

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

    2009-12-01

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

  2. 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.

  3. Diagnostic Specificity of Neurophysiological Endophenotypes in Schizophrenia and Bipolar Disorder

    PubMed Central

    Johannesen, Jason K.

    2013-01-01

    Background: The utility of an endophenotype depends on its ability to reduce complex disorders into stable, genetically linked phenotypes. P50 and P300 event-related potential (ERP) measures are endophenotype candidates for schizophrenia; however, their abnormalities are broadly observed across neuropsychiatric disorders. This study examined the diagnostic efficiency of P50 and P300 in schizophrenia as compared with healthy and bipolar disorder samples. Supplemental ERP measures and a multivariate classification approach were evaluated as methods to improve specificity. Methods: Diagnostic classification was first modeled in schizophrenia (SZ = 50) and healthy normal (HN = 50) samples using hierarchical logistic regression with predictors blocked by 4 levels of analysis: (1) P50 suppression, P300 amplitude, and P300 latency; (2) N100 amplitude; (3) evoked spectral power; and (4) P50 and P300 hemispheric asymmetry. The optimal model was cross-validated in a holdout sample (SZ = 34, HN = 31) and tested against a bipolar (BP = 50) sample. Results: P50 and P300 endophenotypes classified SZ from HN with 71% accuracy (sensitivity = .70, specificity = .72) but did not differentiate SZ from BP above chance level. N100 and spectral power measures improved classification accuracy of SZ vs HN to 79% (sensitivity = .78, specificity = .80) and SZ vs BP to 72% (sensitivity = .74, specificity = .70). Cross validation analyses supported the stability of these models. Conclusions: Although traditional P50 and P300 measures failed to differentiate schizophrenia from bipolar participants, N100 and evoked spectral power measures added unique variance to classification models and improved accuracy to nearly the same level achieved in comparison of schizophrenia to healthy individuals. PMID:22927673

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. 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

  7. 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

  8. Neuropsychological endophenotypes in ADHD with and without epilepsy.

    PubMed

    MacAllister, William S; Vasserman, Marsha; Vekaria, Pooja; Miles-Mason, Eavan; Hochsztein, Natanya; Bender, Heidi A

    2012-01-01

    Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy. Despite similarities in behavioral manifestations of inattention and hyperactivity, it is unclear whether the neuropsychological endophenotypes of children with developmental ADHD differ from those with ADHD in the context of epilepsy. The present study compared groups of clinically referred children with both ADHD-Inattentive subtype (ADHD-I) and ADHD-Combined subtype (ADHD-C) to children with ADHD-I and ADHD-C and epilepsy on neuropsychological measures of intellectual functioning, auditory attention, working memory, and sustained attention and response inhibition. Those with ADHD and epilepsy performed more poorly on measures of intellectual function (e.g., Full-Scale IQ, Verbal IQ, Performance IQ) as well as auditory attention and working memory. Differences across the groups were also seen on a continuous performance test. Follow-up correlational analyses showed that variables such as seizure frequency and number of antiepilepsy medications predicted cognitive dysfunction in the epilepsy groups. Overall results suggest that the neuropsychological endophenotypes in developmental ADHD versus ADHD in epilepsy differ with seizure-related variables predicting cognitive dysfunction.

  9. 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

  10. 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

  11. Reduced Sleep Spindles in Schizophrenia: A Treatable Endophenotype That Links Risk Genes to Impaired Cognition?

    PubMed

    Manoach, Dara S; Pan, Jen Q; Purcell, Shaun M; Stickgold, Robert

    2016-10-15

    Although schizophrenia (SZ) is defined by waking phenomena, abnormal sleep is a common feature. In particular, there is accumulating evidence of a sleep spindle deficit. Sleep spindles, a defining thalamocortical oscillation of non-rapid eye movement stage 2 sleep, correlate with IQ and are thought to promote long-term potentiation and enhance memory consolidation. We review evidence that reduced spindle activity in SZ is an endophenotype that impairs sleep-dependent memory consolidation, contributes to symptoms, and is a novel treatment biomarker. Studies showing that spindles can be pharmacologically enhanced in SZ and that increasing spindles improves memory in healthy individuals suggest that treating spindle deficits in patients with SZ may improve cognition. Spindle activity is highly heritable, and recent large-scale genome-wide association studies have identified SZ risk genes that may contribute to spindle deficits and illuminate their mechanisms. For example, the SZ risk gene CACNA1I encodes a calcium channel that is abundantly expressed in the thalamic spindle generator and plays a critical role in spindle activity based on a mouse knockout. Future genetic studies of animals and humans can delineate the role of this and other genes in spindles. Such cross-disciplinary research, by forging empirical links in causal chains from risk genes to proteins and cellular functions to endophenotypes, cognitive impairments, symptoms, and diagnosis, has the potential to advance the mechanistic understanding, treatment, and prevention of SZ. This review highlights the importance of deficient sleep-dependent memory consolidation among the cognitive deficits of SZ and implicates reduced sleep spindles as a potentially treatable mechanism.

  12. 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.

  13. Subcortical and cortical morphological anomalies as an endophenotype in obsessive-compulsive disorder.

    PubMed

    Shaw, P; Sharp, W; Sudre, G; Wharton, A; Greenstein, D; Raznahan, A; Evans, A; Chakravarty, M M; Lerch, J P; Rapoport, J

    2015-02-01

    Endophentoypes, quantifiable traits lying on the causal chain between a clinical phenotype and etiology, can be used to accelerate genomic discovery in obsessive-compulsive disorder (OCD). Here we identify the neuroanatomic changes that are shared by 22 OCD adult and adolescent patients and 25 of their unaffected siblings who are at genetic risk for the disorder. Comparisons were made against 47 age and sex matched healthy controls. We defined the surface morphology of the striatum, globus pallidus and thalamus, and thickness of the cerebral cortex. Patients with OCD show significant surface expansion compared with healthy controls, following adjustment for multiple comparisons, in interconnected regions of the caudate, thalamus and right orbitofrontal cortex. Their unaffected siblings show similar, significant expansion, most marked in the ventromedial caudate bilaterally, the right pulvinar thalamic nucleus and the right orbitofrontal cortex. These regions define a network that has been consistently implicated in OCD. In addition, both patients with OCD and unaffected siblings showed similar increased thickness of the right precuneus, which receives rich input from the thalamic pulvinar nuclei and the left medial temporal cortex. Anatomic change within the orbitofrontostriatal and posterior brain circuitry thus emerges as a promising endophenotype for OCD.

  14. Accumulating evidence for the association and shared pathogenic mechanisms between psoriasis and cardiovascular-related comorbidities.

    PubMed

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

    2014-12-01

    The International Psoriasis Council, a global nonprofit 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, Mass. 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. The International Psoriasis Council 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.

  15. Accumulating evidence for the association and shared pathogenic mechanisms between psoriasis and cardiovascular-related comorbidities.

    PubMed

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

    2014-12-01

    The International Psoriasis Council, a global nonprofit 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, Mass. 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. The International Psoriasis Council 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

  16. 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.

  17. Sharing milk but not messages: campylobacteriosis associated with consumption of raw milk from a cow-share program in Alaska, 2011.

    PubMed

    Castrodale, L J; Gerlach, R F; Xavier, C M; Smith, B J; Cooper, M P; McLaughlin, J B

    2013-05-01

    Alaska public and environmental health authorities investigated a cluster of campylobacteriosis cases among people who had consumed raw, unpasteurized milk obtained from a cow-share program in Alaska. Although raw milk is not permitted by law to be offered commercially, consumers can enter into cow-share agreements whereby they contribute funds for the upkeep of cows and in turn receive a share of the milk for their personal use. Laboratory testing of stool specimens collected from ill persons and from cows on the farm revealed an indistinguishable strain of Campylobacter. In this outbreak, numerous confirmed and suspected cases were not among cow shareholders; therefore, these individuals had not been advised of the potential health hazards associated with consumption of raw milk nor were they informed of the outbreak developments.

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

    PubMed Central

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

    2015-01-01

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

  19. Recent incarceration independently associated with syringe sharing by injection drug users.

    PubMed Central

    Wood, Evan; Li, Kathy; Small, Will; Montaner, Julio S.; Schechter, Martin T.; Kerr, Thomas

    2005-01-01

    OBJECTIVES: Few prospective studies are available on the relationship between incarceration and HIV risk among injection drug users (IDUs). The authors evaluated self-reported rates of syringe sharing and incarceration among a cohort of IDUs. METHODS: This study analyzed syringe lending by HIV-infected IDUs and syringe borrowing by HIV-negative IDUs among participants enrolled in the Vancouver Injection Drug Users Study (VIDUS). Since serial measures for each individual were available, variables potentially associated with each outcome (syringe lending and borrowing) were evaluated using generalized estimating equations for binary outcomes. RESULTS: The study sample consisted of 1,475 IDUs who were enrolled into the VIDUS cohort from May 1996 through May 2002. At baseline, 1,123 (76%) reported a history of incarceration since they first began injecting drugs. Of these individuals, 351 (31%) reported at baseline that they had injected drugs while incarcerated. Among 318 baseline HIV-infected IDUs, having been incarcerated in the six months prior to each interview remained independently associated with syringe lending during the same period (adjusted odds ratio [OR]=1.33; 95% confidence interval [CI] 1.06, 1.69; p=0.015). Similarly, among the 1,157 baseline HIV-negative IDUs, having been incarcerated in the six months prior to each interview remained independently associated with reporting syringe borrowing during the same period (adjusted OR=1.26; 95% CI 1.12, 1.44; p<0.001). CONCLUSIONS: Incarceration was independently associated with risky needle sharing for HIV-infected and HIV-negative IDUs. This evidence of HIV risk behavior should reinforce public health concerns about the high rates of incarceration among IDUs. PMID:15842116

  20. Susceptibility genes for schizophrenia: mutant models, endophenotypes and psychobiology.

    PubMed

    O'Tuathaigh, Colm M P; Desbonnet, Lieve; Moran, Paula M; Waddington, John L

    2012-01-01

    Schizophrenia is characterised by a multifactorial aetiology that involves genetic liability interacting with epigenetic and environmental factors to increase risk for developing the disorder. A consensus view is that the genetic component involves several common risk alleles of small effect and/or rare but penetrant copy number variations. Furthermore, there is increasing evidence for broader, overlapping genetic-phenotypic relationships in psychosis; for example, the same susceptibility genes also confer risk for bipolar disorder. Phenotypic characterisation of genetic models of candidate risk genes and/or putative pathophysiological processes implicated in schizophrenia, as well as examination of epidemiologically relevant gene × environment interactions in these models, can illuminate molecular and pathobiological mechanisms involved in schizophrenia. The present chapter outlines both the evidence from phenotypic studies in mutant mouse models related to schizophrenia and recently described mutant models addressing such gene × environment interactions. Emphasis is placed on evaluating the extent to which mutant phenotypes recapitulate the totality of the disease phenotype or model selective endophenotypes. We also discuss new developments and trends in relation to the functional genomics of psychosis which might help to inform on the construct validity of mutant models of schizophrenia and highlight methodological challenges in phenotypic evaluation that relate to such models.

  1. Using endophenotypes for pathway clusters to map complex disease genes.

    PubMed

    Pan, Wen-Harn; Lynn, Ke-Shiuan; Chen, Chun-Houh; Wu, Yi-Lin; Lin, Chung-Yen; Chang, Hsing-Yi

    2006-02-01

    Nature determines the complexity of disease etiology and the likelihood of revealing disease genes. While culprit genes for many monogenic diseases have been successfully unraveled, efforts to map major complex disease genes have not been as productive as hoped. The conceptual framework currently adopted to deal with the heterogeneous nature of complex diseases focuses on using homogeneous internal features of the disease phenotype for mapping. However, phenotypic homogeneity does not equal genotypic homogeneity. In this report, we advocate working with well-measured phenotypes portrayed by amounts of transcripts and activities of gene products or their metabolites, which are pertinent to relatively small pathway clusters. Reliable and controlled measures for oligogenic traits resulting from proper dissection efforts may enhance statistical power. The large amounts of information obtained on gene and protein expression from technological advances can add to the power of gene finding, particularly for diseases with unclear etiology. Data-mining tools for dimension reduction can assist biologists to reveal novel molecular endophenotypes. However, there are still hurdles to overcome, including high cost, relatively poor reproducibility and comparability among platforms, the cross-sectional nature of the information, and the accessibility of human tissues. Concerted efforts are required to carry out large-scale prospective studies that are integrated at the levels of phenotype characterization, high throughput experimental techniques, data analyses, and beyond.

  2. 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

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

    PubMed

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

    2016-10-01

    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.

  4. Membrane antigens shared by renal proximal tubules and other epithelia associated with absorption and excretion.

    PubMed Central

    Miettinen, A; Linder, E

    1976-01-01

    The distribution of shared antigens in specialized surface membranes of epithelia associated with absorption and excretion was studied using antisera against isolated epithelial brush borders of renal proximal tubules. Rabbits were immunized with a membrane fraction isolated from rat kidneys and the reactions of the resulting heterologous antisera with different rat organs were studied by immunofluorescence. The antisera reacted with the following structures: epithelial brush border of renal proximal tubules, bile canaliculi and bile duct epithelium of the liver, epithelial brush border of the intestinal villi, luminal parts of some epididymal tubules, allantochorionic epithelium, and apical parts of the exocrine epithelium of the pancreatic, salivary and lacrimal glands. Both quantitative and qualitative differences in antigen contents were suggested by absorption experiments. Images Fig. 2 PMID:780015

  5. 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

  6. 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. PMID:24024963

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

    PubMed Central

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

    2014-01-01

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

  8. [18F]FDOPA PET as an endophenotype for Parkinson's Disease linkage studies.

    PubMed

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

    2006-04-01

    Parkinson disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies, since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than 3 standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to "PET definite PD." The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14 +/- 0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36 +/- 1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree. PMID:16528749

  9. [18F]FDOPA PET as an Endophenotype for Parkinson’s Disease Linkage Studies

    PubMed Central

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

    2008-01-01

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

  10. 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

  11. 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

  12. Molecular detection of tumor-associated antigens shared by human cutaneous melanomas and gliomas.

    PubMed Central

    Chi, D. D.; Merchant, R. E.; Rand, R.; Conrad, A. J.; Garrison, D.; Turner, R.; Morton, D. L.; Hoon, D. S.

    1997-01-01

    Both melanocytes and glial cells are derived embryologically from the neural ectoderm. Their malignant transformed counterparts, melanoma and glioma cells, respectively, may share common antigens. Numerous tumor-associated antigens have been identified in melanomas but only a few a gliomas. Using an established reverse transcriptase polymerase chain reaction plus Southern blot assay, we compared the mRNA expression of melanoma-associated antigens (MAAs) of melanomas to brain tumors primarily derived from glial cells. The MAAs studied included tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2), gp100, human melanoma antigen-encoding genes 1 and 3 (MAGE-1 and MAGE-3), and melanotransferrin (p97). Glioblastoma multiforme (n = 21), anaplastic astrocytoma (n = 3), ependymoma (n = 2), meningioma (n = 3), oligodendroglioma (n = 1), and melanoma (n = 12) tumor specimens were assayed for MAA mRNA expression. Glioblastoma multiforme, astrocytoma, and melanoma cell lines were also assayed. We observed that individual MAA mRNAs were expressed in these brain tumors and cell lines at varying frequencies. The melanogenesis-pathway-related MAAs Tyr, TRP-1, TRP-2, and gp100 mRNAs were also expressed at different levels in normal brain tissues but at a much lower frequency than in glioblastoma multiforme and melanoma. MAGE-1 and MAGE-3 mRNA were expressed in different types of tumor specimens and cell lines but never in normal brain tissue. Tumor antigen p97 was expressed in all types of tumors and also in normal brain tissues. These studies demonstrate that melanomas and primary brain tumors express common MAAs and could be exploited in patients with malignant glioma by active specific immunotherapy against these common MAAs. Images Figure 1 Figure 2 Figure 3 PMID:9176405

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

    PubMed Central

    2014-01-01

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

  14. Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia.

    PubMed

    Yao, Jeffrey K; Dougherty, George G; Gautier, Clara H; Haas, Gretchen L; Condray, Ruth; Kasckow, John W; Kisslinger, Benjamin L; Gurklis, John A; Messamore, Erik

    2016-03-01

    The skin flush response to niacin is abnormally blunted among a subset of patients with schizophrenia (SZ), preferentially associates with SZ compared to other mental illnesses, occurs frequently in nonpsychotic members of SZ-affected families, appears heritable, and shows evidence of genetic association. The niacin response abnormality (NRA) may prove to be a useful SZ endophenotype. Using a laser Doppler flowmeter, we undertook this study to estimate the prevalence of NRA in SZ (n = 70), bipolar disorder (BP, n = 59), and healthy control (HC, n = 87) groups, and to estimate its specificity for the illness. From the dose-response curves, we calculated the concentration of methylnicotinate required to elicit a half-maximal blood flow (MBF) response (EC50 value) and MBF value for each subject. The median log10EC50 of the SZ was above the third quartile of log10EC50 of either the HC or BP groups, whereas the MBF was significantly lower in the SZ than in the HC or BP groups. With a definition of NRA of having both EC50 above the ninetieth percentile of the control samples and MBF response below the sixtieth percentile for the control range, the NRA predicted SZ with 31% sensitivity and 97% specificity. Moreover, the NRA was not influenced by age, gender, race, and cigarette smoking. In summary, the NRA may define a SZ subtype with a clinically significant phospholipid signaling defect. Understanding its molecular origins may shed light on the pathophysiology of SZ and suggest new tools for its early diagnosis and treatment. PMID:26371338

  15. The serotonin transporter polymorphism (5-HTTLPR) and personality: response style as a new endophenotype for anxiety.

    PubMed

    Plieger, Thomas; Montag, Christian; Felten, Andrea; Reuter, Martin

    2014-06-01

    Although the serotonin transporter length polymorphic region (5-HTTLPR) polymorphism is an extensively-investigated genetic marker of anxiety related personality traits (neuroticism and harm avoidance) and affective disorders, effect sizes in meta-analyses are small, if present at all, and all available primary studies to date lack mandatory statistical power. Moreover, questionnaire data is prone to confounding by variables such as social desirability. Therefore, extreme response style (ERS) is suggested as a new approach to elucidate the relationship between 5-HTTLPR and negative emotionality, as it is more implicit and of high reliability. N = 1075 healthy subjects were genotyped for 5-HTTLPR and a flanking polymorphism (rs25531) and filled out the NEO Five Factor Inventory and the Temperament Character Inventory. As dependent variable the number of extreme responses across all items was calculated. Using the common genotype or the triallelic approach (including rs25531) the meta-analytic findings could not be replicated. However, there was a significant association between 5-HTTLPR and extreme response style. Carriers of the L-allele or the L'-allele, respectively, had a significantly higher number of extreme responses than homozygous SS carriers across all items of the NEO Five Factor Inventory. This finding could be replicated in an alternative personality questionnaire (Affective Neuroscience Personality Scales, ANPS). There is a long tradition in psychological assessment indicating that ERS is an implicit measure of personality. Given the positive findings of the present study, ERS qualifies as a promising endophenotype in future genetic association studies on personality and affective disorders.

  16. Preschool children's attachment security is associated with their sharing with others.

    PubMed

    Paulus, Markus; Becker, Eva; Scheub, Annemarie; König, Lilith

    2016-01-01

    The current study examined relations between preschool children's attachment pattern and their sharing behavior. To this end, 26 German children aged five years (15 girls) were first administered an Attachment Story Completion Task to assess their attachment pattern and the degree of their attachment security. Immediately thereafter, they participated in an established paradigm, a mini-dictator game, that assessed their inclination to share costly as well as noncostly with a friend, a disliked other, and a stranger. Analyses showed that degree of attachment security was positively correlated with children's generosity towards a disliked other and their inclination to engage in costly sharing. Moreover, the absence of an organized attachment pattern was related to a general decrease in generosity towards all recipients. The results point to the functional role of children's attachment for the early development of sharing behavior.

  17. Preschool children's attachment security is associated with their sharing with others.

    PubMed

    Paulus, Markus; Becker, Eva; Scheub, Annemarie; König, Lilith

    2016-01-01

    The current study examined relations between preschool children's attachment pattern and their sharing behavior. To this end, 26 German children aged five years (15 girls) were first administered an Attachment Story Completion Task to assess their attachment pattern and the degree of their attachment security. Immediately thereafter, they participated in an established paradigm, a mini-dictator game, that assessed their inclination to share costly as well as noncostly with a friend, a disliked other, and a stranger. Analyses showed that degree of attachment security was positively correlated with children's generosity towards a disliked other and their inclination to engage in costly sharing. Moreover, the absence of an organized attachment pattern was related to a general decrease in generosity towards all recipients. The results point to the functional role of children's attachment for the early development of sharing behavior. PMID:26524972

  18. 31 CFR 50.36 - Allocation of premium income associated with entities that do share profits and losses with...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  19. 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...

