Dimensions of Temperament and Depressive Symptoms: Replicating a Three-Way Interaction

PubMed Central

Vasey, Michael W.; Harbaugh, Casaundra N.; Lonigan, Chistopher J.; Phillips, Beth M.; Hankin, Benjamin L.; Willem, Lore; Bijttebier, Patricia

2014-01-01

High negative emotionality (NE), low positive emotionality (PE), and low self-regulatory capacity (i.e., effortful control or EC) are related to depressive symptoms and furthermore, may moderate one another’s relations to such symptoms. Indeed, preliminary evidence suggests they may operate in a three-way interaction (Dinovo & Vasey, 2011), but the replicability of that finding remains unknown. Therefore, we tested this NExPExEC interaction in association with depressive symptoms in 5 independent samples. This interaction was significant in 4 of the 5 samples and a combined sample and approached significance in the fifth sample. In contrast, the NExPExEC interaction was unrelated to general anxious symptoms and thus may be specific to symptoms of depression. Implications, directions for future research, and limitations are discussed. PMID:24493906

Cultural Generality of the Integration of Obligation and Other Motives

ERIC Educational Resources Information Center

Yang, Jen-Shou

2012-01-01

The purpose of the present study is twofold. One is to assess the cultural generality of the information integration rule for moral obligation. The other is to examine how people integrate moral obligation and self-interest. Two studies were implemented following the functional measurement methodology with Chinese samples. Study 1 replicated the…

The importance of replication in wildlife research

USGS Publications Warehouse

Johnson, D.H.

2002-01-01

Wildlife ecology and management studies have been widely criticized for deficiencies in design or analysis. Manipulative experiments--with controls, randomization, and replication in space and time--provide powerful ways of learning about natural systems and establishing causal relationships, but such studies are rare in our field. Observational studies and sample surveys are more common; they also require appropriate design and analysis. More important than the design and analysis of individual studies is metareplication: replication of entire studies. Similar conclusions obtained from studies of the same phenomenon conducted under widely differing conditions will give us greater confidence in the generality of those findings than would any single study, however well designed and executed.

Intuitive intellectual property law: A nationally-representative test of the plagiarism fallacy.

PubMed

Fast, Anne A; Olson, Kristina R; Mandel, Gregory N

2017-01-01

Studies with convenience samples have suggested that the lay public's conception of intellectual property laws, including how the laws should regulate and why they should exist, are largely incommensurate with the actual intended purpose of intellectual property laws and their history in the United States. In this paper, we test whether these findings generalize to a more diverse and representative sample. The major findings from past work were replicated in the current study. When presented with several potential reasons for IP protection, the lay public endorsed plagiarism and felt that acknowledging the original source of a creative work should make copying that work permissible-viewpoints strongly divergent from lawmakers' intent and the law itself. In addition, we replicate the finding that lay people know remarkably little about intellectual property laws more generally and report little experience as users or creators of creative works.

Intuitive intellectual property law: A nationally-representative test of the plagiarism fallacy

PubMed Central

Olson, Kristina R.; Mandel, Gregory N.

2017-01-01

Studies with convenience samples have suggested that the lay public’s conception of intellectual property laws, including how the laws should regulate and why they should exist, are largely incommensurate with the actual intended purpose of intellectual property laws and their history in the United States. In this paper, we test whether these findings generalize to a more diverse and representative sample. The major findings from past work were replicated in the current study. When presented with several potential reasons for IP protection, the lay public endorsed plagiarism and felt that acknowledging the original source of a creative work should make copying that work permissible—viewpoints strongly divergent from lawmakers’ intent and the law itself. In addition, we replicate the finding that lay people know remarkably little about intellectual property laws more generally and report little experience as users or creators of creative works. PMID:28863170

A Typology of Maritally Violent Men and Correlates of Violence in a Community Sample.

ERIC Educational Resources Information Center

Delsol, Catherine; Margolin, Gyala; John, Richard S.

2003-01-01

Tests A. Holtzworth-Munroe and G. L. Stuart's (1994) typology of male batterers in a community sample. Analyses based on severity of physical aggression, generality of violence, and psychopathology partially replicated the Holtzworth-Munroe and Stuart typology by identifying 3 types of violent men: family-only, medium-violence, and generally…

Psychometrics of the screen for adult anxiety related disorders (SCAARED)- A new scale for the assessment of DSM-5 anxiety disorders.

PubMed

Angulo, Melina; Rooks, Brian T; Gill, MaryKay; Goldstein, Tina; Sakolsky, Dara; Goldstein, Benjamin; Monk, Kelly; Hickey, Mary Beth; Diler, Rasim S; Hafeman, Danella; Merranko, John; Axelson, David; Birmaher, Boris

2017-07-01

To examine the psychometrics of the Screen for Adult Anxiety Related Disorders (SCAARED). The SCAARED was adapted from the Screen for Child Anxiety Related Emotional Disorders. Participants (N=336) ages 18-27 years old were evaluated using the Structured Clinical Interview for DSM-IV Disorders (SCID). The SCAARED was completed at or within two-weeks before the SCID. The psychometrics of the SCAARED were analyzed using standard statistical analyses including principal components, and Receiver Operant Curve analyses. A replication was performed in an age/sex matched independent sample (N=158). The SCAARED showed four factors: somatic/panic/agoraphobia, generalized anxiety, separation anxiety, and social anxiety. The total and each factor scores demonstrated good internal consistency (α=0.86-0.97) and good discriminant validity between anxiety and other disorders and within anxiety disorders for generalized and social anxiety. Area Under the Curve for the total and each of the factor scores ranged between 0.72 and 0.84 (p<0.0001). These results were replicated in the independent sample. The SCAARED showed excellent psychometric properties supporting its use to screen adults for anxiety disorders, longitudinal studies following youth into adulthood and studies comparing child and adult populations. Further replication studies in larger community and clinical samples are indicated. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Lack of association between digit ratio (2D:4D) and assertiveness: replication in a large sample.

PubMed

Voracek, Martin

2009-12-01

Findings regarding within-sex associations of digit ratio (2D:4D), a putative pointer to long-lasting effects of prenatal androgen action, and sexually differentiated personality traits have generally been inconsistent or unreplicable, suggesting that effects in this domain, if any, are likely small. In contrast to evidence from Wilson's important 1983 study, a forerunner of modern 2D:4D research, two recent studies in 2005 and 2008 by Freeman, et al. and Hampson, et al. showed assertiveness, a presumably male-typed personality trait, was not associated with 2D:4D; however, these studies were clearly statistically underpowered. Hence this study examined this question anew, based on a large sample of 491 men and 627 women. Assertiveness was only modestly sexually differentiated, favoring men, and a positive correlate of age and education and a negative correlate of weight and Body Mass Index among women, but not men. Replicating the two prior studies, 2D:4D was throughout unrelated to assertiveness scores. This null finding was preserved with controls for correlates of assertiveness, also in nonparametric analysis and with tests for curvilinear relations. Discussed are implications of this specific null finding, now replicated in a large sample, for studies of 2D:4D and personality in general and novel research approaches to proceed in this field.

Inferring category characteristics from sample characteristics: inductive reasoning and social projection.

PubMed

Krueger, J; Clement, R W

1996-03-01

Inductive reasoning involves generalization from sample observations to categories. This research examined the conditions under which generalizations go beyond the boundaries of the sampled categories. In Experiment 1, participants sampled colored chips from urns. When categorization was not salient, participants revised their estimates of the probability of a particular color even in urns they had not sampled. As categorization became more salient, generalization became limited to the sampled urn. In Experiment 2 the salience of categorization in social induction was varied. When social categorization was not salient, participants projected their own responses to test items to members of a laboratory group even when they themselves did not belong to this group. When salience increased, projection decreased among nonmembers but not among members. In Experiment 3 these results were replicated in a field setting.

Hierarchical Bayesian modelling of gene expression time series across irregularly sampled replicates and clusters.

PubMed

Hensman, James; Lawrence, Neil D; Rattray, Magnus

2013-08-20

Time course data from microarrays and high-throughput sequencing experiments require simple, computationally efficient and powerful statistical models to extract meaningful biological signal, and for tasks such as data fusion and clustering. Existing methodologies fail to capture either the temporal or replicated nature of the experiments, and often impose constraints on the data collection process, such as regularly spaced samples, or similar sampling schema across replications. We propose hierarchical Gaussian processes as a general model of gene expression time-series, with application to a variety of problems. In particular, we illustrate the method's capacity for missing data imputation, data fusion and clustering.The method can impute data which is missing both systematically and at random: in a hold-out test on real data, performance is significantly better than commonly used imputation methods. The method's ability to model inter- and intra-cluster variance leads to more biologically meaningful clusters. The approach removes the necessity for evenly spaced samples, an advantage illustrated on a developmental Drosophila dataset with irregular replications. The hierarchical Gaussian process model provides an excellent statistical basis for several gene-expression time-series tasks. It has only a few additional parameters over a regular GP, has negligible additional complexity, is easily implemented and can be integrated into several existing algorithms. Our experiments were implemented in python, and are available from the authors' website: http://staffwww.dcs.shef.ac.uk/people/J.Hensman/.

Replication of a rare protective allele in the noradrenaline transporter gene and ADHD

PubMed Central

Xu, X; Hawi, Z; Brookes, KJ; Anney, R; Bellgrove, M; Franke, B; Barry, E; Chen, W; Kuntsi, J; Banaschewski, T; Buitelaar, J; Ebstein, R; Fitzgerald, M; Miranda, A; Oades, RD; Roeyers, H; Rothenberger, A; Sergeant, J; Sonuga-Barke, E; Steinhausen, H-C; Faraone, SV; Gill, M

2008-01-01

Objective Replication is a key to resolving whether a reported genetic association represents a false positive finding or an actual genetic risk factor. In a previous study screening 51 candidate genes for association with ADHD in a multi-centre European sample (the IMAGE project), two single nucleotide polymorphisms (SNPs) within the norepinephrine transporter (SLC6A2) gene were found to be associated with attention deficit hyperactivity disorder (ADHD). The same SNP alleles were also reported to be associated with ADHD in a separate study from the Massachusetts General Hospital in the US. Method Using two independent samples of ADHD DSM-IV combined subtype trios we attempted to replicate the reported associations with SNPs rs11568324 and rs3785143 in SLC6A2. Results Significant association of the two markers was not observed in the two independent replication samples. However, across all four datasets the overall evidence of association with ADHD was significant (for SNP rs11568324 P=0.0001; average odds ratio=0.33; for SNP rs3785143 P=0.008; average odds ratio=1.3). Conclusions The data were consistent for rs11568324, suggesting the existence of a rare allele conferring protection for ADHD within the SLC6A2 gene. Further investigations should focus on identifying the mechanisms underlying the protective effect. PMID:18937296

The Structure of The Extended Psychosis Phenotype in Early Adolescence—A Cross-sample Replication

PubMed Central

Wigman, Johanna T. W.; Vollebergh, Wilma A. M.; Raaijmakers, Quinten A. W.; Iedema, Jurjen; van Dorsselaer, Saskia; Ormel, Johan; Verhulst, Frank C.; van Os, Jim

2011-01-01

The extended psychosis phenotype, or the expression of nonclinical positive psychotic experiences, is already prevalent in adolescence and has a dose-response risk relationship with later psychotic disorder. In 2 large adolescent general population samples (n = 5422 and n = 2230), prevalence and structure of the extended psychosis phenotype was investigated. Positive psychotic experiences, broadly defined, were reported by the majority of adolescents. Exploratory analysis with Structural Equation Modelling (Exploratory Factor Analysis followed by Confirmatory Factor Analysis [CFA]) in sample 1 suggested that psychotic experiences were best represented by 5 underlying dimensions; CFA in sample 2 provided a replication of this model. Dimensions were labeled Hallucinations, Delusions, Paranoia, Grandiosity, and Paranormal beliefs. Prevalences differed strongly, Hallucinations having the lowest and Paranoia having the highest rates. Girls reported more experiences on all dimensions, except Grandiosity, and from age 12 to 16 years rates increased. Hallucinations, Delusions, and Paranoia, but not Grandiosity and Paranormal beliefs, were associated with distress and general measures of psychopathology. Thus, only some of the dimensions of the extended psychosis phenotype in young people may represent a continuum with more severe psychopathology and predict later psychiatric disorder. PMID:20044595

Death anxiety in Kuwaiti middle-aged personnel.

PubMed

Abdel-Khalek, Ahmed M; Al-Kandari, Yagoub

2007-01-01

The present study aimed to examine the level of death anxiety, the sex-related differences among a middle-aged Kuwaiti personnel sample, and to explore the replicability of the Arabic Scale of Death Anxiety (ASDA) factors. A sample of 236 volunteer Kuwaiti personnel took part in the study. The mean ages of men and women were 41.5 (SD = 7.5) and 40.9 (SD = 7.1), respectively. The alpha reliability of the ASDA was found to be high (.93). Women had a significantly higher mean total score on the ASDA as well as on 17 out of its 20 items. Middle-aged personnel had a significantly lower mean ASDA total score than younger college students (M age = 22). The factor analysis of the ASDA items yielded three factors: fear of dead people and tombs; fear of postmortem events; and fear of lethal disease. These factors were highly replicable with previous factors extracted from a Kuwaiti college student sample. On the basis of the present findings, there are three general conclusions as follows: death anxiety is negatively associated with age; the sex-related differences on death anxiety are salient in the Arab samples; and the ASDA has a highly replicable factor structure.

Analysis of host response to bacterial infection using error model based gene expression microarray experiments

PubMed Central

Stekel, Dov J.; Sarti, Donatella; Trevino, Victor; Zhang, Lihong; Salmon, Mike; Buckley, Chris D.; Stevens, Mark; Pallen, Mark J.; Penn, Charles; Falciani, Francesco

2005-01-01

A key step in the analysis of microarray data is the selection of genes that are differentially expressed. Ideally, such experiments should be properly replicated in order to infer both technical and biological variability, and the data should be subjected to rigorous hypothesis tests to identify the differentially expressed genes. However, in microarray experiments involving the analysis of very large numbers of biological samples, replication is not always practical. Therefore, there is a need for a method to select differentially expressed genes in a rational way from insufficiently replicated data. In this paper, we describe a simple method that uses bootstrapping to generate an error model from a replicated pilot study that can be used to identify differentially expressed genes in subsequent large-scale studies on the same platform, but in which there may be no replicated arrays. The method builds a stratified error model that includes array-to-array variability, feature-to-feature variability and the dependence of error on signal intensity. We apply this model to the characterization of the host response in a model of bacterial infection of human intestinal epithelial cells. We demonstrate the effectiveness of error model based microarray experiments and propose this as a general strategy for a microarray-based screening of large collections of biological samples. PMID:15800204

Characterizing rare-event property distributions via replicate molecular dynamics simulations of proteins.

PubMed

Krishnan, Ranjani; Walton, Emily B; Van Vliet, Krystyn J

2009-11-01

As computational resources increase, molecular dynamics simulations of biomolecules are becoming an increasingly informative complement to experimental studies. In particular, it has now become feasible to use multiple initial molecular configurations to generate an ensemble of replicate production-run simulations that allows for more complete characterization of rare events such as ligand-receptor unbinding. However, there are currently no explicit guidelines for selecting an ensemble of initial configurations for replicate simulations. Here, we use clustering analysis and steered molecular dynamics simulations to demonstrate that the configurational changes accessible in molecular dynamics simulations of biomolecules do not necessarily correlate with observed rare-event properties. This informs selection of a representative set of initial configurations. We also employ statistical analysis to identify the minimum number of replicate simulations required to sufficiently sample a given biomolecular property distribution. Together, these results suggest a general procedure for generating an ensemble of replicate simulations that will maximize accurate characterization of rare-event property distributions in biomolecules.

General and substance-specific predictors of young adult nicotine dependence, alcohol use disorder, and problem behavior: replication in two samples.

PubMed

Bailey, J A; Samek, D R; Keyes, M A; Hill, K G; Hicks, B M; McGue, M; Iacono, W G; Epstein, M; Catalano, R F; Haggerty, K P; Hawkins, J D

2014-05-01

This paper presents two replications of a heuristic model for measuring environment in studies of gene-environment interplay in the etiology of young adult problem behaviors. Data were drawn from two longitudinal, U.S. studies of the etiology of substance use and related behaviors: the Raising Healthy Children study (RHC; N=1040, 47% female) and the Minnesota Twin Family Study (MTFS; N=1512, 50% female). RHC included a Pacific Northwest, school-based, community sample. MTFS included twins identified from state birth records in Minnesota. Both studies included commensurate measures of general family environment and family substance-specific environments in adolescence (RHC ages 10-18; MTFS age 18), as well as young adult nicotine dependence, alcohol and illicit drug use disorders, HIV sexual risk behavior, and antisocial behavior (RHC ages 24, 25; MTFS age 25). Results from the two samples were highly consistent and largely supported the heuristic model proposed by Bailey et al. (2011). Adolescent general family environment, family smoking environment, and family drinking environment predicted shared variance in problem behaviors in young adulthood. Family smoking environment predicted unique variance in young adult nicotine dependence. Family drinking environment did not appear to predict unique variance in young adult alcohol use disorder. Organizing environmental predictors and outcomes into general and substance-specific measures provides a useful way forward in modeling complex environments and phenotypes. Results suggest that programs aimed at preventing young adult problem behaviors should target general family environment and family smoking and drinking environments in adolescence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The association between attention-deficit/hyperactivity (ADHD) symptoms and self-employment.

PubMed

Verheul, Ingrid; Rietdijk, Wim; Block, Joern; Franken, Ingmar; Larsson, Henrik; Thurik, Roy

2016-08-01

Attention-deficit/hyperactivity (ADHD) symptoms have been associated with the decision to become self-employed. Although these symptoms are generally regarded as disadvantageous, there may also be a bright side. To our knowledge, however, there has been no systematic, epidemiological evidence to support this claim. This paper examines the association between ADHD symptoms and self-employment in a population-based sample from the STAGE cohort of the Swedish Twin Registry (N = 7208). For replication, we used a sample of Dutch students who participated in the Global University Entrepreneurial Spirit Students' Survey (N = 13,112). In the Swedish sample, we found a positive association with self-employment for both general ADHD symptoms [odds ratio (OR) 1.13; 95 % confidence intervals (CI) 1.04-1.23] and hyperactivity symptoms [OR 1.19; 95 % CI 1.08-1.32], whereas no association was found for attention-deficit symptoms [OR 0.99; 95 % CI 0.89-1.10]. The positive association between hyperactivity and self-employment was replicated in the Dutch student sample [OR 1.09; 95 % CI 1.03-1.15]. Our results show that certain aspects of ADHD, in particular hyperactivity, can have a bright side, as they are positively associated with self-employment.

The (non-)replicability of regulatory resource depletion: A field report employing non-invasive brain stimulation

PubMed Central

Martijn, Carolien; Alberts, Hugo J. E. M.; Thomson, Alix C.; David, Bastian; Kessler, Daniel

2017-01-01

Cognitive effort and self-control are exhausting. Although evidence is ambiguous, behavioural studies have repeatedly suggested that control-demanding tasks seem to deplete a limited cache of self-regulatory resources leading to performance degradations and fatigue. While resource depletion has indirectly been associated with a decline in right prefrontal cortex capacity, its precise neural underpinnings have not yet been revealed. This study consisted of two independent experiments, which set out to investigate the causal role of the right dorsolateral prefrontal cortex (DLPFC) in a classic dual phase depletion paradigm employing non-invasive brain stimulation. In Experiment 1 we demonstrated a general depletion effect, which was significantly eliminated by anodal transcranial Direct Current Stimulation to the right DLPFC. In Experiment 2, however, we failed to replicate the basic psychological depletion effect within a second independent sample. The dissimilar results are discussed in the context of the current ‘replication crisis’ and suggestions for future studies are offered. While our current results do not allow us to firmly argue for or against the existence of resource depletion, we outline why it is crucial to further clarify which specific external and internal circumstances lead to limited replicability of the described effect. We showcase and discuss the current inter-lab replication problem based on two independent samples tested within one research group (intra-lab). PMID:28362843

Variance Estimation Using Replication Methods in Structural Equation Modeling with Complex Sample Data

ERIC Educational Resources Information Center

Stapleton, Laura M.

2008-01-01

This article discusses replication sampling variance estimation techniques that are often applied in analyses using data from complex sampling designs: jackknife repeated replication, balanced repeated replication, and bootstrapping. These techniques are used with traditional analyses such as regression, but are currently not used with structural…

Influence of androgen receptor repeat polymorphisms on personality traits in men

PubMed Central

Westberg, Lars; Henningsson, Susanne; Landén, Mikael; Annerbrink, Kristina; Melke, Jonas; Nilsson, Staffan; Rosmond, Roland; Holm, Göran; Anckarsäter, Henrik; Eriksson, Elias

2009-01-01

Background Testosterone has been attributed importance for various aspects of behaviour. The aim of our study was to investigate the potential influence of 2 functional polymorphisms in the amino terminal of the androgen receptor on personality traits in men. Methods We assessed and genotyped 141 men born in 1944 recruited from the general population. We used 2 different instruments: the Karolinska Scales of Personality and the Temperament and Character Inventory. For replication, we similarly assessed 63 men recruited from a forensic psychiatry study group. Results In the population-recruited sample, the lengths of the androgen receptor repeats were associated with neuroticism, extraversion and self-transcendence. The association with extraversion was replicated in the independent sample. Limitations Our 2 samples differed in size; sample 1 was of moderate size and sample 2 was small. In addition, the homogeneity of sample 1 probably enhanced our ability to detect significant associations between genotype and phenotype. Conclusion Our results suggest that the repeat polymorphisms in the androgen receptor gene may influence personality traits in men. PMID:19448851

U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--QA ANALYTICAL RESULTS FOR METALS IN REPLICATE SAMPLES

EPA Science Inventory

The Metals in Replicate Samples data set contains the analytical results of measurements of up to 2 metals in 172 replicate (duplicate) samples from 86 households. Measurements were made in samples of blood. Duplicate samples for a small percentage of the total number of sample...

Constraints on Generality (COG): A Proposed Addition to All Empirical Papers.

PubMed

Simons, Daniel J; Shoda, Yuichi; Lindsay, D Stephen

2017-11-01

Psychological scientists draw inferences about populations based on samples-of people, situations, and stimuli-from those populations. Yet, few papers identify their target populations, and even fewer justify how or why the tested samples are representative of broader populations. A cumulative science depends on accurately characterizing the generality of findings, but current publishing standards do not require authors to constrain their inferences, leaving readers to assume the broadest possible generalizations. We propose that the discussion section of all primary research articles specify Constraints on Generality (i.e., a "COG" statement) that identify and justify target populations for the reported findings. Explicitly defining the target populations will help other researchers to sample from the same populations when conducting a direct replication, and it could encourage follow-up studies that test the boundary conditions of the original finding. Universal adoption of COG statements would change publishing incentives to favor a more cumulative science.

NHEXAS PHASE I ARIZONA STUDY--QA ANALYTICAL RESULTS FOR METALS IN REPLICATE SAMPLES

EPA Science Inventory

The Metals in Replicate Samples data set contains the analytical results of measurements of up to 27 metals in 133 replicate (duplicate) samples from 62 households. Measurements were made in samples of soil, blood, tap water, and drinking water. Duplicate samples for a small pe...

Quantile regression of microgeographic variation in population characteristics of an invasive vertebrate predator

USGS Publications Warehouse

Siers, Shane R.; Savidge, Julie A.; Reed, Robert

2017-01-01

Localized ecological conditions have the potential to induce variation in population characteristics such as size distributions and body conditions. The ability to generalize the influence of ecological characteristics on such population traits may be particularly meaningful when those traits influence prospects for successful management interventions. To characterize variability in invasive Brown Treesnake population attributes within and among habitat types, we conducted systematic and seasonally-balanced surveys, collecting 100 snakes from each of 18 sites: three replicates within each of six major habitat types comprising 95% of Guam’s geographic expanse. Our study constitutes one of the most comprehensive and controlled samplings of any published snake study. Quantile regression on snake size and body condition indicated significant ecological heterogeneity, with a general trend of relative consistency of size classes and body conditions within and among scrub and Leucaena forest habitat types and more heterogeneity among ravine forest, savanna, and urban residential sites. Larger and more robust snakes were found within some savanna and urban habitat replicates, likely due to relative availability of larger prey. Compared to more homogeneous samples in the wet season, variability in size distributions and body conditions was greater during the dry season. Although there is evidence of habitat influencing Brown Treesnake populations at localized scales (e.g., the higher prevalence of larger snakes—particularly males—in savanna and urban sites), the level of variability among sites within habitat types indicates little ability to make meaningful predictions about these traits at unsampled locations. Seasonal variability within sites and habitats indicates that localized population characterization should include sampling in both wet and dry seasons. Extreme values at single replicates occasionally influenced overall habitat patterns, while pooling replicates masked variability among sites. A full understanding of population characteristics should include an assessment of variability both at the site and habitat level.

Quantile regression of microgeographic variation in population characteristics of an invasive vertebrate predator

PubMed Central

Siers, Shane R.; Savidge, Julie A.; Reed, Robert N.

2017-01-01

Localized ecological conditions have the potential to induce variation in population characteristics such as size distributions and body conditions. The ability to generalize the influence of ecological characteristics on such population traits may be particularly meaningful when those traits influence prospects for successful management interventions. To characterize variability in invasive Brown Treesnake population attributes within and among habitat types, we conducted systematic and seasonally-balanced surveys, collecting 100 snakes from each of 18 sites: three replicates within each of six major habitat types comprising 95% of Guam’s geographic expanse. Our study constitutes one of the most comprehensive and controlled samplings of any published snake study. Quantile regression on snake size and body condition indicated significant ecological heterogeneity, with a general trend of relative consistency of size classes and body conditions within and among scrub and Leucaena forest habitat types and more heterogeneity among ravine forest, savanna, and urban residential sites. Larger and more robust snakes were found within some savanna and urban habitat replicates, likely due to relative availability of larger prey. Compared to more homogeneous samples in the wet season, variability in size distributions and body conditions was greater during the dry season. Although there is evidence of habitat influencing Brown Treesnake populations at localized scales (e.g., the higher prevalence of larger snakes—particularly males—in savanna and urban sites), the level of variability among sites within habitat types indicates little ability to make meaningful predictions about these traits at unsampled locations. Seasonal variability within sites and habitats indicates that localized population characterization should include sampling in both wet and dry seasons. Extreme values at single replicates occasionally influenced overall habitat patterns, while pooling replicates masked variability among sites. A full understanding of population characteristics should include an assessment of variability both at the site and habitat level. PMID:28570632

Quantile regression of microgeographic variation in population characteristics of an invasive vertebrate predator.

PubMed

Siers, Shane R; Savidge, Julie A; Reed, Robert N

2017-01-01

Localized ecological conditions have the potential to induce variation in population characteristics such as size distributions and body conditions. The ability to generalize the influence of ecological characteristics on such population traits may be particularly meaningful when those traits influence prospects for successful management interventions. To characterize variability in invasive Brown Treesnake population attributes within and among habitat types, we conducted systematic and seasonally-balanced surveys, collecting 100 snakes from each of 18 sites: three replicates within each of six major habitat types comprising 95% of Guam's geographic expanse. Our study constitutes one of the most comprehensive and controlled samplings of any published snake study. Quantile regression on snake size and body condition indicated significant ecological heterogeneity, with a general trend of relative consistency of size classes and body conditions within and among scrub and Leucaena forest habitat types and more heterogeneity among ravine forest, savanna, and urban residential sites. Larger and more robust snakes were found within some savanna and urban habitat replicates, likely due to relative availability of larger prey. Compared to more homogeneous samples in the wet season, variability in size distributions and body conditions was greater during the dry season. Although there is evidence of habitat influencing Brown Treesnake populations at localized scales (e.g., the higher prevalence of larger snakes-particularly males-in savanna and urban sites), the level of variability among sites within habitat types indicates little ability to make meaningful predictions about these traits at unsampled locations. Seasonal variability within sites and habitats indicates that localized population characterization should include sampling in both wet and dry seasons. Extreme values at single replicates occasionally influenced overall habitat patterns, while pooling replicates masked variability among sites. A full understanding of population characteristics should include an assessment of variability both at the site and habitat level.

Replication of a Modified Factor Structure for the Eating Disorder Examination-Questionnaire: Extension to Clinical Eating Disorder and Non-clinical Samples in Portugal.

PubMed

Machado, Paulo P P; Grilo, Carlos M; Crosby, Ross D

2018-01-01

Psychometric investigations of the Eating Disorder Examination-Questionnaire (EDE-Q) have generally not supported the original scale structure. The present study tested an alternative brief factor structure in two large Portuguese samples: (1) a non-clinical sample of N = 4117 female students and (2) a treatment-seeking sample of N = 609 patients diagnosed with eating disorders. Confirmatory factor analysis revealed a poor fit for the original EDE-Q structure in both the non-clinical and the clinical samples but revealed a good fit for the alternative 7-item 3-factor structure (dietary restraint, shape/weight overvaluation and body dissatisfaction). Factor loadings were invariant across samples and across the different specific eating disorder diagnoses in the clinical sample. These confirmatory factor analysis findings, which replicate findings from studies with diverse predominately overweight/obese samples, supported a modified 7-item, 3-factor structure for the EDE-Q. The reliable findings across different non-clinical and clinical eating disorder groups provide confidence regarding the potential utility of this brief version. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

NHEXAS PHASE I MARYLAND STUDY--QA ANALYTICAL RESULTS FOR PESTICIDES IN REPLICATE SAMPLES

EPA Science Inventory

The Pesticides in Replicates data set contains the analytical results of measurements of up to 10 pesticides in 68 replicate (duplicate) samples from 41 households. Measurements were made in samples of indoor air, dust, soil, drinking water, food, and beverages. Duplicate sampl...

Connecting Solubility, Equilibrium, and Periodicity in a Green, Inquiry Experiment for the General Chemistry Laboratory

ERIC Educational Resources Information Center

Cacciatore, Kristen L.; Amado, Jose; Evans, Jason J.; Sevian, Hannah

2008-01-01

We present a novel first-year chemistry laboratory experiment that connects solubility, equilibrium, and chemical periodicity concepts. It employs a unique format that asks students to replicate experiments described in different sample lab reports, each lacking some essential information, rather than follow a scripted procedure. This structure is…

Coach-Initiated Motivational Climate and Cohesion in Youth Sport

ERIC Educational Resources Information Center

Eys, Mark A.; Jewitt, Eryn; Evans, M. Blair; Wolf, Svenja; Bruner, Mark W.; Loughead, Todd M.

2013-01-01

Purpose: The general purpose of the present study was to examine the link between cohesion and motivational climate in youth sport. The first specific objective was to determine if relationships demonstrated in previous research with adult basketball and handball participants would be replicated in a younger sample and with a more heterogeneous…

Sequential and Simultaneous Processing in Children with Learning Disabilities: An Attempted Replication.

ERIC Educational Resources Information Center

Bain, Sherry K.

1993-01-01

Analysis of Kaufman Assessment Battery for Children (K-ABC) Sequential and Simultaneous Processing scores of 94 children (ages 6-12) with learning disabilities produced factor patterns generally supportive of the traditional K-ABC Mental Processing structure with the exception of Spatial Memory. The sample exhibited relative processing strengths…

Normalization Approaches for Removing Systematic Biases Associated with Mass Spectrometry and Label-Free Proteomics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Callister, Stephen J.; Barry, Richard C.; Adkins, Joshua N.

2006-02-01

Central tendency, linear regression, locally weighted regression, and quantile techniques were investigated for normalization of peptide abundance measurements obtained from high-throughput liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR MS). Arbitrary abundances of peptides were obtained from three sample sets, including a standard protein sample, two Deinococcus radiodurans samples taken from different growth phases, and two mouse striatum samples from control and methamphetamine-stressed mice (strain C57BL/6). The selected normalization techniques were evaluated in both the absence and presence of biological variability by estimating extraneous variability prior to and following normalization. Prior to normalization, replicate runs from each sample setmore » were observed to be statistically different, while following normalization replicate runs were no longer statistically different. Although all techniques reduced systematic bias, assigned ranks among the techniques revealed significant trends. For most LC-FTICR MS analyses, linear regression normalization ranked either first or second among the four techniques, suggesting that this technique was more generally suitable for reducing systematic biases.« less

NHEXAS PHASE I MARYLAND STUDY--QA ANALYTICAL RESULTS FOR METALS IN REPLICATE SAMPLES

EPA Science Inventory

The Metals in Replicates data set contains the analytical results of measurements of up to 11 metals in 88 replicate (duplicate) samples from 52 households. Measurements were made in samples of indoor and outdoor air, drinking water, food, and beverages. Duplicate samples for a...

Interim results of quality-control sampling of surface water for the Upper Colorado River National Water-Quality Assessment Study Unit, water years 1995-96

USGS Publications Warehouse

Spahr, N.E.; Boulger, R.W.

1997-01-01

Quality-control samples provide part of the information needed to estimate the bias and variability that result from sample collection, processing, and analysis. Quality-control samples of surface water collected for the Upper Colorado River National Water-Quality Assessment study unit for water years 1995?96 are presented and analyzed in this report. The types of quality-control samples collected include pre-processing split replicates, concurrent replicates, sequential replicates, post-processing split replicates, and field blanks. Analysis of the pre-processing split replicates, concurrent replicates, sequential replicates, and post-processing split replicates is based on differences between analytical results of the environmental samples and analytical results of the quality-control samples. Results of these comparisons indicate that variability introduced by sample collection, processing, and handling is low and will not affect interpretation of the environmental data. The differences for most water-quality constituents is on the order of plus or minus 1 or 2 lowest rounding units. A lowest rounding unit is equivalent to the magnitude of the least significant figure reported for analytical results. The use of lowest rounding units avoids some of the difficulty in comparing differences between pairs of samples when concentrations span orders of magnitude and provides a measure of the practical significance of the effect of variability. Analysis of field-blank quality-control samples indicates that with the exception of chloride and silica, no systematic contamination of samples is apparent. Chloride contamination probably was the result of incomplete rinsing of the dilute cleaning solution from the outlet ports of the decaport sample splitter. Silica contamination seems to have been introduced by the blank water. Sampling and processing procedures for water year 1997 have been modified as a result of these analyses.

10 CFR 74.45 - Measurements and measurement control.

Code of Federal Regulations, 2013 CFR

2013-01-01

... measurements, obtaining samples, and performing laboratory analyses for element concentration and isotope... of random error behavior. On a predetermined schedule, the program shall include, as appropriate: (i) Replicate analyses of individual samples; (ii) Analysis of replicate process samples; (iii) Replicate volume...

10 CFR 74.45 - Measurements and measurement control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... measurements, obtaining samples, and performing laboratory analyses for element concentration and isotope... of random error behavior. On a predetermined schedule, the program shall include, as appropriate: (i) Replicate analyses of individual samples; (ii) Analysis of replicate process samples; (iii) Replicate volume...

10 CFR 74.45 - Measurements and measurement control.

Code of Federal Regulations, 2012 CFR

2012-01-01

... measurements, obtaining samples, and performing laboratory analyses for element concentration and isotope... of random error behavior. On a predetermined schedule, the program shall include, as appropriate: (i) Replicate analyses of individual samples; (ii) Analysis of replicate process samples; (iii) Replicate volume...

Analytical performance of reciprocal isotope labeling of proteome digests for quantitative proteomics and its application for comparative studies of aerobic and anaerobic Escherichia coli proteomes.

PubMed

Lo, Andy; Weiner, Joel H; Li, Liang

2013-09-17

Due to limited sample amounts, instrument time considerations, and reagent costs, only a small number of replicate experiments are typically performed for quantitative proteome analyses. Generation of reproducible data that can be readily assessed for consistency within a small number of datasets is critical for accurate quantification. We report our investigation of a strategy using reciprocal isotope labeling of two comparative samples as a tool for determining proteome changes. Reciprocal labeling was evaluated to determine the internal consistency of quantified proteome changes from Escherichia coli grown under aerobic and anaerobic conditions. Qualitatively, the peptide overlap between replicate analyses of the same sample and reverse labeled samples were found to be within 8%. Quantitatively, reciprocal analyses showed only a slight increase in average overall inconsistency when compared with replicate analyses (1.29 vs. 1.24-fold difference). Most importantly, reverse labeling was successfully used to identify spurious values resulting from incorrect peptide identifications and poor peak fitting. After removal of 5% of the peptide data with low reproducibility, a total of 275 differentially expressed proteins (>1.50-fold difference) were consistently identified and were then subjected to bioinformatics analysis. General considerations and guidelines for reciprocal labeling experimental design and biological significance of obtained results are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Are quantitative trait-dependent sampling designs cost-effective for analysis of rare and common variants?

PubMed

Yilmaz, Yildiz E; Bull, Shelley B

2011-11-29

Use of trait-dependent sampling designs in whole-genome association studies of sequence data can reduce total sequencing costs with modest losses of statistical efficiency. In a quantitative trait (QT) analysis of data from the Genetic Analysis Workshop 17 mini-exome for unrelated individuals in the Asian subpopulation, we investigate alternative designs that sequence only 50% of the entire cohort. In addition to a simple random sampling design, we consider extreme-phenotype designs that are of increasing interest in genetic association analysis of QTs, especially in studies concerned with the detection of rare genetic variants. We also evaluate a novel sampling design in which all individuals have a nonzero probability of being selected into the sample but in which individuals with extreme phenotypes have a proportionately larger probability. We take differential sampling of individuals with informative trait values into account by inverse probability weighting using standard survey methods which thus generalizes to the source population. In replicate 1 data, we applied the designs in association analysis of Q1 with both rare and common variants in the FLT1 gene, based on knowledge of the generating model. Using all 200 replicate data sets, we similarly analyzed Q1 and Q4 (which is known to be free of association with FLT1) to evaluate relative efficiency, type I error, and power. Simulation study results suggest that the QT-dependent selection designs generally yield greater than 50% relative efficiency compared to using the entire cohort, implying cost-effectiveness of 50% sample selection and worthwhile reduction of sequencing costs.

Bayesian evaluation of effect size after replicating an original study

PubMed Central

van Aert, Robbie C. M.; van Assen, Marcel A. L. M.

2017-01-01

The vast majority of published results in the literature is statistically significant, which raises concerns about their reliability. The Reproducibility Project Psychology (RPP) and Experimental Economics Replication Project (EE-RP) both replicated a large number of published studies in psychology and economics. The original study and replication were statistically significant in 36.1% in RPP and 68.8% in EE-RP suggesting many null effects among the replicated studies. However, evidence in favor of the null hypothesis cannot be examined with null hypothesis significance testing. We developed a Bayesian meta-analysis method called snapshot hybrid that is easy to use and understand and quantifies the amount of evidence in favor of a zero, small, medium and large effect. The method computes posterior model probabilities for a zero, small, medium, and large effect and adjusts for publication bias by taking into account that the original study is statistically significant. We first analytically approximate the methods performance, and demonstrate the necessity to control for the original study’s significance to enable the accumulation of evidence for a true zero effect. Then we applied the method to the data of RPP and EE-RP, showing that the underlying effect sizes of the included studies in EE-RP are generally larger than in RPP, but that the sample sizes of especially the included studies in RPP are often too small to draw definite conclusions about the true effect size. We also illustrate how snapshot hybrid can be used to determine the required sample size of the replication akin to power analysis in null hypothesis significance testing and present an easy to use web application (https://rvanaert.shinyapps.io/snapshot/) and R code for applying the method. PMID:28388646

DAMe: a toolkit for the initial processing of datasets with PCR replicates of double-tagged amplicons for DNA metabarcoding analyses.

PubMed

Zepeda-Mendoza, Marie Lisandra; Bohmann, Kristine; Carmona Baez, Aldo; Gilbert, M Thomas P

2016-05-03

DNA metabarcoding is an approach for identifying multiple taxa in an environmental sample using specific genetic loci and taxa-specific primers. When combined with high-throughput sequencing it enables the taxonomic characterization of large numbers of samples in a relatively time- and cost-efficient manner. One recent laboratory development is the addition of 5'-nucleotide tags to both primers producing double-tagged amplicons and the use of multiple PCR replicates to filter erroneous sequences. However, there is currently no available toolkit for the straightforward analysis of datasets produced in this way. We present DAMe, a toolkit for the processing of datasets generated by double-tagged amplicons from multiple PCR replicates derived from an unlimited number of samples. Specifically, DAMe can be used to (i) sort amplicons by tag combination, (ii) evaluate PCR replicates dissimilarity, and (iii) filter sequences derived from sequencing/PCR errors, chimeras, and contamination. This is attained by calculating the following parameters: (i) sequence content similarity between the PCR replicates from each sample, (ii) reproducibility of each unique sequence across the PCR replicates, and (iii) copy number of the unique sequences in each PCR replicate. We showcase the insights that can be obtained using DAMe prior to taxonomic assignment, by applying it to two real datasets that vary in their complexity regarding number of samples, sequencing libraries, PCR replicates, and used tag combinations. Finally, we use a third mock dataset to demonstrate the impact and importance of filtering the sequences with DAMe. DAMe allows the user-friendly manipulation of amplicons derived from multiple samples with PCR replicates built in a single or multiple sequencing libraries. It allows the user to: (i) collapse amplicons into unique sequences and sort them by tag combination while retaining the sample identifier and copy number information, (ii) identify sequences carrying unused tag combinations, (iii) evaluate the comparability of PCR replicates of the same sample, and (iv) filter tagged amplicons from a number of PCR replicates using parameters of minimum length, copy number, and reproducibility across the PCR replicates. This enables an efficient analysis of complex datasets, and ultimately increases the ease of handling datasets from large-scale studies.

"Falsifiability is not optional": Correction to LeBel et al. (2017).

PubMed

2017-11-01

Reports an error in "Falsifiability is not optional" by Etienne P. LeBel, Derek Berger, Lorne Campbell and Timothy J. Loving ( Journal of Personality and Social Psychology , 2017[Aug], Vol 113[2], 254-261). In the reply, there were two errors in the References list. The publishing year for the 14th and 21st articles was cited incorrectly as 2016. The in-text acronym associated with these citations should read instead as FER2017 and LCL2017. The correct References list citations should read as follows, respectively: Finkel, E. J., Eastwick, P. W., & Reis, H. T. (2017). Replicability and other features of a high-quality science: Toward a balanced and empirical approach. Journal of Personality and Social Psychology , 113, 244-253. http://dx.doi.org/10.1037/pspi0000075 LeBel, E. P., Campbell, L., & Loving, T. J. (2017). Benefits of open and high-powered research outweigh costs. Journal of Personality and Social Psychology , 113, 230-243. http://dx.doi.org/10 .1037/pspi0000049. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2017-30567-003.) Finkel, Eastwick, and Reis (2016; FER2016) argued the post-2011 methodological reform movement has focused narrowly on replicability, neglecting other essential goals of research. We agree multiple scientific goals are essential, but argue, however, a more fine-grained language, conceptualization, and approach to replication is needed to accomplish these goals. Replication is the general empirical mechanism for testing and falsifying theory. Sufficiently methodologically similar replications, also known as direct replications, test the basic existence of phenomena and ensure cumulative progress is possible a priori. In contrast, increasingly methodologically dissimilar replications, also known as conceptual replications, test the relevance of auxiliary hypotheses (e.g., manipulation and measurement issues, contextual factors) required to productively investigate validity and generalizability. Without prioritizing replicability, a field is not empirically falsifiable. We also disagree with FER2016's position that "bigger samples are generally better, but . . . that very large samples could have the downside of commandeering resources that would have been better invested in other studies" (abstract). We identify problematic assumptions involved in FER2016's modifications of our original research-economic model, and present an improved model that quantifies when (and whether) it is reasonable to worry that increasing statistical power will engender potential trade-offs. Sufficiently powering studies (i.e., >80%) maximizes both research efficiency and confidence in the literature (research quality). Given that we are in agreement with FER2016 on all key open science points, we are eager to start seeing the accelerated rate of cumulative knowledge development of social psychological phenomena such a sufficiently transparent, powered, and falsifiable approach will generate. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

One-year prospective replication study of an untreated sample of community dysthymia subjects.

PubMed

McCullough, J P; McCune, K J; Kaye, A L; Braith, J A; Friend, R; Roberts, W C; Belyea-Caldwell, S; Norris, S L; Hampton, C

1994-07-01

This study replicates an earlier naturalistic-prospective investigation of nontreatment, community DSM-III-R dysthymia subjects. Major goals were to determine spontaneous remission rates and monitor the stability of psychosocial functioning levels over time. Twenty-four dysthymia subjects were followed for 1 year. Three remissions (13%) were diagnosed at the final interview. At a 4-year diagnostic follow-up contact with the remitters only, one remitter had relapsed and two remained in remission. Subjects were monitored for depressive symptom intensity, personality functioning, general medical distress, cognitive functioning, coping stylistics, interpersonal functioning, quality of their social support resources, and general family functioning. Stable levels of psychosocial functioning were maintained across all measures over the 1-year period. Current psychometric findings confirm the conclusions of the earlier nontreatment prospective study that dysthymia is a chronic mood disorder with stable psychosocial features and is unlikely to remit spontaneously over time.

Replicable Facets of Positive Emotionality and Their Relations to Psychopathology.

PubMed

Stanton, Kasey; Watson, David

2015-12-01

General individual differences in positive emotionality are negatively related to depression, social anxiety, and schizotypy/schizophrenia, and positively related to mania. However, the structure of positive emotionality remains unclear at the facet level, as there are significant disparities in the types of content assessed across emotionality measures. This study analyzed the lower order structure of positive emotionality in two samples, finding evidence for a replicable two-factor structure of Joviality and Experience Seeking. These factors demonstrated a markedly different pattern of relations in both direction and magnitude with internalizing, externalizing, and schizotypal symptoms. Joviality seems to represent an adaptive variant of positive emotionality, as it showed strong positive relations with well-being and moderate negative relations with measures of depression, social anxiety, and social anhedonia. In contrast, Experience Seeking appears to be somewhat maladaptive. It generally related positively to psychopathology, correlating most strongly with indicators of manic and externalizing symptoms. © The Author(s) 2014.

Auditory emotion recognition impairments in Schizophrenia: Relationship to acoustic features and cognition

PubMed Central

Gold, Rinat; Butler, Pamela; Revheim, Nadine; Leitman, David; Hansen, John A.; Gur, Ruben; Kantrowitz, Joshua T.; Laukka, Petri; Juslin, Patrik N.; Silipo, Gail S.; Javitt, Daniel C.

2013-01-01

Objective Schizophrenia is associated with deficits in ability to perceive emotion based upon tone of voice. The basis for this deficit, however, remains unclear and assessment batteries remain limited. We evaluated performance in schizophrenia on a novel voice emotion recognition battery with well characterized physical features, relative to impairments in more general emotional and cognitive function. Methods We studied in a primary sample of 92 patients relative to 73 controls. Stimuli were characterized according to both intended emotion and physical features (e.g., pitch, intensity) that contributed to the emotional percept. Parallel measures of visual emotion recognition, pitch perception, general cognition, and overall outcome were obtained. More limited measures were obtained in an independent replication sample of 36 patients, 31 age-matched controls, and 188 general comparison subjects. Results Patients showed significant, large effect size deficits in voice emotion recognition (F=25.4, p<.00001, d=1.1), and were preferentially impaired in recognition of emotion based upon pitch-, but not intensity-features (group X feature interaction: F=7.79, p=.006). Emotion recognition deficits were significantly correlated with pitch perception impairments both across (r=56, p<.0001) and within (r=.47, p<.0001) group. Path analysis showed both sensory-specific and general cognitive contributions to auditory emotion recognition deficits in schizophrenia. Similar patterns of results were observed in the replication sample. Conclusions The present study demonstrates impairments in auditory emotion recognition in schizophrenia relative to acoustic features of underlying stimuli. Furthermore, it provides tools and highlights the need for greater attention to physical features of stimuli used for study of social cognition in neuropsychiatric disorders. PMID:22362394

Temperament factors and dimensional, latent bifactor models of child psychopathology: Transdiagnostic and specific associations in two youth samples.

PubMed

Hankin, Benjamin L; Davis, Elysia Poggi; Snyder, Hannah; Young, Jami F; Glynn, Laura M; Sandman, Curt A

2017-06-01

Common emotional and behavioral symptoms co-occur and are associated with core temperament factors. This study investigated links between temperament and dimensional, latent psychopathology factors, including a general common psychopathology factor (p factor) and specific latent internalizing and externalizing liabilities, as captured by a bifactor model, in two independent samples of youth. Specifically, we tested the hypothesis that temperament factors of negative affectivity (NA), positive affectivity (PA), and effortful control (EC) could serve as both transdiagnostic and specific risks in relation to recent bifactor models of child psychopathology. Sample 1 included 571 youth (average age 13.6, SD =2.37, range 9.3-17.5) with both youth and parent report. Sample 2 included 554 preadolescent children (average age 7.7, SD =1.35, range =5-11 years) with parent report. Structural equation modeling showed that the latent bifactor models fit in both samples. Replicated in both samples, the p factor was associated with lower EC and higher NA (transdiagnostic risks). Several specific risks replicated in both samples after controlling for co-occurring symptoms via the p factor: internalizing was associated with higher NA and lower PA, lower EC related to externalizing problems. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

75 FR 31420 - Magnuson Stevens Act Provisions; General Provisions for Domestic Fisheries; Application for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... survey designed to estimate the population size of Pacific sardine. NMFS requests public comment on the... use of 4200 mt to replicate the summer survey conducted under the EFP approved in 2009 and expand the sample size and area covered. In addition to the summer survey, the applicants proposed to use 800 mt of...

Motivations for Choosing Teaching as a Career: Effects on General Pedagogical Knowledge during Initial Teacher Education

ERIC Educational Resources Information Center

Konig, Johannes; Rothland, Martin

2012-01-01

The authors first ask to what extent future teachers in Germany endorse teaching motivations indicated by the FIT-Choice scale. This includes reporting on the confirmatory factor analysis they carried out to examine and to replicate the FIT-Choice scale structure in the specific cultural context of Germany with a sample of 1287 preservice…

SERE: single-parameter quality control and sample comparison for RNA-Seq.

PubMed

Schulze, Stefan K; Kanwar, Rahul; Gölzenleuchter, Meike; Therneau, Terry M; Beutler, Andreas S

2012-10-03

Assessing the reliability of experimental replicates (or global alterations corresponding to different experimental conditions) is a critical step in analyzing RNA-Seq data. Pearson's correlation coefficient r has been widely used in the RNA-Seq field even though its statistical characteristics may be poorly suited to the task. Here we present a single-parameter test procedure for count data, the Simple Error Ratio Estimate (SERE), that can determine whether two RNA-Seq libraries are faithful replicates or globally different. Benchmarking shows that the interpretation of SERE is unambiguous regardless of the total read count or the range of expression differences among bins (exons or genes), a score of 1 indicating faithful replication (i.e., samples are affected only by Poisson variation of individual counts), a score of 0 indicating data duplication, and scores >1 corresponding to true global differences between RNA-Seq libraries. On the contrary the interpretation of Pearson's r is generally ambiguous and highly dependent on sequencing depth and the range of expression levels inherent to the sample (difference between lowest and highest bin count). Cohen's simple Kappa results are also ambiguous and are highly dependent on the choice of bins. For quantifying global sample differences SERE performs similarly to a measure based on the negative binomial distribution yet is simpler to compute. SERE can therefore serve as a straightforward and reliable statistical procedure for the global assessment of pairs or large groups of RNA-Seq datasets by a single statistical parameter.

SERE: Single-parameter quality control and sample comparison for RNA-Seq

PubMed Central

2012-01-01

Background Assessing the reliability of experimental replicates (or global alterations corresponding to different experimental conditions) is a critical step in analyzing RNA-Seq data. Pearson’s correlation coefficient r has been widely used in the RNA-Seq field even though its statistical characteristics may be poorly suited to the task. Results Here we present a single-parameter test procedure for count data, the Simple Error Ratio Estimate (SERE), that can determine whether two RNA-Seq libraries are faithful replicates or globally different. Benchmarking shows that the interpretation of SERE is unambiguous regardless of the total read count or the range of expression differences among bins (exons or genes), a score of 1 indicating faithful replication (i.e., samples are affected only by Poisson variation of individual counts), a score of 0 indicating data duplication, and scores >1 corresponding to true global differences between RNA-Seq libraries. On the contrary the interpretation of Pearson’s r is generally ambiguous and highly dependent on sequencing depth and the range of expression levels inherent to the sample (difference between lowest and highest bin count). Cohen’s simple Kappa results are also ambiguous and are highly dependent on the choice of bins. For quantifying global sample differences SERE performs similarly to a measure based on the negative binomial distribution yet is simpler to compute. Conclusions SERE can therefore serve as a straightforward and reliable statistical procedure for the global assessment of pairs or large groups of RNA-Seq datasets by a single statistical parameter. PMID:23033915

Risk Factors as Major Determinants of Resilience: A Replication Study.

PubMed

Eshel, Yohanan; Kimhi, Shaul; Lahad, Mooli; Leykin, Dmitry; Goroshit, Marina

2018-03-16

The present study was conducted in the context of current concerns about replication in psychological research. It claims that risk factors should be regarded as an integral part of the definition of individual resilience, which should be defined in terms of the balance between individual strength or protective factors, and individual vulnerability or risk factors (IND-SVR). Five independent samples, including 3457 Israeli participants, were employed to determine the effects of resilience promoting and resilience suppressing variables on the IND-SVR index of resilience, and on its two components: recovery from adversity, and distress symptoms. Five path analyses were employed for determining the role of distress symptoms as a measure of psychological resilience, as compared to other indices of this resilience. Results indicated the major role of risk factors (distress symptoms) as an integral component of resilience. This role was generally replicated in the five investigated samples. Risk factors are legitimate, valid, and useful parts of the definition of psychological resilience. Resilience research has shifted away from studying individual risk factors to investigating the process through which individuals overcome the hardships they experience. The present data seem to suggest that this shift should be reexamined.

Replicating studies in which samples of participants respond to samples of stimuli.

PubMed

Westfall, Jacob; Judd, Charles M; Kenny, David A

2015-05-01

In a direct replication, the typical goal is to reproduce a prior experimental result with a new but comparable sample of participants in a high-powered replication study. Often in psychology, the research to be replicated involves a sample of participants responding to a sample of stimuli. In replicating such studies, we argue that the same criteria should be used in sampling stimuli as are used in sampling participants. Namely, a new but comparable sample of stimuli should be used to ensure that the original results are not due to idiosyncrasies of the original stimulus sample, and the stimulus sample must often be enlarged to ensure high statistical power. In support of the latter point, we discuss the fact that in experiments involving samples of stimuli, statistical power typically does not approach 1 as the number of participants goes to infinity. As an example of the importance of sampling new stimuli, we discuss the bygone literature on the risky shift phenomenon, which was almost entirely based on a single stimulus sample that was later discovered to be highly unrepresentative. We discuss the use of both resampled and expanded stimulus sets, that is, stimulus samples that include the original stimuli plus new stimuli. © The Author(s) 2015.

Failure to Replicate a Genetic Association May Provide Important Clues About Genetic Architecture

PubMed Central

Greene, Casey S.; Penrod, Nadia M.; Williams, Scott M.; Moore, Jason H.

2009-01-01

Replication has become the gold standard for assessing statistical results from genome-wide association studies. Unfortunately this replication requirement may cause real genetic effects to be missed. A real result can fail to replicate for numerous reasons including inadequate sample size or variability in phenotype definitions across independent samples. In genome-wide association studies the allele frequencies of polymorphisms may differ due to sampling error or population differences. We hypothesize that some statistically significant independent genetic effects may fail to replicate in an independent dataset when allele frequencies differ and the functional polymorphism interacts with one or more other functional polymorphisms. To test this hypothesis, we designed a simulation study in which case-control status was determined by two interacting polymorphisms with heritabilities ranging from 0.025 to 0.4 with replication sample sizes ranging from 400 to 1600 individuals. We show that the power to replicate the statistically significant independent main effect of one polymorphism can drop dramatically with a change of allele frequency of less than 0.1 at a second interacting polymorphism. We also show that differences in allele frequency can result in a reversal of allelic effects where a protective allele becomes a risk factor in replication studies. These results suggest that failure to replicate an independent genetic effect may provide important clues about the complexity of the underlying genetic architecture. We recommend that polymorphisms that fail to replicate be checked for interactions with other polymorphisms, particularly when samples are collected from groups with distinct ethnic backgrounds or different geographic regions. PMID:19503614

Tigers on trails: occupancy modeling for cluster sampling.

PubMed

Hines, J E; Nichols, J D; Royle, J A; MacKenzie, D I; Gopalaswamy, A M; Kumar, N Samba; Karanth, K U

2010-07-01

Occupancy modeling focuses on inference about the distribution of organisms over space, using temporal or spatial replication to allow inference about the detection process. Inference based on spatial replication strictly requires that replicates be selected randomly and with replacement, but the importance of these design requirements is not well understood. This paper focuses on an increasingly popular sampling design based on spatial replicates that are not selected randomly and that are expected to exhibit Markovian dependence. We develop two new occupancy models for data collected under this sort of design, one based on an underlying Markov model for spatial dependence and the other based on a trap response model with Markovian detections. We then simulated data under the model for Markovian spatial dependence and fit the data to standard occupancy models and to the two new models. Bias of occupancy estimates was substantial for the standard models, smaller for the new trap response model, and negligible for the new spatial process model. We also fit these models to data from a large-scale tiger occupancy survey recently conducted in Karnataka State, southwestern India. In addition to providing evidence of a positive relationship between tiger occupancy and habitat, model selection statistics and estimates strongly supported the use of the model with Markovian spatial dependence. This new model provides another tool for the decomposition of the detection process, which is sometimes needed for proper estimation and which may also permit interesting biological inferences. In addition to designs employing spatial replication, we note the likely existence of temporal Markovian dependence in many designs using temporal replication. The models developed here will be useful either directly, or with minor extensions, for these designs as well. We believe that these new models represent important additions to the suite of modeling tools now available for occupancy estimation in conservation monitoring. More generally, this work represents a contribution to the topic of cluster sampling for situations in which there is a need for specific modeling (e.g., reflecting dependence) for the distribution of the variable(s) of interest among subunits.

Consistency of Bottom Fish Communities in the Beaufort Sea Within and Between Years

NASA Astrophysics Data System (ADS)

Norcross, B.; Holladay, B.

2016-02-01

Fish communities in the Arctic may be indicators of change due to climate and oil and gas exploration. An initial benchmark is generally established by sampling a set of sites in multiple years sequentially to estimate interannual variability. Standard practice is to conduct one trawl haul per station. Establishing the annual frequency of sampling and minimum number of hauls per station necessary to detect changes in demersal fish communities is essential to designing a monitoring program. Using small bottom trawls, we assessed interannual variability of bottom fish communities between 2013 and 2014 in the eastern US Beaufort Sea at eight depths 20-1000 m on each of four transects. In 2014, to determine if one haul per station was representative of a site, replicate hauls were made at stations along one transect at the US-Canada border. The similarity among replicate hauls within a single year was excellent, indicating that one haul per station was representative of fish communities. There were distinctly different bottom fish communities on the Beaufort Sea shelf (20-100 m) and slope (200-1000 m). Shelf communities had higher abundances of smaller fishes; whereas slope communities had fewer, but larger, individuals. There was no change in fish abundance between years, but there was interannual variability in the biomass of fish communities on the slope. However, as few fishes were captured at deep stations, the difference between catching and not catching a single large heavy fish affected relative biomass significantly, which may distort the conclusion of interannual variability. Furthermore, these replicate hauls occurred in the eastern Beaufort Sea, which appears to have fewer fish species and in lower abundance than the western Beaufort Sea. The similarity within replicates may not be as striking in a more diverse environment, however this study shows that in this region of the Arctic, it is likely sufficient to forego replicate sampling at a station in one year and season, and sequential years of sampling in that season, when characterizing bottom fish communities within a long-term study of community stability.

"Replicability and other features of a high-quality science: Toward a balanced and empirical approach": Correction to Finkel et al. (2017).

PubMed

2017-11-01

Reports an error in "Replicability and other features of a high-quality science: Toward a balanced and empirical approach" by Eli J. Finkel, Paul W. Eastwick and Harry T. Reis ( Journal of Personality and Social Psychology , 2017[Aug], Vol 113[2], 244-253). In the commentary, there was an error in the References list. The publishing year for the 18th article was cited incorrectly as 2016. The in-text acronym associated with this citation should read instead as LCL2017. The correct References list citation should read as follows: LeBel, E. P., Campbell, L., & Loving, T. J. (2017). Benefits of open and high-powered research outweigh costs. Journal of Personality and Social Psychology , 113, 230-243. http://dx.doi.org/10 .1037/pspi0000049. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2017-30567-002.) Finkel, Eastwick, and Reis (2015; FER2015) argued that psychological science is better served by responding to apprehensions about replicability rates with contextualized solutions than with one-size-fits-all solutions. Here, we extend FER2015's analysis to suggest that much of the discussion of best research practices since 2011 has focused on a single feature of high-quality science-replicability-with insufficient sensitivity to the implications of recommended practices for other features, like discovery, internal validity, external validity, construct validity, consequentiality, and cumulativeness. Thus, although recommendations for bolstering replicability have been innovative, compelling, and abundant, it is difficult to evaluate their impact on our science as a whole, especially because many research practices that are beneficial for some features of scientific quality are harmful for others. For example, FER2015 argued that bigger samples are generally better, but also noted that very large samples ("those larger than required for effect sizes to stabilize"; p. 291) could have the downside of commandeering resources that would have been better invested in other studies. In their critique of FER2015, LeBel, Campbell, and Loving (2016) concluded, based on simulated data, that ever-larger samples are better for the efficiency of scientific discovery (i.e., that there are no tradeoffs). As demonstrated here, however, this conclusion holds only when the replicator's resources are considered in isolation. If we widen the assumptions to include the original researcher's resources as well, which is necessary if the goal is to consider resource investment for the field as a whole, the conclusion changes radically-and strongly supports a tradeoff-based analysis. In general, as psychologists seek to strengthen our science, we must complement our much-needed work on increasing replicability with careful attention to the other features of a high-quality science. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A meta-data based method for DNA microarray imputation.

PubMed

Jörnsten, Rebecka; Ouyang, Ming; Wang, Hui-Yu

2007-03-29

DNA microarray experiments are conducted in logical sets, such as time course profiling after a treatment is applied to the samples, or comparisons of the samples under two or more conditions. Due to cost and design constraints of spotted cDNA microarray experiments, each logical set commonly includes only a small number of replicates per condition. Despite the vast improvement of the microarray technology in recent years, missing values are prevalent. Intuitively, imputation of missing values is best done using many replicates within the same logical set. In practice, there are few replicates and thus reliable imputation within logical sets is difficult. However, it is in the case of few replicates that the presence of missing values, and how they are imputed, can have the most profound impact on the outcome of downstream analyses (e.g. significance analysis and clustering). This study explores the feasibility of imputation across logical sets, using the vast amount of publicly available microarray data to improve imputation reliability in the small sample size setting. We download all cDNA microarray data of Saccharomyces cerevisiae, Arabidopsis thaliana, and Caenorhabditis elegans from the Stanford Microarray Database. Through cross-validation and simulation, we find that, for all three species, our proposed imputation using data from public databases is far superior to imputation within a logical set, sometimes to an astonishing degree. Furthermore, the imputation root mean square error for significant genes is generally a lot less than that of non-significant ones. Since downstream analysis of significant genes, such as clustering and network analysis, can be very sensitive to small perturbations of estimated gene effects, it is highly recommended that researchers apply reliable data imputation prior to further analysis. Our method can also be applied to cDNA microarray experiments from other species, provided good reference data are available.

Low-Pathogenic Avian Influenza Viruses in Wild House Mice

PubMed Central

Shriner, Susan A.; VanDalen, Kaci K.; Mooers, Nicole L.; Ellis, Jeremy W.; Sullivan, Heather J.; Root, J. Jeffrey; Pelzel, Angela M.; Franklin, Alan B.

2012-01-01

Background Avian influenza viruses are known to productively infect a number of mammal species, several of which are commonly found on or near poultry and gamebird farms. While control of rodent species is often used to limit avian influenza virus transmission within and among outbreak sites, few studies have investigated the potential role of these species in outbreak dynamics. Methodology/Principal Findings We trapped and sampled synanthropic mammals on a gamebird farm in Idaho, USA that had recently experienced a low pathogenic avian influenza outbreak. Six of six house mice (Mus musculus) caught on the outbreak farm were presumptively positive for antibodies to type A influenza. Consequently, we experimentally infected groups of naïve wild-caught house mice with five different low pathogenic avian influenza viruses that included three viruses derived from wild birds and two viruses derived from chickens. Virus replication was efficient in house mice inoculated with viruses derived from wild birds and more moderate for chicken-derived viruses. Mean titers (EID50 equivalents/mL) across all lung samples from seven days of sampling (three mice/day) ranged from 103.89 (H3N6) to 105.06 (H4N6) for the wild bird viruses and 102.08 (H6N2) to 102.85 (H4N8) for the chicken-derived viruses. Interestingly, multiple regression models indicated differential replication between sexes, with significantly (p<0.05) higher concentrations of avian influenza RNA found in females compared with males. Conclusions/Significance Avian influenza viruses replicated efficiently in wild-caught house mice without adaptation, indicating mice may be a risk pathway for movement of avian influenza viruses on poultry and gamebird farms. Differential virus replication between males and females warrants further investigation to determine the generality of this result in avian influenza disease dynamics. PMID:22720076

The Social Interaction Phobia Scale: Continued support for the psychometric validity of the SIPS using clinical and non-clinical samples.

PubMed

Menatti, Alison R; Weeks, Justin W; Carleton, R Nicholas; Morrison, Amanda S; Heimberg, Richard G; Hope, Debra A; Blanco, Carlos; Schneier, Franklin R; Liebowitz, Michael R

2015-05-01

The present study sought to extend findings supporting the psychometric validity of a promising measure of social anxiety (SA) symptoms, the Social Interaction Phobia Scale (SIPS; Carleton et al., 2009). Analyses were conducted using three samples: social anxiety disorder (SAD) patients, generalized anxiety disorder (GAD) patients, and healthy controls. SIPS scores of SAD patients demonstrated internal consistency and construct validity, and the previously demonstrated three-factor structure of the SIPS was replicated. Further, the SIPS total score uniquely predicted SA symptoms, and SIPS scores were significantly higher for SAD patients than GAD patients or controls. Two cut-off scores that discriminated SAD patients from GAD patients and from healthy controls were identified. The current study is the first to replicate the SIPS three-factor model in a large, treatment-seeking sample of SAD patients and establish a cut-off score discriminating SAD from GAD patients. Findings support the SIPS as a valid, SAD-specific assessment instrument. Copyright © 2015 Elsevier Ltd. All rights reserved.

Distrust As a Disease Avoidance Strategy: Individual Differences in Disgust Sensitivity Regulate Generalized Social Trust.

PubMed

Aarøe, Lene; Osmundsen, Mathias; Petersen, Michael Bang

2016-01-01

Throughout human evolutionary history, cooperative contact with others has been fundamental for human survival. At the same time, social contact has been a source of threats. In this article, we focus on one particular viable threat, communicable disease, and investigate how motivations to avoid pathogens influence people's propensity to interact and cooperate with others, as measured by individual differences in generalized social trust. While extant studies on pathogen avoidance have argued that such motivations should prompt people to avoid interactions with outgroups specifically, we argue that these motivations should prompt people to avoid others more broadly. Empirically, we utilize two convenience samples and a large nationally representative sample of US citizens to demonstrate the existence of a robust and replicable effect of individual differences in pathogen disgust sensitivity on generalized social trust. We furthermore compare the effects of pathogen disgust sensitivity on generalized social trust and outgroup prejudice and explore whether generalized social trust to some extent constitutes a pathway between pathogen avoidance motivations and prejudice.

Distrust As a Disease Avoidance Strategy: Individual Differences in Disgust Sensitivity Regulate Generalized Social Trust

PubMed Central

Aarøe, Lene; Osmundsen, Mathias; Petersen, Michael Bang

2016-01-01

Throughout human evolutionary history, cooperative contact with others has been fundamental for human survival. At the same time, social contact has been a source of threats. In this article, we focus on one particular viable threat, communicable disease, and investigate how motivations to avoid pathogens influence people's propensity to interact and cooperate with others, as measured by individual differences in generalized social trust. While extant studies on pathogen avoidance have argued that such motivations should prompt people to avoid interactions with outgroups specifically, we argue that these motivations should prompt people to avoid others more broadly. Empirically, we utilize two convenience samples and a large nationally representative sample of US citizens to demonstrate the existence of a robust and replicable effect of individual differences in pathogen disgust sensitivity on generalized social trust. We furthermore compare the effects of pathogen disgust sensitivity on generalized social trust and outgroup prejudice and explore whether generalized social trust to some extent constitutes a pathway between pathogen avoidance motivations and prejudice. PMID:27516744

Three Conceptual Replication Studies in Group Theory

ERIC Educational Resources Information Center

Melhuish, Kathleen

2018-01-01

Many studies in mathematics education research occur with a nonrepresentative sample and are never replicated. To challenge this paradigm, I designed a large-scale study evaluating student conceptions in group theory that surveyed a national, representative sample of students. By replicating questions previously used to build theory around student…

Optimization of an RNA-Seq Differential Gene Expression Analysis Depending on Biological Replicate Number and Library Size

PubMed Central

Lamarre, Sophie; Frasse, Pierre; Zouine, Mohamed; Labourdette, Delphine; Sainderichin, Elise; Hu, Guojian; Le Berre-Anton, Véronique; Bouzayen, Mondher; Maza, Elie

2018-01-01

RNA-Seq is a widely used technology that allows an efficient genome-wide quantification of gene expressions for, for example, differential expression (DE) analysis. After a brief review of the main issues, methods and tools related to the DE analysis of RNA-Seq data, this article focuses on the impact of both the replicate number and library size in such analyses. While the main drawback of previous relevant studies is the lack of generality, we conducted both an analysis of a two-condition experiment (with eight biological replicates per condition) to compare the results with previous benchmark studies, and a meta-analysis of 17 experiments with up to 18 biological conditions, eight biological replicates and 100 million (M) reads per sample. As a global trend, we concluded that the replicate number has a larger impact than the library size on the power of the DE analysis, except for low-expressed genes, for which both parameters seem to have the same impact. Our study also provides new insights for practitioners aiming to enhance their experimental designs. For instance, by analyzing both the sensitivity and specificity of the DE analysis, we showed that the optimal threshold to control the false discovery rate (FDR) is approximately 2−r, where r is the replicate number. Furthermore, we showed that the false positive rate (FPR) is rather well controlled by all three studied R packages: DESeq, DESeq2, and edgeR. We also analyzed the impact of both the replicate number and library size on gene ontology (GO) enrichment analysis. Interestingly, we concluded that increases in the replicate number and library size tend to enhance the sensitivity and specificity, respectively, of the GO analysis. Finally, we recommend to RNA-Seq practitioners the production of a pilot data set to strictly analyze the power of their experimental design, or the use of a public data set, which should be similar to the data set they will obtain. For individuals working on tomato research, on the basis of the meta-analysis, we recommend at least four biological replicates per condition and 20 M reads per sample to be almost sure of obtaining about 1000 DE genes if they exist. PMID:29491871

NHEXAS PHASE I REGION 5 STUDY--QA ANALYTICAL RESULTS FOR VOCS IN REPLICATES

EPA Science Inventory

This data set includes analytical results for measurements of VOCs in 204 duplicate (replicate) samples. Measurements were made for up to 23 VOCs in samples of air, water, and blood. Duplicate samples (samples collected along with or next to the original samples) were collected t...

NHEXAS PHASE I REGION 5 STUDY--QA ANALYTICAL RESULTS FOR METALS IN REPLICATES

EPA Science Inventory

This data set includes analytical results for measurements of metals in 490 duplicate (replicate) samples and for particles in 130 duplicate samples. Measurements were made for up to 11 metals in samples of air, dust, water, blood, and urine. Duplicate samples (samples collected ...

Delineating the Structure of Normal and Abnormal Personality: An Integrative Hierarchical Approach

PubMed Central

Markon, Kristian E.; Krueger, Robert F.; Watson, David

2008-01-01

Increasing evidence indicates that normal and abnormal personality can be treated within a single structural framework. However, identification of a single integrated structure of normal and abnormal personality has remained elusive. Here, a constructive replication approach was used to delineate an integrative hierarchical account of the structure of normal and abnormal personality. This hierarchical structure, which integrates many Big Trait models proposed in the literature, replicated across a meta-analysis as well as an empirical study, and across samples of participants as well as measures. The proposed structure resembles previously suggested accounts of personality hierarchy and provides insight into the nature of personality hierarchy more generally. Potential directions for future research on personality and psychopathology are discussed. PMID:15631580

Delineating the structure of normal and abnormal personality: an integrative hierarchical approach.

PubMed

Markon, Kristian E; Krueger, Robert F; Watson, David

2005-01-01

Increasing evidence indicates that normal and abnormal personality can be treated within a single structural framework. However, identification of a single integrated structure of normal and abnormal personality has remained elusive. Here, a constructive replication approach was used to delineate an integrative hierarchical account of the structure of normal and abnormal personality. This hierarchical structure, which integrates many Big Trait models proposed in the literature, replicated across a meta-analysis as well as an empirical study, and across samples of participants as well as measures. The proposed structure resembles previously suggested accounts of personality hierarchy and provides insight into the nature of personality hierarchy more generally. Potential directions for future research on personality and psychopathology are discussed.

Analysis of Duplicated Multiple-Samples Rank Data Using the Mack-Skillings Test.