  20. 31 CFR 50.36 - Allocation of premium income associated with entities that do share profits and losses with...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  1. 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...

  2. 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…

  3. 31 CFR 50.36 - Allocation of premium income associated with entities that do share profits and losses with...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Allocation of premium income associated with entities that do share profits and losses with private sector insurers. 50.36 Section 50.36 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE...

  4. 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

  5. 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…

  6. 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…

  7. 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

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

    PubMed

    2015-02-01

    [In the article "Association of Pyoderma Gangrenosum, Acne, and Suppurative Hidradenitis (PASH) Shares Genetic and Cytokine Profiles With Other Autoinflammatory Diseases", which appeared in Volume 93, Issue 27 of Medicine, one of Orietta M. Borghi's affiliations was omitted. The article should have stated that Orietta M. Borghi is associated with the IRCCS Istituto Auxologico Italiano, Milano, Italy as well as the Dipartimento di Scienze Cliniche e di Comunità, Università di Milano.].

  9. The association between law enforcement encounters and syringe sharing among IDUs on skid row: a mixed methods analysis.

    PubMed

    Wagner, Karla D; Simon-Freeman, Rebecca; Bluthenthal, Ricky N

    2013-10-01

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

  10. 12 CFR 563b.505 - May my directors, officers, and their associates freely trade shares?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... certificate of stock that a director or officer purchases during the conversion or receives in connection with a stock dividend, stock split, or otherwise with respect to such restricted shares. (c) You must..., DEPARTMENT OF THE TREASURY CONVERSIONS FROM MUTUAL TO STOCK FORM Standard Conversions Post-Conversion §...

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

    PubMed Central

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

    2013-01-01

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

  12. Sharing mates and nest boxes is associated with female "friendship" in European starlings, Sturnus vulgaris.

    PubMed

    Henry, Laurence; Bourguet, Cécile; Coulon, Marion; Aubry, Christine; Hausberger, Martine

    2013-02-01

    Breeding decisions in birds involve both mate and nest choice, and there is increasing evidence that social influences may modulate individual choices. Female preferences may be affected by other females' preferences and mutual choice cannot always be excluded, which makes the whole pattern more complex than assumed by most sexual selection models. Social transmission may be facilitated by particular social bonds, therefore prebreeding social networks may influence later mate choices. The other case where females share mate or resources is polygyny, generally viewed to only benefit males. If mutual benefits may arise then mechanisms should evolve to reduce the reproductive cost for females such as to reduce the cost of aggression by sharing their mate with a preferred same-sex social partner. We tested the hypothesis that females' mating decisions may be influenced by the prebreeding social network and that social partner relations established prior to breeding may share decisions (mate/sites) in a facultatively polygynous species, the European starling. Two experiments were designed to test the relative importance of male or nest by following the whole dynamics of the breeding cycle from the prebreeding period until mate and nest selection. In both cases socially isolated females tended to be excluded from breeding, while prebreeding social partners tended to share mates and to nest in close proximity, mate copying leading in some case to polygyny. The final pattern resulted both from female "likes and dislikes" and male preferences for some females. Aggressive interactions between females were rare. Vocal sharing between females may have been a clue for males as to the degree of social integration of these females. PMID:23106801

  13. Trends and Factors Associated with Bed-Sharing: The National Infant Sleep Position Study (NISP) 1993–2010

    PubMed Central

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

    2013-01-01

    Objective Determine trends and factors associated with bed-sharing. Design National Infant Sleep Position Study: Annual telephone surveys. Setting 48 contiguous United States. Participants Nighttime caregivers of infants born within the last 7 months between 1993 and 2010. Approximately 1000 interviews annually. Main Outcome Measure Infant usually bed-sharing. Results Of 18,986 participants, 11% reported usually bed-sharing. Bed-sharing increased between 1993 (6.0%) and 2010 (13.5%). While there was an increase for Whites from 1993 to 2000 (p<0.001), there was no significant increase from 2001 to 2010 (p=0.48). Blacks and Hispanics showed increase in bed-sharing throughout the period 1993 to 2010, with no difference between the two time periods (p=0.63 and 0.77, respectively). After accounting for study year, factors associated with increase in usually bed-sharing included: compared to college or more, maternal education less than high school (AOR = 1.4; 95% CI, 1.1–1.8), compared to White race, maternal race or ethnicity Black (AOR = 3.5; 95% CI, 3.0–4.1), Hispanic (AOR = 1.3; 95% CI, 1.1–1.6) and Other (AOR 2.5; 95% CI, 2.0–3.0), compared to household income ≥$50,000, less than $20 000 (AOR = 1.7; 95% CI, 1.4–2.0) and $20–$50,000 (AOR=1.3; 95%CI 1.1–1.5), compared with living in the Midwest, living in the West (AOR=1.6; 95%CI 1.4–1.9) or South (AOR=1.5; 95% CI=1.3–1.7), compared with infant age ≥16 weeks, less than 8 weeks (AOR = 1.5; 95%CI 1.2–1.7 and 8–15 weeks (AOR-1.3; 95% CI=1.2–1.5) and being born prematurely (AOR = 1.4; 95% CI, 1.2–1.6). Thirty-six percent of the participants reported talking to a doctor about bed-sharing. Compared with those who did not talk to a doctor, those who reported their doctors had a negative attitude were less likely to bed-share (AOR 0.66 (95% 0.53, 0.82), whereas a neutral attitude was associated with increased bed-sharing. (AOR 1.4; 95%CI 1.1–1.8). Conclusion Our findings of the continual

  14. Association between Drug Insurance Cost Sharing Strategies and Outcomes in Patients with Chronic Diseases: A Systematic Review

    PubMed Central

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

    2014-01-01

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

  15. Can risk-taking be an endophenotype for bipolar disorder? A study on patients with bipolar disorder type I and their first-degree relatives.

    PubMed

    Hıdıroğlu, Ceren; Demirci Esen, Özlem; Tunca, Zeliha; Neslihan Gűrz Yalçìn, Sehnaz; Lombardo, Lauren; Glahn, David C; Özerdem, Ayşegül

    2013-04-01

    Risk-taking behavior and impulsivity are core features of bipolar disorder. Whether they are part of the inherited aspect of the illness is not clear. We aimed to evaluate risk-taking behavior as a potential endophenotype for bipolar disorders, and its relationship with impulsivity and illness features. The Balloon Analogue Risk Task (BART) and Barratt Impulsiveness Scale-11 (BIS-11) were used to assess risk-taking behavior and impulsivity respectively in 30 euthymic bipolar I patients (BD), their 25 asymptomatic first-degree relatives (BD-R), and 30 healthy controls (HC). The primary BART outcome measure was the behavioral adjustment score (number of pumps after trials where the balloon did not pop minus the number of pumps after trials where the balloon popped). BD (p < .001) and BD-R (p = .001) had similar and significantly lower adjustment scores than HC. Only BD scored significantly higher on BIS-11 total (p = .01) and motor (p = .04) subscales than HC. Neither the BART, nor impulsivity scores associated with illness features. A limitation of this study is medicated patients and a heterogeneous BD-R were included. Riskiness may be a candidate endophenotype for bipolar disorder as it appears independently from illness features, presents similarly in BD and BD-R groups and differs from impulsivity. PMID:23410848

  16. 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

  17. 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

  18. 141 Gene Discovery and Data Sharing in Genome Wide Association Analyses: lessons form AIDS genetic restriction genes

    PubMed Central

    O'Brien, Stephen J; Svitin, Anton; Malov, Sergey; Cherkazov, Nikolay; Dobrynin, Pavel; Geerts, Paul; Troyer, Jennifer; Hendrickson-Lambert, Sher; Sezgin, Efe; Hutcheson, Holli

    2014-01-01

    As genome wide association studies plus whole genome sequence analyses for complex human disease determinants are expanding, it seems useful to develop strategies to facilitate large data sharing, rapid replication and validation of provocative statistical associations that straddle the threshold for genome wide significance. At this conference, we shall announce GWATCH, (Genome Wide Association Tracks Chromosome Highway) a web based data release platform that can freely display and inspect unabridged genome tracked association data without compromising privacy or Informed Consent constrictions, allowing for rapid discovery and replication opportunities. We illustrate the utility with HIV-AIDS resistance genes screened in combined large multicenter cohort studies GWAS (MACS, HGDS, MHGS, ALLIVE, LSOCA HOMER) developed and studied over the last decades.

  19. Social sharing of Gulf War experiences: association with trauma-related psychological symptoms.

    PubMed

    Southwick, S M; Morgan, C A; Rosenberg, R

    2000-10-01

    It commonly is believed that talking with family and friends (social sharing) about stressful or traumatic experiences can be therapeutic with regard to stress-related psychological symptoms. Two years after serving in the Gulf War, 58 National Guard Reservists completed the Mississippi Posttraumatic Stress Disorder Scale (PTSD), the Brief Symptom Inventory, and a measure of social sharing that asked how much they had talked to family and friends about their experiences in the Gulf during the 2-year period since returning from the war. Subjects had a broad range of Mississippi PTSD scores. Six subjects met Mississippi criteria for PTSD. Degree of talking to family and friends about Gulf War experiences did not account for a significant portion of the variance in the prediction of PTSD symptoms but did significantly contribute to prediction of scores for interpersonal sensitivity, depression, and psychoticism. Thus, degree of talking with family and friends was not found to be related to PTSD symptoms, although it may have influenced some symptoms of general psychopathology, such as depression, that are not specific to PTSD.

  20. 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

  1. 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

    2016-01-01

    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. 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

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

    PubMed

    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

  4. 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

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

    PubMed

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

    2009-01-01

    The objective of this study is to investigate prevalence and associated factors of commercial sex behaviors and condom use at commercial sex, as well as prevalence of needle sharing among injecting drug users (IDUs) in China. In this study, 162 IDUs were recruited by peer workers in Dazhou, Sichuan and were anonymously interviewed by using a structured questionnaire. Univariate and multivariate logistic regression analyses were performed and interaction between gender and the studied independent variables were tested for significance. The results of this study showed that the male and female respondents, respectively 11.7 and 16.9% were HIV positive; 34.0 and 40.7% engaged in commercial sex and 23.3 and 11.9% shared needles with others in the last six months. Percent using a condom in the last episode of commercial sex was 30.3% for males and 76.2% for females. The multivariate analyses showed that higher drug dosage (OR=0.3, 95% CI: 0.1-0.9) and reduced sexual drive (OR=0.3, 95% CI: 0.1-0.9) were associated with lower likelihood for commercial sex among male IDUs while higher drug dosage (OR=9.1, 95% CI: 1.0-86.0), perceived difficulty in finding a job (OR=5.1, 95% CI: 1.3-20.1) and lack of family support (OR=4.0, 95% CI: 1.1-15.4) were associated with commercial sex among female IDUs. Similarly, unknown HIV status (OR=8.2, 95% CI: 1.7-9.2) and having a regular sex partner (OR=3.7, 95% CI: 1.3-10.9) was associated with needle sharing. It is concluded that male and female IDUs were sexually active and often engaged in commercial sex. Drug dosage and reduced sexual drive were relevant but did not stop commercial sex behaviors. More supportive social environment is required to prevent female IDUs to enter sex work. PMID:19085218

  6. Revealing a Brain Network Endophenotype in Families with Idiopathic Generalised Epilepsy

    PubMed Central

    FitzGerald, Thomas H. B.; Elwes, Robert D. C.; Nashef, Lina; Terry, John R.; Richardson, Mark P.

    2014-01-01

    Idiopathic generalised epilepsy (IGE) has a genetic basis. The mechanism of seizure expression is not fully known, but is assumed to involve large-scale brain networks. We hypothesised that abnormal brain network properties would be detected using EEG in patients with IGE, and would be manifest as a familial endophenotype in their unaffected first-degree relatives. We studied 117 participants: 35 patients with IGE, 42 unaffected first-degree relatives, and 40 normal controls, using scalp EEG. Graph theory was used to describe brain network topology in five frequency bands for each subject. Frequency bands were chosen based on a published Spectral Factor Analysis study which demonstrated these bands to be optimally robust and independent. Groups were compared, using Bonferroni correction to account for nonindependent measures and multiple groups. Degree distribution variance was greater in patients and relatives than controls in the 6–9 Hz band (p = 0.0005, p = 0.0009 respectively). Mean degree was greater in patients than healthy controls in the 6–9 Hz band (p = 0.0064). Clustering coefficient was higher in patients and relatives than controls in the 6–9 Hz band (p = 0.0025, p = 0.0013). Characteristic path length did not differ between groups. No differences were found between patients and unaffected relatives. These findings suggest brain network topology differs between patients with IGE and normal controls, and that some of these network measures show similar deviations in patients and in unaffected relatives who do not have epilepsy. This suggests brain network topology may be an inherited endophenotype of IGE, present in unaffected relatives who do not have epilepsy, as well as in affected patients. We propose that abnormal brain network topology may be an endophenotype of IGE, though not in itself sufficient to cause epilepsy. PMID:25302690

  7. 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

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

    PubMed

    2007-06-01

    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 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

  9. 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.

  10. The importance of genetic and shared environmental factors for the associations between job demands, control, support and burnout.

    PubMed

    Blom, Victoria; Bodin, Lennart; Bergström, Gunnar; Hallsten, Lennart; Svedberg, Pia

    2013-01-01

    Within occupational health research, one of the most influential models is the Job Demands-Control-Support model. Numerous studies have applied the model to different domains, with both physical and psychological health outcomes, such as burnout. The twin design provides a unique and powerful research methodology for examining the effects of environmental risk factors on burnout while taking familial factors (genetic and shared environment) into account. The aim of the present study was to investigate the impact of familial factors on the associations of burnout with job demands, control and support. A total of 14,516 individuals from the Swedish Twin Registry, who were born between 1959 and 1986, and who participated in the Study of Twin Adults: Genes and Environment (STAGE) by responding to a web-based questionnaire in 2005, were included in the analyses. Of these, there were 5108 individuals in complete same-sex twin pairs. Co-twin control analyses were performed using linear mixed modeling, comparing between-pairs effects and within-pair effects, stratified also by zygosity and sex. The results indicate that familial factors are of importance in the association between support and burnout in both women and men, but not between job demands and burnout. There are also tendencies towards familial factors being involved in the association between control and burnout in men. These results offer increased understanding of the mechanisms involved in the associations between work stress and burnout.

  11. Granuloma faciale: a cutaneous lesion sharing features with IgG4-associated sclerosing diseases.

    PubMed

    Cesinaro, Anna Maria; Lonardi, Silvia; Facchetti, Fabio

    2013-01-01

    The pathogenesis of granuloma faciale (GF), framed in the group of cutaneous vasculopathic dermatitis, is poorly understood. The present study investigated whether GF might be part of the spectrum of IgG4-related sclerosing diseases (IgG4-RD). Erythema elevatum diutinum (EED), believed to belong to the same group of disorders as GF, was also studied for comparison. Thirty-one biopsies of GF obtained from 25 patients (18 men, 7 women) and 5 cases of EED (4 women and 1 man) were analyzed morphologically and for the expression of IgG and IgG4 by immunohistochemistry. The distribution of Th1, T regulatory and Th2 T-cell subsets, respectively, identified by anti-T-bet, anti-FoxP3, and anti-GATA-3 antibodies, was also evaluated. The dermal inflammatory infiltrate in GF contained eosinophils and plasma cells in variable proportions. Obliterative venulitis was found in 16 cases, and storiform fibrosis, a typical feature of IgG4-RD, was observed in 8 cases and was prominent in 3 of them. On immunohistochemical analysis 7 of 31 biopsies (22.6%) from 6 GF patients fulfilled the criteria for IgG4-RD (IgG4/IgG ratio >40%, and absolute number of IgG4 per high-power field >50). Interestingly, the 6 patients were male, and 4 showed recurrent and/or multiple lesions. In an additional 5 cases, only the IgG4/IgG ratio was abnormal. None of the 5 EED cases fulfilled the criteria for IgG4-RD. The T-cell subsets in GF were quite variable in number, GATA-3 lymphocytes were generally more abundant, but no relationship with the number of IgG4 plasma cells was found. The study indicates that a significant number of GF cases are associated with an abnormal content of IgG4 plasma cells; this association was particularly obvious in male patients and in cases presenting with multiple or recurrent lesions. As morphologic changes typically found in IgG4-RD, such as obliterative vascular inflammation and storiform sclerosis, are found in GF, we suggest that GF might represent a localized form of

  12. 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…

  13. 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).

  14. 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

  15. Cognitive Endophenotypes Inform Genome-Wide Expression Profiling in Schizophrenia

    PubMed Central

    Zheutlin, Amanda B.; Viehman, Rachael W.; Fortgang, Rebecca; Borg, Jacqueline; Smith, Desmond J.; Suvisaari, Jaana; Therman, Sebastian; Hultman, Christina M.; Cannon, Tyrone D.

    2015-01-01

    OBJECTIVE We performed a whole-genome expression study to clarify the nature of the biological processes mediating between inherited genetic variations and cognitive dysfunction in schizophrenia. METHOD Gene expression was assayed from peripheral blood mononuclear cells using Illumina Human WG6 v3.0 chips in twins discordant for schizophrenia or bipolar disorder and control twins. After quality control, expression levels of 18,559 genes were screened for association with California Verbal Learning Test (CVLT) performance, and any memory-related probes were then evaluated for variation by diagnostic status in the discovery sample (N = 190), and in an independent replication sample (N = 73). Heritability of gene expression using the twin design was also assessed. RESULTS After Bonferroni correction (p < 2.69 × 10−6), CVLT performance was significantly related to expression levels for 76 genes, 43 of which were differentially expressed in schizophrenia patients, with comparable effect sizes in the same direction in the replication sample. For 41 of these 43 transcripts, expression levels were heritable. Nearly all identified genes contain common or de novo mutations associated with schizophrenia in prior studies. CONCLUSION Genes increasing risk for schizophrenia appear to do so in part via effects on signaling cascades influencing memory. The genes implicated in these processes are enriched for those related to RNA processing and DNA replication and include genes influencing G-protein coupled signal transduction, cytokine signaling, and oligodendrocyte function. PMID:26710095

  16. Quantitative linkage analysis to the autism endophenotype social responsiveness identifies genome-wide significant linkage to two regions on chromosome 8

    PubMed Central

    Lowe, Jennifer K.; Werling, Donna M.; Constantino, John N.; Cantor, Rita M.; Geschwind, Daniel H.

    2015-01-01

    Objective Autism Spectrum Disorder (ASD) is characterized by deficits in social function and the presence of repetitive and restrictive behaviors. Following a previous test of principle, we adopted a quantitative approach to discovering genes contributing to the broader autism phenotype by using social responsiveness as an endophenotype for ASD. Method Linkage analyses using scores from the Social Responsiveness Scale (SRS) were performed in 590 families from AGRE, a largely multiplex ASD cohort. Regional and genome-wide association analyses were performed to search for common variants contributing to social responsiveness. Results SRS is unimodally distributed in male offspring from multiplex autism families, in contrast with a bimodal distribution observed in females. In correlated analyses differing by SRS respondent, genome-wide significant linkage for social responsiveness was identified at chr8p21.3 (multi-point LOD=4.11; teacher/parent scores) and chr8q24.22 (multi-point LOD=4.54; parent-only scores), respectively. Genome-wide or linkage-directed association analyses did not detect common variants contributing to social responsiveness. Conclusions The sex-differential distributions of SRS in multiplex autism families likely reflect mechanisms contributing to the sex ratio for autism observed in the general population and form a quantitative signature of reduced penetrance of inherited liability to ASD among females. The identification of two strong loci for social responsiveness validates the endophenotype approach for the identification of genetic variants contributing to complex traits such as ASD. While causal mutations have yet to be identified, these findings are consistent with segregation of rare genetic variants influencing social responsiveness and underscore the increasingly recognized role of rare inherited variants in the genetic architecture of ASD. PMID:25727539

  17. 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.

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

    PubMed

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

    2011-11-01

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

  20. Revisiting the suitability of antisaccade performance as an endophenotype in schizophrenia.

    PubMed

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

    2011-11-01

    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 patients and relatives, and sought to establish whether antisaccade measures could differentiate between two patients clusters identified in the Western Australian Family Study of Schizophrenia with either pervasive cognitive deficits (CD) or cognitively spared (CS). Ninety-three patients (CD=47, CS=46), 99 relatives and 62 healthy controls carried out a standard antisaccade task. Results showed: (i) significantly greater error rate, and prolonged latencies to correct responses and self-correction saccades in patients compared with controls; (ii) high error rates in relatives of poorly performing patients; (iii) longer latencies of self-correction saccades in relatives compared to controls; and (iv) higher error rate and longer latencies of self-correction saccades in the CD subgroup compared with CS. Unaffected relatives as a group were unimpaired in error rate as compared to healthy controls. These findings suggest that the antisaccade error rate and latency of self-correction saccades are useful measures in specific applications of genetic research in schizophrenia, without fully meeting endophenotype co-familiality requirements.

  1. S-SCAM, a rare copy number variation gene, induces schizophrenia-related endophenotypes in transgenic mouse model.

    PubMed

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

    2015-02-01

    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.

  2. 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

  3. 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

    2013-08-01

    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.

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  5. 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.

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2016-10-01

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

  9. 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

  10. 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

  11. 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

  12. Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens.

    PubMed

    Xu, Jun; Saunders, Charles W; Hu, Ping; Grant, Raymond A; Boekhout, Teun; Kuramae, Eiko E; Kronstad, James W; Deangelis, Yvonne M; Reeder, Nancy L; Johnstone, Kevin R; Leland, Meredith; Fieno, Angela M; Begley, William M; Sun, Yiping; Lacey, Martin P; Chaudhary, Tanuja; Keough, Thomas; Chu, Lien; Sears, Russell; Yuan, Bo; Dawson, Thomas L

    2007-11-20

    Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably little is known at the molecular level. We describe the genome, secretory proteome, and expression of selected genes of Malassezia globosa. Further, we report a comparative survey of the genome and secretory proteome of Malassezia restricta, a close relative implicated in similar skin disorders. Adaptation to the skin environment and associated pathogenicity may be due to unique metabolic limitations and capabilities. For example, the lipid dependence of M. globosa can be explained by the apparent absence of a fatty acid synthase gene. The inability to synthesize fatty acids may be complemented by the presence of multiple secreted lipases to aid in harvesting host lipids. In addition, an abundance of genes encoding secreted hydrolases (e.g., lipases, phospholipases, aspartyl proteases, and acid sphingomyelinases) was found in the M. globosa genome. In contrast, the phylogenetically closely related plant pathogen Ustilago maydis encodes a different arsenal of extracellular hydrolases with more copies of glycosyl hydrolase genes. M. globosa shares a similar arsenal of extracellular hydrolases with the phylogenetically distant human pathogen, Candida albicans, which occupies a similar niche, indicating the importance of host-specific adaptation. The M. globosa genome sequence also revealed the presence of mating-type genes, providing an indication that Malassezia may be capable of sex. PMID:18000048

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

    PubMed

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

    2016-05-01

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

  14. Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders

    PubMed Central

    Yamasaki, Nobuyuki; Maekawa, Motoko; Kobayashi, Katsunori; Kajii, Yasushi; Maeda, Jun; Soma, Miho; Takao, Keizo; Tanda, Koichi; Ohira, Koji; Toyama, Keiko; Kanzaki, Kouji; Fukunaga, Kohji; Sudo, Yusuke; Ichinose, Hiroshi; Ikeda, Masashi; Iwata, Nakao; Ozaki, Norio; Suzuki, Hidenori; Higuchi, Makoto; Suhara, Tetsuya; Yuasa, Shigeki; Miyakawa, Tsuyoshi

    2008-01-01

    Elucidating the neural and genetic factors underlying psychiatric illness is hampered by current methods of clinical diagnosis. The identification and investigation of clinical endophenotypes may be one solution, but represents a considerable challenge in human subjects. Here we report that mice heterozygous for a null mutation of the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha-CaMKII+/-) have profoundly dysregulated behaviours and impaired neuronal development in the dentate gyrus (DG). The behavioral abnormalities include a severe working memory deficit and an exaggerated infradian rhythm, which are similar to symptoms seen in schizophrenia, bipolar mood disorder and other psychiatric disorders. Transcriptome analysis of the hippocampus of these mutants revealed that the expression levels of more than 2000 genes were significantly changed. Strikingly, among the 20 most downregulated genes, 5 had highly selective expression in the DG. Whereas BrdU incorporated cells in the mutant mouse DG was increased by more than 50 percent, the number of mature neurons in the DG was dramatically decreased. Morphological and physiological features of the DG neurons in the mutants were strikingly similar to those of immature DG neurons in normal rodents. Moreover, c-Fos expression in the DG after electric footshock was almost completely and selectively abolished in the mutants. Statistical clustering of human post-mortem brains using 10 genes differentially-expressed in the mutant mice were used to classify individuals into two clusters, one of which contained 16 of 18 schizophrenic patients. Nearly half of the differentially-expressed probes in the schizophrenia-enriched cluster encoded genes that are involved in neurogenesis or in neuronal migration/maturation, including calbindin, a marker for mature DG neurons. Based on these results, we propose that an "immature DG" in adulthood might induce alterations in behavior and serve as a promising

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

    PubMed

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

    2016-05-01

    Attention deficit hyperactivity disorder (ADHD) frequently persists into adulthood. A reduction in visual short-term memory (vSTM) storage capacity was recently suggested as a potential neuro-cognitive endophenotype, i.e., a testable marker of an individual's liability for developing ADHD. This study aimed at identifying markers of the brain abnormalities underlying vSTM reductions in adult ADHD. We combined behavioral parameter-based assessment with electrophysiology in groups of adult ADHD patients and healthy age-matched controls. Amplitudes of ERP markers of vSTM storage capacity, the contralateral delay activity (CDA) and the P3b, were analyzed according to (i) differences between individuals with higher vs. lower storage capacity K and (ii) differences between ADHD patients and control participants. We replicated the finding of reduced storage capacity in adult ADHD. Across groups, individuals with higher relative to lower storage capacity showed a larger CDA and P3b. We further found differences between the patient and control groups in the ERPs: The CDA amplitude was attenuated in an early time window for ADHD patients compared to control participants, and was negatively correlated with ADHD patients' symptom severity ratings. Furthermore, the P3b was larger in ADHD patients relative to control participants. These electrophysiological findings indicate altered brain mechanisms underlying visual storage capacity in ADHD, which are characterized by deficient encoding and maintenance, and increased recruitment of control processes. Accordingly, (quantifiable) ERP markers of vSTM in adult ADHD bear candidacy as neuro-cognitive endophenotypes of the disease. PMID:26972967

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

    ERIC Educational Resources Information Center

    Han, Jisu; Neuharth-Pritchett, Stacey

    2015-01-01

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

  17. Taiwan Schizophrenia Linkage Study: lessons learned from endophenotype-based genome-wide linkage scans and perspective.

    PubMed

    Chen, Wei J

    2013-10-01

    Taiwan Schizophrenia Linkage Study (TSLS) was initiated with a linkage strategy for locating multiple genes, each of small to moderate effect, and aimed to recruit a large enough sample of pairs of affected siblings and their families ascertained from a multisite study. With a sample of 607 families successfully recruited, a total of 2,242 individuals (1,207 affected and 1,035 unaffected) from 557 families were genotyped using 386 microsatellite markers spaced at an average of 9-cM intervals. Here the author reviews the establishment of TSLS and initial signal derived from linkage scan using the diagnosis of schizophrenia. Based on the limited success of the initial linkage analysis, a sufficient-component causal model is proposed to incorporate endophenotypes and genes for schizophrenia. Four types of candidate endophenotype measured in TSLS, including schizotypal personality, Continuous Performance Test, Wisconsin Card Sorting Test, and niacin skin flush test, are briefly described. The author discusses different strategies of linkage analysis incorporating these endophenotypes, including quantitative trait loci (QTL) linkage analysis, clustering-derived subgroups, ordered subset analysis (OSA), and latent classes for linkage scan. Then the author summarizes the linkage signals generated from seven studies of endophenotype-based linkage analysis using TSLS, including QTL scan of neurocognitive performance, QTL scan of niacin skin flush, the family cluster of attention deficit and execution deficit, OSA by schizophrenia-schizotypy factors, nested OSA by age at onset and neurocognitive performance, and the latent class of deficit schizophrenia for linkage analysis. The perspective of combining next-generation sequencing with linkage analysis of families is also discussed.

  18. 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.

  19. Performance of Verbal Fluency as an Endophenotype in Patients with Familial versus Sporadic Schizophrenia and Their Parents.

    PubMed

    Liang, Sugai; Deng, Wei; Wang, Qiang; Ma, Xiaohong; Li, Mingli; Brown, Matthew R G; Hu, Xun; Li, Xinmin; Greenshaw, Andrew J; Li, Tao

    2016-01-01

    What's the neurocognitive deficit as an endophenotype to familial schizophrenia? Here, we investigate the neurocognitive endophenotype in first-episode patients with familial schizophrenia (FS) and sporadic schizophrenia (SS), and their parents. 98 FS patients and their 105 parents; 190 SS patients and their 207 parents; 195 controls matched with patients, and 190 controls matched with the patients' parents, were assessed with the short version of the Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC), the immediate and delayed logical memory tests from the Wechsler Memory Scale-Revised in China (WMS-RC), the Verbal Fluency Test (VFT), the Trail Making Test Parts A and B-Modified (TMA, TMB-M), and the Modified Wisconsin Card Sorting Test (WCST-M). The results showed that with age, gender, and education as covariates, after controlling for false discovery rates, the FS group and their parent group performed worse than the SS group and their parent group on VFT. No significant differences were found for other neurocognitive tests between the FS and SS patient groups, and their respective parent groups. Our findings suggest the patients with familial and sporadic schizophrenia and their respective parent groups may have a different genetic predisposition in relation to a cognitive endophenotype. PMID:27581658

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

    PubMed Central

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

    2015-01-01

    Several forms of eye movement dysfunction (EMD) are regarded as promising candidate endophenotypes of schizophrenia. Discrepancies in individual study results have led to inconsistent conclusions regarding particular aspects of EMD in relatives of schizophrenia patients. To quantitatively evaluate and compare the candidacy of smooth pursuit, saccade and fixation deficits in first-degree biological relatives, we conducted a set of meta-analytic investigations. Among 16 measures of EMD, memory-guided saccade accuracy and error rate, global smooth pursuit dysfunction, intrusive saccades during fixation, antisaccade error rate and smooth pursuit closed loop gain emerged as best differentiating relatives from controls (standardized mean differences ranged from .46 to .66), with no significant differences among these measures. Anticipatory saccades, but no other smooth pursuit component measures were also increased in relatives. Visually-guided reflexive saccades were largely normal. Moderator analyses examining design characteristics revealed few variables affecting the magnitude of the meta-analytically observed effects. Moderate effect sizes of relatives v. controls in selective aspects of EMD supports their endophenotype potential. Future work should focus on facilitating endophenotype utility through attention to heterogeneity of EMD performance, relationships among forms of EMD, and application in molecular genetics studies. PMID:18930572

  1. Performance of Verbal Fluency as an Endophenotype in Patients with Familial versus Sporadic Schizophrenia and Their Parents

    PubMed Central

    Liang, Sugai; Deng, Wei; Wang, Qiang; Ma, Xiaohong; Li, Mingli; Brown, Matthew R. G.; Hu, Xun; Li, Xinmin; Greenshaw, Andrew J.; Li, Tao

    2016-01-01

    What’s the neurocognitive deficit as an endophenotype to familial schizophrenia? Here, we investigate the neurocognitive endophenotype in first-episode patients with familial schizophrenia (FS) and sporadic schizophrenia (SS), and their parents. 98 FS patients and their 105 parents; 190 SS patients and their 207 parents; 195 controls matched with patients, and 190 controls matched with the patients’ parents, were assessed with the short version of the Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC), the immediate and delayed logical memory tests from the Wechsler Memory Scale-Revised in China (WMS-RC), the Verbal Fluency Test (VFT), the Trail Making Test Parts A and B-Modified (TMA, TMB-M), and the Modified Wisconsin Card Sorting Test (WCST-M). The results showed that with age, gender, and education as covariates, after controlling for false discovery rates, the FS group and their parent group performed worse than the SS group and their parent group on VFT. No significant differences were found for other neurocognitive tests between the FS and SS patient groups, and their respective parent groups. Our findings suggest the patients with familial and sporadic schizophrenia and their respective parent groups may have a different genetic predisposition in relation to a cognitive endophenotype. PMID:27581658

  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. 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.

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

    PubMed

    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 to

  6. 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

  7. Striatal shape abnormalities as novel neurodevelopmental endophenotypes in schizophrenia: a longitudinal study.

    PubMed

    Chakravarty, M Mallar; Rapoport, Judith L; Giedd, Jay N; Raznahan, Armin; Shaw, Philip; Collins, D Louis; Lerch, Jason P; Gogtay, Nitin

    2015-04-01

    There are varying, often conflicting, reports with respect to altered striatal volume and morphometry in the major psychoses due to the influences of antipsychotic medications on striatal volume. Thus, disassociating disease effects from those of medication become exceedingly difficult. For the first time, using a longitudinally studied sample of structural magnetic resonance images from patients with childhood onset schizophrenia (COS; neurobiologically contiguous with the adult onset form of schizophrenia), their nonpsychotic siblings (COSSIBs), and novel shape mapping algorithms that are volume independent, we report the familial contribution of striatal morphology in schizophrenia. The results of our volumetric analyses demonstrate age-related increases in overall striatal volumes specific only to COS. However, both COS and COSSIBs showed overlapping shape differences in the striatal head, which normalized in COSSIBs by late adolescence. These results mirror previous studies from our group, demonstrating cortical thickness deficits in COS and COSSIBs as these deficits normalize in COSSIBs in the same age range as our striatal findings. Finally, there is a single region of nonoverlapping outward displacement in the dorsal aspect of the caudate body, potentially indicative of a response to medication. Striatal shape may be considered complimentary to volume as an endophenotype, and, in some cases may provide information that is not detectable using standard volumetric techniques. Our striatal shape findings demonstrate the striking localization of abnormalities in striatal the head. The neuroanatomical localization of these findings suggest the presence of abnormalities in the striatal-prefrontal circuits in schizophrenia and resilience mechanisms in COSSIBs with age dependent normalization.

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

    PubMed Central

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

    2016-01-01

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

  9. Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence.

    PubMed

    Lisiecka, D M; Holt, R; Tait, R; Ford, M; Lai, M-C; Chura, L R; Baron-Cohen, S; Spencer, M D; Suckling, J

    2015-01-01

    During adolescence, white matter microstructure undergoes an important stage of development. It is hypothesized that the alterations of brain connectivity that have a key role in autism spectrum conditions (ASCs) may interact with the development of white matter microstructure. This interaction may be present beyond the phenotype of autism in siblings of individuals with ASC, who are 10 to 20 times more likely to develop certain forms of ASC. We use diffusion tensor imaging to examine how white matter microstructure measurements correlate with age in typically developing individuals, and how this correlation differs in n=43 adolescents with ASC and their n=38 siblings. Correlations observed in n=40 typically developing individuals match developmental changes noted in previous longitudinal studies. In comparison, individuals with ASC display weaker negative correlation between age and mean diffusivity in a broad area centred in the right superior longitudinal fasciculus. These differences may be caused either by increased heterogeneity in ASC or by temporal alterations in the group's developmental pattern. Siblings of individuals with ASC also show diminished negative correlation between age and one component of mean diffusivity-second diffusion eigenvalue-in the right superior longitudinal fasciculus. As the observed differences match for location and correlation directionality in our comparison of typically developing individuals to those with ASC and their siblings, we propose that these alterations constitute a part of the endophenotype of autism.

  10. 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

  11. Facial Characteristics and Olfactory Dysfunction: Two Endophenotypes Related to Nonsyndromic Cleft Lip and/or Palate

    PubMed Central

    Roosenboom, J.; Saey, I.; Peeters, H.; Devriendt, K.; Claes, P.; Hens, G.

    2015-01-01

    Evidence exists for the presence of a specific facial phenotype in nonaffected first-degree relatives of persons with CL/P. An increased risk for olfactory dysfunction has also been reported in CL/P-relatives. These phenotypic features can probably be explained via the presence of CL/P-related susceptibility genes. We aimed at confirming the occurrence of these endophenotypic traits in first-degree CL/P-relatives, and we investigated the link between the facial phenotype and the smell capacity in this group. We studied the facial morphology of 88 nonaffected first-degree relatives of patients with CL/P and 33 control subjects without family history of facial clefting by 3D surface imaging and a spatially dense analysis of the images. Smell testing was performed in 30 relatives and compared with 23 control subjects. Nonaffected relatives showed midface retrusion, hypertelorism, and olfactory dysfunction, compared to controls. In addition, we show for the first time that olfactory dysfunction in relatives is correlated to a smaller upper nasal region. This might be explained by a smaller central olfactory system. The different facial morphology in the relatives with olfactory impairment as compared to the total group may be an illustration of the contribution of different genetic backgrounds to the occurrence of CL/P via different biological pathways. PMID:26064961

  12. Facial Characteristics and Olfactory Dysfunction: Two Endophenotypes Related to Nonsyndromic Cleft Lip and/or Palate.

    PubMed

    Roosenboom, J; Saey, I; Peeters, H; Devriendt, K; Claes, P; Hens, G

    2015-01-01

    Evidence exists for the presence of a specific facial phenotype in nonaffected first-degree relatives of persons with CL/P. An increased risk for olfactory dysfunction has also been reported in CL/P-relatives. These phenotypic features can probably be explained via the presence of CL/P-related susceptibility genes. We aimed at confirming the occurrence of these endophenotypic traits in first-degree CL/P-relatives, and we investigated the link between the facial phenotype and the smell capacity in this group. We studied the facial morphology of 88 nonaffected first-degree relatives of patients with CL/P and 33 control subjects without family history of facial clefting by 3D surface imaging and a spatially dense analysis of the images. Smell testing was performed in 30 relatives and compared with 23 control subjects. Nonaffected relatives showed midface retrusion, hypertelorism, and olfactory dysfunction, compared to controls. In addition, we show for the first time that olfactory dysfunction in relatives is correlated to a smaller upper nasal region. This might be explained by a smaller central olfactory system. The different facial morphology in the relatives with olfactory impairment as compared to the total group may be an illustration of the contribution of different genetic backgrounds to the occurrence of CL/P via different biological pathways.

  13. Shared Intentionality

    ERIC Educational Resources Information Center

    Tomasello, Michael; Carpenter, Malinda

    2007-01-01

    We argue for the importance of processes of shared intentionality in children's early cognitive development. We look briefly at four important social-cognitive skills and how they are transformed by shared intentionality. In each case, we look first at a kind of individualistic version of the skill--as exemplified most clearly in the behavior of…

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

    PubMed Central

    2013-01-01

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

  15. 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. PMID:26385997

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

    PubMed Central

    Ángel, Romero-Martínez; Luis, Moya-Albiol

    2015-01-01

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

  17. 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.

  18. Socialization of Early Prosocial Behavior: Parents’ Talk about Emotions is Associated with Sharing and Helping in Toddlers

    PubMed Central

    Brownell, Celia A.; Svetlova, Margarita; Anderson, Ranita; Nichols, Sara R.; Drummond, Jesse

    2012-01-01

    What role does socialization play in the origins of prosocial behavior? We examined one potential socialization mechanism, parents’ discourse about others’ emotions with very young children in whom prosocial behavior is still nascent. Two studies are reported, one of sharing in 18- and 24-month-olds (n = 29), and one of instrumental and empathy-based helping in 18- and 30-month-olds (n = 62). In both studies, parents read age-appropriate picture books to their children and the content and structure of their emotion-related and internal state discourse were coded. Results showed that children who helped and shared more quickly and more often, especially in tasks that required more complex emotion understanding, had parents who more often asked them to label and explain the emotions depicted in the books. Moreover, it was parents’ elicitation of children’s talk about emotions rather than parents’ own production of emotion labels and explanations that explained children’s prosocial behavior, even after controlling for age. Thus, it is the quality, not the quantity, of parents’ talk about emotions with their toddlers that matters for early prosocial behavior. PMID:23264753

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

    PubMed

    Liley, James; Wallace, Chris

    2015-02-01

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

  20. A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.

    PubMed

    Hinds, David A; McMahon, George; Kiefer, Amy K; Do, Chuong B; Eriksson, Nicholas; Evans, David M; St Pourcain, Beate; Ring, Susan M; Mountain, Joanna L; Francke, Uta; Davey-Smith, George; Timpson, Nicholas J; Tung, Joyce Y

    2013-08-01

    Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P<5×10(-8), including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P=5.3×10(-21)); 6p21.33 near HLA-C and MICA (rs9266772, P=3.2×10(-12)); 5p13.1 near PTGER4 (rs7720838, P=8.2×10(-11)); 2q33.1 in PLCL1 (rs10497813, P=6.1×10(-10)), 3q28 in LPP (rs9860547, P=1.2×10(-9)); 20q13.2 in NFATC2 (rs6021270, P=6.9×10(-9)), 4q27 in ADAD1 (rs17388568, P=3.9×10(-8)); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P=4.8×10(-8)). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P=1.7×10(-12)), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease. PMID:23817569

  1. 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.