PubMed

Carabante, Kennet Mariano; Alonso-Marenco, Jose Ramon; Chokumnoyporn, Napapan; Sriwattana, Sujinda; Prinyawiwatkul, Witoon

2016-07-01

Appropriate analysis for duplicated multiple-samples rank data is needed. This study compared analysis of duplicated rank preference data using the Friedman versus Mack-Skillings tests. Panelists (n = 125) ranked twice 2 orange juice sets: different-samples set (100%, 70%, vs. 40% juice) and similar-samples set (100%, 95%, vs. 90%). These 2 sample sets were designed to get contrasting differences in preference. For each sample set, rank sum data were obtained from (1) averaged rank data of each panelist from the 2 replications (n = 125), (2) rank data of all panelists from each of the 2 separate replications (n = 125 each), (3) jointed rank data of all panelists from the 2 replications (n = 125), and (4) rank data of all panelists pooled from the 2 replications (n = 250); rank data (1), (2), and (4) were separately analyzed by the Friedman test, although those from (3) by the Mack-Skillings test. The effect of sample sizes (n = 10 to 125) was evaluated. For the similar-samples set, higher variations in rank data from the 2 replications were observed; therefore, results of the main effects were more inconsistent among methods and sample sizes. Regardless of analysis methods, the larger the sample size, the higher the χ(2) value, the lower the P-value (testing H0 : all samples are not different). Analyzing rank data (2) separately by replication yielded inconsistent conclusions across sample sizes, hence this method is not recommended. The Mack-Skillings test was more sensitive than the Friedman test. Furthermore, it takes into account within-panelist variations and is more appropriate for analyzing duplicated rank data. © 2016 Institute of Food Technologists®

Quality-control results for ground-water and surface-water data, Sacramento River Basin, California, National Water-Quality Assessment, 1996-1998

USGS Publications Warehouse

Munday, Cathy; Domagalski, Joseph L.

2003-01-01

Evaluating the extent that bias and variability affect the interpretation of ground- and surface-water data is necessary to meet the objectives of the National Water-Quality Assessment (NAWQA) Program. Quality-control samples used to evaluate the bias and variability include annual equipment blanks, field blanks, field matrix spikes, surrogates, and replicates. This report contains quality-control results for the constituents critical to the ground- and surface-water components of the Sacramento River Basin study unit of the NAWQA Program. A critical constituent is one that was detected frequently (more than 50 percent of the time in blank samples), was detected at amounts exceeding water-quality standards or goals, or was important for the interpretation of water-quality data. Quality-control samples were collected along with ground- and surface-water samples during the high intensity phase (cycle 1) of the Sacramento River Basin NAWQA beginning early in 1996 and ending in 1998. Ground-water field blanks indicated contamination of varying levels of significance when compared with concentrations detected in environmental ground-water samples for ammonia, dissolved organic carbon, aluminum, and copper. Concentrations of aluminum in surface-water field blanks were significant when compared with environmental samples. Field blank samples collected for pesticide and volatile organic compound analyses revealed no contamination in either ground- or surface-water samples that would effect the interpretation of environmental data, with the possible exception of the volatile organic compound trichloromethane (chloroform) in ground water. Replicate samples for ground water and surface water indicate that variability resulting from sample collection, processing, and analysis was generally low. Some of the larger maximum relative percentage differences calculated for replicate samples occurred between samples having lowest absolute concentration differences and(or) values near the reporting limit. Surrogate recoveries for pesticides analyzed by gas chromatography/mass spectrometry (GC/MS), pesticides analyzed by high performance liquid chromatography (HPLC), and volatile organic compounds in ground- and surface-water samples were within the acceptable limits of 70 to 130 percent and median recovery values between 82 and 113 percent. The recovery percentages for surrogate compounds analyzed by HPLC had the highest standard deviation, 20 percent for ground-water samples and 16 percent for surface-water samples, and the lowest median values, 82 percent for ground-water samples and 91 percent for surface-water samples. Results were consistent with the recovery results described for the analytical methods. Field matrix spike recoveries for pesticide compounds analyzed using GC/MS in ground- and surface-water samples were comparable with published recovery data. Recoveries of carbofuran, a critical constituent in ground- and surface-water studies, and desethyl atrazine, a critical constituent in the ground-water study, could not be calculated because of problems with the analytical method. Recoveries of pesticides analyzed using HPLC in ground- and surface-water samples were generally low and comparable with published recovery data. Other methodological problems for HPLC analytes included nondetection of the spike compounds and estimated values of spike concentrations. Recovery of field matrix spikes for volatile organic compounds generally were within the acceptable range, 70 and 130 percent for both ground- and surface-water samples, and median recoveries from 62 to 127 percent. High or low recoveries could be related to errors in the field, such as double spiking or using spike solution past its expiration date, rather than problems during analysis. The methodological changes in the field spike protocol during the course of the Sacramento River Basin study, which included decreasing the amount of spike solu

Discrimination of fish populations using parasites: Random Forests on a 'predictable' host-parasite system.

PubMed

Pérez-Del-Olmo, A; Montero, F E; Fernández, M; Barrett, J; Raga, J A; Kostadinova, A

2010-10-01

We address the effect of spatial scale and temporal variation on model generality when forming predictive models for fish assignment using a new data mining approach, Random Forests (RF), to variable biological markers (parasite community data). Models were implemented for a fish host-parasite system sampled along the Mediterranean and Atlantic coasts of Spain and were validated using independent datasets. We considered 2 basic classification problems in evaluating the importance of variations in parasite infracommunities for assignment of individual fish to their populations of origin: multiclass (2-5 population models, using 2 seasonal replicates from each of the populations) and 2-class task (using 4 seasonal replicates from 1 Atlantic and 1 Mediterranean population each). The main results are that (i) RF are well suited for multiclass population assignment using parasite communities in non-migratory fish; (ii) RF provide an efficient means for model cross-validation on the baseline data and this allows sample size limitations in parasite tag studies to be tackled effectively; (iii) the performance of RF is dependent on the complexity and spatial extent/configuration of the problem; and (iv) the development of predictive models is strongly influenced by seasonal change and this stresses the importance of both temporal replication and model validation in parasite tagging studies.

Neighborhood Disorder and Children’s Antisocial Behavior: The Protective Effect of Family Support Among Mexican American and African American Families

PubMed Central

Conger, Rand D.; Conger, Katherine J.; Martin, Monica J.; Brody, Gene; Simons, Ronald; Cutrona, Carolyn

2012-01-01

Using data from a sample of 673 Mexican Origin families, the current investigation examined the degree to which family supportiveness acted as a protective buffer between neighborhood disorder and antisocial behavior during late childhood (i.e. intent to use controlled substances, externalizing, and association with deviant peers). Children’s perceptions of neighborhood disorder fully mediated associations between census and observer measures of neighborhood disorder and their antisocial behavior. Family support buffered children from the higher rates of antisocial behavior generally associated with living in disorderly neighborhoods. An additional goal of the current study was to replicate these findings in a second sample of 897 African American families, and that replication was successful. These findings suggest that family support may play a protective role for children living in dangerous or disadvantaged neighborhoods. They also suggest that neighborhood interventions should consider several points of entry including structural changes, resident perceptions of their neighborhood and family support. PMID:22089092

Zuckerman's revised alternative five-factor model: validation of the Zuckerman-Kuhlman-Aluja Personality Questionnaire in four French-speaking countries.

PubMed

Rossier, Jérôme; Hansenne, Michel; Baudin, Nicolas; Morizot, Julien

2012-01-01

The aim of this study was to analyze the replicability of Zuckerman's revised Alternative Five-factor model in a French-speaking context by validating the Zuckerman-Kuhlman-Aluja Personality Questionnaire (ZKA-PQ) simultaneously in 4 French-speaking countries. The total sample was made up of 1,497 subjects from Belgium, Canada, France, and Switzerland. The internal consistencies for all countries were generally similar to those found for the normative U.S. and Spanish samples. A factor analysis confirmed that the normative structure replicated well and was stable within this French-speaking context. Moreover, multigroup confirmatory factor analyses have shown that the ZKA-PQ reaches scalar invariance across these 4 countries. Mean scores were slightly different for women and men, with women scoring higher on Neuroticism but lower on Sensation Seeking. Globally, mean score differences across countries were small. Overall, the ZKA-PQ seems an interesting alternative to assess both lower and higher order personality traits for applied or research purposes.

A hierarchy of distress and invariant item ordering in the General Health Questionnaire-12.

PubMed

Doyle, F; Watson, R; Morgan, K; McBride, O

2012-06-01

Invariant item ordering (IIO) is defined as the extent to which items have the same ordering (in terms of item difficulty/severity - i.e. demonstrating whether items are difficult [rare] or less difficult [common]) for each respondent who completes a scale. IIO is therefore crucial for establishing a scale hierarchy that is replicable across samples, but no research has demonstrated IIO in scales of psychological distress. We aimed to determine if a hierarchy of distress with IIO exists in a large general population sample who completed a scale measuring distress. Data from 4107 participants who completed the 12-item General Health Questionnaire (GHQ-12) from the Northern Ireland Health and Social Wellbeing Survey 2005-6 were analysed. Mokken scaling was used to determine the dimensionality and hierarchy of the GHQ-12, and items were investigated for IIO. All items of the GHQ-12 formed a single, strong unidimensional scale (H=0.58). IIO was found for six of the 12 items (H-trans=0.55), and these symptoms reflected the following hierarchy: anhedonia, concentration, participation, coping, decision-making and worthlessness. The cross-sectional analysis needs replication. The GHQ-12 showed a hierarchy of distress, but IIO is only demonstrated for six of the items, and the scale could therefore be shortened. Adopting brief, hierarchical scales with IIO may be beneficial in both clinical and research contexts. Copyright © 2011 Elsevier B.V. All rights reserved.

Chaotic interactions of self-replicating RNA.

PubMed

Forst, C V

1996-03-01

A general system of high-order differential equations describing complex dynamics of replicating biomolecules is given. Symmetry relations and coordinate transformations of general replication systems leading to topologically equivalent systems are derived. Three chaotic attractors observed in Lotka-Volterra equations of dimension n = 3 are shown to represent three cross-sections of one and the same chaotic regime. Also a fractal torus in a generalized three-dimensional Lotka-Volterra Model has been linked to one of the chaotic attractors. The strange attractors are studied in the equivalent four-dimensional catalytic replicator network. The fractal torus has been examined in adapted Lotka-Volterra equations. Analytic expressions are derived for the Lyapunov exponents of the flow in the replicator system. Lyapunov spectra for different pathways into chaos has been calculated. In the generalized Lotka-Volterra system a second inner rest point--coexisting with (quasi)-periodic orbits--can be observed; with an abundance of different bifurcations. Pathways from chaotic tori, via quasi-periodic tori, via limit cycles, via multi-periodic orbits--emerging out of periodic doubling bifurcations--to "simple" chaotic attractors can be found.

Sample preparation composite and replicate strategy case studies for assay of solid oral drug products.

PubMed

Nickerson, Beverly; Harrington, Brent; Li, Fasheng; Guo, Michele Xuemei

2017-11-30

Drug product assay is one of several tests required for new drug products to ensure the quality of the product at release and throughout the life cycle of the product. Drug product assay testing is typically performed by preparing a composite sample of multiple dosage units to obtain an assay value representative of the batch. In some cases replicate composite samples may be prepared and the reportable assay value is the average value of all the replicates. In previously published work by Harrington et al. (2014) [5], a sample preparation composite and replicate strategy for assay was developed to provide a systematic approach which accounts for variability due to the analytical method and dosage form with a standard error of the potency assay criteria based on compendia and regulatory requirements. In this work, this sample preparation composite and replicate strategy for assay is applied to several case studies to demonstrate the utility of this approach and its application at various stages of pharmaceutical drug product development. Copyright © 2017 Elsevier B.V. All rights reserved.

A Bayesian Perspective on the Reproducibility Project: Psychology

PubMed Central

Etz, Alexander; Vandekerckhove, Joachim

2016-01-01

We revisit the results of the recent Reproducibility Project: Psychology by the Open Science Collaboration. We compute Bayes factors—a quantity that can be used to express comparative evidence for an hypothesis but also for the null hypothesis—for a large subset (N = 72) of the original papers and their corresponding replication attempts. In our computation, we take into account the likely scenario that publication bias had distorted the originally published results. Overall, 75% of studies gave qualitatively similar results in terms of the amount of evidence provided. However, the evidence was often weak (i.e., Bayes factor < 10). The majority of the studies (64%) did not provide strong evidence for either the null or the alternative hypothesis in either the original or the replication, and no replication attempts provided strong evidence in favor of the null. In all cases where the original paper provided strong evidence but the replication did not (15%), the sample size in the replication was smaller than the original. Where the replication provided strong evidence but the original did not (10%), the replication sample size was larger. We conclude that the apparent failure of the Reproducibility Project to replicate many target effects can be adequately explained by overestimation of effect sizes (or overestimation of evidence against the null hypothesis) due to small sample sizes and publication bias in the psychological literature. We further conclude that traditional sample sizes are insufficient and that a more widespread adoption of Bayesian methods is desirable. PMID:26919473

A Bayesian Perspective on the Reproducibility Project: Psychology.

PubMed

Etz, Alexander; Vandekerckhove, Joachim

2016-01-01

We revisit the results of the recent Reproducibility Project: Psychology by the Open Science Collaboration. We compute Bayes factors-a quantity that can be used to express comparative evidence for an hypothesis but also for the null hypothesis-for a large subset (N = 72) of the original papers and their corresponding replication attempts. In our computation, we take into account the likely scenario that publication bias had distorted the originally published results. Overall, 75% of studies gave qualitatively similar results in terms of the amount of evidence provided. However, the evidence was often weak (i.e., Bayes factor < 10). The majority of the studies (64%) did not provide strong evidence for either the null or the alternative hypothesis in either the original or the replication, and no replication attempts provided strong evidence in favor of the null. In all cases where the original paper provided strong evidence but the replication did not (15%), the sample size in the replication was smaller than the original. Where the replication provided strong evidence but the original did not (10%), the replication sample size was larger. We conclude that the apparent failure of the Reproducibility Project to replicate many target effects can be adequately explained by overestimation of effect sizes (or overestimation of evidence against the null hypothesis) due to small sample sizes and publication bias in the psychological literature. We further conclude that traditional sample sizes are insufficient and that a more widespread adoption of Bayesian methods is desirable.

Trauma Coping Self-Efficacy: A Context Specific Self-Efficacy Measure for Traumatic Stress

PubMed Central

Benight, Charles C.; Shoji, Kotaro; James, Lori E.; Waldrep, Edward E.; Delahanty, Douglas L.; Cieslak, Roman

2015-01-01

The psychometric properties of a Trauma Coping Self-Efficacy (CSE-T) scale that assesses general trauma-related coping self-efficacy perceptions were assessed. Measurement equivalence was assessed using several different samples: hospitalized trauma patients (n1 = 74, n2 = 69, n3 = 60), three samples of disaster survivors (n1 = 273, n2 = 227, n3 = 138), and trauma exposed college students (N = 242). This is the first multi-sample evaluation of the psychometric properties for a general trauma-related CSE measure. Results showed that a brief and parsimonious 9-item version of the CSE performed well across the samples with a robust factor structure; factor structure and factor loadings were similar across study samples. The 9-item scale CSE-T demonstrated measurement equivalence across samples indicating that the underlying concept of general post-traumatic CSE is organized in a similar manner in the different trauma-exposed groups. These results offer strong support for cross-event construct validity of the CSE-T scale. Associations of the CSE-T with important expected covariates showed significant evidence for convergent validity. Finally, discriminant validity was also supported. Replication of the factor structure, internal reliability, and other evidence for construct validity is a critical next step for future research. PMID:26524542

Meta-analysis of Parkinson's disease: identification of a novel locus, RIT2.

PubMed

Pankratz, Nathan; Beecham, Gary W; DeStefano, Anita L; Dawson, Ted M; Doheny, Kimberly F; Factor, Stewart A; Hamza, Taye H; Hung, Albert Y; Hyman, Bradley T; Ivinson, Adrian J; Krainc, Dmitri; Latourelle, Jeanne C; Clark, Lorraine N; Marder, Karen; Martin, Eden R; Mayeux, Richard; Ross, Owen A; Scherzer, Clemens R; Simon, David K; Tanner, Caroline; Vance, Jeffery M; Wszolek, Zbigniew K; Zabetian, Cyrus P; Myers, Richard H; Payami, Haydeh; Scott, William K; Foroud, Tatiana

2012-03-01

Genome-wide association (GWAS) methods have identified genes contributing to Parkinson's disease (PD); we sought to identify additional genes associated with PD susceptibility. A 2-stage design was used. First, individual level genotypic data from 5 recent PD GWAS (Discovery Sample: 4,238 PD cases and 4,239 controls) were combined. Following imputation, a logistic regression model was employed in each dataset to test for association with PD susceptibility and results from each dataset were meta-analyzed. Second, 768 single-nucleotide polymorphisms (SNPs) were genotyped in an independent Replication Sample (3,738 cases and 2,111 controls). Genome-wide significance was reached for SNPs in SNCA (rs356165; G: odds ratio [OR]=1.37; p=9.3×10(-21)), MAPT (rs242559; C: OR=0.78; p=1.5×10(-10)), GAK/DGKQ (rs11248051; T: OR=1.35; p=8.2×10(-9)/rs11248060; T: OR=1.35; p=2.0×10(-9)), and the human leukocyte antigen (HLA) region (rs3129882; A: OR=0.83; p=1.2×10(-8)), which were previously reported. The Replication Sample confirmed the associations with SNCA, MAPT, and the HLA region and also with GBA (E326K; OR=1.71; p=5×10(-8) Combined Sample) (N370; OR=3.08; p=7×10(-5) Replication sample). A novel PD susceptibility locus, RIT2, on chromosome 18 (rs12456492; p=5×10(-5) Discovery Sample; p=1.52×10(-7) Replication sample; p=2×10(-10) Combined Sample) was replicated. Conditional analyses within each of the replicated regions identified distinct SNP associations within GBA and SNCA, suggesting that there may be multiple risk alleles within these genes. We identified a novel PD susceptibility locus, RIT2, replicated several previously identified loci, and identified more than 1 risk allele within SNCA and GBA. Copyright © 2012 American Neurological Association.

Meta-analysis of Parkinson disease: Identification of a novel locus, RIT2

PubMed Central

Pankratz, Nathan; Beecham, Gary W.; DeStefano, Anita L.; Dawson, Ted M.; Doheny, Kimberly F.; Factor, Stewart A.; Hamza, Taye H.; Hung, Albert Y.; Hyman, Bradley T.; Ivinson, Adrian J.; Krainc, Dmitri; Latourelle, Jeanne C.; Clark, Lorraine N.; Marder, Karen; Martin, Eden R.; Mayeux, Richard; Ross, Owen A.; Scherzer, Clemens R.; Simon, David K.; Tanner, Caroline; Vance, Jeffery M.; Wszolek, Zbigniew K.; Zabetian, Cyrus P.; Myers, Richard H.; Payami, Haydeh; Scott, William K.; Foroud, Tatiana

2011-01-01

Objective Genome-wide association (GWAS) methods have identified genes contributing to Parkinson disease (PD); we sought to identify additional genes associated with PD susceptibility. Methods A two stage design was used. First, individual level genotypic data from five recent PD GWAS (Discovery Sample: 4,238 PD cases and 4,239 controls) were combined. Following imputation, a logistic regression model was employed in each dataset to test for association with PD susceptibility and results from each dataset were meta-analyzed. Second, 768 SNPs were genotyped in an independent Replication Sample (3,738 cases and 2,111 controls). Results Genome-wide significance was reached for SNPs in SNCA (rs356165, G: odds ratio (OR)=1.37; p=9.3 × 10−21), MAPT (rs242559, C: OR=0.78; p=1.5 × 10−10), GAK/DGKQ (rs11248051, T:OR=1.35; p=8.2 × 10−9/ rs11248060, T: OR=1.35; p=2.0×10−9), and the HLA region (rs3129882, A: OR=0.83; p=1.2 × 10−8), which were previously reported. The Replication Sample confirmed the associations with SNCA, MAPT, and the HLA region and also with GBA (E326K OR=1.71; p=5 × 10−8 Combined Sample) (N370 OR=3.08; p=7 × 10−5 Replication sample). A novel PD susceptibility locus, RIT2, on chromosome 18 (rs12456492; p=5 × 10−5 Discovery Sample; p=1.52 × 10−7 Replication sample; p=2 × 10−10 Combined Sample) was replicated. Conditional analyses within each of the replicated regions identified distinct SNP associations within GBA and SNCA, suggesting that there may be multiple risk alleles within these genes. Interpretation We identified a novel PD susceptibility locus, RIT2, replicated several previously identified loci, and identified more than one risk allele within SNCA and GBA. PMID:22451204

Increased global transcription activity as a mechanism of replication stress in cancer

PubMed Central

Kotsantis, Panagiotis; Silva, Lara Marques; Irmscher, Sarah; Jones, Rebecca M.; Folkes, Lisa; Gromak, Natalia; Petermann, Eva

2016-01-01

Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRASV12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRASV12, elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer. PMID:27725641

Increased global transcription activity as a mechanism of replication stress in cancer.

PubMed

Kotsantis, Panagiotis; Silva, Lara Marques; Irmscher, Sarah; Jones, Rebecca M; Folkes, Lisa; Gromak, Natalia; Petermann, Eva

2016-10-11

Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRAS V12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRAS V12 , elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer.

Assessment of psychometric properties of the Postpartum Bonding Questionnaire (PBQ) in Spanish mothers.

PubMed

Garcia-Esteve, Lluïsa; Torres, Anna; Lasheras, Gracia; Palacios-Hernández, Bruma; Farré-Sender, Borja; Subirà, Susana; Valdés, Manuel; Brockington, Ian Fraser

2016-04-01

The Postpartum Bonding Questionnaire (PBQ) was developed to assess mother-infant bonding disturbances in the postpartum period. The aim of this study was to examine the psychometric properties of the Spanish version of the PBQ in a sample of Spanish postpartum women. Eight hundred forty mothers were recruited in the postpartum visit (4-6 weeks after delivery): 513 from a gynecology unit (forming the general population sample) and 327 mothers from a perinatal psychiatry program (forming the clinical sample). All women were assessed by means of the Edinburgh Postnatal Depression Scale (EPDS) and the PBQ. Neither the original four-factor structure nor alternative structures (Reck et al. 2006; Wittkowski et al. 2010) were replicated by the confirmatory factor analyses. An exploratory factor analysis showed a four-factor solution. The Schmid-Leiman transformation found a general factor that accounted for 61% of the variance of the PBQ. Bonding impairment showed higher associations with depressive symptomatology in both samples. The Spanish version of the PBQ showed adequate psychometric properties for use with clinical and general populations of Spanish postpartum women. The results suggest that the PBQ could be summarized by a general factor and confirm the utility of the use of the total score for detecting bonding impairment.

In vitro test of external Qigong

PubMed Central

Yount, Garret; Solfvin, Jerry; Moore, Dan; Schlitz, Marilyn; Reading, Melissa; Aldape, Ken; Qian, Yifang

2004-01-01

Background Practitioners of the alternative medical practice 'external Qigong' generally claim the ability to emit or direct "healing energy" to treat patients. We investigated the ability of experienced Qigong practitioners to enhance the healthy growth of cultured human cells in a series of studies, each following a rigorously designed protocol with randomization, blinding and controls for variability. Methods Qigong practitioners directed healing intentionality toward normal brain cell cultures in a basic science laboratory. Qigong treatments were delivered for 20 minutes from a minimum distance of 10 centimeters. Cell proliferation was measured by a standard colony-forming efficiency (CFE) assay and a CFE ratio (CFE for treated samples/CFE for sham samples) was the dependent measure for each experiment. Results During a pilot study (8 experiments), a trend of increased cell proliferation in Qigong-treated samples (CFE Qigong/sham ratios > 1.0) was observed (P = 0.162). In a formal study (28 experiments), a similar trend was observed, with Qigong-treated samples showing on average more colony formation than sham samples (P = 0.036). In a replication study (60 experiments), no significant difference between Qigong-treated samples and sham samples was observed (P = 0.465). Conclusion We observed an apparent increase in the proliferation of cultured cells following external Qigong treatment by practitioners under strictly controlled conditions, but we did not observe this effect in a replication study. These results suggest the need for more controlled and thorough investigation of external Qigong before scientific validation is claimed. PMID:15102336

Archaeal DNA replication.

PubMed

Kelman, Lori M; Kelman, Zvi

2014-01-01

DNA replication is essential for all life forms. Although the process is fundamentally conserved in the three domains of life, bioinformatic, biochemical, structural, and genetic studies have demonstrated that the process and the proteins involved in archaeal DNA replication are more similar to those in eukaryal DNA replication than in bacterial DNA replication, but have some archaeal-specific features. The archaeal replication system, however, is not monolithic, and there are some differences in the replication process between different species. In this review, the current knowledge of the mechanisms governing DNA replication in Archaea is summarized. The general features of the replication process as well as some of the differences are discussed.

Systematic Determination of Replication Activity Type Highlights Interconnections between Replication, Chromatin Structure and Nuclear Localization

PubMed Central

Polten, Andreas; Hezroni, Hadas; Eldar, Yonina C.; Meshorer, Eran; Yakhini, Zohar; Simon, Itamar

2012-01-01

DNA replication is a highly regulated process, with each genomic locus replicating at a distinct time of replication (ToR). Advances in ToR measurement technology enabled several genome-wide profiling studies that revealed tight associations between ToR and general genomic features and a remarkable ToR conservation in mammals. Genome wide studies further showed that at the hundreds kb-to-megabase scale the genome can be divided into constant ToR regions (CTRs) in which the replication process propagates at a faster pace due to the activation of multiple origins and temporal transition regions (TTRs) in which the replication process propagates at a slower pace. We developed a computational tool that assigns a ToR to every measured locus and determines its replication activity type (CTR versus TTR). Our algorithm, ARTO (Analysis of Replication Timing and Organization), uses signal processing methods to fit a constant piece-wise linear curve to the measured raw data. We tested our algorithm and provide performance and usability results. A Matlab implementation of ARTO is available at http://bioinfo.cs.technion.ac.il/people/zohar/ARTO/. Applying our algorithm to ToR data measured in multiple mouse and human samples allowed precise genome-wide ToR determination and replication activity type characterization. Analysis of the results highlighted the plasticity of the replication program. For example, we observed significant ToR differences in 10–25% of the genome when comparing different tissue types. Our analyses also provide evidence for activity type differences in up to 30% of the probes. Integration of the ToR data with multiple aspects of chromosome organization characteristics suggests that ToR plays a role in shaping the regional chromatin structure. Namely, repressive chromatin marks, are associated with late ToR both in TTRs and CTRs. Finally, characterization of the differences between TTRs and CTRs, with matching ToR, revealed that TTRs are associated with compact chromatin and are located significantly closer to the nuclear envelope. Supplementary material is available. Raw and processed data were deposited in Geo (GSE17236). PMID:23145042

Is psychology suffering from a replication crisis? What does "failure to replicate" really mean?

PubMed

Maxwell, Scott E; Lau, Michael Y; Howard, George S

2015-09-01

Psychology has recently been viewed as facing a replication crisis because efforts to replicate past study findings frequently do not show the same result. Often, the first study showed a statistically significant result but the replication does not. Questions then arise about whether the first study results were false positives, and whether the replication study correctly indicates that there is truly no effect after all. This article suggests these so-called failures to replicate may not be failures at all, but rather are the result of low statistical power in single replication studies, and the result of failure to appreciate the need for multiple replications in order to have enough power to identify true effects. We provide examples of these power problems and suggest some solutions using Bayesian statistics and meta-analysis. Although the need for multiple replication studies may frustrate those who would prefer quick answers to psychology's alleged crisis, the large sample sizes typically needed to provide firm evidence will almost always require concerted efforts from multiple investigators. As a result, it remains to be seen how many of the recently claimed failures to replicate will be supported or instead may turn out to be artifacts of inadequate sample sizes and single study replications. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

FISH-detected delay in replication timing of mutated FMR1 alleles on both active and inactive X-chromosomes.

PubMed

Yeshaya, J; Shalgi, R; Shohat, M; Avivi, L

1999-01-01

X-chromosome inactivation and the size of the CGG repeat number are assumed to play a role in the clinical, physical, and behavioral phenotype of female carriers of a mutated FMR1 allele. In view of the tight relationship between replication timing and the expression of a given DNA sequence, we have examined the replication timing of FMR1 alleles on active and inactive X-chromosomes in cell samples (lymphocytes or amniocytes) of 25 females: 17 heterozygous for a mutated FMR1 allele with a trinucleotide repeat number varying from 58 to a few hundred, and eight homozygous for a wild-type allele. We have applied two-color fluorescence in situ hybridization (FISH) with FMR1 and X-chromosome alpha-satellite probes to interphase cells of the various genotypes: the alpha-satellite probe was used to distinguish between early replicating (active) and late replicating (inactive) X-chromosomes, and the FMR1 probe revealed the replication pattern of this locus. All samples, except one with a large trinucleotide expansion, showed an early replicating FMR1 allele on the active X-chromosome and a late replicating allele on the inactive X-chromosome. In samples of mutation carriers, both the early and the late alleles showed delayed replication compared with normal alleles, regardless of repeat size. We conclude therefore that: (1) the FMR1 locus is subjected to X-inactivation; (2) mutated FMR1 alleles, regardless of repeat size, replicate later than wild-type alleles on both the active and inactive X-chromosomes; and (3) the delaying effect of the trinucleotide expansion, even with a low repeat size, is superimposed on the delay in replication associated with X-inactivation.

Generalized estimators of avian abundance from count survey data

USGS Publications Warehouse

Royle, J. Andrew

2004-01-01

I consider modeling avian abundance from spatially referenced bird count data collected according to common protocols such as capture?recapture, multiple observer, removal sampling and simple point counts. Small sample sizes and large numbers of parameters have motivated many analyses that disregard the spatial indexing of the data, and thus do not provide an adequate treatment of spatial structure. I describe a general framework for modeling spatially replicated data that regards local abundance as a random process, motivated by the view that the set of spatially referenced local populations (at the sample locations) constitute a metapopulation. Under this view, attention can be focused on developing a model for the variation in local abundance independent of the sampling protocol being considered. The metapopulation model structure, when combined with the data generating model, define a simple hierarchical model that can be analyzed using conventional methods. The proposed modeling framework is completely general in the sense that broad classes of metapopulation models may be considered, site level covariates on detection and abundance may be considered, and estimates of abundance and related quantities may be obtained for sample locations, groups of locations, unsampled locations. Two brief examples are given, the first involving simple point counts, and the second based on temporary removal counts. Extension of these models to open systems is briefly discussed.

A closer look at the size of the gaze-liking effect: a preregistered replication.

PubMed

Tipples, Jason; Pecchinenda, Anna

2018-04-30

This study is a direct replication of gaze-liking effect using the same design, stimuli and procedure. The gaze-liking effect describes the tendency for people to rate objects as more likeable when they have recently seen a person repeatedly gaze toward rather than away from the object. However, as subsequent studies show considerable variability in the size of this effect, we sampled a larger number of participants (N = 98) than the original study (N = 24) to gain a more precise estimate of the gaze-liking effect size. Our results indicate a much smaller standardised effect size (d z  = 0.02) than that of the original study (d z  = 0.94). Our smaller effect size was not due to general insensitivity to eye-gaze effects because the same sample showed a clear (d z  = 1.09) gaze-cuing effect - faster reaction times when eyes looked toward vs away from target objects. We discuss the implications of our findings for future studies wishing to study the gaze-liking effect.

Genome-scale cluster analysis of replicated microarrays using shrinkage correlation coefficient.

PubMed

Yao, Jianchao; Chang, Chunqi; Salmi, Mari L; Hung, Yeung Sam; Loraine, Ann; Roux, Stanley J

2008-06-18

Currently, clustering with some form of correlation coefficient as the gene similarity metric has become a popular method for profiling genomic data. The Pearson correlation coefficient and the standard deviation (SD)-weighted correlation coefficient are the two most widely-used correlations as the similarity metrics in clustering microarray data. However, these two correlations are not optimal for analyzing replicated microarray data generated by most laboratories. An effective correlation coefficient is needed to provide statistically sufficient analysis of replicated microarray data. In this study, we describe a novel correlation coefficient, shrinkage correlation coefficient (SCC), that fully exploits the similarity between the replicated microarray experimental samples. The methodology considers both the number of replicates and the variance within each experimental group in clustering expression data, and provides a robust statistical estimation of the error of replicated microarray data. The value of SCC is revealed by its comparison with two other correlation coefficients that are currently the most widely-used (Pearson correlation coefficient and SD-weighted correlation coefficient) using statistical measures on both synthetic expression data as well as real gene expression data from Saccharomyces cerevisiae. Two leading clustering methods, hierarchical and k-means clustering were applied for the comparison. The comparison indicated that using SCC achieves better clustering performance. Applying SCC-based hierarchical clustering to the replicated microarray data obtained from germinating spores of the fern Ceratopteris richardii, we discovered two clusters of genes with shared expression patterns during spore germination. Functional analysis suggested that some of the genetic mechanisms that control germination in such diverse plant lineages as mosses and angiosperms are also conserved among ferns. This study shows that SCC is an alternative to the Pearson correlation coefficient and the SD-weighted correlation coefficient, and is particularly useful for clustering replicated microarray data. This computational approach should be generally useful for proteomic data or other high-throughput analysis methodology.

A New Replicator: A theoretical framework for analysing replication

PubMed Central

2010-01-01

Background Replicators are the crucial entities in evolution. The notion of a replicator, however, is far less exact than the weight of its importance. Without identifying and classifying multiplying entities exactly, their dynamics cannot be determined appropriately. Therefore, it is importance to decide the nature and characteristics of any multiplying entity, in a detailed and formal way. Results Replication is basically an autocatalytic process which enables us to rest on the notions of formal chemistry. This statement has major implications. Simple autocatalytic cycle intermediates are considered as non-informational replicators. A consequence of which is that any autocatalytically multiplying entity is a replicator, be it simple or overly complex (even nests). A stricter definition refers to entities which can inherit acquired changes (informational replicators). Simple autocatalytic molecules (and nests) are excluded from this group. However, in turn, any entity possessing copiable information is to be named a replicator, even multicellular organisms. In order to deal with the situation, an abstract, formal framework is presented, which allows the proper identification of various types of replicators. This sheds light on the old problem of the units and levels of selection and evolution. A hierarchical classification for the partition of the replicator-continuum is provided where specific replicators are nested within more general ones. The classification should be able to be successfully applied to known replicators and also to future candidates. Conclusion This paper redefines the concept of the replicator from a bottom-up theoretical approach. The formal definition and the abstract models presented can distinguish between among all possible replicator types, based on their quantity of variable and heritable information. This allows for the exact identification of various replicator types and their underlying dynamics. The most important claim is that replication, in general, is basically autocatalysis, with a specific defined environment and selective force. A replicator is not valid unless its working environment, and the selective force to which it is subject, is specified. PMID:20219099

Thresher: an improved algorithm for peak height thresholding of microbial community profiles.

PubMed

Starke, Verena; Steele, Andrew

2014-11-15

This article presents Thresher, an improved technique for finding peak height thresholds for automated rRNA intergenic spacer analysis (ARISA) profiles. We argue that thresholds must be sample dependent, taking community richness into account. In most previous fragment analyses, a common threshold is applied to all samples simultaneously, ignoring richness variations among samples and thereby compromising cross-sample comparison. Our technique solves this problem, and at the same time provides a robust method for outlier rejection, selecting for removal any replicate pairs that are not valid replicates. Thresholds are calculated individually for each replicate in a pair, and separately for each sample. The thresholds are selected to be the ones that minimize the dissimilarity between the replicates after thresholding. If a choice of threshold results in the two replicates in a pair failing a quantitative test of similarity, either that threshold or that sample must be rejected. We compare thresholded ARISA results with sequencing results, and demonstrate that the Thresher algorithm outperforms conventional thresholding techniques. The software is implemented in R, and the code is available at http://verenastarke.wordpress.com or by contacting the author. vstarke@ciw.edu or http://verenastarke.wordpress.com Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Replicability and Robustness of GWAS for Behavioral Traits

PubMed Central

Rietveld, Cornelius A.; Conley, Dalton; Eriksson, Nicholas; Esko, Tõnu; Medland, Sarah E.; Vinkhuyzen, Anna A.E.; Yang, Jian; Boardman, Jason D.; Chabris, Christopher F.; Dawes, Christopher T.; Domingue, Benjamin W.; Hinds, David A.; Johannesson, Magnus; Kiefer, Amy K.; Laibson, David; Magnusson, Patrik K. E.; Mountain, Joanna L.; Oskarsson, Sven; Rostapshova, Olga; Teumer, Alexander; Tung, Joyce Y.; Visscher, Peter M.; Benjamin, Daniel J.; Cesarini, David; Koellinger, Philipp D.

2015-01-01

A recent genome-wide association study (GWAS) of educational attainment identified three single-nucleotide polymorphisms (SNPs) that, despite their small effect sizes (each R2 ≈ 0.02%), reached genome-wide significance (p < 5×10−8) in a large discovery sample and replicated in an independent sample (p < 0.05). The study also reported associations between educational attainment and indices of SNPs called “polygenic scores.” We evaluate the robustness of these findings. Study 1 finds that all three SNPs replicate in another large (N = 34,428) independent sample. We also find that the scores remain predictive (R2 ≈ 2%) with stringent controls for stratification (Study 2) and in new within-family analyses (Study 3). Our results show that large and therefore well-powered GWASs can identify replicable genetic associations with behavioral traits. The small effect sizes of individual SNPs are likely to be a major contributing explanation for the striking contrast between our results and the disappointing replication record of most candidate gene studies. PMID:25287667

Replication and contradiction of highly cited research papers in psychiatry: 10-year follow-up.

PubMed

Tajika, Aran; Ogawa, Yusuke; Takeshima, Nozomi; Hayasaka, Yu; Furukawa, Toshi A

2015-10-01

Contradictions and initial overestimates are not unusual among highly cited studies. However, this issue has not been researched in psychiatry. Aims: To assess how highly cited studies in psychiatry are replicated by subsequent studies. We selected highly cited studies claiming effective psychiatric treatments in the years 2000 through 2002. For each of these studies we searched for subsequent studies with a better-controlled design, or with a similar design but a larger sample. Among 83 articles recommending effective interventions, 40 had not been subject to any attempt at replication, 16 were contradicted, 11 were found to have substantially smaller effects and only 16 were replicated. The standardised mean differences of the initial studies were overestimated by 132%. Studies with a total sample size of 100 or more tended to produce replicable results. Caution is needed when a study with a small sample size reports a large effect. © The Royal College of Psychiatrists 2015.

Use of the internet to study the utility values of the public.

PubMed Central

Lenert, Leslie A.; Sturley, Ann E.

2002-01-01

One of the most difficult tasks in cost-effectiveness analysis is the measurement of quality weights (utilities) for health states. The task is difficult because subjects often lack familiarity with health states they are asked to rate and because utilities measures such as the standard gamble, ask subjects to perform tasks that are complex and far from everyday experience. A large body of research suggests that computer methods can play an important role in explaining health states and measuring utilities. However, administering computer surveys to a "general public" sample, the most relevant sample for cost-effectiveness analysis, is logistically difficult. In this paper, we describe a software system designed to allow the study of general population preferences in a volunteer Internet survey panel. The approach, which relied on over sampling of ethnic groups and older members of the panel, produced a data set with an ethnically, chronologically and geographically diverse group of respondents, but was not successful in replicating the joint distribution of demographic patterns in the population. PMID:12463862

Adaptation of the Athlete Burnout Questionnaire in a Spanish sample of athletes.

PubMed

Arce, Constantino; De Francisco, Cristina; Andrade, Elena; Seoane, Gloria; Raedeke, Thomas

2012-11-01

In this paper, we offer a general version of the Spanish adaptation of Athlete Burnout Questionnaire (ABQ) designed to measure the syndrome of burnout in athletes of different sports. In previous works, the Spanish version of ABQ was administered to different samples of soccer players. Its psychometric properties were appropriate and similar to the findings in original ABQ. The purpose of this study was to examine the generalization to others sports of the Spanish adaptation. We started from this adaptation, but we included three alternative statements (one for each dimension of the questionnaire), and we replaced the word "soccer" with the word "sport". An 18-item version was administered to a sample of 487 athletes aged 13 and 29 years old. Confirmatory factor analyses replicated the factor structure, but two items modification were necessary in order to obtain a good overall fit of the model. The internal consistency and test-retest reliability of the questionnaire were satisfactory.

The more information, the more negative stigma towards schizophrenia: Brazilian general population and psychiatrists compared.

PubMed

Loch, Alexandre Andrade; Hengartner, Michael Pascal; Guarniero, Francisco Bevilacqua; Lawson, Fabio Lorea; Wang, Yuan-Pang; Gattaz, Wagner Farid; Rössler, Wulf

2013-02-28

Findings on stigmatizing attitudes toward individuals with schizophrenia have been inconsistent in comparisons between mental health professionals and members of the general public. In this regard, it is important to obtain data from understudied sociocultural settings, and to examine how attitudes toward mental illness vary in such settings. Nationwide samples of 1015 general population individuals and 1414 psychiatrists from Brazil were recruited between 2009 and 2010. Respondents from the general population were asked to identify an unlabeled schizophrenia case vignette. Psychiatrists were instructed to consider "someone with stabilized schizophrenia". Stereotypes, perceived prejudice and social distance were assessed. For the general population, stigma determinants replicated findings from the literature. The level of the vignette's identification constituted an important correlate. For psychiatrists, determinants correlated in the opposite direction. When both samples were compared, psychiatrists showed the highest scores in stereotypes and perceived prejudice; for the general population, the better they recognized the vignette, the higher they scored in those dimensions. Psychiatrists reported the lowest social distance scores compared with members of the general population. Knowledge about schizophrenia thus constituted an important determinant of stigma; consequently, factors influencing stigma should be further investigated in the general population and in psychiatrists as well. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Validation of diagnoses of distress disorders in the US National Comorbidity Survey Replication Adolescent (NCS-A) Supplement

PubMed Central

Green, Jennifer Greif; Avenevoli, Shelli; Gruber, Michael; Kessler, Ronald C.; Lakoma, Matthew; Merikangas, Kathleen R.; Sampson, Nancy A.; Zaslavsky, Alan M.

2012-01-01

Research diagnostic interviews need to discriminate between closely related disorders in order to allow comorbidity among mental disorders to be studied reliably. Yet conventional studies of diagnostic validity generally focus on single disorders and do not examine discriminant validity. The current study examines the validity of fully-structured diagnoses of closely-related distress disorders (generalized anxiety disorder, post-traumatic stress disorder, major depressive episode, and dysthymic disorder) in the lay-administered Composite International Diagnostic Interview Version 3.0 (CIDI) with independent clinical diagnoses based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) in the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A). The NCS-A is a national survey of DSM-IV mental disorders among 10,148 adolescents. A probability subsample of 347 of these adolescents and their parents were administered blinded follow-up K-SADS interviews. Good concordance (AUC; area under the receiver operating characteristic curve) was found between diagnoses based on the CIDI and the K-SADS for generalized anxiety disorder (AUC = .78), post-traumatic stress disorder (AUC = .79), and major depressive episode/dysthymic disorder (AUC = .86). Further, the CIDI was able to effectively discriminate among different types of distress disorders in the sub-sample of respondents with any distress disorder. PMID:22086845

rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data.

PubMed

Shen, Shihao; Park, Juw Won; Lu, Zhi-xiang; Lin, Lan; Henry, Michael D; Wu, Ying Nian; Zhou, Qing; Xing, Yi

2014-12-23

Ultra-deep RNA sequencing (RNA-Seq) has become a powerful approach for genome-wide analysis of pre-mRNA alternative splicing. We previously developed multivariate analysis of transcript splicing (MATS), a statistical method for detecting differential alternative splicing between two RNA-Seq samples. Here we describe a new statistical model and computer program, replicate MATS (rMATS), designed for detection of differential alternative splicing from replicate RNA-Seq data. rMATS uses a hierarchical model to simultaneously account for sampling uncertainty in individual replicates and variability among replicates. In addition to the analysis of unpaired replicates, rMATS also includes a model specifically designed for paired replicates between sample groups. The hypothesis-testing framework of rMATS is flexible and can assess the statistical significance over any user-defined magnitude of splicing change. The performance of rMATS is evaluated by the analysis of simulated and real RNA-Seq data. rMATS outperformed two existing methods for replicate RNA-Seq data in all simulation settings, and RT-PCR yielded a high validation rate (94%) in an RNA-Seq dataset of prostate cancer cell lines. Our data also provide guiding principles for designing RNA-Seq studies of alternative splicing. We demonstrate that it is essential to incorporate biological replicates in the study design. Of note, pooling RNAs or merging RNA-Seq data from multiple replicates is not an effective approach to account for variability, and the result is particularly sensitive to outliers. The rMATS source code is freely available at rnaseq-mats.sourceforge.net/. As the popularity of RNA-Seq continues to grow, we expect rMATS will be useful for studies of alternative splicing in diverse RNA-Seq projects.

Social Dating Goals in Female College Students: Failure to Replicate in a Diverse Sample

ERIC Educational Resources Information Center

Killeya-Jones, Ley A.

2004-01-01

This article reports a failure to replicate aspects of the Social Dating Goals Scale (SDGS; Sanderson & Cantor, 1995) with an ethnically diverse group of female college students. The SDGS was developed and validated with predominantly White samples. In the present study, a diverse sample of 82 Asian, Black, Hispanic and White female college…

Logical and Methodological Issues Affecting Genetic Studies of Humans Reported in Top Neuroscience Journals.

PubMed

Grabitz, Clara R; Button, Katherine S; Munafò, Marcus R; Newbury, Dianne F; Pernet, Cyril R; Thompson, Paul A; Bishop, Dorothy V M

2018-01-01

Genetics and neuroscience are two areas of science that pose particular methodological problems because they involve detecting weak signals (i.e., small effects) in noisy data. In recent years, increasing numbers of studies have attempted to bridge these disciplines by looking for genetic factors associated with individual differences in behavior, cognition, and brain structure or function. However, different methodological approaches to guarding against false positives have evolved in the two disciplines. To explore methodological issues affecting neurogenetic studies, we conducted an in-depth analysis of 30 consecutive articles in 12 top neuroscience journals that reported on genetic associations in nonclinical human samples. It was often difficult to estimate effect sizes in neuroimaging paradigms. Where effect sizes could be calculated, the studies reporting the largest effect sizes tended to have two features: (i) they had the smallest samples and were generally underpowered to detect genetic effects, and (ii) they did not fully correct for multiple comparisons. Furthermore, only a minority of studies used statistical methods for multiple comparisons that took into account correlations between phenotypes or genotypes, and only nine studies included a replication sample or explicitly set out to replicate a prior finding. Finally, presentation of methodological information was not standardized and was often distributed across Methods sections and Supplementary Material, making it challenging to assemble basic information from many studies. Space limits imposed by journals could mean that highly complex statistical methods were described in only a superficial fashion. In summary, methods that have become standard in the genetics literature-stringent statistical standards, use of large samples, and replication of findings-are not always adopted when behavioral, cognitive, or neuroimaging phenotypes are used, leading to an increased risk of false-positive findings. Studies need to correct not just for the number of phenotypes collected but also for the number of genotypes examined, genetic models tested, and subsamples investigated. The field would benefit from more widespread use of methods that take into account correlations between the factors corrected for, such as spectral decomposition, or permutation approaches. Replication should become standard practice; this, together with the need for larger sample sizes, will entail greater emphasis on collaboration between research groups. We conclude with some specific suggestions for standardized reporting in this area.

Assessing Dispositions Toward Ridicule and Laughter in the Workplace: Adapting and Validating the PhoPhiKat-9 Questionnaire

PubMed Central

Hofmann, Jennifer; Ruch, Willibald; Proyer, René T.; Platt, Tracey; Gander, Fabian

2017-01-01

The current paper addresses the measurement of three dispositions toward ridicule and laughter; i.e., gelotophobia (the fear of being laughed at), gelotophilia (the joy of being laughed at), and katagelasticism (the joy of laughing at others). These traits explain inter-individual differences in responses to humor, laughter, and social situations related to humorous encounters. First, an ultra-short form of the PhoPhiKat-45 (Ruch and Proyer, 2009) was adapted in two independent samples (Construction Sample N = 157; Replication Sample N = 1,774). Second, we tested the validity of the PhoPhiKat-9 in two further independent samples. Results showed that the psychometric properties of the ultra-short form were acceptable and the proposed factor structure could be replicated. In Validation Sample 1 (N = 246), we investigated the relation of the three traits to responses in a ridicule and teasing scenario questionnaire. The results replicated findings from earlier studies by showing that gelotophobes assigned the same emotions to friendly teasing and malicious ridicule (predominantly low joy, high fear, and shame). Gelotophilia was mainly predicted by relating joy to both, teasing and ridicule scenarios, while katagelasticism was predicted by assigning joy and contempt to ridicule scenarios. In Validation Sample 2 (N = 1,248), we investigated whether the fear of being laughed at is a vulnerability at the workplace: If friendly teasing and laughter of co-workers, superiors, or customers are misperceived as being malicious, individuals may feel less satisfied and more stressed. The results from a representative sample of Swiss employees showed that individuals with a fear of being laughed at are generally less satisfied with life and work and experience more work stress. Moreover, gelotophilia went along with positive evaluations of one's life and work, while katagelasticism was negatively related to work satisfaction and positively related to work stress. In order to establish good work practices and build procedures against workplace bullying, one needs to consider that individual differences impact on a person's perception of being bullied and assessing the three dispositions may give important insights into team processes. PMID:28553241

Nontraditional families and childhood progress through school: a comment on Rosenfeld.

PubMed

Allen, Douglas W; Pakaluk, Catherine; Price, Joseph

2013-06-01

We reexamine Rosenfeld's (2010) study on the association between child outcomes and same-sex family structure. Using the same data set, we replicate and generalize Rosenfeld's findings and show that the implications of his study are different when using either alternative comparison groups or alternative sample restrictions. Compared with traditional married households, we find that children being raised by same-sex couples are 35 % less likely to make normal progress through school; this difference is statistically significant at the 1 % level.

Pattern of cell kinetics in colorectal mucosa of patients with different types of adenomatous polyps of the large bowel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roncucci, L.; Scalmati, A.; Ponz de Leon, M.

1991-08-15

It is generally accepted that adenomatous polyps represent the natural precursor of many colorectal malignancies. The sequence, however, which leads from a normally appearing mucosa to cancer is complex and involves many steps, including a hyperproliferative mucosa with an upward expansion of the replicative compartment. The current study evaluates cell replication in normal colorectal mucosa of patients with adenomatous polyps of various types and relates the observed findings to the main clinical and morphologic features of adenomas. Forty-four patients with polyps and 27 controls entered the study. Samples of colorectal mucosa were taken at endoscopy and cell replication was evaluatedmore » with a standard autoradiographic procedure. Cell replication was expressed as labeling index (LI), in the whole crypt and in each of the five longitudinal compartments in which the crypts were divided. Total LI and LI per crypt compartment were significantly higher (P less than 0.02 and P less than 0.01, respectively) than in controls. There was no appreciable difference of LI values between patients with single or multiple, tubular or tubulovillous, small or large adenomas, but in all of these subgroups LI was significantly higher than in controls. In conclusion, in normally appearing colorectal mucosa of patients with adenomatous polyps there was a significant increase of cell replication and a marked upward expansion of the proliferative zone; these changes were more evident in the left colon and in the rectum. Finally, cell replication did not seem to be related to the number of polyps, to the most common histotypes, or to the pattern of recurrence.« less

The impact of sampling, PCR, and sequencing replication on discerning changes in drinking water bacterial community over diurnal time-scales.

PubMed

Bautista-de Los Santos, Quyen Melina; Schroeder, Joanna L; Blakemore, Oliver; Moses, Jonathan; Haffey, Mark; Sloan, William; Pinto, Ameet J

2016-03-01

High-throughput and deep DNA sequencing, particularly amplicon sequencing, is being increasingly utilized to reveal spatial and temporal dynamics of bacterial communities in drinking water systems. Whilst the sampling and methodological biases associated with PCR and sequencing have been studied in other environments, they have not been quantified for drinking water. These biases are likely to have the greatest effect on the ability to characterize subtle spatio-temporal patterns influenced by process/environmental conditions. In such cases, intra-sample variability may swamp any underlying small, systematic variation. To evaluate this, we undertook a study with replication at multiple levels including sampling sites, sample collection, PCR amplification, and high throughput sequencing of 16S rRNA amplicons. The variability inherent to the PCR amplification and sequencing steps is significant enough to mask differences between bacterial communities from replicate samples. This was largely driven by greater variability in detection of rare bacteria (relative abundance <0.01%) across PCR/sequencing replicates as compared to replicate samples. Despite this, we captured significant changes in bacterial community over diurnal time-scales and find that the extent and pattern of diurnal changes is specific to each sampling location. Further, we find diurnal changes in bacterial community arise due to differences in the presence/absence of the low abundance bacteria and changes in the relative abundance of dominant bacteria. Finally, we show that bacterial community composition is significantly different across sampling sites for time-periods during which there are typically rapid changes in water use. This suggests hydraulic changes (driven by changes in water demand) contribute to shaping the bacterial community in bulk drinking water over diurnal time-scales. Copyright © 2015 Elsevier Ltd. All rights reserved.

Support, shape and number of replicate samples for tree foliage analysis.

PubMed

Luyssaert, Sebastiaan; Mertens, Jan; Raitio, Hannu

2003-06-01

Many fundamental features of a sampling program are determined by the heterogeneity of the object under study and the settings for the error (alpha), the power (beta), the effect size (ES), the number of replicate samples, and sample support, which is a feature that is often overlooked. The number of replicates, alpha, beta, ES, and sample support are interconnected. The effect of the sample support and its shape on the required number of replicate samples was investigated by means of a resampling method. The method was applied to a simulated distribution of Cd in the crown of a Salix fragilis L. tree. Increasing the dimensions of the sample support results in a decrease in the variance of the element concentration under study. Analysis of the variance is often the foundation of statistical tests, therefore, valid statistical testing requires the use of a fixed sample support during the experiment. This requirement might be difficult to meet in time-series analyses and long-term monitoring programs. Sample supports have their largest dimension in the direction with the largest heterogeneity, i.e. the direction representing the crown height, and this will give more accurate results than supports with other shapes. Taking the relationships between the sample support and the variance of the element concentrations in tree crowns into account provides guidelines for sampling efficiency in terms of precision and costs. In terms of time, the optimal support to test whether the average Cd concentration of the crown exceeds a threshold value is 0.405 m3 (alpha = 0.05, beta = 0.20, ES = 1.0 mg kg(-1) dry mass). The average weight of this support is 23 g dry mass, and 11 replicate samples need to be taken. It should be noted that in this case the optimal support applies to Cd under conditions similar to those of the simulation, but not necessarily all the examinations for this tree species, element, and hypothesis test.

Patterns and predictors of ADHD persistence into adulthood: Results from the National Comorbidity Survey Replication

PubMed Central

Kessler, Ronald C.; Adler, Lenard A.; Barkley, Russell; Biederman, Joseph; Conners, C. Keith; Faraone, Stephen V.; Greenhill, Laurence L.; Jaeger, Savina; Secnik, Kristina; Spencer, Thomas; Üstün, T. Bedirhan; Zaslavsky, Alan M.

2010-01-01

BACKGROUND Despite growing interest in adult ADHD, little is known about predictors of persistence of childhood cases into adulthood. METHODS A retrospective assessment of childhood ADHD, childhood risk factors, and a screen for adult ADHD were included in a sample of 3197 18–44 year old respondents in the National Comorbidity Survey Replication (NCS-R). Blinded adult ADHD clinical reappraisal interviews were administered to a sub-sample of respondents. Multiple imputation (MI) was used to estimate adult persistence of childhood ADHD. Logistic regression was used to study retrospectively reported childhood predictors of persistence. Potential predictors included socio-demographics, childhood ADHD severity, childhood adversity, traumatic life experiences, and comorbid DSM-IV child-adolescent disorders (anxiety, mood, impulse-control, and substance disorders). RESULTS 36.3% of respondents with retrospectively assessed childhood ADHD were classified by blinded clinical interviews as meeting DSM-IV criteria for current ADHD. Childhood ADHD severity and childhood treatment significantly predicted persistence. Controlling for severity and excluding treatment, none of the other variables significantly predicted persistence even though they were significantly associated with childhood ADHD. CONCLUSIONS No modifiable risk factors were found for adult persistence of ADHD. Further research, ideally based on prospective general population samples, is needed to search for modifiable determinants of adult persistence of ADHD. PMID:15950019

Genome-wide scan of job-related exhaustion with three replication studies implicate a susceptibility variant at the UST gene locus

PubMed Central

Sulkava, Sonja; Ollila, Hanna M.; Ahola, Kirsi; Partonen, Timo; Viitasalo, Katriina; Kettunen, Johannes; Lappalainen, Maarit; Kivimäki, Mika; Vahtera, Jussi; Lindström, Jaana; Härmä, Mikko; Puttonen, Sampsa; Salomaa, Veikko; Paunio, Tiina

2013-01-01

Job-related exhaustion is the core dimension of burnout, a work-related stress syndrome that has several negative health consequences. In this study, we explored the molecular genetic background of job-related exhaustion. A genome-wide analysis of job-related exhaustion was performed in the GENMETS subcohort (n = 1256) of the Finnish population-based Health 2000 study. Replication analyses included an analysis of the strongest associations in the rest of the Health 2000 sample (n = 1660 workers) and in three independent populations (the FINRISK population cohort, n = 10 753; two occupational cohorts, total n = 1451). Job-related exhaustion was ascertained using a standard self-administered questionnaire (the Maslach Burnout Inventory (MBI)-GS exhaustion scale in the Health 2000 sample and the occupational cohorts) or a single question (FINRISK). A variant located in an intron of UST, uronyl-2-sulfotransferase (rs13219957), gave the strongest statistical evidence in the initial genome-wide study (P = 1.55 × 10−7), and was associated with job-related exhaustion in all the replication sets (P < 0.05; P = 6.75 × 10−7 from the meta-analysis). Consistent with studies of mood disorders, individual common genetic variants did not have any strong effect on job-related exhaustion. However, the nominally significant signals from the allelic variant of UST in four separate samples suggest that this variant might be a weak risk factor for job-related exhaustion. Together with the previously reported associations of other dermatan/chondroitin sulfate genes with mood disorders, these results indicate a potential molecular pathway for stress-related traits and mark a candidate region for further studies of job-related and general exhaustion. PMID:23620144

Relationship and variation of qPCR and culturable enterococci estimates in ambient surface waters are predictable

USGS Publications Warehouse

Whitman, Richard L.; Ge, Zhongfu; Nevers, Meredith B.; Boehm, Alexandria B.; Chern, Eunice C.; Haugland, Richard A.; Lukasik, Ashley M.; Molina, Marirosa; Przybyla-Kelly, Kasia; Shively, Dawn A.; White, Emily M.; Zepp, Richard G.; Byappanahalli, Muruleedhara N.

2010-01-01

The quantitative polymerase chain reaction (qPCR) method provides rapid estimates of fecal indicator bacteria densities that have been indicated to be useful in the assessment of water quality. Primarily because this method provides faster results than standard culture-based methods, the U.S. Environmental Protection Agency is currently considering its use as a basis for revised ambient water quality criteria. In anticipation of this possibility, we sought to examine the relationship between qPCR-based and culture-based estimates of enterococci in surface waters. Using data from several research groups, we compared enterococci estimates by the two methods in water samples collected from 37 sites across the United States. A consistent linear pattern in the relationship between cell equivalents (CCE), based on the qPCR method, and colony-forming units (CFU), based on the traditional culturable method, was significant (P 10CFU > 2.0/100 mL) while uncertainty increases at lower CFU values. It was further noted that the relative error in replicated qPCR estimates was generally higher than that in replicated culture counts even at relatively high target levels, suggesting a greater need for replicated analyses in the qPCR method to reduce relative error. Further studies evaluating the relationship between culture and qPCR should take into account analytical uncertainty as well as potential differences in results of these methods that may arise from sample variability, different sources of pollution, and environmental factors.

DEIsoM: a hierarchical Bayesian model for identifying differentially expressed isoforms using biological replicates

PubMed Central

Peng, Hao; Yang, Yifan; Zhe, Shandian; Wang, Jian; Gribskov, Michael; Qi, Yuan

2017-01-01

Abstract Motivation High-throughput mRNA sequencing (RNA-Seq) is a powerful tool for quantifying gene expression. Identification of transcript isoforms that are differentially expressed in different conditions, such as in patients and healthy subjects, can provide insights into the molecular basis of diseases. Current transcript quantification approaches, however, do not take advantage of the shared information in the biological replicates, potentially decreasing sensitivity and accuracy. Results We present a novel hierarchical Bayesian model called Differentially Expressed Isoform detection from Multiple biological replicates (DEIsoM) for identifying differentially expressed (DE) isoforms from multiple biological replicates representing two conditions, e.g. multiple samples from healthy and diseased subjects. DEIsoM first estimates isoform expression within each condition by (1) capturing common patterns from sample replicates while allowing individual differences, and (2) modeling the uncertainty introduced by ambiguous read mapping in each replicate. Specifically, we introduce a Dirichlet prior distribution to capture the common expression pattern of replicates from the same condition, and treat the isoform expression of individual replicates as samples from this distribution. Ambiguous read mapping is modeled as a multinomial distribution, and ambiguous reads are assigned to the most probable isoform in each replicate. Additionally, DEIsoM couples an efficient variational inference and a post-analysis method to improve the accuracy and speed of identification of DE isoforms over alternative methods. Application of DEIsoM to an hepatocellular carcinoma (HCC) dataset identifies biologically relevant DE isoforms. The relevance of these genes/isoforms to HCC are supported by principal component analysis (PCA), read coverage visualization, and the biological literature. Availability and implementation The software is available at https://github.com/hao-peng/DEIsoM Contact pengh@alumni.purdue.edu Supplementary information Supplementary data are available at Bioinformatics online. PMID:28595376

Challenges in reproducibility of genetic association studies: lessons learned from the obesity field.

PubMed

Li, A; Meyre, D

2013-04-01

A robust replication of initial genetic association findings has proved to be difficult in human complex diseases and more specifically in the obesity field. An obvious cause of non-replication in genetic association studies is the initial report of a false positive result, which can be explained by a non-heritable phenotype, insufficient sample size, improper correction for multiple testing, population stratification, technical biases, insufficient quality control or inappropriate statistical analyses. Replication may, however, be challenging even when the original study describes a true positive association. The reasons include underpowered replication samples, gene × gene, gene × environment interactions, genetic and phenotypic heterogeneity and subjective interpretation of data. In this review, we address classic pitfalls in genetic association studies and provide guidelines for proper discovery and replication genetic association studies with a specific focus on obesity.

Assessment of volatile organic compounds in surface water at West Branch Canal Creek, Aberdeen Proving Ground, Maryland, 1999

USGS Publications Warehouse

Olsen, Lisa D.; Spencer, Tracey A.

2000-01-01

The U.S. Geological Survey (USGS) collected 13 surface-water samples and 3 replicates from 5 sites in the West Branch Canal Creek area at Aberdeen Proving Ground from February through August 1999, as a part of an investigation of ground-water contamination and natural attenuation processes. The samples were analyzed for volatile organic compounds, including trichloroethylene, 1,1,2,2-tetrachloroethane, carbon tetrachloride, and chloroform, which are the four major contaminants that were detected in ground water in the Canal Creek area in earlier USGS studies. Field blanks were collected during the sampling period to assess sample bias. Field replicates were used to assess sample variability, which was expressed as relative percent difference. The mean variability of the surface-water replicate analyses was larger (35.4 percent) than the mean variability of ground-water replicate analyses (14.6 percent) determined for West Branch Canal Creek from 1995 through 1996. The higher variability in surface-water analyses is probably due to heterogeneities in the composition of the surface water rather than differences in sampling or analytical procedures. The most frequently detected volatile organic compound was 1,1,2,2- tetrachloroethane, which was detected in every sample and in two of the replicates. The surface-water contamination is likely the result of cross-media transfer of contaminants from the ground water and sediments along the West Branch Canal Creek. The full extent of surface-water contamination in West Branch Canal Creek and the locations of probable contaminant sources cannot be determined from this limited set of data. Tidal mixing, creek flow patterns, and potential effects of a drought that occurred during the sampling period also complicate the evaluation of surface-water contamination.

Precise replication of antireflective nanostructures from biotemplates

NASA Astrophysics Data System (ADS)

Gao, Hongjun; Liu, Zhongfan; Zhang, Jin; Zhang, Guoming; Xie, Guoyong

2007-03-01

The authors report herein a new type of nanonipple structures on the cicada's eye and the direct structural replication of the complex micro- and nanostructures for potential functional emulation. A two-step direct molding process is developed to replicate these natural micro- and nanostructures using epoxy resin with high fidelity, which demonstrates a general way of fabricating functional nanostructures by direct replication of natural biotemplates via a suitable physicochemical process. Measurements of spectral reflectance showed that this kind of replicated nanostructure has remarkable antireflective property, suggestive of its potential applications to optical devices.

Detection of human parvovirus 4 viremia in the follow-up blood samples from seropositive individuals suggests the existence of persistent viral replication or reactivation of latent viral infection.

PubMed

Chen, Mao-Yuan; Hung, Chien-Ching; Lee, Kuang-Lun

2015-06-19

The transmission routes for human parvovirus 4 (PARV4) infections in areas with high seroprevalence are not known. In the work described here, persistent PARV4 viral replication was investigated by conducting a longitudinal study. Ten healthcare workers each provided a blood sample at the beginning of the study (first sample) and 12 months later (second sample). The paired samples were tested for PARV4-positivity by immunoblotting analysis and nested polymerase chain reactions. IgG antibodies against PARV4 were detected in six participants, three of whom also had IgM antibodies against PARV4. The immunoblotting results did not vary over time. PARV4 DNA was detected in the first blood sample from one participant who had IgG antibodies against PARV4 and in the second blood samples from 2 participants who had IgG and IgM antibodies against PARV4. Detection of PARV4 DNA in the second blood samples from two seropositive participants suggests the existence of persistent PARV4 replication or reactivation of inactive virus in the tissues. The finding of persistent or intermittent PARV4 replication in individuals with past infections provides an important clue toward unraveling the non-parenteral transmission routes of PARV4 infection in areas where the virus is endemic.

Origins of DNA Replication and Amplification in the Breast Cancer Genome

DTIC Science & Technology

2011-09-01

AD_________________ Award Number: W81XWH-10-1-0463 TITLE: Origins of DNA Replication and...hypothesis we need to map origins of DNA replication in the genome and ask which of these coincide with sites of DNA amplification and with ER...Spring Harbor DNA Replication meetings this summer/earlyfall. Figures from the posters and also the abstracts are attached. The samples have been

Footedness Is Associated with Self-reported Sporting Performance and Motor Abilities in the General Population

PubMed Central

Tran, Ulrich S.; Voracek, Martin

2016-01-01

Left-handers may have strategic advantages over right-handers in interactive sports and innate superior abilities that are beneficial for sports. Previous studies relied on differing criteria for handedness classification and mostly did not investigate mixed preferences and footedness. Footedness appears to be less influenced by external and societal factors than handedness. Utilizing latent class analysis and structural equation modeling, we investigated in a series of studies (total N > 15300) associations of handedness and footedness with self-reported sporting performance and motor abilities in the general population. Using a discovery and a replication sample (ns = 7658 and 5062), Study 1 revealed replicable beneficial effects of mixed-footedness and left-footedness in team sports, martial arts and fencing, dancing, skiing, and swimming. Study 2 (n = 2592) showed that footedness for unskilled bipedal movement tasks, but not for skilled unipedal tasks, was beneficial for sporting performance. Mixed- and left-footedness had effects on motor abilities that were consistent with published results on better brain interhemispheric communication, but also akin to testosterone-induced effects regarding flexibility, strength, and endurance. Laterality effects were only small. Possible neural and hormonal bases of observed effects need to be examined in future studies. PMID:27559326

Generalized trust and intelligence in the United States.

PubMed

Carl, Noah; Billari, Francesco C

2014-01-01

Generalized trust refers to trust in other members of society; it may be distinguished from particularized trust, which corresponds to trust in the family and close friends. An extensive empirical literature has established that generalized trust is an important aspect of civic culture. It has been linked to a variety of positive outcomes at the individual level, such as entrepreneurship, volunteering, self-rated health, and happiness. However, two recent studies have found that it is highly correlated with intelligence, which raises the possibility that the other relationships in which it has been implicated may be spurious. Here we replicate the association between intelligence and generalized trust in a large, nationally representative sample of U.S. adults. We also show that, after adjusting for intelligence, generalized trust continues to be strongly associated with both self-rated health and happiness. In the context of substantial variation across countries, these results bolster the view that generalized trust is a valuable social resource, not only for the individual but for the wider society as well.

Generalized Trust and Intelligence in the United States

PubMed Central

Carl, Noah; Billari, Francesco C.

2014-01-01

Generalized trust refers to trust in other members of society; it may be distinguished from particularized trust, which corresponds to trust in the family and close friends. An extensive empirical literature has established that generalized trust is an important aspect of civic culture. It has been linked to a variety of positive outcomes at the individual level, such as entrepreneurship, volunteering, self-rated health, and happiness. However, two recent studies have found that it is highly correlated with intelligence, which raises the possibility that the other relationships in which it has been implicated may be spurious. Here we replicate the association between intelligence and generalized trust in a large, nationally representative sample of U.S. adults. We also show that, after adjusting for intelligence, generalized trust continues to be strongly associated with both self-rated health and happiness. In the context of substantial variation across countries, these results bolster the view that generalized trust is a valuable social resource, not only for the individual but for the wider society as well. PMID:24619035

Element concentrations in soils and other surficial materials of Alaska

USGS Publications Warehouse

Gough, L.P.; Severson, R.C.; Shacklette, H.T.

1988-01-01

Mean concentrations of 35 elements, ash yields, and pH have been estimated for samples of sils and other unconsolidated surficial materials from 266 collection locations throughout Alaska. These background values can be applied to studies of environmental geochemistry and health, wildlife management, and soil-forming processes in cold climates and to computation of element abundances on a regional or worldwide scale. Limited data for an additoinal eight elements are also presented. Materials were collected using a one-way, three-level, analysis-of-variance samplling design in which collecting procedures were simplified for the convenience of the many volunteer field workers. The sample collectors were asked to avoid locations of known mineral deposits and obvious contamination, to take samples at a depth of about 20 cm where possible, and to take a replicate sample about 100 m distant from the first sample collected. With more than 60 percent of the samples replicated and 14 percent of the samples split for duplicate laboratory analyses, reliable estimates were made of the variability in element concentrations at two geographic scales and of the error associated with sample handling and laboratory procedures. Mean concentrations of most elements in surficial materials from the state of alaska correspond well with those reported in similar materials from the conterminous United STatess. Most element concentrations and ranges in samples of stream and lake sediments from Alaska, however, as reported in the literature, do not correspond well with those found in surficial materials of this study. This lack of correspondence is attributed to (1) a merger of two kinds ofsediments (stream and lake) for calculating means; (2) elimination from the sediment mean calculations of values below the limit of quantitative determination; (3) analytical methods different from those of the surficial materials study; and (4) most importantly, the inherent differences in chemistry of the materials. The distribution of variability in element concentrations o Alaskan surficial-material samples was, for most elements, largely among sampling locations, with only a samll part of the variability occurring between replicate samples at a location. The geochemical uniformity within sampling locations in Alaska is an expression of uniform geochemical cycling processes within small geographic areas. The concentration values for 35 elements in 266 samples were plotted on maps by symbols representing classes of concentration frequency distributions. These plotted symbols form patterns that may or may not be possible to interpret but nevertheless show differences that are observable at several geographical scales. The largest pattern is one generally low concentrations of many elements in materials from arctic and oceanic tundra regions, as contrasted to their often high concentrations in samples from interior and southeastern Alaska. The patttern for sodium isespecially pronounced. Intermediate-sized patterns are shown, for example, by the generally high values for magnesium and low values for silicon in the coastal forest region of southeastern Alaska. Many elements occur at low concentratoins in samples from the Alaskan peninsula and the Aleutian Islands. The degree of confidence in patterns of element abundance is expected to be in direct proportion to the number of samples included in the area. As the patterns become smaller, the probability increases that the patterns are not reproducible.

A replication of a factor analysis of motivations for trapping

USGS Publications Warehouse

Schroeder, Susan; Fulton, David C.

2015-01-01

Using a 2013 sample of Minnesota trappers, we employed confirmatory factor analysis to replicate an exploratory factor analysis of trapping motivations conducted by Daigle, Muth, Zwick, and Glass (1998).  We employed the same 25 items used by Daigle et al. and tested the same five-factor structure using a recent sample of Minnesota trappers. We also compared motivations in our sample to those reported by Daigle et el.

A Tumor-stroma Targeted Oncolytic Adenovirus Replicated in Human Ovary Cancer Samples and Inhibited Growth of Disseminated Solid Tumors in Mice

PubMed Central

Lopez, M Veronica; Rivera, Angel A; Viale, Diego L; Benedetti, Lorena; Cuneo, Nicasio; Kimball, Kristopher J; Wang, Minghui; Douglas, Joanne T; Zhu, Zeng B; Bravo, Alicia I; Gidekel, Manuel; Alvarez, Ronald D; Curiel, David T; Podhajcer, Osvaldo L

2012-01-01

Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 1010 v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15–40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression. PMID:22948673

Estimation of genetic parameters and their sampling variances of quantitative traits in the type 2 modified augmented design

USDA-ARS?s Scientific Manuscript database

We proposed a method to estimate the error variance among non-replicated genotypes, thus to estimate the genetic parameters by using replicated controls. We derived formulas to estimate sampling variances of the genetic parameters. Computer simulation indicated that the proposed methods of estimatin...