  2. 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. PMID:25745955

  3. 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. PMID:26974007

  4. 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

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

    PubMed Central

    Peyrot, WJ; Lee, SH; Milaneschi, Y; Abdellaoui, A; Byrne, EM; Esko, T; de Geus, EJC; Hemani, G; Hottenga, JJ; Kloiber, S; Levinson, DF; Lucae, S; Martin, NG; Medland, SE; Metspalu, A; Milani, L; Noethen, MM; Potash, JB; Rietschel, M; Rietveld, CA; Ripke, S; Shi, J; Willemsen, G; Zhu, Z; Boomsma, DI; Wray, NR; Penninx, BWJH

    2015-01-01

    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 9,662 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 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 ten-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 due to measurable pleiotropic genetic effects, which suggests that environmental factors could be involved such as, for example, socioeconomic status. PMID:25917368

  6. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-07-01

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

  9. 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

  10. Exocrine pancreatic insufficiency in adults: A shared position statement of the Italian association for the study of the pancreas

    PubMed Central

    Pezzilli, Raffaele; Andriulli, Angelo; Bassi, Claudio; Balzano, Gianpaolo; Cantore, Maurizio; Delle Fave, Gianfranco; Falconi, Massimo; Frulloni, Luca

    2013-01-01

    This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas (AISP). We covered the main diseases associated with exocrine pancreatic insufficiency (EPI) which are of common interest to internists/gastroenterologists, oncologists and surgeons, fully aware that EPI may also occur together with many other diseases, but less frequently. A preliminary manuscript based on an extended literature search (Medline/PubMed, Cochrane Library and Google Scholar) of published reports was prepared, and key recommendations were proposed. The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012. Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached. The final draft of the manuscript was then sent to the AISP Council for approval and/or modification. All concerned parties approved the final version of the manuscript in June 2013. PMID:24307787

  11. 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

    2016-01-01

    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

  12. 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. PMID:26192919

  13. 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

  14. Shared and distinct gray matter abnormalities in schizophrenia, schizophrenia relatives and bipolar disorder in association with cognitive impairment.

    PubMed

    Knöchel, Christian; Stäblein, Michael; Prvulovic, David; Ghinea, Denisa; Wenzler, Sofia; Pantel, Johannes; Alves, Gilberto; Linden, David E J; Harrison, Octavia; Carvalho, Andre; Reif, Andreas; Oertel-Knöchel, Viola

    2016-03-01

    Cognitive impairments have been linked to structural and functional alterations in frontal and subcortical brain regions, ultimately leading to fronto-thalamic connectivity disturbances. We hypothesized that such neuronal disruptions in frontal and subcortical structures may account for neuropsychological deficits in schizophrenia (SZ), schizophrenia relatives and bipolar disorder (BD). We acquired T1-weighted anatomical MRI sequences in 209 participants: 57 SZ patients, 47 first-degree relatives of SZ patients, 48 BD I patients and 57 healthy controls. We computed group comparisons of gray matter (GM) volume in frontal and basal ganglia regions-of-interest, followed by correlation analysis between psychomotor speed, executive functioning and learning and GM volumes in candidate regions. Several frontal GM volume reductions as well as GM increases in the thalamus and the putamen were exhibited in SZ patients as compared to controls. The same finding was observed - less pronounced - when comparing SZ relatives and controls. BD patients presented GM volume increases in the basal ganglia in comparison to controls. In SZ patients, increases in bilateral thalamus GM volume and decreases in left middle and superior frontal gyrus volume were significantly associated with worse cognitive performance. In summary, our results indicate distinct imbalances across frontal-subcortical circuits in BD, SZ relatives and SZ. The functional relevance of the findings were mainly limited to the SZ patients group: in this group, abnormalities were directly associated with cognitive performance. This result is in line with the finding that the volume alterations were strongest in SZ patients and followed by BD patients and SZ relatives. PMID:26833265

  15. 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.

  16. Sharing Physician Notes Through an Electronic Portal is Associated With Improved Medication Adherence: Quasi-Experimental Study

    PubMed Central

    Darer, Jonathan; Tang, Xiaoqin; Thompson, Jason; Tusing, Lorraine; Fossa, Alan; Delbanco, Tom

    2015-01-01

    Background In surveys, interviews, and focus groups, patients taking medications and offered Web portal access to their primary care physicians’ (PCPs) notes report improved adherence to their regimens. However, objective confirmation has yet to be reported. Objective To evaluate the association between patient Internet portal access to primary care physician visit notes and medication adherence. Methods This study is a retrospective comparative analysis at one site of the OpenNotes quasi-experimental trial. The setting includes primary care practices at the Geisinger Health System (GHS) in Danville, Pennsylvania. Participants include patients 18 years of age or older with electronic portal access, GHS primary care physicians, and Geisinger health plan insurance, and taking at least one antihypertensive or antihyperlipidemic agent from March 2009 to June 2011. Starting in March 2010, intervention patients were invited and reminded to read their PCPs' notes. Control patients also had Web portal access throughout, but their PCPs' notes were not available. From prescription claims, adherence was assessed by using the proportion of days covered (PDC). Patients with a PDC ≥.80 were considered adherent and were compared across groups using generalized linear models. Results A total of 2147 patients (756 intervention participants, 35.21%; 1391 controls, 64.79%) were included in the analysis. Compared to those without access, patients invited to review notes were more adherent to antihypertensive medications—adherence rate 79.7% for intervention versus 75.3% for control group; adjusted risk ratio, 1.06 (95% CI 1.00-1.12). Adherence was similar among patient groups taking antihyperlipidemic agents—adherence rate 77.6% for intervention versus 77.3% for control group; adjusted risk ratio, 1.01 (95% CI 0.95-1.07). Conclusions Availability of notes following PCP visits was associated with improved adherence by patients prescribed antihypertensive, but not

  17. 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.

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

    PubMed Central

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

    2015-01-01

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

  19. 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

  20. 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.

  1. 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

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

    PubMed

    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

  3. 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

  4. Exploring the associations shared by mood, pain-related attention and pain outcomes related to sleep disturbance in a chronic pain sample

    PubMed Central

    Harrison, Lee; Wilson, Sue; Heron, Jon; Stannard, Catherine; Munafò, Marcus R.

    2016-01-01

    Objective Sleep disturbance in chronic pain is common, occurring in two-thirds of patients. There is a complex relationship between chronic pain and sleep; pain can disrupt sleep and poor sleep can exaggerate pain intensity. This may have an impact on both depressive symptoms and attention to pain. This study aims to evaluate the relationship between chronic pain and sleep, and the role of mood and attention. Methods Chronic pain patients, recruited from a secondary care outpatient clinic, completed self-report measures of pain, sleep, depressive symptoms and attention to pain. Hierarchical regression and structural equation modelling were used to explore the relationships between these measures. Participants (n = 221) were aged between 20 and 84 (mean = 52) years. Results The majority of participants were found to be ‘poor sleepers’ (86%) with increased pain severity, depressive symptoms and attention to pain. Both analytical approaches indicated that sleep disturbance is indirectly associated with increased pain severity Instead the relationship shared by sleep disturbance and pain severity was further associated with depressive symptoms and attention to pain. Conclusions Our results indicate that sleep disturbance may contribute to clinical pain severity indirectly though changes in mood and attention. Prospective studies exploring lagged associations between these constructs could have critical information relevant to the treatment of chronic pain. PMID:26726076

  5. 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

  6. Associations of mRNA:microRNA for the Shared Downstream Molecules of EGFR and Alternative Tyrosine Kinase Receptors in Non-small Cell Lung Cancer

    PubMed Central

    Wang, Fengfeng; Meng, Fei; Wang, Lili; Wong, S. C. Cesar; Cho, William C. S.; Chan, Lawrence W. C.

    2016-01-01

    Lung cancer is the top cancer killer worldwide with high mortality rate. Majority belong to non-small cell lung cancers (NSCLCs). The epidermal growth factor receptor (EGFR) has been broadly explored as a drug target for therapy. However, the drug responses are not durable due to the acquired resistance. MicroRNAs (miRNAs) are small non-coding and endogenous molecules that can inhibit mRNA translation initiation and degrade mRNAs. We wonder if some downstream molecules shared by EGFR and the other tyrosine kinase receptors (TKRs) further transduce the signals alternatively, and some miRNAs play the key roles in affecting the expression of these downstream molecules. In this study, we investigated the mRNA:miRNA associations for the direct EGFR downstream molecules in the EGFR signaling pathway shared with the other TKRs, including c-MET (hepatocyte growth factor receptor), Ron (a protein tyrosine kinase related to c-MET), PDGFR (platelet-derived growth factor receptor), and IGF-1R (insulin-like growth factor receptor-1). The multiple linear regression and support vector regression (SVR) models were used to discover the statistically significant and the best weighted miRNAs regulating the mRNAs of these downstream molecules. These two models revealed the similar mRNA:miRNA associations. It was found that the miRNAs significantly affecting the mRNA expressions in the multiple regression model were also those with the largest weights in the SVR model. To conclude, we effectively identified a list of meaningful mRNA:miRNA associations: phospholipase C, gamma 1 (PLCG1) with miR-34a, phosphoinositide-3-kinase, regulatory subunit 2 (PIK3R2) with miR-30a-5p, growth factor receptor-bound protein 2 (GRB2) with miR-27a, and Janus kinase 1 (JAK1) with miR-302b and miR-520e. These associations could make great contributions to explore new mechanism in NSCLCs. These candidate miRNAs may be regarded as the potential drug targets for treating NSCLCs with acquired drug resistance

  7. Semantic fluency and executive functions as candidate endophenotypes for the early diagnosis of schizophrenia in Han Chinese.

    PubMed

    Hu, Maorong; Chen, Jindong; Li, Lehua; Zheng, Yingjun; Wang, Juan; Guo, Xiaofeng; Wu, Renrong; Zhao, Jingping

    2011-09-20

    Neurocognitive deficits are recognized as core features of schizophrenia. The aim of this study was to compare the cognitive performance of antipsychotic, drug-naive patients with first-episode schizophrenia (FES patients) to their healthy siblings and to healthy controls from the Han Chinese population for exploring potential endophenotypes for the early detection of schizophrenia. A battery of cognitive assessment tools was used to measure seven cognitive domains in matched groups consisting of 56 subjects each. Cognitive tests included the grooved pegboard test (GPT), the category fluency test (CFT), the trail making test A (TMT-A), the Wechsler memory scale-III spatial span test (WMS-III SST), the Hopkins verbal learning test-revised (HVLT-R), the brief visuospatial memory test-revised (BVMT-R), the paced auditory serial addition test (PASAT), and the Wisconsin card sorting test-64 cards version (WCST-64). The performances of FEP patients were inferior to normal controls on all neuropsychological tests, while siblings were lower than healthy controls in many of the same tasks. Patients' performances were lower than siblings' on all tests except for the CFT, the WMS-III SST backward test, and four subtests of the WCST-64. Our data suggest that FEP patients exhibited pronounced impairment of fine motor skills, speed of processing, attention, verbal memory, visual memory, and executive function, while siblings exhibited deficits intermediate between those of schizophrenic patients and the control group. Semantic fluency function and executive function may be potential endophenotypes for the early diagnosis of schizophrenia. PMID:21827833

  8. Association of AKT1 with verbal learning, verbal memory, and regional cortical gray matter density in twins.

    PubMed

    Pietiläinen, Olli P H; Paunio, Tiina; Loukola, Anu; Tuulio-Henriksson, Annamari; Kieseppä, Tuula; Thompson, Paul; Toga, Arthur W; van Erp, Theo G M; Silventoinen, Karri; Soronen, Pia; Hennah, William; Turunen, Joni A; Wedenoja, Juho; Palo, Outi M; Silander, Kaisa; Lönnqvist, Jouko; Kaprio, Jaakko; Cannon, Tyrone D; Peltonen, Leena

    2009-07-01

    AKT1, encoding the protein kinase B, has been associated with the genetic etiology of schizophrenia and bipolar disorder. However, minuscule data exist on the role of different alleles of AKT1 in measurable quantitative endophenotypes, such as cognitive abilities and neuroanatomical features, showing deviations in schizophrenia and bipolar disorder. We evaluated the contribution of AKT1 to quantitative cognitive traits and 3D high-resolution neuroanatomical images in a Finnish twin sample consisting of 298 twins: 61 pairs with schizophrenia (8 concordant), 31 pairs with bipolar disorder (5 concordant) and 65 control pairs matched for age, sex and demographics. An AKT1 allele defined by the SNP rs1130214 located in the UTR of the gene revealed association with cognitive traits related to verbal learning and memory (P = 0.0005 for a composite index). This association was further fortified by a higher degree of resemblance of verbal memory capacity in pairs sharing the rs1130214 genotype compared to pairs not sharing the genotype. Furthermore, the same allele was also associated with decreased gray matter density in medial and dorsolateral prefrontal cortex (P < 0.05). Our findings support the role of AKT1 in the genetic background of cognitive and anatomical features, known to be affected by psychotic disorders. The established association of the same allelic variant of AKT1 with both cognitive and neuroanatomical aberrations could suggest that AKT1 exerts its effect on verbal learning and memory via neural networks involving prefrontal cortex. PMID:19051289

  9. Diagnostic value of anti-cyclic citrullinated peptides and association with HLA-DRB1 shared epitope alleles in African rheumatoid arthritis patients

    PubMed Central

    2010-01-01

    Introduction The purpose of this study was to examine the diagnostic performance of autoantibodies against citrullinated peptides/proteins (ACPA) and to determine the prevalence of HLA-DRB1 shared epitope alleles (SE) in African patients with rheumatoid arthritis (RA). Methods Serum levels of anti-cyclic citrullinated peptides antibodies (anti-CCP2, anti-CCP3), IgM and IgA rheumatoid factors (RF) were measured by enzyme-linked immunosorbent assay in the serum of 56 consecutive RA patients regularly followed in the Rheumatology Unit of the School of Medicine, University of Yaoundé, Yaoundé, Cameroon. Genotyping of HLA-DRB1 alleles was performed by polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes on microbeads arrays. Fifty-one patients with other inflammatory rheumatic diseases and 50 healthy individuals were included as controls. Results An anti-CCP2 assay showed the best diagnosis sensitivity (82%) and specificity (98%) with high positive predictive (PPV) (96%) and negative predictive values (NPV) (91%). Thirty percent of RA patients were carrying at least one copy of the HLA-DRB1 shared epitope (SE) compared to 10% and 14% of patients with other inflammatory rheumatic diseases and healthy individuals, respectively. The presence of the SE was associated with the production of ACPA. Conclusions Anti-CCP2 antibodies are useful markers of RA in African patients. In this cohort, the prevalence of the SE is higher in RA patients than in controls but lower than that reported in patient cohorts of European ancestry. The discrepancy between the high prevalence of ACPA-positive patients and the relatively low number of SE-positive cases suggest that, in addition to SE, other genetic factors control the development of ACPA in African RA patients. PMID:20196860

  10. 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.

  11. CMT-associated mutations in glycyl- and tyrosyl-tRNA synthetases exhibit similar pattern of toxicity and share common genetic modifiers in Drosophila

    PubMed Central

    Ermanoska, Biljana; Motley, William W.; Leitão-Gonçalves, Ricardo; Asselbergh, Bob; Lee, LaTasha H.; De Rijk, Peter; Sleegers, Kristel; Ooms, Tinne; Godenschwege, Tanja A.; Timmerman, Vincent; Fischbeck, Kenneth H.; Jordanova, Albena

    2014-01-01

    Aminoacyl-tRNA synthetases are ubiquitously expressed proteins that charge tRNAs with their cognate amino acids. By ensuring the fidelity of protein synthesis, these enzymes are essential for viability of every cell. Yet, mutations in six tRNA synthetases specifically affect the peripheral nerves and cause Charcot-Marie-Tooth disease (CMT). The CMT-causing mutations in tyrosyl- and glycyl-tRNA synthetases (YARS and GARS, respectively) alter the activity of the proteins in a range of ways (some mutations do not impact charging function, while others abrogate it), making a loss of function in tRNA charging unlikely to be the cause of disease pathology. It is currently unknown which cellular mechanisms are triggered by the mutant enzymes and how this leads to neurodegeneration. Here, by expressing two pathogenic mutations (G240R, P234KY) in Drosophila, we generated a model for GARS-associated neuropathy. We observed compromised viability, and behavioral, electrophysiological and morphological impairment in flies expressing the cytoplasmic isoform of mutant GARS. Their features recapitulated several hallmarks of CMT pathophysiology and were similar to the phenotypes identified in our previously described Drosophila model of YARS-associated neuropathy. Furthermore, CG8316 and CG15599 – genes identified in a retinal degeneration screen to modify mutant YARS, also modified the mutant GARS phenotypes. Our study presents genetic evidence for common mutant-specific interactions between two CMT-associated aminoacyl-tRNA synthetases, lending support for a shared mechanism responsible for the synthetase-induced peripheral neuropathies. PMID:24807208

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

    PubMed Central

    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

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

    PubMed

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

    2014-06-01

    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

  14. Intranasally applied neuropeptide S shifts a high-anxiety electrophysiological endophenotype in the ventral hippocampus towards a "normal"-anxiety one.

    PubMed

    Dine, Julien; Ionescu, Irina A; Avrabos, Charilaos; Yen, Yi-Chun; Holsboer, Florian; Landgraf, Rainer; Schmidt, Ulrike; Eder, Matthias

    2015-01-01

    The neurobiological basis of pathological anxiety and the improvement of its pharmacological treatment are a matter of intensive investigation. Here, using electrophysiological techniques in brain slices from animals of the high anxiety-related behavior (HAB) and normal anxiety-related behavior (NAB) mouse model, we show that basal neurotransmission at ventral hippocampal CA3-CA1 synapses is weaker in HAB compared to NAB mice. We further demonstrate that paired-pulse facilitation (PPF) and long-term potentiation (LTP) at these synapses are more pronounced in slices from HAB animals. Based on previous findings, we also examined whether intranasal delivery of neuropeptide S (NPS), which increasingly emerges as a potential novel treatment option for anxiety symptoms occurring in a variety of diseases like anxiety disorders, posttraumatic stress disorder, and major depression, impacts on the high-anxiety electrophysiological endophenotype in HAB mice. Strikingly, we detected enhanced basal neurotransmission and reduced PPF and LTP in slices from NPS-treated HAB animals. Collectively, our study uncovers a multifaceted high-anxiety neurophysiological endophenotype in the murine ventral hippocampus and provides the first evidence that an intranasally applied neuropeptide can shift such an endophenotype in an anxiety-regulating brain structure towards a "normal"-anxiety one.

  15. Association between secondhand smoke exposure at home and cigarette gifting and sharing in Zhejiang, China: a repeat cross-sectional study

    PubMed Central

    Xu, Yue; Xu, ShuiYang; Wu, QingQing; Guo, YuJie

    2016-01-01

    Objectives The aims of the current study were to assess the prevalence of household cigarette gifting and sharing, and to evaluate the relationship between secondhand smoke (SHS) exposure, and cigarette gifting and sharing, in Zhejiang, China. Design A repeat cross-sectional design. Setting 10 sites in 5 cities in Zhejiang, China. Participants Two surveys were conducted with adults in Zhejiang, China, in 2010 (N=2112) and 2012 (N=2279), respectively. At both waves, the same questionnaire was used; respondents were asked questions on residence, number of family smokers, indoor smoking rules, household income and cigarette gifting and sharing. Results The findings revealed that more than half of respondents’ families (54.50% in 2010, 52.79% in 2012) reported exposure to SHS. Many families (54.73% in 2010, 47.04% in 2012) shared cigarettes with others, and a minority (14.91% in 2010, 14.17% in 2012) reported their family giving cigarettes as a gift. There was a significant decrease in cigarette sharing from 2010 to 2012, irrespective of household with SHS exposure status; and the cigarette gifting was significantly decreased in household without SHS exposure. Conclusions Compared to households without SHS exposure, the prevalence of cigarette gifting and sharing in households with SHS exposure was more obvious. Encouraging and promoting a smoke-free household environment is necessary to change public smoking customs in Zhejiang, China. PMID:26940109

  16. Association of a Nonsynonymous Variant of DAOA with Visuospatial Ability in a Bipolar Family Sample

    PubMed Central

    Soronen, Pia; Silander, Kaisa; Antila, Mervi; Palo, Outi M.; Tuulio-Henriksson, Annamari; Kieseppä, Tuula; Ellonen, Pekka; Wedenoja, Juho; Turunen, Joni A.; Pietiläinen, Olli P.H.; Hennah, William; Lönnqvist, Jouko; Peltonen, Leena; Partonen, Timo; Paunio, Tiina

    2008-01-01

    Background Bipolar disorder and schizophrenia are hypothesized to share some genetic background. Methods In a two-phase study, we evaluated the effect of five promising candidate genes for psychotic disorders, DAOA, COMT, DTNBP1, NRG1, and AKT1, on bipolar spectrum disorder, psychotic disorder, and related cognitive endophenotypes in a Finnish family-based sample ascertained for bipolar disorder. Results In initial screening of 362 individuals from 63 families, we found only marginal evidence for association with the diagnosis-based dichotomous classification. Those associations did not strengthen when we genotyped the complete sample of 723 individuals from 180 families. We observed a significant association of DAOA variants rs3916966 and rs2391191 with visuospatial ability (Quantitative Transmission Disequilibrium Test [QTDT]; p = 4 × 10−6 and 5 × 10−6, respectively) (n = 159) with the two variants in almost complete linkage disequilibrium. The COMT variant rs165599 also associated with visuospatial ability, and in our dataset, we saw an additive effect of DAOA and COMT variants on this neuropsychological trait. Conclusions The ancestral allele (Arg) of the nonsynonymous common DAOA variant rs2391191 (Arg30Lys) was found to predispose to impaired performance. The DAOA gene may play a role in predisposing individuals to a mixed phenotype of psychosis and mania and to impairments in related neuropsychological traits. PMID:18466879

  17. Can power be shared?

    PubMed

    Ten Pas, William S

    2013-01-01

    Dental insurance began with a partnership between dental service organizations and state dental associations with a view toward expanding the number of Americans receiving oral health care and as a means for permitting firms and other organizations to offer employee benefits. The goals have been achieved, but the alliance between dentistry and insurance has become strained. A lack of dialogue has fostered mutual misconceptions, some of which are reviewed in this paper. It is possible that the public, the profession, and the dental insurance industry can all be strengthened, but only through power-sharing around the original common objective.

  18. Can power be shared?

    PubMed

    Ten Pas, William S

    2013-01-01

    Dental insurance began with a partnership between dental service organizations and state dental associations with a view toward expanding the number of Americans receiving oral health care and as a means for permitting firms and other organizations to offer employee benefits. The goals have been achieved, but the alliance between dentistry and insurance has become strained. A lack of dialogue has fostered mutual misconceptions, some of which are reviewed in this paper. It is possible that the public, the profession, and the dental insurance industry can all be strengthened, but only through power-sharing around the original common objective. PMID:24761578

  19. 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…

  20. 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

  1. Shared clinical decision making

    PubMed Central

    AlHaqwi, Ali I.; AlDrees, Turki M.; AlRumayyan, Ahmad; AlFarhan, Ali I.; Alotaibi, Sultan S.; AlKhashan, Hesham I.; Badri, Motasim

    2015-01-01

    Objectives: To determine preferences of patients regarding their involvement in the clinical decision making process and the related factors in Saudi Arabia. Methods: This cross-sectional study was conducted in a major family practice center in King Abdulaziz Medical City, Riyadh, Saudi Arabia, between March and May 2012. Multivariate multinomial regression models were fitted to identify factors associated with patients preferences. Results: The study included 236 participants. The most preferred decision-making style was shared decision-making (57%), followed by paternalistic (28%), and informed consumerism (14%). The preference for shared clinical decision making was significantly higher among male patients and those with higher level of education, whereas paternalism was significantly higher among older patients and those with chronic health conditions, and consumerism was significantly higher in younger age groups. In multivariate multinomial regression analysis, compared with the shared group, the consumerism group were more likely to be female [adjusted odds ratio (AOR) =2.87, 95% confidence interval [CI] 1.31-6.27, p=0.008] and non-dyslipidemic (AOR=2.90, 95% CI: 1.03-8.09, p=0.04), and the paternalism group were more likely to be older (AOR=1.03, 95% CI: 1.01-1.05, p=0.04), and female (AOR=2.47, 95% CI: 1.32-4.06, p=0.008). Conclusion: Preferences of patients for involvement in the clinical decision-making varied considerably. In our setting, underlying factors that influence these preferences identified in this study should be considered and tailored individually to achieve optimal treatment outcomes. PMID:26620990

  2. 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.

  3. 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

  4. Job Sharing in Education.

    ERIC Educational Resources Information Center

    Davidson, Wilma; Kline, Susan

    1979-01-01

    The author presents the advantages of job sharing for all school personnel, saying that education is particularly adaptable to this new form of employment. Current job sharing programs in Massachusetts, California, and New Jersey schools are briefly discussed. (SJL)

  5. Share Your Values

    MedlinePlus

    ... Español Text Size Email Print Share Share Your Values Page Content Article Body Today, teenagers are bombarded ... mid-twenties. The Most Effective Way to Instill Values? By Example Your words will carry more weight ...

  6. Job Sharing in Geography.

    ERIC Educational Resources Information Center

    Kay, Jeanne

    1982-01-01

    Job sharing is an employment alternative in which two qualified individuals manage the responsibilities of a single position. Discusses the barriers to and the potential, advantages, disadvantages, pitfalls, and challenges of job sharing. Focuses on job sharing in the geography profession. (Author/JN)

  7. LACC Shared Governance Model.

    ERIC Educational Resources Information Center

    Spangler, Mary

    This document discusses Los Angeles City College's (LACC) (California) Shared Governance Model. In response to California Assembly Bill 1725, LACC set forth a plan to implement the statutory requirements of shared governance. Shared governance is a concept grounded in the idea that decision-making is a process that affects the entire campus…

  8. 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

  9. Electronic Resource Sharing. SPEC Kit 222.

    ERIC Educational Resources Information Center

    Hogan, Donna R., Comp.; Dahlbach, Barbara J., Comp.

    The Systems and Procedures Exchange Center (SPEC) surveyed Association of Research Libraries (ARL) institutions to measure the degree of electronic resource sharing in ARL libraries; to discover which resources are being shared and between what kinds of institutions; and what documentation is available. Of the 119 ARL institutions surveyed, 53…

  10. 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.

  11. 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. PMID:20360734

  12. Mother and Adolescent Reports of Associations between Child Behavior Problems and Mother-Child Relationship Qualities: Separating Shared Variance from Individual Variance

    ERIC Educational Resources Information Center

    Burk, William J.; Laursen, Brett

    2010-01-01

    This study contrasts results from different correlational methods for examining links between mother and child (N = 72 dyads) reports of early adolescent (M = 11.5 years) behavior problems and relationship negativity and support. Simple (Pearson) correlations revealed a consistent pattern of statistically significant associations, regardless of…

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

    PubMed Central

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

    2014-01-01

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

  15. Novel ssDNA virus recovered from estuarine Mollusc (Amphibola crenata) whose replication associated protein (Rep) shares similarities with Rep-like sequences of bacterial origin.

    PubMed

    Dayaram, Anisha; Goldstien, Sharyn; Zawar-Reza, Peyman; Gomez, Christopher; Harding, Jon S; Varsani, Arvind

    2013-05-01

    Over the past couple of years highly diverse novel ssDNA viruses have been discovered. Here, we present the first ssDNA virus, Gastropod-associated circular ssDNA virus (GaCSV), recovered from a mollusc Amphibola crenata Martyn 1784, which is a deposit feeder that grazes micro-organisms and organic detritus on the surface of tidal mudflats. The GaCSV (2351 nt) genome contains two large bidirectionally transcribed ORFs. The smaller ORF (874 nt) has similarities to viral replication-associated protein (Rep) sequences of some bacteria and circoviruses, whereas the larger ORF (955 nt) does not relate to any sequences in public databases and we presume it potentially encodes the capsid protein. Phylogenetic analysis shows that the GaCSV Rep clusters with Rep-like sequences of bacterial origin, highlighting the role of ssDNA viruses in horizontal gene transfer. The occurrence of previously unknown viruses in organisms associated with human pollution is a relatively unexplored field. PMID:23364192

  16. 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. PMID:12961834

  17. Work Sharing Case Studies.

    ERIC Educational Resources Information Center

    McCarthy, Maureen E.; And Others

    Designed to provide private sector employers with the practical information necessary to select and then to design and implement work sharing arrangements, this book presents case studies of some 36 work sharing programs. Topics covered in the case studies include the circumstances leading to adoption of the program, details of compensation and…

  18. 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…

  19. 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…

  20. 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

  1. 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

  2. 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.

  3. Chimpanzees share forbidden fruit.

    PubMed

    Hockings, Kimberley J; Humle, Tatyana; Anderson, James R; Biro, Dora; Sousa, Claudia; Ohashi, Gaku; Matsuzawa, Tetsuro

    2007-01-01

    The sharing of wild plant foods is infrequent in chimpanzees, but in chimpanzee communities that engage in hunting, meat is frequently used as a 'social tool' for nurturing alliances and social bonds. Here we report the only recorded example of regular sharing of plant foods by unrelated, non-provisioned wild chimpanzees, and the contexts in which these sharing behaviours occur. From direct observations, adult chimpanzees at Bossou (Republic of Guinea, West Africa) very rarely transferred wild plant foods. In contrast, they shared cultivated plant foods much more frequently (58 out of 59 food sharing events). Sharing primarily consists of adult males allowing reproductively cycling females to take food that they possess. We propose that hypotheses focussing on 'food-for-sex and -grooming' and 'showing-off' strategies plausibly account for observed sharing behaviours. A changing human-dominated landscape presents chimpanzees with fresh challenges, and our observations suggest that crop-raiding provides adult male chimpanzees at Bossou with highly desirable food commodities that may be traded for other currencies.

  4. Shared-Reality Development in Childhood.

    PubMed

    Higgins, E Tory

    2016-07-01

    Many significant changes occur during human childhood, including cognitive, social-cognitive, and socioemotional changes. This article reviews some key phenomena associated with some of these changes and attempts to capture them within a single conceptual umbrella-changes in children's shared realities with others Shared reality is the experience that you have an inner state about something (e.g., a feeling or belief or concern about something) that is shared by others (a person or group). Four phases of shared-reality development are proposed: Phase 1 (6-12 months) shared feelings; Phase 2 (18-24 months) shared practices; Phase 3 (3-5 years) shared self-guides; Phase 4 (9-13 years) shared coordinated roles In each phase, a new way that children interact with and relate to others emerges, and the emergence of each new shared-reality mode has significant self-regulatory and social consequences. These consequences include both major benefits for children and potential costs-trade-offs of being human. PMID:27474136

  5. Shared-Reality Development in Childhood.

    PubMed

    Higgins, E Tory

    2016-07-01

    Many significant changes occur during human childhood, including cognitive, social-cognitive, and socioemotional changes. This article reviews some key phenomena associated with some of these changes and attempts to capture them within a single conceptual umbrella-changes in children's shared realities with others Shared reality is the experience that you have an inner state about something (e.g., a feeling or belief or concern about something) that is shared by others (a person or group). Four phases of shared-reality development are proposed: Phase 1 (6-12 months) shared feelings; Phase 2 (18-24 months) shared practices; Phase 3 (3-5 years) shared self-guides; Phase 4 (9-13 years) shared coordinated roles In each phase, a new way that children interact with and relate to others emerges, and the emergence of each new shared-reality mode has significant self-regulatory and social consequences. These consequences include both major benefits for children and potential costs-trade-offs of being human.

  6. Sharing a Faculty Position.

    ERIC Educational Resources Information Center

    O'Kane, Patricia K.; Meyer, Mary

    1982-01-01

    Describes the experience of two nursing faculty members who shared an assistant professor of nursing position. Discusses positive and negative aspects of the experience and notes that a unified and creative approach must be taken for it to succeed. (JOW)

  7. 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.

  8. Shared decision making

    MedlinePlus

    ... Shared decision making to improve care and reduce costs. N Engl J Med . 2013 Jan 3;368(1):6-8. ... UW Medicine, School of Medicine, University of Washington, Seattle, WA. Also reviewed by David ...

  9. 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)

  10. Secure Information Sharing

    2005-09-09

    We are develoing a peer-to-peer system to support secure, location independent information sharing in the scientific community. Once complete, this system will allow seamless and secure sharing of information between multiple collaborators. The owners of information will be able to control how the information is stored, managed. ano shared. In addition, users will have faster access to information updates within a collaboration. Groups collaborating on scientific experiments have a need to share information and data.more » This information and data is often represented in the form of files and database entries. In a typical scientific collaboration, there are many different locations where data would naturally be stored. This makes It difficult for collaborators to find and access the information they need. Our goal is to create a lightweight file-sharing system that makes it’easy for collaborators to find and use the data they need. This system must be easy-to-use, easy-to-administer, and secure. Our information-sharing tool uses group communication, in particular the InterGroup protocols, to reliably deliver each query to all of the current participants in a scalable manner, without having to discover all of their identities. We will use the Secure Group Layer (SGL) and Akenti to provide security to the participants of our environment, SGL will provide confldentiality, integrity, authenticity, and authorization enforcement for the InterGroup protocols and Akenti will provide access control to other resources.« less

  11. Information partnerships--shared data, shared scale.

    PubMed

    Konsynski, B R; McFarlan, F W

    1990-01-01

    How can one company gain access to another's resources or customers without merging ownership, management, or plotting a takeover? The answer is found in new information partnerships, enabling diverse companies to develop strategic coalitions through the sharing of data. The key to cooperation is a quantum improvement in the hardware and software supporting relational databases: new computer speeds, cheaper mass-storage devices, the proliferation of fiber-optic networks, and networking architectures. Information partnerships mean that companies can distribute the technological and financial exposure that comes with huge investments. For the customer's part, partnerships inevitably lead to greater simplification on the desktop and more common standards around which vendors have to compete. The most common types of partnership are: joint marketing partnerships, such as American Airline's award of frequent flyer miles to customers who use Citibank's credit card; intraindustry partnerships, such as the insurance value-added network service (which links insurance and casualty companies to independent agents); customer-supplier partnerships, such as Baxter Healthcare's electronic channel to hospitals for medical and other equipment; and IT vendor-driven partnerships, exemplified by ESAB (a European welding supplies and equipment company), whose expansion strategy was premised on a technology platform offered by an IT vendor. Partnerships that succeed have shared vision at the top, reciprocal skills in information technology, concrete plans for an early success, persistence in the development of usable information for all partners, coordination on business policy, and a new and imaginative business architecture.

  12. 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.

  13. TEL (ETV6)-AML1 (RUNX1) initiates self-renewing fetal pro-B cells in association with a transcriptional program shared with embryonic stem cells in mice.

    PubMed

    Tsuzuki, Shinobu; Seto, Masao

    2013-02-01

    The initial steps involved in the pathogenesis of acute leukemia are poorly understood. The TEL-AML1 fusion gene usually arises before birth, producing a persistent and covert preleukemic clone that may convert to precursor B cell leukemia following the accumulation of secondary genetic "hits." Here, we show that TEL-AML1 can induce persistent self-renewing pro-B cells in mice. TEL-AML1+ cells nevertheless differentiate terminally in the long term, providing a "window" period that may allow secondary genetic hits to accumulate and lead to leukemia. TEL-AML1-mediated self-renewal is associated with a transcriptional program shared with embryonic stem cells (ESCs), within which Mybl2, Tgif2, Pim2, and Hmgb3 are critical and sufficient components to establish self-renewing pro-B cells. We further show that TEL-AML1 increases the number of leukemia-initiating cells that are generated in collaboration with additional genetic hits, thus providing an overall basis for the development of novel therapeutic and preventive measures targeting the TEL-AML1-associated transcriptional program. PMID:23135987

  14. 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. PMID:26163733

  15. 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.

  16. 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

  17. 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

  18. 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.…

  19. A Shared Praxis Approach.

    ERIC Educational Resources Information Center

    Street, James L.

    1988-01-01

    Develops an educational philosophy for Christian religious education as it touches the AIDS crisis. Grounded in Thomas Groome's "shared Christian praxis" model and directed toward religious educators, the philosophy contains five components: present action, critical reflection, dialog, story, and vision. Examines each component, stating that…

  20. Sharing Expertise: Consulting

    ERIC Educational Resources Information Center

    Graves, Bill

    2011-01-01

    A special breed of superintendents who have developed expertise in a particular area find ways of sharing it in other venues as outside consultants. They pull extra duty to put their special skills into practice, to give back to their communities, to stay current and grounded in the field, or to enhance their professional reputations. They teach…

  1. 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…

  2. Bidirectional Quantum States Sharing

    NASA Astrophysics Data System (ADS)

    Peng, Jia-Yin; Bai, Ming-qiang; Mo, Zhi-Wen

    2016-05-01

    With the help of the shared entanglement and LOCC, multidirectional quantum states sharing is considered. We first put forward a protocol for implementing four-party bidirectional states sharing (BQSS) by using eight-qubit cluster state as quantum channel. In order to extend BQSS, we generalize this protocol from four sharers to multi-sharers utilizing two multi-qubit GHZ-type states as channel, and propose two multi-party BQSS schemes. On the other hand, we generalize the three schemes from two senders to multi-senders with multi GHZ-type states of multi-qubit as quantum channel, and give a multidirectional quantum states sharing protocol. In our schemes, all receivers can reconstruct the original unknown single-qubit state if and only if all sharers can cooperate. Only Pauli operations, Bell-state measurement and single-qubit measurement are used in our schemes, so these schemes are easily realized in physical experiment and their successful probabilities are all one.

  3. Hints on Sharing Books.

    ERIC Educational Resources Information Center

    Dorsey, Mary E., Comp.; Horne, Ulysses G., Comp.

    Based on the realization that each child must be given the opportunity to develop as a unique individual and that exposure to books expands a child's world, stimulating his creative thinking and his desire for new experiences, this booklet presents in outline form a variety of suggestions for encouraging children to share the books they have read.…

  4. 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.…

  5. 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…

  6. Think before You Share

    ERIC Educational Resources Information Center

    Read, Brock

    2006-01-01

    Students in the US are increasingly discovering that online socializing is far from private and that sharing personal details on social-networking Web sites, such as Facebook, can have unintended consequences. A growing number of colleges are moving to disabuse students of the notion that the Internet is their private playground and what they type…

  7. 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.

  8. Breastfeeding, Bed-Sharing, and Maternal Cortisol.

    PubMed

    Simon, Clarissa D; Adam, Emma K; McKinney, Chelsea O; Krohn, Julie B; Shalowitz, Madeleine U

    2016-05-01

    Prior studies have found that close mother-child sleep proximity helps increase rates of breastfeeding, and breastfeeding itself is linked to better maternal and infant health. In this study, we examine whether breastfeeding and infant bed-sharing are related to daily rhythms of the stress-responsive hormone cortisol. We found that bed-sharing was related to flatter diurnal cortisol slopes, and there was a marginal effect for breastfeeding to predict steeper cortisol slopes. Furthermore, mothers who breastfeed but do not bed-share had the steepest diurnal cortisol slopes, whereas mothers who bed-shared and did not breastfeed had the flattest slopes (P < .05). These results were significant after controlling for subjective sleep quality, perceived stress, depression, socioeconomic status, race, and maternal age. Findings from this study indicate that infant parenting choices recommended for infants (breastfeeding and separate sleep surfaces for babies) may also be associated with more optimal stress hormone profiles for mothers. PMID:26330120

  9. Shared Activity Coordination

    NASA Technical Reports Server (NTRS)

    Clement, Bradley J.; Barrett, Anthony C.

    2003-01-01

    Interacting agents that interleave planning and execution must reach consensus on their commitments to each other. In domains where agents have varying degrees of interaction and different constraints on communication and computation, agents will require different coordination protocols in order to efficiently reach consensus in real time. We briefly describe a largely unexplored class of real-time, distributed planning problems (inspired by interacting spacecraft missions), new challenges they pose, and a general approach to solving the problems. These problems involve self-interested agents that have infrequent communication but collaborate on joint activities. We describe a Shared Activity Coordination (SHAC) framework that provides a decentralized algorithm for negotiating the scheduling of shared activities in a dynamic environment, a soft, real-time approach to reaching consensus during execution with limited communication, and a foundation for customizing protocols for negotiating planner interactions. We apply SHAC to a realistic simulation of interacting Mars missions and illustrate the simplicity of protocol development.

  10. 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.

  11. Shared health governance.

    PubMed

    Ruger, Jennifer Prah

    2011-07-01

    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

  12. 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

  13. Shared health governance.

    PubMed

    Ruger, Jennifer Prah

    2011-07-01

    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.

  14. Bonobos Share with Strangers

    PubMed Central

    Tan, Jingzhi; Hare, Brian

    2013-01-01

    Humans are thought to possess a unique proclivity to share with others – including strangers. This puzzling phenomenon has led many to suggest that sharing with strangers originates from human-unique language, social norms, warfare and/or cooperative breeding. However, bonobos, our closest living relative, are highly tolerant and, in the wild, are capable of having affiliative interactions with strangers. In four experiments, we therefore examined whether bonobos will voluntarily donate food to strangers. We show that bonobos will forego their own food for the benefit of interacting with a stranger. Their prosociality is in part driven by unselfish motivation, because bonobos will even help strangers acquire out-of-reach food when no desirable social interaction is possible. However, this prosociality has its limitations because bonobos will not donate food in their possession when a social interaction is not possible. These results indicate that other-regarding preferences toward strangers are not uniquely human. Moreover, language, social norms, warfare and cooperative breeding are unnecessary for the evolution of xenophilic sharing. Instead, we propose that prosociality toward strangers initially evolves due to selection for social tolerance, allowing the expansion of individual social networks. Human social norms and language may subsequently extend this ape-like social preference to the most costly contexts. PMID:23300956

  15. The shared reward dilemma.

    PubMed

    Cuesta, J A; Jiménez, R; Lugo, H; Sánchez, A

    2008-03-21

    One of the most direct human mechanisms of promoting cooperation is rewarding it. We study the effect of sharing a reward among cooperators in the most stringent form of social dilemma, namely the prisoner's dilemma (PD). Specifically, for a group of players that collect payoffs by playing a pairwise PD game with their partners, we consider an external entity that distributes a fixed reward equally among all cooperators. Thus, individuals confront a new dilemma: on the one hand, they may be inclined to choose the shared reward despite the possibility of being exploited by defectors; on the other hand, if too many players do that, cooperators will obtain a poor reward and defectors will outperform them. By appropriately tuning the amount to be shared a vast variety of scenarios arises, including the traditional ones in the study of cooperation as well as more complex situations where unexpected behavior can occur. We provide a complete classification of the equilibria of the n-player game as well as of its evolutionary dynamics.