Synthesizing Results from Replication Studies Using Robust Variance Estimation: Corrections When the Number of Studies Is Small

ERIC Educational Resources Information Center

Tipton, Elizabeth

2014-01-01

Replication studies allow for making comparisons and generalizations regarding the effectiveness of an intervention across different populations, versions of a treatment, settings and contexts, and outcomes. One method for making these comparisons across many replication studies is through the use of meta-analysis. A recent innovation in…

Ancient diversification of eukaryotic MCM DNA replication proteins

PubMed Central

Liu, Yuan; Richards, Thomas A; Aves, Stephen J

2009-01-01

Background Yeast and animal cells require six mini-chromosome maintenance proteins (Mcm2-7) for pre-replication complex formation, DNA replication initiation and DNA synthesis. These six individual MCM proteins form distinct heterogeneous subunits within a hexamer which is believed to form the replicative helicase and which associates with the essential but non-homologous Mcm10 protein during DNA replication. In contrast Archaea generally only possess one MCM homologue which forms a homohexameric MCM helicase. In some eukaryotes Mcm8 and Mcm9 paralogues also appear to be involved in DNA replication although their exact roles are unclear. Results We used comparative genomics and phylogenetics to reconstruct the diversification of the eukaryotic Mcm2-9 gene family, demonstrating that Mcm2-9 were formed by seven gene duplication events before the last common ancestor of the eukaryotes. Mcm2-7 protein paralogues were present in all eukaryote genomes studied suggesting that no gene loss or functional replacements have been tolerated during the evolutionary diversification of eukaryotes. Mcm8 and 9 are widely distributed in eukaryotes and group together on the MCM phylogenetic tree to the exclusion of all other MCM paralogues suggesting co-ancestry. Mcm8 and Mcm9 are absent in some taxa, including Trichomonas and Giardia, and appear to have been secondarily lost in some fungi and some animals. The presence and absence of Mcm8 and 9 is concordant in all taxa sampled with the exception of Drosophila species. Mcm10 is present in most eukaryotes sampled but shows no concordant pattern of presence or absence with Mcm8 or 9. Conclusion A multifaceted and heterogeneous Mcm2-7 hexamer evolved during the early evolution of the eukaryote cell in parallel with numerous other acquisitions in cell complexity and prior to the diversification of extant eukaryotes. The conservation of all six paralogues throughout the eukaryotes suggests that each Mcm2-7 hexamer component has an exclusive functional role, either by a combination of unique lock and key interactions between MCM hexamer subunits and/or by a range of novel side interactions. Mcm8 and 9 evolved early in eukaryote cell evolution and their pattern of presence or absence suggests that they may have linked functions. Mcm8 is highly divergent in all Drosophila species and may not provide a good model for Mcm8 in other eukaryotes. PMID:19292915

Method for replicating an array of nucleic acid probes

DOEpatents

Cantor, Charles R.; Przetakiewicz, Marek; Smith, Cassandra L.; Sano, Takeshi

1998-01-01

The invention relates to the replication of probe arrays and methods for replicating arrays of probes which are useful for the large scale manufacture of diagnostic aids used to screen biological samples for specific target sequences. Arrays created using PCR technology may comprise probes with 5'- and/or 3'-overhangs.

Association of genetic risk scores with body mass index in Swiss psychiatric cohorts.

PubMed

Saigi-Morgui, Núria; Vandenberghe, Frederik; Delacrétaz, Aurélie; Quteineh, Lina; Gholamrezaee, Mehdi; Aubry, Jean-Michel; von Gunten, Armin; Kutalik, Zoltán; Conus, Philippe; Eap, Chin B

2016-05-01

Weight gain is associated with psychiatric disorders and/or with psychotropic drug treatments. We analyzed in three psychiatric cohorts under psychotropic treatment the association of weighted genetic risk scores (w-GRSs) with BMI by integrating BMI-related polymorphisms from the candidate-gene approach and Genome-Wide Association Studies (GWAS). w-GRS of 32 polymorphisms associated previously with BMI in general population GWAS and 20 polymorphisms associated with antipsychotics-induced weight gain were investigated in three independent psychiatric samples. w-GRS of 32 polymorphisms were significantly associated with BMI in the psychiatric sample 1 (n=425) and were replicated in another sample (n=177). Those at the percentile 95 (p95) of the score had 2.26 and 2.99 kg/m(2) higher predicted BMI compared with individuals at the percentile 5 (p5) in sample 1 and in sample 3 (P=0.009 and 0.04, respectively). When combining all samples together (n=750), a significant difference of 1.89 kg/m(2) predicted BMI was found between p95 and p5 individuals at 12 months of treatment. Stronger associations were found among men (difference: 2.91 kg/m(2) of predicted BMI between p95 and p5, P=0.0002), whereas no association was found among women. w-GRS of 20 polymorphisms was not associated with BMI. The w-GRS of 52 polymorphisms and the clinical variables (age, sex, treatment) explained 1.99 and 3.15%, respectively, of BMI variability. The present study replicated in psychiatric cohorts previously identified BMI risk variants obtained in GWAS analyses from population-based samples. Sex-specific analysis should be considered in further analysis.

General, crystallized and fluid intelligence are not associated with functional global network efficiency: A replication study with the human connectome project 1200 data set.

PubMed

Kruschwitz, J D; Waller, L; Daedelow, L S; Walter, H; Veer, I M

2018-05-01

One hallmark example of a link between global topological network properties of complex functional brain connectivity and cognitive performance is the finding that general intelligence may depend on the efficiency of the brain's intrinsic functional network architecture. However, although this association has been featured prominently over the course of the last decade, the empirical basis for this broad association of general intelligence and global functional network efficiency is quite limited. In the current study, we set out to replicate the previously reported association between general intelligence and global functional network efficiency using the large sample size and high quality data of the Human Connectome Project, and extended the original study by testing for separate association of crystallized and fluid intelligence with global efficiency, characteristic path length, and global clustering coefficient. We were unable to provide evidence for the proposed association between general intelligence and functional brain network efficiency, as was demonstrated by van den Heuvel et al. (2009), or for any other association with the global network measures employed. More specifically, across multiple network definition schemes, ranging from voxel-level networks to networks of only 100 nodes, no robust associations and only very weak non-significant effects with a maximal R 2 of 0.01 could be observed. Notably, the strongest (non-significant) effects were observed in voxel-level networks. We discuss the possibility that the low power of previous studies and publication bias may have led to false positive results fostering the widely accepted notion of general intelligence being associated to functional global network efficiency. Copyright © 2018 Elsevier Inc. All rights reserved.

Cross-Cultural Study of Information Processing Biases in Chronic Fatigue Syndrome: Comparison of Dutch and UK Chronic Fatigue Patients.

PubMed

Hughes, Alicia M; Hirsch, Colette R; Nikolaus, Stephanie; Chalder, Trudie; Knoop, Hans; Moss-Morris, Rona

2018-02-01

This study aims to replicate a UK study, with a Dutch sample to explore whether attention and interpretation biases and general attentional control deficits in chronic fatigue syndrome (CFS) are similar across populations and cultures. Thirty eight Dutch CFS participants were compared to 52 CFS and 51 healthy participants recruited from the UK. Participants completed self-report measures of symptoms, functioning, and mood, as well as three experimental tasks (i) visual-probe task measuring attentional bias to illness (somatic symptoms and disability) versus neutral words, (ii) interpretive bias task measuring positive versus somatic interpretations of ambiguous information, and (iii) the Attention Network Test measuring general attentional control. Compared to controls, Dutch and UK participants with CFS showed a significant attentional bias for illness-related words and were significantly more likely to interpret ambiguous information in a somatic way. These effects were not moderated by attentional control. There were no significant differences between the Dutch and UK CFS groups on attentional bias, interpretation bias, or attentional control scores. This study replicated the main findings of the UK study, with a Dutch CFS population, indicating that across these two cultures, people with CFS demonstrate biases in how somatic information is attended to and interpreted. These illness-specific biases appear to be unrelated to general attentional control deficits.

Social Exclusion Index-for Health Surveys (SEI-HS): a prospective nationwide study to extend and validate a multidimensional social exclusion questionnaire.

PubMed

van Bergen, Addi P L; Hoff, Stella J M; Schreurs, Hanneke; van Loon, Annelies; van Hemert, Albert M

2017-03-14

Social exclusion (SE) refers to the inability of certain groups or individuals to fully participate in society. SE is associated with socioeconomic inequalities in health, and its measurement in routine public health monitoring is considered key to designing effective health policies. In an earlier retrospective analysis we demonstrated that in all four major Dutch cities, SE could largely be measured with existing local public health monitoring data. The current prospective study is aimed at constructing and validating an extended national measure for SE that optimally employs available items. In 2012, a stratified general population sample of 258,928 Dutch adults completed a version of the Netherlands Public Health Monitor (PHM) questionnaire in which 9 items were added covering aspects of SE that were found to be missing in our previous research. Items were derived from the SCP social exclusion index, a well-constructed 15-item instrument developed by the Netherlands Institute for Social Research (SCP). The dataset was randomly divided into a development sample (N =129,464) and a validation sample (N = 129,464). Canonical correlation analysis was conducted in the development sample. The psychometric properties were studied and compared with those of the original SCP index. All analyses were then replicated in the validation sample. The analysis yielded a four dimensional index, the Social Exclusion Index for Health Surveys (SEI-HS), containing 8 SCP items and 9 PHM items. The four dimensions: "lack of social participation", "material deprivation", "lack of normative integration" and "inadequate access to basic social rights", were each measured with 3 to 6 items. The SEI-HS showed adequate internal consistency for both the general index and for two of four dimension scales. The internal structure and construct validity of the SEI-HS were satisfactory and similar to the original SCP index. Replication of the SEI-HS in the validation sample confirmed its generalisability. This study demonstrates that the SEI-HS offers epidemiologists and public health researchers a uniform, reliable, valid and efficient means of assessing social exclusion and its underlying dimensions. The study also provides valuable insights in how to develop embedded measures for public health surveillance.

Sources of work motivation of business leaders in the USA and South Africa: a cross-cultural comparison using the Motivational Sources Inventory.

PubMed

Barbuto, John E; Gifford, Gregory T

2007-10-01

Motivational differences in response to the Motivation Sources Inventory were tested between U.S. (n = 138) and South-African (n = 114) work samples. Analysis indicated that American managers scored significantly higher on intrinsic process (fun), while South-African managers scored significantly higher on self-concept external and goal internalization when measured using ratio analysis. Replication and extension with large groups representative of populations of interest in conjunction with Hofstede's cultural dimensions could allow generalization.

Re-examination of assertiveness and aggressiveness as potential moderators of verbal intentions.

PubMed

Swanson, S R

1999-06-01

This research reports the results of a replication of Swanson and McIntyre's 1998 study of assertiveness and aggressiveness as potential moderators of verbal intentions. A convenience sample of 119 women and 71 men participated. Nonassertive subjects were least likely, while Resort-to-Aggressive subjects were the most likely, to talk with acquaintances and others. Nonassertive and Assertive subjects were significantly more likely than Aggressive ones to make recommendations. Finally, men and women scored equally assertive, but men were more likely to score aggressive. The findings generally support the earlier work.

Automated solid-phase extraction workstations combined with quantitative bioanalytical LC/MS.

PubMed

Huang, N H; Kagel, J R; Rossi, D T

1999-03-01

An automated solid-phase extraction workstation was used to develop, characterize and validate an LC/MS/MS method for quantifying a novel lipid-regulating drug in dog plasma. Method development was facilitated by workstation functions that allowed wash solvents of varying organic composition to be mixed and tested automatically. Precision estimates for this approach were within 9.8% relative standard deviation (RSD) across the calibration range. Accuracy for replicate determinations of quality controls was between -7.2 and +6.2% relative error (RE) over 5-1,000 ng/ml(-1). Recoveries were evaluated for a wide variety of wash solvents, elution solvents and sorbents. Optimized recoveries were generally > 95%. A sample throughput benchmark for the method was approximately equal 8 min per sample. Because of parallel sample processing, 100 samples were extracted in less than 120 min. The approach has proven useful for use with LC/MS/MS, using a multiple reaction monitoring (MRM) approach.

You Cannot Step Into the Same River Twice: When Power Analyses Are Optimistic.

PubMed

McShane, Blakeley B; Böckenholt, Ulf

2014-11-01

Statistical power depends on the size of the effect of interest. However, effect sizes are rarely fixed in psychological research: Study design choices, such as the operationalization of the dependent variable or the treatment manipulation, the social context, the subject pool, or the time of day, typically cause systematic variation in the effect size. Ignoring this between-study variation, as standard power formulae do, results in assessments of power that are too optimistic. Consequently, when researchers attempting replication set sample sizes using these formulae, their studies will be underpowered and will thus fail at a greater than expected rate. We illustrate this with both hypothetical examples and data on several well-studied phenomena in psychology. We provide formulae that account for between-study variation and suggest that researchers set sample sizes with respect to our generally more conservative formulae. Our formulae generalize to settings in which there are multiple effects of interest. We also introduce an easy-to-use website that implements our approach to setting sample sizes. Finally, we conclude with recommendations for quantifying between-study variation. © The Author(s) 2014.

Death Anxiety, Reliability, Validity, and Factorial Structure of the Farsi Form of the Arabic Scale of Death Anxiety in Iranian Old-Aged Persons

PubMed Central

Dadfar, Mahboubeh; Lester, David

2016-01-01

The present study is aimed at examining the level of death anxiety and the sex-related differences among old-aged Iranian individuals sample to compare the old-aged persons with young college students and to explore the psychometric properties of the Arabic Scale of Death Anxiety (ASDA) factors in old-aged sample. A sample of 146 volunteer Iranian individuals took part in the study. The mean ages were 68.58 (SD = 7.10), men 68.81 (SD = 7.44) and women 68.28 (SD = 6.76), respectively. The mean score of the ASDA was 51.09 (SD = 20.19). Cronbach's alpha of the ASDA was found to be high (0.94); and Spearman-Brown coefficient was 0.92. Women had a significantly higher mean total score on the ASDA. Old-aged individuals had a significantly higher mean ASDA total score than younger college students (M age = 25.77). The factor analysis of the ASDA items yielded three factors accounting for 67.88% of the total variance labeled (F1) fear of dead people and tombs; (F2) fear of lethal disease and postmortem events; and (F3) death fear. These factors were highly replicable with previous factors extracted from a middle-aged Kuwaiti sample. On the basis of the present results, there are the following three general conclusions: death anxiety is not significantly correlated with age; the sex-related differences on death anxiety are striking in the Iranian samples; and the ASDA has a highly replicable factor structure among two Iranian and Arab countries. PMID:27867662

Death Anxiety, Reliability, Validity, and Factorial Structure of the Farsi Form of the Arabic Scale of Death Anxiety in Iranian Old-Aged Persons.

PubMed

Dadfar, Mahboubeh; Lester, David; Bahrami, Fazel

2016-01-01

The present study is aimed at examining the level of death anxiety and the sex-related differences among old-aged Iranian individuals sample to compare the old-aged persons with young college students and to explore the psychometric properties of the Arabic Scale of Death Anxiety (ASDA) factors in old-aged sample. A sample of 146 volunteer Iranian individuals took part in the study. The mean ages were 68.58 (SD = 7.10), men 68.81 (SD = 7.44) and women 68.28 (SD = 6.76), respectively. The mean score of the ASDA was 51.09 (SD = 20.19). Cronbach's alpha of the ASDA was found to be high (0.94); and Spearman-Brown coefficient was 0.92. Women had a significantly higher mean total score on the ASDA. Old-aged individuals had a significantly higher mean ASDA total score than younger college students (M age = 25.77). The factor analysis of the ASDA items yielded three factors accounting for 67.88% of the total variance labeled (F1) fear of dead people and tombs; (F2) fear of lethal disease and postmortem events; and (F3) death fear. These factors were highly replicable with previous factors extracted from a middle-aged Kuwaiti sample. On the basis of the present results, there are the following three general conclusions: death anxiety is not significantly correlated with age; the sex-related differences on death anxiety are striking in the Iranian samples; and the ASDA has a highly replicable factor structure among two Iranian and Arab countries.

The post-event processing questionnaire in a clinical sample with social phobia.

PubMed

McEvoy, Peter M; Kingsep, Patrick

2006-11-01

Post-event processing (PEP) involving rumination about perceived inadequacy in a past social situation has been proposed as an important maintaining factor in social phobia. The three aims of this study were to examine (a) the factor structure and internal reliability of a modified version of the Post-Event Processing Questionnaire [Rachman, S., Grüter-Andrew, J., & Shafran, R. (2000). Post-event processing in social anxiety. Behaviour Research and Therapy, 38, 611-617] in a clinical sample with social phobia (N=117), (b) the associations between PEP and symptoms of anxiety and depression, and (c) the relationship between perspective-taking ('field' and 'observer') and anxiety. Principal axis factor analysis yielded a highly reliable one-factor solution in our clinical sample, which generally replicated Rachman et al.'s findings with a sample of undergraduate students. PEP was most strongly and independently associated with state anxiety when depression, general anxiety and stress were controlled for. Contrary to expectations, PEP was not related to measures of social anxiety. The relationship between perspective-taking and anxiety was more complex than expected. Theoretical implications of these findings are discussed with reference to contemporary cognitive-behavioural models of social phobia.

Derived Basic Ability Factors: A Factor Analysis Replication Study.

ERIC Educational Resources Information Center

Lee, Mickey, M.; Lee, Lynda Newby

The purpose of this study was to replicate the study conducted by Potter, Sagraves, and McDonald to determine whether their recommended analysis could separate criterion variables into similar factors that were stable from year to year and from school to school. The replication samples consisted of all students attending Louisiana State University…

Method for replicating an array of nucleic acid probes

DOEpatents

Cantor, C.R.; Przetakiewicz, M.; Smith, C.L.; Sano, T.

1998-08-18

The invention relates to the replication of probe arrays and methods for replicating arrays of probes which are useful for the large scale manufacture of diagnostic aids used to screen biological samples for specific target sequences. Arrays created using PCR technology may comprise probes with 5{prime}- and/or 3{prime}-overhangs. 16 figs.

Proteasome-dependent degradation of replisome components regulates faithful DNA replication.

PubMed

Roseaulin, Laura C; Noguchi, Chiaki; Noguchi, Eishi

2013-08-15

The replication machinery, or the replisome, collides with a variety of obstacles during the normal process of DNA replication. In addition to damaged template DNA, numerous chromosome regions are considered to be difficult to replicate owing to the presence of DNA secondary structures and DNA-binding proteins. Under these conditions, the replication fork stalls, generating replication stress. Stalled forks are prone to collapse, posing serious threats to genomic integrity. It is generally thought that the replication checkpoint functions to stabilize the replisome and replication fork structure upon replication stress. This is important in order to allow DNA replication to resume once the problem is solved. However, our recent studies demonstrated that some replisome components undergo proteasome-dependent degradation during DNA replication in the fission yeast Schizosaccharomyces pombe. Our investigation has revealed the involvement of the SCF(Pof3) (Skp1-Cullin/Cdc53-F-box) ubiquitin ligase in replisome regulation. We also demonstrated that forced accumulation of the replisome components leads to abnormal DNA replication upon replication stress. Here we review these findings and present additional data indicating the importance of replisome degradation for DNA replication. Our studies suggest that cells activate an alternative pathway to degrade replisome components in order to preserve genomic integrity.

Replicating Health Economic Models: Firm Foundations or a House of Cards?

PubMed

Bermejo, Inigo; Tappenden, Paul; Youn, Ji-Hee

2017-11-01

Health economic evaluation is a framework for the comparative analysis of the incremental health gains and costs associated with competing decision alternatives. The process of developing health economic models is usually complex, financially expensive and time-consuming. For these reasons, model development is sometimes based on previous model-based analyses; this endeavour is usually referred to as model replication. Such model replication activity may involve the comprehensive reproduction of an existing model or 'borrowing' all or part of a previously developed model structure. Generally speaking, the replication of an existing model may require substantially less effort than developing a new de novo model by bypassing, or undertaking in only a perfunctory manner, certain aspects of model development such as the development of a complete conceptual model and/or comprehensive literature searching for model parameters. A further motivation for model replication may be to draw on the credibility or prestige of previous analyses that have been published and/or used to inform decision making. The acceptability and appropriateness of replicating models depends on the decision-making context: there exists a trade-off between the 'savings' afforded by model replication and the potential 'costs' associated with reduced model credibility due to the omission of certain stages of model development. This paper provides an overview of the different levels of, and motivations for, replicating health economic models, and discusses the advantages, disadvantages and caveats associated with this type of modelling activity. Irrespective of whether replicated models should be considered appropriate or not, complete replicability is generally accepted as a desirable property of health economic models, as reflected in critical appraisal checklists and good practice guidelines. To this end, the feasibility of comprehensive model replication is explored empirically across a small number of recent case studies. Recommendations are put forward for improving reporting standards to enhance comprehensive model replicability.

Reproducibility of R-fMRI metrics on the impact of different strategies for multiple comparison correction and sample sizes.

PubMed

Chen, Xiao; Lu, Bin; Yan, Chao-Gan

2018-01-01

Concerns regarding reproducibility of resting-state functional magnetic resonance imaging (R-fMRI) findings have been raised. Little is known about how to operationally define R-fMRI reproducibility and to what extent it is affected by multiple comparison correction strategies and sample size. We comprehensively assessed two aspects of reproducibility, test-retest reliability and replicability, on widely used R-fMRI metrics in both between-subject contrasts of sex differences and within-subject comparisons of eyes-open and eyes-closed (EOEC) conditions. We noted permutation test with Threshold-Free Cluster Enhancement (TFCE), a strict multiple comparison correction strategy, reached the best balance between family-wise error rate (under 5%) and test-retest reliability/replicability (e.g., 0.68 for test-retest reliability and 0.25 for replicability of amplitude of low-frequency fluctuations (ALFF) for between-subject sex differences, 0.49 for replicability of ALFF for within-subject EOEC differences). Although R-fMRI indices attained moderate reliabilities, they replicated poorly in distinct datasets (replicability < 0.3 for between-subject sex differences, < 0.5 for within-subject EOEC differences). By randomly drawing different sample sizes from a single site, we found reliability, sensitivity and positive predictive value (PPV) rose as sample size increased. Small sample sizes (e.g., < 80 [40 per group]) not only minimized power (sensitivity < 2%), but also decreased the likelihood that significant results reflect "true" effects (PPV < 0.26) in sex differences. Our findings have implications for how to select multiple comparison correction strategies and highlight the importance of sufficiently large sample sizes in R-fMRI studies to enhance reproducibility. Hum Brain Mapp 39:300-318, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Blood pressure loci identified with a gene-centric array.

PubMed

Johnson, Toby; Gaunt, Tom R; Newhouse, Stephen J; Padmanabhan, Sandosh; Tomaszewski, Maciej; Kumari, Meena; Morris, Richard W; Tzoulaki, Ioanna; O'Brien, Eoin T; Poulter, Neil R; Sever, Peter; Shields, Denis C; Thom, Simon; Wannamethee, Sasiwarang G; Whincup, Peter H; Brown, Morris J; Connell, John M; Dobson, Richard J; Howard, Philip J; Mein, Charles A; Onipinla, Abiodun; Shaw-Hawkins, Sue; Zhang, Yun; Davey Smith, George; Day, Ian N M; Lawlor, Debbie A; Goodall, Alison H; Fowkes, F Gerald; Abecasis, Gonçalo R; Elliott, Paul; Gateva, Vesela; Braund, Peter S; Burton, Paul R; Nelson, Christopher P; Tobin, Martin D; van der Harst, Pim; Glorioso, Nicola; Neuvrith, Hani; Salvi, Erika; Staessen, Jan A; Stucchi, Andrea; Devos, Nabila; Jeunemaitre, Xavier; Plouin, Pierre-François; Tichet, Jean; Juhanson, Peeter; Org, Elin; Putku, Margus; Sõber, Siim; Veldre, Gudrun; Viigimaa, Margus; Levinsson, Anna; Rosengren, Annika; Thelle, Dag S; Hastie, Claire E; Hedner, Thomas; Lee, Wai K; Melander, Olle; Wahlstrand, Björn; Hardy, Rebecca; Wong, Andrew; Cooper, Jackie A; Palmen, Jutta; Chen, Li; Stewart, Alexandre F R; Wells, George A; Westra, Harm-Jan; Wolfs, Marcel G M; Clarke, Robert; Franzosi, Maria Grazia; Goel, Anuj; Hamsten, Anders; Lathrop, Mark; Peden, John F; Seedorf, Udo; Watkins, Hugh; Ouwehand, Willem H; Sambrook, Jennifer; Stephens, Jonathan; Casas, Juan-Pablo; Drenos, Fotios; Holmes, Michael V; Kivimaki, Mika; Shah, Sonia; Shah, Tina; Talmud, Philippa J; Whittaker, John; Wallace, Chris; Delles, Christian; Laan, Maris; Kuh, Diana; Humphries, Steve E; Nyberg, Fredrik; Cusi, Daniele; Roberts, Robert; Newton-Cheh, Christopher; Franke, Lude; Stanton, Alice V; Dominiczak, Anna F; Farrall, Martin; Hingorani, Aroon D; Samani, Nilesh J; Caulfield, Mark J; Munroe, Patricia B

2011-12-09

Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Is spacing really the “friend of induction”?

PubMed Central

Verkoeijen, Peter P. J. L.; Bouwmeester, Samantha

2014-01-01

Inductive learning takes place when people learn a new concept or category by observing a variety of exemplars. Kornell and Bjork (2008) asked participants to learn new painting styles either by presenting different paintings of the same artist consecutively (massed presentation) or by mixing paintings of different artists (spaced presentation). In their second experiment, Kornell and Bjork (2008) showed with a final style recognition test, that spacing resulted in better inductive learning than massing. Also, by using this style recognition test, they ruled out the possibility that spacing merely resulted in a better memory for the labels of the newly learned painting styles. The findings from Kornell and Bjork’s (2008) second experiment are important because they show that the benefit of spaced learning generalizes to complex learning tasks and outcomes, and that it is not confined to rote memory learning. However, the findings from Kornell and Bjork’s (2008) second experiment have never been replicated. In the present study we performed an exact and high-powered replication of Kornell and Bjork’s (2008) second experiment with a Web-based sample. Such a replication contributes to establish the reliability of the original finding and hence to more conclusive evidence of the spacing effect in inductive learning. The findings from the present replication attempt revealed a medium-sized advantage of spacing over massing in inductive learning, which was comparable to the original effect in the experiment by Kornell and Bjork (2008). Also, the 95% confidence intervals (CI) of the effect sizes from both experiments overlapped considerably. Hence, the findings from the present replication experiment and the original experiment clearly reinforce each other. PMID:24744742

Simple systems that exhibit self-directed replication

NASA Technical Reports Server (NTRS)

Reggia, James A.; Armentrout, Steven L.; Chou, Hui-Hsien; Peng, Yun

1993-01-01

Biological experience and intuition suggest that self-replication is an inherently complex phenomenon, and early cellular automata models support that conception. More recently, simpler computational models of self-directed replication called sheathed loops have been developed. It is shown here that 'unsheathing' these structures and altering certain assumptions about the symmetry of their components leads to a family of nontrivial self-replicating structures some substantially smaller and simpler than those previously reported. The dependence of replication time and transition function complexity on initial structure size, cell state symmetry, and neighborhood are examined. These results support the view that self-replication is not an inherently complex phenomenon but rather an emergent property arising from local interactions in systems that can be much simpler than is generally believed.

Trajectory of Externalizing Child Behaviors in a KEEP Replication

ERIC Educational Resources Information Center

Uretsky, Mathew C.; Lee, Bethany R.; Greeno, Elizabeth J.; Barth, Richard P.

2017-01-01

Objective: The purpose of this study is to examine the correlates of child behavior change over time in a replication of the KEEP intervention. Method: The study sample was drawn from the treatment group of the Maryland replication of KEEP (n=65). Change over time was analyzed using multilevel linear mixed modeling. Results: Parents' use of…

Validation of the self-beliefs related to social anxiety scale: a replication and extension.

PubMed

Wong, Quincy J J; Moulds, Michelle L; Rapee, Ronald M

2014-06-01

The importance of self-beliefs in prominent models of social phobia has led to the development of measures that tap this cognitive construct. The Self-Beliefs Related to Social Anxiety (SBSA) Scale is one such measure and taps the three maladaptive belief types proposed in Clark and Wells's model of social phobia. This study aimed to replicate and extend previous research on the psychometric properties of the SBSA. Replicating previous research, in an (undiagnosed) undergraduate sample (n = 235), the SBSA was found to have a correlated three-factor structure using confirmatory factor analyses, and the SBSA and its subscales demonstrated good internal consistency and test-retest reliability. The SBSA and its subscales also had unique relationships with social anxiety and depression, the majority of which replicated previous research. Extending previous research, the SBSA and its subscales showed good incremental validity in the undergraduate sample and good discriminative validity using the undergraduate sample and a sample of individuals with social phobia (n = 33). The SBSA's strong theoretical basis and the findings of this study suggest that the SBSA is an ideal research and clinical tool to assess the cognitions characteristic of social phobia. © The Author(s) 2013.

Particle size and chemical control of heavy metals in bed sediment from the Rouge River, southeast Michigan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murray, K.S.; Cauvet, D.; Lybeer, M.

1999-04-01

Anthropogenic activities related to 100 years of industrialization in the metropolitan Detroit area have significantly enriched the bed sediment of the lower reaches of the Rouge River in Cr, Cu, Fe, Ni, Pb, and Zn. These enriched elements, which may represent a threat to biota, are predominantly present in sequentially extracted reducible and oxidizable chemical phases with small contributions from residual phases. In size-fractionated samples trace metal concentrations generally increase with decreasing particle size, with the greatest contribution to this increase from the oxidizable phase. Experimental results obtained on replicate samples of river sediment demonstrate that the accuracy of themore » sequential extraction procedure, evaluated by comparing the sums of the three individual fractions, is generally better than 10%. Oxidizable and reducible phases therefore constitute important sources of potentially available heavy metals that need to be explicitly considered when evaluating sediment and water quality impacts on biota.« less

Importance of the efficiency of double-stranded DNA formation in cDNA synthesis for the imprecision of microarray expression analysis.

PubMed

Thormar, Hans G; Gudmundsson, Bjarki; Eiriksdottir, Freyja; Kil, Siyoen; Gunnarsson, Gudmundur H; Magnusson, Magnus Karl; Hsu, Jason C; Jonsson, Jon J

2013-04-01

The causes of imprecision in microarray expression analysis are poorly understood, limiting the use of this technology in molecular diagnostics. Two-dimensional strandness-dependent electrophoresis (2D-SDE) separates nucleic acid molecules on the basis of length and strandness, i.e., double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), and RNA·DNA hybrids. We used 2D-SDE to measure the efficiency of cDNA synthesis and its importance for the imprecision of an in vitro transcription-based microarray expression analysis. The relative amount of double-stranded cDNA formed in replicate experiments that used the same RNA sample template was highly variable, ranging between 0% and 72% of the total DNA. Microarray experiments showed an inverse relationship between the difference between sample pairs in probe variance and the relative amount of dsDNA. Approximately 15% of probes showed between-sample variation (P < 0.05) when the dsDNA percentage was between 12% and 35%. In contrast, only 3% of probes showed between-sample variation when the dsDNA percentage was 69% and 72%. Replication experiments of the 35% dsDNA and 72% dsDNA samples were used to separate sample variation from probe replication variation. The estimated SD of the sample-to-sample variation and of the probe replicates was lower in 72% dsDNA samples than in 35% dsDNA samples. Variation in the relative amount of double-stranded cDNA synthesized can be an important component of the imprecision in T7 RNA polymerase-based microarray expression analysis. © 2013 American Association for Clinical Chemistry

Hierarchical cluster analysis of technical replicates to identify interferents in untargeted mass spectrometry metabolomics.

PubMed

Caesar, Lindsay K; Kvalheim, Olav M; Cech, Nadja B

2018-08-27

Mass spectral data sets often contain experimental artefacts, and data filtering prior to statistical analysis is crucial to extract reliable information. This is particularly true in untargeted metabolomics analyses, where the analyte(s) of interest are not known a priori. It is often assumed that chemical interferents (i.e. solvent contaminants such as plasticizers) are consistent across samples, and can be removed by background subtraction from blank injections. On the contrary, it is shown here that chemical contaminants may vary in abundance across each injection, potentially leading to their misidentification as relevant sample components. With this metabolomics study, we demonstrate the effectiveness of hierarchical cluster analysis (HCA) of replicate injections (technical replicates) as a methodology to identify chemical interferents and reduce their contaminating contribution to metabolomics models. Pools of metabolites with varying complexity were prepared from the botanical Angelica keiskei Koidzumi and spiked with known metabolites. Each set of pools was analyzed in triplicate and at multiple concentrations using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). Before filtering, HCA failed to cluster replicates in the data sets. To identify contaminant peaks, we developed a filtering process that evaluated the relative peak area variance of each variable within triplicate injections. These interferent peaks were found across all samples, but did not show consistent peak area from injection to injection, even when evaluating the same chemical sample. This filtering process identified 128 ions that appear to originate from the UPLC-MS system. Data sets collected for a high number of pools with comparatively simple chemical composition were highly influenced by these chemical interferents, as were samples that were analyzed at a low concentration. When chemical interferent masses were removed, technical replicates clustered in all data sets. This work highlights the importance of technical replication in mass spectrometry-based studies, and presents a new application of HCA as a tool for evaluating the effectiveness of data filtering prior to statistical analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

Replication of associations between LRP5 and ESRRA variants and bone density in premenopausal women.

PubMed

Giroux, S; Elfassihi, L; Cole, D E C; Rousseau, F

2008-12-01

Replication is a critical step to validate positive genetic associations. In this study, we tested two previously reported positive associations. The low density lipoprotein receptor-related protein 5 (LRP5) Val667Met and lumbar spine bone density are replicated. This result is in line with results from large consortiums such as Genomos. However, the estrogen-related receptor alpha (ESRRA) repeat in the promoter is not replicated although the polymorphism studied was functional and could have been a causative variant. We sought to validate associations previously reported between LRP5 V667M polymorphism and lumbar spine (LS, p = 0.013) and femoral neck (FN, p = 0.0002) bone mineral density (BMD), and between ESRRA 23 base pair repeat polymorphism and LS BMD (p = 0.0036) in a sample of premenopausal Caucasian women using an independent sample. For the replication sample, we recruited 673 premenopausal women from the Toronto metropolitan area. All women were Caucasian and had BMD measured. LRP5 V667M was genotyped by allele-specific PCR and ESRRA repeats by sizing of PCR products on agarose gels. We reproduced the same association as we reported previously between LRP5 V667M and LS BMD (p = 0.015) but not with FN BMD (p = 0.254). The combined data from the two populations indicate an effect size of 0.28SD for LS BMD (p = 0.00048) and an effect size of 0.26 SD for FN BMD (p = 0.00037). In contrast, the association we reported earlier between ESRRA repeats and LS BMD was not replicated in the sample from Toronto (p = 0.645). The association between LRP5 V667M and LS BMD is confirmed but not that between ESRRA repeats and LS BMD. This result indicates that it is imperative to validate any positive association in an independent sample.

Psychometric properties of the Generalized Anxiety Disorder Inventory in a Canadian sample.

PubMed

Henderson, Leigh C; Antony, Martin M; Koerner, Naomi

2014-05-01

The Generalized Anxiety Disorder Inventory is a recently developed self-report measure that assesses symptoms of generalized anxiety disorder. Its psychometric properties have not been investigated further since its original development. The current study investigated its psychometric properties in a Canadian student/community sample. Exploratory principal component analysis replicated the original three-component structure. The total scale and subscales demonstrated excellent internal consistency reliability (α = 0.84-0.94) and correlated strongly with the Penn State Worry Questionnaire (r = 0.41-0.74, all ps <0.001) and Generalized Anxiety Disorder-7 (r = 0.55-0.84, all ps <0.001). However, only the total scale and cognitive subscale (r = 0.48-0.49, all ps <0.05) significantly predicted generalized anxiety disorder diagnosis established by diagnostic interview. The somatic subscale in particular may require revision to improve predictive validity. Revision may also be necessary given changes in required somatic symptoms for generalized anxiety disorder diagnostic criteria in more recent versions of the Diagnostic and Statistical Manual of Mental Disorders (i.e. although major changes occurred from Diagnostic and Statistical Manual of Mental Disorders-III-R to Diagnostic and Statistical Manual of Mental Disorders-IV, changes in Diagnostic and Statistical Manual of Mental Disorders-5 were minimal) and the possibility of changes in the upcoming 11th revision of the International Classification of Diseases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, Wade C.

Oak Ridge Institute for Science and Education (ORISE) personnel visited the United Nuclear Corporation (UNC) Naval Products site on three separate occasions during the months of October and November 2011. The purpose of these visits was to conduct confirmatory surveys of soils associated with the Argyle Street sewer line that was being removed. Soil samples were collected from six different, judgmentally determined locations in the Argyle Street sewer trench. In addition to the six soil samples collected by ORISE, four replicate soil samples were collected by Cabrera Services, Inc. (CSI) for analysis by the ORISE laboratory. Replicate samples S0010 andmore » S0011 were final status survey (FSS) bias samples; S0012 was an FSS systematic sample; and S0015 was a waste characterization sample. Six soil samples were also collected for background determination. Uranium-235 and uranium-238 concentrations were determined via gamma spectroscopy; the spectra were also reviewed for other identifiable photopeaks. Radionuclide concentrations for these soil samples are provided. In addition to the replicate samples and the samples collected by ORISE, CSI submitted three soil samples for inter-laboratory comparison analyses. One sample was from the background reference area, one was from waste characterization efforts (material inside the sewer line), and one was a FSS sample. The inter-laboratory comparison analyses results between ORISE and CSI were in agreement, except for one sample collected in the reference area. Smear results For Argyle Street sewer pipes are tabulated.« less

Antimycotic-Antibiotic Amphotericin B Promotes Influenza Virus Replication in Cell Culture ▿

PubMed Central

Roethl, Elisabeth; Gassner, Manuela; Krenn, Brigitte M.; Romanovskaya-Romanko, Ekaterina A.; Seper, Helena; Romanova, Julia; Nakowitsch, Sabine; Sturlan, Sanda; Wolschek, Markus; Sirotkin, Alexej; Kiselev, Oleg; Muster, Thomas; Egorov, Andrej

2011-01-01

In general, antibiotics are not rated as substances that inhibit or support influenza virus replication. We describe here the enhancing effect of the polyene antibiotic amphotericin B (AmB) on influenza virus growth in Vero cells. We show that isolation rates of influenza A and B viruses from clinical samples can be dramatically enhanced by adding AmB to the culture medium. We demonstrate that AmB promotes the viral uptake and endocytic processing of the virus particles. This effect is specific for Vero and human nasal epithelial cells and was not observed in Madin-Darby canine kidney cells. The effect of AmB was subtype specific and more prominent for human seasonal influenza strains but absent for H5N1 human viruses. The AmB-enhancing effect seemed to be solely due to the viral hemagglutinin function. Our results indicate that the use of AmB may facilitate influenza virus isolation and production in Vero cells. PMID:21849438

Problem solving during artificial selection of self-replicating loops

NASA Astrophysics Data System (ADS)

Chou, Hui-Hsien; Reggia, James A.

1998-05-01

Past cellular automata models of self-replication have generally done only one thing: replicate themselves. However, it has recently been demonstrated that such self-replicating structures can be programmed to also carry out a task during the replication process. Past models of this sort have been limited in that the “program” involved is copied unchanged from parent to child, so that each generation of replicants is executing exactly the same program on exactly the same data. Here we take a different approach in which each replicant receives a distinct partial solution that is modified during replication. Under artificial selection, replicants with promising solutions proliferate while those with failed solutions are lost. We show that this approach can be applied successfully to solve an NP-complete problem, the satisfiability problem. Bounds are given on the cellular space size and time needed to solve a given problem, and simulations demonstrate that this approach works effectively. These and other recent results raise the possibility of evolving self-replicating structures that have a simulated metabolism or that carry out useful tasks.

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

PubMed Central

Zheng, Hou-Feng; Forgetta, Vincenzo; Hsu, Yi-Hsiang; Estrada, Karol; Rosello-Diez, Alberto; Leo, Paul J; Dahia, Chitra L; Park-Min, Kyung Hyun; Tobias, Jonathan H; Kooperberg, Charles; Kleinman, Aaron; Styrkarsdottir, Unnur; Liu, Ching-Ti; Uggla, Charlotta; Evans, Daniel S; Nielson, Carrie M; Walter, Klaudia; Pettersson-Kymmer, Ulrika; McCarthy, Shane; Eriksson, Joel; Kwan, Tony; Jhamai, Mila; Trajanoska, Katerina; Memari, Yasin; Min, Josine; Huang, Jie; Danecek, Petr; Wilmot, Beth; Li, Rui; Chou, Wen-Chi; Mokry, Lauren E; Moayyeri, Alireza; Claussnitzer, Melina; Cheng, Chia-Ho; Cheung, Warren; Medina-Gómez, Carolina; Ge, Bing; Chen, Shu-Huang; Choi, Kwangbom; Oei, Ling; Fraser, James; Kraaij, Robert; Hibbs, Matthew A; Gregson, Celia L; Paquette, Denis; Hofman, Albert; Wibom, Carl; Tranah, Gregory J; Marshall, Mhairi; Gardiner, Brooke B; Cremin, Katie; Auer, Paul; Hsu, Li; Ring, Sue; Tung, Joyce Y; Thorleifsson, Gudmar; Enneman, Anke W; van Schoor, Natasja M; de Groot, Lisette C.P.G.M.; van der Velde, Nathalie; Melin, Beatrice; Kemp, John P; Christiansen, Claus; Sayers, Adrian; Zhou, Yanhua; Calderari, Sophie; van Rooij, Jeroen; Carlson, Chris; Peters, Ulrike; Berlivet, Soizik; Dostie, Josée; Uitterlinden, Andre G; Williams, Stephen R.; Farber, Charles; Grinberg, Daniel; LaCroix, Andrea Z; Haessler, Jeff; Chasman, Daniel I; Giulianini, Franco; Rose, Lynda M; Ridker, Paul M; Eisman, John A; Nguyen, Tuan V; Center, Jacqueline R; Nogues, Xavier; Garcia-Giralt, Natalia; Launer, Lenore L; Gudnason, Vilmunder; Mellström, Dan; Vandenput, Liesbeth; Karlsson, Magnus K; Ljunggren, Östen; Svensson, Olle; Hallmans, Göran; Rousseau, François; Giroux, Sylvie; Bussière, Johanne; Arp, Pascal P; Koromani, Fjorda; Prince, Richard L; Lewis, Joshua R; Langdahl, Bente L; Hermann, A Pernille; Jensen, Jens-Erik B; Kaptoge, Stephen; Khaw, Kay-Tee; Reeve, Jonathan; Formosa, Melissa M; Xuereb-Anastasi, Angela; Åkesson, Kristina; McGuigan, Fiona E; Garg, Gaurav; Olmos, Jose M; Zarrabeitia, Maria T; Riancho, Jose A; Ralston, Stuart H; Alonso, Nerea; Jiang, Xi; Goltzman, David; Pastinen, Tomi; Grundberg, Elin; Gauguier, Dominique; Orwoll, Eric S; Karasik, David; Davey-Smith, George; Smith, Albert V; Siggeirsdottir, Kristin; Harris, Tamara B; Zillikens, M Carola; van Meurs, Joyce BJ; Thorsteinsdottir, Unnur; Maurano, Matthew T; Timpson, Nicholas J; Soranzo, Nicole; Durbin, Richard; Wilson, Scott G; Ntzani, Evangelia E; Brown, Matthew A; Stefansson, Kari; Hinds, David A; Spector, Tim; Cupples, L Adrienne; Ohlsson, Claes; Greenwood, Celia MT; Jackson, Rebecca D; Rowe, David W; Loomis, Cynthia A; Evans, David M; Ackert-Bicknell, Cheryl L; Joyner, Alexandra L; Duncan, Emma L; Kiel, Douglas P; Rivadeneira, Fernando; Richards, J Brent

2016-01-01

SUMMARY The extent to which low-frequency (minor allele frequency [MAF] between 1–5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is largely unknown. Bone mineral density (BMD) is highly heritable, is a major predictor of osteoporotic fractures and has been previously associated with common genetic variants1–8, and rare, population-specific, coding variants9. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n=2,882 from UK10K), whole-exome sequencing (n= 3,549), deep imputation of genotyped samples using a combined UK10K/1000Genomes reference panel (n=26,534), and de-novo replication genotyping (n= 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size 4-fold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564[T], MAF = 1.7%, replication effect size = +0.20 standard deviations [SD], Pmeta = 2×10−14), which was also associated with a decreased risk of fracture (OR = 0.85; P = 2×10−11; ncases = 98,742 and ncontrols = 409,511). Using an En1Cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, likely as a consequence of high bone turn-over. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817[T], MAF = 1.1%, replication effect size = +0.39 SD, Pmeta = 1×10−11). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population. PMID:26367794

Vehicles, Replicators, and Intercellular Movement of Genetic Information: Evolutionary Dissection of a Bacterial Cell

PubMed Central

Jalasvuori, Matti

2012-01-01

Prokaryotic biosphere is vastly diverse in many respects. Any given bacterial cell may harbor in different combinations viruses, plasmids, transposons, and other genetic elements along with their chromosome(s). These agents interact in complex environments in various ways causing multitude of phenotypic effects on their hosting cells. In this discussion I perform a dissection for a bacterial cell in order to simplify the diversity into components that may help approach the ocean of details in evolving microbial worlds. The cell itself is separated from all the genetic replicators that use the cell vehicle for preservation and propagation. I introduce a classification that groups different replicators according to their horizontal movement potential between cells and according to their effects on the fitness of their present host cells. The classification is used to discuss and improve the means by which we approach general evolutionary tendencies in microbial communities. Moreover, the classification is utilized as a tool to help formulating evolutionary hypotheses and to discuss emerging bacterial pathogens as well as to promote understanding on the average phenotypes of different replicators in general. It is also discussed that any given biosphere comprising prokaryotic cell vehicles and genetic replicators may naturally evolve to have horizontally moving replicators of various types. PMID:22567533

Evaluation of the reproducibility of amplicon sequencing with Illumina MiSeq platform

PubMed Central

Van Nostrand, Joy D.; Ning, Daliang; Sun, Bo; Xue, Kai; Liu, Feifei; Deng, Ye; Liang, Yuting; Zhou, Jizhong

2017-01-01

Illumina’s MiSeq has become the dominant platform for gene amplicon sequencing in microbial ecology studies; however, various technical concerns, such as reproducibility, still exist. To assess reproducibility, 16S rRNA gene amplicons from 18 soil samples of a reciprocal transplantation experiment were sequenced on an Illumina MiSeq. The V4 region of 16S rRNA gene from each sample was sequenced in triplicate with each replicate having a unique barcode. The average OTU overlap, without considering sequence abundance, at a rarefaction level of 10,323 sequences was 33.4±2.1% and 20.2±1.7% between two and among three technical replicates, respectively. When OTU sequence abundance was considered, the average sequence abundance weighted OTU overlap was 85.6±1.6% and 81.2±2.1% for two and three replicates, respectively. Removing singletons significantly increased the overlap for both (~1–3%, p<0.001). Increasing the sequencing depth to 160,000 reads by deep sequencing increased OTU overlap both when sequence abundance was considered (95%) and when not (44%). However, if singletons were not removed the overlap between two technical replicates (not considering sequence abundance) plateaus at 39% with 30,000 sequences. Diversity measures were not affected by the low overlap as α-diversities were similar among technical replicates while β-diversities (Bray-Curtis) were much smaller among technical replicates than among treatment replicates (e.g., 0.269 vs. 0.374). Higher diversity coverage, but lower OTU overlap, was observed when replicates were sequenced in separate runs. Detrended correspondence analysis indicated that while there was considerable variation among technical replicates, the reproducibility was sufficient for detecting treatment effects for the samples examined. These results suggest that although there is variation among technical replicates, amplicon sequencing on MiSeq is useful for analyzing microbial community structure if used appropriately and with caution. For example, including technical replicates, removing spurious sequences and unrepresentative OTUs, using a clustering method with a high stringency for OTU generation, estimating treatment effects at higher taxonomic levels, and adapting the unique molecular identifier (UMI) and other newly developed methods to lower PCR and sequencing error and to identify true low abundance rare species all can increase reproducibility. PMID:28453559

Evaluation of the reproducibility of amplicon sequencing with Illumina MiSeq platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wen, Chongqing; Wu, Liyou; Qin, Yujia

Illumina's MiSeq has become the dominant platform for gene amplicon sequencing in microbial ecology studies; however, various technical concerns, such as reproducibility, still exist. To assess reproducibility, 16S rRNA gene amplicons from 18 soil samples of a reciprocal transplantation experiment were sequenced on an Illumina MiSeq. The V4 region of 16S rRNA gene from each sample was sequenced in triplicate with each replicate having a unique barcode. The average OTU overlap, without considering sequence abundance, at a rarefaction level of 10,323 sequences was 33.4±2.1% and 20.2±1.7% between two and among three technical replicates, respectively. When OTU sequence abundance was considered,more » the average sequence abundance weighted OTU overlap was 85.6±1.6% and 81.2±2.1% for two and three replicates, respectively. Removing singletons significantly increased the overlap for both (~1-3%, p<0.001). Increasing the sequencing depth to 160,000 reads by deep sequencing increased OTU overlap both when sequence abundance was considered (95%) and when not (44%). However, if singletons were not removed the overlap between two technical replicates (not considering sequence abundance) plateaus at 39% with 30,000 sequences. Diversity measures were not affected by the low overlap as α-diversities were similar among technical replicates while β-diversities (Bray-Curtis) were much smaller among technical replicates than among treatment replicates (e.g., 0.269 vs. 0.374). Higher diversity coverage, but lower OTU overlap, was observed when replicates were sequenced in separate runs. Detrended correspondence analysis indicated that while there was considerable variation among technical replicates, the reproducibility was sufficient for detecting treatment effects for the samples examined. These results suggest that although there is variation among technical replicates, amplicon sequencing on MiSeq is useful for analyzing microbial community structure if used appropriately and with caution. For example, including technical replicates, removing spurious sequences and unrepresentative OTUs, using a clustering method with a high stringency for OTU generation, estimating treatment effects at higher taxonomic levels, and adapting the unique molecular identifier (UMI) and other newly developed methods to lower PCR and sequencing error and to identify true low abundance rare species all can increase reproducibility.« less

Evaluation of the reproducibility of amplicon sequencing with Illumina MiSeq platform

DOE PAGES

Wen, Chongqing; Wu, Liyou; Qin, Yujia; ...

2017-04-28

Illumina's MiSeq has become the dominant platform for gene amplicon sequencing in microbial ecology studies; however, various technical concerns, such as reproducibility, still exist. To assess reproducibility, 16S rRNA gene amplicons from 18 soil samples of a reciprocal transplantation experiment were sequenced on an Illumina MiSeq. The V4 region of 16S rRNA gene from each sample was sequenced in triplicate with each replicate having a unique barcode. The average OTU overlap, without considering sequence abundance, at a rarefaction level of 10,323 sequences was 33.4±2.1% and 20.2±1.7% between two and among three technical replicates, respectively. When OTU sequence abundance was considered,more » the average sequence abundance weighted OTU overlap was 85.6±1.6% and 81.2±2.1% for two and three replicates, respectively. Removing singletons significantly increased the overlap for both (~1-3%, p<0.001). Increasing the sequencing depth to 160,000 reads by deep sequencing increased OTU overlap both when sequence abundance was considered (95%) and when not (44%). However, if singletons were not removed the overlap between two technical replicates (not considering sequence abundance) plateaus at 39% with 30,000 sequences. Diversity measures were not affected by the low overlap as α-diversities were similar among technical replicates while β-diversities (Bray-Curtis) were much smaller among technical replicates than among treatment replicates (e.g., 0.269 vs. 0.374). Higher diversity coverage, but lower OTU overlap, was observed when replicates were sequenced in separate runs. Detrended correspondence analysis indicated that while there was considerable variation among technical replicates, the reproducibility was sufficient for detecting treatment effects for the samples examined. These results suggest that although there is variation among technical replicates, amplicon sequencing on MiSeq is useful for analyzing microbial community structure if used appropriately and with caution. For example, including technical replicates, removing spurious sequences and unrepresentative OTUs, using a clustering method with a high stringency for OTU generation, estimating treatment effects at higher taxonomic levels, and adapting the unique molecular identifier (UMI) and other newly developed methods to lower PCR and sequencing error and to identify true low abundance rare species all can increase reproducibility.« less

Evaluation of the reproducibility of amplicon sequencing with Illumina MiSeq platform.

PubMed

Wen, Chongqing; Wu, Liyou; Qin, Yujia; Van Nostrand, Joy D; Ning, Daliang; Sun, Bo; Xue, Kai; Liu, Feifei; Deng, Ye; Liang, Yuting; Zhou, Jizhong

2017-01-01

Illumina's MiSeq has become the dominant platform for gene amplicon sequencing in microbial ecology studies; however, various technical concerns, such as reproducibility, still exist. To assess reproducibility, 16S rRNA gene amplicons from 18 soil samples of a reciprocal transplantation experiment were sequenced on an Illumina MiSeq. The V4 region of 16S rRNA gene from each sample was sequenced in triplicate with each replicate having a unique barcode. The average OTU overlap, without considering sequence abundance, at a rarefaction level of 10,323 sequences was 33.4±2.1% and 20.2±1.7% between two and among three technical replicates, respectively. When OTU sequence abundance was considered, the average sequence abundance weighted OTU overlap was 85.6±1.6% and 81.2±2.1% for two and three replicates, respectively. Removing singletons significantly increased the overlap for both (~1-3%, p<0.001). Increasing the sequencing depth to 160,000 reads by deep sequencing increased OTU overlap both when sequence abundance was considered (95%) and when not (44%). However, if singletons were not removed the overlap between two technical replicates (not considering sequence abundance) plateaus at 39% with 30,000 sequences. Diversity measures were not affected by the low overlap as α-diversities were similar among technical replicates while β-diversities (Bray-Curtis) were much smaller among technical replicates than among treatment replicates (e.g., 0.269 vs. 0.374). Higher diversity coverage, but lower OTU overlap, was observed when replicates were sequenced in separate runs. Detrended correspondence analysis indicated that while there was considerable variation among technical replicates, the reproducibility was sufficient for detecting treatment effects for the samples examined. These results suggest that although there is variation among technical replicates, amplicon sequencing on MiSeq is useful for analyzing microbial community structure if used appropriately and with caution. For example, including technical replicates, removing spurious sequences and unrepresentative OTUs, using a clustering method with a high stringency for OTU generation, estimating treatment effects at higher taxonomic levels, and adapting the unique molecular identifier (UMI) and other newly developed methods to lower PCR and sequencing error and to identify true low abundance rare species all can increase reproducibility.

Replication and extension of a hierarchical model of social anxiety and depression: fear of positive evaluation as a key unique factor in social anxiety.

PubMed

Weeks, Justin W

2015-01-01

Wang, Hsu, Chiu, and Liang (2012, Journal of Anxiety Disorders, 26, 215-224) recently proposed a hierarchical model of social interaction anxiety and depression to account for both the commonalities and distinctions between these conditions. In the present paper, this model was extended to more broadly encompass the symptoms of social anxiety disorder, and replicated in a large unselected, undergraduate sample (n = 585). Structural equation modeling (SEM) and hierarchical regression analyses were employed. Negative affect and positive affect were conceptualized as general factors shared by social anxiety and depression; fear of negative evaluation (FNE) and disqualification of positive social outcomes were operationalized as specific factors, and fear of positive evaluation (FPE) was operationalized as a factor unique to social anxiety. This extended hierarchical model explicates structural relationships among these factors, in which the higher-level, general factors (i.e., high negative affect and low positive affect) represent vulnerability markers of both social anxiety and depression, and the lower-level factors (i.e., FNE, disqualification of positive social outcomes, and FPE) are the dimensions of specific cognitive features. Results from SEM and hierarchical regression analyses converged in support of the extended model. FPE is further supported as a key symptom that differentiates social anxiety from depression.

The clinical effectiveness of cognitive behaviour therapy for chronic insomnia: implementation and evaluation of a sleep clinic in general medical practice.

PubMed

Espie, C A; Inglis, S J; Tessier, S; Harvey, L

2001-01-01

Chronic insomnia is a very common clinical condition which may respond well to non-pharmacological treatment. Indeed, the literature supports the efficacy of cognitive behaviour therapy (CBT). However, there has been no substantial study of clinical effectiveness. Since insomniacs typically present in general medical practice this is a crucial gap in the outcome research. This study, therefore, specifically investigated the clinical effectiveness of CBT delivered by Health Visitors (primary care nurses) trained as therapists. One hundred and thirty-nine insomniacs (mean age 51 yr) were randomised to CBT or Self-Monitoring Control (SMC) in a controlled trial. CBT comprised six group sessions (n=4 to 6 patients). After the controlled phase, SMC patients entered deferred treatment (CBT-DEF), allowing both treatment replication and long-term outcome to be investigated for a sizeable, treated sample. Repeated measures ANOVAs demonstrated superiority of CBT over SMC in substantially reducing sleep latency and wakefulness during the night. CBT-DEF replicated similar effects and maintained improvement was observed in both groups one year later. Furthermore, total sleep increased significantly during follow-up and 84% of patients initially using hypnotics remained drug-free. Results suggest that CBT administered by Health Visitors offers a clinically effective treatment for insomnia.

Variation: Use It or Misuse It--Replication and Its Variants

ERIC Educational Resources Information Center

Drummond, Gordon B.; Vowler, Sarah L.

2012-01-01

In this article, the authors talk about variation and how variation between measurements may be reduced if sampling is not random. They also talk about replication and its variants. A replicate is a repeated measurement from the same experimental unit. An experimental unit is the smallest part of an experiment or a study that can be subject to a…

Intervention for First Graders with Limited Number Knowledge: Large-Scale Replication of a Randomized Controlled Trial

ERIC Educational Resources Information Center

Gersten, Russell; Rolfhus, Eric; Clarke, Ben; Decker, Lauren E.; Wilkins, Chuck; Dimino, Joseph

2015-01-01

Replication studies are extremely rare in education. This randomized controlled trial (RCT) is a scale-up replication of Fuchs et al., which in a sample of 139 found a statistically significant positive impact for Number Rockets, a small-group intervention for at-risk first graders that focused on building understanding of number operations. The…

Replication of a Test-Retest Factorial Validity Study with the Piers-Harris Children's Self Concept Scale.

ERIC Educational Resources Information Center

Platten, Marvin R.; Williams, Larry R.

1981-01-01

This study largely replicates the findings of a previous study reported by the authors. Further research involving the physical dimension as a possible facet of general self-concept is suggested. (Author/BW)

Detecting the response of fish assemblages to stream restoration: Effects of different sampling designsf

USGS Publications Warehouse

Baldigo, Barry P.; Warren, D.R.

2008-01-01

Increased trout production within limited stream reaches is a popular goal for restoration projects, yet investigators seldom monitor, assess, or publish the associated effects on fish assemblages. Fish community data from a total of 40 surveys at restored and reference reaches in three streams of the Catskill Mountains, New York, were analyzed a posteriori to determine how the ability to detect significant changes in biomass of brown trout Salmo trutta, all salmonids, or the entire fish community differs with effect size, number of streams assessed, process used to quantify the index response, and number of replicates collected before and after restoration. Analyses of statistical power (probability of detecting a meaningful difference or effect) and integrated power (average power over all possible ??-values) were combined with before-after, control-impact analyses to assess the effectiveness of alternate sampling and analysis designs. In general, the more robust analyses indicated that biomass of brown trout and salmonid populations increased significantly in restored reaches but that the net increases (relative to the reference reach) were significant only at two of four restored reaches. Restoration alone could not account for the net increases in total biomass of fish communities. Power analyses generally showed that integrated power was greater than 0.95 when (1) biomass increases were larger than 5.0 g/m2, (2) the total number of replicates ranged from 4 to 8, and (3) coefficients of variation (CVs) for responses were less than 40%. Integrated power was often greater than 0.95 for responses as low as 1.0 g/m2 if the response CVs were less than 30%. Considering that brown trout, salmonid, and community biomass increased by 2.99 g/m2 on average (SD= 1.17 g/m2) in the four restored reaches, use of two to three replicates both before and after restoration would have an integrated power of about 0.95 and would help detect significant changes in fish biomass under similar situations. ?? Copyright by the American Fisheries Society 2008.

Brain structure mediates the association between height and cognitive ability.

PubMed

Vuoksimaa, Eero; Panizzon, Matthew S; Franz, Carol E; Fennema-Notestine, Christine; Hagler, Donald J; Lyons, Michael J; Dale, Anders M; Kremen, William S

2018-05-11

Height and general cognitive ability are positively associated, but the underlying mechanisms of this relationship are not well understood. Both height and general cognitive ability are positively associated with brain size. Still, the neural substrate of the height-cognitive ability association is unclear. We used a sample of 515 middle-aged male twins with structural magnetic resonance imaging data to investigate whether the association between height and cognitive ability is mediated by cortical size. In addition to cortical volume, we used genetically, ontogenetically and phylogenetically distinct cortical metrics of total cortical surface area and mean cortical thickness. Height was positively associated with general cognitive ability and total cortical volume and cortical surface area, but not with mean cortical thickness. Mediation models indicated that the well-replicated height-general cognitive ability association is accounted for by individual differences in total cortical volume and cortical surface area (highly heritable metrics related to global brain size), and that the genetic association between cortical surface area and general cognitive ability underlies the phenotypic height-general cognitive ability relationship.

Water-quality data for water- and wastewater-treatment plants along the Red River of the North, North Dakota and Minnesota, January through October 2006

USGS Publications Warehouse

Damschen, William C.; Hansel, John A.; Nustad, Rochelle A.

2008-01-01

From January through October 2006, six sets of water-quality samples were collected at 28 sites, which included inflow and outflow from seven major municipal water-treatment plants (14 sites) and influent and effluent samples from seven major municipal wastewater treatment plants (14 sites) along the Red River of the North in North Dakota and Minnesota. Samples were collected in cooperation with the Bureau of Reclamation for use in the development of return-flow boundary conditions in a 2006 water-quality model for the Red River of the North. All samples were analyzed for nutrients and major ions. For one set of effluent samples from each of the wastewater-treatment plants, water was analyzed for Eschirichia coli, fecal coliform, 20-day biochemical oxygen demand, 20-day nitrogenous biochemical oxygen demand, total organic carbon, and dissolved organic carbon. In general, results from the field equipment blank and replicate samples indicate that the overall process of sample collection, processing, and analysis did not introduce substantial contamination and that consistent results were obtained.

Polygenic risk for psychiatric disorders correlates with executive function in typical development.

PubMed

Schork, A J; Brown, T T; Hagler, D J; Thompson, W K; Chen, C-H; Dale, A M; Jernigan, T L; Akshoomoff, N

2018-04-16

Executive functions are a diverse and critical suite of cognitive abilities that are often disrupted in individuals with psychiatric disorders. Despite their moderate to high heritability, little is known about the molecular genetic factors that contribute to variability in executive functions and how these factors may be related to those that predispose to psychiatric disorders. We examined the relationship between polygenic risk scores built from large genome-wide association studies of psychiatric disorders and executive functioning in typically developing children. In our discovery sample (N = 417), consistent with previous reports on general cognitive abilities, polygenic risk for autism spectrum disorder was associated with better performance on the Dimensional Change Card Sort test from the NIH Cognition Toolbox, with the largest effect in the youngest children. Polygenic risk for major depressive disorder was associated with poorer performance on the Flanker test in the same sample. This second association replicated for performance on the Penn Conditional Exclusion Test in an independent cohort (N = 3681). Our results suggest that the molecular genetic factors contributing to variability in executive function during typical development are at least partially overlapping with those associated with psychiatric disorders, although larger studies and further replication are needed. © 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

A field test of the effect of spiked ivermectin concentrations on the biodiversity of coprophagous dung insects in Switzerland.

PubMed

Jochmann, Ralf; Lipkow, Erhard; Blanckenhorn, Wolf U

2016-08-01

Veterinary medical product residues can cause severe damage in the dung ecosystem. Depending on the manner of application and the time after treatment, the excreted concentration of a given pharmaceutical varies. The popular anthelmintic drug ivermectin can be applied to livestock in several different ways and is fecally excreted over a period of days to months after application. In a field experiment replicated in summer and autumn, the authors mixed 6 ivermectin concentrations plus a null control into fresh cow dung to assess the reaction of the dung insect community. Taxon richness of the insect dung fauna emerging from the dung, but not Hill diversity ((1) D) or the total number of individuals (abundance), decreased as ivermectin concentration increased. Corresponding declines in the number of emerging insects were found for most larger brachyceran flies and hymenopteran parasitoids, but not for most smaller nematoceran flies or beetles (except Hydrophilidae). Parallel pitfall traps recovered all major dung organism groups that emerged from the experimental dung, although at times in vastly different numbers. Ivermectin generally did not change the attractiveness of dung: differences in emergence therefore reflect differences in survival of coprophagous offspring of colonizing insects. Because sample size was limited to 6 replicates, the authors generally recommend more than 10 (seasonal) replicates and also testing higher concentrations than used in the present study as positive controls in future studies. Results accord with parallel experiments in which the substance was applied and passed through the cow's digestive system. In principle, therefore, the authors' experimental design is suitable for such higher-tier field tests of the response of the entire dung community to pharmaceutical residues, at least for ivermectin. Environ Toxicol Chem 2016;35:1947-1952. © 2015 SETAC. © 2015 SETAC.

Variants in TTC25 affect autistic trait in patients with autism spectrum disorder and general population.

PubMed

Vojinovic, Dina; Brison, Nathalie; Ahmad, Shahzad; Noens, Ilse; Pappa, Irene; Karssen, Lennart C; Tiemeier, Henning; van Duijn, Cornelia M; Peeters, Hilde; Amin, Najaf

2017-08-01

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder with a complex genetic architecture. To identify genetic variants underlying ASD, we performed single-variant and gene-based genome-wide association studies using a dense genotyping array containing over 2.3 million single-nucleotide variants in a discovery sample of 160 families with at least one child affected with non-syndromic ASD using a binary (ASD yes/no) phenotype and a quantitative autistic trait. Replication of the top findings was performed in Psychiatric Genomics Consortium and Erasmus Rucphen Family (ERF) cohort study. Significant association of quantitative autistic trait was observed with the TTC25 gene at 17q21.2 (effect size=10.2, P-value=3.4 × 10 -7 ) in the gene-based analysis. The gene also showed nominally significant association in the cohort-based ERF study (effect=1.75, P-value=0.05). Meta-analysis of discovery and replication improved the association signal (P-value meta =1.5 × 10 -8 ). No genome-wide significant signal was observed in the single-variant analysis of either the binary ASD phenotype or the quantitative autistic trait. Our study has identified a novel gene TTC25 to be associated with quantitative autistic trait in patients with ASD. The replication of association in a cohort-based study and the effect estimate suggest that variants in TTC25 may also be relevant for broader ASD phenotype in the general population. TTC25 is overexpressed in frontal cortex and testis and is known to be involved in cilium movement and thus an interesting candidate gene for autistic trait.

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

PubMed

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

2012-09-01

Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP (~2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n = 6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n = 527-6,032). Suggestive association (P = 8 × 10(-8)) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P < 6.09 × 10(-6)) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P < 0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits. Copyright © 2012 Wiley Periodicals, Inc.

A Comparison Study of Sampling and Analyzing Volatile Organic Compounds in Air in Kuwait by Using Tedlar Bags/Canisters and GC-MS with a Cryogenic Trap

PubMed Central

Tang, Hongmao; Beg, Khaliq R.; Al-Otaiba, Yousef

2006-01-01

Kuwait experiences desert climatic weather. Due to the extreme hot and dry conditions in this country, some analytical phenomena have been discovered. Therefore, a systematic study of sampling and analyzing volatile organic compounds in air by using GC-MS with a cryogenic trap is reported in this paper. This study included comparisons of using different sample containers such as Tedlar bags and SUMMA canisters, and different cryogenic freezing-out air volumes in the trap. Calibration curves for different compounds and improvement of replicated analysis results were also reported here. The study found that using different sample containers produced different results. Analysis of ambient air samples collected in Tedlar bags obtained several volatile organic compounds with large concentrations compared to using SUMMA canisters. Therefore, to choose a sample container properly is a key element for successfully completing a project. Because GC-MS with a cryogenic trap often generates replicated results with poor agreement, an internal standard added to gas standards and air samples by using a gas syringe was tested. The study results proved that it helped to improve the replicated results. PMID:16699723

A comparison study of sampling and analyzing volatile organic compounds in air in Kuwait by using Tedlar bags/canisters and GC-MS with a cryogenic trap.

PubMed

Tang, Hongmao; Beg, Khaliq R; Al-Otaiba, Yousef

2006-05-12

Kuwait experiences desert climatic weather. Due to the extreme hot and dry conditions in this country, some analytical phenomena have been discovered. Therefore, a systematic study of sampling and analyzing volatile organic compounds in air by using GC-MS with a cryogenic trap is reported in this paper. This study included comparisons of using different sample containers such as Tedlar bags and SUMMA canisters, and different cryogenic freezing-out air volumes in the trap. Calibration curves for different compounds and improvement of replicated analysis results were also reported here. The study found that using different sample containers produced different results. Analysis of ambient air samples collected in Tedlar bags obtained several volatile organic compounds with large concentrations compared to using SUMMA canisters. Therefore, to choose a sample container properly is a key element for successfully completing a project. Because GC-MS with a cryogenic trap often generates replicated results with poor agreement, an internal standard added to gas standards and air samples by using a gas syringe was tested. The study results proved that it helped to improve the replicated results.

Proteomic Workflows for Biomarker Identification Using Mass Spectrometry — Technical and Statistical Considerations during Initial Discovery

PubMed Central

Orton, Dennis J.; Doucette, Alan A.

2013-01-01

Identification of biomarkers capable of differentiating between pathophysiological states of an individual is a laudable goal in the field of proteomics. Protein biomarker discovery generally employs high throughput sample characterization by mass spectrometry (MS), being capable of identifying and quantifying thousands of proteins per sample. While MS-based technologies have rapidly matured, the identification of truly informative biomarkers remains elusive, with only a handful of clinically applicable tests stemming from proteomic workflows. This underlying lack of progress is attributed in large part to erroneous experimental design, biased sample handling, as well as improper statistical analysis of the resulting data. This review will discuss in detail the importance of experimental design and provide some insight into the overall workflow required for biomarker identification experiments. Proper balance between the degree of biological vs. technical replication is required for confident biomarker identification. PMID:28250400

36 CFR 910.64 - Replication.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Replication. 910.64 Section 910.64 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION GENERAL GUIDELINES AND UNIFORM STANDARDS FOR URBAN PLANNING AND DESIGN OF DEVELOPMENT WITHIN THE PENNSYLVANIA AVENUE...

36 CFR 910.64 - Replication.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Replication. 910.64 Section 910.64 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION GENERAL GUIDELINES AND UNIFORM STANDARDS FOR URBAN PLANNING AND DESIGN OF DEVELOPMENT WITHIN THE PENNSYLVANIA AVENUE...

Fluid sampling apparatus and method

DOEpatents

Yeamans, David R.

1998-01-01

Incorporation of a bellows in a sampling syringe eliminates ingress of contaminants, permits replication of amounts and compression of multiple sample injections, and enables remote sampling for off-site analysis.

Cross-cultural investigation into cognitive underpinnings of individual differences in early arithmetic.

PubMed

Rodic, Maja; Zhou, Xinlin; Tikhomirova, Tatiana; Wei, Wei; Malykh, Sergei; Ismatulina, Victoria; Sabirova, Elena; Davidova, Yulia; Tosto, Maria Grazia; Lemelin, Jean-Pascal; Kovas, Yulia

2015-01-01

The present study evaluated 626 5-7-year-old children in the UK, China, Russia, and Kyrgyzstan on a cognitive test battery measuring: (1) general skills; (2) non-symbolic number sense; (3) symbolic number understanding; (4) simple arithmetic - operating with numbers; and (5) familiarity with numbers. Although most inter-population differences were small, 13% of the variance in arithmetic skills could be explained by the sample, replicating the pattern, previously found with older children in PISA. Furthermore, the same cognitive skills were related to early arithmetic in these diverse populations. Only understanding of symbolic number explained variation in mathematical performance in all samples. We discuss the results in terms of potential influences of socio-demographic, linguistic and genetic factors on individual differences in mathematics. © 2014 John Wiley & Sons Ltd.

Generalist genes and learning disabilities: a multivariate genetic analysis of low performance in reading, mathematics, language and general cognitive ability in a sample of 8000 12-year-old twins.

PubMed

Haworth, Claire M A; Kovas, Yulia; Harlaar, Nicole; Hayiou-Thomas, Marianna E; Petrill, Stephen A; Dale, Philip S; Plomin, Robert

2009-10-01

Our previous investigation found that the same genes influence poor reading and mathematics performance in 10-year-olds. Here we assess whether this finding extends to language and general cognitive disabilities, as well as replicating the earlier finding for reading and mathematics in an older and larger sample. Using a representative sample of 4000 pairs of 12-year-old twins from the UK Twins Early Development Study, we investigated the genetic and environmental overlap between internet-based batteries of language and general cognitive ability tests in addition to tests of reading and mathematics for the bottom 15% of the distribution using DeFries-Fulker extremes analysis. We compared these results to those for the entire distribution. All four traits were highly correlated at the low extreme (average group phenotypic correlation = .58). and in the entire distribution (average phenotypic correlation = .59). Genetic correlations for the low extreme were consistently high (average = .67), and non-shared environmental correlations were modest (average = .23). These results are similar to those seen across the entire distribution (.68 and .23, respectively). The 'Generalist Genes Hypothesis' holds for language and general cognitive disabilities, as well as reading and mathematics disabilities. Genetic correlations were high, indicating a strong degree of overlap in genetic influences on these diverse traits. In contrast, non-shared environmental influences were largely specific to each trait, causing phenotypic differentiation of traits.

Design and Field Procedures in the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A)

PubMed Central

Kessler, Ronald C.; Avenevoli, Shelli; Costello, E. Jane; Green, Jennifer Greif; Gruber, Michael J.; Heeringa, Steven; Merikangas, Kathleen R.; Pennell, Beth-Ellen; Sampson, Nancy A.; Zaslavsky, Alan M.

2009-01-01

An overview is presented of the design and field procedures of the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a US face-to-face household survey of the prevalence and correlates of DSM-IV mental disorders. The survey was based on a dual-frame design that included 904 adolescent residents of the households that participated in the US National Comorbidity Survey Replication (85.9% response rate) and 9,244 adolescent students selected from a nationally representative sample of 320 schools (74.7% response rate). After expositing the logic of dual-frame designs, comparisons are presented of sample and population distributions on Census socio-demographic variables and, in the school sample, school characteristics. These document only minor differences between the samples and the population. The results of statistical analysis of the bias-efficiency trade-off in weight trimming are then presented. These show that modest trimming meaningfully reduces mean squared error. Analysis of comparative sample efficiency shows that the household sample is more efficient than the school sample, leading to the household sample getting a higher weight relative to its size in the consolidated sample relative to the school sample. Taken together, these results show that the NCS-A is an efficient sample of the target population with good representativeness on a range of socio-demographic and geographic variables. PMID:19507169

Relative impact of key sources of systematic noise in Affymetrix and Illumina gene-expression microarray experiments.

PubMed

Kitchen, Robert R; Sabine, Vicky S; Simen, Arthur A; Dixon, J Michael; Bartlett, John M S; Sims, Andrew H

2011-12-01

Systematic processing noise, which includes batch effects, is very common in microarray experiments but is often ignored despite its potential to confound or compromise experimental results. Compromised results are most likely when re-analysing or integrating datasets from public repositories due to the different conditions under which each dataset is generated. To better understand the relative noise-contributions of various factors in experimental-design, we assessed several Illumina and Affymetrix datasets for technical variation between replicate hybridisations of Universal Human Reference (UHRR) and individual or pooled breast-tumour RNA. A varying degree of systematic noise was observed in each of the datasets, however in all cases the relative amount of variation between standard control RNA replicates was found to be greatest at earlier points in the sample-preparation workflow. For example, 40.6% of the total variation in reported expressions were attributed to replicate extractions, compared to 13.9% due to amplification/labelling and 10.8% between replicate hybridisations. Deliberate probe-wise batch-correction methods were effective in reducing the magnitude of this variation, although the level of improvement was dependent on the sources of noise included in the model. Systematic noise introduced at the chip, run, and experiment levels of a combined Illumina dataset were found to be highly dependent upon the experimental design. Both UHRR and pools of RNA, which were derived from the samples of interest, modelled technical variation well although the pools were significantly better correlated (4% average improvement) and better emulated the effects of systematic noise, over all probes, than the UHRRs. The effect of this noise was not uniform over all probes, with low GC-content probes found to be more vulnerable to batch variation than probes with a higher GC-content. The magnitude of systematic processing noise in a microarray experiment is variable across probes and experiments, however it is generally the case that procedures earlier in the sample-preparation workflow are liable to introduce the most noise. Careful experimental design is important to protect against noise, detailed meta-data should always be provided, and diagnostic procedures should be routinely performed prior to downstream analyses for the detection of bias in microarray studies.

Relative impact of key sources of systematic noise in Affymetrix and Illumina gene-expression microarray experiments

PubMed Central

2011-01-01

Background Systematic processing noise, which includes batch effects, is very common in microarray experiments but is often ignored despite its potential to confound or compromise experimental results. Compromised results are most likely when re-analysing or integrating datasets from public repositories due to the different conditions under which each dataset is generated. To better understand the relative noise-contributions of various factors in experimental-design, we assessed several Illumina and Affymetrix datasets for technical variation between replicate hybridisations of Universal Human Reference (UHRR) and individual or pooled breast-tumour RNA. Results A varying degree of systematic noise was observed in each of the datasets, however in all cases the relative amount of variation between standard control RNA replicates was found to be greatest at earlier points in the sample-preparation workflow. For example, 40.6% of the total variation in reported expressions were attributed to replicate extractions, compared to 13.9% due to amplification/labelling and 10.8% between replicate hybridisations. Deliberate probe-wise batch-correction methods were effective in reducing the magnitude of this variation, although the level of improvement was dependent on the sources of noise included in the model. Systematic noise introduced at the chip, run, and experiment levels of a combined Illumina dataset were found to be highly dependant upon the experimental design. Both UHRR and pools of RNA, which were derived from the samples of interest, modelled technical variation well although the pools were significantly better correlated (4% average improvement) and better emulated the effects of systematic noise, over all probes, than the UHRRs. The effect of this noise was not uniform over all probes, with low GC-content probes found to be more vulnerable to batch variation than probes with a higher GC-content. Conclusions The magnitude of systematic processing noise in a microarray experiment is variable across probes and experiments, however it is generally the case that procedures earlier in the sample-preparation workflow are liable to introduce the most noise. Careful experimental design is important to protect against noise, detailed meta-data should always be provided, and diagnostic procedures should be routinely performed prior to downstream analyses for the detection of bias in microarray studies. PMID:22133085

Cross-cultural confirmation of bi-factor models of a symptom distress measure: Symptom Checklist-90-Revised in clinical samples.

PubMed

Urbán, Róbert; Arrindell, Willem A; Demetrovics, Zsolt; Unoka, Zsolt; Timman, Reinier

2016-05-30

Four decades have elapsed since the introduction for clinical and research purposes of the Symptom Checklist-90(-R). Yet, its underlying dimensional structure has not been clearly delineated. A shift has been observed in the methods utilized-from predominantly exploratory factor analytic in nature in the first two decades or so to different confirmatory methods in recent years. A need remains to search for a structure that remains invariant across samples and nations. In that context, the present study attempted to replicate and extend recent findings yielded in a Hungarian general population sample (N=2,874) with two psychiatric patient samples from Hungary (N=972) and The Netherlands (N=1,902). In doing so, four models were contrasted: the one-factor model, Derogatis' nine factor model, a second-ordered factor model, and a bi-factor model. The bi-factor model was shown to yield the closest fit to the data in both countries. Further studies are needed to determine the stable number and kind of subscale scores that reflect the specific (primary) symptoms best, that is, those subscales with minimal shared variance with the overall general psychological distress dimension. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A comparison of technical replicate (cuts) effect on lamb Warner-Bratzler shear force measurement precision.

PubMed

Holman, B W B; Alvarenga, T I R C; van de Ven, R J; Hopkins, D L

2015-07-01

The Warner-Bratzler shear force (WBSF) of 335 lamb m. longissimus lumborum (LL) caudal and cranial ends was measured to examine and simulate the effect of replicate number (r: 1-8) on the precision of mean WBSF estimates and to compare LL caudal and cranial end WBSF means. All LL were sourced from two experimental flocks as part of the Information Nucleus slaughter programme (CRC for Sheep Industry Innovation) and analysed using a Lloyd Texture analyser with a Warner-Bratzler blade attachment. WBSF data were natural logarithm (ln) transformed before statistical analysis. Mean ln(WBSF) precision improved as r increased; however the practical implications support an r equal to 6, as precision improves only marginally with additional replicates. Increasing LL sample replication results in better ln(WBSF) precision compared with increasing r, provided that sample replicates are removed from the same LL end. Cranial end mean WBSF was 11.2 ± 1.3% higher than the caudal end. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Sampling design trade-offs in occupancy studies with imperfect detection: examples and software

USGS Publications Warehouse

Bailey, L.L.; Hines, J.E.; Nichols, J.D.

2007-01-01

Researchers have used occupancy, or probability of occupancy, as a response or state variable in a variety of studies (e.g., habitat modeling), and occupancy is increasingly favored by numerous state, federal, and international agencies engaged in monitoring programs. Recent advances in estimation methods have emphasized that reliable inferences can be made from these types of studies if detection and occupancy probabilities are simultaneously estimated. The need for temporal replication at sampled sites to estimate detection probability creates a trade-off between spatial replication (number of sample sites distributed within the area of interest/inference) and temporal replication (number of repeated surveys at each site). Here, we discuss a suite of questions commonly encountered during the design phase of occupancy studies, and we describe software (program GENPRES) developed to allow investigators to easily explore design trade-offs focused on particularities of their study system and sampling limitations. We illustrate the utility of program GENPRES using an amphibian example from Greater Yellowstone National Park, USA.

Fluid sampling apparatus and method

DOEpatents

Yeamans, D.R.

1998-02-03

Incorporation of a bellows in a sampling syringe eliminates ingress of contaminants, permits replication of amounts and compression of multiple sample injections, and enables remote sampling for off-site analysis. 3 figs.

Response interruption and redirection for vocal stereotypy in children with autism: a systematic replication.

PubMed

Cassella, Megan Duffy; Sidener, Tina M; Sidener, David W; Progar, Patrick R

2011-01-01

This study systematically replicated and extended previous research on response interruption and redirection (RIRD) by assessing instructed responses of a different topography than the target behavior, percentage of session spent in treatment, generalization of behavior reduction, and social validity of the intervention. Results showed that RIRD produced substantial decreases in vocal stereotypy. Limitations of this study were that behavior reduction did not generalize to novel settings or with novel instructors and that appropriate vocalizations did not improve.

Interlaboratory comparison for the determination of the soluble fraction of metals in welding fume samples.

PubMed

Berlinger, Balazs; Harper, Martin

2018-02-01

There is interest in the bioaccessible metal components of aerosols, but this has been minimally studied because standardized sampling and analytical methods have not yet been developed. An interlaboratory study (ILS) has been carried out to evaluate a method for determining the water-soluble component of realistic welding fume (WF) air samples. Replicate samples were generated in the laboratory and distributed to participating laboratories to be analyzed according to a standardized procedure. Within-laboratory precision of replicate sample analysis (repeatability) was very good. Reproducibility between laboratories was not as good, but within limits of acceptability for the analysis of typical aerosol samples. These results can be used to support the development of a standardized test method.

Leveraging Genomic Annotations and Pleiotropic Enrichment for Improved Replication Rates in Schizophrenia GWAS

PubMed Central

Wang, Yunpeng; Thompson, Wesley K.; Schork, Andrew J.; Holland, Dominic; Chen, Chi-Hua; Bettella, Francesco; Desikan, Rahul S.; Li, Wen; Witoelar, Aree; Zuber, Verena; Devor, Anna; Nöthen, Markus M.; Rietschel, Marcella; Chen, Qiang; Werge, Thomas; Cichon, Sven; Weinberger, Daniel R.; Djurovic, Srdjan; O’Donovan, Michael; Visscher, Peter M.; Andreassen, Ole A.; Dale, Anders M.

2016-01-01

Most of the genetic architecture of schizophrenia (SCZ) has not yet been identified. Here, we apply a novel statistical algorithm called Covariate-Modulated Mixture Modeling (CM3), which incorporates auxiliary information (heterozygosity, total linkage disequilibrium, genomic annotations, pleiotropy) for each single nucleotide polymorphism (SNP) to enable more accurate estimation of replication probabilities, conditional on the observed test statistic (“z-score”) of the SNP. We use a multiple logistic regression on z-scores to combine information from auxiliary information to derive a “relative enrichment score” for each SNP. For each stratum of these relative enrichment scores, we obtain nonparametric estimates of posterior expected test statistics and replication probabilities as a function of discovery z-scores, using a resampling-based approach that repeatedly and randomly partitions meta-analysis sub-studies into training and replication samples. We fit a scale mixture of two Gaussians model to each stratum, obtaining parameter estimates that minimize the sum of squared differences of the scale-mixture model with the stratified nonparametric estimates. We apply this approach to the recent genome-wide association study (GWAS) of SCZ (n = 82,315), obtaining a good fit between the model-based and observed effect sizes and replication probabilities. We observed that SNPs with low enrichment scores replicate with a lower probability than SNPs with high enrichment scores even when both they are genome-wide significant (p < 5x10-8). There were 693 and 219 independent loci with model-based replication rates ≥80% and ≥90%, respectively. Compared to analyses not incorporating relative enrichment scores, CM3 increased out-of-sample yield for SNPs that replicate at a given rate. This demonstrates that replication probabilities can be more accurately estimated using prior enrichment information with CM3. PMID:26808560

Sample-interpolation timing: an optimized technique for the digital measurement of time of flight for γ rays and neutrons at relatively low sampling rates

NASA Astrophysics Data System (ADS)

Aspinall, M. D.; Joyce, M. J.; Mackin, R. O.; Jarrah, Z.; Boston, A. J.; Nolan, P. J.; Peyton, A. J.; Hawkes, N. P.

2009-01-01

A unique, digital time pick-off method, known as sample-interpolation timing (SIT) is described. This method demonstrates the possibility of improved timing resolution for the digital measurement of time of flight compared with digital replica-analogue time pick-off methods for signals sampled at relatively low rates. Three analogue timing methods have been replicated in the digital domain (leading-edge, crossover and constant-fraction timing) for pulse data sampled at 8 GSa s-1. Events arising from the 7Li(p, n)7Be reaction have been detected with an EJ-301 organic liquid scintillator and recorded with a fast digital sampling oscilloscope. Sample-interpolation timing was developed solely for the digital domain and thus performs more efficiently on digital signals compared with analogue time pick-off methods replicated digitally, especially for fast signals that are sampled at rates that current affordable and portable devices can achieve. Sample interpolation can be applied to any analogue timing method replicated digitally and thus also has the potential to exploit the generic capabilities of analogue techniques with the benefits of operating in the digital domain. A threshold in sampling rate with respect to the signal pulse width is observed beyond which further improvements in timing resolution are not attained. This advance is relevant to many applications in which time-of-flight measurement is essential.

Hepatitis C serosorting among people who inject drugs in rural Puerto Rico.

PubMed

Duncan, Ian; Curtis, Ric; Reyes, Juan Carlos; Abadie, Roberto; Khan, Bilal; Dombrowski, Kirk

2017-06-01

Due to the high cost of treatment, preventative measures to limit Hepatitis C (HCV) transmission among people who inject drugs (PWID) are encouraged by many public health officials. A key one of these is serosorting, where PWID select risk partners based on concordant HCV status. Research on the general U.S. population by Smith et al. (2013) found that knowledge of one's own HCV status facilitated serosorting behaviors among PWID, such that respondents with knowledge of their own status were more likely to ask potential partners about their status prior to sharing risk. Our objective was to see if this held true in rural Puerto Rico. We replicate this study using a sample of PWID in rural Puerto Rico to draw comparisons. We used respondent driven sampling to survey 315 participants, and have a final analytic sample of 154. The survey was heavily modeled after the National HIV Behavioral Survey, which was the dataset used by the previous researchers. We found that among PWID in rural Puerto Rico, unlike in the general population, knowledge of one's own HCV status had no significant effect on the selection of one's most recent injection partner, based on his/her HCV status. We conclude that PWID in rural Puerto Rico differ from the general U.S. population when it comes to serosorting behaviors, and that these differences should be taken into account in future outreaches and intervention strategies.

Patterns of stigma toward schizophrenia among the general population: a latent profile analysis.

PubMed

Loch, Alexandre A; Wang, Yuan-Pang; Guarniero, Francisco B; Lawson, Fabio L; Hengartner, Michael P; Rössler, Wulf; Gattaz, Wagner F

2014-09-01

Our purpose was to assess stigma toward schizophrenia in a representative sample of the Brazilian general population. The sample consisted of 1015 individuals interviewed by telephone. A vignette describing someone with schizophrenia was read, and four stigma aspects regarding this hypothetical individual were assessed: stereotypes, restrictions, perceived prejudice and social distance. Latent profile analysis searched for stigma profiles among the sample. Multinomial logistic regression was used to find correlates of each class. Four stigma profiles were found; 'no stigma' individuals (n = 251) mostly displayed positive opinions. 'Labelers' (n = 222) scored high on social distance; they more often had familial contact with mental illness and more often labeled the vignette's disorder as schizophrenia. 'Discriminators', the group with the majority of individuals (n = 302), showed high levels of stigmatizing beliefs in all dimensions; discriminators were significantly older. 'Unobtrusive stigma' individuals (n = 240) seemed to demonstrate uncertainty or low commitment since they mostly answered items with the middle/impartial option. Some findings from the international literature were replicated; however, familial contact increased stigma, possibly denoting a locally modulated determinant. Hereby, our study also adds important cross-cultural data by showing that stigma toward schizophrenia is high in a Latin-American setting. We highlight the importance of analyzing the general population as a heterogeneous group, aiming to better elaborate anti-stigma campaigns. © The Author(s) 2013.

Failure to replicate depletion of self-control.

PubMed

Xu, Xiaomeng; Demos, Kathryn E; Leahey, Tricia M; Hart, Chantelle N; Trautvetter, Jennifer; Coward, Pamela; Middleton, Kathryn R; Wing, Rena R

2014-01-01

The limited resource or strength model of self-control posits that the use of self-regulatory resources leads to depletion and poorer performance on subsequent self-control tasks. We conducted four studies (two with community samples, two with young adult samples) utilizing a frequently used depletion procedure (crossing out letters protocol) and the two most frequently used dependent measures of self-control (handgrip perseverance and modified Stroop). In each study, participants completed a baseline self-control measure, a depletion or control task (randomized), and then the same measure of self-control a second time. There was no evidence for significant depletion effects in any of these four studies. The null results obtained in four attempts to replicate using strong methodological approaches may indicate that depletion has more limited effects than implied by prior publications. We encourage further efforts to replicate depletion (particularly among community samples) with full disclosure of positive and negative results.

Occupancy models for monitoring marine fish: a bayesian hierarchical approach to model imperfect detection with a novel gear combination.

PubMed

Coggins, Lewis G; Bacheler, Nathan M; Gwinn, Daniel C

2014-01-01

Occupancy models using incidence data collected repeatedly at sites across the range of a population are increasingly employed to infer patterns and processes influencing population distribution and dynamics. While such work is common in terrestrial systems, fewer examples exist in marine applications. This disparity likely exists because the replicate samples required by these models to account for imperfect detection are often impractical to obtain when surveying aquatic organisms, particularly fishes. We employ simultaneous sampling using fish traps and novel underwater camera observations to generate the requisite replicate samples for occupancy models of red snapper, a reef fish species. Since the replicate samples are collected simultaneously by multiple sampling devices, many typical problems encountered when obtaining replicate observations are avoided. Our results suggest that augmenting traditional fish trap sampling with camera observations not only doubled the probability of detecting red snapper in reef habitats off the Southeast coast of the United States, but supplied the necessary observations to infer factors influencing population distribution and abundance while accounting for imperfect detection. We found that detection probabilities tended to be higher for camera traps than traditional fish traps. Furthermore, camera trap detections were influenced by the current direction and turbidity of the water, indicating that collecting data on these variables is important for future monitoring. These models indicate that the distribution and abundance of this species is more heavily influenced by latitude and depth than by micro-scale reef characteristics lending credence to previous characterizations of red snapper as a reef habitat generalist. This study demonstrates the utility of simultaneous sampling devices, including camera traps, in aquatic environments to inform occupancy models and account for imperfect detection when describing factors influencing fish population distribution and dynamics.

Occupancy Models for Monitoring Marine Fish: A Bayesian Hierarchical Approach to Model Imperfect Detection with a Novel Gear Combination

PubMed Central

Coggins, Lewis G.; Bacheler, Nathan M.; Gwinn, Daniel C.

2014-01-01

Occupancy models using incidence data collected repeatedly at sites across the range of a population are increasingly employed to infer patterns and processes influencing population distribution and dynamics. While such work is common in terrestrial systems, fewer examples exist in marine applications. This disparity likely exists because the replicate samples required by these models to account for imperfect detection are often impractical to obtain when surveying aquatic organisms, particularly fishes. We employ simultaneous sampling using fish traps and novel underwater camera observations to generate the requisite replicate samples for occupancy models of red snapper, a reef fish species. Since the replicate samples are collected simultaneously by multiple sampling devices, many typical problems encountered when obtaining replicate observations are avoided. Our results suggest that augmenting traditional fish trap sampling with camera observations not only doubled the probability of detecting red snapper in reef habitats off the Southeast coast of the United States, but supplied the necessary observations to infer factors influencing population distribution and abundance while accounting for imperfect detection. We found that detection probabilities tended to be higher for camera traps than traditional fish traps. Furthermore, camera trap detections were influenced by the current direction and turbidity of the water, indicating that collecting data on these variables is important for future monitoring. These models indicate that the distribution and abundance of this species is more heavily influenced by latitude and depth than by micro-scale reef characteristics lending credence to previous characterizations of red snapper as a reef habitat generalist. This study demonstrates the utility of simultaneous sampling devices, including camera traps, in aquatic environments to inform occupancy models and account for imperfect detection when describing factors influencing fish population distribution and dynamics. PMID:25255325

Separating Common from Unique Variance Within Emotional Distress: An Examination of Reliability and Relations to Worry.

PubMed

Marshall, Andrew J; Evanovich, Emma K; David, Sarah Jo; Mumma, Gregory H

2018-01-17

High comorbidity rates among emotional disorders have led researchers to examine transdiagnostic factors that may contribute to shared psychopathology. Bifactor models provide a unique method for examining transdiagnostic variables by modelling the common and unique factors within measures. Previous findings suggest that the bifactor model of the Depression Anxiety and Stress Scale (DASS) may provide a method for examining transdiagnostic factors within emotional disorders. This study aimed to replicate the bifactor model of the DASS, a multidimensional measure of psychological distress, within a US adult sample and provide initial estimates of the reliability of the general and domain-specific factors. Furthermore, this study hypothesized that Worry, a theorized transdiagnostic variable, would show stronger relations to general emotional distress than domain-specific subscales. Confirmatory factor analysis was used to evaluate the bifactor model structure of the DASS in 456 US adult participants (279 females and 177 males, mean age 35.9 years) recruited online. The DASS bifactor model fitted well (CFI = 0.98; RMSEA = 0.05). The General Emotional Distress factor accounted for most of the reliable variance in item scores. Domain-specific subscales accounted for modest portions of reliable variance in items after accounting for the general scale. Finally, structural equation modelling indicated that Worry was strongly predicted by the General Emotional Distress factor. The DASS bifactor model is generalizable to a US community sample and General Emotional Distress, but not domain-specific factors, strongly predict the transdiagnostic variable Worry.

Characterizing the replicability of cell types defined by single cell RNA-sequencing data using MetaNeighbor.

PubMed

Crow, Megan; Paul, Anirban; Ballouz, Sara; Huang, Z Josh; Gillis, Jesse

2018-02-28

Single-cell RNA-sequencing (scRNA-seq) technology provides a new avenue to discover and characterize cell types; however, the experiment-specific technical biases and analytic variability inherent to current pipelines may undermine its replicability. Meta-analysis is further hampered by the use of ad hoc naming conventions. Here we demonstrate our replication framework, MetaNeighbor, that quantifies the degree to which cell types replicate across datasets, and enables rapid identification of clusters with high similarity. We first measure the replicability of neuronal identity, comparing results across eight technically and biologically diverse datasets to define best practices for more complex assessments. We then apply this to novel interneuron subtypes, finding that 24/45 subtypes have evidence of replication, which enables the identification of robust candidate marker genes. Across tasks we find that large sets of variably expressed genes can identify replicable cell types with high accuracy, suggesting a general route forward for large-scale evaluation of scRNA-seq data.

Differential effects of lipid biosynthesis inhibitors on Zika and Semliki Forest viruses.

PubMed

Royle, Jamie; Donald, Claire L; Merits, Andres; Kohl, Alain; Varjak, Margus

2017-12-01

The recent outbreak of infection with Zika virus (ZIKV; Flaviviridae) has attracted attention to this previously neglected mosquito-borne pathogen and the need for efficient therapies. Since flavivirus replication is generally known to be dependent on fatty acid biosynthesis, two inhibitors of this pathway, 5-(tetradecyloxyl)-2-furoic acid (TOFA) and cerulenin, were tested for their potentiality to inhibit virus replication. At concentrations previously shown to inhibit the replication of other flaviviruses, neither drug had a significant antiviral affect against ZIKV, but reduced the replication of the non-related mosquito-borne Semliki Forest virus (Togaviridae). Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mink parvoviruses and interferons: in vitro studies.

PubMed Central

Wiedbrauk, D L; Bloom, M E; Lodmell, D L

1986-01-01

Although interferons can inhibit the replication of a number of viruses, little is known about their ability to inhibit parvovirus replication. Therefore, in vitro experiments were done to determine if Aleutian disease virus and mink enteritis virus, two autonomously replicating mink parvoviruses, induced interferon, were sensitive to the effects of interferon, or inhibited the production of interferon. The results indicated that these parvoviruses neither induced nor were sensitive to the effects of interferon. Furthermore, preexisting parvovirus infections did not inhibit poly(I).poly(C)-induced interferon production. This independence from the interferon system may, therefore, be a general property of the autonomously replicating parvoviruses. PMID:2431162

Statistical correction of the Winner’s Curse explains replication variability in quantitative trait genome-wide association studies

PubMed Central

Pe’er, Itsik

2017-01-01

Genome-wide association studies (GWAS) have identified hundreds of SNPs responsible for variation in human quantitative traits. However, genome-wide-significant associations often fail to replicate across independent cohorts, in apparent inconsistency with their apparent strong effects in discovery cohorts. This limited success of replication raises pervasive questions about the utility of the GWAS field. We identify all 332 studies of quantitative traits from the NHGRI-EBI GWAS Database with attempted replication. We find that the majority of studies provide insufficient data to evaluate replication rates. The remaining papers replicate significantly worse than expected (p < 10−14), even when adjusting for regression-to-the-mean of effect size between discovery- and replication-cohorts termed the Winner’s Curse (p < 10−16). We show this is due in part to misreporting replication cohort-size as a maximum number, rather than per-locus one. In 39 studies accurately reporting per-locus cohort-size for attempted replication of 707 loci in samples with similar ancestry, replication rate matched expectation (predicted 458, observed 457, p = 0.94). In contrast, ancestry differences between replication and discovery (13 studies, 385 loci) cause the most highly-powered decile of loci to replicate worse than expected, due to difference in linkage disequilibrium. PMID:28715421

Initiation of DNA replication requires actin dynamics and formin activity.

PubMed

Parisis, Nikolaos; Krasinska, Liliana; Harker, Bethany; Urbach, Serge; Rossignol, Michel; Camasses, Alain; Dewar, James; Morin, Nathalie; Fisher, Daniel

2017-11-02

Nuclear actin regulates transcriptional programmes in a manner dependent on its levels and polymerisation state. This dynamics is determined by the balance of nucleocytoplasmic shuttling, formin- and redox-dependent filament polymerisation. Here, using Xenopus egg extracts and human somatic cells, we show that actin dynamics and formins are essential for DNA replication. In proliferating cells, formin inhibition abolishes nuclear transport and initiation of DNA replication, as well as general transcription. In replicating nuclei from transcriptionally silent Xenopus egg extracts, we identified numerous actin regulators, and disruption of actin dynamics abrogates nuclear transport, preventing NLS (nuclear localisation signal)-cargo release from RanGTP-importin complexes. Nuclear formin activity is further required to promote loading of cyclin-dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) onto chromatin, as well as initiation and elongation of DNA replication. Therefore, actin dynamics and formins control DNA replication by multiple direct and indirect mechanisms. © 2017 The Authors.

Design and optimization of reverse-transcription quantitative PCR experiments.

PubMed

Tichopad, Ales; Kitchen, Rob; Riedmaier, Irmgard; Becker, Christiane; Ståhlberg, Anders; Kubista, Mikael

2009-10-01

Quantitative PCR (qPCR) is a valuable technique for accurately and reliably profiling and quantifying gene expression. Typically, samples obtained from the organism of study have to be processed via several preparative steps before qPCR. We estimated the errors of sample withdrawal and extraction, reverse transcription (RT), and qPCR that are introduced into measurements of mRNA concentrations. We performed hierarchically arranged experiments with 3 animals, 3 samples, 3 RT reactions, and 3 qPCRs and quantified the expression of several genes in solid tissue, blood, cell culture, and single cells. A nested ANOVA design was used to model the experiments, and relative and absolute errors were calculated with this model for each processing level in the hierarchical design. We found that intersubject differences became easily confounded by sample heterogeneity for single cells and solid tissue. In cell cultures and blood, the noise from the RT and qPCR steps contributed substantially to the overall error because the sampling noise was less pronounced. We recommend the use of sample replicates preferentially to any other replicates when working with solid tissue, cell cultures, and single cells, and we recommend the use of RT replicates when working with blood. We show how an optimal sampling plan can be calculated for a limited budget. .

Estimating replicate time shifts using Gaussian process regression

PubMed Central

Liu, Qiang; Andersen, Bogi; Smyth, Padhraic; Ihler, Alexander

2010-01-01

Motivation: Time-course gene expression datasets provide important insights into dynamic aspects of biological processes, such as circadian rhythms, cell cycle and organ development. In a typical microarray time-course experiment, measurements are obtained at each time point from multiple replicate samples. Accurately recovering the gene expression patterns from experimental observations is made challenging by both measurement noise and variation among replicates' rates of development. Prior work on this topic has focused on inference of expression patterns assuming that the replicate times are synchronized. We develop a statistical approach that simultaneously infers both (i) the underlying (hidden) expression profile for each gene, as well as (ii) the biological time for each individual replicate. Our approach is based on Gaussian process regression (GPR) combined with a probabilistic model that accounts for uncertainty about the biological development time of each replicate. Results: We apply GPR with uncertain measurement times to a microarray dataset of mRNA expression for the hair-growth cycle in mouse back skin, predicting both profile shapes and biological times for each replicate. The predicted time shifts show high consistency with independently obtained morphological estimates of relative development. We also show that the method systematically reduces prediction error on out-of-sample data, significantly reducing the mean squared error in a cross-validation study. Availability: Matlab code for GPR with uncertain time shifts is available at http://sli.ics.uci.edu/Code/GPRTimeshift/ Contact: ihler@ics.uci.edu PMID:20147305

Dynamics of DNA replication during premeiosis and early meiosis in wheat.

PubMed

Rey, María-Dolores; Prieto, Pilar

2014-01-01

Meiosis is a specialised cell division that involves chromosome replication, two rounds of chromosome segregation and results in the formation of the gametes. Meiotic DNA replication generally precedes chromosome pairing, recombination and synapsis in sexually developing eukaryotes. In this work, replication has been studied during premeiosis and early meiosis in wheat using flow cytometry, which has allowed the quantification of the amount of DNA in wheat anther in each phase of the cell cycle during premeiosis and each stage of early meiosis. Flow cytometry has been revealed as a suitable and user-friendly tool to detect and quantify DNA replication during early meiosis in wheat. Chromosome replication was detected in wheat during premeiosis and early meiosis until the stage of pachytene, when chromosomes are associated in pairs to further recombine and correctly segregate in the gametes. In addition, the effect of the Ph1 locus, which controls chromosome pairing and affects replication in wheat, was also studied by flow cytometry. Here we showed that the Ph1 locus plays an important role on the length of meiotic DNA replication in wheat, particularly affecting the rate of replication during early meiosis in wheat.

Dynamics of DNA Replication during Premeiosis and Early Meiosis in Wheat

PubMed Central

Rey, María-Dolores; Prieto, Pilar

2014-01-01

Meiosis is a specialised cell division that involves chromosome replication, two rounds of chromosome segregation and results in the formation of the gametes. Meiotic DNA replication generally precedes chromosome pairing, recombination and synapsis in sexually developing eukaryotes. In this work, replication has been studied during premeiosis and early meiosis in wheat using flow cytometry, which has allowed the quantification of the amount of DNA in wheat anther in each phase of the cell cycle during premeiosis and each stage of early meiosis. Flow cytometry has been revealed as a suitable and user-friendly tool to detect and quantify DNA replication during early meiosis in wheat. Chromosome replication was detected in wheat during premeiosis and early meiosis until the stage of pachytene, when chromosomes are associated in pairs to further recombine and correctly segregate in the gametes. In addition, the effect of the Ph1 locus, which controls chromosome pairing and affects replication in wheat, was also studied by flow cytometry. Here we showed that the Ph1 locus plays an important role on the length of meiotic DNA replication in wheat, particularly affecting the rate of replication during early meiosis in wheat. PMID:25275307

Aggregate and individual replication probability within an explicit model of the research process.

PubMed

Miller, Jeff; Schwarz, Wolf

2011-09-01

We study a model of the research process in which the true effect size, the replication jitter due to changes in experimental procedure, and the statistical error of effect size measurement are all normally distributed random variables. Within this model, we analyze the probability of successfully replicating an initial experimental result by obtaining either a statistically significant result in the same direction or any effect in that direction. We analyze both the probability of successfully replicating a particular experimental effect (i.e., the individual replication probability) and the average probability of successful replication across different studies within some research context (i.e., the aggregate replication probability), and we identify the conditions under which the latter can be approximated using the formulas of Killeen (2005a, 2007). We show how both of these probabilities depend on parameters of the research context that would rarely be known in practice. In addition, we show that the statistical uncertainty associated with the size of an initial observed effect would often prevent accurate estimation of the desired individual replication probability even if these research context parameters were known exactly. We conclude that accurate estimates of replication probability are generally unattainable.

A primary care Web-based Intervention Modeling Experiment replicated behavior changes seen in earlier paper-based experiment.

PubMed

Treweek, Shaun; Francis, Jill J; Bonetti, Debbie; Barnett, Karen; Eccles, Martin P; Hudson, Jemma; Jones, Claire; Pitts, Nigel B; Ricketts, Ian W; Sullivan, Frank; Weal, Mark; MacLennan, Graeme

2016-12-01

Intervention Modeling Experiments (IMEs) are a way of developing and testing behavior change interventions before a trial. We aimed to test this methodology in a Web-based IME that replicated the trial component of an earlier, paper-based IME. Three-arm, Web-based randomized evaluation of two interventions (persuasive communication and action plan) and a "no intervention" comparator. The interventions were designed to reduce the number of antibiotic prescriptions in the management of uncomplicated upper respiratory tract infection. General practitioners (GPs) were invited to complete an online questionnaire and eight clinical scenarios where an antibiotic might be considered. One hundred twenty-nine GPs completed the questionnaire. GPs receiving the persuasive communication did not prescribe an antibiotic in 0.70 more scenarios (95% confidence interval [CI] = 0.17-1.24) than those in the control arm. For the action plan, GPs did not prescribe an antibiotic in 0.63 (95% CI = 0.11-1.15) more scenarios than those in the control arm. Unlike the earlier IME, behavioral intention was unaffected by the interventions; this may be due to a smaller sample size than intended. A Web-based IME largely replicated the findings of an earlier paper-based study, providing some grounds for confidence in the IME methodology. Copyright © 2016 Elsevier Inc. All rights reserved.

Symmetry of interactions rules in incompletely connected random replicator ecosystems.

PubMed

Kärenlampi, Petri P

2014-06-01

The evolution of an incompletely connected system of species with speciation and extinction is investigated in terms of random replicators. It is found that evolving random replicator systems with speciation do become large and complex, depending on speciation parameters. Antisymmetric interactions result in large systems, whereas systems with symmetric interactions remain small. A co-dominating feature is within-species interaction pressure: large within-species interaction increases species diversity. Average fitness evolves in all systems, however symmetry and connectivity evolve in small systems only. Newcomers get extinct almost immediately in symmetric systems. The distribution in species lifetimes is determined for antisymmetric systems. The replicator systems investigated do not show any sign of self-organized criticality. The generalized Lotka-Volterra system is shown to be a tedious way of implementing the replicator system.

Genome-wide association analysis and replication of coronary artery disease in South Korea suggests a causal variant common to diverse populations

PubMed Central

Cho, Eun Young; Jang, Yangsoo; Shin, Eun Soon; Jang, Hye Yoon; Yoo, Yeon-Kyeong; Kim, Sook; Jang, Ji Hyun; Lee, Ji Yeon; Yun, Min Hye; Park, Min Young; Chae, Jey Sook; Lim, Jin Woo; Shin, Dong Jik; Park, Sungha; Lee, Jong Ho; Han, Bok Ghee; Rae, Kim Hyung; Cardon, Lon R; Morris, Andrew P; Lee, Jong Eun; Clarke, Geraldine M

2010-01-01

Background Recent genome-wide association (GWA) studies have identified and replicated several genetic loci associated with the risk of development of coronary artery disease (CAD) in samples from populations of Caucasian and Asian descent. However, only chromosome 9p21 has been confirmed as a major susceptibility locus conferring risk for development of CAD across multiple ethnic groups. The authors aimed to find evidence of further similarities and differences in genetic risk of CAD between Korean and other populations. Methods The authors performed a GWA study comprising 230 cases and 290 controls from a Korean population typed on 490 032 single nucleotide polymorphisms (SNPs). A total of 3148 SNPs were taken forward for genotyping in a subsequent replication study using an independent sample of 1172 cases and 1087 controls from the same population. Results The association previously observed on chromosome 9p21 was independently replicated (p=3.08e–07). Within this region, the same risk haplotype was observed in samples from both Korea and of Western European descent, suggesting that the causal mutation carried on this background occurred on a single ancestral allele. Other than 9p21, the authors were unable to replicate any of the previously reported signals for association with CAD. Furthermore, no evidence of association was found at chromosome 1q41 for risk of myocardial infarction, previously identified as conferring risk in a Japanese population. Conclusion A common causal variant is likely to be responsible for risk of CAD in Korean and Western European populations at chromosome 9p21.3. Further investigations are required to confirm non-replication of any other cross-race genetic risk factors. PMID:27325954

Determination of total tin in geological materials by electrothermal atomic-absorption spectrophotometry using a tungsten-impregnated graphite furnace

USGS Publications Warehouse

Zhou, L.; Chao, T.T.; Meier, A.L.

1984-01-01

An electrothermal atomic-absorption spectrophotometric method is described for the determination of total tin in geological materials, with use of a tungsten-impregnated graphite furnace. The sample is decomposed by fusion with lithium metaborate and the melt is dissolved in 10% hydrochloric acid. Tin is then extracted into trioctylphosphine oxide-methyl isobutyl ketone prior to atomization. Impregnation of the furnace with a sodium tungstate solution increases the sensitivity of the determination and improves the precision of the results. The limits of determination are 0.5-20 ppm of tin in the sample. Higher tin values can be determined by dilution of the extract. Replicate analyses of eighteen geological reference samples with diverse matrices gave relative standard deviations ranging from 2.0 to 10.8% with an average of 4.6%. Average tin values for reference samples were in general agreement with, but more precise than, those reported by others. Apparent recoveries of tin added to various samples ranged from 95 to 111% with an average of 102%. ?? 1984.

Attitude Toward Ambiguity: Empirically Robust Factors in Self-Report Personality Scales.

PubMed

Lauriola, Marco; Foschi, Renato; Mosca, Oriana; Weller, Joshua

2016-06-01

Two studies were conducted to examine the factor structure of attitude toward ambiguity, a broad personality construct that refers to personal reactions to perceived ambiguous stimuli in a variety of context and situations. Using samples from two countries, Study 1 mapped the hierarchical structure of 133 items from seven tolerance-intolerance of ambiguity scales (N = 360, Italy; N = 306, United States). Three major factors-Discomfort with Ambiguity, Moral Absolutism/Splitting, and Need for Complexity and Novelty-were recovered in each country with high replicability coefficients across samples. In Study 2 (N = 405, Italian community sample; N =366, English native speakers sample), we carried out a confirmatory analysis on selected factor markers. A bifactor model had an acceptable fit for each sample and reached the construct-level invariance for general and group factors. Convergent validity with related traits was assessed in both studies. We conclude that attitude toward ambiguity can be best represented a multidimensional construct involving affective (Discomfort with Ambiguity), cognitive (Moral Absolutism/Splitting), and epistemic (Need for Complexity and Novelty) components. © The Author(s) 2015.

Genetic characterization of Greek population isolates reveals strong genetic drift at missense and trait-associated variants

PubMed Central

Panoutsopoulou, Kalliope; Hatzikotoulas, Konstantinos; Xifara, Dionysia Kiara; Colonna, Vincenza; Farmaki, Aliki-Eleni; Ritchie, Graham R. S.; Southam, Lorraine; Gilly, Arthur; Tachmazidou, Ioanna; Fatumo, Segun; Matchan, Angela; Rayner, Nigel W.; Ntalla, Ioanna; Mezzavilla, Massimo; Chen, Yuan; Kiagiadaki, Chrysoula; Zengini, Eleni; Mamakou, Vasiliki; Athanasiadis, Antonis; Giannakopoulou, Margarita; Kariakli, Vassiliki-Eirini; Nsubuga, Rebecca N.; Karabarinde, Alex; Sandhu, Manjinder; McVean, Gil; Tyler-Smith, Chris; Tsafantakis, Emmanouil; Karaleftheri, Maria; Xue, Yali; Dedoussis, George; Zeggini, Eleftheria

2014-01-01

Isolated populations are emerging as a powerful study design in the search for low-frequency and rare variant associations with complex phenotypes. Here we genotype 2,296 samples from two isolated Greek populations, the Pomak villages (HELIC-Pomak) in the North of Greece and the Mylopotamos villages (HELIC-MANOLIS) in Crete. We compare their genomic characteristics to the general Greek population and establish them as genetic isolates. In the MANOLIS cohort, we observe an enrichment of missense variants among the variants that have drifted up in frequency by more than fivefold. In the Pomak cohort, we find novel associations at variants on chr11p15.4 showing large allele frequency increases (from 0.2% in the general Greek population to 4.6% in the isolate) with haematological traits, for example, with mean corpuscular volume (rs7116019, P=2.3 × 10−26). We replicate this association in a second set of Pomak samples (combined P=2.0 × 10−36). We demonstrate significant power gains in detecting medical trait associations. PMID:25373335

Characterization of helium diffusion behavior from continuous heating experiments: Sample screening and identification of multiple 4He components

NASA Astrophysics Data System (ADS)

McDannell, K. T.; Idleman, B. D.; Zeitler, P. K.

2015-12-01

Old, slowly cooled apatites often yield overdispersed helium ages due to factors such as parent zonation, He implantation, radiation damage, crystal defects, and fluid inclusions. Careful mineral selection and many replicate analyses can mitigate the impact of some of these effects. However, this approach adds unnecessary costs in time and resources when dating well-behaved apatites and is generally ineffective at identifying the root cause of age dispersion and providing suitable age corrections for poorly behaved samples. We assess a new technique utilizing static-gas measurement during continuous heating as a means to rapidly screen apatite samples. In about the time required for a conventional total-gas analysis, this method can discriminate between samples showing the volume-diffusion behavior expected for apatite and those showing anomalous release patterns, inconsistent with their use in thermochronologic applications. This method may also have the potential to quantify and discriminate between the radiogenic and extraneous 4He fractions released by a sample. Continuously heated samples that outgas by volume diffusion during a linear heating schedule should produce a characteristic sigmoidal 4He fractional loss profile, with the exact shape and position of these profiles (in loss vs. heating time space) controlled by sample kinetics, grain size, and heating rate. Secondary factors such as sample zoning and alpha-loss distribution have a relatively minor impact on such profiles. Well-behaved examples such as the Durango standard and other apatites with good age reproducibility show the expected smooth, sigmoidal gas release with complete exhaustion by temperatures predicted for volume diffusion using typical apatite kinetics (e.g., by ~900˚C for linear heating at 20˚C/minute). In contrast, "bad actor" samples that do not replicate well show significant degrees of helium release deferred to higher temperatures. We report on screening results for a range of samples including a suite of slowly cooled Cretaceous apatites from the Hangay Dome in central Mongolia, assessing the degree to which screening using cumulative heating can reliably identify bad-actor grains, and possibly, correct their ages.

Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs.

PubMed

Delacrétaz, Aurélie; Lagares Santos, Patricia; Saigi Morgui, Nuria; Vandenberghe, Frederik; Glatard, Anaïs; Gholam-Rezaee, Mehdi; von Gunten, Armin; Conus, Philippe; Eap, Chin B

2017-12-01

Dyslipidemia represents a major health issue in psychiatry. We determined whether weighted polygenic risk scores (wPRSs) combining multiple single-nucleotide polymorphisms (SNPs) associated with lipid levels in the general population are associated with lipid levels [high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides] and/or dyslipidemia in patients receiving weight gain-inducing psychotropic drugs. We also determined whether genetics improve the predictive power of dyslipidemia. The influence of wPRS on lipid levels was firstly assessed in a discovery psychiatric sample (n=332) and was then tested for replication in an independent psychiatric sample (n=140). The contribution of genetic markers to predict dyslipidemia was evaluated in the combined psychiatric sample. wPRSs were significantly associated with the four lipid traits in the discovery (P≤0.02) and in the replication sample (P≤0.03). Patients whose wPRS was higher than the median wPRS had significantly higher LDL, TC, and triglyceride levels (0.20, 0.32 and 0.26 mmol/l, respectively; P≤0.004) and significantly lower HDL levels (0.13 mmol/l; P<0.0001) compared with others. Adding wPRS to clinical data significantly improved dyslipidemia prediction of HDL (P=0.03) and a trend for improvement was observed for the prediction of TC dyslipidemia (P=0.08). Population-based wPRSs have thus significant effects on lipid levels in the psychiatric population. As genetics improved the predictive power of dyslipidemia development, only 24 patients need to be genotyped to prevent the development of one case of HDL hypocholesterolemia. If confirmed by further prospective investigations, the present results could be used for individualizing psychotropic treatment.

Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs.

PubMed

Delacrétaz, Aurélie; Zdralovic, Adna; Vandenberghe, Frederik; Saigi-Morgui, Nuria; Glatard, Anaïs; Quteineh, Lina; Gholam-Rezaee, Mehdi; Raffoul, Wassim; Applegate, Lee Ann; Jafari, Paris; Gamma, Franziska; von Gunten, Armin; Conus, Philippe; Eap, Chin B

2017-09-10

Genetic factors associated with Body Mass Index (BMI) have been widely studied over the last decade. We examined whether genetic variants previously associated with BMI in the general population are associated with cardiometabolic parameter worsening in the psychiatric population receiving psychotropic drugs, a high-risk group for metabolic disturbances. Classification And Regression Trees (CARTs) were used as a tool capable of describing hierarchical associations, to pinpoint genetic variants best predicting worsening of cardiometabolic parameters (i.e total, HDL and LDL-cholesterol, triglycerides, body mass index, waist circumference, fasting glucose, and blood pressure) following prescription of psychotropic drugs inducing weight gain in a discovery sample of 357 Caucasian patients. Significant findings were tested for replication in a second Caucasian psychiatric sample (n=140). SH2B1 rs3888190C>A was significantly associated with LDL levels in the discovery and in the replication sample, with A-allele carriers having 0.2mmol/l (p=0.005) and 0.36mmol/l (p=0.007) higher LDL levels compared to others, respectively. G-allele carriers of RABEP1 rs1000940A>G had lower fasting glucose levels compared to others in both samples (-0.16mmol/l; p<0.001 and -0.77mmol/l; p=0.03 respectively). The present study is the first to observe such associations in human subjects, which may in part be explained by a high risk towards dyslipidemia and diabetes in psychiatric patients receiving psychotropic treatments compared to population-based individuals. These results may therefore give new insight into the etiology of LDL-cholesterol and glucose regulation in psychiatric patients under psychotropic drug therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

The temporal program of chromosome replication: genomewide replication in clb5{Delta} Saccharomyces cerevisiae.

PubMed

McCune, Heather J; Danielson, Laura S; Alvino, Gina M; Collingwood, David; Delrow, Jeffrey J; Fangman, Walton L; Brewer, Bonita J; Raghuraman, M K

2008-12-01

Temporal regulation of origin activation is widely thought to explain the pattern of early- and late-replicating domains in the Saccharomyces cerevisiae genome. Recently, single-molecule analysis of replication suggested that stochastic processes acting on origins with different probabilities of activation could generate the observed kinetics of replication without requiring an underlying temporal order. To distinguish between these possibilities, we examined a clb5Delta strain, where origin firing is largely limited to the first half of S phase, to ask whether all origins nonspecifically show decreased firing (as expected for disordered firing) or if only some origins ("late" origins) are affected. Approximately half the origins in the mutant genome show delayed replication while the remainder replicate largely on time. The delayed regions can encompass hundreds of kilobases and generally correspond to regions that replicate late in wild-type cells. Kinetic analysis of replication in wild-type cells reveals broad windows of origin firing for both early and late origins. Our results are consistent with a temporal model in which origins can show some heterogeneity in both time and probability of origin firing, but clustering of temporally like origins nevertheless yields a genome that is organized into blocks showing different replication times.

TFAP2B Influences the Effect of Dietary Fat on Weight Loss under Energy Restriction

PubMed Central

Banasik, Karina; Harder, Marie N.; Taylor, Moira A.; Hager, Jörg; Arner, Peter; Oppert, Jean-Michel; Martinez, J. Alfredo; Polak, Jan; Rousseau, Francis; Langin, Dominique; Rössner, Stephan; Holst, Claus; MacDonald, Ian A.; Kamatani, Yoichiro; Pfeiffer, Andreas F. H.; Kunesova, Marie; Saris, Wim H. M.; Hansen, Torben; Pedersen, Oluf; Astrup, Arne; Sørensen, Thorkild I. A.

2012-01-01

Background Numerous gene loci are related to single measures of body weight and shape. We investigated if 55 SNPs previously associated with BMI or waist measures, modify the effects of fat intake on weight loss and waist reduction under energy restriction. Methods and Findings Randomized controlled trial of 771 obese adults. (Registration: ISRCTN25867281.) One SNP was selected for replication in another weight loss intervention study of 934 obese adults. The original trial was a 10-week 600 kcal/d energy-deficient diet with energy percentage from fat (fat%) in range of 20–25 or 40–45. The replication study used an 8-weeks diet of 880 kcal/d and 20 fat%; change in fat% intake was used for estimation of interaction effects. The main outcomes were intervention weight loss and waist reduction. In the trial, mean change in fat% intake was −12/+4 in the low/high-fat groups. In the replication study, it was −23/−12 among those reducing fat% more/less than the median. TFAP2B-rs987237 genotype AA was associated with 1.0 kg (95% CI, 0.4; 1.6) greater weight loss on the low-fat, and GG genotype with 2.6 kg (1.1; 4.1) greater weight loss on the high-fat (interaction p-value; p = 0.00007). The replication study showed a similar (non-significant) interaction pattern. Waist reduction results generally were similar. Study-strengths include (i) the discovery study randomised trial design combined with the replication opportunity (ii) the strict dietary intake control in both studies (iii) the large sample sizes of both studies. Limitations are (i) the low minor allele frequency of the TFAP2B polymorphism, making it hard to investigate non-additive genetic effects (ii) the different interventions preventing identical replication-discovery study designs (iii) some missing data for non-completers and dietary intake. No adverse effects/outcomes or side-effects were observed. Conclusions Under energy restriction, TFAP2B may modify the effect of dietary fat intake on weight loss and waist reduction. PMID:22952648

Does a single session of reading literary fiction prime enhanced mentalising performance? Four replication experiments of Kidd and Castano (2013).

PubMed

Samur, Dalya; Tops, Mattie; Koole, Sander L

2018-02-01

Prior experiments indicated that reading literary fiction improves mentalising performance relative to reading popular fiction, non-fiction, or not reading. However, the experiments had relatively small sample sizes and hence low statistical power. To address this limitation, the present authors conducted four high-powered replication experiments (combined N = 1006) testing the causal impact of reading literary fiction on mentalising. Relative to the original research, the present experiments used the same literary texts in the reading manipulation; the same mentalising task; and the same kind of participant samples. Moreover, one experiment was pre-registered as a direct replication. In none of the experiments did reading literary fiction have any effect on mentalising relative to control conditions. The results replicate earlier findings that familiarity with fiction is positively correlated with mentalising. Taken together, the present findings call into question whether a single session of reading fiction leads to immediate improvements in mentalising.

Optimal source coding, removable noise elimination, and natural coordinate system construction for general vector sources using replicator neural networks

NASA Astrophysics Data System (ADS)

Hecht-Nielsen, Robert

1997-04-01

A new universal one-chart smooth manifold model for vector information sources is introduced. Natural coordinates (a particular type of chart) for such data manifolds are then defined. Uniformly quantized natural coordinates form an optimal vector quantization code for a general vector source. Replicator neural networks (a specialized type of multilayer perceptron with three hidden layers) are the introduced. As properly configured examples of replicator networks approach minimum mean squared error (e.g., via training and architecture adjustment using randomly chosen vectors from the source), these networks automatically develop a mapping which, in the limit, produces natural coordinates for arbitrary source vectors. The new concept of removable noise (a noise model applicable to a wide variety of real-world noise processes) is then discussed. Replicator neural networks, when configured to approach minimum mean squared reconstruction error (e.g., via training and architecture adjustment on randomly chosen examples from a vector source, each with randomly chosen additive removable noise contamination), in the limit eliminate removable noise and produce natural coordinates for the data vector portions of the noise-corrupted source vectors. Consideration regarding selection of the dimension of a data manifold source model and the training/configuration of replicator neural networks are discussed.

Low template STR typing: effect of replicate number and consensus method on genotyping reliability and DNA database search results.

PubMed

Benschop, Corina C G; van der Beek, Cornelis P; Meiland, Hugo C; van Gorp, Ankie G M; Westen, Antoinette A; Sijen, Titia

2011-08-01

To analyze DNA samples with very low DNA concentrations, various methods have been developed that sensitize short tandem repeat (STR) typing. Sensitized DNA typing is accompanied by stochastic amplification effects, such as allele drop-outs and drop-ins. Therefore low template (LT) DNA profiles are interpreted with care. One can either try to infer the genotype by a consensus method that uses alleles confirmed in replicate analyses, or one can use a statistical model to evaluate the strength of the evidence in a direct comparison with a known DNA profile. In this study we focused on the first strategy and we show that the procedure by which the consensus profile is assembled will affect genotyping reliability. In order to gain insight in the roles of replicate number and requested level of reproducibility, we generated six independent amplifications of samples of known donors. The LT methods included both increased cycling and enhanced capillary electrophoresis (CE) injection [1]. Consensus profiles were assembled from two to six of the replications using four methods: composite (include all alleles), n-1 (include alleles detected in all but one replicate), n/2 (include alleles detected in at least half of the replicates) and 2× (include alleles detected twice). We compared the consensus DNA profiles with the DNA profile of the known donor, studied the stochastic amplification effects and examined the effect of the consensus procedure on DNA database search results. From all these analyses we conclude that the accuracy of LT DNA typing and the efficiency of database searching improve when the number of replicates is increased and the consensus method is n/2. The most functional number of replicates within this n/2 method is four (although a replicate number of three suffices for samples showing >25% of the alleles in standard STR typing). This approach was also the optimal strategy for the analysis of 2-person mixtures, although modified search strategies may be needed to retrieve the minor component in database searches. From the database searches follows the recommendation to specifically mark LT DNA profiles when entering them into the DNA database. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Methods for sampling geographically mobile female traders in an East African market setting

PubMed Central

Achiro, Lillian; Kwena, Zachary A.; McFarland, Willi; Neilands, Torsten B.; Cohen, Craig R.; Bukusi, Elizabeth A.; Camlin, Carol S.

2018-01-01

Background The role of migration in the spread of HIV in sub-Saharan Africa is well-documented. Yet migration and HIV research have often focused on HIV risks to male migrants and their partners, or migrants overall, often failing to measure the risks to women via their direct involvement in migration. Inconsistent measures of mobility, gender biases in those measures, and limited data sources for sex-specific population-based estimates of mobility have contributed to a paucity of research on the HIV prevention and care needs of migrant and highly mobile women. This study addresses an urgent need for novel methods for developing probability-based, systematic samples of highly mobile women, focusing on a population of female traders operating out of one of the largest open air markets in East Africa. Our method involves three stages: 1.) identification and mapping of all market stall locations using Global Positioning System (GPS) coordinates; 2.) using female market vendor stall GPS coordinates to build the sampling frame using replicates; and 3.) using maps and GPS data for recruitment of study participants. Results The location of 6,390 vendor stalls were mapped using GPS. Of these, 4,064 stalls occupied by women (63.6%) were used to draw four replicates of 128 stalls each, and a fifth replicate of 15 pre-selected random alternates for a total of 527 stalls assigned to one of five replicates. Staff visited 323 stalls from the first three replicates and from these successfully recruited 306 female vendors into the study for a participation rate of 94.7%. Mobilization strategies and involving traders association representatives in participant recruitment were critical to the study’s success. Conclusion The study’s high participation rate suggests that this geospatial sampling method holds promise for development of probability-based samples in other settings that serve as transport hubs for highly mobile populations. PMID:29324780

Intrapulmonary Human Cytomegalovirus Replication in Lung Transplant Recipients Is Associated With a Rise of CCL-18 and CCL-20 Chemokine Levels.

PubMed

Weseslindtner, Lukas; Görzer, Irene; Roedl, Kevin; Küng, Erik; Jaksch, Peter; Klepetko, Walter; Puchhammer-Stöckl, Elisabeth

2017-01-01

In lung transplant recipients (LTRs), human cytomegalovirus (HCMV) DNA detection in the bronchoalveolar lavage fluid (BALF) indicates HCMV replication in the pulmonary compartment. Such local HCMV replication episodes may remain asymptomatic or may lead to symptomatic HCMV disease. Here, we investigated LTRs with intrapulmonary HCMV replication for the chemokines CCL-18 and CCL-20. In particular, we analyzed whether these chemokines rise in the allograft and/or the blood and are associated with HCMV disease. CCL-18 and CCL-20 levels were quantitated by ELISA in BALF and serum samples from 60 LTRs. During the posttransplant follow-up, these LTRs displayed HCMV DNA detection in the BALF by PCR, whereas other infectious agents were undetectable. Furthermore, we investigated samples from 10 controls who did not display any HCMV replication episode during the follow-up. HCMV replication in the allograft was associated with a significant increase of CCL-18 and CCL-20 BALF levels (P < 0.001, Wilcoxon signed-rank test) and a significant rise of CCL-20 (P < 0.0001, Wilcoxon signed-rank test) but not of CCL-18 in the blood. In controls, no such chemokine increase was observed. Furthermore, CCL-18 BALF levels were significantly higher in 8 LTRs who additionally developed HCMV disease, as compared with the other 52 patients in whom HCMV replication remained asymptomatic (P < 0.001, Mann-Whitney U test). HCMV replication in the allograft causes an intrapulmonary increase of CCL-18 and CCL-20 and a systemic rise of CCL-20 serum levels. Strong intrapulmonary CCL-18 responses are associated with symptomatic HCMV disease, proposing that CCL-18 BALF levels could serve as a marker.

Speeding Up Non-Parametric Bootstrap Computations for Statistics Based on Sample Moments in Small/Moderate Sample Size Applications

PubMed Central

Chaibub Neto, Elias

2015-01-01

In this paper we propose a vectorized implementation of the non-parametric bootstrap for statistics based on sample moments. Basically, we adopt the multinomial sampling formulation of the non-parametric bootstrap, and compute bootstrap replications of sample moment statistics by simply weighting the observed data according to multinomial counts instead of evaluating the statistic on a resampled version of the observed data. Using this formulation we can generate a matrix of bootstrap weights and compute the entire vector of bootstrap replications with a few matrix multiplications. Vectorization is particularly important for matrix-oriented programming languages such as R, where matrix/vector calculations tend to be faster than scalar operations implemented in a loop. We illustrate the application of the vectorized implementation in real and simulated data sets, when bootstrapping Pearson’s sample correlation coefficient, and compared its performance against two state-of-the-art R implementations of the non-parametric bootstrap, as well as a straightforward one based on a for loop. Our investigations spanned varying sample sizes and number of bootstrap replications. The vectorized bootstrap compared favorably against the state-of-the-art implementations in all cases tested, and was remarkably/considerably faster for small/moderate sample sizes. The same results were observed in the comparison with the straightforward implementation, except for large sample sizes, where the vectorized bootstrap was slightly slower than the straightforward implementation due to increased time expenditures in the generation of weight matrices via multinomial sampling. PMID:26125965

On the cross-cultural replicability of the resilient, undercontrolled, and overcontrolled personality types.

PubMed

Alessandri, Guido; Vecchione, Michele; Donnellan, Brent M; Eisenberg, Nancy; Caprara, Gian Vittorio; Cieciuch, Jan

2014-08-01

Personality types reflect typical configurations of personality attributes within individuals. Over the last 20 years, researchers have identified a set of three replicable personality types: resilient (R), undercontrolled (U), and overcontrolled (O) types. In this study, we examined the cross-cultural replicability of the RUO types in Italy, Poland, Spain, and the United States. Personality types were identified using cluster analyses of Big Five profiles in large samples of college students from Italy (n = 322), the United States (n = 499), Spain (n = 420), and Poland (n = 235). Prior to clustering the profiles, the measurement invariance of the Big Five measure across samples was tested. We found evidence for the RUO types in all four samples. The three-cluster solution showed a better fit over alternative solutions and had a relatively high degree of cross-cultural generalizability. The RUO types are evident in samples from four countries with distinct linguistic and cultural traditions. Results were discussed in light of the importance of considering how traits are organized within individuals for advancing contemporary personality psychology. © 2013 Wiley Periodicals, Inc.

Rapid discrimination of the causal agents of urinary tract infection using ToF-SIMS with chemometric cluster analysis

NASA Astrophysics Data System (ADS)

Fletcher, John S.; Henderson, Alexander; Jarvis, Roger M.; Lockyer, Nicholas P.; Vickerman, John C.; Goodacre, Royston

2006-07-01

Advances in time of flight secondary ion mass spectrometry (ToF-SIMS) have enabled this technique to become a powerful tool for the analysis of biological samples. Such samples are often very complex and as a result full interpretation of the acquired data can be extremely difficult. To simplify the interpretation of these information rich data, the use of chemometric techniques is becoming widespread in the ToF-SIMS community. Here we discuss the application of principal components-discriminant function analysis (PC-DFA) to the separation and classification of a number of bacterial samples that are known to be major causal agents of urinary tract infection. A large data set has been generated using three biological replicates of each isolate and three machine replicates were acquired from each biological replicate. Ordination plots generated using the PC-DFA are presented demonstrating strain level discrimination of the bacteria. The results are discussed in terms of biological differences between certain species and with reference to FT-IR, Raman spectroscopy and pyrolysis mass spectrometric studies of similar samples.

BinQuasi: a peak detection method for ChIP-sequencing data with biological replicates.

PubMed

Goren, Emily; Liu, Peng; Wang, Chao; Wang, Chong

2018-04-19

ChIP-seq experiments that are aimed at detecting DNA-protein interactions require biological replication to draw inferential conclusions, however there is no current consensus on how to analyze ChIP-seq data with biological replicates. Very few methodologies exist for the joint analysis of replicated ChIP-seq data, with approaches ranging from combining the results of analyzing replicates individually to joint modeling of all replicates. Combining the results of individual replicates analyzed separately can lead to reduced peak classification performance compared to joint modeling. Currently available methods for joint analysis may fail to control the false discovery rate at the nominal level. We propose BinQuasi, a peak caller for replicated ChIP-seq data, that jointly models biological replicates using a generalized linear model framework and employs a one-sided quasi-likelihood ratio test to detect peaks. When applied to simulated data and real datasets, BinQuasi performs favorably compared to existing methods, including better control of false discovery rate than existing joint modeling approaches. BinQuasi offers a flexible approach to joint modeling of replicated ChIP-seq data which is preferable to combining the results of replicates analyzed individually. Source code is freely available for download at https://cran.r-project.org/package=BinQuasi, implemented in R. pliu@iastate.edu or egoren@iastate.edu. Supplementary material is available at Bioinformatics online.

Response Interruption and Redirection for Vocal Stereotypy in Children with Autism: A Systematic Replication

ERIC Educational Resources Information Center

Cassella, Megan Duffy; Sidener, Tina M.; Sidener, David W.; Progar, Patrick R.

2011-01-01

This study systematically replicated and extended previous research on response interruption and redirection (RIRD) by assessing instructed responses of a different topography than the target behavior, percentage of session spent in treatment, generalization of behavior reduction, and social validity of the intervention. Results showed that RIRD…

Structural Model for Antisocial Behavior: Generalization to Single-Mother Families.

ERIC Educational Resources Information Center

Baldwin, David V.; Skinner, Martie L.

1989-01-01

The purpose of this study was to replicate the "basic training" structural model in Patterson's (1982) coercion theory, extending its scope to single-mother families with younger (six- to eight-year-old) boys. Significance of the successful replication was seen to lie in implications for the generalizability of the model across family…

Evaluating the Factor Validity of the Children's Organizational Skills Scale in Youth with ADHD.

PubMed

Molitor, Stephen J; Langberg, Joshua M; Evans, Steven W; Dvorsky, Melissa R; Bourchtein, Elizaveta; Eddy, Laura D; Smith, Zoe R; Oddo, Lauren E

2017-06-01

Children and adolescents with ADHD often have difficulties with organization, time management, and planning (OTMP) skills, and these skills are a common target of intervention. A limited array of tools for measuring these abilities in youth is available, and one of the most prominent measures is the Children's Organizational Skills Scale (COSS). Although the COSS fills an important need, a replication of the COSS factor structure outside of initial measure development has not been conducted in any population. Given that the COSS is frequently used in ADHD research, the current study evaluated the factor structure of the parent-rated COSS in a sample ( N = 619) of adolescents with ADHD. Results indicated that the original factor structure could be replicated, although the use of item parcels appeared to affect model fit statistics. An alternative bi-factor model was also tested that did not require the use of parcels, with results suggesting similar model fit in comparison to the original factor structure. Exploratory validity tests indicated that the domain-general factor of the bi-factor model appears related to broad executive functioning abilities.

Cross-cultural validity of the scale for interpersonal behavior.

PubMed

Nota, Laura; Arrindell, Willem A; Soresi, Salvatore; van der Ende, Jan; Sanavio, Ezio

2011-01-01

The Scale for Interpersonal Behavior (SIB) is a 50-item multidimensional measure of difficulty and distress in assertiveness. The SIB assesses negative assertion, expression of and dealing with personal limitations, initiating assertiveness and positive assertion. The SIB was originally developed in the Netherlands. The present study attempted to replicate the original factors with an Italian student sample (n = 995). The four distress and four performance factors were replicable across two methods of analysis (the multiple group method of confirmatory analysis and Tucker's coefficient of congruence (phi). The corresponding scales were internally consistent and showed predicted patterns of correlations with a measure of self-efficacy. Sex and age differences in assertiveness were generally negligible. Italian students had higher positive assertion-performance scores than the Dutch and comparable scores on other performance scales; by contrast, the Italian subjects had significantly higher scores on all SIB distress scales than their Dutch equivalents. This was ascribed to the stronger pressure on people in Italian society to behave assertively (Hofstede's National Masculinity score = 70) as opposed to the Dutch society (National Masculinity score = 14).

Impact of variation in the BDNF gene on social stress sensitivity and the buffering impact of positive emotions: replication and extension of a gene-environment interaction.

PubMed

van Winkel, Mark; Peeters, Frenk; van Winkel, Ruud; Kenis, Gunter; Collip, Dina; Geschwind, Nicole; Jacobs, Nele; Derom, Catherine; Thiery, Evert; van Os, Jim; Myin-Germeys, Inez; Wichers, Marieke

2014-06-01

A previous study reported that social stress sensitivity is moderated by the brain-derived-neurotrophic-factor(Val66Met) (BDNF rs6265) genotype. Additionally, positive emotions partially neutralize this moderating effect. The current study aimed to: (i) replicate in a new independent sample of subjects with residual depressive symptoms the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity, (ii) replicate the neutralizing impact of positive emotions, (iii) extend these analyses to other variations in the BDNF gene in the new independent sample and the original sample of non-depressed individuals. Previous findings were replicated in an experience sampling method (ESM) study. Negative Affect (NA) responses to social stress were stronger in "Val/Met" carriers of BDNF(Val66Met) compared to "Val/Val" carriers. Positive emotions neutralized the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity in a dose-response fashion. Finally, two of four additional BDNF SNPs (rs11030101, rs2049046) showed similar moderating effects on social stress-sensitivity across both samples. The neutralizing effect of positive emotions on the moderating effects of these two additional SNPs was found in one sample. In conclusion, ESM has important advantages in gene-environment (GxE) research and may attribute to more consistent findings in future GxE research. This study shows how the impact of BDNF genetic variation on depressive symptoms may be explained by its impact on subtle daily life responses to social stress. Further, it shows that the generation of positive affect (PA) can buffer social stress sensitivity and partially undo the genetic susceptibility. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Ability of WRF to Simulate Rainfall Distribution Over West Africa: Role of Horizontal Resolution and Dynamical Processes

NASA Astrophysics Data System (ADS)

Kouadio, K.; Konare, A.; Bastin, S.; Ajayi, V. O.

2016-12-01

This research work focused on the thorny problem of the representation of rainfall over West Africa and particularly in the Gulf of Guinea and its surroundings by Regional Climate Models (RCMs). The sensitivities of Weather Research and Forecasting (WRF) Model are tested for changes in horizontal resolution (convective permitting versus parameterized) on the replication of West African Climate in year 2014 and also changes in microphysics (MP) and planetary boundary layer (PBL) schemes on June 2014. The sensitivity to horizontal resolution study show that both runs at 24km and 4km (explicit convection) resolution fairly replicate the general distribution of the rainfall over West African region. The analysis also reveals a good replication of the dynamical features of West African monsoon system including Tropical Easterly Jet (TEJ), African Easterly Jet (AEJ), monsoon flow and the West African Heat Low (WAHL). Some differences have been noticed between WRF and ERA-interim outputs irrespective to the spectral nudging used in the experiment which then suggest strong interactions between scales. The link between the seasonal displacement of the WAHL and the spatial distribution of the rainfall and the Sahelian onset is confirmed in this study. The results also show an improvement on the replication of rainfall with the very high resolution run observed at daily scale over the Sahel while a dry bias is observed in WRF simulations of the rainfall over Ivorian Coast and in the Gulf of Guinea. Generally, over the Guinean coast the high resolution run did not provide subsequent improvement on the replication of rainfall. The sensitivity of WRF to MP and PBL on rainfall replication study reveals that the most significant added value over the Guinean coast and surroundings area is provided by the configurations that used the PBL Asymmetric Convective Model V2 (ACM2) suggesting more influence of the PBL compared to MP. The change on microphysics and planetary boundary layer schemes in general, seems to have less effect on the explicit runs into the replication of the rainfall over the Gulf of Guinea and the surroundings seaboard.

Autonomous model protocell division driven by molecular replication.

PubMed

Taylor, J W; Eghtesadi, S A; Points, L J; Liu, T; Cronin, L

2017-08-10

The coupling of compartmentalisation with molecular replication is thought to be crucial for the emergence of the first evolvable chemical systems. Minimal artificial replicators have been designed based on molecular recognition, inspired by the template copying of DNA, but none yet have been coupled to compartmentalisation. Here, we present an oil-in-water droplet system comprising an amphiphilic imine dissolved in chloroform that catalyses its own formation by bringing together a hydrophilic and a hydrophobic precursor, which leads to repeated droplet division. We demonstrate that the presence of the amphiphilic replicator, by lowering the interfacial tension between droplets of the reaction mixture and the aqueous phase, causes them to divide. Periodic sampling by a droplet-robot demonstrates that the extent of fission is increased as the reaction progresses, producing more compartments with increased self-replication. This bridges a divide, showing how replication at the molecular level can be used to drive macroscale droplet fission.Coupling compartmentalisation and molecular replication is essential for the development of evolving chemical systems. Here the authors show an oil-in-water droplet containing a self-replicating amphiphilic imine that can undergo repeated droplet division.

Repliscan: a tool for classifying replication timing regions.

PubMed

Zynda, Gregory J; Song, Jawon; Concia, Lorenzo; Wear, Emily E; Hanley-Bowdoin, Linda; Thompson, William F; Vaughn, Matthew W

2017-08-07

Replication timing experiments that use label incorporation and high throughput sequencing produce peaked data similar to ChIP-Seq experiments. However, the differences in experimental design, coverage density, and possible results make traditional ChIP-Seq analysis methods inappropriate for use with replication timing. To accurately detect and classify regions of replication across the genome, we present Repliscan. Repliscan robustly normalizes, automatically removes outlying and uninformative data points, and classifies Repli-seq signals into discrete combinations of replication signatures. The quality control steps and self-fitting methods make Repliscan generally applicable and more robust than previous methods that classify regions based on thresholds. Repliscan is simple and effective to use on organisms with different genome sizes. Even with analysis window sizes as small as 1 kilobase, reliable profiles can be generated with as little as 2.4x coverage.