  16. Shared mission operations concept

    NASA Technical Reports Server (NTRS)

    Spradlin, Gary L.; Rudd, Richard P.; Linick, Susan H.

    1994-01-01

    Historically, new JPL flight projects have developed a Mission Operations System (MOS) as unique as their spacecraft, and have utilized a mission-dedicated staff to monitor and control the spacecraft through the MOS. NASA budgetary pressures to reduce mission operations costs have led to the development and reliance on multimission ground system capabilities. The use of these multimission capabilities has not eliminated an ongoing requirement for a nucleus of personnel familiar with a given spacecraft and its mission to perform mission-dedicated operations. The high cost of skilled personnel required to support projects with diverse mission objectives has the potential for significant reduction through shared mission operations among mission-compatible projects. Shared mission operations are feasible if: (1) the missions do not conflict with one another in terms of peak activity periods, (2) a unique MOS is not required, and (3) there is sufficient similarity in the mission profiles so that greatly different skills would not be required to support each mission. This paper will further develop this shared mission operations concept. We will illustrate how a Discovery-class mission would enter a 'partner' relationship with the Voyager Project, and can minimize MOS development and operations costs by early and careful consideration of mission operations requirements.

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

    PubMed

    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

    2015-06-16

    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.

  18. 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

  19. 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…

  20. 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.

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

    PubMed

    Van Tuyl, Steven; Whitmire, Amanda L

    2016-01-01

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

  2. 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…

  3. Examining impulsivity as an endophenotype using a behavioral approach: a DRD2 TaqI A and DRD4 48-bp VNTR association study

    PubMed Central

    Eisenberg, Dan TA; MacKillop, James; Modi, Meera; Beauchemin, Joshua; Dang, David; Lisman, Stephen A; Lum, J Koji; Wilson, David S

    2007-01-01

    Background Research on the genetic basis for impulsivity has revealed an array of ambiguous findings. This may be a result of limitations to self-report assessments of impulsivity. Behavioral measures that assess more narrowly defined aspects of impulsivity may clarify genetic influences. This study examined the relationship between possession of the DRD2 TaqI A and DRD4 48 bp VNTR genetic polymorphisms and performance on a behavioral measure of impulsivity, the delay discounting task (DDT), and three traditional self-report measures. Methods 195 individuals (42% male) were recruited from a university campus and were assessed in small group sessions using personal computers. Genotyping was conducted using previously established protocols. For the DRD2 TaqI A locus, individuals were designated as possessing at least one copy of the A1 allele (A1+) or not (A1-), and for the DRD4 48-bp VNTR locus, individuals were designated as having at least one long allele (7 repeats or longer, L+) or not (L-). Principal analyses used multiple univariate factorial 2 (A1+/A1-) × 2 (L+/L-) analyses of variance. Results A significant main effect of A1+ status on DDT performance was evident (p = .006) as well as a significant interaction effect (p = .006) between both genes. No other significant effects were evident on the self-report measures, with the exception of a trend toward an interaction effect on the Sensation Seeking Scale. Exploratory analyses suggested that the significant effects were not a function of population stratification or gender. Discussion These data suggest that the DRD2 TaqI A and DRD4 VNTR polymorphisms influence impulsivity as measured with a delay discounting task. Specifically, these findings suggest that an interaction between the functional effects of the two unlinked genotypes results in significant difference in the balance of mesolimbic dopaminergic activation relative to frontal-parietal activation. However, these findings are also the first in this area and must be replicated. Conclusion These findings suggest a meaningful interaction between the DRD2 TaqI A and DRD4 VNTR polymorphisms in the expression of impulsivity and provide initial support for the utility of using behavioral measures for clarifying genetic influences on impulsivity. PMID:17214892

  4. Vaccines, our shared responsibility.

    PubMed

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

    2015-05-01

    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. PMID:25749248

  5. Vaccines, our shared responsibility.

    PubMed

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

    2015-05-01

    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.

  6. 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.

  7. Job-Sharing the Principalship.

    ERIC Educational Resources Information Center

    Brown, Shelley; Feltham, Wendy

    1997-01-01

    The coprincipals of a California elementary school share their ideas for building a successful job-sharing partnership. They suggest it is important to find the right partner, develop and present a job-sharing proposal, establish systems of communication with each other, evaluate one's progress, focus on the principalship, and provide leadership…

  8. 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…

  9. 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…

  10. Cloning and characterization of the novel thyroid and eye muscle shared protein G2s: autoantibodies against G2s are closely associated with ophthalmopathy in patients with Graves' hyperthyroidism.

    PubMed

    Gunji, K; De Bellis, A; Li, A W; Yamada, M; Kubota, S; Ackrell, B; Wengrowicz, S; Bellastella, A; Bizzarro, A; Sinisi, A; Wall, J R

    2000-04-01

    Serum autoantibodies against eye muscle antigens are closely linked with thyroid-associated ophthalmopathy (TAO), although their significance is unclear. The two antigens that are most often recognized are eye muscle membrane proteins with molecular masses of 55 and 64 kDa, as determined from immunoblotting with crude human or porcine eye muscle membranes. We cloned a fragment of the 55-kDa protein by screening an eye muscle expression library with affinity-purified anti-55 kDa protein antibody prepared from a TAO patient's serum. A complementary DNA (cDNA) encoding a novel protein, which we have called G2s, was sequenced on both strands, and its size was 411 bp. The open reading frame of G2s corresponded to a 121-amino acid peptide with a size of 1.4 kb. Using the rapid amplification of 5'-cDNA ends technique we were able to clone an additional 0.3 kb of the protein. G2s did not share significant homologies with any other entered protein in computer databases and had one putative transmembrane domain. Using the 1.4 kb cDNA as probe in Northern blotting of a panel of messenger ribonucleic acids prepared from human tissues, the parent protein was shown to correspond to a large molecule of about 5.8 kb with a calculated molecular mass of approximately 220 kDa, consistent with earlier immunoblot studies performed in the absence of reducing agents. G2s was strongly expressed in eye muscle, thyroid, and other skeletal muscle and to a lesser extent in pancreas, liver, lung, and heart muscle, but not in kidney or orbital fibroblasts. We tested sera from patients with Graves' hyperthyroidism with and without ophthalmopathy and from control patients and subjects for antibodies against a G2s fusion protein by immunoblotting and enzyme-linked immunosorbent assay. In immunoblotting, antibodies reactive with G2s were identified in 70% of patients with TAO of less than 3 yr duration, 53% with TAO of more than 3 yr duration, 36% with Graves' hyperthyroidism without evident

  11. 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. PMID:26406139

  12. 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.

  13. Sharing Medicine: The Candidacy of Medicines and Other Household Items for Sharing, Dominican Republic

    PubMed Central

    Dohn, Michael N.; Pilkington, Hugo

    2014-01-01

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

  14. 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.

  15. 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.

  16. 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.

  17. 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

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

    PubMed Central

    2016-01-01

    Sharing of research data has begun to gain traction in many areas of the sciences in the past few years because of changing expectations from the scientific community, funding agencies, and academic journals. National Science Foundation (NSF) requirements for a data management plan (DMP) went into effect in 2011, with the intent of facilitating the dissemination and sharing of research results. Many projects that were funded during 2011 and 2012 should now have implemented the elements of the data management plans required for their grant proposals. In this paper we define ‘data sharing’ and present a protocol for assessing whether data have been shared and how effective the sharing was. We then evaluate the data sharing practices of researchers funded by the NSF at Oregon State University in two ways: by attempting to discover project-level research data using the associated DMP as a starting point, and by examining data sharing associated with journal articles that acknowledge NSF support. Sharing at both the project level and the journal article level was not carried out in the majority of cases, and when sharing was accomplished, the shared data were often of questionable usability due to access, documentation, and formatting issues. We close the article by offering recommendations for how data producers, journal publishers, data repositories, and funding agencies can facilitate the process of sharing data in a meaningful way. PMID:26886581

  19. 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

  20. 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

  1. The science of sharing and the sharing of science.

    PubMed

    Milkman, Katherine L; Berger, Jonah

    2014-09-16

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

  2. Sharing the Preservation Burden

    SciTech Connect

    Giaretta, D.

    2008-07-01

    Preserving digitally encoded information which is not just to be rendered, as a document, but which must processed, like data, is even harder than one might think, because understandability of the information which is encoded in the digital object(s) is what is required. Information about Nuclear Waste will include both documents as well as data. Moreover one must be able to understand the relationship between the many individual pieces of information. Furthermore the volume of information involved will require us to allow automated processing of such information. Preserving the ability to understand and process digitally encoded information over long periods of time is especially hard when so many things will change, including hardware, software, environment and the tacit and implicit knowledge that people have. Since we cannot predict these changes this cannot be just a one-off action; continued effort is required. However it seems reasonable to say that no organization, project or person can ever say for certain that their ability to provide this effort is going to last forever. What can be done? Can anything be guaranteed? Probably not guaranteed - but at least one can try to reduce the risk of losing the information. We argue that if no single organization, project or person can guarantee funding or effort (or even interest), then somehow we must share the 'preservation load', and this is more than a simple chain of preservation consisting of handing on the collection of bits from one holder to the next. Clearly the bits must be passed on (but may be transformed along the way), however something more is required - because of the need to maintain understandability, not just access. This paper describes the tools, techniques and infrastructure components which the CASPAR project is producing to help in sharing the preservation burden. In summary: CASPAR is attempting to use OAIS concepts rigorously and to the fullest extent possible, supplementing these where

  3. 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

  4. 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" (Marilyn…

  5. 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.

  6. 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.

  7. 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

  8. 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…

  9. 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…

  10. 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…

  11. 47 CFR 27.1305 - Shared wireless broadband network.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  12. 47 CFR 90.1405 - Shared wireless broadband network.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  13. Folie a Trois: Atypical Presentation as Shared Transient Psychotic Episode

    PubMed Central

    Aravind, V. K.; Krishnaram, V. D.; Vimala, Rupavathy A.

    2014-01-01

    Shared psychotic disorder or induced delusional disorder can occur in different clinical settings and profile and is not uncommon. A case of Folie a trois with atypical clinical presentation as shared acute transient episode in a bereavement setting is reported. Suggestibility, close association and intimacy of the affected persons and major stress as psychological trigger act as psychopathological factors. PMID:24860230

  14. 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. PMID:23600613

  15. 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…

  16. 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.

  17. 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.

  18. Job Sharing in the Schools.

    ERIC Educational Resources Information Center

    Moorman, Barbara; 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 is a guide for teachers and administrators on the implementation and use of job sharing…

  19. Knowledge Sharing: Developing from within

    ERIC Educational Resources Information Center

    Patrick, Keith; Dotsika, Fefie

    2007-01-01

    Purpose: If collaboration and knowledge sharing lie at the core of providing added-value to either services or products can we improve this process? The purpose of this paper is to suggest that it can be improved and this lies in how we develop the systems that support collaboration and knowledge sharing. This can be achieved within the…

  20. 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…

  1. The Future of Shared Governance

    ERIC Educational Resources Information Center

    Crellin, Matthew A.

    2010-01-01

    Higher education has relied on the power of collaborative decision making on college and university campuses through the model of shared governance since the early 1900s. However, the principles of shared governance are now more thoroughly tested than ever before. In response to these simultaneous pressures and challenges, the leadership of…

  2. Shared Governance: The Next Generation.

    ERIC Educational Resources Information Center

    Lovas, John C.; And Others

    This document contains three papers which present information from various perspectives on aspects of shared governance at De Anza College, in Cupertino, California. First, "Shared Governance: The Next Generation," by John C. Lovas, provides a brief history of governance in the Foothill-De Anza Community College District, and suggests some of the…

  3. 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…

  4. Food sharing and social cognition.

    PubMed

    Legg, Edward William; Ostojić, Ljerka; Clayton, Nicola Susan

    2015-01-01

    Many non-human animals share food with each other, with kin, mates, and other unrelated individuals. When individuals share food with others they lose a valuable resource. Thus, traditionally much research has investigated how this behavior can be an evolutionarily stable strategy. Only recently has food-sharing behavior been exploited to investigate non-human cognition. Certain evolutionarily stable strategies that have been proposed as accounts for food-sharing behaviors, such as reciprocity and interchange, may rely on complex cognitive abilities. In these cases, individuals may calculate the benefit they may receive from sharing with the recipient. In some species, sharing of food can facilitate the recipients' rate and extent of learning. This form of teaching may be cognitively complex if the donor takes into account the level of the recipient's abilities. In addition, an animal's food-sharing behavior, which in itself may be based on a simple cognitive mechanism, could be used as a tool to investigate the extent to which the individual may be capable of complex cognitive abilities, for example, mental-state attribution. These three areas of research, reciprocity, teaching, and mental-state attribution, illustrate how food-sharing behavior can be used as a valuable natural behavior to investigate cognition in non-human animals. PMID:26263068

  5. Is shared governance still relevant?

    PubMed

    Porter-O'Grady, T

    2001-10-01

    Is shared governance still relevant in this era of significant changes in healthcare? Requisites to support nurses and others are more important now than ever before. Shared decision-making is not only relevant, it is essential. The road to empowerment is not easy. Many patterns of organization and relationship must be changed forever through commitment and leadership today.

  6. Sharing Public Health Research Data

    PubMed Central

    Bull, Susan

    2015-01-01

    It is increasingly recognized that effective and appropriate data sharing requires the development of models of good data-sharing practice capable of taking seriously both the potential benefits to be gained and the importance of ensuring that the rights and interests of participants are respected and that risk of harms is minimized. Calls for the greater sharing of individual-level data from biomedical and public health research are receiving support among researchers and research funders. Despite its potential importance, data sharing presents important ethical, social, and institutional challenges in low-income settings. In this article, we report on qualitative research conducted in five low- and middle-income countries exploring the experiences of key research stakeholders and their views about what constitutes good data-sharing practice. PMID:26297744

  7. 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.

  8. 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. PMID:26845819

  9. 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.

  10. 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. PMID:25140334

  11. 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

  12. 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.

  13. 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. PMID:26607304

  14. 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.

  15. 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.

  16. 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 PMID:21789944

  17. Information Sharing and Environmental Policies

    PubMed Central

    Antoniou, Fabio; Koundouri, Phoebe; Tsakiris, Nikos

    2010-01-01

    Based on the assumption that in a standard eco-dumping model governments are uncertain about future product demand and allowing governments to obtain information from firms, we examine governments’ and firms’ incentives to share information. We show that when governments regulate polluting firms through emission standards, then governments and firms will reach an agreement concerning information sharing. The opposite holds when governments regulate pollution through emission taxes. PMID:21139849

  18. 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.

  19. 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.

  20. 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.

  1. Capacity sharing of water reservoirs

    NASA Astrophysics Data System (ADS)

    Dudley, Norman J.; Musgrave, Warren F.

    1988-05-01

    The concept of a water use property right is developed which does not apply to water volumes as such but to a share of the capacity (not contents) of river storage reservoirs and their inflows. The shareholders can withdraw water from their share over time in accordance with their preferences for stability of water deliveries. The reservoir authority does not manage reservoir releases but keeps record of individual shareholder's withdrawals and net inflows to monitor the quantity of water in each shareholder's capacity share. A surplus of total reservoir contents over the sum of the contents of the individual shareholder's capacity shares will accrue over time. Two different criteria for its periodic distribution among shareholders are compared. A previous paper Dudley (this issue(b)) noted a loss of short-run economic efficiency as reservoir and farm management decision making become separated. This is largely overcome by capacity sharing which allows each user to integrate the management of their portion of the reservoir and their farming operations. The nonattenuated nature of the capacity sharing water rights also promotes long-run economic efficiency.

  2. 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.

  3. Job Sharing--Opportunities or Headaches?

    ERIC Educational Resources Information Center

    Leighton, Patricia

    1986-01-01

    Discusses the issue of job sharing as a new alternative available to workers. Topics covered include (1) a profile of job sharers, (2) response to job sharing, (3) establishing a job share, (4) job sharing in operation, and (5) legal analysis of job sharing. (CH)

  4. 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.

  5. Shared resources, shared costs--leveraging biocuration resources.

    PubMed

    Orchard, Sandra; Hermjakob, Henning

    2015-01-01

    The manual curation of the information in biomedical resources is an expensive task. This article argues the value of this approach in comparison with other apparently less costly options, such as automated annotation or text-mining, then discusses ways in which databases can make cost savings by sharing infrastructure and tool development. Sharing curation effort is a model already being adopted by several data resources. Approaches taken by two of these, the Gene Ontology annotation effort and the IntAct molecular interaction database, are reviewed in more detail. These models help to ensure long-term persistence of curated data and minimizes redundant development of resources by multiple disparate groups.

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

    PubMed Central

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

    2006-01-01

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

  7. 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

  8. CATCHR, HOPS and CORVET tethering complexes share a similar architecture.

    PubMed

    Chou, Hui-Ting; Dukovski, Danijela; Chambers, Melissa G; Reinisch, Karin M; Walz, Thomas

    2016-08-01

    We show here that the Saccharomyces cerevisiae GARP complex and the Cog1-4 subcomplex of the COG complex, both members of the complexes associated with tethering containing helical rods (CATCHR) family of multisubunit tethering complexes, share the same subunit organization. We also show that HOPS, a tethering complex acting in the endolysosomal pathway, shares a similar architecture, thus suggesting that multisubunit tethering complexes use related structural frameworks. PMID:27428774

  9. Best Practices for Data Sharing in Phylogenetic Research

    PubMed Central

    Cranston, Karen; Harmon, Luke J.; O'Leary, Maureen A.; Lisle, Curtis

    2014-01-01

    As phylogenetic data becomes increasingly available, along with associated data on species’ genomes, traits, and geographic distributions, the need to ensure data availability and reuse become more and more acute. In this paper, we provide ten “simple rules” that we view as best practices for data sharing in phylogenetic research. These rules will help lead towards a future phylogenetics where data can easily be archived, shared, reused, and repurposed across a wide variety of projects. PMID:24987572

  10. 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…

  11. Data sharing for pharmacokinetic studies.

    PubMed

    Anderson, Brian J; Merry, Alan F

    2009-10-01

    Pooling data from different pediatric studies can provide a single robust pharmacokinetic analysis that allows covariate analysis and hypothesis testing. Data sharing should be driven by the altruistic purpose of improving drug understanding to the clinical benefit of children. Electronic communications have rendered the sharing of data relatively easy, and data sharing within the wider scientific community has become commonplace. Data sharing allows verification of results, save costs and time, allows new interpretation of old data, and can fulfill teaching benefits. It may stimulate cooperative competition between researchers and allow individual researchers to concentrate on unique aspects of the scientific puzzle. However, there is occasionally a reluctance to share, in part because of fear of others stealing the hard work of a research group, which may not be recognized in subsequent publications that reuse data. Providing data may require additional effort for presentation in a suitable format. Data may be abused or used for purposes other than those for which they were collected. Propriety claims may limit access to industry-sponsored drug research. The question of who has ownership of data is contentious. Investigators often consider data they have collected to be their own property. Reputations and grants may be hinge on ownership of a data set. However, other team members, institutions, funding agencies, and the public also have a stake. The difficulties identified in the general scientific community also apply to data sharing for pediatric pharmacokinetic studies. There are few clearly established rules at present, and consideration of the issues hinges on ethical and philosophical arguments. The development of databases will depend on collaboration and cooperation and greater clarity and consensus over appropriate processes and procedures. PMID:19558615

  12. 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.