Population description and its role in the interpretation of genetic association

PubMed Central

Yu, Joon-Ho; Crouch, Julia; Fryer-Edwards, Kelly; Burke, Wylie

2010-01-01

Despite calls for greater clarity and precision of population description, studies have documented persistent ambiguity in the use of race/ethnicity terms in genetic research. It is unclear why investigators tolerate such ambiguity, or what effect these practices have on the evaluation of reported associations. To explore the way that population description is used to replicate and/or extend previously reported genetic observations, we examined articles describing the association of the peroxisome proliferator-activated receptor-gamma-γ Pro12Ala polymorphism with type 2 diabetes mellitus and related phenotypes, published between 1997 and 2005. The 80 articles identified were subjected to a detailed content analysis to determine (1) how sampled populations were described, (2) whether and how the choice of sample was explained, and (3) how the allele frequency and genetic association findings identified were contextualized and interpreted. In common with previous reports, we observed a variety of sample descriptions and little explanation for the choice of population investigated. Samples of European origin were typically described with greater specificity than samples of other origin. However, findings from European samples were nearly always compared to samples described as “Caucasian” and sometimes generalized to all Caucasians or to all humans. These findings suggest that care with population description, while important, may not fully address analytical concerns regarding the interpretation of variable study outcomes or ethical concerns regarding the attribution of genetic observations to broad social groups. Instead, criteria which help investigators better distinguish justified and unjustified forms of population generalization may be required. PMID:20157827

Association of High Myopia with Crystallin Beta A4 (CRYBA4) Gene Polymorphisms in the Linkage-Identified MYP6 Locus

PubMed Central

Ho, Daniel W. H.; Yap, Maurice K. H.; Ng, Po Wah; Fung, Wai Yan; Yip, Shea Ping

2012-01-01

Background Myopia is the most common ocular disorder worldwide and imposes tremendous burden on the society. It is a complex disease. The MYP6 locus at 22 q12 is of particular interest because many studies have detected linkage signals at this interval. The MYP6 locus is likely to contain susceptibility gene(s) for myopia, but none has yet been identified. Methodology/Principal Findings Two independent subject groups of southern Chinese in Hong Kong participated in the study an initial study using a discovery sample set of 342 cases and 342 controls, and a follow-up study using a replication sample set of 316 cases and 313 controls. Cases with high myopia were defined by spherical equivalent ≤ -8 dioptres and emmetropic controls by spherical equivalent within ±1.00 dioptre for both eyes. Manual candidate gene selection from the MYP6 locus was supported by objective in silico prioritization. DNA samples of discovery sample set were genotyped for 178 tagging single nucleotide polymorphisms (SNPs) from 26 genes. For replication, 25 SNPs (tagging or located at predicted transcription factor or microRNA binding sites) from 4 genes were subsequently examined using the replication sample set. Fisher P value was calculated for all SNPs and overall association results were summarized by meta-analysis. Based on initial and replication studies, rs2009066 located in the crystallin beta A4 (CRYBA4) gene was identified to be the most significantly associated with high myopia (initial study: P = 0.02; replication study: P = 1.88e-4; meta-analysis: P = 1.54e-5) among all the SNPs tested. The association result survived correction for multiple comparisons. Under the allelic genetic model for the combined sample set, the odds ratio of the minor allele G was 1.41 (95% confidence intervals, 1.21-1.64). Conclusions/Significance A novel susceptibility gene (CRYBA4) was discovered for high myopia. Our study also signified the potential importance of appropriate gene prioritization in candidate selection. PMID:22792142

Characterization of Macroinvertebrate Communities in the Hyporheic Zone of River Ecosystems Reflects the Pump-Sampling Technique Used

PubMed Central

Dole-Olivier, Marie-José; Galassi, Diana M. P.; Hogan, John-Paul; Wood, Paul J.

2016-01-01

The hyporheic zone of river ecosystems provides a habitat for a diverse macroinvertebrate community that makes a vital contribution to ecosystem functioning and biodiversity. However, effective methods for sampling this community have proved difficult to establish, due to the inaccessibility of subsurface sediments. The aim of this study was to compare the two most common semi-quantitative macroinvertebrate pump-sampling techniques: Bou-Rouch and vacuum-pump sampling. We used both techniques to collect replicate samples in three contrasting temperate-zone streams, in each of two biogeographical regions (Atlantic region, central England, UK; Continental region, southeast France). Results were typically consistent across streams in both regions: Bou-Rouch samples provided significantly higher estimates of taxa richness, macroinvertebrate abundance, and the abundance of all UK and eight of 10 French common taxa. Seven and nine taxa which were rare in Bou-Rouch samples were absent from vacuum-pump samples in the UK and France, respectively; no taxon was repeatedly sampled exclusively by the vacuum pump. Rarefaction curves (rescaled to the number of incidences) and non-parametric richness estimators indicated no significant difference in richness between techniques, highlighting the capture of more individuals as crucial to Bou-Rouch sampling performance. Compared to assemblages in replicate vacuum-pump samples, multivariate analyses indicated greater distinction among Bou-Rouch assemblages from different streams, as well as significantly greater consistency in assemblage composition among replicate Bou-Rouch samples collected in one stream. We recommend Bou-Rouch sampling for most study types, including rapid biomonitoring surveys and studies requiring acquisition of comprehensive taxon lists that include rare taxa. Despite collecting fewer macroinvertebrates, vacuum-pump sampling remains an important option for inexpensive and rapid sample collection. PMID:27723819

In Search of the Perfect Phenotype: An Analysis of Linkage and Association Studies of Reading and Reading-Related Processes

PubMed Central

Skiba, Thomas; Landi, Nicole; Wagner, Richard

2011-01-01

Reading ability and specific reading disability (SRD) are complex traits involving several cognitive processes and are shaped by a complex interplay of genetic and environmental forces. Linkage studies of these traits have identified several susceptibility loci. Association studies have gone further in detecting candidate genes that might underlie these signals. These results have been obtained in samples of mainly European ancestry, which vary in their languages, inclusion criteria, and phenotype assessments. Such phenotypic heterogeneity across samples makes understanding the relationship between reading (dis)ability and reading-related processes and the genetic factors difficult; in addition, it may negatively influence attempts at replication. In moving forward, the identification of preferable phenotypes for future sample collection may improve the replicability of findings. This review of all published linkage and association results from the past 15 years was conducted to determine if certain phenotypes produce more replicable and consistent results than others. PMID:21243420

Open chromatin encoded in DNA sequence is the signature of ‘master’ replication origins in human cells

PubMed Central

Audit, Benjamin; Zaghloul, Lamia; Vaillant, Cédric; Chevereau, Guillaume; d'Aubenton-Carafa, Yves; Thermes, Claude; Arneodo, Alain

2009-01-01

For years, progress in elucidating the mechanisms underlying replication initiation and its coupling to transcriptional activities and to local chromatin structure has been hampered by the small number (approximately 30) of well-established origins in the human genome and more generally in mammalian genomes. Recent in silico studies of compositional strand asymmetries revealed a high level of organization of human genes around 1000 putative replication origins. Here, by comparing with recently experimentally identified replication origins, we provide further support that these putative origins are active in vivo. We show that regions ∼300-kb wide surrounding most of these putative replication origins that replicate early in the S phase are hypersensitive to DNase I cleavage, hypomethylated and present a significant enrichment in genomic energy barriers that impair nucleosome formation (nucleosome-free regions). This suggests that these putative replication origins are specified by an open chromatin structure favored by the DNA sequence. We discuss how this distinctive attribute makes these origins, further qualified as ‘master’ replication origins, priviledged loci for future research to decipher the human spatio-temporal replication program. Finally, we argue that these ‘master’ origins are likely to play a key role in genome dynamics during evolution and in pathological situations. PMID:19671527

Electron Microscopy of Ebola Virus-Infected Cells.

PubMed

Noda, Takeshi

2017-01-01

Ebola virus (EBOV) replicates in host cells, where both viral and cellular components show morphological changes during the process of viral replication from entry to budding. These steps in the replication cycle can be studied using electron microscopy (EM), including transmission electron microscopy (TEM) and scanning electron microscopy (SEM), which is one of the most useful methods for visualizing EBOV particles and EBOV-infected cells at the ultrastructural level. This chapter describes conventional methods for EM sample preparation of cultured cells infected with EBOV.

Multiscale analysis of replication technique efficiency for 3D roughness characterization of manufactured surfaces

NASA Astrophysics Data System (ADS)

Jolivet, S.; Mezghani, S.; El Mansori, M.

2016-09-01

The replication of topography has been generally restricted to optimizing material processing technologies in terms of statistical and single-scale features such as roughness. By contrast, manufactured surface topography is highly complex, irregular, and multiscale. In this work, we have demonstrated the use of multiscale analysis on replicates of surface finish to assess the precise control of the finished replica. Five commercial resins used for surface replication were compared. The topography of five standard surfaces representative of common finishing processes were acquired both directly and by a replication technique. Then, they were characterized using the ISO 25178 standard and multiscale decomposition based on a continuous wavelet transform, to compare the roughness transfer quality at different scales. Additionally, atomic force microscope force modulation mode was used in order to compare the resins’ stiffness properties. The results showed that less stiff resins are able to replicate the surface finish along a larger wavelength band. The method was then tested for non-destructive quality control of automotive gear tooth surfaces.

Self-replication with magnetic dipolar colloids

NASA Astrophysics Data System (ADS)

Dempster, Joshua M.; Zhang, Rui; Olvera de la Cruz, Monica

2015-10-01

Colloidal self-replication represents an exciting research frontier in soft matter physics. Currently, all reported self-replication schemes involve coating colloidal particles with stimuli-responsive molecules to allow switchable interactions. In this paper, we introduce a scheme using ferromagnetic dipolar colloids and preprogrammed external magnetic fields to create an autonomous self-replication system. Interparticle dipole-dipole forces and periodically varying weak-strong magnetic fields cooperate to drive colloid monomers from the solute onto templates, bind them into replicas, and dissolve template complexes. We present three general design principles for autonomous linear replicators, derived from a focused study of a minimalist sphere-dimer magnetic system in which single binding sites allow formation of dimeric templates. We show via statistical models and computer simulations that our system exhibits nonlinear growth of templates and produces nearly exponential growth (low error rate) upon adding an optimized competing electrostatic potential. We devise experimental strategies for constructing the required magnetic colloids based on documented laboratory techniques. We also present qualitative ideas about building more complex self-replicating structures utilizing magnetic colloids.

Learned Attention in Adult Language Acquisition: A Replication and Generalization Study and Meta-Analysis

ERIC Educational Resources Information Center

Ellis, Nick C.; Sagarra, Nuria

2011-01-01

This study investigates associative learning explanations of the limited attainment of adult compared to child language acquisition in terms of learned attention to cues. It replicates and extends Ellis and Sagarra (2010) in demonstrating short- and long-term learned attention in the acquisition of temporal reference in Latin. In Experiment 1,…

[Teachers' knowledge, misconceptions, and lacks concerning Attention Deficit Hyperactivity Disorder].

PubMed

Jarque Fernández, Sonia; Tárraga Mínguez, Raúl; Miranda Casas, Ana

2007-11-01

This study was designed to analyze the knowledge, misconceptions, and lacks about Attention Deficit Hyperactivity Disorder (ADHD) in a sample of 193 teachers, as a replication of the study carried by Sciutto, Terjesen and Bender in 2000. Teachers completed the Knowledge of Attention Deficit Hyperactivity Disorder (KADDS) (Spanish version), adapted by the authors of this research, to measure knowledge of ADHD in three content areas: general knowledge, symptoms/diagnosis, and treatment. Results indicated an average of correct responses of 31.67, 63.88 and 40.46% in general knowledge, symptoms/diagnosis and treatment, respectively. Teachers displayed significantly more knowledge in the Symptoms/Diagnosis scale than in the other scales. Their knowledge correlated positively with: years of experience with hyperactive children, number of hyperactive pupils in their classrooms, and level of perceived self-efficacy. These findings are consistent with those obtained by Sciutto and colleagues.

Making sense of the noise: Replication difficulties of Correll's (2008) modulation of 1/f noise in a racial bias task.

PubMed

Madurski, Christine; LeBel, Etienne P

2015-08-01

Correll (Journal of Personality and Social Psychology, 94, 48-59, 2008; Study 2) found that instructions to use or avoid race information decreased the emission of 1/f noise in a weapon identification task (WIT). These results suggested that 1/f noise in racial bias tasks reflected an effortful deliberative process, providing new insights regarding the mechanisms underlying implicit racial biases. Given the potential theoretical and applied importance of understanding the psychological processes underlying implicit racial biases - and in light of the growing demand for independent direct replications of findings to ensure the cumulative nature of our science - we attempted to replicate Correll's finding in two high-powered studies. Despite considerable effort to closely duplicate all procedural and methodological details of the original study (i.e., same cover story, experimental manipulation, implicit measure task, original stimuli, task instructions, sampling frame, population, and statistical analyses), both replication attempts were unsuccessful in replicating the original finding challenging the theoretical account that 1/f noise in racial bias tasks reflects a deliberative process. However, the emission of 1/f noise did consistently emerge across samples in each of our conditions. Hence, future research is needed to clarify the psychological significance of 1/f noise in racial bias tasks.

Educational Attainment: A Genome Wide Association Study in 9538 Australians

PubMed Central

Martin, Nicolas W.; Medland, Sarah E.; Verweij, Karin J. H.; Lee, S. Hong; Nyholt, Dale R.; Madden, Pamela A.; Heath, Andrew C.; Montgomery, Grant W.; Wright, Margaret J.; Martin, Nicholas G.

2011-01-01

Background Correlations between Educational Attainment (EA) and measures of cognitive performance are as high as 0.8. This makes EA an attractive alternative phenotype for studies wishing to map genes affecting cognition due to the ease of collecting EA data compared to other cognitive phenotypes such as IQ. Methodology In an Australian family sample of 9538 individuals we performed a genome-wide association scan (GWAS) using the imputed genotypes of ∼2.4 million single nucleotide polymorphisms (SNP) for a 6-point scale measure of EA. Top hits were checked for replication in an independent sample of 968 individuals. A gene-based test of association was then applied to the GWAS results. Additionally we performed prediction analyses using the GWAS results from our discovery sample to assess the percentage of EA and full scale IQ variance explained by the predicted scores. Results The best SNP fell short of having a genome-wide significant p-value (p = 9.77×10−7). In our independent replication sample six SNPs among the top 50 hits pruned for linkage disequilibrium (r2<0.8) had a p-value<0.05 but only one of these SNPs survived correction for multiple testing - rs7106258 (p = 9.7*10−4) located in an intergenic region of chromosome 11q14.1. The gene based test results were non-significant and our prediction analyses show that the predicted scores explained little variance in EA in our replication sample. Conclusion While we have identified a polymorphism chromosome 11q14.1 associated with EA, further replication is warranted. Overall, the absence of genome-wide significant p-values in our large discovery sample confirmed the high polygenic architecture of EA. Only the assembly of large samples or meta-analytic efforts will be able to assess the implication of common DNA polymorphisms in the etiology of EA. PMID:21694764

Activation of human herpesvirus replication by apoptosis.

PubMed

Prasad, Alka; Remick, Jill; Zeichner, Steven L

2013-10-01

A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.

Activation of Human Herpesvirus Replication by Apoptosis

PubMed Central

Prasad, Alka; Remick, Jill

2013-01-01

A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance. PMID:23885073

Replicating empirical research in behavioral ecology: how and why it should be done but rarely ever is.

PubMed

Kelly, Clint D

2006-09-01

That empirical evidence is replicable is the foundation of science. Ronald Fisher a founding father of biostatistics, recommended that a null hypothesis be rejected more than once because "no isolated experiment, however significant in itself can suffice for the experimental demonstration of any natural phenomenon" (Fisher 1974:14). Despite this demand, animal behaviorists and behavioral ecologists seldom replicate studies. This practice is not part of our scientific culture, as it is in chemistry or physics, due to a number of factors, including a general disdain by journal editors and thesis committees for unoriginal work. I outline why and how we should replicate empirical studies, which studies should be given priority, and then elaborate on why we do not engage in this necessary endeavor. I also explain how to employ various statistics to test the replicability of a series of studies and illustrate these using published studies from the literature.

Ribozyme-catalysed RNA synthesis using triplet building blocks.

PubMed

Attwater, James; Raguram, Aditya; Morgunov, Alexey S; Gianni, Edoardo; Holliger, Philipp

2018-05-15

RNA-catalyzed RNA replication is widely believed to have supported a primordial biology. However, RNA catalysis is dependent upon RNA folding, and this yields structures that can block replication of such RNAs. To address this apparent paradox we have re-examined the building blocks used for RNA replication. We report RNA-catalysed RNA synthesis on structured templates when using trinucleotide triphosphates (triplets) as substrates, catalysed by a general and accurate triplet polymerase ribozyme that emerged from in vitro evolution as a mutualistic RNA heterodimer. The triplets cooperatively invaded and unraveled even highly stable RNA secondary structures, and support non-canonical primer-free and bidirectional modes of RNA synthesis and replication. Triplet substrates thus resolve a central incongruity of RNA replication, and here allow the ribozyme to synthesise its own catalytic subunit '+' and '-' strands in segments and assemble them into a new active ribozyme. © 2018, Attwater et al.

Clinical characteristics of an Afrikaner founder population recruited for a schizophrenia genetic study.

PubMed

Roos, Johannes Lodewikus; Pretorius, Herman Walter; Karayiorgou, Maria

2009-01-01

The clinical characteristics of an Afrikaner founder population sample recruited for a schizophrenia genetic study are described. Comparisons on several clinical characteristics between this sample and a U.S. sample of schizophrenia patients show that generalization of findings in a founder population to the population at large is applicable. The assessment of the frequency of the 22q11 deletion in Afrikaner schizophrenia patients is approximately 2%, similar to findings in a U.S. sample. Results of analysis of early non-psychotic deviant behavior in subjects under the age of 10 years in the Afrikaner population broadly replicated findings in a U.S. sample. Approximately half of male schizophrenia patients and a quarter of female patients in the Afrikaner schizophrenia database used or abused cannabis. Male users of cannabis with severe early deviant behavior had the lowest mean age of criteria onset, namely 18.4 years. These findings confirm previous findings, indicating that early deviance is linked to later outcome of disease. The clinical characteristics and premorbid variables in 12 childhood-onset Afrikaner schizophrenia patients thus far recruited in this study compare favorably with what is known about childhood-onset schizophrenia in a U.S. sample. The prevalence of co-morbid OCD/OCS in this Afrikaner schizophrenia founder sample was 13.2% which is in keeping with that of co-morbid OCD in schizophrenia, estimated at 12.2% by the U.S. National Institute of Mental Health. These findings confirm that the clinical characteristics of a schizophrenia sample drawn from the Afrikaner founder population can be generalized to the schizophrenia population at large when compared to findings reported in the literature.

40 CFR 796.2750 - Sediment and soil adsorption isotherm.

Code of Federal Regulations, 2011 CFR

2011-07-01

... size analysis” is the determination of the various amounts of the different particle sizes in a sample... °C. (iii) Replications. Three replications of the experimental treatments shall be used. (iv) Soil...) Decrease the water content, air or oven-dry soils at or below 50 °C. (B) Reduce aggregate size before and...

40 CFR 796.2750 - Sediment and soil adsorption isotherm.

Code of Federal Regulations, 2010 CFR

2010-07-01

... size analysis” is the determination of the various amounts of the different particle sizes in a sample... °C. (iii) Replications. Three replications of the experimental treatments shall be used. (iv) Soil...) Decrease the water content, air or oven-dry soils at or below 50 °C. (B) Reduce aggregate size before and...

RENP Replication Unlikely Without Federal Support. Technical Appendices Supporting RMC Report UR 327.

ERIC Educational Resources Information Center

Errecart, Michael T.

The Response to Educational Needs Project (RENP) focuses on training teachers as a vehicle for promoting student achievement in a compensatory education program. This document supplements a report on RENP replication and provides information on cost analysis, methodology, and sample and data collection. In Appendix A the following questions are…

Teacher Perceptions of School Consultant Social Influence Strategies: Replication and Expansion

ERIC Educational Resources Information Center

Owens, Julie Sarno; Schwartz, Madeline E.; Erchul, William P.; Himawan, Lina; Evans, Steven W.; Coles, Erika K.; Schulte, Ann C.

2017-01-01

The goals were to (a) replicate the findings of Erchul, Raven, and Whichard (2001) with regard to the Consultee/Teacher Version of the Interpersonal Power Inventory (IPI; Raven, Schwarzwald, & Koslowsky, 1998), and (b) advance the literature by examining IPI scores about a current consultation relationship. Sample 1 included 99 elementary…

Exploring the dimensionality of digit span.

PubMed

Bowden, Stephen C; Petrauskas, Vilija M; Bardenhagen, Fiona J; Meade, Catherine E; Simpson, Leonie C

2013-04-01

The Digit Span subtest from the Wechsler Scales is used to measure Freedom from Distractibility or Working Memory. Some published research suggests that Digit Span forward should be interpreted differently from Digit Span backward. The present study explored the dimensionality of the Wechsler Memory Scale-III Digit Span (forward and backward) items in a sample of heterogeneous neuroscience patients (n = 267) using confirmatory factor analysis (CFA) for dichotomous items. Results suggested that four correlated factors underlie Digit Span, reflecting easy and hard items in both forward and backward presentation orders. The model for Digit Span was then cross-validated in a seizure disorders sample (n = 223) by replication of the CFA and by examination of measurement invariance. Measurement invariance tests of the precise numerical generalization of trait estimation across groups. Results supported measurement invariance and it was concluded that forward and backward digit span scores should be interpreted as measures of the same cognitive ability.

Responding to Anxiety with Rumination and Hopelessness: Mechanism of Anxiety-Depression Symptom Co-Occurrence?

PubMed Central

Davila, Joanne

2012-01-01

The current research proposes that certain anxiety response styles (specifically, responding to anxiety symptoms with rumination or hopeless cognitions) may increase risk of depressive symptoms, contributing to anxiety-depression comorbidity. We delineate preliminary evidence for this model in three studies. In Study 1, controlling for anxiety response styles significantly reduced the association between anxiety and depressive symptoms in an undergraduate sample. In Study 2, these findings were replicated controlling for conceptually related variables, and anxiety interacted with anxiety response styles to predict greater depressive symptoms. In Study 3, anxiety response styles moderated the prospective association between anxiety and later depression in a generalized anxiety disorder sample. Results support a role for anxiety response styles in anxiety-depression co-occurrence, and show that hopeless/ruminative anxiety response styles can be measured with high reliability and convergent and divergent validity. PMID:22865943

Development of replicated optics for AXAF-1 XDA testing

NASA Technical Reports Server (NTRS)

Engelhaupt, Darell; Wilson, Michele; Martin, Greg

1995-01-01

Advanced optical systems for applications such as grazing incidence Wolter I x-ray mirror assemblies require extraordinary mirror surfaces in terms of fine finish and surface figure. The impeccable mirror surface is on the inside of the rotational mirror form. One practical method of producing devices with these requirements is to first fabricate an exterior surface for the optical device then replicate that surface to have the inverse component with lightweight characteristics. The replicated optic is not better than the master or mandrel from which it is made. This task identifies methods and materials for forming these extremely low roughness optical components. The objectives of this contract were to (1) prepare replication samples of electroless nickel coated aluminum, and determine process requirements for plating XDA test optic; (2) prepare and assemble plating equipment required to process a demonstration optic; (3) characterize mandrels, replicas and test samples for residual stress, surface contamination and surface roughness and figure using equipment at MSFC and; (4) provide technical expertise in establishing the processes, procedures, supplies and equipment needed to process the XDA test optics.

Can concurrent memory load reduce distraction? A replication study and beyond.

PubMed

Gil-Gómez de Liaño, Beatriz; Stablum, Franca; Umiltà, Carlo

2016-01-01

The effects of concurrent working memory load in attentional processes have been 1 of the most puzzling issues in cognitive psychology. Studies have shown detrimental effects, no effects, and even beneficial effects of working memory load in different attentional tasks. In the present study we attempted to replicate Kim, Kim, and Chun's (2005, Experiment 3b) findings of beneficial effects of concurrent working memory load in a spatial Stroop-like task. In 3 experiments in which our sample was 3 times larger than that in the original Kim et al. study, we could not replicate their findings. The results are discussed in terms of what may have produced the conflicting results, trying to shed light on how working memory load affects attentional tasks. Also, we emphasize the importance of using adequately large samples in cognitive research. Although we acknowledge the relevance of meta-analyses to analyze conflicting results, in the present article we stress (perhaps more important) the power of an essential trademark in science for research development: replicability. (c) 2015 APA, all rights reserved).

Persistent topographic quantitative EEG sequelae of chronic marihuana use: a replication study and initial discriminant function analysis.

PubMed

Struve, F A; Straumanis, J J; Patrick, G

1994-04-01

In a previous pilot study using psychiatric patients we reported that daily marihuana users had significant elevations of (1) Absolute Alpha Power, (2) Relative Alpha Power, and (3) Interhemispheric Alpha Coherence over both frontal and frontal-central areas when contrasted with subjects who did not use marihuana. We referred to this phenomenon as Hyperfrontality of Alpha. The study presented here is a successful replication of our previous findings using new samples of subjects and identical methods. Post hoc analyses based on the combined sample from both studies suggest that variables of psychiatric diagnoses and medication did not bias our results. In addition, a discriminant function analysis using quantitative EEG variables as candidate predictors generated a 95% correct THC user versus nonuser classification accuracy which received a successful jackknife replication.

Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample.

PubMed

Greenberg, B D; Li, Q; Lucas, F R; Hu, S; Sirota, L A; Benjamin, J; Lesch, K P; Hamer, D; Murphy, D L

2000-04-03

The serotonin transporter (5-HTT) regulates serotonergic neurotransmission and is thought to influence emotion. A 5-HTT-linked polymorphic region (5-HTTLPR) has two common variants, short (s) and long (l). We previously found population and within-family associations between the lower-expressing s allele and neuroticism, a trait related to anxiety, hostility, and depression, on a standard measure (the NEO Personality Inventory, Revised [NEO-PI-R]) in a primarily male population (n=505), and that the s allele was dominant. We investigated this association in a new sample (n=397, 84% female, primarily sib-pairs). The results robustly replicated the 5-HTTLPR neuroticism association, and the dominance of the s allele. Combined data from the two studies (n=902) showed a highly significant association between the s allele and higher NEO Neuroticism both across individuals and within families. Association between genotype and a related measure, Anxiety on the 16PF inventory, was replicated in the new population and within families in the combined sample. Association to another trait, estimated TPQ Harm Avoidance, was not replicated in the new sample but found only within the combined sibship group. Another association found in our original study, between the s allele and lower scores on NEO-PI-R Agreeableness, was also replicated and was more robust in the current and the combined samples. Associations between the functional 5-HTTLPR polymorphism were similar in women and men. These results help to define specific personality features reproducibly associated with 5-HTTLPR genotype. Such associations were strongest for traits defined by the NEO, enhancing the attractiveness of the five-factor personality model in genetic research on complex behavioral dimensions. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:202-216, 2000. Published 2000 Wiley-Liss, Inc.

Detecting Initiation or Risk for Initiation of Substance Use before High School during Pediatric Well-Child Check-Ups

PubMed Central

Ridenour, Ty A.; Willis, David; Bogen, Debra L.; Novak, Scott; Scherer, Jennifer; Reynolds, Maureen D.; Zhai, Zu Wei; Tarter, Ralph E.

2015-01-01

Background Youth substance use (SU) is prevalent and costly, affecting mental and physical health. American Academy of Pediatrics and Affordable Care Act call for SU screening and prevention. The Youth Risk Index© (YRI) was tested as a screening tool for having initiated and propensity to initiate SU before high school (which forecasts SU disorder). YRI was hypothesized to have good to excellent psychometrics, feasibility and stakeholder acceptability for use during well-child check-ups. Design A high-risk longitudinal design with two cross-sectional replication samples, ages 9–13 was used. Analyses included receiver operating characteristics and regression analyses. Participants A one-year longitudinal sample (N=640) was used for YRI derivation. Replication samples were a cross-sectional sample (N=345) and well-child check-up patients (N=105) for testing feasibility, validity and acceptability as a screening tool. Results YRI has excellent test-retest reliability and good sensitivity and specificity for concurrent and one-year-later SU (odds ratio=7.44 CI=4.3–13.0) and conduct problems (odds ratios=7.33 CI=3.9–13.7). Results were replicated in both cross-sectional samples. Well-child patients, parents and pediatric staff rated YRI screening as important, acceptable, and a needed service. Conclusions Identifying at-risk youth prior to age 13 could reap years of opportunity to intervene before onset of SU disorder. Most results pertained to YRI’s association with concurrent or recent past risky behaviors; further replication ought to specify its predictive validity, especially adolescent-onset risky behaviors. YRI well identifies youth at risk for SU and conduct problems prior to high school, is feasible and valid for screening during well-child check-ups, and is acceptable to stakeholders. PMID:25765481

Association between obesity and depressive disorder in adolescents at high risk for depression.

PubMed

Hammerton, G; Thapar, A; Thapar, A K

2014-04-01

To examine the relationship between Body Mass Index (BMI) and depressive disorder in adolescents at high risk for depression. Prospective longitudinal 3-wave study of offspring of parents with recurrent depression. Replication in population-based cohort study. Three hundred and thirty-seven families where offspring were aged 9-17 years at baseline and 10-19 years at the final data point. Replication sample of adolescents from population-based cohort study aged 11-13 years at first assessment and 14-17 years at follow-up. High risk sample used BMI, skin-fold thickness, Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)-defined major depressive disorder and depression symptoms using the Child and Adolescent Psychiatric Assessment (CAPA). Replication sample used BMI, DSM-IV depressive disorder and depression symptoms using the Development and Well-Being Assessment (DAWBA). Two hundred and eighty-nine adolescents were included in the primary analyses. The mean BMI for each age group in this sample were significantly higher than population norms. There was no significant longitudinal association between categories of weight (or BMI) and new onset depressive disorder or depression symptoms. Similar results were found for skin-fold thickness. The association was also tested in a replication population-based sample and found to be non-significant in the subsample of offspring with mothers who had experienced recurrent depression in the past. BMI at age 12 years was, however, a significant predictor of depression symptoms but not of depressive disorder at age 15 years for the total unselected population. BMI does not significantly predict the development of depression in the offspring of parents with recurrent depression.

Validation of the Self-Beliefs Related to Social Anxiety Scale

PubMed Central

Moulds, Michelle L.; Rapee, Ronald M.

2014-01-01

The importance of self-beliefs in prominent models of social phobia has led to the development of measures that tap this cognitive construct. The Self-Beliefs Related to Social Anxiety (SBSA) Scale is one such measure and taps the three maladaptive belief types proposed in Clark and Wells’s model of social phobia. This study aimed to replicate and extend previous research on the psychometric properties of the SBSA. Replicating previous research, in an (undiagnosed) undergraduate sample (n = 235), the SBSA was found to have a correlated three-factor structure using confirmatory factor analyses, and the SBSA and its subscales demonstrated good internal consistency and test–retest reliability. The SBSA and its subscales also had unique relationships with social anxiety and depression, the majority of which replicated previous research. Extending previous research, the SBSA and its subscales showed good incremental validity in the undergraduate sample and good discriminative validity using the undergraduate sample and a sample of individuals with social phobia (n = 33). The SBSA’s strong theoretical basis and the findings of this study suggest that the SBSA is an ideal research and clinical tool to assess the cognitions characteristic of social phobia. PMID:23575344

Preliminary evidence for an association between a dopamine D3 receptor gene variant and obsessive-compulsive personality disorder in patients with major depression.

PubMed

Light, Katrina J; Joyce, Peter R; Luty, Suzanne E; Mulder, Roger T; Frampton, Christropher M A; Joyce, Laura R M; Miller, Allison L; Kennedy, Martin A

2006-06-05

We have previously reported that the Ser9Gly dopamine D3 receptor (DRD3) polymorphism was associated with increased rates of obsessive-compulsive personality disorder (OCPD) symptomology. We tested the replicability of this association within a further two independent groups of individuals with a history of depression, from a clinical sample (n = 149) and a family study (n = 213). The data from the replication samples and the original sample, within which the association was found, were compiled within a meta-analysis. Although the independent samples did not replicate the original finding, the meta-analysis elucidated significant evidence supporting the association. An individual with Gly/Gly genotype is 2.4 (P = 0.017) times more likely to be diagnosed with OCPD. Male gender was also found to be a significant predictor of OCPD diagnosis (OR = 2.82, P = 0.001). An exploration of an association of DRD3 with Axis I anxiety disorder diagnoses and Temperament and Character Inventory (TCI) traits, in particular persistence, revealed no support for an association. We conclude that DRD3 may contribute to the development of OCPD.

DigOut: viewing differential expression genes as outliers.

PubMed

Yu, Hui; Tu, Kang; Xie, Lu; Li, Yuan-Yuan

2010-12-01

With regards to well-replicated two-conditional microarray datasets, the selection of differentially expressed (DE) genes is a well-studied computational topic, but for multi-conditional microarray datasets with limited or no replication, the same task is not properly addressed by previous studies. This paper adopts multivariate outlier analysis to analyze replication-lacking multi-conditional microarray datasets, finding that it performs significantly better than the widely used limit fold change (LFC) model in a simulated comparative experiment. Compared with the LFC model, the multivariate outlier analysis also demonstrates improved stability against sample variations in a series of manipulated real expression datasets. The reanalysis of a real non-replicated multi-conditional expression dataset series leads to satisfactory results. In conclusion, a multivariate outlier analysis algorithm, like DigOut, is particularly useful for selecting DE genes from non-replicated multi-conditional gene expression dataset.

A Systematic Replication and Extension of Using Incremental Rehearsal to Improve Multiplication Skills: An Investigation of Generalization

ERIC Educational Resources Information Center

Codding, Robin S.; Archer, Jillian; Connell, James

2010-01-01

The purpose of this study was to replicate and extend a previous study by Burns ("Education and Treatment of Children" 28: 237-249, 2005) examining the effectiveness of incremental rehearsal on computation performance. A multiple-probe design across multiplication problem sets was employed for one participant to examine digits correct per minute…

The pitfalls of platform comparison: DNA copy number array technologies assessed

PubMed Central

2009-01-01

Background The accurate and high resolution mapping of DNA copy number aberrations has become an important tool by which to gain insight into the mechanisms of tumourigenesis. There are various commercially available platforms for such studies, but there remains no general consensus as to the optimal platform. There have been several previous platform comparison studies, but they have either described older technologies, used less-complex samples, or have not addressed the issue of the inherent biases in such comparisons. Here we describe a systematic comparison of data from four leading microarray technologies (the Affymetrix Genome-wide SNP 5.0 array, Agilent High-Density CGH Human 244A array, Illumina HumanCNV370-Duo DNA Analysis BeadChip, and the Nimblegen 385 K oligonucleotide array). We compare samples derived from primary breast tumours and their corresponding matched normals, well-established cancer cell lines, and HapMap individuals. By careful consideration and avoidance of potential sources of bias, we aim to provide a fair assessment of platform performance. Results By performing a theoretical assessment of the reproducibility, noise, and sensitivity of each platform, notable differences were revealed. Nimblegen exhibited between-replicate array variances an order of magnitude greater than the other three platforms, with Agilent slightly outperforming the others, and a comparison of self-self hybridizations revealed similar patterns. An assessment of the single probe power revealed that Agilent exhibits the highest sensitivity. Additionally, we performed an in-depth visual assessment of the ability of each platform to detect aberrations of varying sizes. As expected, all platforms were able to identify large aberrations in a robust manner. However, some focal amplifications and deletions were only detected in a subset of the platforms. Conclusion Although there are substantial differences in the design, density, and number of replicate probes, the comparison indicates a generally high level of concordance between platforms, despite differences in the reproducibility, noise, and sensitivity. In general, Agilent tended to be the best aCGH platform and Affymetrix, the superior SNP-CGH platform, but for specific decisions the results described herein provide a guide for platform selection and study design, and the dataset a resource for more tailored comparisons. PMID:19995423

Replication Rate, Framing, and Format Affect Attitudes and Decisions about Science Claims.

PubMed

Barnes, Ralph M; Tobin, Stephanie J; Johnston, Heather M; MacKenzie, Noah; Taglang, Chelsea M

2016-01-01

A series of five experiments examined how the evaluation of a scientific finding was influenced by information about the number of studies that had successfully replicated the initial finding. The experiments also tested the impact of frame (negative, positive) and numeric format (percentage, natural frequency) on the evaluation of scientific findings. In Experiments 1 through 4, an attitude difference score served as the dependent measure, while a measure of choice served as the dependent measure in Experiment 5. Results from a diverse sample of 188 non-institutionalized U.S. adults (Experiment 2) and 730 undergraduate college students (Experiments 1, 3, and 4) indicated that attitudes became more positive as the replication rate increased and attitudes were more positive when the replication information was framed positively. The results also indicate that the manner in which replication rate was framed had a greater impact on attitude than the replication rate itself. The large effect for frame was attenuated somewhat when information about replication was presented in the form of natural frequencies rather than percentages. A fifth study employing 662 undergraduate college students in a task in which choice served as the dependent measure confirmed the framing effect and replicated the replication rate effect in the positive frame condition, but provided no evidence that the use of natural frequencies diminished the effect.

Evaluation of the Factor Structure of the Rosenberg Self-Esteem Scale in Older Adults

PubMed Central

Mullen, Sean P.; Gothe, Neha P.; McAuley, Edward

2012-01-01

The Rosenberg Self-Esteem Scale is the most utilized measure of global self-esteem. Although psychometric studies have generally supported the uni-dimensionality of this 10-item scale, more recently, a stable, response-bias has been associated with the wording of the items (Marsh, Scalas, & Nagengast, 2010). The purpose of this report was to replicate Marsh et al.’s findings in a sample of older adults and to test for invariance across time, gender and levels of education. Our results indicated that indeed a response-bias does exist in esteem responses. Researchers should investigate ways to meaningfully examine and practically overcome the methodological challenges associated with the RSE scale. PMID:23185099

The Apollo 16 microbial response to space environment experiment

NASA Technical Reports Server (NTRS)

Taylor, G. R.

1975-01-01

The effect was evaluated of a particular space flight on the survival rate of nine different species. Although a reasonable variety of organisms (viruses, yeasts, filamentous fungi, bacteria, and an invertebrate) were tested under several different conditions, no statistically valid differences could be detected in the survival of flight samples when compared to corresponding ground-based controls. In general, these evaluations were based on multiple observations of from ten to thirty replicates of up to one million cells each. While the results conflict with those of certain other space flight investigations, it is observed that the conditions of a particular space flight cannot be exactly duplicated, and therefore results from different flights are not directly comparable.

Evaluation of the Factor Structure of the Rosenberg Self-Esteem Scale in Older Adults.

PubMed

Mullen, Sean P; Gothe, Neha P; McAuley, Edward

2013-01-01

The Rosenberg Self-Esteem Scale is the most utilized measure of global self-esteem. Although psychometric studies have generally supported the uni-dimensionality of this 10-item scale, more recently, a stable, response-bias has been associated with the wording of the items (Marsh, Scalas, & Nagengast, 2010). The purpose of this report was to replicate Marsh et al.'s findings in a sample of older adults and to test for invariance across time, gender and levels of education. Our results indicated that indeed a response-bias does exist in esteem responses. Researchers should investigate ways to meaningfully examine and practically overcome the methodological challenges associated with the RSE scale.

An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies.

PubMed

Komatsu, Tetsuro; Nagata, Kyosuke; Wodrich, Harald

2016-02-01

Promyelocytic leukemia protein nuclear bodies (PML-NBs) are subnuclear domains implicated in cellular antiviral responses. Despite the antiviral activity, several nuclear replicating DNA viruses use the domains as deposition sites for the incoming viral genomes and/or as sites for viral DNA replication, suggesting that PML-NBs are functionally relevant during early viral infection to establish productive replication. Although PML-NBs and their components have also been implicated in the adenoviral life cycle, it remains unclear whether incoming adenoviral genome complexes target PML-NBs. Here we show using immunofluorescence and live-cell imaging analyses that incoming adenovirus genome complexes neither localize at nor recruit components of PML-NBs during early phases of infection. We further show that the viral DNA binding protein (DBP), an early expressed viral gene and essential DNA replication factor, independently targets PML-NBs. We show that DBP oligomerization is required to selectively recruit the PML-NB components Sp100 and USP7. Depletion experiments suggest that the absence of one PML-NB component might not affect the recruitment of other components toward DBP oligomers. Thus, our findings suggest a model in which an adenoviral DNA replication factor, but not incoming viral genome complexes, targets and modulates PML-NBs to support a conducive state for viral DNA replication and argue against a generalized concept that PML-NBs target incoming viral genomes. The immediate fate upon nuclear delivery of genomes of incoming DNA viruses is largely unclear. Early reports suggested that incoming genomes of herpesviruses are targeted and repressed by PML-NBs immediately upon nuclear import. Genome localization and/or viral DNA replication has also been observed at PML-NBs for other DNA viruses. Thus, it was suggested that PML-NBs may immediately sense and target nuclear viral genomes and hence serve as sites for deposition of incoming viral genomes and/or subsequent viral DNA replication. Here we performed a detailed analyses of the spatiotemporal distribution of incoming adenoviral genome complexes and found, in contrast to the expectation, that an adenoviral DNA replication factor, but not incoming genomes, targets PML-NBs. Thus, our findings may explain why adenoviral genomes could be observed at PML-NBs in earlier reports but argue against a generalized role for PML-NBs in targeting invading viral genomes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases.

PubMed

Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

2016-01-01

There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and "others"). We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and "true" effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. The differences in reliability between biological psychiatry, neurology and somatic diseases suggest that there is room for improvement, at least in some subdomains.

Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

PubMed Central

Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

2016-01-01

Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability between biological psychiatry, neurology and somatic diseases suggest that there is room for improvement, at least in some subdomains. PMID:27336301

DNA replication restart and cellular dynamics of Hef helicase/nuclease protein in Haloferax volcanii.

PubMed

Lestini, Roxane; Delpech, Floriane; Myllykallio, Hannu

2015-11-01

Understanding how frequently spontaneous replication arrests occur and how archaea deal with these arrests are very interesting and challenging research topics. Here we will described how genetic and imaging studies have revealed the central role of the archaeal helicase/nuclease Hef belonging to the XPF/MUS81/FANCM family of endonucleases in repair of arrested replication forks. Special focus will be on description of a recently developed combination of genetic and imaging tools to study the dynamic localization of a functional Hef::GFP (Green Fluorescent Protein) fusion protein in the living cells of halophilic archaea Haloferax volcanii. As Archaea provide an excellent and unique model for understanding how DNA replication is regulated to allow replication of a circular DNA molecule either from single or multiple replication origins, we will also summarize recent studies that have revealed peculiar features regarding DNA replication, particularly in halophilic archaea. We strongly believe that fundamental knowledge of our on-going studies will shed light on the evolutionary history of the DNA replication machinery and will help to establish general rules concerning replication restart and the key role of recombination proteins not only in bacteria, yeast and higher eukaryotes but also in archaea. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Coupled replicator equations for the dynamics of learning in multiagent systems

NASA Astrophysics Data System (ADS)

Sato, Yuzuru; Crutchfield, James P.

2003-01-01

Starting with a group of reinforcement-learning agents we derive coupled replicator equations that describe the dynamics of collective learning in multiagent systems. We show that, although agents model their environment in a self-interested way without sharing knowledge, a game dynamics emerges naturally through environment-mediated interactions. An application to rock-scissors-paper game interactions shows that the collective learning dynamics exhibits a diversity of competitive and cooperative behaviors. These include quasiperiodicity, stable limit cycles, intermittency, and deterministic chaos—behaviors that should be expected in heterogeneous multiagent systems described by the general replicator equations we derive.

Evidence for Sequential and Increasing Activation of Replication Origins along Replication Timing Gradients in the Human Genome

PubMed Central

Guilbaud, Guillaume; Rappailles, Aurélien; Baker, Antoine; Chen, Chun-Long; Arneodo, Alain; Goldar, Arach; d'Aubenton-Carafa, Yves; Thermes, Claude; Audit, Benjamin; Hyrien, Olivier

2011-01-01

Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients with practically no regions larger than 100 kb replicating at less than 2 kb/min. Therefore, HeLa cells lack large regions of unidirectional fork progression. Temporal transition regions are replicated by sequential activation of origins at a rate that increases during S phase and replication timing gradients are set by the delay and the spacing between successive origin firings rather than by the velocity of single forks. Activation of internal origins in a specific temporal transition region is directly demonstrated by DNA combing of the IGH locus in HeLa cells. Analysis of published origin maps in HeLa cells and published replication timing and DNA combing data in several other cell types corroborate these findings, with the interesting exception of embryonic stem cells where regions of unidirectional fork progression seem more abundant. These results can be explained if origins fire independently of each other but under the control of long-range chromatin structure, or if replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA. These findings shed a new light on the replication timing program of mammalian genomes and provide a general model for their replication kinetics. PMID:22219720

Domestication of Lambda Phage Genes into a Putative Third Type of Replicative Helicase Matchmaker

PubMed Central

Brézellec, Pierre; Petit, Marie-Agnès; Pasek, Sophie; Vallet-Gely, Isabelle; Possoz, Christophe

2017-01-01

Abstract At the onset of the initiation of chromosome replication, bacterial replicative helicases are recruited and loaded on the DnaA-oriC nucleoprotein platform, assisted by proteins like DnaC/DnaI or DciA. Two orders of bacteria appear, however, to lack either of these factors, raising the question of the essentiality of these factors in bacteria. Through a phylogenomic approach, we identified a pair of genes that could have substituted for dciA. The two domesticated genes are specific of the dnaC/dnaI- and dciA-lacking organisms and apparently domesticated from lambdoid phage genes. They derive from λO and λP and were renamed dopC and dopE, respectively. DopE is expected to bring the replicative helicase to the bacterial origin of replication, while DopC might assist DopE in this function. The confirmation of the implication of DopCE in the handling of the replicative helicase at the onset of replication in these organisms would generalize to all bacteria and therefore to all living organisms the need for specific factors dedicated to this function. PMID:28854626

RNA interference inhibits herpes simplex virus type 1 isolated from saliva samples and mucocutaneous lesions.

PubMed

Silva, Amanda Perse da; Lopes, Juliana Freitas; Paula, Vanessa Salete de

2014-01-01

The aim of this study was to evaluate the use of RNA interference to inhibit herpes simplex virus type-1 replication in vitro. For herpes simplex virus type-1 gene silencing, three different small interfering RNAs (siRNAs) targeting the herpes simplex virus type-1 UL39 gene (sequence si-UL 39-1, si-UL 39-2, and si-UL 39-3) were used, which encode the large subunit of ribonucleotide reductase, an essential enzyme for DNA synthesis. Herpes simplex virus type-1 was isolated from saliva samples and mucocutaneous lesions from infected patients. All mucocutaneous lesions' samples were positive for herpes simplex virus type-1 by real-time PCR and by virus isolation; all herpes simplex virus type-1 from saliva samples were positive by real-time PCR and 50% were positive by virus isolation. The levels of herpes simplex virus type-1 DNA remaining after siRNA treatment were assessed by real-time PCR, whose results demonstrated that the effect of siRNAs on gene expression depends on siRNA concentration. The three siRNA sequences used were able to inhibit viral replication, assessed by real-time PCR and plaque assays and among them, the sequence si-UL 39-1 was the most effective. This sequence inhibited 99% of herpes simplex virus type-1 replication. The results demonstrate that silencing herpes simplex virus type-1 UL39 expression by siRNAs effectively inhibits herpes simplex virus type-1 replication, suggesting that siRNA based antiviral strategy may be a potential therapeutic alternative. Copyright © 2014. Published by Elsevier Editora Ltda.

Does Literacy Skill Level Predict Performance in Community College Courses: A Replication and Extension

ERIC Educational Resources Information Center

Allen, Nancy J.; DeLauro, Kimberly A.; Perry, Julia K.; Carman, Carol A.

2017-01-01

Previous research has found a positive relationship between students who had completed a sequence of developmental reading and writing courses and success in a reading-intensive college-level course. This study replicates and expands upon the previous research of Goldstein and Perin (2008) by utilizing a differently diverse sample and an…

Examining the Validity of Cyclothymic Disorder in a Youth Sample: Replication and Extension

ERIC Educational Resources Information Center

Van Meter, Anna; Youngstrom, Eric A.; Demeter, Christine; Findling, Robert L.

2013-01-01

DSM-IV-TR defines four subtypes of bipolar disorder (BP): bipolar I, bipolar II, cyclothymic disorder and bipolar not otherwise specified (NOS). However, cyclothymic disorder in children is rarely researched, or often subsumed in an "NOS" category. The present study tests the replicability of findings from an earlier study, and expands on the…

A Replication of the Technical Adequacy of the Student Subjective Wellbeing Questionnaire

ERIC Educational Resources Information Center

Renshaw, Tyler L.

2015-01-01

The present study reports on a replication of the technical adequacy of the Student Subjective Wellbeing Questionnaire (SSWQ), which is a 16-item self-report instrument for assessing youth's academic efficacy, educational purpose, joy of learning, and school connectedness, with a sample of adolescents in Grades 6 to 7 (N = 438). Findings confirmed…

Teacher Perceptions of School Consultant Social Influence Strategies: Replication and Expansion

ERIC Educational Resources Information Center

Owens, Julie Sarno; Schwartz, Madeleine E.; Erchul, William P.; Himawan, Lina K.; Evans, Steven W.; Coles, Erika K.; Schulte, Ann C.

2017-01-01

The goals were to (a) replicate the findings of previous research with regard to the Consultee/Teacher Version of the Interpersonal Power Inventory (IPI), and (b) advance the literature by examining IPI scores about a current consultation relationship. Sample 1 included 99 elementary school teachers (44.4% Hispanic) who completed the IPI. Results…

Improved Diagnostic Validity of the ADOS Revised Algorithms: A Replication Study in an Independent Sample

ERIC Educational Resources Information Center

Oosterling, Iris; Roos, Sascha; de Bildt, Annelies; Rommelse, Nanda; de Jonge, Maretha; Visser, Janne; Lappenschaar, Martijn; Swinkels, Sophie; van der Gaag, Rutger Jan; Buitelaar, Jan

2010-01-01

Recently, Gotham et al. ("2007") proposed revised algorithms for the Autism Diagnostic Observation Schedule (ADOS) with improved diagnostic validity. The aim of the current study was to replicate predictive validity, factor structure, and correlations with age and verbal and nonverbal IQ of the ADOS revised algorithms for Modules 1 and 2…

Decomposing the relationship between cognitive functioning and self-referent memory beliefs in older adulthood: What’s memory got to do with it?

PubMed Central

Payne, Brennan R.; Gross, Alden L.; Hill, Patrick L.; Parisi, Jeanine M.; Rebok, George W.; Stine-Morrow, Elizabeth A. L.

2018-01-01

With advancing age, episodic memory performance shows marked declines along with concurrent reports of lower subjective memory beliefs. Given that normative age-related declines in episodic memory co-occur with declines in other cognitive domains, we examined the relationship between memory beliefs and multiple domains of cognitive functioning. Confirmatory bi-factor structural equation models were used to parse the shared and independent variance among factors representing episodic memory, psychomotor speed, and executive reasoning in one large cohort study (Senior Odyssey, N = 462), and replicated using another large cohort of healthy older adults (ACTIVE, N = 2,802). Accounting for a general fluid cognitive functioning factor (comprised of the shared variance among measures of episodic memory, speed, and reasoning) attenuated the relationship between objective memory performance and subjective memory beliefs in both samples. Moreover, the general cognitive functioning factor was the strongest predictor of memory beliefs in both samples. These findings are consistent with the notion that dispositional memory beliefs may reflect perceptions of cognition more broadly. This may be one reason why memory beliefs have broad predictive validity for interventions that target fluid cognitive ability. PMID:27685541

Decomposing the relationship between cognitive functioning and self-referent memory beliefs in older adulthood: what's memory got to do with it?

PubMed

Payne, Brennan R; Gross, Alden L; Hill, Patrick L; Parisi, Jeanine M; Rebok, George W; Stine-Morrow, Elizabeth A L

2017-07-01

With advancing age, episodic memory performance shows marked declines along with concurrent reports of lower subjective memory beliefs. Given that normative age-related declines in episodic memory co-occur with declines in other cognitive domains, we examined the relationship between memory beliefs and multiple domains of cognitive functioning. Confirmatory bi-factor structural equation models were used to parse the shared and independent variance among factors representing episodic memory, psychomotor speed, and executive reasoning in one large cohort study (Senior Odyssey, N = 462), and replicated using another large cohort of healthy older adults (ACTIVE, N = 2802). Accounting for a general fluid cognitive functioning factor (comprised of the shared variance among measures of episodic memory, speed, and reasoning) attenuated the relationship between objective memory performance and subjective memory beliefs in both samples. Moreover, the general cognitive functioning factor was the strongest predictor of memory beliefs in both samples. These findings are consistent with the notion that dispositional memory beliefs may reflect perceptions of cognition more broadly. This may be one reason why memory beliefs have broad predictive validity for interventions that target fluid cognitive ability.

Dimensional assessment of personality in an out-patient sample: relations of the systems of Millon and Cloninger.

PubMed

Bayon, C; Hill, K; Svrakic, D M; Przybeck, T R; Cloninger, C R

1996-01-01

The Cloninger Temperament and Character Inventory (TCI) and the Millon Clinical Multiaxial Inventory (MCMI-II) are both self-report inventories that can be used to assess personality reliably in clinical samples. Both instruments were administered to 103 consecutive psychiatric out-patients with or without personality disorders. The goals were to assess the convergent validity of the two instruments, to replicate the findings of Svrakic et al. (1993) Archives of General Psychiatry, 50, 991-999, about the differential diagnosis of Axis II disorders, and to analyse the relations of Millon's measures of Axis I disorders with Cloninger's measures. We observed a strong convergent validity between the instruments; the seven dimensions of the TCI accounted for most of the variance in MCMI-II measures of both Axis 1 and Axis 2 disorders. As reported by Svrakic et al. (1993) Archives of General Psychiatry, 50, 991-999, in in-patients, low self-directedness and low cooperativeness were confirmed to be the essential features of all personality disorders in out-patients. In addition, self-transcendence, the third of Cloninger's character dimensions, was observed to be a strong correlate of severe Axis-1 psychopathology, including manic and delusional disorders.

Indirect Transmission of Influenza A Virus between Pig Populations under Two Different Biosecurity Settings

PubMed Central

Allerson, Matt W.; Cardona, Carol J.; Torremorell, Montserrat

2013-01-01

Respiratory disease due to influenza virus is common in both human and swine populations around the world with multiple transmission routes capable of transmitting influenza virus, including indirect routes. The objective of this study was to evaluate the role of fomites in influenza A virus (IAV) transmission between pig populations separated by two different biosecurity settings. Thirty-five pigs were divided into four experimental groups: 10 pigs (1 replicate) were assigned to the infected group (I), 10 pigs (2 replicates of 5 pigs) were assigned to the low biosecurity sentinel group (LB), 10 pigs (2 replicates of 5 pigs) were assigned to the medium biosecurity sentinel group (MB), and 5 pigs (1 replicate) were assigned to the negative control group (NC). Eight of 10 pigs in the infected group were inoculated with IAV and 36 hours following inoculation, personnel movement events took place in order to move potentially infectious clothing and personal protective equipment (PPE) to sentinel pig rooms. Following contact with the infected group, personnel moved to the MB group after designated hygiene measures while personnel moved directly to the LB group. Nasal swabs and blood samples were collected from pigs to assess IAV infection status and fomites were sampled and tested via RRT-PCR. All experimentally inoculated pigs were infected with IAV and 11 of the 144 fomite samples collected following contact with infected pigs were low level positive for IAV genome. One replicate of each sentinel groups LB and MB became infected with IAV and all five pigs were infected over time. This study provides evidence that fomites can serve as an IAV transmission route from infected to sentinel pigs and highlights the need to focus on indirect routes as well as direct routes of transmission for IAV. PMID:23805306

Why threefold-replication of families?

NASA Astrophysics Data System (ADS)

Fitzpatrick, Gerald L.

1998-04-01

In spite of the many successes of the standard model of particle physics, the observed proliferation of matter-fields, in the form of ``replicated'' generations or families, is a major unsolved problem. In this paper, I explore some of the algebraic, geometric and physical consequences of a new organizing principle for fundamental fermions (quarks and leptons)(Gerald L. Fitzpatrick, phThe Family Problem--New Internal Algebraic and Geometric Regularities), Nova Scientific Press, Issaquah, Washington, 1997. Read more about this book (ISBN 0--9655695--0--0) and its subject matter at: http://www.tp.umu.se/TIPTOP and/or http://www.amazon.com.. The essence of the new organizing principle is the idea that the standard-model concept of scalar fermion numbers f can be generalized. In particular, a ``generalized fermion number,'' which consists of a 2× 2 matrix F that ``acts'' on an internal 2-space, instead of spacetime, is taken to describe certain internal properties of fundamental fermions. This generalization automatically introduces internal degrees of freedom that ``explain,'' among other things, family replication and the number (three) of families observed in nature.

Recovery and Enumeration of Cryptosporidium parvum from Animal Fecal Matrices

PubMed Central

Davies, Cheryl M.; Kaucner, Christine; Deere, Daniel; Ashbolt, Nicholas J.

2003-01-01

Accurate quantification of Cryptosporidium parvum oocysts in animal fecal deposits on land is an essential starting point for estimating watershed C. parvum loads. Due to the general poor performance and variable recovery efficiency of existing enumeration methods, protocols were devised based on initial dispersion of oocysts from feces by vortexing in 2 mM tetrasodium pyrophosphate, followed by immunomagnetic separation. The protocols were validated by using an internal control seed preparation to determine the levels of oocyst recovery for a range of fecal types. The levels of recovery of 102 oocysts from cattle feces (0.5 g of processed feces) ranged from 31 to 46%, and the levels of recovery from sheep feces (0.25 g of processed feces) ranged from 21% to 35%. The within-sample coefficients of variation for the percentages of recovery from five replicates ranged from 10 to 50%. The ranges for levels of recovery of oocysts from cattle, kangaroo, pig, and sheep feces (juveniles and adults) collected in a subsequent watershed animal fecal survey were far wider than the ranges predicted by the validation data. Based on the use of an internal control added to each fecal sample, the levels of recovery ranged from 0 to 83% for cattle, from 4 to 62% for sheep, from 1 to 42% for pigs, and from 40 to 73% for kangaroos. Given the variation in the levels of recovery of oocysts from different fecal matrices, it is recommended that an internal control be added to at least one replicate of every fecal sample analyzed to determine the percentage of recovery. Depending on the animal type and based on the lowest approximate percentages of recovery, between 10 and 100 oocysts g of feces−1 must be present to be detected. PMID:12732556

Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

PubMed Central

Benyamin, B; Pourcain, BSt; Davis, OS; Davies, G; Hansell, NK; Brion, M-JA; Kirkpatrick, RM; Cents, RAM; Franić, S; Miller, MB; Haworth, CMA; Meaburn, E; Price, TS; Evans, DM; Timpson, N; Kemp, J; Ring, S; McArdle, W; Medland, SE; Yang, J; Harris, SE; Liewald, DC; Scheet, P; Xiao, X; Hudziak, JJ; de Geus, EJC; Jaddoe, VWV; Starr, JM; Verhulst, FC; Pennell, C; Tiemeier, H; Iacono, WG; Palmer, LJ; Montgomery, GW; Martin, NG; Boomsma, DI; Posthuma, D; McGue, M; Wright, MJ; Smith, G Davey; Deary, IJ; Plomin, R; Visscher, PM

2014-01-01

Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6–18 years) from 17 989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22–46% of phenotypic variation in childhood intelligence in the three largest cohorts (P = 3.9 × 10−15, 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P = 0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P = 6 × 10−5), 3.5% (P = 10−3) and 0.5% (P = 6 × 10−5) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance. PMID:23358156

Genome-wide association study identifies nine novel loci for 2D:4D finger ratio, a putative retrospective biomarker of testosterone exposure in utero

PubMed Central

Warrington, Nicole M; Shevroja, Enisa; Hemani, Gibran; Hysi, Pirro G; Jiang, Yunxuan; Auton, Adam; Boer, Cindy G; Mangino, Massimo; Wang, Carol A; Kemp, John P; McMahon, George; Medina-Gomez, Carolina; Hickey, Martha; Trajanoska, Katerina; Wolke, Dieter; Ikram, M Arfan; Montgomery, Grant W; Felix, Janine F; Wright, Margaret J; Mackey, David A; Jaddoe, Vincent W; Martin, Nicholas G; Tung, Joyce Y; Davey Smith, George; Pennell, Craig E; Spector, Tim D; van Meurs, Joyce; Rivadeneira, Fernando; Medland, Sarah E; Evans, David M

2018-01-01

Abstract The ratio of the length of the index finger to that of the ring finger (2D:4D) is sexually dimorphic and is commonly used as a non-invasive biomarker of prenatal androgen exposure. Most association studies of 2D:4D ratio with a diverse range of sex-specific traits have typically involved small sample sizes and have been difficult to replicate, raising questions around the utility and precise meaning of the measure. In the largest genome-wide association meta-analysis of 2D:4D ratio to date (N = 15 661, with replication N = 75 821), we identified 11 loci (9 novel) explaining 3.8% of the variance in mean 2D:4D ratio. We also found weak evidence for association (β = 0.06; P = 0.02) between 2D:4D ratio and sensitivity to testosterone [length of the CAG microsatellite repeat in the androgen receptor (AR) gene] in females only. Furthermore, genetic variants associated with (adult) testosterone levels and/or sex hormone-binding globulin were not associated with 2D:4D ratio in our sample. Although we were unable to find strong evidence from our genetic study to support the hypothesis that 2D:4D ratio is a direct biomarker of prenatal exposure to androgens in healthy individuals, our findings do not explicitly exclude this possibility, and pathways involving testosterone may become apparent as the size of the discovery sample increases further. Our findings provide new insight into the underlying biology shaping 2D:4D variation in the general population. PMID:29659830

Molecular-genetic correlates of infant attachment: A cautionary tale

PubMed Central

Booth-Laforce, Cathryn; Belsky, Jay; Burt, Keith B.; Groh, Ashley M.

2014-01-01

This paper advises caution in relation to the increasing interest in molecular-genetic association studies in developmental psychology based on a set of empirical examples from the NICHD Study of Early Child Care and Youth Development (SECCYD) that highlight the fragility of effects reported in the literature on the molecular-genetic correlates of infant attachment. Specifically, this paper updates and provides three extensions to results reported in Luijk et al. (2011), which recently failed to replicate evidence from smaller-sample studies that a set of dopaminergic, serotonergic, and oxytonergic markers are significantly associated with infant attachment security or disorganization. First, we report here that the average effect of “usual suspect” polymorphisms on infant attachment security and disorganization in the SECCYD is approximately zero. Second, because Luijk et al. (2011) reported data based exclusively on the White infants in the SECCYD, this paper reveals that the average effect of polymorphisms featured in this literature is also of trivial magnitude in the non-White sub-sample (cf. Chen, Barth, Johnson, Gotlib, & Johnson, 2011). Third, this paper attempts, but fails, to replicate a recent finding by Raby et al. (2012) suggesting that, although molecular-genetic polymorphisms might not be implicated in security versus insecurity, the serotonin transporter gene contributes to variation in emotional distress during the Strange Situation Procedure. Implications for future research on the genetics of developmental phenotypes in general and attachment in particular are discussed, with a focus on statistical power and model-based theory testing. PMID:23421800

A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments.

PubMed

Robinson, Mark D; De Souza, David P; Keen, Woon Wai; Saunders, Eleanor C; McConville, Malcolm J; Speed, Terence P; Likić, Vladimir A

2007-10-29

Gas chromatography-mass spectrometry (GC-MS) is a robust platform for the profiling of certain classes of small molecules in biological samples. When multiple samples are profiled, including replicates of the same sample and/or different sample states, one needs to account for retention time drifts between experiments. This can be achieved either by the alignment of chromatographic profiles prior to peak detection, or by matching signal peaks after they have been extracted from chromatogram data matrices. Automated retention time correction is particularly important in non-targeted profiling studies. A new approach for matching signal peaks based on dynamic programming is presented. The proposed approach relies on both peak retention times and mass spectra. The alignment of more than two peak lists involves three steps: (1) all possible pairs of peak lists are aligned, and similarity of each pair of peak lists is estimated; (2) the guide tree is built based on the similarity between the peak lists; (3) peak lists are progressively aligned starting with the two most similar peak lists, following the guide tree until all peak lists are exhausted. When two or more experiments are performed on different sample states and each consisting of multiple replicates, peak lists within each set of replicate experiments are aligned first (within-state alignment), and subsequently the resulting alignments are aligned themselves (between-state alignment). When more than two sets of replicate experiments are present, the between-state alignment also employs the guide tree. We demonstrate the usefulness of this approach on GC-MS metabolic profiling experiments acquired on wild-type and mutant Leishmania mexicana parasites. We propose a progressive method to match signal peaks across multiple GC-MS experiments based on dynamic programming. A sensitive peak similarity function is proposed to balance peak retention time and peak mass spectra similarities. This approach can produce the optimal alignment between an arbitrary number of peak lists, and models explicitly within-state and between-state peak alignment. The accuracy of the proposed method was close to the accuracy of manually-curated peak matching, which required tens of man-hours for the analyzed data sets. The proposed approach may offer significant advantages for processing of high-throughput metabolomics data, especially when large numbers of experimental replicates and multiple sample states are analyzed.

Contextual mediation of perceptions during hauntings and poltergeist-like experiences: a replication and extension.

PubMed

Harte, T M

2000-10-01

This study is a replication of the experiment by Lange, Houran, Harte, and Havens (1996 on contextual variables, in which hallucinations appear to be affected by the environmental context. These contextual variables are influential in the reporting of haunting and poltergeist-like episodes. This study extended the previous study by adding new factors of time of day, climactic conditions, and emotional feelings. These were analyzed for a different sample, looking for further congruency between experiential content and the context. The sample (N=8431 were reports found on the Internet and in one book. The Lange, et al. study was replicated in that contextual variables were identified in 99.2% of the reports, the content of the reports was judged to be consistent with the nature of the contextual variables in 58.8% of the reports, and contextual variables were related to the percipients' state of arousal and the modalities of experience.

Masculinity constructs as protective buffers and risk factors for men's health.

PubMed

Levant, Ronald F; Wimer, David J

2014-03-01

This study was designed to replicate the study of Levant, Wimer, and Williams (2011), which reported complex relationships between masculinity and health behaviors using a more diverse sample and updated measures. A sample of 589 college and community-dwelling men responded to an online survey consisting of five scales. Levant et al.'s (2011) study was partially replicated-some masculinity constructs were identified as protective buffers for some health behaviors and others as risk factors. The vast majority of the findings that were replicated were risk factors, suggesting that traditional masculinity is more of risk than a buffer, and occurred in the analyses involving Avoiding Anger and Stress and Avoiding Substance Use subscales, suggesting that these health behaviors are most closely associated with masculinity. The results are discussed in terms of limitations, suggestions for future research, and implications for health care practice.

High-throughput state-machine replication using software transactional memory.

PubMed

Zhao, Wenbing; Yang, William; Zhang, Honglei; Yang, Jack; Luo, Xiong; Zhu, Yueqin; Yang, Mary; Luo, Chaomin

2016-11-01

State-machine replication is a common way of constructing general purpose fault tolerance systems. To ensure replica consistency, requests must be executed sequentially according to some total order at all non-faulty replicas. Unfortunately, this could severely limit the system throughput. This issue has been partially addressed by identifying non-conflicting requests based on application semantics and executing these requests concurrently. However, identifying and tracking non-conflicting requests require intimate knowledge of application design and implementation, and a custom fault tolerance solution developed for one application cannot be easily adopted by other applications. Software transactional memory offers a new way of constructing concurrent programs. In this article, we present the mechanisms needed to retrofit existing concurrency control algorithms designed for software transactional memory for state-machine replication. The main benefit for using software transactional memory in state-machine replication is that general purpose concurrency control mechanisms can be designed without deep knowledge of application semantics. As such, new fault tolerance systems based on state-machine replications with excellent throughput can be easily designed and maintained. In this article, we introduce three different concurrency control mechanisms for state-machine replication using software transactional memory, namely, ordered strong strict two-phase locking, conventional timestamp-based multiversion concurrency control, and speculative timestamp-based multiversion concurrency control. Our experiments show that speculative timestamp-based multiversion concurrency control mechanism has the best performance in all types of workload, the conventional timestamp-based multiversion concurrency control offers the worst performance due to high abort rate in the presence of even moderate contention between transactions. The ordered strong strict two-phase locking mechanism offers the simplest solution with excellent performance in low contention workload, and fairly good performance in high contention workload.

High-throughput state-machine replication using software transactional memory

PubMed Central

Yang, William; Zhang, Honglei; Yang, Jack; Luo, Xiong; Zhu, Yueqin; Yang, Mary; Luo, Chaomin

2017-01-01

State-machine replication is a common way of constructing general purpose fault tolerance systems. To ensure replica consistency, requests must be executed sequentially according to some total order at all non-faulty replicas. Unfortunately, this could severely limit the system throughput. This issue has been partially addressed by identifying non-conflicting requests based on application semantics and executing these requests concurrently. However, identifying and tracking non-conflicting requests require intimate knowledge of application design and implementation, and a custom fault tolerance solution developed for one application cannot be easily adopted by other applications. Software transactional memory offers a new way of constructing concurrent programs. In this article, we present the mechanisms needed to retrofit existing concurrency control algorithms designed for software transactional memory for state-machine replication. The main benefit for using software transactional memory in state-machine replication is that general purpose concurrency control mechanisms can be designed without deep knowledge of application semantics. As such, new fault tolerance systems based on state-machine replications with excellent throughput can be easily designed and maintained. In this article, we introduce three different concurrency control mechanisms for state-machine replication using software transactional memory, namely, ordered strong strict two-phase locking, conventional timestamp-based multiversion concurrency control, and speculative timestamp-based multiversion concurrency control. Our experiments show that speculative timestamp-based multiversion concurrency control mechanism has the best performance in all types of workload, the conventional timestamp-based multiversion concurrency control offers the worst performance due to high abort rate in the presence of even moderate contention between transactions. The ordered strong strict two-phase locking mechanism offers the simplest solution with excellent performance in low contention workload, and fairly good performance in high contention workload. PMID:29075049

Roles of Long and Short Replication Initiation Proteins in the Fate of IncP-1 Plasmids

PubMed Central

Yano, Hirokazu; Deckert, Gail E.; Rogers, Linda M.

2012-01-01

Broad-host-range IncP-1 plasmids generally encode two replication initiation proteins, TrfA1 and TrfA2. TrfA2 is produced from an internal translational start site within trfA1. While TrfA1 was previously shown to be essential for replication in Pseudomonas aeruginosa, its role in other bacteria within its broad host range has not been established. To address the role of TrfA1 and TrfA2 in other hosts, efficiency of transformation, plasmid copy number (PCN), and plasmid stability were first compared between a mini-IncP-1β plasmid and its trfA1 frameshift variant in four phylogenetically distant hosts: Escherichia coli, Pseudomonas putida, Sphingobium japonicum, and Cupriavidus necator. TrfA2 was sufficient for replication in these hosts, but the presence of TrfA1 enhanced transformation efficiency and PCN. However, TrfA1 did not contribute to, and even negatively affected, long-term plasmid persistence. When trfA genes were cloned under a constitutive promoter in the chromosomes of the four hosts, strains expressing either both TrfA1 and TrfA2 or TrfA1 alone, again, generally elicited a higher PCN of an IncP1-β replicon than strains expressing TrfA2 alone. When a single species of TrfA was produced at different concentrations in E. coli cells, TrfA1 maintained a 3- to 4-fold higher PCN than TrfA2 at the same TrfA concentrations, indicating that replication mediated by TrfA1 is more efficient than that by TrfA2. These results suggest that the broad-host-range properties of IncP-1 plasmids are essentially conferred by TrfA2 and the intact replication origin alone but that TrfA1 is nonetheless important to efficiently establish plasmid replication upon transfer into a broad range of hosts. PMID:22228734

Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts

PubMed Central

Lopez, Lorna M; Harris, Sarah E; Luciano, Michelle; Liewald, Dave; Davies, Gail; Gow, Alan J; Tenesa, Albert; Payton, Antony; Ke, Xiayi; Whalley, Lawrence J; Fox, Helen; Haggerty, Paul; Ollier, William; Pickles, Andrew; Porteous, David J; Horan, Michael A; Pendleton, Neil; Starr, John M; Deary, Ian J

2012-01-01

Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P=0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities. PMID:22045296

Replication domains are self-interacting structural chromatin units of human chromosomes

NASA Astrophysics Data System (ADS)

Arneodo, Alain

2011-03-01

In higher eukaryotes, the absence of specific sequence motifs marking the origins of replication has been a serious hindrance to the understanding of the mechanisms that regulate the initiation and the maintenance of the replication program in different cell types. In silico analysis of nucleotide compositional skew has predicted the existence, in the germline, of replication N-domains bordered by putative replication origins and where the skew decreases rather linearly as the signature of a progressive inversion of the average fork polarity. Here, from the demonstration that the average fork polarity can be directly extracted from the derivative of replication timing profiles, we develop a wavelet-based pattern recognition methodology to delineate replication U-domains where the replication timing profile is shaped as a U and its derivative as a N. Replication U-domains are robustly found in seven cell lines as covering a significant portion (40-50%) of the human genome where the replication timing data actually displays some plasticity between cell lines. The early replication initiation zones at U-domains borders are found to be hypersensitive to DNase I cleavage, to be associated with transcriptional activity and to present a significant enrichment in insular-binding proteins CTCF, the hallmark of an open chromatin structure. A comparative analysis of genome-wide chromatin interaction (HiC) data shows that replication-U domains correspond to self-interacting structural high order chromatin units of megabase characteristic size. Taken together, these findings provide evidence that the epigenetic compartmentalization of the human genome into autonomous replication U-domains comes along with an extensive remodelling of the threedimensional chromosome architecture during development or in specific diseases. The observed cell specific conservation of the replication timing between the human and mouse genomes strongly suggests that this chromosome organization into self-interacting structural and functional units is a general feature of mammalian organisms.

Unstable genomes elevate transcriptome dynamics

PubMed Central

Stevens, Joshua B.; Liu, Guo; Abdallah, Batoul Y.; Horne, Steven D.; Ye, Karen J.; Bremer, Steven W.; Ye, Christine J.; Krawetz, Stephen A.; Heng, Henry H.