  13. A cross-sectional population-based study on the association of personality traits with anxiety and psychological stress: Joint modeling of mixed outcomes using shared random effects approach

    PubMed Central

    Feizi, Awat; Keshteli, Ammar Hassanzadeh; Nouri, Fatemeh; Roohafza, Hamidreza; Adibi, Peyman

    2014-01-01

    Background: Previous studies have showed some evidences about the relationship between personality traits particularly neuroticism and extroversion, separately, with psychological stress and anxiety. In the current study, we clarified the magnitude of joint interdependence (co-morbidity) of anxiety (continuous) and Psychological stress (dichotomous) as dependent variables of mixed type with five-factor personality traits as independent variables. Materials and Methods: Data from 3180 participants who attended in the cross-sectional population-based “study on the epidemiology of psychological, alimentary health and nutrition” and completed self-administered questionnaires about demographic and life style, gastrointestinal disorders, personality traits, perceived intensity of stress, social support, and psychological outcome was analyzed using shared random effect approach in R Free software. Results: The results indicated high scores of neuroticism increase the chance of high psychological stress (odds ratio [OR] = 5.1; P < 0.001) and anxiety score (B = 1.73; P < 0.001) after adjustment for the probable confounders. In contrast, those who had higher scores of extraversion and conscientiousness experienced lower levels of anxiety score (B = −0.54 and −0.23, respectively, P < 0.001) and psychological stress (OR = 0.36 and 0.65, respectively, P < 0.001). Furthermore, higher score of agreeableness had significant negative relationship with anxiety (B = −0.32, P < 0.001). Conclusion: The present study indicated that the scores of neuroticism, extraversion, agreeableness and conscientiousness strongly predict both anxiety and psychological stress in Iranian adult population. Due to likely mechanism of genetic and environmental factors on the relationships between personality traits and psychological disorders, it is suggested to perform longitudinal studies focusing on both genetic and environmental factors in Iranian population. PMID:25535497

  14. Job Sharing: One District's Experience.

    ERIC Educational Resources Information Center

    Lantz, Mahlon L.

    1983-01-01

    Describes responses of principals, teachers, and parents to a job sharing program instituted to reduce impact of staff layoffs. Principals were satisfied overall; teachers believed that students benefited from interaction with two instructors; and a majority of parents felt likewise. (TE)

  15. Shared Family Care Program Guidelines.

    ERIC Educational Resources Information Center

    Price, Amy; Barth, Richard P.

    Shared family care has been defined as the planned provision of out-of-home care to parents and their children so that the parents, supported by the host caregiver, cares for the child and works toward independent in-house care; this approach is an alternative to the trauma of separation and lack of continuity inherent to foster care placement.…

  16. Sharing Practice through Socratic Seminars

    ERIC Educational Resources Information Center

    Mangrum, Jennifer R.

    2010-01-01

    Developing systems and opportunities for effective dialogue is critical if schools wish to help teachers work collectively. One school used Socratic seminars, structured conversations about selected texts. These seminars helped teachers to build relationships, share practice, and change curriculum and policy. The seminars also were critical to…

  17. New "Teaching" Idea: Sharing Mistakes

    ERIC Educational Resources Information Center

    Zhou, Zhifa

    2007-01-01

    Learning from mistakes is one way of basic learning. Currently both primary and secondary schools, even colleges and universities, have focused on their teaching practice that students learn from their own mistakes, not from teachers'. This paper proposes that teachers share their own rational mistakes with their students in the process of…

  18. Interlibrary Cooperation and Resource Sharing.

    ERIC Educational Resources Information Center

    Kittel, Dorothy

    Based on fiscal year 1986 annual reports from 48 states, Guam, Puerto Rico, and the Virgin Islands, this report describes interlibrary cooperation and resource sharing activities supported by the Library Services and Construction Act (LSCA), Title III, funds. In response to the 1984 amendment to Title III (which required each state to include in…

  19. Interlibrary Cooperation and Resource Sharing.

    ERIC Educational Resources Information Center

    Kittel, Dorothy

    Based on fiscal year 1985 annual reports from 48 states, this report describes interlibrary cooperation and resource-sharing activities supported by Library Services and Construction Act (LSCA), Title III, funds during 1985. A summary of types of activities reported includes the establishment, maintenance, and expansion of communication networks…

  20. Sharing Writing through Computer Networking.

    ERIC Educational Resources Information Center

    Fey, Marion H.

    1997-01-01

    Suggests computer networking can support the essential purposes of the collaborative-writing movement, offering opportunities for sharing writing. Notes that literacy teachers are exploring the connectivity of computer networking through numerous designs that use either real-time or asynchronous communication. Discusses new roles for students and…

  1. 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…

  2. 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…

  3. A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

    PubMed Central

    Chouraki, V; De Bruijn, RFAG; Chapuis, J; Bis, JC; Reitz, C; Schraen, S; Ibrahim-Verbaas, CA; Grenier-Boley, B; Delay, C; Rogers, R; Demiautte, F; Mounier, A; Fitzpatrick, AL; Berr, C; Dartigues, J-F; Uitterlinden, AG; Hofman, A; Breteler, M; Becker, JT; Lathrop, M; Schupf, N; Alpérovitch, A; Mayeux, R; van Duijn, CM; Buée, L; Amouyel, P; Lopez, OL; Ikram, MA; Tzourio, C; Lambert, J-C

    2014-01-01

    Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides’ functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ1–40 and Aβ1–42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10−5). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ1–42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ1–42 secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites. PMID:24535457

  4. A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly.

    PubMed

    Chouraki, V; De Bruijn, R F A G; Chapuis, J; Bis, J C; Reitz, C; Schraen, S; Ibrahim-Verbaas, C A; Grenier-Boley, B; Delay, C; Rogers, R; Demiautte, F; Mounier, A; Fitzpatrick, A L; Berr, C; Dartigues, J-F; Uitterlinden, A G; Hofman, A; Breteler, M; Becker, J T; Lathrop, M; Schupf, N; Alpérovitch, A; Mayeux, R; van Duijn, C M; Buée, L; Amouyel, P; Lopez, O L; Ikram, M A; Tzourio, C; Lambert, J-C

    2014-12-01

    Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ1-40 and Aβ1-42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10(-)(5)). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ1-42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ1-42 secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.

  5. From shared data to sharing workflow: merging PACS and teleradiology.

    PubMed

    Benjamin, Menashe; Aradi, Yinon; Shreiber, Reuven

    2010-01-01

    Due to a host of technological, interface, operational and workflow limitations, teleradiology and PACS/RIS were historically developed as separate systems serving different purposes. PACS/RIS handled local radiology storage and workflow management while teleradiology addressed remote access to images. Today advanced PACS/RIS support complete site radiology workflow for attending physicians, whether on-site or remote. In parallel, teleradiology has emerged into a service of providing remote, off-hours, coverage for emergency radiology and to a lesser extent subspecialty reading to subscribing sites and radiology groups. When attending radiologists use teleradiology for remote access to a site, they may share all relevant patient data and participate in the site's workflow like their on-site peers. The operation gets cumbersome and time consuming when these radiologists serve multi-sites, each requiring a different remote access, or when the sites do not employ the same PACS/RIS/Reporting Systems and do not share the same ownership. The least efficient operation is of teleradiology companies engaged in reading for multiple facilities. As these services typically employ non-local radiologists, they are allowed to share some of the available patient data necessary to provide an emergency report but, by enlarge, they do not share the workflow of the sites they serve. Radiology stakeholders usually prefer to have their own radiologists perform all radiology tasks including interpretation of off-hour examinations. It is possible with current technology to create a system that combines the benefits of local radiology services to multiple sites with the advantages offered by adding subspecialty and off-hours emergency services through teleradiology. Such a system increases efficiency for the radiology groups by enabling all users, regardless of location, to work "local" and fully participate in the workflow of every site. We refer to such a system as SuperPACS. PMID

  6. Work-Sharing: Panacea or Palliative?

    ERIC Educational Resources Information Center

    Dawkins, Peter J.

    1983-01-01

    Recently, high unemployment and a high perceived rate of technological change have created interest in work-sharing. Definitions of different types of work-sharing and theoretical and practical issues related to work-sharing are covered. Work-sharing is not necessarily a panacea, but it does show the potential to help. (Author/IS)

  7. The Complete Guide to Job Sharing.

    ERIC Educational Resources Information Center

    Hohn, Marcia D.

    This booklet provides information on job sharing that resulted from the research and experience of the Merrimack Valley Job Sharing Project. An overview of the topic considers the need for job sharing, employer benefits, types of jobs shared, job division, benefits, employer costs and savings, financial considerations for job sharers, perspectives…

  8. 24 CFR 206.23 - Shared appreciation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... been no sale or transfer involving satisfaction of the mortgage at the time the mortgagee's share of... shared premium option (§ 206.107) may provide for shared appreciation. At the time the mortgage becomes... value is computed as follows: (1) If the mortgage balance at the time the mortgagee's share of...

  9. 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... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Cost share. 204.61...

  10. 50 CFR 85.40 - Cost sharing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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 or... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Cost sharing. 85.40 Section 85.40...

  11. Addressing Global Data Sharing Challenges

    PubMed Central

    Alter, George C.

    2015-01-01

    This issue of the Journal of Empirical Research on Human Research Ethics highlights the ethical issues that arise when researchers conducting projects in low- and middle-income countries seek to share the data they produce. Although sharing data is considered a best practice, the barriers to doing so are considerable and there is a need for guidance and examples. To that end, the authors of this article reviewed the articles in this special issue to identify challenges common to the five countries and to offer some practical advice to assist researchers in navigating this “uncharted territory,” as some termed it. Concerns around informed consent, data management, data dissemination, and validation of research contributions were cited frequently as particularly challenging areas, so the authors focused on these four topics with the goal of providing specific resources to consult as well as examples of successful projects attempting to solve many of the problems raised. PMID:26297753

  12. Addressing Global Data Sharing Challenges.

    PubMed

    Alter, George C; Vardigan, Mary

    2015-07-01

    This issue of the Journal of Empirical Research on Human Research Ethics highlights the ethical issues that arise when researchers conducting projects in low- and middle-income countries seek to share the data they produce. Although sharing data is considered a best practice, the barriers to doing so are considerable and there is a need for guidance and examples. To that end, the authors of this article reviewed the articles in this special issue to identify challenges common to the five countries and to offer some practical advice to assist researchers in navigating this "uncharted territory," as some termed it. Concerns around informed consent, data management, data dissemination, and validation of research contributions were cited frequently as particularly challenging areas, so the authors focused on these four topics with the goal of providing specific resources to consult as well as examples of successful projects attempting to solve many of the problems raised. PMID:26297753

  13. Addressing Global Data Sharing Challenges.

    PubMed

    Alter, George C; Vardigan, Mary

    2015-07-01

    This issue of the Journal of Empirical Research on Human Research Ethics highlights the ethical issues that arise when researchers conducting projects in low- and middle-income countries seek to share the data they produce. Although sharing data is considered a best practice, the barriers to doing so are considerable and there is a need for guidance and examples. To that end, the authors of this article reviewed the articles in this special issue to identify challenges common to the five countries and to offer some practical advice to assist researchers in navigating this "uncharted territory," as some termed it. Concerns around informed consent, data management, data dissemination, and validation of research contributions were cited frequently as particularly challenging areas, so the authors focused on these four topics with the goal of providing specific resources to consult as well as examples of successful projects attempting to solve many of the problems raised.

  14. Continual coordination through shared activities

    NASA Technical Reports Server (NTRS)

    Clement, Bradley J.; Barrett, Anthony C.

    2003-01-01

    Interacting agents that interleave planning and execution must reach consensus on their commitments to each other. In domains where agents have varying degrees of interaction and different constraints on communication and computation, agents will require different coordination protocols in order to efficiently reach consensus in real time. We briefly describe a largely unexplored class of realtime, distributed planning problems (inspired by interacting spacecraft missions), new challenges they pose, and a general approach to solving the problems. These problems involve self-interested agents that have infrequent communication but collaborate on joint activities. We describe a Shared Activity Coordination (SHAC) framework that provides a decentralized algorithm for negotiating the scheduling of shared activities over the lifetimes of separate missions, a soft, real-time approach to reaching consensus during execution with limited communication, and a foundation for customizing protocols for negotiating planner interactions. We apply SHAC to a realistic simulation of interacting Mars missions and illustrate the simplicity of protocol development.

  15. Sound-Color Associations in Psychosis-Prone Individuals.

    PubMed

    Berman, Brady; Serper, Mark

    2016-08-01

    Synesthetic-pseudosynesthetic characteristics have been hypothesized to be a schizophrenia endophenotype, a developmental feature, and/or a symptom of psychosis. Few studies to date, however, have examined whether individuals at risk for psychosis have synesthetic symptoms. We examined the relationship between hue and pitch in high psychosis prone (HP; n = 30) and low psychosis prone individuals (LP; n = 31). Synesthesia was evaluated using self-report and two performance-based tasks. Results revealed that HP subjects experienced more synesthetic experiences than the LP only on the self-report measure. These results suggest that high psychotic prone patients report unusual experiences but are no more likely to exhibit synesthesia than LP individuals. HP individuals, however, were more likely to choose shorter wavelength colors than LP individuals on performance tasks. These results are consistent with the notion that psychosis vulnerability is associated with a preference to light wavelengths associated with increasing emotional valence and negative affect. PMID:27218222

  16. 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...

  17. Population genetics and benefit sharing.

    PubMed

    Knoppers, B M

    2000-01-01

    The majority of international or national guidelines, specific to human genetics concentrate on actual or potential clinical applications. In contrast, the Ethics Committee of the Human Genome Organisation (HUGO) attempts to provide guidance to the bench scientists engaged in fundamental research in genomics prior to any clinical applications. Often confused as constituting the Human Genome Project (HGP) itself, HUGO's (Human Genome Organization) ultimate goal is to assist in the worldwide collaboration underpinning the HGP. It is an international organisation with 1,229 members in approximately 60 countries. The Ethics Committee is one of HUGO's six international advisory committees. Composed of experts from a number of countries and disciplines, the HUGO Ethics Committee promotes discussion and understanding of social, legal, and ethical issues as they relate to the conduct of, and knowledge derived from, the Genome Initiative. Currently, it has 13 members from 11 difference countries. It has produced statements on the conduct of genetic research, on cloning, and, has most recently presented a 'Statement on Benefit-Sharing', April 11, 2000. The Intellectual Property Committee of HUGO has been active in the controversial area of patenting. The issue of benefit-sharing is one that has its source in the mandate of both committees. How to avoid both commodification of the person through payment for access to DNA and biopiracy with no return to benefits to the families or community? While patents are a legitimate form of recognition for innovation, there seems to be no therapeutic exception to some of its stringent rules and the 'morality' exclusion has lain dormant. The HUGO 'Statement on Benefit-Sharing' examines the issues of defining community, common heritage, distributive justice and solidarity before arriving at its conclusions in benefit-sharing. This communication reviews some of these issues. PMID:11878345

  18. 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.

  19. Data sharing in Surface Science

    NASA Astrophysics Data System (ADS)

    Kitchin, John R.

    2016-05-01

    Surface Science has an editorial policy that atomic positions that are determined in a publication (experimental and computational) be made accessible to its readers. In this Prospective, we suggest an even broader need in data and methodology sharing. We illustrate an approach we have used to embed experimental and computational data as well as code in manuscripts and supporting information files, and we show how it results in reusable data and code.

  20. Mine or yours? Development of sharing in toddlers in relation to ownership understanding.

    PubMed

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

    2013-01-01

    To examine early developments in other-oriented resource sharing, fifty-one 18- and 24-month-old children were administered 6 tasks with toys or food that could be shared with an adult playmate who had none. On each task the playmate communicated her desire for the items in a series of progressively more explicit cues. Twenty-four-month-olds shared frequently and spontaneously. Eighteen-month-olds shared when given multiple opportunities and when the partner provided enough communicative support. Younger children engaged in self-focused and hypothesis-testing behavior in lieu of sharing more often than did older children. Ownership understanding, separately assessed, was positively associated with sharing and negatively associated with non-sharing behavior, independent of age and language ability. PMID:23145536

  1. Mine or yours? Development of sharing in toddlers in relation to ownership understanding.

    PubMed

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

    2013-01-01

    To examine early developments in other-oriented resource sharing, fifty-one 18- and 24-month-old children were administered 6 tasks with toys or food that could be shared with an adult playmate who had none. On each task the playmate communicated her desire for the items in a series of progressively more explicit cues. Twenty-four-month-olds shared frequently and spontaneously. Eighteen-month-olds shared when given multiple opportunities and when the partner provided enough communicative support. Younger children engaged in self-focused and hypothesis-testing behavior in lieu of sharing more often than did older children. Ownership understanding, separately assessed, was positively associated with sharing and negatively associated with non-sharing behavior, independent of age and language ability.

  2. 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

  3. 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.

  4. The Dash Data Sharing System

    NASA Technical Reports Server (NTRS)

    Hasan, David A.; Slaughter, Brooks

    1994-01-01

    The Data Sharing system (DASH) project was recently undertaken at NASA Johnson Space Center to introduce distributed data sharing into the Mission Control Center (MCC). Although the project focused on MCC communications, the solution is a general one. This paper describes that project. DASH allows applications to share data. It provides callable interfaces for applications wishing to export or import data. The system consists of several processes: publishers make exported data available to subscribers, which provide it to interested importing applications. A network registration service provides network location transparency, allowing the other processes to reside at arbitrary network locations. These processes act as intermediaries between external producing and consuming applications. DASH has been demonstrated in the MCC where it transmits Shuttle electrical bus data from the Bus Loss Smart System to the Configurable Realtime Analysis System. In addition, the Failure Impact and Procedure Analysis system used DASH to transmit Shuttle remote manipulator data from an expert system to a version of CRANS. DASH is currently being used to integrate a knowledge acquisition application and the CLIPS expert system shell.

  5. RACE pulls for shared control

    NASA Astrophysics Data System (ADS)

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

    1993-02-01

    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.

  6. RACE pulls for shared control

    NASA Astrophysics Data System (ADS)

    Leahy, Michael B., Jr.; Cassiday, Brian K.

    1992-11-01

    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. 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. The 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 ALCs 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.

  7. Drivers of parasite sharing among Neotropical freshwater fishes.

    PubMed

    Braga, Mariana P; Razzolini, Emanuel; Boeger, Walter A

    2015-03-01

    Because host-parasite interactions are so ubiquitous, it is of primary interest for ecologists to understand the factors that generate, maintain and constrain these associations. Phylogenetic comparative studies have found abundant evidence for host-switching to relatively unrelated hosts, sometimes related to diversification events, in a variety of host-parasite systems. For Monogenoidea (Platyhelminthes) parasites, it has been suggested that the co-speciation model alone cannot explain host occurrences, hence host-switching and/or non-vicariant modes of speciation should be associated with the origins and diversification of several monogenoid taxa. The factors that shape broad patterns of parasite sharing were investigated using path analysis as a way to generate hypotheses about the origins of host-parasite interactions between monogenoid gill parasites and Neotropical freshwater fishes. Parasite sharing was assessed from an interaction matrix, and explanatory variables included phylogenetic relationships, environmental preferences, biological traits and geographic distribution for each host species. Although geographic distribution of hosts and host ecology are important factors to understand host-parasite interactions, especially within host lineages that share a relatively recent evolutionary history, phylogeny had the strongest overall direct effect on parasite sharing. Phylogenetic contiguity of host communities may allow a 'stepping-stone' mode of host-switching, which increases parasite sharing. Our results reinforce the importance of including evolutionary history in the study of ecological associations, including emerging infectious diseases risk assessment.

  8. Drivers of parasite sharing among Neotropical freshwater fishes.

    PubMed

    Braga, Mariana P; Razzolini, Emanuel; Boeger, Walter A

    2015-03-01

    Because host-parasite interactions are so ubiquitous, it is of primary interest for ecologists to understand the factors that generate, maintain and constrain these associations. Phylogenetic comparative studies have found abundant evidence for host-switching to relatively unrelated hosts, sometimes related to diversification events, in a variety of host-parasite systems. For Monogenoidea (Platyhelminthes) parasites, it has been suggested that the co-speciation model alone cannot explain host occurrences, hence host-switching and/or non-vicariant modes of speciation should be associated with the origins and diversification of several monogenoid taxa. The factors that shape broad patterns of parasite sharing were investigated using path analysis as a way to generate hypotheses about the origins of host-parasite interactions between monogenoid gill parasites and Neotropical freshwater fishes. Parasite sharing was assessed from an interaction matrix, and explanatory variables included phylogenetic relationships, environmental preferences, biological traits and geographic distribution for each host species. Although geographic distribution of hosts and host ecology are important factors to understand host-parasite interactions, especially within host lineages that share a relatively recent evolutionary history, phylogeny had the strongest overall direct effect on parasite sharing. Phylogenetic contiguity of host communities may allow a 'stepping-stone' mode of host-switching, which increases parasite sharing. Our results reinforce the importance of including evolutionary history in the study of ecological associations, including emerging infectious diseases risk assessment. PMID:25283218

  9. The association of the HOPA(12bp) polymorphism with schizophrenia in the NIMH Genetics Initiative for Schizophrenia sample.

    PubMed

    Philibert, Robert A; Bohle, Phil; Secrest, Dianna; Deaderick, Jessica; Sandhu, Harinder; Crowe, Raymond; Black, Donald W

    2007-09-01

    HOPA (MED12) is an X-chromosome gene that codes for a critical member of the Mediator Complex, a group of proteins that regulates transcription via the nuclear receptor, Wnt and Receptor Tyrosine Kinase pathways. In prior association and meta-analyses, we have shown that the presence of an evolutionarily conserved, 12 bp (4 amino acid) insertional polymorphism in exon 43 of this gene is associated with increased risk for an endophenotype of schizophrenia. In this communication, we describe the results of our work with subjects and data from the National Institutes of Mental Health (NIMH) Genetics Initiative for Schizophrenia. We report that the presence of the HOPA(12bp) polymorphism is associated with increased risk for schizophrenia in subjects of European ancestry. In the light of this new study and the prior wealth of clinical and basic science data, we conclude that the HOPA(12bp) allele is a risk factor for schizophrenia in subjects of European ancestry and suggest that further studies to define the endophenotype and mechanisms of illness associated with this polymorphism are indicated.