2015-01-01

The challenge of identifying common expression signatures in cancer is well known, however the reason behind this is largely unclear. Traditionally variation in expression signatures has been attributed to technological problems, however recent evidence suggests that chromosome instability (CIN) and resultant karyotypic heterogeneity may be a large contributing factor. Using a well-defined model of immortalization, we systematically compared the pattern of genome alteration and expression dynamics during somatic evolution. Co-measurement of global gene expression and karyotypic alteration throughout the immortalization process reveals that karyotype changes influence gene expression as major structural and numerical karyotypic alterations result in large gene expression deviation. Replicate samples from stages with stable genomes are more similar to each other than are replicate samples with karyotypic heterogeneity. Karyotypic and gene expression change during immortalization is dynamic as each stage of progression has a unique expression pattern. This was further verified by comparing global expression in two replicates grown in one flask with known karyotypes. Replicates with higher karyotypic instability were found to be less similar than replicates with stable karyotypes. This data illustrates the karyotype, transcriptome, and transcriptome determined pathways are in constant flux during somatic cellular evolution (particularly during the macroevolutionary phase) and this flux is an inextricable feature of CIN and essential for cancer formation. The findings presented here underscore the importance of understanding the evolutionary process of cancer in order to design improved treatment modalities. PMID:24122714

A Genome-Wide Association Study of Depressive Symptoms

PubMed Central

Cornelis, Marilyn C.; Amin, Najaf; Bakshis, Erin; Baumert, Jens; Ding, Jingzhong; Liu, Yongmei; Marciante, Kristin; Meirelles, Osorio; Nalls, Michael A.; Sun, Yan V.; Vogelzangs, Nicole; Yu, Lei; Bandinelli, Stefania; Benjamin, Emelia J.; Bennett, David A.; Boomsma, Dorret; Cannas, Alessandra; Coker, Laura H.; de Geus, Eco; De Jager, Philip L.; Diez-Roux, Ana V.; Purcell, Shaun; Hu, Frank B.; Rimma, Eric B.; Hunter, David J.; Jensen, Majken K.; Curhan, Gary; Rice, Kenneth; Penman, Alan D.; Rotter, Jerome I.; Sotoodehnia, Nona; Emeny, Rebecca; Eriksson, Johan G.; Evans, Denis A.; Ferrucci, Luigi; Fornage, Myriam; Gudnason, Vilmundur; Hofman, Albert; Illig, Thomas; Kardia, Sharon; Kelly-Hayes, Margaret; Koenen, Karestan; Kraft, Peter; Kuningas, Maris; Massaro, Joseph M.; Melzer, David; Mulas, Antonella; Mulder, Cornelis L.; Murray, Anna; Oostra, Ben A.; Palotie, Aarno; Penninx, Brenda; Petersmann, Astrid; Pilling, Luke C.; Psaty, Bruce; Rawal, Rajesh; Reiman, Eric M.; Schulz, Andrea; Shulman, Joshua M.; Singleton, Andrew B.; Smith, Albert V.; Sutin, Angelina R.; Uitterlinden, André G.; Völzke, Henry; Widen, Elisabeth; Yaffe, Kristine; Zonderman, Alan B.; Cucca, Francesco; Harris, Tamara; Ladwig, Karl-Heinz; Llewellyn, David J.; Räikkönen, Katri; Tanaka, Toshiko

2013-01-01

Background Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. Methods In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p < 1 × 10−5) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. Results The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05 × 10−7). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19 × 10−3). This 5q21 region reached genome-wide significance (p = 4.78 × 10−8) in the overall meta-analysis combining discovery and replication studies (n = 51,258). Conclusions The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms. PMID:23290196

Monitoring carnivore populations at the landscape scale: occupancy modelling of tigers from sign surveys

USGS Publications Warehouse

Karanth, Kota Ullas; Gopalaswamy, Arjun M.; Kumar, Narayanarao Samba; Vaidyanathan, Srinivas; Nichols, James D.; MacKenzie, Darryl I.

2011-01-01

1. Assessing spatial distributions of threatened large carnivores at landscape scales poses formidable challenges because of their rarity and elusiveness. As a consequence of logistical constraints, investigators typically rely on sign surveys. Most survey methods, however, do not explicitly address the central problem of imperfect detections of animal signs in the field, leading to underestimates of true habitat occupancy and distribution. 2. We assessed habitat occupancy for a tiger Panthera tigris metapopulation across a c. 38 000-km2 landscape in India, employing a spatially replicated survey to explicitly address imperfect detections. Ecological predictions about tiger presence were confronted with sign detection data generated from occupancy sampling of 205 sites, each of 188 km2. 3. A recent occupancy model that considers Markovian dependency among sign detections on spatial replicates performed better than the standard occupancy model (ΔAIC = 184·9). A formulation of this model that fitted the data best showed that density of ungulate prey and levels of human disturbance were key determinants of local tiger presence. Model averaging resulted in a replicate-level detection probability [inline image] = 0·17 (0·17) for signs and a tiger habitat occupancy estimate of [inline image] = 0·665 (0·0857) or 14 076 (1814) km2 of potential habitat of 21 167 km2. In contrast, a traditional presence-versus-absence approach underestimated occupancy by 47%. Maps of probabilities of local site occupancy clearly identified tiger source populations at higher densities and matched observed tiger density variations, suggesting their potential utility for population assessments at landscape scales. 4. Synthesis and applications. Landscape-scale sign surveys can efficiently assess large carnivore spatial distributions and elucidate the factors governing their local presence, provided ecological and observation processes are both explicitly modelled. Occupancy sampling using spatial replicates can be used to reliably and efficiently identify tiger population sources and help monitor metapopulations. Our results reinforce earlier findings that prey depletion and human disturbance are key drivers of local tiger extinctions and tigers can persist even in human-dominated landscapes through effective protection of source populations. Our approach facilitates efficient targeting of tiger conservation interventions and, more generally, provides a basis for the reliable integration of large carnivore monitoring data between local and landscape scales.

An examination of the RCMAS-2 scores across gender, ethnic background, and age in a large Asian school sample.

PubMed

Ang, Rebecca P; Lowe, Patricia A; Yusof, Noradlin

2011-12-01

The present study investigated the factor structure, reliability, convergent and discriminant validity, and U.S. norms of the Revised Children's Manifest Anxiety Scale, Second Edition (RCMAS-2; C. R. Reynolds & B. O. Richmond, 2008a) scores in a Singapore sample of 1,618 school-age children and adolescents. Although there were small statistically significant differences in the average RCMAS-2 T scores found across various demographic groupings, on the whole, the U.S. norms appear adequate for use in the Asian Singapore sample. Results from item bias analyses suggested that biased items detected had small effects and were counterbalanced across gender and ethnicity, and hence, their relative impact on test score variation appears to be minimal. Results of factor analyses on the RCMAS-2 scores supported the presence of a large general anxiety factor, the Total Anxiety factor, and the 5-factor structure found in U.S. samples was replicated. Both the large general anxiety factor and the 5-factor solution were invariant across gender and ethnic background. Internal consistency estimates ranged from adequate to good, and 2-week test-retest reliability estimates were comparable to previous studies. Evidence providing support for convergent and discriminant validity of the RCMAS-2 scores was also found. Taken together, findings provide additional cross-cultural evidence of the appropriateness and usefulness of the RCMAS-2 as a measure of anxiety in Asian Singaporean school-age children and adolescents.

Perceived control and voice handicap in patients with voice disorders.

PubMed

Frazier, Patricia; Merians, Addie; Misono, Stephanie

2017-11-01

The purpose of the study was to replicate and extend previous research on the relation between perceived present control and voice handicap and to further examine the psychometric properties of a present control scale adapted for patients with voice disorders (Misono, Meredith, Peterson, & Frazier, 2016). Sample 1 consisted of 1,129 patients recruited from a voice disorder clinic who completed measures of perceived present control, distress, and voice handicap in the clinic. Sample 2 consisted of 62 patients from the same clinic who completed measures of present control, distress, voice handicap, and general control beliefs online at baseline and measures of present control and voice handicap again 3 weeks later (n = 59). With regard to the psychometric properties of the voice-adapted present control scale, alpha coefficients were above .80 and the 3-week test-reliability coefficient was .69. There was mixed support for the hypothesized 1-factor structure of the scale. In Sample 1, present control was more strongly associated with lower voice handicap than was distress and accounted for significant variance in voice handicap controlling for distress. In Sample 2, present control at baseline predicted later voice handicap, controlling for general control beliefs and distress. Present control appears to be a promising target for adjunctive interventions for patients with voice disorders. An evidence-based online present control intervention (Hintz, Frazier, & Meredith, 2015) is being adapted for this patient population. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Replication Rate, Framing, and Format Affect Attitudes and Decisions about Science Claims

PubMed Central

Barnes, Ralph M.; Tobin, Stephanie J.; Johnston, Heather M.; MacKenzie, Noah; Taglang, Chelsea M.

2016-01-01

A series of five experiments examined how the evaluation of a scientific finding was influenced by information about the number of studies that had successfully replicated the initial finding. The experiments also tested the impact of frame (negative, positive) and numeric format (percentage, natural frequency) on the evaluation of scientific findings. In Experiments 1 through 4, an attitude difference score served as the dependent measure, while a measure of choice served as the dependent measure in Experiment 5. Results from a diverse sample of 188 non-institutionalized U.S. adults (Experiment 2) and 730 undergraduate college students (Experiments 1, 3, and 4) indicated that attitudes became more positive as the replication rate increased and attitudes were more positive when the replication information was framed positively. The results also indicate that the manner in which replication rate was framed had a greater impact on attitude than the replication rate itself. The large effect for frame was attenuated somewhat when information about replication was presented in the form of natural frequencies rather than percentages. A fifth study employing 662 undergraduate college students in a task in which choice served as the dependent measure confirmed the framing effect and replicated the replication rate effect in the positive frame condition, but provided no evidence that the use of natural frequencies diminished the effect. PMID:27920743

Genome complexity, robustness and genetic interactions in digital organisms

NASA Astrophysics Data System (ADS)

Lenski, Richard E.; Ofria, Charles; Collier, Travis C.; Adami, Christoph

1999-08-01

Digital organisms are computer programs that self-replicate, mutate and adapt by natural selection. They offer an opportunity to test generalizations about living systems that may extend beyond the organic life that biologists usually study. Here we have generated two classes of digital organism: simple programs selected solely for rapid replication, and complex programs selected to perform mathematical operations that accelerate replication through a set of defined `metabolic' rewards. To examine the differences in their genetic architecture, we introduced millions of single and multiple mutations into each organism and measured the effects on the organism's fitness. The complex organisms are more robust than the simple ones with respect to the average effects of single mutations. Interactions among mutations are common and usually yield higher fitness than predicted from the component mutations assuming multiplicative effects; such interactions are especially important in the complex organisms. Frequent interactions among mutations have also been seen in bacteria, fungi and fruitflies. Our findings support the view that interactions are a general feature of genetic systems.

Genome complexity, robustness and genetic interactions in digital organisms.

PubMed

Lenski, R E; Ofria, C; Collier, T C; Adami, C

1999-08-12

Digital organisms are computer programs that self-replicate, mutate and adapt by natural selection. They offer an opportunity to test generalizations about living systems that may extend beyond the organic life that biologists usually study. Here we have generated two classes of digital organism: simple programs selected solely for rapid replication, and complex programs selected to perform mathematical operations that accelerate replication through a set of defined 'metabolic' rewards. To examine the differences in their genetic architecture, we introduced millions of single and multiple mutations into each organism and measured the effects on the organism's fitness. The complex organisms are more robust than the simple ones with respect to the average effects of single mutations. Interactions among mutations are common and usually yield higher fitness than predicted from the component mutations assuming multiplicative effects; such interactions are especially important in the complex organisms. Frequent interactions among mutations have also been seen in bacteria, fungi and fruitflies. Our findings support the view that interactions are a general feature of genetic systems.

Is General or Alcohol-Specific Perceived Social Support Associated with Depression among Adults in Substance Use Treatment?

PubMed Central

Shorey, Ryan C.; Dawson, Anne E.; Haynes, Ellen; Strauss, Catherine; Elmquist, JoAnna; Anderson, Scott; Stuart, Gregory L.

2017-01-01

Alcohol use disorders are among the most common mental health disorders in the world and incur considerable costs for individuals and society. Previous research has demonstrated that Perceived social support (PSS) may decrease rates of depression and relapse in individuals seeking treatment for alcohol use. The current study developed and investigated a self-report measure for perceived social support for sobriety from alcohol (PSSA) in a sample of men and women in residential treatment for substance use (N = 231), and examined the relationship between general or alcohol-specific perceived social support and depression. Analyses demonstrated sound factor structure, reliability, and validity for the PSSA. Additionally, the new measure of PSS for alcohol sobriety was negatively and uniquely associated with depression, even after controlling for general PSS, enacted social support, and negative social interactions. Overall, findings demonstrated that the PSSA was associated with fewer depressive symptoms, even after accounting for other known correlates of depression. Future research should replicate and extend these findings and examine whether this new measure predicts abstinence from alcohol following treatment. PMID:27627959

Assessing the validity of social anxiety disorder subtypes using a nationally representative sample.

PubMed

El-Gabalawy, Renée; Cox, Brian; Clara, Ian; Mackenzie, Corey

2010-03-01

The purpose of this study was to examine and validate social anxiety disorder subtypes using the nationally representative National Comorbidity Survey Replication (N=9282). Generalized and non-generalized subtypes were defined as fearing at least 8 (i.e., most) and fewer than 7 of 14 possible social situations, respectively, following the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Results indicated that in those with social anxiety disorder, the odds of having comorbid major depression, a comorbid anxiety disorder, and suicidal ideation were significantly greater in the generalized subtype. However, differences were no longer significant when adjusting for the number of feared social situations. Results further indicated that the number of feared social situations was significantly associated with comorbid major depression, a comorbid anxiety disorder, and suicidal ideation. These findings call into question the validity of DSM-IV-defined subtypes and provide additional support for the notion that clinicians and researchers should consider viewing this disorder on a single continuum with greater number of feared situations associated with greater clinical severity. Copyright 2009 Elsevier Ltd. All rights reserved.

Random catalytic reaction networks

NASA Astrophysics Data System (ADS)

Stadler, Peter F.; Fontana, Walter; Miller, John H.

1993-03-01

We study networks that are a generalization of replicator (or Lotka-Volterra) equations. They model the dynamics of a population of object types whose binary interactions determine the specific type of interaction product. Such a system always reduces its dimension to a subset that contains production pathways for all of its members. The network equation can be rewritten at a level of collectives in terms of two basic interaction patterns: replicator sets and cyclic transformation pathways among sets. Although the system contains well-known cases that exhibit very complicated dynamics, the generic behavior of randomly generated systems is found (numerically) to be extremely robust: convergence to a globally stable rest point. It is easy to tailor networks that display replicator interactions where the replicators are entire self-sustaining subsystems, rather than structureless units. A numerical scan of random systems highlights the special properties of elementary replicators: they reduce the effective interconnectedness of the system, resulting in enhanced competition, and strong correlations between the concentrations.

DNA replication fading as proliferating cells advance in their commitment to terminal differentiation.

PubMed

Estefanía, Monturus Ma; Ganier, Olivier; Hernández, Pablo; Schvartzman, Jorge B; Mechali, Marcel; Krimer, Dora B

2012-01-01

Terminal differentiation is the process by which cycling cells stop proliferating to start new specific functions. It involves dramatic changes in chromatin organization as well as gene expression. In the present report we used cell flow cytometry and genome wide DNA combing to investigate DNA replication during murine erythroleukemia-induced terminal cell differentiation. The results obtained indicated that the rate of replication fork movement slows down and the inter-origin distance becomes shorter during the precommitment and commitment periods before cells stop proliferating and accumulate in G1. We propose this is a general feature caused by the progressive heterochromatinization that characterizes terminal cell differentiation.

Effects of replicative fitness on competing HIV strains.

PubMed

Chirove, Faraimunashe; Lungu, Edward M

2013-07-01

We develop an n-strain model to show the effects of replicative fitness of competing viral strains exerting selective density-dependant infective pressure on each other. A two strain model is used to illustrate the results. A perturbation technique and numerical simulations were used to establish the existence and stability of steady states. More than one infected steady states governed by the replicative fitness resulted from the model exhibiting either strain replacement or co-infection. We found that the presence of two or more HIV strains could result in a disease-free state that, in general, is not globally stable. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Network-scale spatial and temporal variation in Chinook salmon (Oncorhynchus tshawytscha) redd distributions: patterns inferred from spatially continuous replicate surveys

Treesearch

Daniel J. Isaak; Russell F. Thurow

2006-01-01

Spatially continuous sampling designs, when temporally replicated, provide analytical flexibility and are unmatched in their ability to provide a dynamic system view. We have compiled such a data set by georeferencing the network-scale distribution of Chinook salmon (Oncorhynchus tshawytscha) redds across a large wilderness basin (7330 km2) in...

Variation of gene expression in Bacillus subtilis samples of fermentation replicates.

PubMed

Zhou, Ying; Yu, Wen-Bang; Ye, Bang-Ce

2011-06-01

The application of comprehensive gene expression profiling technologies to compare wild and mutated microorganism samples or to assess molecular differences between various treatments has been widely used. However, little is known about the normal variation of gene expression in microorganisms. In this study, an Agilent customized microarray representing 4,106 genes was used to quantify transcript levels of five-repeated flasks to assess normal variation in Bacillus subtilis gene expression. CV analysis and analysis of variance were employed to investigate the normal variance of genes and the components of variance, respectively. The results showed that above 80% of the total variation was caused by biological variance. For the 12 replicates, 451 of 4,106 genes exhibited variance with CV values over 10%. The functional category enrichment analysis demonstrated that these variable genes were mainly involved in cell type differentiation, cell type localization, cell cycle and DNA processing, and spore or cyst coat. Using power analysis, the minimal biological replicate number for a B. subtilis microarray experiment was determined to be six. The results contribute to the definition of the baseline level of variability in B. subtilis gene expression and emphasize the importance of replicate microarray experiments.

Double silencing of relevant genes suggests the existence of the direct link between DNA replication/repair and central carbon metabolism in human fibroblasts.

PubMed

Wieczorek, Aneta; Fornalewicz, Karolina; Mocarski, Łukasz; Łyżeń, Robert; Węgrzyn, Grzegorz

2018-04-15

Genetic evidence for a link between DNA replication and glycolysis has been demonstrated a decade ago in Bacillus subtilis, where temperature-sensitive mutations in genes coding for replication proteins could be suppressed by mutations in genes of glycolytic enzymes. Then, a strong influence of dysfunctions of particular enzymes from the central carbon metabolism (CCM) on DNA replication and repair in Escherichia coli was reported. Therefore, we asked if such a link occurs only in bacteria or it is a more general phenomenon. Here, we demonstrate that effects of silencing (provoked by siRNA) of expression of genes coding for proteins involved in DNA replication and repair (primase, DNA polymerase ι, ligase IV, and topoisomerase IIIβ) on these processes (less efficient entry into the S phase of the cell cycle and decreased level of DNA synthesis) could be suppressed by silencing of specific genes of enzymes from CMM. Silencing of other pairs of replication/repair and CMM genes resulted in enhancement of the negative effects of lower expression levels of replication/repair genes. We suggest that these results may be proposed as a genetic evidence for the link between DNA replication/repair and CMM in human cells, indicating that it is a common biological phenomenon, occurring from bacteria to humans. Copyright © 2018 Elsevier B.V. All rights reserved.

Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) normative elevation rates: comparisons with epidemiological prevalence rates.

PubMed

Tarescavage, Anthony M; Marek, Ryan J; Finn, Jacob A; Hicks, Adam; Rapier, Jessica L; Ben-Porath, Yossef S

2013-01-01

Odland, Berthelson, Sharma, Martin, and Mittenberg ( 2013 ) caution that clinically elevated scale scores produced by members of the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008 /2011) normative sample raise concerns about the potential for false positive findings of psychopathology. However, the MMPI-2-RF normative sample is intended to represent the general population of the United States, 26.2% of which met criteria for a Diagnostic and Statistical Manual-IV (APA, 1994 ) disorder in a 12-month period (Kessler, Chiu, Demler, & Walters, 2005 ). In the current study we compare scale elevation rates in the MMPI-2-RF normative sample to prevalence rates of mental disorders primarily drawn from the National Comorbidity Study Replication (Kessler et al., 2005 ). Our objective was to evaluate MMPI-2-RF elevation rates in an epidemiological context. Results indicate that MMPI-2-RF scale elevation rates were generally consistent with epidemiological data when examined in the context of standard interpretation guidelines for the inventory. We also reiterate Ben-Porath and Tellegen's (2008/2011) caution that MMPI-2-RF scale elevations alone are not sufficient to indicate the presence of psychiatric disorder. Rather they are best viewed as indications of the need to evaluate the individual for possible disorder(s). Implications of these results, limitations of this study, and future directions in research are discussed.

Succession of insects on unreclaimed coal strip mine spoil banks in Indiana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schrock, J.R.

1984-01-01

Selected sites at a western Indiana unreclaimed coal strip mine and adjacent undisturbed area sampled by Munsee in 1964 were restudied in 1981. Slope and exposure, soil pH and texture, vegetation and tree tallies, on-site rainfall and local weather records were used to characterize 18 spoilbanks and two unmined sites. Surface-active arthropods were sampled by replicated pitfall taps the summer of 1981 at the same locations and dates trapped by Munsee in 1964. Plant cover was sampled by a modified point-contact method. Trees over one inch dbh were tallied and measured for basal area. Clustering by similarity based on chi-squaremore » differences was performed for plants, trees, ants, springtails and ground beetles, using the undisturbed forest and a highly acid un-revegetated mined site as the extremes. Soil pH and texture changed rapidly on one moist spoilbank. Soil moisture levels generally decreased between 1964 and 1981 and depth of water penetration generally increased. Ant, springtail and carabid populations changed on revegetating sites. Myrmica spatulata and Smithistruma clypeata were major new ants on the sites in 1981. Iridomyrmex pruinosus analis and Pheidole bicarinata characteristic of barren spoilbanks in 1964 survived on only one remaining barren site in 1981. The collembolan Entomobrya quadrilineata decreased while Hypogastrura denticulata increased on the revegetating sites. Known habitat preference of some of these insects matched their occurrence on the spoilbanks.« less

Variability in Pesticide Deposition and Source Contributions to Snowpack in Western US National Parks

PubMed Central

Hageman, Kimberly J.; Hafner, William D.; Campbell, Donald H.; Jaffe, Daniel A; Landers, Dixon H.; Simonic, Staci L. Massey

2010-01-01

Fifty-six seasonal snowpack samples were collected at remote alpine, sub-arctic, and arctic sites in eight Western US national parks during three consecutive years (2003–2005). Four current-use pesticides (CUPs) (dacthal (DCPA), chlorpyrifos, endosulfan, and γ-hexachlorocyclohexane (HCH)) and four historic-use pesticides (HUPs) (dieldrin, α-HCH, chlordane, and hexachlorobenzene (HCB)) were commonly measured at all sites, during all years. The mean coefficient of variation for pesticide concentrations was 15% for site replicate samples, 41% for intra-park replicate samples, and 59% for inter-annual replicate samples. The relative pesticide concentration profiles were consistent from year to year but unique for individual parks, indicating a regional source effect. HUP concentrations were well-correlated with regional cropland intensity when the effect of temperature on snow-air partitioning was considered. The mass of individual CUPs used in regions located one-day upwind of the parks was calculated using air mass back trajectories and this was used to explain the distribution of CUPs among the parks. The percent of the snowpack pesticide concentration due to regional transport was high (>75%) for the majority of pesticides in all parks. These results suggest that the majority of pesticide contamination in US national parks is due to pesticide use in North America. PMID:20499934

Variability in pesticide deposition and source contributions to snowpack in western U.S. National Parks

USGS Publications Warehouse

Hageman, Kimberly J.; Hafner, William D.; Campbell, Donald H.; Jaffe, Daniel A.; Landers, Dixon H.; Massey Simonich, Staci L.

2010-01-01

Fifty-six seasonal snowpack samples were collected at remote alpine, subarctic, and arctic sites in eight Western U.S. national parks during three consecutive years (2003−2005). Four current-use pesticides (CUPs) (dacthal (DCPA), chlorpyrifos, endosulfans, and γ-hexachlorocyclohexane (HCH)) and four historic-use pesticides (HUPs) (dieldrin, α-HCH, chlordanes, and hexachlorobenzene (HCB)) were commonly measured at all sites, during all years. The mean coefficient of variation for pesticide concentrations was 15% for site replicate samples, 41% for intrapark replicate samples, and 59% for interannual replicate samples. The relative pesticide concentration profiles were consistent from year to year but unique for individual parks, indicating a regional source effect. HUP concentrations were well-correlated with regional cropland intensity when the effect of temperature on snow-air partitioning was considered. The mass of individual CUPs used in regions located one-day upwind of the parks was calculated using air mass back trajectories, and this was used to explain the distribution of CUPs among the parks. The percent of the snowpack pesticide concentration due to regional transport was high (>75%) for the majority of pesticides in all parks. These results suggest that the majority of pesticide contamination in U.S. national parks is due to regional pesticide use in North America.

Radiochemical and Chemical Constituents in Water from Selected Wells and Springs from the Southern Boundary of the Idaho National Engineering and Environmental Laboratory to the Hagerman Area, Idaho, 2002

USGS Publications Warehouse

Rattray, Gordon W.; Campbell, Linford J.

2004-01-01

The U.S. Geological Survey, Idaho Department of Water Resources, and the State of Idaho INEEL Oversight Program, in cooperation with the U.S. Department of Energy, sampled water from 17 sites as part of the sixth round of a long-term project to monitor water quality of the eastern Snake River Plain aquifer from the southern boundary of the Idaho National Engineering and Environmental Laboratory to the Hagerman area. The samples were collected from eight irrigation wells, three domestic wells, one stock well, one dairy well, one commercial well, one observation well, and two springs and analyzed for selected radiochemical and chemical constituents. One quality-assurance sample, a sequential replicate, also was collected and analyzed. Many of the radionuclide and inorganic-constituent concentrations were greater than the reporting levels and most of the organic-constituent concentrations were less than the reporting levels. However, none of the reported radiochemical- or chemical-constituent concentrations exceeded the maximum contaminant levels for drinking water established by the U.S. Environmental Protection Agency. Statistical evaluation of the replicate sample pair indicated that, with 95 percent confidence, 132 of the 135 constituent concentrations of the replicate pair were equivalent.

Variability in pesticide deposition and source contributions to snowpack in Western U.S. national parks.

PubMed

Hageman, Kimberly J; Hafner, William D; Campbell, Donald H; Jaffe, Daniel A; Landers, Dixon H; Simonich, Staci L Massey

2010-06-15

Fifty-six seasonal snowpack samples were collected at remote alpine, subarctic, and arctic sites in eight Western U.S. national parks during three consecutive years (2003-2005). Four current-use pesticides (CUPs) (dacthal (DCPA), chlorpyrifos, endosulfans, and gamma-hexachlorocyclohexane (HCH)) and four historic-use pesticides (HUPs) (dieldrin, alpha-HCH, chlordanes, and hexachlorobenzene (HCB)) were commonly measured at all sites, during all years. The mean coefficient of variation for pesticide concentrations was 15% for site replicate samples, 41% for intrapark replicate samples, and 59% for interannual replicate samples. The relative pesticide concentration profiles were consistent from year to year but unique for individual parks, indicating a regional source effect. HUP concentrations were well-correlated with regional cropland intensity when the effect of temperature on snow-air partitioning was considered. The mass of individual CUPs used in regions located one-day upwind of the parks was calculated using air mass back trajectories, and this was used to explain the distribution of CUPs among the parks. The percent of the snowpack pesticide concentration due to regional transport was high (>75%) for the majority of pesticides in all parks. These results suggest that the majority of pesticide contamination in U.S. national parks is due to regional pesticide use in North America.

Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn disease susceptibility

PubMed Central

Parkes, Miles; Barrett, Jeffrey C; Prescott, Natalie; Tremelling, Mark; Anderson, Carl A; Fisher, Sheila A; Roberts, Roland G; Nimmo, Elaine R; Cummings, Fraser R; Soars, Dianne; Drummond, Hazel; Lees, Charlie W; Khawaja, Saud A; Bagnall, Richard; Burke, Denis A; Todhunter, Catherine E; Ahmad, Tariq; Onnie, Clive M; McArdle, Wendy; Strachan, David; Bethel, Graeme; Bryan, Claire; Deloukas, Panos; Forbes, Alastair; Sanderson, Jeremy; Jewell, Derek P; Satsangi, Jack; Mansfield, John C; Cardon, Lon; Mathew, Christopher G

2008-01-01

A genome-wide association scan in Crohn disease by the Wellcome Trust Case Control Consortium1 detected strong association at 6 novel loci. We tested 37 SNPs from these and other loci for association in an independent case control sample. Replication was obtained for the IRGM gene on chromosome 5q33.1 which induces autophagy (replication P = 6.6 × 10−4, combined P = 2.1 × 10−10), and for 9 other loci including NKX2-3 and gene deserts on chromosomes 1q and 5p13. PMID:17554261

Influence of MCHR2 and MCHR2-AS1 Genetic Polymorphisms on Body Mass Index in Psychiatric Patients and In Population-Based Subjects with Present or Past Atypical Depression.

PubMed

Delacrétaz, Aurélie; Preisig, Martin; Vandenberghe, Frederik; Saigi Morgui, Nuria; Quteineh, Lina; Choong, Eva; Gholam-Rezaee, Mehdi; Kutalik, Zoltan; Magistretti, Pierre; Aubry, Jean-Michel; von Gunten, Armin; Castelao, Enrique; Vollenweider, Peter; Waeber, Gerard; Conus, Philippe; Eap, Chin B

2015-01-01

Obesity development during psychotropic treatments represents a major health issue in psychiatry. Melanin-concentrating hormone receptor 2 (MCHR2) is a central receptor involved in energy homeostasis. MCHR2 shares its promoter region with MCHR2-AS1, a long antisense non-coding RNA. The aim of this study was to determine whether tagging single nucleotide polymorphisms (tSNPs) of MCHR2 and MCHR2-AS1 are associated with the body mass index (BMI) in the psychiatric and in the general population. The influence of MCHR2 and MCHR2-AS1 tSNPs on BMI was firstly investigated in a discovery psychiatric sample (n1 = 474). Positive results were tested for replication in two other psychiatric samples (n2 = 164, n3 = 178) and in two population-based samples (CoLaus, n4 = 5409; GIANT, n5 = 113809). In the discovery sample, TT carriers of rs7754794C>T had 1.08 kg/m2 (p = 0.04) lower BMI as compared to C-allele carriers. This observation was replicated in an independent psychiatric sample (-2.18 kg/m2; p = 0.009). The association of rs7754794C>T and BMI seemed stronger in subjects younger than 45 years (median of age). In the population-based sample, a moderate association was observed (-0.17 kg/m2; p = 0.02) among younger individuals (<45y). Interestingly, this association was totally driven by patients meeting lifetime criteria for atypical depression, i.e. major depressive episodes characterized by symptoms such as an increased appetite. Indeed, patients with atypical depression carrying rs7754794-TT had 1.17 kg/m2 (p = 0.04) lower BMI values as compared to C-allele carriers, the effect being stronger in younger individuals (-2.50 kg/m2; p = 0.03; interaction between rs7754794 and age: p-value = 0.08). This study provides new insights on the possible influence of MCHR2 and/or MCHR2-AS1 on obesity in psychiatric patients and on the pathophysiology of atypical depression.

Influence of MCHR2 and MCHR2-AS1 Genetic Polymorphisms on Body Mass Index in Psychiatric Patients and In Population-Based Subjects with Present or Past Atypical Depression

PubMed Central

Delacrétaz, Aurélie; Preisig, Martin; Vandenberghe, Frederik; Saigi Morgui, Nuria; Quteineh, Lina; Choong, Eva; Gholam-Rezaee, Mehdi; Kutalik, Zoltan; Magistretti, Pierre; Aubry, Jean-Michel; von Gunten, Armin; Castelao, Enrique; Vollenweider, Peter; Waeber, Gerard; Conus, Philippe; Eap, Chin B.

2015-01-01

Obesity development during psychotropic treatments represents a major health issue in psychiatry. Melanin-concentrating hormone receptor 2 (MCHR2) is a central receptor involved in energy homeostasis. MCHR2 shares its promoter region with MCHR2-AS1, a long antisense non-coding RNA. The aim of this study was to determine whether tagging single nucleotide polymorphisms (tSNPs) of MCHR2 and MCHR2-AS1 are associated with the body mass index (BMI) in the psychiatric and in the general population. The influence of MCHR2 and MCHR2-AS1 tSNPs on BMI was firstly investigated in a discovery psychiatric sample (n1 = 474). Positive results were tested for replication in two other psychiatric samples (n2 = 164, n3 = 178) and in two population-based samples (CoLaus, n4 = 5409; GIANT, n5 = 113809). In the discovery sample, TT carriers of rs7754794C>T had 1.08 kg/m2 (p = 0.04) lower BMI as compared to C-allele carriers. This observation was replicated in an independent psychiatric sample (-2.18 kg/m2; p = 0.009). The association of rs7754794C>T and BMI seemed stronger in subjects younger than 45 years (median of age). In the population-based sample, a moderate association was observed (-0.17 kg/m2; p = 0.02) among younger individuals (<45y). Interestingly, this association was totally driven by patients meeting lifetime criteria for atypical depression, i.e. major depressive episodes characterized by symptoms such as an increased appetite. Indeed, patients with atypical depression carrying rs7754794-TT had 1.17 kg/m2 (p = 0.04) lower BMI values as compared to C-allele carriers, the effect being stronger in younger individuals (-2.50 kg/m2; p = 0.03; interaction between rs7754794 and age: p-value = 0.08). This study provides new insights on the possible influence of MCHR2 and/or MCHR2-AS1 on obesity in psychiatric patients and on the pathophysiology of atypical depression. PMID:26461262

Robust gene selection methods using weighting schemes for microarray data analysis.

PubMed

Kang, Suyeon; Song, Jongwoo

2017-09-02

A common task in microarray data analysis is to identify informative genes that are differentially expressed between two different states. Owing to the high-dimensional nature of microarray data, identification of significant genes has been essential in analyzing the data. However, the performances of many gene selection techniques are highly dependent on the experimental conditions, such as the presence of measurement error or a limited number of sample replicates. We have proposed new filter-based gene selection techniques, by applying a simple modification to significance analysis of microarrays (SAM). To prove the effectiveness of the proposed method, we considered a series of synthetic datasets with different noise levels and sample sizes along with two real datasets. The following findings were made. First, our proposed methods outperform conventional methods for all simulation set-ups. In particular, our methods are much better when the given data are noisy and sample size is small. They showed relatively robust performance regardless of noise level and sample size, whereas the performance of SAM became significantly worse as the noise level became high or sample size decreased. When sufficient sample replicates were available, SAM and our methods showed similar performance. Finally, our proposed methods are competitive with traditional methods in classification tasks for microarrays. The results of simulation study and real data analysis have demonstrated that our proposed methods are effective for detecting significant genes and classification tasks, especially when the given data are noisy or have few sample replicates. By employing weighting schemes, we can obtain robust and reliable results for microarray data analysis.

Intelligence in the brain: a theory of how it works and how to build it.

PubMed

Werbos, Paul J

2009-04-01

This paper presents a theory of how general-purpose learning-based intelligence is achieved in the mammal brain, and how we can replicate it. It reviews four generations of ever more powerful general-purpose learning designs in Adaptive, Approximate Dynamic Programming (ADP), which includes reinforcement learning as a special case. It reviews empirical results which fit the theory, and suggests important new directions for research, within the scope of NSF's recent initiative on Cognitive Optimization and Prediction. The appendices suggest possible connections to the realms of human subjective experience, comparative cognitive neuroscience, and new challenges in electric power. The major challenge before us today in mathematical neural networks is to replicate the "mouse level", but the paper does contain a few thoughts about building, understanding and nourishing levels of general intelligence beyond the mouse.

Psychometric properties and measurement invariance of the Beck hopelessness scale (BHS): results from a German representative population sample.

PubMed

Kliem, Sören; Lohmann, Anna; Mößle, Thomas; Brähler, Elmar

2018-04-25

The Beck Hopelessness Scale (BHS) has been the most frequently used instrument for the measurement of hopelessness in the past 40 years. Only recently has it officially been translated into German. The psychometric properties and factor structure of the BHS have been cause for intensive debate in the past. Based on a representative sample of the German population (N = 2450) item analysis including item sensitivity, item-total correlation and item difficulty was performed. Confirmatory factor analyses (CFA) for several factor solutions from the literature were performed. Multiple group factor analysis was performed to assess measurement invariance. Construct validity was assessed via the replication of well-established correlations with concurrently assessed measures. Most items exhibited adequate properties. Items #4, #8 and #13 exhibited poor item characteristics- each of these items had previously received negative evaluations in international studies. A one-dimensional factor solution, favorable for the calculation and interpretation of a sum score, was regarded as adequate. A bi-factor model with one content factor and two method factors (defined by positive/negative item coding) resulted in an excellent model fit. Cronbach's alpha in the current sample was .87. Hopelessness, as measured by the BHS, significantly correlated in the expected direction with suicidal ideation (r = .36), depression (r = .53) and life satisfaction (r = -.53). Strict measurement invariance could be established regarding gender and depression status. Due to limited research regarding the interpretation of fit indices with dichotomous data, interpretation of CFA results needs to remain tentative. The BHS is a valid measure of hopelessness in various subgroups of the general population. Future research could aim at replicating these findings using item response theory and cross-cultural samples. A one-dimensional bi-factor model seems appropriate even in a non-clinical population.

Multivariate analyses of peripheral blood leukocyte transcripts distinguish Alzheimer's, Parkinson's, control, and those at risk for developing Alzheimer's.

PubMed

Delvaux, Elaine; Mastroeni, Diego; Nolz, Jennifer; Chow, Nienwen; Sabbagh, Marwan; Caselli, Richard J; Reiman, Eric M; Marshall, Frederick J; Coleman, Paul D

2017-10-01

The need for a reliable, simple, and inexpensive blood test for Alzheimer's disease (AD) suitable for use in a primary care setting is widely recognized. This has led to a large number of publications describing blood tests for AD, which have, for the most part, not been replicable. We have chosen to examine transcripts expressed by the cellular, leukocyte compartment of blood. We have used hypothesis-based cDNA arrays and quantitative PCR to quantify the expression of selected sets of genes followed by multivariate analyses in multiple independent samples. Rather than a single study with no replicates, we chose an experimental design in which there were multiple replicates using different platforms and different sample populations. We have divided 177 blood samples and 27 brain samples into multiple replicates to demonstrate the ability to distinguish early clinical AD (Clinical Dementia Rating scale 0.5), Parkinson's disease (PD), and cognitively unimpaired APOE4 homozygotes, as well as to determine persons at risk for future cognitive impairment with significant accuracy. We assess our methods in a training/test set and also show that the variables we use distinguish AD, PD, and control brain. Importantly, we describe the variability of the weights assigned to individual transcripts in multivariate analyses in repeated studies and suggest that the variability we describe may be the cause of inability to repeat many earlier studies. Our data constitute a proof of principle that multivariate analysis of the transcriptome related to cell stress and inflammation of peripheral blood leukocytes has significant potential as a minimally invasive and inexpensive diagnostic tool for diagnosis and early detection of risk for AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Lack of Norovirus Replication and Histo-Blood Group Antigen Expression in 3-Dimensional Intestinal Epithelial Cells

PubMed Central

Radtke, Andrea L.; Lay, Margarita K.; Hjelm, Brooke E.; Bolick, Alice N.; Sarker, Shameema S.; Atmar, Robert L.; Kingsley, David H.; Arntzen, Charles J.; Estes, Mary K.; Nickerson, Cheryl A.

2013-01-01

Noroviruses (NoVs) are a leading cause of gastroenteritis worldwide. An in vitro model for NoV replication remains elusive, making study of the virus difficult. A previous study, which used a 3-dimensional (3-D) intestinal model derived from INT-407 cells reported NoV replication and extensive cytopathic effects (CPE). Using the same 3-D model, but with highly purified Norwalk virus (NV), we attempted to replicate this study. Our results showed no evidence of NV replication by real-time PCR of viral RNA or by immunocytochemical detection of viral structural and nonstructural proteins. Immunocytochemical analysis of the 3-D cultures also showed no detectable presence of histo-blood group antigens that participate in NV binding and host tropism. To determine the potential cause of CPE observed in the previous study, we exposed 3-D cultures to lipopolysaccharide concentrations consistent with contaminated stool samples and observed morphologic features similar to CPE. We conclude that the 3-D INT-407 model does not support NV replication. PMID:23622517

Impacts of exploratory drilling for oil and gas on the benthic environment of Georges Bank

USGS Publications Warehouse

Neff, J. M.; Bothner, Michael H.; Maciolek, N. J.; Grassle, J. F.

1989-01-01

Cluster analysis revealed a strong relationship between community structure and both sediment type and water depth. Little seasonal variation was detected, but some interannual differences were revealed by cluster analysis and correspondence analysis. The replicates from a station always resembled each other more than they resembled any replicates from other stations. In addition, the combined replicates from a station always clustered with samples from that station taken on other cruises. This excellent replication and uniformity of the benthic infaunal community at a station over time made it possible to detect very subtle changes in community parameters that might be related to discharges of drilling fluid and drill cuttings. Nevertheless, no changes were detected in benthic communities of Georges Bank that could be attributed to drilling activities.

The Construct Validity of the Dutch Personality Inventory for DSM-5 Personality Disorders (PID-5) in a Clinical Sample.

PubMed

Bastiaens, Tim; Claes, Laurence; Smits, Dirk; De Clercq, Barbara; De Fruyt, Filip; Rossi, Gina; Vanwalleghem, Dominique; Vermote, Rudi; Lowyck, Benedicte; Claes, Stephan; De Hert, Marc

2016-02-01

The factor structure and the convergent validity of the Personality Inventory for DSM-5 (PID-5), a self-report questionnaire designed to measure personality pathology as advocated in the fifth edition, Section III of Diagnostic and Statistical Manual of Mental Disorders (DSM-5), are already demonstrated in general population samples, but need replication in clinical samples. In 240 Flemish inpatients, we examined the factor structure of the PID-5 by means of exploratory structural equation modeling. Additionally, we investigated differences in PID-5 higher order domain scores according to gender, age and educational level, and explored convergent and discriminant validity by relating the PID-5 with the Dimensional Assessment of Personality Pathology-Basic Questionnaire and by comparing PID-5 scores of inpatients with and without a DSM-IV categorical personality disorder diagnosis. Our results confirmed the original five-factor structure of the PID-5. The reliability and the convergent and discriminant validity of the PID-5 proved to be adequate. Implications for future research are discussed. © The Author(s) 2015.

Age, memory type, and the phenomenology of autobiographical memory: findings from an Italian sample.

PubMed

Montebarocci, Ornella; Luchetti, Martina; Sutin, Angelina R

2014-01-01

The present research explored differences in phenomenology between two types of memories, a general self-defining memory and an earliest childhood memory. A sample of 76 Italian participants were selected and categorised into two age groups: 20-30 years and 31-40 years. The Memory Experiences Questionnaire (MEQ) was administered, taking note of latency and duration times of the narratives. Consistent with the literature, the self-defining memory differed significantly from the earliest childhood memory in terms of phenomenology, with the recency of the memory associated with more intense phenomenological experience. The self-defining memory took longer to retrieve and narrate than the earliest childhood memory. Meaningful differences also emerged between the two age groups: Participants in their 30s rated their self-defining memory as more vivid, coherent, and accessible than participants in their 20s. According to latency findings, these differences suggest an expanded period of identity consolidation for younger adults. Further applications of the MEQ should be carried out to replicate these results with other samples of young adults.

The Dark Triad Traits from a Life History Perspective in Six Countries.

PubMed

Jonason, Peter K; Foster, Joshua D; Egorova, Marina S; Parshikova, Oksana; Csathó, Árpád; Oshio, Atsushi; Gouveia, Valdiney V

2017-01-01

Work on the Dark Triad traits has benefited from the use of a life history framework but it has been limited to primarily Western samples and indirect assessments of life history strategies. Here, we examine how the Dark Triad traits (i.e., psychopathy, Machiavellianism, and narcissism) relate to two measures of individual differences in life history strategies. In Study 1 ( N = 937), we replicated prior observed links between life history strategies, as measured by the Mini- K , and the Dark Triad traits using samples recruited from three countries. In Study 2 ( N = 1032), we measured life history strategies using the Consideration of Future Consequences Scale and correlated it with the Dark Triad traits in samples recruited from three additional countries. While there was some variability across participants' sex and country, the results were generally consistent in that psychopathy and (to a lesser extent) Machiavellianism were related to faster life history strategies and narcissism was related to slower life history strategies. These results add cross-cultural data and the use of two measures of life history speed to understand the Dark Triad traits from a life history perspective.

Towards robust and repeatable sampling methods in eDNA based studies.

PubMed

Dickie, Ian A; Boyer, Stephane; Buckley, Hannah; Duncan, Richard P; Gardner, Paul; Hogg, Ian D; Holdaway, Robert J; Lear, Gavin; Makiola, Andreas; Morales, Sergio E; Powell, Jeff R; Weaver, Louise

2018-05-26

DNA based techniques are increasingly used for measuring the biodiversity (species presence, identity, abundance and community composition) of terrestrial and aquatic ecosystems. While there are numerous reviews of molecular methods and bioinformatic steps, there has been little consideration of the methods used to collect samples upon which these later steps are based. This represents a critical knowledge gap, as methodologically sound field sampling is the foundation for subsequent analyses. We reviewed field sampling methods used for metabarcoding studies of both terrestrial and freshwater ecosystem biodiversity over a nearly three-year period (n = 75). We found that 95% (n = 71) of these studies used subjective sampling methods, inappropriate field methods, and/or failed to provide critical methodological information. It would be possible for researchers to replicate only 5% of the metabarcoding studies in our sample, a poorer level of reproducibility than for ecological studies in general. Our findings suggest greater attention to field sampling methods and reporting is necessary in eDNA-based studies of biodiversity to ensure robust outcomes and future reproducibility. Methods must be fully and accurately reported, and protocols developed that minimise subjectivity. Standardisation of sampling protocols would be one way to help to improve reproducibility, and have additional benefits in allowing compilation and comparison of data from across studies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation.

PubMed

Fabbri, C; Tansey, K E; Perlis, R H; Hauser, J; Henigsberg, N; Maier, W; Mors, O; Placentino, A; Rietschel, M; Souery, D; Breen, G; Curtis, C; Sang-Hyuk, L; Newhouse, S; Patel, H; Guipponi, M; Perroud, N; Bondolfi, G; O'Donovan, M; Lewis, G; Biernacka, J M; Weinshilboum, R M; Farmer, A; Aitchison, K J; Craig, I; McGuffin, P; Uher, R; Lewis, C M

2017-11-21

Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. Significant findings were investigated in NEWMEDS consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) for replication. A total of 7062 950 SNPs were analyzed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (P=1.80e-08, ITGA9 (integrin α9)) and rs76191705 (P=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At the gene level, no consistent effect was found. At the pathway level, the Gene Ontology (GO) terms GO: 0005694 (chromosome) and GO: 0044427 (chromosomal part) were associated with improvement (corrected P=0.007 and 0.045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (P=0.047), whereas rs76191705 was not. The two SNPs did not replicate in NEWMEDS. ITGA9 codes for a membrane receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, replication was partial. Further studies may help in clarifying their role.The Pharmacogenomics Journal advance online publication, 21 November 2017; doi:10.1038/tpj.2017.44.

Genome-wide association study of antisocial personality disorder

PubMed Central

Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

2016-01-01

The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53–3.14), P=1.9 × 10-5). Two polymorphisms at 6p21.2 LINC00951–LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37–1.85), P=1.6 × 10−9) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder. PMID:27598967

Genome-wide association study of antisocial personality disorder.

PubMed

Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

2016-09-06

The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53-3.14), P=1.9 × 10(-5)). Two polymorphisms at 6p21.2 LINC00951-LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37-1.85), P=1.6 × 10(-9)) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder.

Removing Batch Effects from Longitudinal Gene Expression - Quantile Normalization Plus ComBat as Best Approach for Microarray Transcriptome Data

PubMed Central

Müller, Christian; Schillert, Arne; Röthemeier, Caroline; Trégouët, David-Alexandre; Proust, Carole; Binder, Harald; Pfeiffer, Norbert; Beutel, Manfred; Lackner, Karl J.; Schnabel, Renate B.; Tiret, Laurence; Wild, Philipp S.; Blankenberg, Stefan

2016-01-01

Technical variation plays an important role in microarray-based gene expression studies, and batch effects explain a large proportion of this noise. It is therefore mandatory to eliminate technical variation while maintaining biological variability. Several strategies have been proposed for the removal of batch effects, although they have not been evaluated in large-scale longitudinal gene expression data. In this study, we aimed at identifying a suitable method for batch effect removal in a large study of microarray-based longitudinal gene expression. Monocytic gene expression was measured in 1092 participants of the Gutenberg Health Study at baseline and 5-year follow up. Replicates of selected samples were measured at both time points to identify technical variability. Deming regression, Passing-Bablok regression, linear mixed models, non-linear models as well as ReplicateRUV and ComBat were applied to eliminate batch effects between replicates. In a second step, quantile normalization prior to batch effect correction was performed for each method. Technical variation between batches was evaluated by principal component analysis. Associations between body mass index and transcriptomes were calculated before and after batch removal. Results from association analyses were compared to evaluate maintenance of biological variability. Quantile normalization, separately performed in each batch, combined with ComBat successfully reduced batch effects and maintained biological variability. ReplicateRUV performed perfectly in the replicate data subset of the study, but failed when applied to all samples. All other methods did not substantially reduce batch effects in the replicate data subset. Quantile normalization plus ComBat appears to be a valuable approach for batch correction in longitudinal gene expression data. PMID:27272489

Assessment of the cPAS-based BGISEQ-500 platform for metagenomic sequencing.

PubMed

Fang, Chao; Zhong, Huanzi; Lin, Yuxiang; Chen, Bing; Han, Mo; Ren, Huahui; Lu, Haorong; Luber, Jacob M; Xia, Min; Li, Wangsheng; Stein, Shayna; Xu, Xun; Zhang, Wenwei; Drmanac, Radoje; Wang, Jian; Yang, Huanming; Hammarström, Lennart; Kostic, Aleksandar D; Kristiansen, Karsten; Li, Junhua

2018-03-01

More extensive use of metagenomic shotgun sequencing in microbiome research relies on the development of high-throughput, cost-effective sequencing. Here we present a comprehensive evaluation of the performance of the new high-throughput sequencing platform BGISEQ-500 for metagenomic shotgun sequencing and compare its performance with that of 2 Illumina platforms. Using fecal samples from 20 healthy individuals, we evaluated the intra-platform reproducibility for metagenomic sequencing on the BGISEQ-500 platform in a setup comprising 8 library replicates and 8 sequencing replicates. Cross-platform consistency was evaluated by comparing 20 pairwise replicates on the BGISEQ-500 platform vs the Illumina HiSeq 2000 platform and the Illumina HiSeq 4000 platform. In addition, we compared the performance of the 2 Illumina platforms against each other. By a newly developed overall accuracy quality control method, an average of 82.45 million high-quality reads (96.06% of raw reads) per sample, with 90.56% of bases scoring Q30 and above, was obtained using the BGISEQ-500 platform. Quantitative analyses revealed extremely high reproducibility between BGISEQ-500 intra-platform replicates. Cross-platform replicates differed slightly more than intra-platform replicates, yet a high consistency was observed. Only a low percentage (2.02%-3.25%) of genes exhibited significant differences in relative abundance comparing the BGISEQ-500 and HiSeq platforms, with a bias toward genes with higher GC content being enriched on the HiSeq platforms. Our study provides the first set of performance metrics for human gut metagenomic sequencing data using BGISEQ-500. The high accuracy and technical reproducibility confirm the applicability of the new platform for metagenomic studies, though caution is still warranted when combining metagenomic data from different platforms.

Maintaining replication origins in the face of genomic change.

PubMed

Di Rienzi, Sara C; Lindstrom, Kimberly C; Mann, Tobias; Noble, William S; Raghuraman, M K; Brewer, Bonita J

2012-10-01

Origins of replication present a paradox to evolutionary biologists. As a collection, they are absolutely essential genomic features, but individually are highly redundant and nonessential. It is therefore difficult to predict to what extent and in what regard origins are conserved over evolutionary time. Here, through a comparative genomic analysis of replication origins and chromosomal replication patterns in the budding yeasts Saccharomyces cerevisiae and Lachancea waltii, we assess to what extent replication origins survived genomic change produced from 150 million years of evolution. We find that L. waltii origins exhibit a core consensus sequence and nucleosome occupancy pattern highly similar to those of S. cerevisiae origins. We further observe that the overall progression of chromosomal replication is similar between L. waltii and S. cerevisiae. Nevertheless, few origins show evidence of being conserved in location between the two species. Among the conserved origins are those surrounding centromeres and adjacent to histone genes, suggesting that proximity to an origin may be important for their regulation. We conclude that, over evolutionary time, origins maintain sequence, structure, and regulation, but are continually being created and destroyed, with the result that their locations are generally not conserved.

Maintaining replication origins in the face of genomic change

PubMed Central

Di Rienzi, Sara C.; Lindstrom, Kimberly C.; Mann, Tobias; Noble, William S.; Raghuraman, M.K.; Brewer, Bonita J.

2012-01-01

Origins of replication present a paradox to evolutionary biologists. As a collection, they are absolutely essential genomic features, but individually are highly redundant and nonessential. It is therefore difficult to predict to what extent and in what regard origins are conserved over evolutionary time. Here, through a comparative genomic analysis of replication origins and chromosomal replication patterns in the budding yeasts Saccharomyces cerevisiae and Lachancea waltii, we assess to what extent replication origins survived genomic change produced from 150 million years of evolution. We find that L. waltii origins exhibit a core consensus sequence and nucleosome occupancy pattern highly similar to those of S. cerevisiae origins. We further observe that the overall progression of chromosomal replication is similar between L. waltii and S. cerevisiae. Nevertheless, few origins show evidence of being conserved in location between the two species. Among the conserved origins are those surrounding centromeres and adjacent to histone genes, suggesting that proximity to an origin may be important for their regulation. We conclude that, over evolutionary time, origins maintain sequence, structure, and regulation, but are continually being created and destroyed, with the result that their locations are generally not conserved. PMID:22665441

Identification of Susceptible Loci and Enriched Pathways for Bipolar II Disorder Using Genome-Wide Association Studies.

PubMed

Kao, Chung-Feng; Chen, Hui-Wen; Chen, Hsi-Chung; Yang, Jenn-Hwai; Huang, Ming-Chyi; Chiu, Yi-Hang; Lin, Shih-Ku; Lee, Ya-Chin; Liu, Chih-Min; Chuang, Li-Chung; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Lu, Ru-Band; Kuo, Po-Hsiu

2016-12-01

This study aimed to identify susceptible loci and enriched pathways for bipolar disorder subtype II. We conducted a genome-wide association scan in discovery samples with 189 bipolar disorder subtype II patients and 1773 controls, and replication samples with 283 bipolar disorder subtype II patients and 500 controls in a Taiwanese Han population using Affymetrix Axiom Genome-Wide CHB1 Array. We performed single-marker and gene-based association analyses, as well as calculated polygeneic risk scores for bipolar disorder subtype II. Pathway enrichment analyses were employed to reveal significant biological pathways. Seven markers were found to be associated with bipolar disorder subtype II in meta-analysis combining both discovery and replication samples (P<5.0×10 -6 ), including markers in or close to MYO16, HSP90AB3P, noncoding gene LOC100507632, and markers in chromosomes 4 and 10. A novel locus, ETF1, was associated with bipolar disorder subtype II (P<6.0×10 -3 ) in gene-based association tests. Results of risk evaluation demonstrated that higher genetic risk scores were able to distinguish bipolar disorder subtype II patients from healthy controls in both discovery (P=3.9×10 -4 ~1.0×10 -3 ) and replication samples (2.8×10 -4 ~1.7×10 -3 ). Genetic variance explained by chip markers for bipolar disorder subtype II was substantial in the discovery (55.1%) and replication (60.5%) samples. Moreover, pathways related to neurodevelopmental function, signal transduction, neuronal system, and cell adhesion molecules were significantly associated with bipolar disorder subtype II. We reported novel susceptible loci for pure bipolar subtype II disorder that is less addressed in the literature. Future studies are needed to confirm the roles of these loci for bipolar disorder subtype II. © The Author 2016. Published by Oxford University Press on behalf of CINP.

The Relationship between Baseline Drinking Status, Peer Motivational Interviewing Microskills, and Drinking Outcomes in a Brief Alcohol Intervention for Matriculating College Students: A Replication

ERIC Educational Resources Information Center

Tollison, Sean J.; Mastroleo, Nadine R.; Mallett, Kimberly A.; Witkiewitz, Katie; Lee, Christine M.; Ray, Anne E.; Larimer, Mary E.

2013-01-01

The purpose of this study was to replicate and extend previous findings (Tollison et al., 2008) on the association between peer facilitator adherence to motivational interviewing (MI) microskills and college student drinking behavior. This study used a larger sample size, multiple follow-up time-points, and latent variable analyses allowing for…

Systematic Replication of the Effects of a Supplementary, Technology-Assisted, Storybook Intervention for Preschool Children with Weak Vocabulary and Comprehension Skills

ERIC Educational Resources Information Center

Greenwood, Charles R.; Carta, Judith J.; Kelley, Elizabeth S.; Guerrero, Gabriela; Kong, Na Young; Atwater, Jane; Goldstein, Howard

2016-01-01

In 2013, Spencer, Goldstein, Sherman, et al. reported the promising effects of a supplemental, technology-assisted, storybook intervention (Tier 2) containing embedded instruction targeting the oral language learning of preschool children at risk for delays. We sought to advance knowledge of the intervention by replicating it in a new sample and…

Rapid and highly fieldable viral diagnostic

DOEpatents

McKnight, Timothy E.

2016-12-20

The present invention relates to a rapid, highly fieldable, nearly reagentless diagnostic to identify active RNA viral replication in a live, infected cells, and more particularly in leukocytes and tissue samples (including biopsies and nasal swabs) using an array of a plurality of vertically-aligned nanostructures that impale the cells and introduce a DNA reporter construct that is expressed and amplified in the presence of active viral replication.

Lymph Node Cellular and Viral Dynamics in Natural Hosts and Impact for HIV Cure Strategies.

PubMed

Huot, Nicolas; Bosinger, Steven E; Paiardini, Mirko; Reeves, R Keith; Müller-Trutwin, Michaela

2018-01-01

Combined antiretroviral therapies (cARTs) efficiently control HIV replication leading to undetectable viremia and drastic increases in lifespan of people living with HIV. However, cART does not cure HIV infection as virus persists in cellular and anatomical reservoirs, from which the virus generally rebounds soon after cART cessation. One major anatomical reservoir are lymph node (LN) follicles, where HIV persists through replication in follicular helper T cells and is also trapped by follicular dendritic cells. Natural hosts of SIV, such as African green monkeys and sooty mangabeys, generally do not progress to disease although displaying persistently high viremia. Strikingly, these hosts mount a strong control of viral replication in LN follicles shortly after peak viremia that lasts throughout infection. Herein, we discuss the potential interplay between viral control in LNs and the resolution of inflammation, which is characteristic for natural hosts. We furthermore detail the differences that exist between non-pathogenic SIV infection in natural hosts and pathogenic HIV/SIV infection in humans and macaques regarding virus target cells and replication dynamics in LNs. Several mechanisms have been proposed to be implicated in the strong control of viral replication in natural host's LNs, such as NK cell-mediated control, that will be reviewed here, together with lessons and limitations of in vivo cell depletion studies that have been performed in natural hosts. Finally, we discuss the impact that these insights on viral dynamics and host responses in LNs of natural hosts have for the development of strategies toward HIV cure.

Direct and conceptual replications of the taxometric analysis of type a behavior.

PubMed

Wilmot, Michael P; Haslam, Nick; Tian, Jingyuan; Ones, Deniz S

2018-05-17

We present direct and conceptual replications of the influential taxometric analysis of Type A Behavior (TAB; Strube, 1989), which reported evidence for the latent typology of the construct. Study 1, the direct replication (N = 2,373), duplicated sampling and methodological procedures of the original study, but results showed that the item indicators used in the original study lacked sufficient validity to unambiguously determine latent structure. Using improved factorial subscale indicators to further test the question, multiple taxometric procedures, in combination with parallel analyses of simulated data, failed to replicate the original typological finding. Study 2, the conceptual replication, tested the latent structure of the wider construct of TAB using the sample from the Caerphilly Prospective Study (N = 2,254), which contains responses to the three most widely used self-report measures of TAB: the Jenkins Activity Survey, Bortner scale, and Framingham scale. Factorial subscale indicators were derived from the measures and submitted to multiple taxometric procedures. Results of Study 2 converged with those of Study 1, providing clear evidence of latent dimensional structure. Overall, results suggest there is no evidence for the type in TAB. Findings imply that theoretical models of TAB, assessment practices, and data analytic procedures that assume a typology should be replaced by dimensional models, factorial subscale measures, and corresponding statistical approaches. Specific subscale measures that tap multiple Big Five trait domains, and show evidence of predictive utility, are also recommended. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Plant Disease Severity Assessment-How Rater Bias, Assessment Method, and Experimental Design Affect Hypothesis Testing and Resource Use Efficiency.

PubMed

Chiang, Kuo-Szu; Bock, Clive H; Lee, I-Hsuan; El Jarroudi, Moussa; Delfosse, Philippe

2016-12-01

The effect of rater bias and assessment method on hypothesis testing was studied for representative experimental designs for plant disease assessment using balanced and unbalanced data sets. Data sets with the same number of replicate estimates for each of two treatments are termed "balanced" and those with unequal numbers of replicate estimates are termed "unbalanced". The three assessment methods considered were nearest percent estimates (NPEs), an amended 10% incremental scale, and the Horsfall-Barratt (H-B) scale. Estimates of severity of Septoria leaf blotch on leaves of winter wheat were used to develop distributions for a simulation model. The experimental designs are presented here in the context of simulation experiments which consider the optimal design for the number of specimens (individual units sampled) and the number of replicate estimates per specimen for a fixed total number of observations (total sample size for the treatments being compared). The criterion used to gauge each method was the power of the hypothesis test. As expected, at a given fixed number of observations, the balanced experimental designs invariably resulted in a higher power compared with the unbalanced designs at different disease severity means, mean differences, and variances. Based on these results, with unbiased estimates using NPE, the recommended number of replicate estimates taken per specimen is 2 (from a sample of specimens of at least 30), because this conserves resources. Furthermore, for biased estimates, an apparent difference in the power of the hypothesis test was observed between assessment methods and between experimental designs. Results indicated that, regardless of experimental design or rater bias, an amended 10% incremental scale has slightly less power compared with NPEs, and that the H-B scale is more likely than the others to cause a type II error. These results suggest that choice of assessment method, optimizing sample number and number of replicate estimates, and using a balanced experimental design are important criteria to consider to maximize the power of hypothesis tests for comparing treatments using disease severity estimates.

Public Attitudes toward Stuttering in Turkey: Probability versus Convenience Sampling

ERIC Educational Resources Information Center

Ozdemir, R. Sertan; St. Louis, Kenneth O.; Topbas, Seyhun

2011-01-01

Purpose: A Turkish translation of the "Public Opinion Survey of Human Attributes-Stuttering" ("POSHA-S") was used to compare probability versus convenience sampling to measure public attitudes toward stuttering. Method: A convenience sample of adults in Eskisehir, Turkey was compared with two replicates of a school-based,…

Statistical considerations in evaluating pharmacogenomics-based clinical effect for confirmatory trials.

PubMed

Wang, Sue-Jane; O'Neill, Robert T; Hung, Hm James

2010-10-01

The current practice for seeking genomically favorable patients in randomized controlled clinical trials using genomic convenience samples. To discuss the extent of imbalance, confounding, bias, design efficiency loss, type I error, and type II error that can occur in the evaluation of the convenience samples, particularly when they are small samples. To articulate statistical considerations for a reasonable sample size to minimize the chance of imbalance, and, to highlight the importance of replicating the subgroup finding in independent studies. Four case examples reflecting recent regulatory experiences are used to underscore the problems with convenience samples. Probability of imbalance for a pre-specified subgroup is provided to elucidate sample size needed to minimize the chance of imbalance. We use an example drug development to highlight the level of scientific rigor needed, with evidence replicated for a pre-specified subgroup claim. The convenience samples evaluated ranged from 18% to 38% of the intent-to-treat samples with sample size ranging from 100 to 5000 patients per arm. The baseline imbalance can occur with probability higher than 25%. Mild to moderate multiple confounders yielding the same directional bias in favor of the treated group can make treatment group incomparable at baseline and result in a false positive conclusion that there is a treatment difference. Conversely, if the same directional bias favors the placebo group or there is loss in design efficiency, the type II error can increase substantially. Pre-specification of a genomic subgroup hypothesis is useful only for some degree of type I error control. Complete ascertainment of genomic samples in a randomized controlled trial should be the first step to explore if a favorable genomic patient subgroup suggests a treatment effect when there is no clear prior knowledge and understanding about how the mechanism of a drug target affects the clinical outcome of interest. When stratified randomization based on genomic biomarker status cannot be implemented in designing a pharmacogenomics confirmatory clinical trial, if there is one genomic biomarker prognostic for clinical response, as a general rule of thumb, a sample size of at least 100 patients may be needed to be considered for the lower prevalence genomic subgroup to minimize the chance of an imbalance of 20% or more difference in the prevalence of the genomic marker. The sample size may need to be at least 150, 350, and 1350, respectively, if an imbalance of 15%, 10% and 5% difference is of concern.

A Leveraged Signal-to-Noise Ratio (LSTNR) Method to Extract Differentially Expressed Genes and Multivariate Patterns of Expression From Noisy and Low-Replication RNAseq Data

PubMed Central

Lozoya, Oswaldo A.; Santos, Janine H.; Woychik, Richard P.

2018-01-01

To life scientists, one important feature offered by RNAseq, a next-generation sequencing tool used to estimate changes in gene expression levels, lies in its unprecedented resolution. It can score countable differences in transcript numbers among thousands of genes and between experimental groups, all at once. However, its high cost limits experimental designs to very small sample sizes, usually N = 3, which often results in statistically underpowered analysis and poor reproducibility. All these issues are compounded by the presence of experimental noise, which is harder to distinguish from instrumental error when sample sizes are limiting (e.g., small-budget pilot tests), experimental populations exhibit biologically heterogeneous or diffuse expression phenotypes (e.g., patient samples), or when discriminating among transcriptional signatures of closely related experimental conditions (e.g., toxicological modes of action, or MOAs). Here, we present a leveraged signal-to-noise ratio (LSTNR) thresholding method, founded on generalized linear modeling (GLM) of aligned read detection limits to extract differentially expressed genes (DEGs) from noisy low-replication RNAseq data. The LSTNR method uses an agnostic independent filtering strategy to define the dynamic range of detected aggregate read counts per gene, and assigns statistical weights that prioritize genes with better sequencing resolution in differential expression analyses. To assess its performance, we implemented the LSTNR method to analyze three separate datasets: first, using a systematically noisy in silico dataset, we demonstrated that LSTNR can extract pre-designed patterns of expression and discriminate between “noise” and “true” differentially expressed pseudogenes at a 100% success rate; then, we illustrated how the LSTNR method can assign patient-derived breast cancer specimens correctly to one out of their four reported molecular subtypes (luminal A, luminal B, Her2-enriched and basal-like); and last, we showed the ability to retrieve five different modes of action (MOA) elicited in livers of rats exposed to three toxicants under three nutritional routes by using the LSTNR method. By combining differential measurements with resolving power to detect DEGs, the LSTNR method offers an alternative approach to interrogate noisy and low-replication RNAseq datasets, which handles multiple biological conditions at once, and defines benchmarks to validate RNAseq experiments with standard benchtop assays. PMID:29868123

Human stem cell–derived astrocytes replicate human prions in a PRNP genotype–dependent manner

PubMed Central

Krejciova, Zuzana; Alibhai, James; Zhao, Chen; Rzechorzek, Nina M.; Ullian, Erik M.; Manson, Jean

2017-01-01

Prions are infectious agents that cause neurodegenerative diseases such as Creutzfeldt–Jakob disease (CJD). The absence of a human cell culture model that replicates human prions has hampered prion disease research for decades. In this paper, we show that astrocytes derived from human induced pluripotent stem cells (iPSCs) support the replication of prions from brain samples of CJD patients. For experimental exposure of astrocytes to variant CJD (vCJD), the kinetics of prion replication occur in a prion protein codon 129 genotype–dependent manner, reflecting the genotype-dependent susceptibility to clinical vCJD found in patients. Furthermore, iPSC-derived astrocytes can replicate prions associated with the major sporadic CJD strains found in human patients. Lastly, we demonstrate the subpassage of prions from infected to naive astrocyte cultures, indicating the generation of prion infectivity in vitro. Our study addresses a long-standing gap in the repertoire of human prion disease research, providing a new in vitro system for accelerated mechanistic studies and drug discovery. PMID:29141869

U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--STANDARD OPERATING PROCEDURE FOR REIMBURSEMENT FOR FIELD COLLECTION OF DIET SAMPLES (UA-F-23.1)

EPA Science Inventory

The purpose of this SOP is to provide a uniform procedure for the financial reimbursement of primary respondents for the collection of diet samples. Respondents were reimbursed for replicate food and beverage samples by type and amount collected over a 24-hour sampling period. ...

NHEXAS PHASE I ARIZONA STUDY--STANDARD OPERATING PROCEDURE FOR REIMBURSEMENT FOR FIELD COLLECTION OF FOOD SAMPLES (UA-F-23.1)

EPA Science Inventory

The purpose of this SOP is to provide a uniform procedure for the financial reimbursement of primary respondents for the collection of diet samples. Respondents were reimbursed for replicate food and beverage samples by type and amount collected over a 24-hour sampling period. ...

Not all cultural values are created equal: Cultural change in China reexamined through Google books.

PubMed

Zhang, Rui; Weng, Liping

2017-06-20

Given its major transformations in recent decades, China has figured prominently in research on cultural change. Previous research converges in showing a general trend towards individualism in contemporary China while noting that rising individualism tends to coexist with enduring collectivism. To further understand this, we tested whether perceived traditional importance of cultural values would modulate the trajectory of cultural change reflected in word usage frequencies in published books. We re-analysed Google's Chinese corpus since 1980 based on a broad sample of words associated with individualism-collectivism. We replicated the pattern of rising individualism and declining collectivism among words of modest and low perceived traditional importance. Most important, however, collectivistic words of high perceived traditional importance increased in usage frequencies with time, thus departing from the general trend towards individualism. Overall, our research underscores the role of core culture in cultural maintenance during times of rapid cultural change. © 2017 International Union of Psychological Science.

Mindful attention and awareness: relationships with psychopathology and emotion regulation.

PubMed

Gregório, Sónia; Pinto-Gouveia, José

2013-01-01

The growing interest in mindfulness from the scientific community has originated several self-report measures of this psychological construct. The Mindful Attention and Awareness Scale (MAAS) is a self-report measure of mindfulness at a trait-level. This paper aims at exploring MAAS psychometric characteristics and validating it for the Portuguese population. The first two studies replicate some of the original author's statistical procedures in two different samples from the Portuguese general community population, in particular confirmatory factor analyses. Results from both analyses confirmed the scale single-factor structure and indicated a very good reliability. Moreover, cross-validation statistics showed that this single-factor structure is valid for different respondents from the general community population. In the third study the Portuguese version of the MAAS was found to have good convergent and discriminant validities. Overall the findings support the psychometric validity of the Portuguese version of MAAS and suggest this is a reliable self-report measure of trait-mindfulness, a central construct in Clinical Psychology research and intervention fields.

Hypnotism as a Function of Trance State Effects, Expectancy, and Suggestibility: An Italian Replication.

PubMed

Pekala, Ronald J; Baglio, Francesca; Cabinio, Monia; Lipari, Susanna; Baglio, Gisella; Mendozzi, Laura; Cecconi, Pietro; Pugnetti, Luigi; Sciaky, Riccardo

2017-01-01

Previous research using stepwise regression analyses found self-reported hypnotic depth (srHD) to be a function of suggestibility, trance state effects, and expectancy. This study sought to replicate and expand that research using a general state measure of hypnotic responsivity, the Phenomenology of Consciousness Inventory: Hypnotic Assessment Procedure (PCI-HAP). Ninety-five participants completed an Italian translation of the PCI-HAP, with srHD scores predicted from the PCI-HAP assessment items. The regression analysis replicated the previous research results. Additionally, stepwise regression analyses were able to predict the srHD score equally well using only the PCI dimension scores. These results not only replicated prior research but suggest how this methodology to assess hypnotic responsivity, when combined with more traditional neurophysiological and cognitive-behavioral methodologies, may allow for a more comprehensive understanding of that enigma called hypnosis.

Strong minor groove base conservation in sequence logos implies DNA distortion or base flipping during replication and transcription initiation.

PubMed

Schneider, T D

2001-12-01

The sequence logo for DNA binding sites of the bacteriophage P1 replication protein RepA shows unusually high sequence conservation ( approximately 2 bits) at a minor groove that faces RepA. However, B-form DNA can support only 1 bit of sequence conservation via contacts into the minor groove. The high conservation in RepA sites therefore implies a distorted DNA helix with direct or indirect contacts to the protein. Here I show that a high minor groove conservation signature also appears in sequence logos of sites for other replication origin binding proteins (Rts1, DnaA, P4 alpha, EBNA1, ORC) and promoter binding proteins (sigma(70), sigma(D) factors). This finding implies that DNA binding proteins generally use non-B-form DNA distortion such as base flipping to initiate replication and transcription.

Tandem duplication dup(X)(q13q22) in a male proband inherited from the mother showing mosaicism of X-inactivation.

PubMed

Steinbach, P; Horstmann, W; Scholz, W

1980-01-01

An aberrant X chromosome containing extra material in the long arm was observed in a psychomotoric retarded boy and his healthy, short-statured mother. The proband showed generalized muscular hypotony, growth retardation, and somatic anomalies including hypoplastic genitalia and cryptorchism. Chromosomal banding techniques suggested a tandem duplication of the segment Xq13 leads to Xq22. In the mother the vast majority of lymphocytes showed late replication of the aberrant X chromosome. Some of her cells, however, contained an apparently active aberrant X. Both the early- and late-replicating aberrant X exhibited late replication patterns very similar to those described for normal X chromosomes in lymphocytes. Asynchrony of DNA replication among the two segments Xq13 leads to Xq22 in the dup(X) was never observed. We consider that the clinical picture of the proband is caused by an excess of active X material.

RNA Recombination In Vivo in the Absence of Viral Replication

PubMed Central

Gallei, Andreas; Pankraz, Alexander; Thiel, Heinz-Jürgen; Becher, Paul

2004-01-01

To study fundamental aspects of RNA recombination, an in vivo RNA recombination system was established. This system allowed the efficient generation of recombinant cytopathogenic pestiviruses after transfection of synthetic, nonreplicatable, subgenomic transcripts in cells infected with a replicating noncytopathogenic virus. Studies addressing the interplay between RNA recombination and replication revealed that cotransfection of noninfected cells with various pairs of nonreplicatable RNA derivatives also led to the emergence of recombinant viral genomes. Remarkably, homologous and nonhomologous recombination occurred between two overlapping transcripts, each lacking different essential parts of the viral RNA-dependent RNA polymerase (RdRp) gene. Apart from the generally accepted viral replicative copy choice recombination, our results prove the existence of a viral RdRp-independent mechanism of RNA recombination that occurs in vivo. It appears likely that such a mechanism not only contributes to the evolution of RNA viruses but also leads to the generation of recombinant cellular RNAs. PMID:15163720

The difference between LSMC and replicating portfolio in insurance liability modeling.

PubMed

Pelsser, Antoon; Schweizer, Janina

2016-01-01

Solvency II requires insurers to calculate the 1-year value at risk of their balance sheet. This involves the valuation of the balance sheet in 1 year's time. As for insurance liabilities, closed-form solutions to their value are generally not available, insurers turn to estimation procedures. While pure Monte Carlo simulation set-ups are theoretically sound, they are often infeasible in practice. Therefore, approximation methods are exploited. Among these, least squares Monte Carlo (LSMC) and portfolio replication are prominent and widely applied in practice. In this paper, we show that, while both are variants of regression-based Monte Carlo methods, they differ in one significant aspect. While the replicating portfolio approach only contains an approximation error, which converges to zero in the limit, in LSMC a projection error is additionally present, which cannot be eliminated. It is revealed that the replicating portfolio technique enjoys numerous advantages and is therefore an attractive model choice.

Membranous Replication Factories Induced by Plus-Strand RNA Viruses

PubMed Central

Romero-Brey, Inés; Bartenschlager, Ralf

2014-01-01

In this review, we summarize the current knowledge about the membranous replication factories of members of plus-strand (+) RNA viruses. We discuss primarily the architecture of these complex membrane rearrangements, because this topic emerged in the last few years as electron tomography has become more widely available. A general denominator is that two “morphotypes” of membrane alterations can be found that are exemplified by flaviviruses and hepaciviruses: membrane invaginations towards the lumen of the endoplasmatic reticulum (ER) and double membrane vesicles, representing extrusions also originating from the ER, respectively. We hypothesize that either morphotype might reflect common pathways and principles that are used by these viruses to form their membranous replication compartments. PMID:25054883

Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time

PubMed Central

Forest, Marie; O'Donnell, Kieran J.; Voisin, Greg; Gaudreau, Helene; MacIsaac, Julia L.; McEwen, Lisa M.; Silveira, Patricia P.; Steiner, Meir; Kobor, Michael S.; Meaney, Michael J.; Greenwood, Celia M.T.

2018-01-01

ABSTRACT Epigenome-wide association studies (EWAS) have focused primarily on DNA methylation as a chemically stable and functional epigenetic modification. However, the stability and accuracy of the measurement of methylation in different tissues and extraction types is still being actively studied, and the longitudinal stability of DNA methylation in commonly studied peripheral tissues is of great interest. Here, we used data from two studies, three tissue types, and multiple time points to assess the stability of DNA methylation measured with the Illumina Infinium HumanMethylation450 BeadChip array. Redundancy analysis enabled visual assessment of agreement of replicate samples overall and showed good agreement after removing effects of tissue type, age, and sex. At the probe level, analysis of variance contrasts separating technical and biological replicates clearly showed better agreement between technical replicates versus longitudinal samples, and suggested increased stability for buccal cells versus blood or blood spots. Intraclass correlations (ICCs) demonstrated that inter-individual variability is of similar magnitude to within-sample variability at many probes; however, as inter-individual variability increased, so did ICC. Furthermore, we were able to demonstrate decreasing agreement in methylation levels with time, despite a maximal sampling interval of only 576 days. Finally, at 6 popular candidate genes, there was a large range of stability across probes. Our findings highlight important sources of technical and biological variation in DNA methylation across different tissues over time. These data will help to inform longitudinal sampling strategies of future EWAS. PMID:29381404

A human fecal contamination score for ranking recreational sites using the HF183/BacR287 quantitative real-time PCR method.

PubMed

Cao, Yiping; Sivaganesan, Mano; Kelty, Catherine A; Wang, Dan; Boehm, Alexandria B; Griffith, John F; Weisberg, Stephen B; Shanks, Orin C

2018-01-01

Human fecal pollution of recreational waters remains a public health concern worldwide. As a result, there is a growing interest in the application of human-associated fecal source identification quantitative real-time PCR (qPCR) technologies for water quality research and management. However, there are currently no standardized approaches for field implementation and interpretation of qPCR data. In this study, a standardized HF183/BacR287 qPCR method was combined with a water sampling strategy and a novel Bayesian weighted average approach to establish a human fecal contamination score (HFS) that can be used to prioritize sampling sites for remediation based on measured human waste levels. The HFS was then used to investigate 975 study design scenarios utilizing different combinations of sites with varying sampling intensities (daily to once per week) and number of qPCR replicates per sample (2-14 replicates). Findings demonstrate that site prioritization with HFS is feasible and that both sampling intensity and number of qPCR replicates influence reliability of HFS estimates. The novel data analysis strategy presented here provides a prescribed approach for the implementation and interpretation of human-associated HF183/BacR287 qPCR data with the goal of site prioritization based on human fecal pollution levels. In addition, information is provided for future users to customize study designs for optimal HFS performance. Published by Elsevier Ltd.

Factors influencing microinjection molding replication quality

NASA Astrophysics Data System (ADS)

Vera, Julie; Brulez, Anne-Catherine; Contraires, Elise; Larochette, Mathieu; Trannoy-Orban, Nathalie; Pignon, Maxime; Mauclair, Cyril; Valette, Stéphane; Benayoun, Stéphane

2018-01-01

In recent years, there has been increased interest in producing and providing high-precision plastic parts that can be manufactured by microinjection molding: gears, pumps, optical grating elements, and so on. For all of these applications, the replication quality is essential. This study has two goals: (1) fabrication of high-precision parts using the conventional injection molding machine; (2) identification of robust parameters that ensure production quality. Thus, different technological solutions have been used: cavity vacuuming and the use of a mold coated with DLC or CrN deposits. AFM and SEM analyses were carried out to characterize the replication profile. The replication quality was studied in terms of the process parameters, coated and uncoated molds and crystallinity of the polymer. Specific studies were processed to quantify the replicability of injection molded parts (ABS, PC and PP). Analysis of the Taguchi experimental designs permits prioritization of the impact of each parameter on the replication quality. A discussion taking into account these new parameters and the thermal and spreading properties on the coatings is proposed. It appeared that, in general, increasing the mold temperature improves the molten polymer fill in submicron features except for the steel insert (for which the presence of a vacuum is the most important factor). Moreover, the DLC coating was the best coating to increase the quality of the replication. This result could be explained by the lower thermal diffusivity of this coating. We noted that the viscosity of the polymers is not a primordial factor of the replication quality.

Regulated transport into the nucleus of herpesviridae DNA replication core proteins.

PubMed

Gualtiero, Alvisi; Jans, David A; Camozzi, Daria; Avanzi, Simone; Loregian, Arianna; Ripalti, Alessandro; Palù, Giorgio

2013-09-16

The Herpesvirdae family comprises several major human pathogens belonging to three distinct subfamilies. Their double stranded DNA genome is replicated in the nuclei of infected cells by a number of host and viral products. Among the latter the viral replication complex, whose activity is strictly required for viral replication, is composed of six different polypeptides, including a two-subunit DNA polymerase holoenzyme, a trimeric primase/helicase complex and a single stranded DNA binding protein. The study of herpesviral DNA replication machinery is extremely important, both because it provides an excellent model to understand processes related to eukaryotic DNA replication and it has important implications for the development of highly needed antiviral agents. Even though all known herpesviruses utilize very similar mechanisms for amplification of their genomes, the nuclear import of the replication complex components appears to be a heterogeneous and highly regulated process to ensure the correct spatiotemporal localization of each protein. The nuclear transport process of these enzymes is controlled by three mechanisms, typifying the main processes through which protein nuclear import is generally regulated in eukaryotic cells. These include cargo post-translational modification-based recognition by the intracellular transporters, piggy-back events allowing coordinated nuclear import of multimeric holoenzymes, and chaperone-assisted nuclear import of specific subunits. In this review we summarize these mechanisms and discuss potential implications for the development of antiviral compounds aimed at inhibiting the Herpesvirus life cycle by targeting nuclear import of the Herpesvirus DNA replicating enzymes.

Phylogenetic congruence of lichenised fungi and algae is affected by spatial scale and taxonomic diversity.

PubMed

Buckley, Hannah L; Rafat, Arash; Ridden, Johnathon D; Cruickshank, Robert H; Ridgway, Hayley J; Paterson, Adrian M

2014-01-01

The role of species' interactions in structuring biological communities remains unclear. Mutualistic symbioses, involving close positive interactions between two distinct organismal lineages, provide an excellent means to explore the roles of both evolutionary and ecological processes in determining how positive interactions affect community structure. In this study, we investigate patterns of co-diversification between fungi and algae for a range of New Zealand lichens at the community, genus, and species levels and explore explanations for possible patterns related to spatial scale and pattern, taxonomic diversity of the lichens considered, and the level sampling replication. We assembled six independent datasets to compare patterns in phylogenetic congruence with varied spatial extent of sampling, taxonomic diversity and level of specimen replication. For each dataset, we used the DNA sequences from the ITS regions of both the fungal and algal genomes from lichen specimens to produce genetic distance matrices. Phylogenetic congruence between fungi and algae was quantified using distance-based redundancy analysis and we used geographic distance matrices in Moran's eigenvector mapping and variance partitioning to evaluate the effects of spatial variation on the quantification of phylogenetic congruence. Phylogenetic congruence was highly significant for all datasets and a large proportion of variance in both algal and fungal genetic distances was explained by partner genetic variation. Spatial variables, primarily at large and intermediate scales, were also important for explaining genetic diversity patterns in all datasets. Interestingly, spatial structuring was stronger for fungal than algal genetic variation. As the spatial extent of the samples increased, so too did the proportion of explained variation that was shared between the spatial variables and the partners' genetic variation. Different lichen taxa showed some variation in their phylogenetic congruence and spatial genetic patterns and where greater sample replication was used, the amount of variation explained by partner genetic variation increased. Our results suggest that the phylogenetic congruence pattern, at least at small spatial scales, is likely due to reciprocal co-adaptation or co-dispersal. However, the detection of these patterns varies among different lichen taxa, across spatial scales and with different levels of sample replication. This work provides insight into the complexities faced in determining how evolutionary and ecological processes may interact to generate diversity in symbiotic association patterns at the population and community levels. Further, it highlights the critical importance of considering sample replication, taxonomic diversity and spatial scale in designing studies of co-diversification.

Replication and robustness in developmental research.

PubMed

Duncan, Greg J; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J

2014-11-01

Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key results are robust across estimation methods, data sets, and demographic subgroups. This article makes the case for prioritizing both explicit replications and, especially, within-study robustness checks in developmental psychology. It provides evidence on variation in effect sizes in developmental studies and documents strikingly different replication and robustness-checking practices in a sample of journals in developmental psychology and a sister behavioral science-applied economics. Our goal is not to show that any one behavioral science has a monopoly on best practices, but rather to show how journals from a related discipline address vital concerns of replication and generalizability shared by all social and behavioral sciences. We provide recommendations for promoting graduate training in replication and robustness-checking methods and for editorial policies that encourage these practices. Although some of our recommendations may shift the form and substance of developmental research articles, we argue that they would generate considerable scientific benefits for the field. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Does it actually feel right? A replication attempt of the rounded price effect.

PubMed

Harms, Christopher; Genau, Hanna A; Meschede, Carolin; Beauducel, André

2018-04-01

How does the roundedness of prices affect product evaluations? The 'rounded price effect' postulates that depending on the context, rounded or non-rounded prices increase the purchase likelihood of consumers. The study presented here is a replication attempt of these findings and the proposed mediation of the effect through a sense of 'feeling right' when evaluating the product. p -Curve analysis and the R-Index are used to assess the robustness of the originally reported statistics since original data were not available. A pre-registered replication of study 5 from the original article was conducted in a sample of N =588 participants. For both the original product and one alternative product neither an interaction between price roundedness and context, nor a mediation through 'a sense of feeling right' was found. Our results suggest that the effect is either smaller than originally reported or contingent on other, not investigated factors. Further studies might investigate contingencies in larger samples.

Does it actually feel right? A replication attempt of the rounded price effect

PubMed Central

Genau, Hanna A.; Meschede, Carolin; Beauducel, André

2018-01-01

How does the roundedness of prices affect product evaluations? The ‘rounded price effect’ postulates that depending on the context, rounded or non-rounded prices increase the purchase likelihood of consumers. The study presented here is a replication attempt of these findings and the proposed mediation of the effect through a sense of ‘feeling right’ when evaluating the product. p-Curve analysis and the R-Index are used to assess the robustness of the originally reported statistics since original data were not available. A pre-registered replication of study 5 from the original article was conducted in a sample of N=588 participants. For both the original product and one alternative product neither an interaction between price roundedness and context, nor a mediation through ‘a sense of feeling right’ was found. Our results suggest that the effect is either smaller than originally reported or contingent on other, not investigated factors. Further studies might investigate contingencies in larger samples. PMID:29765625

Colwater fish in rivers

EPA Science Inventory

A standard sampling protocol to assess the fish assemblages and abundances in large, coldwater rivers is most accurate and precise if consistent gears and levels of effort are used at each site. This requires thorough crew training, quality control audits, and replicate sampling...

An Array-Based Analysis of MicroRNA Expression Comparing Matched Frozen and Formalin-Fixed Paraffin-Embedded Human Tissue Samples

PubMed Central

Zhang, Xiao; Chen, Jiamin; Radcliffe, Tom; LeBrun, Dave P.; Tron, Victor A.; Feilotter, Harriet

2008-01-01

MicroRNAs (miRNAs) are small, noncoding RNAs that suppress gene expression at the posttranscriptional level via an antisense RNA-RNA interaction. miRNAs used for array-based profiling are generally purified from either snap-frozen or fresh samples. Because tissues found in most pathology departments are available only in formalin-fixed and paraffin-embedded (FFPE) states, we sought to evaluate miRNA derived from FFPE samples for microarray analysis. In this study, miRNAs extracted from matched snap-frozen and FFPE samples were profiled using the Agilent miRNA array platform (Agilent, Santa Clara, CA). Each miRNA sample was hybridized to arrays containing probes interrogating 470 human miRNAs. Seven cases were compared in either duplicate or triplicate. Intrachip and interchip analyses demonstrated that the processes of miRNA extraction, labeling, and hybridization from both frozen and FFPE samples are highly reproducible and add little variation to the results; technical replicates showed high correlations with one another (Kendall tau, 0.722 to 0.853; Spearman rank correlation coefficient, 0.891 to 0.954). Our results showed consistent high correlations between matched frozen and FFPE samples (Kendall tau, 0.669 to 0.815; Spearman rank correlation coefficient, 0.847 to 0.948), supporting the use of FFPE-derived miRNAs for array-based, gene expression profiling. PMID:18832457

Polygenic Risk Score for Alzheimer's Disease: Implications for Memory Performance and Hippocampal Volumes in Early Life.

PubMed

Axelrud, Luiza K; Santoro, Marcos L; Pine, Daniel S; Talarico, Fernanda; Gadelha, Ary; Manfro, Gisele G; Pan, Pedro M; Jackowski, Andrea; Picon, Felipe; Brietzke, Elisa; Grassi-Oliveira, Rodrigo; Bressan, Rodrigo A; Miguel, Eurípedes C; Rohde, Luis A; Hakonarson, Hakon; Pausova, Zdenka; Belangero, Sintia; Paus, Tomas; Salum, Giovanni A

2018-06-01

Alzheimer's disease is a heritable neurodegenerative disorder in which early-life precursors may manifest in cognition and brain structure. The authors evaluate this possibility by examining, in youths, associations among polygenic risk score for Alzheimer's disease, cognitive abilities, and hippocampal volume. Participants were children 6-14 years of age in two Brazilian cities, constituting the discovery (N=364) and replication samples (N=352). As an additional replication, data from a Canadian sample (N=1,029), with distinct tasks, MRI protocol, and genetic risk, were included. Cognitive tests quantified memory and executive function. Reading and writing abilities were assessed by standardized tests. Hippocampal volumes were derived from the Multiple Automatically Generated Templates (MAGeT) multi-atlas segmentation brain algorithm. Genetic risk for Alzheimer's disease was quantified using summary statistics from the International Genomics of Alzheimer's Project. Analyses showed that for the Brazilian discovery sample, each one-unit increase in z-score for Alzheimer's polygenic risk score significantly predicted a 0.185 decrement in z-score for immediate recall and a 0.282 decrement for delayed recall. Findings were similar for the Brazilian replication sample (immediate and delayed recall, β=-0.259 and β=-0.232, both significant). Quantile regressions showed lower hippocampal volumes bilaterally for individuals with high polygenic risk scores. Associations fell short of significance for the Canadian sample. Genetic risk for Alzheimer's disease may affect early-life cognition and hippocampal volumes, as shown in two independent samples. These data support previous evidence that some forms of late-life dementia may represent developmental conditions with roots in childhood. This result may vary depending on a sample's genetic risk and may be specific to some types of memory tasks.

Sample size calculations for randomized clinical trials published in anesthesiology journals: a comparison of 2010 versus 2016.

PubMed

Chow, Jeffrey T Y; Turkstra, Timothy P; Yim, Edmund; Jones, Philip M

2018-06-01

Although every randomized clinical trial (RCT) needs participants, determining the ideal number of participants that balances limited resources and the ability to detect a real effect is difficult. Focussing on two-arm, parallel group, superiority RCTs published in six general anesthesiology journals, the objective of this study was to compare the quality of sample size calculations for RCTs published in 2010 vs 2016. Each RCT's full text was searched for the presence of a sample size calculation, and the assumptions made by the investigators were compared with the actual values observed in the results. Analyses were only performed for sample size calculations that were amenable to replication, defined as using a clearly identified outcome that was continuous or binary in a standard sample size calculation procedure. The percentage of RCTs reporting all sample size calculation assumptions increased from 51% in 2010 to 84% in 2016. The difference between the values observed in the study and the expected values used for the sample size calculation for most RCTs was usually > 10% of the expected value, with negligible improvement from 2010 to 2016. While the reporting of sample size calculations improved from 2010 to 2016, the expected values in these sample size calculations often assumed effect sizes larger than those actually observed in the study. Since overly optimistic assumptions may systematically lead to underpowered RCTs, improvements in how to calculate and report sample sizes in anesthesiology research are needed.

Selenium concentrations in leaf material from Astragalus oxyphysus (Diablo Locoweed) and Atriplex lentiformis (quail bush) in the interior coast ranges and the western San Joaquin Valley, California

DOE Office of Scientific and Technical Information (OSTI.GOV)

Izbicki, J.A.; Harms, T.F.

1986-01-01

Leaf material from selenium accumulating plants was collected and analyzed for selenium to obtain a relative indication of selenium concentrations in soils and identify sites suitable for further soil study. Selenium concentrations of 14 samples of leaf material from Astragalus oxyphysus ranged from 0.08 to 3.5 microg/g dry weight and had a median concentration of 0.25 microg/g. Five replicate samples of A. oxyphysus had a mean selenium concentration of 0.22 microg/g and a standard deviation of 0.07. Selenium concentrations of 17 samples of leaf material from Atriplex lentiformis ranged from 0.08 to 7.5 microg/g and had a median concentration ofmore » 0.35 microg/g. As a general guideline, the National Academy of Sciences recommends a maximum safe tolerance level of 2 microg/g of selenium in animal feeds. One sample of A. oxyphysus, collected in the Panoche Creek drainage, exceeded 2 microg/g. Three samples of A. lentiformis, collected in Klipstein Canyon, Tumey Fan, and Panoche Fan, equaled or exceeded 2 microg/g. These sites may be suitable. 34 refs., 5 figs., 2 tabs.« less

MMPI-2 characteristics of the Old Order Amish: a comparison of clinical, nonclinical, and United States normative samples.

PubMed

Knabb, Joshua J; Vogt, Ronald G; Newgren, Kevin P

2011-12-01

[Correction Notice: An erratum for this article was reported in Vol 23(4) of Psychological Assessment (see record 2011-12640-001). The article contains an error under the Participants and Procedure heading. This is addressed in the correction.] In the current study, we investigated Minnesota Multiphasic Personality Inventory-2 (MMPI-2) characteristics in an Old Order Amish nonclinical sample (N = 84), comparing these data with both the United States normative sample (N = 2,600) and a sample of Old Order Amish outpatients (N = 136). Consistent with our hypothesis, the Old Order Amish nonclinical group scored similarly to the United States normative sample and lower than the Old Order Amish outpatients on most scales. Thus, overall, the MMPI-2 appears to be sensitive to psychopathology, especially depression and psychosis, among Old Order Amish test takers. Still, several Validity, Clinical, Supplementary, Content, and Personality Psychopathology Five (PSY-5) scale score differences materialized between the Old Order Amish nonclinical group and the United States group, suggesting that certain MMPI-2 scales may need to be interpreted differently for Old Order Amish test takers. Further MMPI-2 research is needed with the Old Order Amish to replicate and generalize our findings. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

In situ passive sampling of sediments in the Lower Duwamish Waterway Superfund site: Replicability, comparison with ex situ measurements, and use of data.

PubMed

Apell, Jennifer N; Gschwend, Philip M

2016-11-01

Superfund sites with sediments contaminated by hydrophobic organic compounds (HOCs) can be difficult to characterize because of the complex nature of sorption to sediments. Porewater concentrations, which are often used to model transport of HOCs from the sediment bed into overlying water, benthic organisms, and the larger food web, are traditionally estimated using sediment concentrations and sorption coefficients estimated using equilibrium partitioning (EqP) theory. However, researchers have begun using polymeric samplers to determine porewater concentrations since this method does not require knowledge of the sediment's sorption properties. In this work, polyethylene passive samplers were deployed into sediments in the field (in situ passive sampling) and mixed with sediments in the laboratory (ex situ active sampling) that were contaminated with polychlorinated biphenyls (PCBs). The results show that porewater concentrations based on in situ and ex situ sampling generally agreed within a factor of two, but in situ concentrations were consistently lower than ex situ porewater concentrations. Imprecision arising from in situ passive sampling procedures does not explain this bias suggesting that field processes like bioirrigation may cause the differences observed between in situ and ex situ polymeric samplers. Copyright © 2016 Elsevier Ltd. All rights reserved.

A content analysis of research published in the Journal of Research in Science Teaching from 1985 through 1989

NASA Astrophysics Data System (ADS)

Horton, Phillip B.; McConney, Andrew A.; Woods, Amanda L.; Barry, Kevin; Krout, Homer L., II; Doyle, Barbara K.

To determine if actual practice was consistent with commonly recommended research methods and procedures, this study examined 130 studies reported over a 5-year period in three volumes of the Journal of Research in Science Teaching (JRST). The results were consistent with similar previous analyses (Shaver & Norton, 1980a, 1980b; Wallen & Fraenkel, 1988a) and indicate that appropriate generalizations beyond the confines of the reported studies may be impossible for most (64%) of the JRST studies surveyed. The findings also show that replication studies, which could be employed to offset deficiencies in generalizability, were not commonly encountered (3%) in these 130 reports. In addition, the study results indicate that many researchers (48%) do not properly restrict their conclusions based on the limits imposed by the accessible populations and samples used; nor do they typically provide possible alternative explanations for the outcomes obtained (76%). These findings prompt the following recommendations:1. A greater awareness and use of replication as a check on generalizability should be encouraged by the science education community.2. Clearly defined populations (target and accessible) and fully described samples warrant increased attention as report components from authors, reviewers, and editorial board members of JRST.3. In light of the difficulties inherent in effecting random selection in educational settings, a greater emphasis should be placed on recognizing the limits that the underlying assumptions of inferential statistics place on research conclusions.The results of this study indicate that the methodological quality of published science education research should remain a concern for both practitioners and readers.

Persistence of ZIKV-RNA in the cellular fraction of semen is accompanied by a surrogate-marker of viral replication. Diagnostic implications for sexual transmission.

PubMed

Biava, Mirella; Caglioti, Claudia; Castilletti, Concetta; Bordi, Licia; Carletti, Fabrizio; Colavita, Francesca; Quartu, Serena; Nicastri, Emanuele; Iannetta, Marco; Vairo, Francesco; Liuzzi, Giuseppina; Taglietti, Fabrizio; Ippolito, Giuseppe; Capobianchi, Maria Rosaria; Lalle, Eleonora

2018-01-01

As asymptomatic infections represent 80% of ZIKV-infected individuals, sexual transmission is a rising concern. Recent studies highlighted a preferential association of ZIKV with the cellular fraction (CF) of different specimen types. Our aim was to evaluate the presence of ZIKV-RNA in different body fluids, focusing on semen specimens to assess the ZIKV-RNA content in either the unfractionated sample, its CF or seminal plasma (SP). In addition, to establish if the presence of ZIKV genome was associated with active virus replication, we measured the levels of negative-strand ZIKV-RNA. ZIKV total-RNA was detected in blood, urine and unfractionated semen, and neg-RNA in semen CF and SP samples longitudinally collected from two ZIKV-positive men followed at the National Institute for Infectious Diseases "L. Spallanzani", Italy. In both patients, ZIKV total-RNA was detected in CF with ct values always lower than in the corresponding unfractionated samples, and was observed even in the CF from negative unfractionated semen samples. In Patient 2, neg-RNA was also detected in CF, suggesting ongoing viral replication. Our results demonstrate higher clinical sensitivity of CF as compared to whole semen testing, emphasizing the need to extend ZIKV-RNA testing to CF, to rule out virus presence and the possible risk of sexual transmission.

Size Matters: Assessing Optimum Soil Sample Size for Fungal and Bacterial Community Structure Analyses Using High Throughput Sequencing of rRNA Gene Amplicons

PubMed Central

Penton, C. Ryan; Gupta, Vadakattu V. S. R.; Yu, Julian; Tiedje, James M.

2016-01-01

We examined the effect of different soil sample sizes obtained from an agricultural field, under a single cropping system uniform in soil properties and aboveground crop responses, on bacterial and fungal community structure and microbial diversity indices. DNA extracted from soil sample sizes of 0.25, 1, 5, and 10 g using MoBIO kits and from 10 and 100 g sizes using a bead-beating method (SARDI) were used as templates for high-throughput sequencing of 16S and 28S rRNA gene amplicons for bacteria and fungi, respectively, on the Illumina MiSeq and Roche 454 platforms. Sample size significantly affected overall bacterial and fungal community structure, replicate dispersion and the number of operational taxonomic units (OTUs) retrieved. Richness, evenness and diversity were also significantly affected. The largest diversity estimates were always associated with the 10 g MoBIO extractions with a corresponding reduction in replicate dispersion. For the fungal data, smaller MoBIO extractions identified more unclassified Eukaryota incertae sedis and unclassified glomeromycota while the SARDI method retrieved more abundant OTUs containing unclassified Pleosporales and the fungal genera Alternaria and Cercophora. Overall, these findings indicate that a 10 g soil DNA extraction is most suitable for both soil bacterial and fungal communities for retrieving optimal diversity while still capturing rarer taxa in concert with decreasing replicate variation. PMID:27313569

A Replication and Extension of the PEERS® for Young Adults Social Skills Intervention: Examining Effects on Social Skills and Social Anxiety in Young Adults with Autism Spectrum Disorder

ERIC Educational Resources Information Center

McVey, Alana J.; Dolan, Bridget K.; Willar, Kirsten S.; Pleiss, Sheryl; Karst, Jeffrey S.; Casnar, Christina L.; Caiozzo, Christina; Vogt, Elisabeth M.; Gordon, Nakia S.; Van Hecke, Amy Vaughan

2016-01-01

Young adults with ASD experience difficulties with social skills, empathy, loneliness, and social anxiety. One intervention, "PEERS® for Young Adults," shows promise in addressing these challenges. The present study replicated and extended the original study by recruiting a larger sample (N = 56), employing a gold standard ASD assessment…

Replication Capacity of Avian Influenza A(H9N2) Virus in Pet Birds and Mammals, Bangladesh.

PubMed

Lenny, Brian J; Shanmuganatham, Karthik; Sonnberg, Stephanie; Feeroz, Mohammed M; Alam, S M Rabiul; Hasan, M Kamrul; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webster, Robert G; Jones, Jeremy C

2015-12-01

Avian influenza A(H9N2) is an agricultural and public health threat. We characterized an H9N2 virus from a pet market in Bangladesh and demonstrated replication in samples from pet birds, swine tissues, human airway and ocular cells, and ferrets. Results implicated pet birds in the potential dissemination and zoonotic transmission of this virus.

Influence of CRTC1 polymorphisms on body mass index and fat mass in psychiatric patients and the general adult population.

PubMed

Choong, Eva; Quteineh, Lina; Cardinaux, Jean-René; Gholam-Rezaee, Mehdi; Vandenberghe, Frederik; Dobrinas, Maria; Bondolfi, Guido; Etter, Manuela; Holzer, Laurent; Magistretti, Pierre; von Gunten, Armin; Preisig, Martin; Vollenweider, Peter; Beckmann, Jacques S; Pralong, François P; Waeber, Gerard; Kutalik, Zoltan; Conus, Philippe; Bochud, Murielle; Eap, Chin B

2013-10-01

There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown. To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population. Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain-inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123,865). Noninterventional studies. Difference in BMI and/or fat mass between CRTC1 genotype groups. Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (P(adjusted) = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain-inducing drugs, G allele carriers (n = 98) had a 1.81-kg/m² lower BMI than noncarriers (n = 226; P < .0001). The strongest association was observed in women younger than 45 years, with a 3.87-kg/m² lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001), explaining 9% of BMI variance. In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r² = 0.7) was associated with lower BMI (sample 5, n = 123,865; P = .01) and fat mass (sample 4, n = 5338; P = .03). The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02). These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.

Co-infection with human polyomavirus BK enhances gene expression and replication of human adenovirus.

PubMed

Bil-Lula, Iwona; Woźniak, Mieczysław

2018-03-26

Immunocompromised patients are susceptible to multiple viral infections. Relevant interactions between co-infecting viruses might result from viral regulatory genes which trans-activate or repress the expression of host cell genes as well as the genes of any co-infecting virus. The aim of the current study was to show that the replication of human adenovirus 5 is enhanced by co-infection with BK polyomavirus and is associated with increased expression of proteins including early region 4 open reading frame 1 and both the large tumor antigen and small tumor antigen. Clinical samples of whole blood and urine from 156 hematopoietic stem cell transplant recipients were tested. We also inoculated adenocarcinomic human alveolar basal epithelial cells with both human adenovirus 5 and BK polyomavirus to evaluate if co-infection of viruses affected their replication. Data showed that adenovirus load was significantly higher in the plasma (mean 7.5 x 10 3  ± 8.5 x 10 2 copies/ml) and urine (mean 1.9 x 10 3  ± 8.0 x 10 2 copies/ml) of samples from patients with co-infections, in comparison to samples from patients with isolated adenovirus infection. In vitro co-infection led to an increased (8.6 times) expression of the adenovirus early region 4 open reading frame gene 48 hours post-inoculation. The expression of the early region 4 open reading frame gene positively correlated with the expression of BK polyomavirus large tumor antigen (r = 0.90, p < 0.0001) and small tumor antigen (r = 0.83, p < 0.001) genes. The enhanced expression of the early region 4 open reading frame gene due to co-infection with BK polyomavirus was associated with enhanced adenovirus, but not BK polyomavirus, replication. The current study provides evidence that co-infection of adenovirus and BK polyomavirus contributes to enhanced adenovirus replication. Data obtained from this study may have significant importance in the clinical setting.

Isolation and identification of age-related DNA methylation markers for forensic age-prediction.

PubMed

Yi, Shao Hua; Xu, Long Chang; Mei, Kun; Yang, Rong Zhi; Huang, Dai Xin

2014-07-01

Age-prediction is an important part of forensic science. There is no available method of individual age-prediction for general forensic biological samples at crime scenes. Accumulating evidence indicates that aging resembles a developmentally regulated process tightly controlled by specific age-associated methylation exists in human genome. This study isolated and identified eight gene fragments in which the degree of cytosine methylation is significantly correlated with age in blood of 40 donors. Furthermore, we validated two CpG sites of each gene fragment and replicated our results in a general population sample of 40 males and 25 females with a wide age-range (11-72 years). The methylation of these fragments is linear with age over a range of six decades (Fragment P1 (r=-0.64), P2 (r=-0.58), P3 (r=-0.79), R1 (r=0.82), R2 (r=0.63), R3 (r=0.59), R4 (r=0.63) and R5 (r=0.62)). Using average methylation of two CpG sites from each fragment, we built a regression model that explained 95% of the variance in age and is able to predict the age of an individual with great accuracy (R(2)=0.918). The predicted values are highly correlated with the observed age in the sample (r=0.91). This study implicates that DNA methylation will be an available biological marker of age-prediction. Furthermore, measurement of relevant sites in the genome could be a tool in routine forensic screening to predict age of biological samples. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Design and Sampling Plan Optimization for RT-qPCR Experiments in Plants: A Case Study in Blueberry.

PubMed

Die, Jose V; Roman, Belen; Flores, Fernando; Rowland, Lisa J

2016-01-01

The qPCR assay has become a routine technology in plant biotechnology and agricultural research. It is unlikely to be technically improved, but there are still challenges which center around minimizing the variability in results and transparency when reporting technical data in support of the conclusions of a study. There are a number of aspects of the pre- and post-assay workflow that contribute to variability of results. Here, through the study of the introduction of error in qPCR measurements at different stages of the workflow, we describe the most important causes of technical variability in a case study using blueberry. In this study, we found that the stage for which increasing the number of replicates would be the most beneficial depends on the tissue used. For example, we would recommend the use of more RT replicates when working with leaf tissue, while the use of more sampling (RNA extraction) replicates would be recommended when working with stems or fruits to obtain the most optimal results. The use of more qPCR replicates provides the least benefit as it is the most reproducible step. By knowing the distribution of error over an entire experiment and the costs at each step, we have developed a script to identify the optimal sampling plan within the limits of a given budget. These findings should help plant scientists improve the design of qPCR experiments and refine their laboratory practices in order to conduct qPCR assays in a more reliable-manner to produce more consistent and reproducible data.

Media multitasking and behavioral measures of sustained attention.

PubMed

Ralph, Brandon C W; Thomson, David R; Seli, Paul; Carriere, Jonathan S A; Smilek, Daniel

2015-02-01

In a series of four studies, self-reported media multitasking (using the media multitasking index; MMI) and general sustained-attention ability, through performance on three sustained-attention tasks: the metronome response task (MRT), the sustained-attention-to-response task (SART), and a vigilance task (here, a modified version of the SART). In Study 1, we found that higher reports of media multitasking were associated with increased response variability (i.e., poor performance) on the MRT. However, in Study 2, no association between reported media multitasking and performance on the SART was observed. These findings were replicated in Studies 3a and 3b, in which we again assessed the relation between media multitasking and performance on both the MRT and SART in two large online samples. Finally, in Study 4, using a large online sample, we tested whether media multitasking was associated with performance on a vigilance task. Although standard vigilance decrements were observed in both sensitivity (A') and response times, media multitasking was not associated with the size of these decrements, nor was media multitasking associated with overall performance, in terms of either sensitivity or response times. Taken together, the results of the studies reported here failed to demonstrate a relation between habitual engagement in media multitasking in everyday life and a general deficit in sustained-attention processes.

Adaptation and initial validation of the Patient Health Questionnaire - 9 (PHQ-9) and the Generalized Anxiety Disorder - 7 Questionnaire (GAD-7) in an Arabic speaking Lebanese psychiatric outpatient sample.

PubMed

Sawaya, Helen; Atoui, Mia; Hamadeh, Aya; Zeinoun, Pia; Nahas, Ziad

2016-05-30

The Patient Health Questionnaire - 9 (PHQ-9) and Generalized Anxiety Disorder - 7 (GAD-7) are short screening measures used in medical and community settings to assess depression and anxiety severity. The aim of this study is to translate the screening tools into Arabic and evaluate their psychometric properties in an Arabic-speaking Lebanese psychiatric outpatient sample. The patients completed the questionnaires, among others, prior to being evaluated by a clinical psychiatrist or psychologist. The scales' internal consistency and factor structure were measured and convergent and discriminant validity were established by comparing the scores with clinical diagnoses and the Psychiatric Diagnostic Screening Questionnaire - MDD subset (PDSQ - MDD). Results showed that the PHQ-9 and GAD-7 are reliable screening tools for depression and anxiety and their factor structures replicated those reported in the literature. Sensitivity and specificity analyses showed that the PHQ-9 is sensitive but not specific at capturing depressive symptoms when compared to clinician diagnoses whereas the GAD-7 was neither sensitive nor specific at capturing anxiety symptoms. The implications of these findings are discussed in reference to the scales themselves and the cultural specificity of the Lebanese population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Maternal prenatal psychological distress and temperament in 1-4 month old infants - A study in a non-western population.

PubMed

Bhat, Amritha; Chowdayya, Roopashree; Selvam, Sumithra; Khan, Arif; Kolts, Russell; Srinivasan, Krishnamachari

2015-05-01

In this longitudinal study, conducted in women attending antenatal visits at the obstetrics and gynecology clinic of a general hospital in Bangalore, India, we aimed to assess the relationship between prenatal distress in mothers, and maternal report of infant temperament at four months. 100 mothers with normal full term deliveries completed the General Health Questionnaire-28 item version (GHQ) in the third trimester and postnatally. Salivary cortisol and temperament (using the Early Infancy Temperament Questionnaire - EITQ) were assessed in their infants aged 1-4 months. In this study, maternal prenatal psychological distress was not significantly associated with maternal report of difficult temperament in infants. Infants of mothers who were a negative screen for psychological distress (GHQ<7), n=85 had higher scores on the adaptability and approach dimensions of temperament. Infant salivary cortisol was significantly higher in infants with higher intensity scores. These results introduce the possibility of cultural differences in the relationship between prenatal distress in the mother and infant temperament. These could be factors linked to child rearing practices or to the measures employed to study infant temperament. These findings derive from a small sample with few mothers with psychological distress, and need replication in a larger sample. Copyright © 2015 Elsevier Inc. All rights reserved.

Replication of Human Herpesviruses Is Associated with Higher HIV DNA Levels during Antiretroviral Therapy Started at Early Phases of HIV Infection

PubMed Central

Anderson, Christy M.; Var, Susanna R.; Oliveira, Michelli F.; Lada, Steven M.; Vargas, Milenka V.; Little, Susan J.; Richman, Douglas D.; Strain, Matthew C.; Pérez-Santiago, Josué; Smith, Davey M.

2016-01-01

ABSTRACT Asymptomatic replication of human herpesviruses (HHV) is frequent in HIV-infected men and is associated with increased T-cell activation and HIV disease progression. We hypothesized that the presence of replication of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) (the most frequently detected HHV) might influence HIV DNA decay during antiretroviral therapy (ART). We investigated 607 peripheral blood mononuclear cell (PBMC) samples from 107 CMV-seropositive, HIV-infected men who have sex with men, who started ART within a median of 3 months from their estimated date of infection (EDI) and were monitored for a median of 19 months thereafter. Levels of HIV, CMV, and EBV DNA and cellular HIV RNA were measured by droplet digital PCR (ddPCR) for each time point. Using a general linear mixed-effect regression model, we evaluated associations between the presence of detectable CMV DNA and EBV DNA levels and HIV DNA decay and cellular HIV RNA levels, while adjusting for peak HIV RNA, nadir CD4+ count, CD4/CD8 ratio, CMV IgG levels, time from EDI to ART initiation, time from ART initiation to virologic suppression, detectable CMV DNA pre-ART, and age. The presence of intermittent CMV DNA in PBMC during ART was significantly associated with slower decay of HIV DNA (P = 0.011) but not with increased cellular HIV RNA transcription or more detectable 2-long terminal repeat circles. Higher levels of EBV DNA were also associated with higher levels of HIV DNA (P < 0.001) and increased unspliced cellular HIV RNA transcription (P = 0.010). These observations suggest that replication of HHV may help maintain a larger HIV DNA reservoir, but the underlying mechanisms remain unclear. IMPORTANCE Over three-fourths of HIV-infected men have at least one actively replicating human herpesvirus (HHV) in their mucosal secretions at any one time. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the most common, and although it is often asymptomatic, such CMV and EBV replication is associated with higher levels of immune activation and HIV disease progression. We hypothesized that HHV-associated activation of HIV-infected CD4+ T cells might lead to increased HIV DNA. This study found that detectable CMV in blood cells of HIV-infected men was associated with slower decay of HIV DNA even during antiretroviral therapy (ART) that was started during early HIV infection. Similarly, levels of EBV DNA were associated with higher levels of HIV DNA during ART. If this observation points to a causal pathway, interventions that control CMV and EBV replication may be able to reduce the HIV reservoir, which might be relevant to current HIV cure efforts. PMID:26842469

Detection of porcine circovirus type 2 and viral replication by in situ hybridization in primary lymphoid organs from naturally and experimentally infected pigs.

PubMed

Hansen, M S; Segalés, J; Fernandes, L T; Grau-Roma, L; Bille-Hansen, V; Larsen, L E; Nielsen, O L

2013-11-01

Porcine circovirus type 2 (PCV2) infection is the cause of postweaning multisystemic wasting syndrome (PMWS). It has been speculated whether cell types permissive of replication are found in the primary lymphoid organs and whether infection of these tissues has an important role in the pathogenesis of PMWS. The aim of this study was to determine if primary lymphoid organ cells support viral replication during PCV2 infection. This was done by histopathological examination of thymus and bone marrow from pigs experimentally inoculated with PCV2 (n = 24), mock-infected pigs (n = 12), pigs naturally affected by PMWS (n = 33), and age-matched healthy control animals (n = 29). In situ hybridization (ISH) techniques were used to detect PCV2 nucleic acid irrespective of replicative status (complementary probe, CP) or to detect only the replicative form of the virus (replicative form probe, RFP). PCV2 was not detected in the experimentally PCV2-inoculated pigs or the control animals. Among the PMWS-affected pigs, 19 of 20 (95%) thymuses were positive for PCV2 by CP ISH, and 7 of 19 (37%) of these also supported viral replication. By CP ISH, PCV2 was detected in 16 of 33 (48%) bone marrow samples, and 5 of 16 (31%) of these also supported replication. The 2 ISH probes labeled the same cell types, which were histiocytes in both organs and lymphocytes in thymus. The RFP labeled fewer cells than the CP. Thus, PCV2 nucleic acids and replication were found in bone marrow and thymus of PMWS-affected pigs, but there was no evidence that primary lymphoid organ cells are major supporters of PCV2 replication.

Analysis of replication factories in human cells by super-resolution light microscopy

PubMed Central

2009-01-01

Background DNA replication in human cells is performed in discrete sub-nuclear locations known as replication foci or factories. These factories form in the nucleus during S phase and are sites of DNA synthesis and high local concentrations of enzymes required for chromatin replication. Why these structures are required, and how they are organised internally has yet to be identified. It has been difficult to analyse the structure of these factories as they are small in size and thus below the resolution limit of the standard confocal microscope. We have used stimulated emission depletion (STED) microscopy, which improves on the resolving power of the confocal microscope, to probe the structure of these factories at sub-diffraction limit resolution. Results Using immunofluorescent imaging of PCNA (proliferating cell nuclear antigen) and RPA (replication protein A) we show that factories are smaller in size (approximately 150 nm diameter), and greater in number (up to 1400 in an early S- phase nucleus), than is determined by confocal imaging. The replication inhibitor hydroxyurea caused an approximately 40% reduction in number and a 30% increase in diameter of replication factories, changes that were not clearly identified by standard confocal imaging. Conclusions These measurements for replication factory size now approach the dimensions suggested by electron microscopy. This agreement between these two methods, that use very different sample preparation and imaging conditions, suggests that we have arrived at a true measurement for the size of these structures. The number of individual factories present in a single nucleus that we measure using this system is greater than has been previously reported. This analysis therefore suggests that each replication factory contains fewer active replication forks than previously envisaged. PMID:20015367

In silico ribozyme evolution in a metabolically coupled RNA population.

PubMed

Könnyű, Balázs; Szilágyi, András; Czárán, Tamás

2015-05-27

The RNA World hypothesis offers a plausible bridge from no-life to life on prebiotic Earth, by assuming that RNA, the only known molecule type capable of playing genetic and catalytic roles at the same time, could have been the first evolvable entity on the evolutionary path to the first living cell. We have developed the Metabolically Coupled Replicator System (MCRS), a spatially explicit simulation modelling approach to prebiotic RNA-World evolution on mineral surfaces, in which we incorporate the most important experimental facts and theoretical considerations to comply with recent knowledge on RNA and prebiotic evolution. In this paper the MCRS model framework has been extended in order to investigate the dynamical and evolutionary consequences of adding an important physico-chemical detail, namely explicit replicator structure - nucleotide sequence and 2D folding calculated from thermodynamical criteria - and their possible mutational changes, to the assumptions of a previously less detailed toy model. For each mutable nucleotide sequence the corresponding 2D folded structure with minimum free energy is calculated, which in turn is used to determine the fitness components (degradation rate, replicability and metabolic enzyme activity) of the replicator. We show that the community of such replicators providing the monomer supply for their own replication by evolving metabolic enzyme activities features an improved propensity for stable coexistence and structural adaptation. These evolutionary advantages are due to the emergent uniformity of metabolic replicator fitnesses imposed on the community by local group selection and attained through replicator trait convergence, i.e., the tendency of replicator lengths, ribozyme activities and population sizes to become similar between the coevolving replicator species that are otherwise both structurally and functionally different. In the most general terms it is the surprisingly high extra viability of the metabolic replicator system that the present model adds to the MCRS concept of the origin of life. Surface-bound, metabolically coupled RNA replicators tend to evolve different, enzymatically active sites within thermodynamically stable secondary structures, and the system as a whole evolves towards the robust coexistence of a complete set of such ribozymes driving the metabolism producing monomers for their own replication.

Foliar and soil chemistry at red spruce sites in the Monongahela National Forest

Treesearch

Stephanie J. Connolly

2010-01-01

In 2005, soil and foliar chemistry were sampled from 10 sites in the Monongahela National Forest which support red spruce. Soils were sampled from hand-dug pits, by horizon, from the O-horizon to bedrock or 152 cm, and each pit was described fully. Replicate, archived samples also were collected.

Building a generalized distributed system model

NASA Technical Reports Server (NTRS)

Mukkamala, Ravi

1991-01-01

A number of topics related to building a generalized distributed system model are discussed. The effects of distributed database modeling on evaluation of transaction rollbacks, the measurement of effects of distributed database models on transaction availability measures, and a performance analysis of static locking in replicated distributed database systems are covered.

Quantitative and qualitative measure of intralaboratory two-dimensional protein gel reproducibility and the effects of sample preparation, sample load, and image analysis.

PubMed

Choe, Leila H; Lee, Kelvin H

2003-10-01

We investigate one approach to assess the quantitative variability in two-dimensional gel electrophoresis (2-DE) separations based on gel-to-gel variability, sample preparation variability, sample load differences, and the effect of automation on image analysis. We observe that 95% of spots present in three out of four replicate gels exhibit less than a 0.52 coefficient of variation (CV) in fluorescent stain intensity (% volume) for a single sample run on multiple gels. When four parallel sample preparations are performed, this value increases to 0.57. We do not observe any significant change in quantitative value for an increase or decrease in sample load of 30% when using appropriate image analysis variables. Increasing use of automation, while necessary in modern 2-DE experiments, does change the observed level of quantitative and qualitative variability among replicate gels. The number of spots that change qualitatively for a single sample run in parallel varies from a CV = 0.03 for fully manual analysis to CV = 0.20 for a fully automated analysis. We present a systematic method by which a single laboratory can measure gel-to-gel variability using only three gel runs.

Efficiently estimating salmon escapement uncertainty using systematically sampled data

USGS Publications Warehouse

Reynolds, Joel H.; Woody, Carol Ann; Gove, Nancy E.; Fair, Lowell F.

2007-01-01

Fish escapement is generally monitored using nonreplicated systematic sampling designs (e.g., via visual counts from towers or hydroacoustic counts). These sampling designs support a variety of methods for estimating the variance of the total escapement. Unfortunately, all the methods give biased results, with the magnitude of the bias being determined by the underlying process patterns. Fish escapement commonly exhibits positive autocorrelation and nonlinear patterns, such as diurnal and seasonal patterns. For these patterns, poor choice of variance estimator can needlessly increase the uncertainty managers have to deal with in sustaining fish populations. We illustrate the effect of sampling design and variance estimator choice on variance estimates of total escapement for anadromous salmonids from systematic samples of fish passage. Using simulated tower counts of sockeye salmon Oncorhynchus nerka escapement on the Kvichak River, Alaska, five variance estimators for nonreplicated systematic samples were compared to determine the least biased. Using the least biased variance estimator, four confidence interval estimators were compared for expected coverage and mean interval width. Finally, five systematic sampling designs were compared to determine the design giving the smallest average variance estimate for total annual escapement. For nonreplicated systematic samples of fish escapement, all variance estimators were positively biased. Compared to the other estimators, the least biased estimator reduced bias by, on average, from 12% to 98%. All confidence intervals gave effectively identical results. Replicated systematic sampling designs consistently provided the smallest average estimated variance among those compared.

Replication Study of the Milwaukee Inventory for Subtypes of Trichotillomania–Adult Version in a Clinically Characterized Sample

PubMed Central

Keuthen, Nancy J.; Tung, Esther S.; Woods, Douglas W.; Franklin, Martin E.; Altenburger, Erin M.; Pauls, David L.; Flessner, Christopher A.

2015-01-01

In the present study, we evaluated the Milwaukee Inventory for Subtypes of Trichotillomania–Adult Version (MIST-A) in a replication sample of clinically characterized hair pullers using exploratory factor analysis (EFA; N = 193). EFA eigenvalues and visual inspection of our scree plot revealed a two-factor solution. Factor structure coefficients and internal consistencies suggested a 13-item scale with an 8-item “Intention” scale and a 5-item “Emotion” scale. Both scales displayed good construct and discriminant validity. These findings indicate the need for a revised scale that provides a more refined assessment of pulling phenomenology that can facilitate future treatment advances. PMID:25868534

Fork rotation and DNA precatenation are restricted during DNA replication to prevent chromosomal instability.

PubMed

Schalbetter, Stephanie A; Mansoubi, Sahar; Chambers, Anna L; Downs, Jessica A; Baxter, Jonathan

2015-08-18

Faithful genome duplication and inheritance require the complete resolution of all intertwines within the parental DNA duplex. This is achieved by topoisomerase action ahead of the replication fork or by fork rotation and subsequent resolution of the DNA precatenation formed. Although fork rotation predominates at replication termination, in vitro studies have suggested that it also occurs frequently during elongation. However, the factors that influence fork rotation and how rotation and precatenation may influence other replication-associated processes are unknown. Here we analyze the causes and consequences of fork rotation in budding yeast. We find that fork rotation and precatenation preferentially occur in contexts that inhibit topoisomerase action ahead of the fork, including stable protein-DNA fragile sites and termination. However, generally, fork rotation and precatenation are actively inhibited by Timeless/Tof1 and Tipin/Csm3. In the absence of Tof1/Timeless, excessive fork rotation and precatenation cause extensive DNA damage following DNA replication. With Tof1, damage related to precatenation is focused on the fragile protein-DNA sites where fork rotation is induced. We conclude that although fork rotation and precatenation facilitate unwinding in hard-to-replicate contexts, they intrinsically disrupt normal chromosome duplication and are therefore restricted by Timeless/Tipin.

Diverse protist grazers select for virulence-related traits in Legionella

PubMed Central

Amaro, Francisco; Wang, Wen; Gilbert, Jack A; Roger Anderson, O; Shuman, Howard A

2015-01-01

It is generally accepted that selection for resistance to grazing by protists has contributed to the evolution of Legionella pneumophila as a pathogen. Grazing resistance is becoming more generally recognized as having an important role in the ecology and evolution of bacterial pathogenesis. However, selection for grazing resistance presupposes the existence of protist grazers that provide the selective pressure. To determine whether there are protists that graze on pathogenic Legionella species, we investigated the existence of such organisms in a variety of environmental samples. We isolated and characterized diverse protists that graze on L. pneumophila and determined the effects of adding L. pneumophila on the protist community structures in microcosms made from these environmental samples. Several unrelated organisms were able to graze efficiently on L. pneumophila. The community structures of all samples were markedly altered by the addition of L. pneumophila. Surprisingly, some of the Legionella grazers were closely related to species that are known hosts for L. pneumophila, indicating the presence of unknown specificity determinants for this interaction. These results provide the first direct support for the hypothesis that protist grazers exert selective pressure on Legionella to acquire and retain adaptations that contribute to survival, and that these properties are relevant to the ability of the bacteria to cause disease in people. We also report a novel mechanism of killing of amoebae by one Legionella species that requires an intact Type IV secretion system but does not involve intracellular replication. We refer to this phenomenon as ‘food poisoning'. PMID:25575308

Working with women prisoners who seriously harm themselves: ratings of staff expressed emotion (EE).

PubMed

Moore, Estelle; Andargachew, Sara; Taylor, Pamela J

2011-02-01

Prison staff are repeatedly exposed to prisoners' suicidal behaviours; this may impair their capacity to care. Expressed emotion (EE), as a descriptor of the 'emotional climate' between people, has been associated with challenging behaviour in closed environments, but not previously applied to working alliances in a prison. To investigate the feasibility of rating EE between staff and suicidal women in prison; to test the hypothesis that most such staff-inmate alliances would be rated high EE. All regular staff on two small UK prison units with high suicidal behaviour rates were invited to participate. An audiotaped five-minute speech sample (FMSS) about work with one nominated suicidal prisoner was embedded in a longer research interview, then rated by two trained raters, independent of the interview process and the prison. Seven prison officers and 8 clinically qualified staff completed interviews; 3 refused, but 17 others were not interviewed, reasons including not having worked long enough with any one such prisoner. Participants and non-participants had similar relevant backgrounds. Contrary to our hypothesis, EE ratings were generally 'low'. As predicted, critical comments were directed at high frequency oppositional behaviour. EE assessments with prison staff are feasible, but our sample was small and turnover of prisoners high, so the study needs replication. Attributions about problem behaviour to illness, and/or traumatic life experience, tend to confirm generally supportive working relationships in this sample. Copyright © 2010 John Wiley & Sons, Ltd.

Collection methods and quality assessment for Esche-richia coli, water quality, and microbial source tracking data within Tumacácori National Historical Park and the upper Santa Cruz River, Arizona, 2015-16

USGS Publications Warehouse

Paretti, Nicholas; Coes, Alissa L.; Kephart, Christopher M.; Mayo, Justine

2018-03-05

Tumacácori National Historical Park protects the culturally important Mission, San José de Tumacácori, while also managing a portion of the ecologically diverse riparian corridor of the Santa Cruz River. This report describes the methods and quality assurance procedures used in the collection of water samples for the analysis of Escherichia coli (E. coli), microbial source tracking markers, suspended sediment, water-quality parameters, turbidity, and the data collection for discharge and stage; the process for data review and approval is also described. Finally, this report provides a quantitative assessment of the quality of the E. coli, microbial source tracking, and suspended sediment data.The data-quality assessment revealed that bias attributed to field and laboratory contamination was minimal, with E. coli detections in only 3 out of 33 field blank samples analyzed. Concentrations in the field blanks were several orders of magnitude lower than environmental concentrations. The microbial source tracking (MST) field blank was below the detection limit for all MST markers analyzed. Laboratory blanks for E. coli at the USGS Arizona Water Science Center and laboratory blanks for MST markers at the USGS Ohio Water Microbiology Laboratory were all below the detection limit. Irreplicate data for E. coli and suspended sediment indicated that bias was not introduced to the data by combining samples collected using discrete sampling methods with samples collected using automatic sampling methods.The split and sequential E. coli replicate data showed consistent analytical variability and a single equation was developed to explain the variability of E. coli concentrations. An additional analysis of analytical variability for E. coli indicated analytical variability around 18 percent relative standard deviation and no trend was observed in the concentration during the processing and analysis of multiple split-replicates. Two replicate samples were collected for MST and individual markers were compared for a base flow and flood sample. For the markers found in common between the two types of samples, the relative standard deviation for the base flow sample was more than 3 times greater than the markers in the flood sample. Sequential suspended sediment replicates had a relative standard deviation of about 1.3 percent, indicating that environmental and analytical variability was minimal.A holding time review and laboratory study analysis supported the extended holding times required for this investigation. Most concentrations for flood and base-flow samples were within the theoretical variability specified in the most probable number approach suggesting that extended hold times did not overly influence the final concentrations reported.

An evaluation of the Bayesian approach to fitting the N-mixture model for use with pseudo-replicated count data

USGS Publications Warehouse

Toribo, S.G.; Gray, B.R.; Liang, S.

2011-01-01

The N-mixture model proposed by Royle in 2004 may be used to approximate the abundance and detection probability of animal species in a given region. In 2006, Royle and Dorazio discussed the advantages of using a Bayesian approach in modelling animal abundance and occurrence using a hierarchical N-mixture model. N-mixture models assume replication on sampling sites, an assumption that may be violated when the site is not closed to changes in abundance during the survey period or when nominal replicates are defined spatially. In this paper, we studied the robustness of a Bayesian approach to fitting the N-mixture model for pseudo-replicated count data. Our simulation results showed that the Bayesian estimates for abundance and detection probability are slightly biased when the actual detection probability is small and are sensitive to the presence of extra variability within local sites.

Escherichia coli sampling reliability at a frequently closed Chicago beach: monitoring and management implications

USGS Publications Warehouse

Whitman, Richard L.; Nevers, Meredith B.

2004-01-01

Monitoring beaches for recreational water quality is becoming more common, but few sampling designs or policy approaches have evaluated the efficacy of monitoring programs. The authors intensively sampled water for E. coli (N=1770) at 63rd Street Beach, Chicago for 6 months in 2000 in order to (1) characterize spatial-temporal trends, (2) determine between and within transect variation, and (3) estimate sample size requirements and determine sampling reliability.E. coli counts were highly variable within and between sampling sites but spatially and diurnally autocorrelated. Variation in counts decreased with water depth and time of day. Required number of samples was high for 70% precision around the critical closure level (i.e., 6 within or 24 between transect replicates). Since spatial replication may be cost prohibitive, composite sampling is an alternative once sources of error have been well defined. The results suggest that beach monitoring programs may be requiring too few samples to fulfill management objectives desired. As the recreational water quality national database is developed, it is important that sampling strategies are empirically derived from a thorough understanding of the sources of variation and the reliability of collected data. Greater monitoring efficacy will yield better policy decisions, risk assessments, programmatic goals, and future usefulness of the information.

Theoretical models for the regulation of DNA replication in fast-growing bacteria

NASA Astrophysics Data System (ADS)

Creutziger, Martin; Schmidt, Mischa; Lenz, Peter

2012-09-01

Growing in always changing environments, Escherichia coli cells are challenged by the task to coordinate growth and division. In particular, adaption of their growth program to the surrounding medium has to guarantee that the daughter cells obtain fully replicated chromosomes. Replication is therefore to be initiated at the right time, which is particularly challenging in media that support fast growth. Here, the mother cell initiates replication not only for the daughter but also for the granddaughter cells. This is possible only if replication occurs from several replication forks that all need to be correctly initiated. Despite considerable efforts during the last 40 years, regulation of this process is still unknown. Part of the difficulty arises from the fact that many details of the relevant molecular processes are not known. Here, we develop a novel theoretical strategy for dealing with this general problem: instead of analyzing a single model, we introduce a wide variety of 128 different models that make different assumptions about the unknown processes. By comparing the predictions of these models we are able to identify the key quantities that allow the experimental discrimination of the different models. Analysis of these quantities yields that out of the 128 models 94 are not consistent with available experimental data. From the remaining 34 models we are able to conclude that mass growth and DNA replication need either to be truly coupled, by coupling DNA replication initiation to the event of cell division, or to the amount of accumulated mass. Finally, we make suggestions for experiments to further reduce the number of possible regulation scenarios.

Differential replication dynamics for large and small Vibrio chromosomes affect gene dosage, expression and location

PubMed Central

Dryselius, Rikard; Izutsu, Kaori; Honda, Takeshi; Iida, Tetsuya

2008-01-01

Background Replication of bacterial chromosomes increases copy numbers of genes located near origins of replication relative to genes located near termini. Such differential gene dosage depends on replication rate, doubling time and chromosome size. Although little explored, differential gene dosage may influence both gene expression and location. For vibrios, a diverse family of fast growing gammaproteobacteria, gene dosage may be particularly important as they harbor two chromosomes of different size. Results Here we examined replication dynamics and gene dosage effects for the separate chromosomes of three Vibrio species. We also investigated locations for specific gene types within the genome. The results showed consistently larger gene dosage differences for the large chromosome which also initiated replication long before the small. Accordingly, large chromosome gene expression levels were generally higher and showed an influence from gene dosage. This was reflected by a higher abundance of growth essential and growth contributing genes of which many locate near the origin of replication. In contrast, small chromosome gene expression levels were low and appeared independent of gene dosage. Also, species specific genes are highly abundant and an over-representation of genes involved in transcription could explain its gene dosage independent expression. Conclusion Here we establish a link between replication dynamics and differential gene dosage on one hand and gene expression levels and the location of specific gene types on the other. For vibrios, this relationship appears connected to a polarisation of genetic content between its chromosomes, which may both contribute to and be enhanced by an improved adaptive capacity. PMID:19032792

Chromosome dynamics in the yeast interphase nucleus.

PubMed

Heun, P; Laroche, T; Shimada, K; Furrer, P; Gasser, S M

2001-12-07

Little is known about the dynamics of chromosomes in interphase nuclei. By tagging four chromosomal regions with a green fluorescent protein fusion to lac repressor, we monitored the movement and subnuclear position of specific sites in the yeast genome, sampling at short time intervals. We found that early and late origins of replication are highly mobile in G1 phase, frequently moving at or faster than 0.5 micrometers/10 seconds, in an energy-dependent fashion. The rapid diffusive movement of chromatin detected in G1 becomes constrained in S phase through a mechanism dependent on active DNA replication. In contrast, telomeres and centromeres provide replication-independent constraint on chromatin movement in both G1 and S phases.

Selection of recombinant MVA by rescue of the essential D4R gene.

PubMed

Ricci, Patricia S; Schäfer, Birgit; Kreil, Thomas R; Falkner, Falko G; Holzer, Georg W

2011-12-12

Modified vaccinia virus Ankara (MVA) has become a promising vaccine vector due to its immunogenicity and its proven safety in humans. As a general approach for stringent and rapid selection of recombinant MVA, we assessed marker rescue of the essential viral D4R gene in an engineered deletion mutant that is fully replication defective in wild-type cells. Recombinant, replicating virus was obtained by re-introduction of the deleted viral gene as a dominant selection marker into the deletion mutant.

Replication and shedding kinetics of infectious hematopoietic necrosis virus in juvenile rainbow trout

USGS Publications Warehouse

Wargo, Andrew R.; Scott, Robert J.; Kerr, Benjamin; Kurath, Gael

2017-01-01

Viral replication and shedding are key components of transmission and fitness, the kinetics of which are heavily dependent on virus, host, and environmental factors. To date, no studies have quantified the shedding kinetics of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss), or how they are associated with replication, making it difficult to ascertain the transmission dynamics of this pathogen of high agricultural and conservation importance. Here, the replication and shedding kinetics of two M genogroup IHNV genotypes were examined in their naturally co-evolved rainbow trout host. Within host virus replication began rapidly, approaching maximum values by day 3 post-infection, after which viral load was maintained or gradually dropped through day 7. Host innate immune response measured as stimulation of Mx-1 gene expression generally followed within host viral loads. Shedding also began very quickly and peaked within 2 days, defining a generally uniform early peak period of shedding from 1 to 4 days after exposure to virus. This was followed by a post-peak period where shedding declined, such that the majority of fish were no longer shedding by day 12 post-infection. Despite similar kinetics, the average shedding rate over the course of infection was significantly lower in mixed compared to single genotype infections, suggesting a competition effect, however, this did not significantly impact the total amount of virus shed. The data also indicated that the duration of shedding, rather than peak amount of virus shed, was correlated with fish mortality. Generally, the majority of virus produced during infection appeared to be shed into the environment rather than maintained in the host, although there was more retention of within host virus during the post-peak period. Viral virulence was correlated with shedding, such that the more virulent of the two genotypes shed more total virus. This fundamental understanding of IHNV shedding kinetics and variation at the individual fish level could assist with management decisions about how to respond to disease outbreaks when they occur.

Replication and shedding kinetics of infectious hematopoietic necrosis virus in juvenile rainbow trout.

PubMed

Wargo, Andrew R; Scott, Robert J; Kerr, Benjamin; Kurath, Gael

2017-01-02

Viral replication and shedding are key components of transmission and fitness, the kinetics of which are heavily dependent on virus, host, and environmental factors. To date, no studies have quantified the shedding kinetics of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss), or how they are associated with replication, making it difficult to ascertain the transmission dynamics of this pathogen of high agricultural and conservation importance. Here, the replication and shedding kinetics of two M genogroup IHNV genotypes were examined in their naturally co-evolved rainbow trout host. Within host virus replication began rapidly, approaching maximum values by day 3 post-infection, after which viral load was maintained or gradually dropped through day 7. Host innate immune response measured as stimulation of Mx-1 gene expression generally followed within host viral loads. Shedding also began very quickly and peaked within 2days, defining a generally uniform early peak period of shedding from 1 to 4days after exposure to virus. This was followed by a post-peak period where shedding declined, such that the majority of fish were no longer shedding by day 12 post-infection. Despite similar kinetics, the average shedding rate over the course of infection was significantly lower in mixed compared to single genotype infections, suggesting a competition effect, however, this did not significantly impact the total amount of virus shed. The data also indicated that the duration of shedding, rather than peak amount of virus shed, was correlated with fish mortality. Generally, the majority of virus produced during infection appeared to be shed into the environment rather than maintained in the host, although there was more retention of within host virus during the post-peak period. Viral virulence was correlated with shedding, such that the more virulent of the two genotypes shed more total virus. This fundamental understanding of IHNV shedding kinetics and variation at the individual fish level could assist with management decisions about how to respond to disease outbreaks when they occur. Copyright © 2016 Elsevier B.V. All rights reserved.

Replication and shedding kinetics of infectious hematopoietic necrosis virus in juvenile rainbow trout

PubMed Central

Wargo, Andrew R.; Scott, Robert J.; Kerr, Benjamin; Kurath, Gael

2016-01-01

Viral replication and shedding are key components of transmission and fitness, the kinetics of which are heavily dependent on virus, host, and environmental factors. To date, no studies have quantified the shedding kinetics of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss), or how they are associated with replication, making it difficult to ascertain the transmission dynamics of this pathogen of high agricultural and conservation importance. Here, the replication and shedding kinetics of two M genogroup IHNV genotypes were examined in their naturally co-evolved rainbow trout host. Within host virus replication began rapidly, approaching maximum values by day 3 post-infection, after which viral load was maintained or gradually dropped through day 7. Host innate immune response measured as stimulation of Mx-1 gene expression generally followed within host viral loads. Shedding also began very quickly and peaked within 2 days, defining a generally uniform early peak period of shedding from 1 to 4 days after exposure to virus. This was followed by a post-peak period where shedding declined, such that the majority offish were no longer shedding by day 12 post-infection. Despite similar kinetics, the average shedding rate over the course of infection was significantly lower in mixed compared to single genotype infections, suggesting a competition effect, however, this did not significantly impact the total amount of virus shed. The data also indicated that the duration of shedding, rather than peak amount of virus shed, was correlated with fish mortality. Generally, the majority of virus produced during infection appeared to be shed into the environment rather than maintained in the host, although there was more retention of within host virus during the post-peak period. Viral virulence was correlated with shedding, such that the more virulent of the two genotypes shed more total virus. This fundamental understanding of IHNV shedding kinetics and variation at the individual fish level could assist with management decisions about how to respond to disease outbreaks when they occur. PMID:27771253

RNA-seq: technical variability and sampling

PubMed Central

2011-01-01

Background RNA-seq is revolutionizing the way we study transcriptomes. mRNA can be surveyed without prior knowledge of gene transcripts. Alternative splicing of transcript isoforms and the identification of previously unknown exons are being reported. Initial reports of differences in exon usage, and splicing between samples as well as quantitative differences among samples are beginning to surface. Biological variation has been reported to be larger than technical variation. In addition, technical variation has been reported to be in line with expectations due to random sampling. However, strategies for dealing with technical variation will differ depending on the magnitude. The size of technical variance, and the role of sampling are examined in this manuscript. Results In this study three independent Solexa/Illumina experiments containing technical replicates are analyzed. When coverage is low, large disagreements between technical replicates are apparent. Exon detection between technical replicates is highly variable when the coverage is less than 5 reads per nucleotide and estimates of gene expression are more likely to disagree when coverage is low. Although large disagreements in the estimates of expression are observed at all levels of coverage. Conclusions Technical variability is too high to ignore. Technical variability results in inconsistent detection of exons at low levels of coverage. Further, the estimate of the relative abundance of a transcript can substantially disagree, even when coverage levels are high. This may be due to the low sampling fraction and if so, it will persist as an issue needing to be addressed in experimental design even as the next wave of technology produces larger numbers of reads. We provide practical recommendations for dealing with the technical variability, without dramatic cost increases. PMID:21645359

Development of a case-mix funding system for adults with combined vision and hearing loss.

PubMed

Guthrie, Dawn M; Poss, Jeffrey W

2013-04-15

Adults with vision and hearing loss, or dual sensory loss (DSL), present with a wide range of needs and abilities. This creates many challenges when attempting to set the most appropriate and equitable funding levels. Case-mix (CM) funding models represent one method for understanding client characteristics that correlate with resource intensity. A CM model was developed based on a derivation sample (n = 182) and tested with a replication sample (n = 135) of adults aged 18+ with known DSL who were living in the community. All items within the CM model came from a standardized, multidimensional assessment, the interRAI Community Health Assessment and the Deafblind Supplement. The main outcome was a summary of formal and informal service costs which included intervenor and interpreter support, in-home nursing, personal support and rehabilitation services. Informal costs were estimated based on a wage rate of half that for a professional service provider ($10/hour). Decision-tree analysis was used to create groups with homogeneous resource utilization. The resulting CM model had 9 terminal nodes. The CM index (CMI) showed a 35-fold range for total costs. In both the derivation and replication sample, 4 groups (out of a total of 18 or 22.2%) had a coefficient of variation value that exceeded the overall level of variation. Explained variance in the derivation sample was 67.7% for total costs versus 28.2% in the replication sample. A strong correlation was observed between the CMI values in the two samples (r = 0.82; p = 0.006). The derived CM funding model for adults with DSL differentiates resource intensity across 9 main groups and in both datasets there is evidence that these CM groups appropriately identify clients based on need for formal and informal support.

Concentrated ERP Delivered in a Group Setting: A Replication Study.

PubMed

Havnen, Audun; Hansen, Bjarne; Öst, Lars-Göran; Kvale, Gerd

2017-09-01

In a previous effectiveness study (Havnen et al., 2014), 35 obsessive compulsive disorder (OCD) patients underwent Concentrated Exposure Treatment (cET), which is a newly developed group treatment format delivered over four consecutive days. The primary aims of the present study were to evaluate the treatment results for a new sample of OCD patients receiving the cET treatment approach and to replicate the effectiveness study described in Havnen et al. (2014). Forty-two OCD patients underwent cET treatment. Treatment was delivered by different therapists than in Havnen et al. (2014), except for two groups led by the developers of the treatment. Assessments of OCD symptom severity, treatment satisfaction, and occupational impairment were included. The results showed a significant reduction in Yale-Brown Obsessive Compulsive Scale scores from pre-treatment to post-treatment, which was maintained at 6-month follow-up. At post-treatment, 74% of the sample was remitted; at 6-month follow-up, 60% were recovered. The sample showed a very high degree of overall treatment satisfaction. The results from the present study were statistically compared with those obtained in the previous study. The analyses showed that the study samples had comparable demographic data and equal application of treatment. The outcome of the present and original study did not differ significantly on primary and secondary outcome measures. This study shows that cET was successfully replicated in a new patient sample treated by different therapists than the original study. The results indicate that cET is well accepted by the patients, and the potential for dissemination is discussed.

Progress in tropical isotope dendroclimatology

NASA Astrophysics Data System (ADS)

Evans, M. N.; Schrag, D. P.; Poussart, P. F.; Anchukaitis, K. J.

2005-12-01

The terrestrial tropics remain an important gap in the growing high resolution proxy network used to characterize the mean state and variability of the hydrological cycle. Here we review early efforts to develop a new class of proxy paleorainfall/humidity indicators using intraseasonal to interannual-resolution stable isotope data from tropical trees. The approach invokes a recently published model of oxygen isotopic composition of alpha-cellulose, rapid methods for cellulose extraction from raw wood, and continuous flow isotope ratio mass spectrometry to develop proxy chronological, rainfall and growth rate estimates from tropical trees, even those lacking annual rings. Isotopically-derived age models may be confirmed for modern intervals using trees of known age, radiocarbon measurements, direct measurements of tree diameter, and time series replication. Studies are now underway at a number of laboratories on samples from Costa Rica, northwestern coastal Peru, Indonesia, Thailand, New Guinea, Paraguay, Brazil, India, and the South American Altiplano. Improved sample extraction chemistry and online pyrolysis techniques should increase sample throughput, precision, and time series replication. Statistical calibration together with simple forward modeling based on the well-observed modern period can provide for objective interpretation of the data. Ultimately, replicated data series with well-defined uncertainties can be entered into multiproxy efforts to define aspects of tropical hydrological variability associated with ENSO, the meridional overturning circulation, and the monsoon systems.