  10. 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. PMID:26112830

  11. 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.

  12. 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.

  13. Continual coordination of shared activities

    NASA Technical Reports Server (NTRS)

    Clement, B. J.; Barrett, A.

    2002-01-01

    Interacting agents that interleave planning and execution must reach consensus on their commitments to each other. For domains with varying degrees of interaction and different constraints on communication and computation, agents will require different coordination protocols in order to efficiently achieve their goals. ShAC (Shared Activity Coordination) is a framework for designing coordination protocols and an algorithm for continually coordinating agents using these protocols during execution. We show how a variety of protocols can be constructed using this framework and describe how ShAC coordinates two rovers and an orbiter in a simulated Mars scenario.

  14. 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…

  15. Job-Sharing at the Greater Victoria Public Library.

    ERIC Educational Resources Information Center

    Miller, Don

    1978-01-01

    Describes the problems associated with the management of part-time library employees and some solutions afforded by a job sharing arrangement in use at the Greater Victoria Public Library. This is a voluntary work arrangement, changing formerly full-time positions into multiple part-time positions. (JVP)

  16. Shared virtual environments for telerehabilitation.

    PubMed

    Popescu, George V; Burdea, Grigore; Boian, Rares

    2002-01-01

    Current VR telerehabilitation systems use offline remote monitoring from the clinic and patient-therapist videoconferencing. Such "store and forward" and video-based systems cannot implement medical services involving patient therapist direct interaction. Real-time telerehabilitation applications (including remote therapy) can be developed using a shared Virtual Environment (VE) architecture. We developed a two-user shared VE for hand telerehabilitation. Each site has a telerehabilitation workstation with a videocamera and a Rutgers Master II (RMII) force feedback glove. Each user can control a virtual hand and interact hapticly with virtual objects. Simulated physical interactions between therapist and patient are implemented using hand force feedback. The therapist's graphic interface contains several virtual panels, which allow control over the rehabilitation process. These controls start a videoconferencing session, collect patient data, or apply therapy. Several experimental telerehabilitation scenarios were successfully tested on a LAN. A Web-based approach to "real-time" patient telemonitoring--the monitoring portal for hand telerehabilitation--was also developed. The therapist interface is implemented as a Java3D applet that monitors patient hand movement. The monitoring portal gives real-time performance on off-the-shelf desktop workstations. PMID:15458115

  17. Sharing Drug 'Snorting Straws' Spreads Hepatitis C

    MedlinePlus

    ... 160112.html Sharing Drug 'Snorting Straws' Spreads Hepatitis C Study highlights more fallout from opioid epidemic To ... snort opioids is a major cause of hepatitis C infection, a new study finds. The sharing of ...

  18. 7 CFR 1980.391 - Equity sharing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... assistance granted on the account. (b) Miscellaneous provisions—(1) Changes in terms. Shared equity will not... section. (c) Affordable housing proposals. Shared equity under an affordable housing innovation (such...

  19. 44 CFR 206.65 - Cost sharing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE Emergency Assistance § 206.65 Cost sharing. The... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Cost sharing. 206.65 Section... costs....

  20. Time-shared Cathode Ray Tube

    NASA Technical Reports Server (NTRS)

    Herndon, E. S.

    1969-01-01

    Time-shared cathode tube provides high quality display at low cost display stations which utilize television moniters. It updates a cluster of graphic displays from a computer and is useful in systems not equipped for graphics time-sharing.

  1. Social Network Analysis of Patient Sharing Among Hospitals in Orange County, California

    PubMed Central

    McGlone, Sarah M.; Song, Yeohan; Avery, Taliser R.; Eubank, Stephen; Chang, Chung-Chou; Bailey, Rachel R.; Wagener, Diane K.; Burke, Donald S.; Platt, Richard; Huang, Susan S.

    2011-01-01

    Objectives. We applied social network analyses to determine how hospitals within Orange County, California, are interconnected by patient sharing, a system which may have numerous public health implications. Methods. Our analyses considered 2 general patient-sharing networks: uninterrupted patient sharing (UPS; i.e., direct interhospital transfers) and total patient sharing (TPS; i.e., all interhospital patient sharing, including patients with intervening nonhospital stays). We considered these networks at 3 thresholds of patient sharing: at least 1, at least 10, and at least 100 patients shared. Results. Geographically proximate hospitals were somewhat more likely to share patients, but many hospitals shared patients with distant hospitals. Number of patient admissions and percentage of cancer patients were associated with greater connectivity across the system. The TPS network revealed numerous connections not seen in the UPS network, meaning that direct transfers only accounted for a fraction of total patient sharing. Conclusions. Our analysis demonstrated that Orange County's 32 hospitals were highly and heterogeneously interconnected by patient sharing. Different hospital populations had different levels of influence over the patient-sharing network. PMID:21330578

  2. 23 CFR 646.212 - Federal share.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Federal share. 646.212 Section 646.212 Highways FEDERAL...-Highway Projects § 646.212 Federal share. (a) General. (1) Federal funds are not eligible to participate... required by a State regulatory agency. (b) The Federal share of railroad/highway crossing projects may...

  3. 23 CFR 646.212 - Federal share.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 false Federal share. 646.212 Section 646.212 Highways FEDERAL...-Highway Projects § 646.212 Federal share. (a) General. (1) Federal funds are not eligible to participate... required by a State regulatory agency. (b) The Federal share of railroad/highway crossing projects may...

  4. 23 CFR 646.212 - Federal share.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false Federal share. 646.212 Section 646.212 Highways FEDERAL...-Highway Projects § 646.212 Federal share. (a) General. (1) Federal funds are not eligible to participate... required by a State regulatory agency. (b) The Federal share of railroad/highway crossing projects may...

  5. 23 CFR 646.212 - Federal share.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 23 Highways 1 2013-04-01 2013-04-01 false Federal share. 646.212 Section 646.212 Highways FEDERAL...-Highway Projects § 646.212 Federal share. (a) General. (1) Federal funds are not eligible to participate... required by a State regulatory agency. (b) The Federal share of railroad/highway crossing projects may...

  6. 23 CFR 646.212 - Federal share.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Federal share. 646.212 Section 646.212 Highways FEDERAL...-Highway Projects § 646.212 Federal share. (a) General. (1) Federal funds are not eligible to participate... required by a State regulatory agency. (b) The Federal share of railroad/highway crossing projects may...

  7. 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…

  8. 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 practices…

  9. 7 CFR 634.24 - Cost sharing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM Participant RCWP Contracts § 634.24 Cost sharing... participant's water rights, cannot be considered a part of the participant's share of the cost. (b) The... offsite water quality, and (2) The matching share requirements would place a burden on the landowner...

  10. 7 CFR 634.24 - Cost sharing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM Participant RCWP Contracts § 634.24 Cost sharing... participant's water rights, cannot be considered a part of the participant's share of the cost. (b) The... offsite water quality, and (2) The matching share requirements would place a burden on the landowner...

  11. 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...

  12. 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...

  13. 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...

  14. 38 CFR 17.274 - Cost sharing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Cost sharing. 17.274 Section 17.274 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Civilian... the beneficiary cost share. (b) In addition to the beneficiary cost share, an annual (calendar...

  15. 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...

  16. Knowledge Sharing over the World Wide Web.

    ERIC Educational Resources Information Center

    Davies, John; Stewart, Scott; Weeks, Richard

    This paper describes a system that facilitates and encourages the sharing of knowledge among groups of users within or across organizations. KSE (Knowledge Sharing Environment) is a system of information agents for organizing, summarizing, and sharing knowledge from a number of sources, including the World Wide Web, an organization's internal…

  17. 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…

  18. 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...

  19. 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...

  20. 7 CFR 634.24 - Cost sharing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... participant's water rights, cannot be considered a part of the participant's share of the cost. (b) The... AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM Participant RCWP Contracts § 634.24 Cost sharing... offsite water quality, and (2) The matching share requirements would place a burden on the landowner...

  1. 7 CFR 634.24 - Cost sharing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... participant's water rights, cannot be considered a part of the participant's share of the cost. (b) The... AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM Participant RCWP Contracts § 634.24 Cost sharing... offsite water quality, and (2) The matching share requirements would place a burden on the landowner...

  2. 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...

  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. 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...

  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. 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...

  7. Shared Service Center vs. Shared Service Network: A Multiple Case Study Analysis of Factors Impacting on Shared Service Configurations

    NASA Astrophysics Data System (ADS)

    Becker, Jörg; Niehaves, Björn; Krause, Andreas

    Shared services have proven to be a key element when it comes to increasing government efficiency by collaboration. Here, we seek to investigate into the shared services phenomenon in the context of government reforms. For this purpose, an interview and document analysis-based multiple case study has been conducted in Germany. The qualitative analysis covers two shared service implementations on the local government level and identifies important preconditions for shared service emergence, namely cost pressure as motive, the existence of key actors promoting the topic and the existence of prior cooperation. Moreover, it is shown that the structure of such previous cooperation determines, if shared services are being organised in a centralised (shared service centre) or decentralised format (shared service network).

  8. 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

  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. 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

  11. 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.

  12. 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.

  13. Depression and Obesity: Do Shared Genes Explain the Relationship?

    PubMed Central

    Afari, Niloofar; Noonan, Carolyn; Goldberg, Jack; Roy-Byrne, Peter; Schur, Ellen; Golnari, Golnaz; Buchwald, Dedra

    2010-01-01

    Background Studies have found a modest association between depression and obesity, especially in women. Given the substantial genetic contribution to both depression and obesity, we sought to determine whether shared genetic influences are responsible for the association between these 2 conditions. Methods Data were obtained from 712 monozygotic and 281 dizygotic female twin pairs who are members of the community-based University of Washington Twin Registry. The presence of depression was determined by self-report of doctor-diagnosed depression. Obesity was defined as body mass index of ≥ 30, based on self-reported height and weight. Generalized estimating regression models were used to assess the age-adjusted association between depression and obesity. Univariate and bivariate structural equation models estimated the components of variance attributable to genetic and environmental influences. Results We found a modest phenotypic association between depression and obesity (Odds Ratio = 1.6, 95% Confidence Interval = 1.2-2.1). Additive genetic effects contributed substantially to depression (57%) and obesity (81%). The best fitting bivariate model indicated that 12% of the genetic component of depression is shared with obesity. Conclusions The association between depression and obesity in women may be in part due to shared genetic risk for both conditions. Future studies should examine the genetic, environmental, social, and cultural mechanisms underlying the relationship between this association. PMID:20821799

  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. 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

  16. Sharing dreams: sex and other sociodemographic variables.

    PubMed

    Schredl, Michael

    2009-08-01

    Dream sharing is a common experience for most people. Factors which might be related to dream sharing in a representative German sample were investigated in the present study. As expected, the frequency of positively toned and neutral dreams and the frequency of negatively toned dreams were related to dream sharing. In addition, an effect of sex was found: women shared their dreams more often than men. Dream sharing differing by social class and education might point to class-specific attitudes toward dreams which have not yet been studied in detail.

  17. Ethical issues in sharing epidemiologic data.

    PubMed

    Hogue, C J

    1991-01-01

    Concurrent with the explosion in large data files and computers capable of handling both linkage of large data sets and analyzing multiple studies for meta-analysis, this decade has seen a rise in professional concern about the need for researchers to share their data. As scientific groups began to address this question, its importance and complexity became quickly apparent. In this paper recent developments on the ethics of data sharing in statistics, sociology, psychology, and other fields related to epidemiology are summarized, followed by a discussion on why data should be shared, what kinds of data should be shared, who among epidemiologists should be sharing data, when it is appropriate to share data, and how data sharing should be conducted.

  18. 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.

  19. 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.

  20. 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

  1. The OSG open facility: A sharing ecosystem

    SciTech Connect

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

    2015-01-01

    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. Furthermore, we believe that expanded access to DHTC is an essential tool for scientific innovation and work continues in expanding this service.

  2. The OSG open facility: A sharing ecosystem

    DOE PAGESBeta

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

    2015-01-01

    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 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

  3. 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.

  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. 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

  6. Heritability and Molecular-Genetic Basis of Resting EEG Activity: A Genome-Wide Association Study

    PubMed Central

    Malone, Stephen M.; Burwell, Scott J.; Vaidyanathan, Uma; Miller, Michael B.; McGue, Matt; Iacono, William G.

    2014-01-01

    Several EEG parameters are potential endophenotypes for different psychiatric disorders. The present study consists of a comprehensive behavioral- and molecular-genetic analysis of such parameters in a large community sample (N = 4,026) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric heritability estimates ranged from .49 to .85, with a median of .78. The additive effect of all SNPs (SNP heritability) varied across electrodes. Although individual SNPs were not significantly associated with EEG parameters, several genes were associated with delta power. We also obtained an association between the GABRA2 gene and beta power (p < .014), consistent with findings reported by others, although this did not survive Bonferroni correction. If EEG parameters conform to a largely polygenic model of inheritance, larger sample sizes will be required to detect individual variants reliably. PMID:25387704

  7. 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.

  8. 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…

  9. 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…

  10. 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…

  11. 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…

  12. "This Is a Bad Dog, You Know...": Constructing Shared Meanings During Sibling Pretend Play

    ERIC Educational Resources Information Center

    Howe, Nina; Petrakos, Hariclia; Rinaldi, Christina M.; LeFebvre, Rachel

    2005-01-01

    The construction of shared meanings in play, pretense enactment, internal state language, and sibling relationship quality were investigated in 40 kindergarteners with an older (M age = 7.10 years) or younger (M age = 3.6 years) sibling. Dyadic strategies to construct shared meanings (e.g., extensions, building on) were positively associated with…

  13. 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.

  14. Cost-sharing: a blunt instrument.

    PubMed

    Remler, Dahlia K; Greene, Jessica

    2009-01-01

    Cost-sharing is a health care cost-containment technique in which health care services are partially paid for by patients out of pocket. Cost-sharing can reduce non-cost-effective care, but it can also undermine the financial protection and access values of health insurance. We review the empirical evidence published since the mid-1980s about cost-sharing's effect on utilization, expenditures, health, and adverse consequences, including how the effects vary by form of care, by health status, and by sociodemographic characteristics. Some cost-sharing, such as emergency department copayments, reduces utilization without any harmful effects, whereas other cost-sharing reduces valuable care such as maintenance drug use among the chronically ill. Cost-sharing should be used judiciously, with attention taken not to reduce highly cost-effective care.

  15. Cost-sharing: a blunt instrument.

    PubMed

    Remler, Dahlia K; Greene, Jessica

    2009-01-01

    Cost-sharing is a health care cost-containment technique in which health care services are partially paid for by patients out of pocket. Cost-sharing can reduce non-cost-effective care, but it can also undermine the financial protection and access values of health insurance. We review the empirical evidence published since the mid-1980s about cost-sharing's effect on utilization, expenditures, health, and adverse consequences, including how the effects vary by form of care, by health status, and by sociodemographic characteristics. Some cost-sharing, such as emergency department copayments, reduces utilization without any harmful effects, whereas other cost-sharing reduces valuable care such as maintenance drug use among the chronically ill. Cost-sharing should be used judiciously, with attention taken not to reduce highly cost-effective care. PMID:18976141

  16. 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,

  17. 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

  18. Association of Academic Physiatrists

    MedlinePlus

    ... RFC Newsletter - Physiatry in Motion Discussion Forums FileShare Libraries Membership Directory About AAP President's Message Mission & Strategic ... children('.slide-panel.notactive').removeClass('notactive'); autoPlay();}); }); Your Academic Home for Physiatry The Association of Academic Physiatrists ( ...

  19. 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…

  20. 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.

  1. DeID - a data sharing tool for neuroimaging studies.

    PubMed

    Song, Xuebo; Wang, James; Wang, Anlin; Meng, Qingping; Prescott, Christian; Tsu, Loretta; Eckert, Mark A

    2015-01-01

    Funding institutions and researchers increasingly expect that data will be shared to increase scientific integrity and provide other scientists with the opportunity to use the data with novel methods that may advance understanding in a particular field of study. In practice, sharing human subject data can be complicated because data must be de-identified prior to sharing. Moreover, integrating varied data types collected in a study can be challenging and time consuming. For example, sharing data from structural imaging studies of a complex disorder requires the integration of imaging, demographic and/or behavioral data in a way that no subject identifiers are included in the de-identified dataset and with new subject labels or identification values that cannot be tracked back to the original ones. We have developed a Java program that users can use to remove identifying information in neuroimaging datasets, while still maintaining the association among different data types from the same subject for further studies. This software provides a series of user interaction wizards to allow users to select data variables to be de-identified, implements functions for auditing and validation of de-identified data, and enables the user to share the de-identified data in a single compressed package through various communication protocols, such as FTPS and SFTP. DeID runs with Windows, Linux, and Mac operating systems and its open architecture allows it to be easily adapted to support a broader array of data types, with the goal of facilitating data sharing. DeID can be obtained at http://www.nitrc.org/projects/deid. PMID:26441500

  2. 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.

  3. 13 CFR 314.5 - Federal Share.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE PROPERTY General... marketing costs. (b) The Federal Share excludes that portion of the current fair market value of the.... If the Property is disposed of when its current fair market is $250, the Federal Share is $125...

  4. Job Sharing: Is It in Your Future?

    ERIC Educational Resources Information Center

    Russell, Thyra K.

    This paper reports the results of a survey of 1,277 libraries in Illinois which investigated the status of job sharing in armed forces, college and university, community college, government, law, medical, public, religious, and special libraries and library systems. Job sharing is described as the division of one full-time job between two or more…

  5. 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)

  6. Job Sharing for the 80's.

    ERIC Educational Resources Information Center

    Notowitz, Carol

    1982-01-01

    Discusses the advantages and disadvantages of job-sharing as an alternative to part-time employment in libraries and describes a job-sharing experiment at the Parson Branch of the Public Library of Columbus and Franklin County. Six references are included. (CHC)

  7. 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....

  8. 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....

  9. 24 CFR 4001.118 - Equity sharing.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Equity sharing. 4001.118 Section... Requirements and Underwriting Procedures § 4001.118 Equity sharing. (a) Initial Equity. For purposes of section 257(k)(1) of the Act, the initial equity created as a direct result of the origination of a...

  10. 24 CFR 4001.118 - Equity sharing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Equity sharing. 4001.118 Section... Requirements and Underwriting Procedures § 4001.118 Equity sharing. (a) Initial Equity. For purposes of section 257(k)(1) of the Act, the initial equity created as a direct result of the origination of a...

  11. 7 CFR 1980.391 - Equity sharing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 14 2011-01-01 2011-01-01 false Equity sharing. 1980.391 Section 1980.391 Agriculture... REGULATIONS (CONTINUED) GENERAL Rural Housing Loans § 1980.391 Equity sharing. The policy of RHS is to collect... described in paragraph (a) of this section occur, if any equity exists in the security. (a) Determining...

  12. 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…

  13. 36 CFR 13.168 - Shared use.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Shared use. 13.168 Section 13.168 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Cabins Cabin Use for Subsistence Purposes § 13.168 Shared use. In...

  14. 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.

  15. Knowledge Searching and Sharing on Virtual Networks.

    ERIC Educational Resources Information Center

    Helokunnas, Tuija; Herrala, Juha

    2001-01-01

    Describes searching and sharing of knowledge on virtual networks, based on experiences gained when hosting virtual knowledge networks at Tampere University of Technology in Finland. Discusses information and knowledge management studies; role of information technology in knowledge searching and sharing; implementation and experiences of the…

  16. 45 CFR 63.22 - Cost sharing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Cost sharing. 63.22 Section 63.22 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GRANT PROGRAMS ADMINISTERED BY THE OFFICE OF THE ASSISTANT SECRETARY FOR PLANNING AND EVALUATION Financial Provisions § 63.22 Cost sharing....

  17. How to Share Data with Families

    ERIC Educational Resources Information Center

    McWilliams, Lorette; Patton, Christine

    2015-01-01

    Students whose parents receive regular and personalized messages with actionable information from teachers are more likely to succeed in school. But effective data-sharing programs require more than simply sending data home. They also encourage educators and families to make connections with each other, sharing observations about how a child…

  18. 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…

  19. 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...

  20. Shared Governance in the Community College

    ERIC Educational Resources Information Center

    Kater, Sue; Levin, John S.

    2004-01-01

    This study examined shared governance in public, unionized community colleges and creates a national inventory of areas in which faculty participate in governance according to the language of collective-bargaining agreements. The findings suggest that community college faculty are engaged in shared governance in both the traditional academic areas…