Common Variants of the Liver Fatty Acid Binding Protein Gene Influence the Risk of Type 2 Diabetes and Insulin Resistance in Spanish Population

PubMed Central

Mansego, Maria Luisa; Martínez, Fernando; Martínez-Larrad, Maria Teresa; Zabena, Carina; Rojo, Gemma; Morcillo, Sonsoles; Soriguer, Federico; Martín-Escudero, Juan Carlos; Serrano-Ríos, Manuel; Redon, Josep; Chaves, Felipe Javier

2012-01-01

Summary The main objective was to evaluate the association between SNPs and haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction with fat intake, in one general Spanish population. The association was replicated in a second population in which HOMA index was also evaluated. Methods 1217 unrelated individuals were selected from a population-based study [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The replication population included 805 subjects from Segovia, a neighboring region of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes). DM2 mellitus was defined in a similar way in both studies. Fifteen SNPs previously associated with metabolic traits or with potential influence in the gene expression within the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were used as covariates in the logistic regression model. Results One polymorphism (rs2197076) and two haplotypes of the FABP-1 showed a strong association with the risk of DM2 in the original population. This association was further confirmed in the second population as well as in the pooled sample. None of the other analyzed variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal interaction between rs2197076 and fat intake. A significant association between the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the replication population. Conclusions The study supports the role of common variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians. PMID:22396741

Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology

PubMed Central

Legendre, Matthieu; Bartoli, Julia; Shmakova, Lyubov; Jeudy, Sandra; Labadie, Karine; Adrait, Annie; Lescot, Magali; Poirot, Olivier; Bertaux, Lionel; Bruley, Christophe; Couté, Yohann; Rivkina, Elizaveta; Abergel, Chantal; Claverie, Jean-Michel

2014-01-01

The largest known DNA viruses infect Acanthamoeba and belong to two markedly different families. The Megaviridae exhibit pseudo-icosahedral virions up to 0.7 μm in diameter and adenine–thymine (AT)-rich genomes of up to 1.25 Mb encoding a thousand proteins. Like their Mimivirus prototype discovered 10 y ago, they entirely replicate within cytoplasmic virion factories. In contrast, the recently discovered Pandoraviruses exhibit larger amphora-shaped virions 1 μm in length and guanine–cytosine-rich genomes up to 2.8 Mb long encoding up to 2,500 proteins. Their replication involves the host nucleus. Whereas the Megaviridae share some general features with the previously described icosahedral large DNA viruses, the Pandoraviruses appear unrelated to them. Here we report the discovery of a third type of giant virus combining an even larger pandoravirus-like particle 1.5 μm in length with a surprisingly smaller 600 kb AT-rich genome, a gene content more similar to Iridoviruses and Marseillevirus, and a fully cytoplasmic replication reminiscent of the Megaviridae. This suggests that pandoravirus-like particles may be associated with a variety of virus families more diverse than previously envisioned. This giant virus, named Pithovirus sibericum, was isolated from a >30,000-y-old radiocarbon-dated sample when we initiated a survey of the virome of Siberian permafrost. The revival of such an ancestral amoeba-infecting virus used as a safe indicator of the possible presence of pathogenic DNA viruses, suggests that the thawing of permafrost either from global warming or industrial exploitation of circumpolar regions might not be exempt from future threats to human or animal health. PMID:24591590

Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology.

PubMed

Legendre, Matthieu; Bartoli, Julia; Shmakova, Lyubov; Jeudy, Sandra; Labadie, Karine; Adrait, Annie; Lescot, Magali; Poirot, Olivier; Bertaux, Lionel; Bruley, Christophe; Couté, Yohann; Rivkina, Elizaveta; Abergel, Chantal; Claverie, Jean-Michel

2014-03-18

The largest known DNA viruses infect Acanthamoeba and belong to two markedly different families. The Megaviridae exhibit pseudo-icosahedral virions up to 0.7 μm in diameter and adenine-thymine (AT)-rich genomes of up to 1.25 Mb encoding a thousand proteins. Like their Mimivirus prototype discovered 10 y ago, they entirely replicate within cytoplasmic virion factories. In contrast, the recently discovered Pandoraviruses exhibit larger amphora-shaped virions 1 μm in length and guanine-cytosine-rich genomes up to 2.8 Mb long encoding up to 2,500 proteins. Their replication involves the host nucleus. Whereas the Megaviridae share some general features with the previously described icosahedral large DNA viruses, the Pandoraviruses appear unrelated to them. Here we report the discovery of a third type of giant virus combining an even larger pandoravirus-like particle 1.5 μm in length with a surprisingly smaller 600 kb AT-rich genome, a gene content more similar to Iridoviruses and Marseillevirus, and a fully cytoplasmic replication reminiscent of the Megaviridae. This suggests that pandoravirus-like particles may be associated with a variety of virus families more diverse than previously envisioned. This giant virus, named Pithovirus sibericum, was isolated from a >30,000-y-old radiocarbon-dated sample when we initiated a survey of the virome of Siberian permafrost. The revival of such an ancestral amoeba-infecting virus used as a safe indicator of the possible presence of pathogenic DNA viruses, suggests that the thawing of permafrost either from global warming or industrial exploitation of circumpolar regions might not be exempt from future threats to human or animal health.

Metabolomic patterns and alcohol consumption in African Americans in the Atherosclerosis Risk in Communities Study123

PubMed Central

Zheng, Yan; Yu, Bing; Alexander, Danny; Steffen, Lyn M; Nettleton, Jennifer A

2014-01-01

Background: Effects of alcohol consumption on health and disease are complex and involve a number of cellular and metabolic processes. Objective: We examined the association between alcohol consumption habits and metabolomic profiles. Design: We conducted a cross-sectional study to explore the association of alcohol consumption habits measured by using a questionnaire with serum metabolites measured by using untargeted mass spectrometry in 1977 African Americans from the Jackson field center in the Atherosclerosis Risk in Communities Study. The whole sample was split into a discovery set (n = 1500) and a replication set (n = 477). Alcohol consumption habits were treated as an ordinal variable, with nondrinkers as the reference group and quartiles of current drinkers as ordinal groups with higher values. For each metabolite, a linear regression was conducted to estimate its relation with alcohol consumption habits separately in both sets. A modified Bonferroni procedure was used in the discovery set to adjust the significance threshold (P < 1.9 × 10−4). Results: In 356 named metabolites, 39 metabolites were significantly associated with alcohol consumption habits in both discovery and replication sets. In general, alcohol consumption was associated with higher levels of most metabolites such as those in amino acid and lipid pathways and with lower levels of γ-glutamyl dipeptides. Three pathways, 2-hydroxybutyrate-related metabolites, γ-glutamyl dipeptides, and lysophosphatidylcholines, which are considered to be involved in inflammation and oxidation, were associated with incident cardiovascular diseases. Conclusions: To our knowledge, this is the largest metabolomic study thus far conducted in nonwhites. Metabolomic biomarkers of alcohol consumption were identified and replicated. The results lend new insight into potential mediating effects between alcohol consumption and future health and disease. PMID:24760976

Patterns of Competence and Adjustment among Adolescents from Authoritative, Authoritarian, Indulgent, and Neglectful Homes: A Replication in a Sample of Serious Juvenile Offenders

ERIC Educational Resources Information Center

Steinberg, Laurence; Blatt-Eisengart, Ilana; Cauffman, Elizabeth

2006-01-01

The correlates of authoritative, authoritarian, indulgent, and neglectful parenting were examined within a sample of 1,355 14- to 18-year-olds adjudicated of serious criminal offenses. The sample is composed primarily of poor, ethnic-minority youth living in impoverished urban neighborhoods. As has been found in community samples, juvenile…

Human stem cell-derived astrocytes replicate human prions in a PRNP genotype-dependent manner.

PubMed

Krejciova, Zuzana; Alibhai, James; Zhao, Chen; Krencik, Robert; Rzechorzek, Nina M; Ullian, Erik M; Manson, Jean; Ironside, James W; Head, Mark W; Chandran, Siddharthan

2017-12-04

Prions are infectious agents that cause neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD). The absence of a human cell culture model that replicates human prions has hampered prion disease research for decades. In this paper, we show that astrocytes derived from human induced pluripotent stem cells (iPSCs) support the replication of prions from brain samples of CJD patients. For experimental exposure of astrocytes to variant CJD (vCJD), the kinetics of prion replication occur in a prion protein codon 129 genotype-dependent manner, reflecting the genotype-dependent susceptibility to clinical vCJD found in patients. Furthermore, iPSC-derived astrocytes can replicate prions associated with the major sporadic CJD strains found in human patients. Lastly, we demonstrate the subpassage of prions from infected to naive astrocyte cultures, indicating the generation of prion infectivity in vitro. Our study addresses a long-standing gap in the repertoire of human prion disease research, providing a new in vitro system for accelerated mechanistic studies and drug discovery. © 2017 Krejciova et al.

A mega-analysis of genome-wide association studies for major depressive disorder.

PubMed

Ripke, Stephan; Wray, Naomi R; Lewis, Cathryn M; Hamilton, Steven P; Weissman, Myrna M; Breen, Gerome; Byrne, Enda M; Blackwood, Douglas H R; Boomsma, Dorret I; Cichon, Sven; Heath, Andrew C; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A F; Martin, Nicholas G; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M; Penninx, Brenda P; Pergadia, Michele L; Potash, James B; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H; Preisig, Martin; Smoller, Jordan W; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R; Bettecken, Thomas; Binder, Elisabeth B; Breuer, René; Castro, Victor M; Churchill, Susanne E; Coryell, William H; Craddock, Nick; Craig, Ian W; Czamara, Darina; De Geus, Eco J; Degenhardt, Franziska; Farmer, Anne E; Fava, Maurizio; Frank, Josef; Gainer, Vivian S; Gallagher, Patience J; Gordon, Scott D; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A; Kohane, Isaac S; Kohli, Martin A; Korszun, Ania; Landen, Mikael; Lawson, William B; Lewis, Glyn; Macintyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M; Middleton, Lefkos; Montgomery, Grant M; Murphy, Shawn N; Nauck, Matthias; Nolen, Willem A; Nyholt, Dale R; O'Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A; Schulz, Andrea; Schulze, Thomas G; Shyn, Stanley I; Sigurdsson, Engilbert; Slager, Susan L; Smit, Johannes H; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J C G; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B; Willemsen, Gonneke; Zitman, Frans G; Neale, Benjamin; Daly, Mark; Levinson, Douglas F; Sullivan, Patrick F

2013-04-01

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.

Depression and blood pressure in high-risk children and adolescents: an investigation using two longitudinal cohorts

PubMed Central

Hammerton, Gemma; Harold, Gordon; Thapar, Anita; Thapar, Ajay

2013-01-01

Objective To examine the relationship between blood pressure and depressive disorder in children and adolescents at high risk for depression. Design Multisample longitudinal design including a prospective longitudinal three-wave high-risk study of offspring of parents with recurrent depression and an on-going birth cohort for replication. Setting Community-based studies. Participants High-risk sample includes 281 families where children were aged 9–17 years at baseline and 10–19 years at the final data point. Replication cohort includes 4830 families where children were aged 11–14 years at baseline and 14–17 years at follow-up and a high-risk subsample of 612 offspring with mothers that had reported recurrent depression. Main outcome measures The new-onset of Diagnostic and Statistical Manual of Mental Disorder, fourth edition defined depressive disorder in the offspring using established research diagnostic assessments—the Child and Adolescent Psychiatric Assessment in the high-risk sample and the Development and Wellbeing Assessment in the replication sample. Results Blood pressure was standardised for age and gender to create SD scores and child's weight was statistically controlled in all analyses. In the high-risk sample, lower systolic blood pressure at wave 1 significantly predicted new-onset depressive disorder in children (OR=0.65, 95% CI 0.44 to 0.96; p=0.029) but diastolic blood pressure did not. Depressive disorder at wave 1 did not predict systolic blood pressure at wave 3. A significant association between lower systolic blood pressure and future depression was also found in the replication cohort in the second subset of high-risk children whose mothers had experienced recurrent depression in the past. Conclusions Lower systolic blood pressure predicts new-onset depressive disorder in the offspring of parents with depression. Further studies are needed to investigate how this association arises. PMID:24071459

Factors Influencing the Successful Completion of the General Educational Development (GED) Preparation Program as Perceived by the Students

ERIC Educational Resources Information Center

Styles, Theresa

2011-01-01

This replicated study (A. Tucho, 2000, "Factors Influencing the General Educational Development [GED] Program at Community College of Philadelphia as Perceived by the GED Students") determined which of the 3 types of educational barriers (institutional, situational, and dispositional) represented the major difficulty preventing adult…

STN1 OB Fold Mutation Alters DNA Binding and Affects Selective Aspects of CST Function

PubMed Central

Bhattacharjee, Anukana; Stewart, Jason; Chaiken, Mary; Price, Carolyn M.

2016-01-01

Mammalian CST (CTC1-STN1-TEN1) participates in multiple aspects of telomere replication and genome-wide recovery from replication stress. CST resembles Replication Protein A (RPA) in that it binds ssDNA and STN1 and TEN1 are structurally similar to RPA2 and RPA3. Conservation between CTC1 and RPA1 is less apparent. Currently the mechanism underlying CST action is largely unknown. Here we address CST mechanism by using a DNA-binding mutant, (STN1 OB-fold mutant, STN1-OBM) to examine the relationship between DNA binding and CST function. In vivo, STN1-OBM affects resolution of endogenous replication stress and telomere duplex replication but telomeric C-strand fill-in and new origin firing after exogenous replication stress are unaffected. These selective effects indicate mechanistic differences in CST action during resolution of different replication problems. In vitro binding studies show that STN1 directly engages both short and long ssDNA oligonucleotides, however STN1-OBM preferentially destabilizes binding to short substrates. The finding that STN1-OBM affects binding to only certain substrates starts to explain the in vivo separation of function observed in STN1-OBM expressing cells. CST is expected to engage DNA substrates of varied length and structure as it acts to resolve different replication problems. Since STN1-OBM will alter CST binding to only some of these substrates, the mutant should affect resolution of only a subset of replication problems, as was observed in the STN1-OBM cells. The in vitro studies also provide insight into CST binding mechanism. Like RPA, CST likely contacts DNA via multiple OB folds. However, the importance of STN1 for binding short substrates indicates differences in the architecture of CST and RPA DNA-protein complexes. Based on our results, we propose a dynamic DNA binding model that provides a general mechanism for CST action at diverse forms of replication stress. PMID:27690379

CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation.

PubMed

Quteineh, L; Bochud, P-Y; Golshayan, D; Crettol, S; Venetz, J-P; Manuel, O; Kutalik, Z; Treyer, A; Lehmann, R; Mueller, N J; Binet, I; van Delden, C; Steiger, J; Mohacsi, P; Dufour, J-F; Soccal, P M; Pascual, M; Eap, C B

2017-01-01

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n 1 =197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n 2 =1294 and n 3 =759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n 4 =46'186, n 5 =123'865, n 6 >100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (P corrected <0.05). CRTC2 rs8450-AA genotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P=0.04). In the combined STCS replication samples, the effect of rs8450-AA genotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus (n=395, OR=2.08, P=0.02) and in non-kidney transplant recipients (OR=2.09, P=0.02). Moreover, rs8450-AA genotype was associated with overweight or obesity (n=1215, OR=1.56, P=0.02), new-onset hyperlipidemia (n=1007, OR=1.76, P=0.007), and lower high-density lipoprotein-cholesterol (n=1214, β=-0.08, P=0.001). In the population-based samples, a proxy of rs8450G>A was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.

The obesity-risk variant of FTO is inversely related with the So-Eum constitutional type: genome-wide association and replication analyses.

PubMed

Cha, Seongwon; Yu, Hyunjoo; Park, Ah Yeon; Oh, Soo A; Kim, Jong Yeol

2015-04-15

Body constitutional types described in the traditional Korean medicine system, Sasang constitutional medicine, are heritable, as has been revealed by twin and family studies. Thus, individuals with the same constitution type usually have similar pathophysiological and psychological traits. In several recent genome-wide association (GWA) analyses performed to identify constitution-associated variants, the association signals were not replicated due to small sample size and dissimilar, non-objective methods for classification of the constitutional types. We conducted GWA analysis and followed replication analysis in two large populations (5,490 subjects: 3,810 subjects at discovery stage and 1,680 subjects at replication stage) to identify the replicable constitution-associated variants, wherein subjects with the highest tertile of constitution probability values versus the reference with the lowest tertile of the values obtained from a recently developed constitution analysis tool were compared. We found that the obesity-risk variant in intron 1 of the fat mass and obesity-associated (FTO) gene was replicably inversely associated with the So-Eum (SE) type, characterized by reduced appetite, slim body, and cautious personality (rs7193144 in combined samples: odds ratio = 0.729, p = 1.47 × 10(-7)), and substantial association signal remained after controlling for body mass index (BMI). In contrast, the association of the variant with the Tae-Eum type, characterized by high body mass, disappeared after controlling BMI. In summary, the obesity-risk variant in FTO intron 1 was inversely associated with the SE type, independent of BMI, which corresponded well with the characteristics of the SE type, such as the lowest body mass and lowest susceptibility to metabolic disorders among the constitutional types. Therefore, the obesity-risk variant of FTO associated with body mass increase might be involved in the determination of body constitution type.

Reproducibility and quantitation of amplicon sequencing-based detection

PubMed Central

Zhou, Jizhong; Wu, Liyou; Deng, Ye; Zhi, Xiaoyang; Jiang, Yi-Huei; Tu, Qichao; Xie, Jianping; Van Nostrand, Joy D; He, Zhili; Yang, Yunfeng

2011-01-01

To determine the reproducibility and quantitation of the amplicon sequencing-based detection approach for analyzing microbial community structure, a total of 24 microbial communities from a long-term global change experimental site were examined. Genomic DNA obtained from each community was used to amplify 16S rRNA genes with two or three barcode tags as technical replicates in the presence of a small quantity (0.1% wt/wt) of genomic DNA from Shewanella oneidensis MR-1 as the control. The technical reproducibility of the amplicon sequencing-based detection approach is quite low, with an average operational taxonomic unit (OTU) overlap of 17.2%±2.3% between two technical replicates, and 8.2%±2.3% among three technical replicates, which is most likely due to problems associated with random sampling processes. Such variations in technical replicates could have substantial effects on estimating β-diversity but less on α-diversity. A high variation was also observed in the control across different samples (for example, 66.7-fold for the forward primer), suggesting that the amplicon sequencing-based detection approach could not be quantitative. In addition, various strategies were examined to improve the comparability of amplicon sequencing data, such as increasing biological replicates, and removing singleton sequences and less-representative OTUs across biological replicates. Finally, as expected, various statistical analyses with preprocessed experimental data revealed clear differences in the composition and structure of microbial communities between warming and non-warming, or between clipping and non-clipping. Taken together, these results suggest that amplicon sequencing-based detection is useful in analyzing microbial community structure even though it is not reproducible and quantitative. However, great caution should be taken in experimental design and data interpretation when the amplicon sequencing-based detection approach is used for quantitative analysis of the β-diversity of microbial communities. PMID:21346791

Size Matters: Assessing Optimum Soil Sample Size for Fungal and Bacterial Community Structure Analyses Using High Throughput Sequencing of rRNA Gene Amplicons

DOE PAGES

Penton, C. Ryan; Gupta, Vadakattu V. S. R.; Yu, Julian; ...

2016-06-02

We examined the effect of different soil sample sizes obtained from an agricultural field, under a single cropping system uniform in soil properties and aboveground crop responses, on bacterial and fungal community structure and microbial diversity indices. DNA extracted from soil sample sizes of 0.25, 1, 5, and 10 g using MoBIO kits and from 10 and 100 g sizes using a bead-beating method (SARDI) were used as templates for high-throughput sequencing of 16S and 28S rRNA gene amplicons for bacteria and fungi, respectively, on the Illumina MiSeq and Roche 454 platforms. Sample size significantly affected overall bacterial and fungalmore » community structure, replicate dispersion and the number of operational taxonomic units (OTUs) retrieved. Richness, evenness and diversity were also significantly affected. The largest diversity estimates were always associated with the 10 g MoBIO extractions with a corresponding reduction in replicate dispersion. For the fungal data, smaller MoBIO extractions identified more unclassified Eukaryota incertae sedis and unclassified glomeromycota while the SARDI method retrieved more abundant OTUs containing unclassified Pleosporales and the fungal genera Alternaria and Cercophora. Overall, these findings indicate that a 10 g soil DNA extraction is most suitable for both soil bacterial and fungal communities for retrieving optimal diversity while still capturing rarer taxa in concert with decreasing replicate variation.« less

Size Matters: Assessing Optimum Soil Sample Size for Fungal and Bacterial Community Structure Analyses Using High Throughput Sequencing of rRNA Gene Amplicons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penton, C. Ryan; Gupta, Vadakattu V. S. R.; Yu, Julian

We examined the effect of different soil sample sizes obtained from an agricultural field, under a single cropping system uniform in soil properties and aboveground crop responses, on bacterial and fungal community structure and microbial diversity indices. DNA extracted from soil sample sizes of 0.25, 1, 5, and 10 g using MoBIO kits and from 10 and 100 g sizes using a bead-beating method (SARDI) were used as templates for high-throughput sequencing of 16S and 28S rRNA gene amplicons for bacteria and fungi, respectively, on the Illumina MiSeq and Roche 454 platforms. Sample size significantly affected overall bacterial and fungalmore » community structure, replicate dispersion and the number of operational taxonomic units (OTUs) retrieved. Richness, evenness and diversity were also significantly affected. The largest diversity estimates were always associated with the 10 g MoBIO extractions with a corresponding reduction in replicate dispersion. For the fungal data, smaller MoBIO extractions identified more unclassified Eukaryota incertae sedis and unclassified glomeromycota while the SARDI method retrieved more abundant OTUs containing unclassified Pleosporales and the fungal genera Alternaria and Cercophora. Overall, these findings indicate that a 10 g soil DNA extraction is most suitable for both soil bacterial and fungal communities for retrieving optimal diversity while still capturing rarer taxa in concert with decreasing replicate variation.« less

Use of the semipermeable membrane device as an in situ sampler of waterborne bioavailable PCDD and PCDF residues at sub-parts-per-quadrillion concentrations

USGS Publications Warehouse

Lebo, Jon A.; Gale, Robert W.; Petty, Jimmie D.; Tillitt, Donald E.; Huckins, James N.; Meadows, John C.; Orazio, Carl E.; Echols, Kathy R.; Schroeder, Dennis J.; Inmon, Lloyd E.

1995-01-01

Semipermeable membrane devices (SPMDs) were used to passively sample aqueous polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in Bayou Meto, AR. The two sites were upstream and downstream from the confluence with a tributary that delivers PCDDs and PCDFs to the Bayou. Following dialysis, cleanup, and fractionation, four replicate 17-9 SPMD samples from each site were analyzed by GUMS, and four were evaluated by H411E bioassay. Traces of only OCDD and HpCDDs were detected in samples from the upstream site. The four samples from below the tributary contained averages of 1550 ± 80 pg of 2,3,7,8-TCDD, 1640 ± 80 pg of 2,3,7,8-TCDF, and lesser quantities of other congeners. The TCDD equivalents obtained by bioassay of replicate SPMD samples agreed well with results obtained by GC/MS. The quantities of 2,3,7,8- TCDD and 2,3,7,8-TCDF sequestered by SPMDs at the downstream site were used to estimate the aqueous concentrations for both compounds as 2 pg/L.

Cellular Restriction Factors of Feline Immunodeficiency Virus

PubMed Central

Zielonka, Jörg; Münk, Carsten

2011-01-01

Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating. Of particular importance are the cellular proteins APOBEC3, TRIM5α and tetherin/BST-2. In general, lentiviruses counteract or escape their species’ own variant of the restriction factor, but are targeted by the orthologous proteins of distantly related species. Most of the knowledge regarding lentiviral restriction factors has been obtained in the HIV-1 system; however, much less is known about their effects on other lentiviruses. We describe here the molecular mechanisms that explain how FIV maintains its replication in feline cells, but is largely prevented from cross-species infections by cellular restriction factors. PMID:22069525

Molecular turnover, the H3.3 dilemma and organismal aging (hypothesis)

PubMed Central

Saade, Evelyne; Pirozhkova, Iryna; Aimbetov, Rakhan; Lipinski, Marc; Ogryzko, Vasily

2015-01-01

The H3.3 histone variant has been a subject of increasing interest in the field of chromatin studies due to its two distinguishing features. First, its incorporation into chromatin is replication independent unlike the replication-coupled deposition of its canonical counterparts H3.1/2. Second, H3.3 has been consistently associated with an active state of chromatin. In accordance, this histone variant should be expected to be causally involved in the regulation of gene expression, or more generally, its incorporation should have downstream consequences for the structure and function of chromatin. This, however, leads to an apparent paradox: In cells that slowly replicate in the organism, H3.3 will accumulate with time, opening the way to aberrant effects on heterochromatin. Here, we review the indications that H3.3 is expected both to be incorporated in the heterochromatin of slowly replicating cells and to retain its functional downstream effects. Implications for organismal aging are discussed. PMID:25720734

Correlative live and super-resolution imaging reveals the dynamic structure of replication domains.

PubMed

Xiang, Wanqing; Roberti, M Julia; Hériché, Jean-Karim; Huet, Sébastien; Alexander, Stephanie; Ellenberg, Jan

2018-06-04

Chromosome organization in higher eukaryotes controls gene expression, DNA replication, and DNA repair. Genome mapping has revealed the functional units of chromatin at the submegabase scale as self-interacting regions called topologically associating domains (TADs) and showed they correspond to replication domains (RDs). A quantitative structural and dynamic description of RD behavior in the nucleus is, however, missing because visualization of dynamic subdiffraction-sized RDs remains challenging. Using fluorescence labeling of RDs combined with correlative live and super-resolution microscopy in situ, we determined biophysical parameters to characterize the internal organization, spacing, and mechanical coupling of RDs. We found that RDs are typically 150 nm in size and contain four co-replicating regions spaced 60 nm apart. Spatially neighboring RDs are spaced 300 nm apart and connected by highly flexible linker regions that couple their motion only <550 nm. Our pipeline allows a robust quantitative characterization of chromosome structure in situ and provides important biophysical parameters to understand general principles of chromatin organization. © 2018 Xiang et al.

Studies in Historical Replication in Psychology VII: The Relative Utility of ``Ancestor Analysis'' from Scientific and Educational Vantages

NASA Astrophysics Data System (ADS)

Ranney, Michael Andrew

2008-05-01

This article discusses, from various vantages, Ryan Tweney’s (this issue) pedagogical technique of employing historical replications of psychological experiments with graduate students in psychology. A prima facie perspective suggests great promise for this sort of academic “ancestor analysis,” particularly given the enthusiasm and skill represented in the activities that culminated in the replicators’ articles. It is suggested that such activities might be enhanced by requiring a contextualization that makes contact with more modern psychological research—particularly regarding expositions of the replications. From a scientific/cognitive methods perspective, the original experimenters’ inexplicit, ambiguous, descriptions provide both challenges and opportunities for students seeking to improve their understandings of their field. Three practical questions are posed herein regarding the general utility of this—or any—proposed instructional intervention. Ultimately, determining and integrating the diverse objectives that essential stakeholders have in graduate psychological training represent critical prerequisites in comprehensively assessing the relative advantages of such historical replications with respect to alternative experiences.

Using the MMPI-2-RF to discriminate psychometrically identified schizotypic college students from a matched comparison sample.

PubMed

Hunter, Helen K; Bolinskey, P Kevin; Novi, Jonathan H; Hudak, Daniel V; James, Alison V; Myers, Kevin R; Schuder, Kelly M

2014-01-01

This study investigates the extent to which the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) profiles of 52 individuals making up a psychometrically identified schizotypes (SZT) sample could be successfully discriminated from the protocols of 52 individuals in a matched comparison (MC) sample. Replication analyses were performed with an additional 53 pairs of SZT and MC participants. Results showed significant differences in mean T-score values between these 2 groups across a variety of MMPI-2-RF scales. Results from discriminant function analyses indicate that schizotypy can be predicted effectively using 4 MMPI-2-RF scales and that this method of classification held up on replication. Additional results demonstrated that these MMPI-2-RF scales nominally outperformed MMPI-2 scales suggested by previous research as being indicative of schizophrenia liability. Directions for future research with the MMPI-2-RF are suggested.

Cross-cultural generalizability of personality dimensions: relating indigenous and imported dimensions in two cultures.

PubMed

Katigbak, M S; Church, A T; Akamine, T X

1996-01-01

The cross-cultural generalizability of personality dimensions was investigated by (a) identifying indigenous Philippine dimensions, (b) testing the cross-cultural replicability of the NEO 5-factor model (P. T. Costa & R.R. McCrae, 1992), and (c) relating Philippine and Western dimensions in Philippine and U.S. samples of college students. Filipino self-ratings (N = 536) on indigenous items were factor analyzed, and 6 Philippine dimensions were obtained. Conclusions about the replicability of the 5-factor model in the Philippines (N = 432) depended on whether exploratory, Procrustes, or confirmatory factor methods were used. In regression and joint factor analyses, moderate to strong associations were found between the Philippine dimensions and (a) dimensions from the 5-factor model in both Philippine (N = 387) and U.S. (N = 610) samples, and (b) the Tellegen model (A. Tellegen, 1985; A. Tellegen & N.G. Waller, in press) in a U.S. sample (N = 603).

Evaluation of the methods for enumerating coliform bacteria from water samples using precise reference standards.

PubMed

Wohlsen, T; Bates, J; Vesey, G; Robinson, W A; Katouli, M

2006-04-01

To use BioBall cultures as a precise reference standard to evaluate methods for enumeration of Escherichia coli and other coliform bacteria in water samples. Eight methods were evaluated including membrane filtration, standard plate count (pour and spread plate methods), defined substrate technology methods (Colilert and Colisure), the most probable number method and the Petrifilm disposable plate method. Escherichia coli and Enterobacter aerogenes BioBall cultures containing 30 organisms each were used. All tests were performed using 10 replicates. The mean recovery of both bacteria varied with the different methods employed. The best and most consistent results were obtained with Petrifilm and the pour plate method. Other methods either yielded a low recovery or showed significantly high variability between replicates. The BioBall is a very suitable quality control tool for evaluating the efficiency of methods for bacterial enumeration in water samples.

Actor and Partner Effects of Attachment on Relationship Satisfaction and Sexual Satisfaction Across the Genders: An APIM Approach.

PubMed

Conradi, Henk Jan; Noordhof, Arjen; Dingemanse, Pieter; Barelds, Dick P H; Kamphuis, Jan H

2017-10-01

Previous studies found gender differences in relationship satisfaction and sexuality. We tested gender differences in associations between attachment, a lasting relationship determinant, and two outcomes, relationship and sexual satisfaction. This study improves on earlier research by examining these associations in one Actor-Partner-Interdependence-Model, making direct statistical testing between outcomes possible. Furthermore, a community and a distressed sample (N = 113 heterosexual couples each) were included to attempt replication across samples and to examine clinical implications. In both genders, actor attachment avoidance negatively affected relationship satisfaction and (with one exception) sexual satisfaction. Also in both genders, partner attachment avoidance negatively affected sexual satisfaction. However, whereas partner attachment avoidance influenced female relationship satisfaction, it did not affect male relationship satisfaction. The findings replicated across samples. Clinical implications are discussed. © 2017 American Association for Marriage and Family Therapy.

Immunochip Analyses of Epistasis in Rheumatoid Arthritis Confirm Multiple Interactions within MHC and Suggest Novel Non-MHC Epistatic Signals.

PubMed

Wei, Wen-Hua; Loh, Chia-Yin; Worthington, Jane; Eyre, Stephen

2016-05-01

Studying statistical gene-gene interactions (epistasis) has been limited by the difficulties in performance, both statistically and computationally, in large enough sample numbers to gain sufficient power. Three large Immunochip datasets from cohort samples recruited in the United Kingdom, United States, and Sweden with European ancestry were used to examine epistasis in rheumatoid arthritis (RA). A full pairwise search was conducted in the UK cohort using a high-throughput tool and the resultant significant epistatic signals were tested for replication in the United States and Swedish cohorts. A forward selection approach was applied to remove redundant signals, while conditioning on the preidentified additive effects. We detected abundant genome-wide significant (p < 1.0e-13) epistatic signals, all within the MHC region. These signals were reduced substantially, but a proportion remained significant (p < 1.0e-03) in conditional tests. We identified 11 independent epistatic interactions across the entire MHC, each explaining on average 0.12% of the phenotypic variance, nearly all replicated in both replication cohorts. We also identified non-MHC epistatic interactions between RA susceptible loci LOC100506023 and IRF5 with Immunochip-wide significance (p < 1.1e-08) and between 2 neighboring single-nucleotide polymorphism near PTPN22 that were in low linkage disequilibrium with independent interaction (p < 1.0e-05). Both non-MHC epistatic interactions were statistically replicated with a similar interaction pattern in the US cohort only. There are multiple but relatively weak interactions independent of the additive effects in RA and a larger sample number is required to confidently assign additional non-MHC epistasis.

Individual and cumulative effects of agriculture, forestry and metal mining activities on the metal and phosphorus content of fluvial fine-grained sediment; Quesnel River Basin, British Columbia, Canada.

PubMed

Smith, Tyler B; Owens, Philip N

2014-10-15

The impact of agriculture, forestry and metal mining on the quality of fine-grained sediment (<63 μm) was investigated in the Quesnel River Basin (QRB) (~11,500 km(2)) in British Columbia, Canada. Samples of fine-grained sediment were collected monthly during the snow-free season in 2008 using time-integrated samplers at replicate sites representative of agriculture, forestry and mining activities in the basin (i.e. "impacted" sites). Samples were also collected from replicate reference sites and also from the main stem of the Quesnel River at the downstream confluence with the Fraser River. Generally, metal(loid) and phosphorus (P) concentrations for "impacted" sites were greater than for reference sites. Furthermore, concentrations of copper (forestry and mining sites), manganese (agriculture and forestry sites) and selenium (agriculture, forestry and mining sites) exceeded upper sediment quality guideline (SQG) thresholds. These results suggest that agriculture, forestry and metal mining activities are having an influence on the concentrations of sediment-associated metal(loid)s and P in the Quesnel basin. Metal(loid) and P concentrations of sediment collected from the downstream site were not significantly greater than values for the reference sites, and were typically lower than the values for the impacted sites. This suggests that the cumulative effects of agriculture, forestry and mining activities in the QRB are presently not having a measureable effect at the river basin-scale. The lack of a cumulative effect at the basin-scale is thought to reflect: (i) the relatively recent occurrence of land use disturbances in this basin; (ii) the dominance of sediment contributions from natural forest and agriculture; and (iii) the potential for storage of contaminants on floodplains and other storage elements between the locations of disturbance activities and the downstream sampling site, which may be attenuating the disturbance signal. Copyright © 2014 Elsevier B.V. All rights reserved.

Three-dimensional distribution of cortical synapses: a replicated point pattern-based analysis

PubMed Central

Anton-Sanchez, Laura; Bielza, Concha; Merchán-Pérez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Larrañaga, Pedro

2014-01-01

The biggest problem when analyzing the brain is that its synaptic connections are extremely complex. Generally, the billions of neurons making up the brain exchange information through two types of highly specialized structures: chemical synapses (the vast majority) and so-called gap junctions (a substrate of one class of electrical synapse). Here we are interested in exploring the three-dimensional spatial distribution of chemical synapses in the cerebral cortex. Recent research has showed that the three-dimensional spatial distribution of synapses in layer III of the neocortex can be modeled by a random sequential adsorption (RSA) point process, i.e., synapses are distributed in space almost randomly, with the only constraint that they cannot overlap. In this study we hypothesize that RSA processes can also explain the distribution of synapses in all cortical layers. We also investigate whether there are differences in both the synaptic density and spatial distribution of synapses between layers. Using combined focused ion beam milling and scanning electron microscopy (FIB/SEM), we obtained three-dimensional samples from the six layers of the rat somatosensory cortex and identified and reconstructed the synaptic junctions. A total volume of tissue of approximately 4500μm3 and around 4000 synapses from three different animals were analyzed. Different samples, layers and/or animals were aggregated and compared using RSA replicated spatial point processes. The results showed no significant differences in the synaptic distribution across the different rats used in the study. We found that RSA processes described the spatial distribution of synapses in all samples of each layer. We also found that the synaptic distribution in layers II to VI conforms to a common underlying RSA process with different densities per layer. Interestingly, the results showed that synapses in layer I had a slightly different spatial distribution from the other layers. PMID:25206325

Three-dimensional distribution of cortical synapses: a replicated point pattern-based analysis.

PubMed

Anton-Sanchez, Laura; Bielza, Concha; Merchán-Pérez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Larrañaga, Pedro

2014-01-01

The biggest problem when analyzing the brain is that its synaptic connections are extremely complex. Generally, the billions of neurons making up the brain exchange information through two types of highly specialized structures: chemical synapses (the vast majority) and so-called gap junctions (a substrate of one class of electrical synapse). Here we are interested in exploring the three-dimensional spatial distribution of chemical synapses in the cerebral cortex. Recent research has showed that the three-dimensional spatial distribution of synapses in layer III of the neocortex can be modeled by a random sequential adsorption (RSA) point process, i.e., synapses are distributed in space almost randomly, with the only constraint that they cannot overlap. In this study we hypothesize that RSA processes can also explain the distribution of synapses in all cortical layers. We also investigate whether there are differences in both the synaptic density and spatial distribution of synapses between layers. Using combined focused ion beam milling and scanning electron microscopy (FIB/SEM), we obtained three-dimensional samples from the six layers of the rat somatosensory cortex and identified and reconstructed the synaptic junctions. A total volume of tissue of approximately 4500μm(3) and around 4000 synapses from three different animals were analyzed. Different samples, layers and/or animals were aggregated and compared using RSA replicated spatial point processes. The results showed no significant differences in the synaptic distribution across the different rats used in the study. We found that RSA processes described the spatial distribution of synapses in all samples of each layer. We also found that the synaptic distribution in layers II to VI conforms to a common underlying RSA process with different densities per layer. Interestingly, the results showed that synapses in layer I had a slightly different spatial distribution from the other layers.

A Maximum-Likelihood Method to Correct for Allelic Dropout in Microsatellite Data with No Replicate Genotypes

PubMed Central

Wang, Chaolong; Schroeder, Kari B.; Rosenberg, Noah A.

2012-01-01

Allelic dropout is a commonly observed source of missing data in microsatellite genotypes, in which one or both allelic copies at a locus fail to be amplified by the polymerase chain reaction. Especially for samples with poor DNA quality, this problem causes a downward bias in estimates of observed heterozygosity and an upward bias in estimates of inbreeding, owing to mistaken classifications of heterozygotes as homozygotes when one of the two copies drops out. One general approach for avoiding allelic dropout involves repeated genotyping of homozygous loci to minimize the effects of experimental error. Existing computational alternatives often require replicate genotyping as well. These approaches, however, are costly and are suitable only when enough DNA is available for repeated genotyping. In this study, we propose a maximum-likelihood approach together with an expectation-maximization algorithm to jointly estimate allelic dropout rates and allele frequencies when only one set of nonreplicated genotypes is available. Our method considers estimates of allelic dropout caused by both sample-specific factors and locus-specific factors, and it allows for deviation from Hardy–Weinberg equilibrium owing to inbreeding. Using the estimated parameters, we correct the bias in the estimation of observed heterozygosity through the use of multiple imputations of alleles in cases where dropout might have occurred. With simulated data, we show that our method can (1) effectively reproduce patterns of missing data and heterozygosity observed in real data; (2) correctly estimate model parameters, including sample-specific dropout rates, locus-specific dropout rates, and the inbreeding coefficient; and (3) successfully correct the downward bias in estimating the observed heterozygosity. We find that our method is fairly robust to violations of model assumptions caused by population structure and by genotyping errors from sources other than allelic dropout. Because the data sets imputed under our model can be investigated in additional subsequent analyses, our method will be useful for preparing data for applications in diverse contexts in population genetics and molecular ecology. PMID:22851645

Early androgen exposure and human gender development.

PubMed

Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

2015-01-01

During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This approach has recently begun to be used, with some promising results relating testosterone during the first few months of postnatal life to later gender-typical play behavior. In replicating and extending these findings, it may be important to assess testosterone when it is maximal (months 1 to 2 postnatal) and to take advantage of the increased reliability afforded by repeated sampling.

Age-related DNA methylation changes for forensic age-prediction.

PubMed

Yi, Shao Hua; Jia, Yun Shu; Mei, Kun; Yang, Rong Zhi; Huang, Dai Xin

2015-03-01

There is no available method of age-prediction for biological samples. The accumulating evidences indicate that DNA methylation patterns change with age. Aging resembles a developmentally regulated process that is tightly controlled by specific epigenetic modifications and age-associated methylation changes exist in human genome. In this study, three age-related methylation fragments were isolated and identified in blood of 40 donors. Age-related methylation changes with each fragment was validated and replicated in a general population sample of 65 donors over a wide age range (11-72 years). Methylation of these fragments is linearly correlated with age over a range of six decades (r = 0.80-0.88). Using average methylation of CpG sites of three fragments, a regression model that explained 95 % of the variance in age was built and is able to predict an individual's age with great accuracy (R (2 )= 0.93). The predicted value is highly correlated with the observed age in the sample (r = 0.96) and has great accuracy of average 4 years difference between predicted age and true age. This study implicates that DNA methylation can be an available biological marker of age-prediction. Further measurement of relevant markers in the genome could be a tool in routine screening to predict age of forensic biological samples.

The Psychometric Properties of the French Version of the Personality Inventory for DSM-5

PubMed Central

Roskam, Isabelle; Galdiolo, Sarah; Hansenne, Michel; Massoudi, Koorosh; Rossier, Jérôme; Gicquel, Ludovic; Rolland, Jean-Pierre

2015-01-01

In the context of the publication of DSM-5, the Personality Inventory for DSM-5 (PID-5) has been proposed as a new dimensional assessment tool for personality disorders. This instrument includes a pool of 220 items organized around 25 facets included in a five-factor second-order domain structure. The examination of the replicability of the trait structure across methods and populations is of primary importance. In view of this need, the main objective of the current study was to validate the French version of the PID-5 among French-speaking adults from a European community sample (N=2,532). In particular, the assumption of unidimensionality of the 25 facet and the five domain scales was tested, as well as the extent to which the five-factor structure of the PID-5 and the DSM-5 personality trait hierarchical structure are replicated in the current sample. The results support the assumption of unidimensionality of both the facets and the domains. Exploratory factor and hierarchical analyses replicated the five-factor structure as initially proposed in the PID-5. PMID:26193699

The Psychometric Properties of the French Version of the Personality Inventory for DSM-5.

PubMed

Roskam, Isabelle; Galdiolo, Sarah; Hansenne, Michel; Massoudi, Koorosh; Rossier, Jérôme; Gicquel, Ludovic; Rolland, Jean-Pierre

2015-01-01

In the context of the publication of DSM-5, the Personality Inventory for DSM-5 (PID-5) has been proposed as a new dimensional assessment tool for personality disorders. This instrument includes a pool of 220 items organized around 25 facets included in a five-factor second-order domain structure. The examination of the replicability of the trait structure across methods and populations is of primary importance. In view of this need, the main objective of the current study was to validate the French version of the PID-5 among French-speaking adults from a European community sample (N=2,532). In particular, the assumption of unidimensionality of the 25 facet and the five domain scales was tested, as well as the extent to which the five-factor structure of the PID-5 and the DSM-5 personality trait hierarchical structure are replicated in the current sample. The results support the assumption of unidimensionality of both the facets and the domains. Exploratory factor and hierarchical analyses replicated the five-factor structure as initially proposed in the PID-5.

Shedding of porcine circovirus type 1 DNA and rotavirus RNA by infants vaccinated with Rotarix®.

PubMed

Mijatovic-Rustempasic, Slavica; Immergluck, Lilly Cheng; Parker, Trisha Chan; Laghaie, Elham; Mohammed, Anaam; McFadden, Terri; Parashar, Umesh D; Bowen, Michael D; Cortese, Margaret M

2017-04-03

Thirty-three infants aged ∼2 months had serial stool samples collected after receipt of Rotarix® vaccine dose 1, and were assessed for shedding of porcine circovirus type 1 DNA and Rotavirus group A RNA by molecular methods. We did not find strong evidence that porcine circovirus type 1 replication occurred. Porcine circovirus type 1 genome with the same sequence as that in Rotarix® was detected in a few infants as late as day ≥ 13; while this timing could suggest there may have been replication and not just transient passage through the gastrointestinal tract, the lack of increase in copy number in any infant supports transient passage and there are inherent limitations to the results. We found that 21% of infants did not shed Rotarix® RVA RNA beyond the day 3 sample, which may suggest lack of vaccine virus replication. Of the infants in whom Rotarix RVA RNA shedding continued, peak copy numbers were reached on days 3-5 for ∼40%, and after day 5 in ∼60%, and shedding can be prolonged (≥ 45 days).

The Dimensional Assessment of Personality Psychopathology Basic Questionnaire: shortened versions item analysis.

PubMed

Aluja, Anton; Blanch, Àngel; Blanco, Eduardo; Martí-Guiu, Maite; Balada, Ferran

2015-01-13

This study has been designed to evaluate and replicate the psychometric properties of the Dimensional Assessment of Personality Psychopathology-Basic Questionnaire (DAPP-BQ) and the DAPP-BQ short form (DAPP-SF) in a large Spanish general population sample. Additionally, we have generated a reduced form called DAPP-90, using a strategy based on a structural equation modeling (SEM) methodology in two independent samples, a calibration and a validation sample. The DAPP-90 scales obtained a more satisfactory fit on SEM adjustment values (average: TLI > .97 and RMSEA < .04) respect to full DAPP-BQ and the 136-item version. According to the factorial congruency coefficients, the DAPP-90 obtains a similar structure to the DAPP-BQ and the DAPP-SF. The DAPP-90 internal consistency is acceptable, with a Cronbach's alpha mean of .75. We did not find any differences in the pattern of relations between the two DAPP-BQ shortened versions and the SCL-90-R factors. The new 90-items version is especially useful when it is difficult to use the long version for diverse reasons, such as the assessment of patients in hospital consultation or in brief psychological assessments.

Assessing adolescents' personality with the NEO PI-R.

PubMed

De Fruyt, F; Mervielde, I; Hoekstra, H A; Rolland, J P

2000-12-01

The suitability of the Revised NEO Personality Inventory (NEO PI-R) to assess adolescents' personality traits was investigated in an unselected heterogeneous sample of 469 adolescents aged 12 to 17 years. They were further administered the Hierarchical Personality Inventory for Children (HiPIC) to allow an examination of convergent and discriminant validity. The adult NEO PI-R factor structure proved to be highly replicable in the sample of adolescents, with all facet scales primarily loading on the expected factors, independent of the age group. Domain and facet internal consistency coefficients were comparable to those obtained in adult samples, with less than 12% of the items showing corrected item-facet correlations below absolute value .20. Although, in general, adolescents reported few difficulties with the comprehensibility of the items, they tend to report more problems with the Openness to Ideas (05) and Openness to Values (06) items. Correlations between NEO PI-R and HiPIC scales underscored the convergent and discriminant validity of the NEO facets and HiPIC scales. It was concluded that the NEO PI-R in its present form is useful for assessing adolescents' traits at the primary level, but additional research is necessary to infer the most appropriate facet level structure.

The Hsk1(Cdc7) Replication Kinase Regulates Origin Efficiency

PubMed Central

Patel, Prasanta K.; Kommajosyula, Naveen; Rosebrock, Adam; Bensimon, Aaron; Leatherwood, Janet; Bechhoefer, John

2008-01-01

Origins of DNA replication are generally inefficient, with most firing in fewer than half of cell cycles. However, neither the mechanism nor the importance of the regulation of origin efficiency is clear. In fission yeast, origin firing is stochastic, leading us to hypothesize that origin inefficiency and stochasticity are the result of a diffusible, rate-limiting activator. We show that the Hsk1-Dfp1 replication kinase (the fission yeast Cdc7-Dbf4 homologue) plays such a role. Increasing or decreasing Hsk1-Dfp1 levels correspondingly increases or decreases origin efficiency. Furthermore, tethering Hsk1-Dfp1 near an origin increases the efficiency of that origin, suggesting that the effective local concentration of Hsk1-Dfp1 regulates origin firing. Using photobleaching, we show that Hsk1-Dfp1 is freely diffusible in the nucleus. These results support a model in which the accessibility of replication origins to Hsk1-Dfp1 regulates origin efficiency and provides a potential mechanistic link between chromatin structure and replication timing. By manipulating Hsk1-Dfp1 levels, we show that increasing or decreasing origin firing rates leads to an increase in genomic instability, demonstrating the biological importance of appropriate origin efficiency. PMID:18799612

Replication initiatives will not salvage the trustworthiness of psychology.

PubMed

Coyne, James C

2016-05-31

Replication initiatives in psychology continue to gather considerable attention from far outside the field, as well as controversy from within. Some accomplishments of these initiatives are noted, but this article focuses on why they do not provide a general solution for what ails psychology. There are inherent limitations to mass replications ever being conducted in many areas of psychology, both in terms of their practicality and their prospects for improving the science. Unnecessary compromises were built into the ground rules for design and publication of the Open Science Collaboration: Psychology that undermine its effectiveness. Some ground rules could actually be flipped into guidance for how not to conduct replications. Greater adherence to best publication practices, transparency in the design and publishing of research, strengthening of independent post-publication peer review and firmer enforcement of rules about data sharing and declarations of conflict of interest would make many replications unnecessary. Yet, it has been difficult to move beyond simple endorsement of these measures to consistent implementation. Given the strong institutional support for questionable publication practices, progress will depend on effective individual and collective use of social media to expose lapses and demand reform. Some recent incidents highlight the necessity of this.

Registered Replication Report: Dijksterhuis and van Knippenberg (1998).

PubMed

O'Donnell, Michael; Nelson, Leif D; Ackermann, Evi; Aczel, Balazs; Akhtar, Athfah; Aldrovandi, Silvio; Alshaif, Nasseem; Andringa, Ronald; Aveyard, Mark; Babincak, Peter; Balatekin, Nursena; Baldwin, Scott A; Banik, Gabriel; Baskin, Ernest; Bell, Raoul; Białobrzeska, Olga; Birt, Angie R; Boot, Walter R; Braithwaite, Scott R; Briggs, Jessie C; Buchner, Axel; Budd, Desiree; Budzik, Kathryn; Bullens, Lottie; Bulley, Richard L; Cannon, Peter R; Cantarero, Katarzyna; Cesario, Joseph; Chambers, Stephanie; Chartier, Christopher R; Chekroun, Peggy; Chong, Clara; Cleeremans, Axel; Coary, Sean P; Coulthard, Jacob; Cramwinckel, Florien M; Denson, Thomas F; Díaz-Lago, Marcos; DiDonato, Theresa E; Drummond, Aaron; Eberlen, Julia; Ebersbach, Titus; Edlund, John E; Finnigan, Katherine M; Fisher, Justin; Frankowska, Natalia; García-Sánchez, Efraín; Golom, Frank D; Graves, Andrew J; Greenberg, Kevin; Hanioti, Mando; Hansen, Heather A; Harder, Jenna A; Harrell, Erin R; Hartanto, Andree; Inzlicht, Michael; Johnson, David J; Karpinski, Andrew; Keller, Victor N; Klein, Olivier; Koppel, Lina; Krahmer, Emiel; Lantian, Anthony; Larson, Michael J; Légal, Jean-Baptiste; Lucas, Richard E; Lynott, Dermot; Magaldino, Corey M; Massar, Karlijn; McBee, Matthew T; McLatchie, Neil; Melia, Nadhilla; Mensink, Michael C; Mieth, Laura; Moore-Berg, Samantha; Neeser, Geraldine; Newell, Ben R; Noordewier, Marret K; Ali Özdoğru, Asil; Pantazi, Myrto; Parzuchowski, Michał; Peters, Kim; Philipp, Michael C; Pollmann, Monique M H; Rentzelas, Panagiotis; Rodríguez-Bailón, Rosa; Philipp Röer, Jan; Ropovik, Ivan; Roque, Nelson A; Rueda, Carolina; Rutjens, Bastiaan T; Sackett, Katey; Salamon, Janos; Sánchez-Rodríguez, Ángel; Saunders, Blair; Schaafsma, Juliette; Schulte-Mecklenbeck, Michael; Shanks, David R; Sherman, Martin F; Steele, Kenneth M; Steffens, Niklas K; Sun, Jessie; Susa, Kyle J; Szaszi, Barnabas; Szollosi, Aba; Tamayo, Ricardo M; Tinghög, Gustav; Tong, Yuk-Yue; Tweten, Carol; Vadillo, Miguel A; Valcarcel, Deisy; Van der Linden, Nicolas; van Elk, Michiel; van Harreveld, Frenk; Västfjäll, Daniel; Vazire, Simine; Verduyn, Philippe; Williams, Matt N; Willis, Guillermo B; Wood, Sarah E; Yang, Chunliang; Zerhouni, Oulmann; Zheng, Robert; Zrubka, Mark

2018-03-01

Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence ("professor") subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence ("soccer hooligans"). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the "professor" category and those primed with the "hooligan" category (0.14%) and no moderation by gender.

Smoking prevalence and seizure control in Chinese males with epilepsy.

PubMed

Gao, Hui; Sander, Josemir W; Du, Xudong; Chen, Jiani; Zhu, Cairong; Zhou, Dong

2017-08-01

Smoking has a negative effect on most diseases, yet it is under-investigated in people with epilepsy; thus its role is not clear in the general population with epilepsy. We performed a retrospective pilot study on males with epilepsy to determine the smoking rate and its relationship with seizure control using univariate analysis to calculate odds ratios (ORs) and also used a multi-variate logistic regression model. The smoking rate in our sample of 278 individuals was 25.5%, which is lower than the general Chinese population smoking rate among males of 52.1%. We used two classifications: the first classified epilepsy as generalized, or by presumed topographic origin (temporal, frontal, parietal and occipital). The second classified the dominant seizure type of an individual as generalized tonic clonic seizure (GTCS), myoclonic seizure (MS), complex partial seizure (CPS), simple partial seizure (SPS), and secondary GTCS (sGTCS). The univariable analysis of satisfactory seizure control profile and smoking rate in both classifications showed a trend towards a beneficial effect of smoking although most were not statistically significant. Considering medication is an important confounding factor that would largely influence seizure control, we also conducted multi-variable analysis for both classifications with drug numbers and dosage. The result of our model also suggested that smoking is a protective factor. Our findings seem to suggest that smoking could have a potential role in seizure control although confounders need exploration particularly in view of the potential long term health effects. Replication in a much larger sample is needed as well as case control studies to elucidate this issue. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis of the temporal program of replication initiation in yeast chromosomes.

PubMed

Friedman, K L; Raghuraman, M K; Fangman, W L; Brewer, B J

1995-01-01

The multiple origins of eukaryotic chromosomes vary in the time of their initiation during S phase. In the chromosomes of Saccharomyces cerevisiae the presence of a functional telomere causes nearby origins to delay initiation until the second half of S phase. The key feature of telomeres that causes the replication delay is the telomeric sequence (C(1-3)A/G(1-3)T) itself and not the proximity of the origin to a DNA end. A second group of late replicating origins has been found at an internal position on chromosome XIV. Four origins, spanning approximately 140 kb, initiate replication in the second half of S phase. At least two of these internal origins maintain their late replication time on circular plasmids. Each of these origins can be separated into two functional elements: those sequences that provide origin function and those that impose late activation. Because the assay for determining replication time is costly and laborious, it has not been possible to analyze in detail these 'late' elements. We report here the development of two new assays for determining replication time. The first exploits the expression of the Escherichia coli dam methylase in yeast and the characteristic period of hemimethylation that transiently follows the passage of a replication fork. The second uses quantitative hybridization to detect two-fold differences in the amount of specific restriction fragments as a function of progress through S phase. The novel aspect of this assay is the creation in vivo of a non-replicating DNA sequence by site-specific pop-out recombination. This non-replicating fragment acts as an internal control for copy number within and between samples. Both of these techniques are rapid and much less costly than the more conventional density transfer experiments that require CsCl gradients to detect replicated DNA. With these techniques it should be possible to identify the sequences responsible for late initiation, to search for other late replicating regions in the genome, and to begin to analyze the effect that altering the temporal program has on chromosome function.

Genome-Wide Analysis of the Core DNA Replication Machinery in the Higher Plants Arabidopsis and Rice1[W][OA

PubMed Central

Shultz, Randall W.; Tatineni, Vinaya M.; Hanley-Bowdoin, Linda; Thompson, William F.

2007-01-01

Core DNA replication proteins mediate the initiation, elongation, and Okazaki fragment maturation functions of DNA replication. Although this process is generally conserved in eukaryotes, important differences in the molecular architecture of the DNA replication machine and the function of individual subunits have been reported in various model systems. We have combined genome-wide bioinformatic analyses of Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) with published experimental data to provide a comprehensive view of the core DNA replication machinery in plants. Many components identified in this analysis have not been studied previously in plant systems, including the GINS (go ichi ni san) complex (PSF1, PSF2, PSF3, and SLD5), MCM8, MCM9, MCM10, NOC3, POLA2, POLA3, POLA4, POLD3, POLD4, and RNASEH2. Our results indicate that the core DNA replication machinery from plants is more similar to vertebrates than single-celled yeasts (Saccharomyces cerevisiae), suggesting that animal models may be more relevant to plant systems. However, we also uncovered some important differences between plants and vertebrate machinery. For example, we did not identify geminin or RNASEH1 genes in plants. Our analyses also indicate that plants may be unique among eukaryotes in that they have multiple copies of numerous core DNA replication genes. This finding raises the question of whether specialized functions have evolved in some cases. This analysis establishes that the core DNA replication machinery is highly conserved across plant species and displays many features in common with other eukaryotes and some characteristics that are unique to plants. PMID:17556508

34 CFR 611.11 - What are the program's general selection criteria?

Code of Federal Regulations, 2011 CFR

2011-07-01

...; (ii) Project outcomes lead directly to improvements in teaching quality and student achievement as... after federal funding ends; and (iv) Project strategies, methods, and accomplishments are replicable...

Efficient experimental design and analysis strategies for the detection of differential expression using RNA-Sequencing

PubMed Central

2012-01-01

Background RNA sequencing (RNA-Seq) has emerged as a powerful approach for the detection of differential gene expression with both high-throughput and high resolution capabilities possible depending upon the experimental design chosen. Multiplex experimental designs are now readily available, these can be utilised to increase the numbers of samples or replicates profiled at the cost of decreased sequencing depth generated per sample. These strategies impact on the power of the approach to accurately identify differential expression. This study presents a detailed analysis of the power to detect differential expression in a range of scenarios including simulated null and differential expression distributions with varying numbers of biological or technical replicates, sequencing depths and analysis methods. Results Differential and non-differential expression datasets were simulated using a combination of negative binomial and exponential distributions derived from real RNA-Seq data. These datasets were used to evaluate the performance of three commonly used differential expression analysis algorithms and to quantify the changes in power with respect to true and false positive rates when simulating variations in sequencing depth, biological replication and multiplex experimental design choices. Conclusions This work quantitatively explores comparisons between contemporary analysis tools and experimental design choices for the detection of differential expression using RNA-Seq. We found that the DESeq algorithm performs more conservatively than edgeR and NBPSeq. With regard to testing of various experimental designs, this work strongly suggests that greater power is gained through the use of biological replicates relative to library (technical) replicates and sequencing depth. Strikingly, sequencing depth could be reduced as low as 15% without substantial impacts on false positive or true positive rates. PMID:22985019

Efficient experimental design and analysis strategies for the detection of differential expression using RNA-Sequencing.

PubMed

Robles, José A; Qureshi, Sumaira E; Stephen, Stuart J; Wilson, Susan R; Burden, Conrad J; Taylor, Jennifer M

2012-09-17

RNA sequencing (RNA-Seq) has emerged as a powerful approach for the detection of differential gene expression with both high-throughput and high resolution capabilities possible depending upon the experimental design chosen. Multiplex experimental designs are now readily available, these can be utilised to increase the numbers of samples or replicates profiled at the cost of decreased sequencing depth generated per sample. These strategies impact on the power of the approach to accurately identify differential expression. This study presents a detailed analysis of the power to detect differential expression in a range of scenarios including simulated null and differential expression distributions with varying numbers of biological or technical replicates, sequencing depths and analysis methods. Differential and non-differential expression datasets were simulated using a combination of negative binomial and exponential distributions derived from real RNA-Seq data. These datasets were used to evaluate the performance of three commonly used differential expression analysis algorithms and to quantify the changes in power with respect to true and false positive rates when simulating variations in sequencing depth, biological replication and multiplex experimental design choices. This work quantitatively explores comparisons between contemporary analysis tools and experimental design choices for the detection of differential expression using RNA-Seq. We found that the DESeq algorithm performs more conservatively than edgeR and NBPSeq. With regard to testing of various experimental designs, this work strongly suggests that greater power is gained through the use of biological replicates relative to library (technical) replicates and sequencing depth. Strikingly, sequencing depth could be reduced as low as 15% without substantial impacts on false positive or true positive rates.

Has Adolescent Suicidality Decreased in the United States? Data from Two National Samples of Adolescents Interviewed in 1995 and 2005

ERIC Educational Resources Information Center

Wolitzky-Taylor, Kate B.; Ruggiero, Kenneth J.; McCart, Michael R.; Smith, Daniel W.; Hanson, Rochelle F.; Resnick, Heidi S.; de Arellano, Michael A.; Saunders, Benjamin E.; Kilpatrick, Dean G.

2010-01-01

We compared the prevalence and correlates of adolescent suicidal ideation and attempts in two nationally representative probability samples of adolescents interviewed in 1995 (National Survey of Adolescents; N = 4,023) and 2005 (National Survey of Adolescents-Replication; N = 3,614). Participants in both samples completed a telephone survey that…

Social Competence in Preschool Children: Replication of Results and Clarification of a Hierarchical Measurement Model

ERIC Educational Resources Information Center

Santos, Antonio J.; Peceguina, Ines; Daniel, Joao R.; Shin, Nana; Vaughn, Brian E.

2013-01-01

This study tested assumptions and conclusions reached in an earlier confirmatory factor analysis (CFA) study of the social competence (SC) construct for preschool children. Two samples (total N = 408; a new Portuguese sample and one from US samples that had participated in the original study) contributed data. Seven SC indicators were tested for…

A replicated molecular genetic basis for subtyping antisocial behavior in children with attention-deficit/hyperactivity disorder.

PubMed

Caspi, Avshalom; Langley, Kate; Milne, Barry; Moffitt, Terrie E; O'Donovan, Michael; Owen, Michael J; Polo Tomas, Monica; Poulton, Richie; Rutter, Michael; Taylor, Alan; Williams, Benjamin; Thapar, Anita

2008-02-01

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder that in some cases is accompanied by antisocial behavior. To test if variations in the catechol O-methyltransferase gene (COMT) would prove useful in identifying the subset of children with ADHD who exhibit antisocial behavior. Three independent samples composed of 1 clinical sample of ADHD cases and 2 birth cohort studies. Participants in the clinical sample were drawn from child psychiatry and child health clinics in England and Wales. The 2 birth cohort studies included 1 sample of 2232 British children born in 1994-1995 and a second sample of 1037 New Zealander children born in 1972-1973. Diagnosis of ADHD and measures of antisocial behavior. We present replicated evidence that the COMT valine/methionine polymorphism at codon 158 (COMT Val158Met) was associated with phenotypic variation among children with ADHD. Across the 3 samples, valine/valine homozygotes had more symptoms of conduct disorder, were more aggressive, and were more likely to be convicted of criminal offenses compared with methionine carriers. The findings confirm the presence of genetic heterogeneity in ADHD and illustrate how genetic information may provide biological evidence pointing to clinical subtypes.

Multiplication of infectious hematopoietic necrosis virus in rainbow trout following immersion infection: whole-body assay and immunohistochemistry

USGS Publications Warehouse

Yamamoto, T.; Batts, W.N.; Arakawa, C.K.; Winton, J.R.

1990-01-01

The sites of replication of infectious hematopoietic necrosis virus (IHNV) in infected tissues were detected in fingerling rainbow trout Oncorhynchus mykiss by in situ histologic techniques following immersion infection. Virus antigens in tissues were detected by a neutralizing mouse monoclonal antibody and a one-step anti-mouse biotin-streptavidin conjugated to horseradish peroxidase. The efficiency of infection and virulence of the virus determined by mortality rates showed high virulence of the selected IHNV isolates, and viral replication in individual fish showed that virus content of the fish increased rapidly from the second day to the seventh day postinfection. The earliest viral lesions following infection were detected in the epidermis of the pectoral fins, opercula, and ventral surface of the body. Virus lesions became evident in kidneys on the third day. By the fifth day, when there was a significant increase in virus titer, foci of viral replication were detected in gill tissue and in the anterior internal tissues below the epidermis. Subsequently, extensive virus replication and tissue destruction were observed in the spleen, dorsal adipose tissues, ventricle, and pseudobranch. Replication in the liver, the muscularis layers of the digestive tract, and the general body musculature followed later. These infection experiments indicated that the epidermis and gills of fish constitute important sites of early IHNV replication.

S175. AMOTIVATION IS ASSOCIATED WITH SMALLER VENTRAL STRIATUM VOLUMES IN OLDER PATIENTS WITH SCHIZOPHRENIA

PubMed Central

Caravaggio, Fernando; Fervaha, Gagan; Iwata, Yusuke; Plitman, Eric; Chung, Jun Ku; Nakajima, Shinichiro; Mar, Wanna; Gerretsen, Philip; Kim, Julia; Chakravarty, Mallar; Mulsant, Benoit; Pollock, Bruce; Mamo, David; Remington, Gary; Graff-Guerrero, Ariel

2018-01-01

Abstract Background Motivational deficits are prevalent in patients with schizophrenia, persist despite antipsychotic treatment, and predict long‐term outcomes. Evidence suggests that patients with greater amotivation have smaller ventral striatum (VS) volumes. We wished to replicate this finding in a sample of older, chronically medicated patients with schizophrenia. Using structural imaging and positron emission tomography, we examined whether amotivation uniquely predicted VS volumes beyond the effects of striatal dopamine D2/3 receptor (D2/3R) blockade by antipsychotics. Methods Data from 41 older schizophrenia patients (mean age: 60.2 ± 6.7; 11 female) were reanalysed from previously published imaging data. We constructed multivariate linear stepwise regression models with VS volumes as the dependent variable and various sociodemographic and clinical variables as the initial predictors: age, gender, total brain volume, and antipsychotic striatal D2/3R occupancy. Amotivation was included as a subsequent step to determine any unique relationships with VS volumes beyond the contribution of the covariates. In a reduced sample (n = 36), general cognition was also included as a covariate. Results Amotivation uniquely explained 8% and 6% of the variance in right and left VS volumes, respectively (right: β = -.38, t = -2.48, P = .01; left: β = -.31, t = -2.17, P = .03). Considering cognition, amotivation levels uniquely explained 9% of the variance in right VS volumes (β = -.43, t = -0.26, P = .03). Discussion We replicate and extend the finding of reduced VS volumes with greater amotivation. We demonstrate this relationship uniquely beyond the potential contributions of striatal D2/3R blockade by antipsychotics. Elucidating the structural correlates of amotivation in schizophrenia may help develop treatments for this presently irremediable deficit.

Use of risk assessment instruments to predict violence and antisocial behaviour in 73 samples involving 24 827 people: systematic review and meta-analysis.

PubMed

Fazel, Seena; Singh, Jay P; Doll, Helen; Grann, Martin

2012-07-24

To investigate the predictive validity of tools commonly used to assess the risk of violence, sexual, and criminal behaviour. Systematic review and tabular meta-analysis of replication studies following PRISMA guidelines. PsycINFO, Embase, Medline, and United States Criminal Justice Reference Service Abstracts. We included replication studies from 1 January 1995 to 1 January 2011 if they provided contingency data for the offending outcome that the tools were designed to predict. We calculated the diagnostic odds ratio, sensitivity, specificity, area under the curve, positive predictive value, negative predictive value, the number needed to detain to prevent one offence, as well as a novel performance indicator-the number safely discharged. We investigated potential sources of heterogeneity using metaregression and subgroup analyses. Risk assessments were conducted on 73 samples comprising 24,847 participants from 13 countries, of whom 5879 (23.7%) offended over an average of 49.6 months. When used to predict violent offending, risk assessment tools produced low to moderate positive predictive values (median 41%, interquartile range 27-60%) and higher negative predictive values (91%, 81-95%), and a corresponding median number needed to detain of 2 (2-4) and number safely discharged of 10 (4-18). Instruments designed to predict violent offending performed better than those aimed at predicting sexual or general crime. Although risk assessment tools are widely used in clinical and criminal justice settings, their predictive accuracy varies depending on how they are used. They seem to identify low risk individuals with high levels of accuracy, but their use as sole determinants of detention, sentencing, and release is not supported by the current evidence. Further research is needed to examine their contribution to treatment and management.

Variation in Gas and Volatile Compound Emissions from Human Urine as It Ages, Measured by an Electronic Nose.

PubMed

Esfahani, Siavash; Sagar, Nidhi M; Kyrou, Ioannis; Mozdiak, Ella; O'Connell, Nicola; Nwokolo, Chuka; Bardhan, Karna D; Arasaradnam, Ramesh P; Covington, James A

2016-01-25

The medical profession is becoming ever more interested in the use of gas-phase biomarkers for disease identification and monitoring. This is due in part to its rapid analysis time and low test cost, which makes it attractive for many different clinical arenas. One technology that is showing promise for analyzing these gas-phase biomarkers is the electronic nose--an instrument designed to replicate the biological olfactory system. Of the possible biological media available to "sniff", urine is becoming ever more important as it is easy to collect and to store for batch testing. However, this raises the question of sample storage shelf-life, even at -80 °C. Here we investigated the effect of storage time (years) on stability and reproducibility of total gas/vapour emissions from urine samples. Urine samples from 87 patients with Type 2 Diabetes Mellitus were collected over a four-year period and stored at -80 °C. These samples were then analyzed using FAIMS (field-asymmetric ion mobility spectrometry--a type of electronic nose). It was discovered that gas emissions (concentration and diversity) reduced over time. However, there was less variation in the initial nine months of storage with greater uniformity and stability of concentrations together with tighter clustering of the total number of chemicals released. This suggests that nine months could be considered a general guide to a sample shelf-life.

Evaluation of Quality-Assurance/Quality-Control Data Collected by the U.S. Geological Survey from Wells and Springs between the Southern Boundary of the Idaho National Engineering and Environmental Laboratory and the Hagerman Area, Idaho, 1989 through 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, L.M.; Bartholomay, R.C.; Campbell, L.J.

1998-10-01

The U.S. Geological (USGS) and the Idaho Department of Water Resources, in cooperation with the U.S. Department of Energy, collected and analyzed water samples to monitor the water quality of the Snake River Plain aquifer from the southern boundary of the Idaho National Engineering and Environmental Laboratory to the Hagerman area, Idaho. Concurrently, replicate samples and blank samples were collected and analyzed as part of the quality-assurance/quality-control program. Samples were analyzed from inorganic constituents, gross radioactivity and radionuclides, organic constituents, and stable isotopes. To evaluate the precision of field and laboratory methods, analytical results of the water-quality and replicate samplesmore » were compared statistically for equivalence on the basis of the precision associated with each result. Statistical comparisons of the data indicated that 95 percent of the results of the replicate pairs were equivalent. Blank-sample analytical results indicated th at the inorganic blank water and volatile organic compound blank water from the USGS National Water Quality Laboratory and the distilled water from the Idaho Department of Water Resources were suitable for blanks; blank water from other sources was not. Equipment-blank analytical results were evaluated to determine if a bias had been introduced and possible sources of bias. Most equipment blanks were analyzed for trace elements and volatile organic compounds; chloroform was found in one equipment blank. Two of the equipment blanks were prepared after collection and analyses of the water-quality samples to determine whether contamination had been introduced during the sampling process. Results of one blank indicated that a hose used to divert water away from pumps and electrical equipment had contaminated the samples with some volatile organic compounds. Results of the other equipment blank, from the apparatus used to filter dissolved organic carbon samples, indicated that the filtering apparatus did not affect water-quality samples.« less

Patterns and Prevalence of Core Profile Types in the WPPSI Standardization Sample.

ERIC Educational Resources Information Center

Glutting, Joseph J.; McDermott, Paul A.

1990-01-01

Found most representative subtest profiles for 1,200 children comprising standardization sample of Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Grouped scaled scores from WPPSI subtests according to similar level and shape using sequential minimum-variance cluster analysis with independent replications. Obtained final solution of…

Same Talker, Different Language: A Replication.

ERIC Educational Resources Information Center

Stockmal, Verna; Bond, Z. S.

This research investigated judgments of language samples produced by bilingual speakers. In the first study, listeners judged whether two language samples produced by bilingual speakers were spoken in the same language or in two different languages. Four bilingual African talkers recorded short passages in Swahili and in their home language (Akan,…

Promoting Teachers' Generalization of Intervention Use through Goal Setting and Performance Feedback

ERIC Educational Resources Information Center

Duncan, Neelima G.; Dufrene, Brad A.; Sterling, Heather E.; Tingstrom, Daniel H.

2013-01-01

Consultation is beneficial for increasing teachers' intervention use for target students. However, little is known about teachers' generalized intervention use. This study is a systematic replication of Riley-Tillman and Eckert ("J Educ Psychol Consult" 12:217-241, 2001) and Martens et al. ("Sch Psychol Q" 12:33-41,…

Object Categorization: Reversals and Explanations of the Basic-Level Advantage

ERIC Educational Resources Information Center

Rogers, Timothy T.; Patterson, Karalyn

2007-01-01

People are generally faster and more accurate to name or categorize objects at the basic level (e.g., dog) relative to more general (animal) or specific (collie) levels, an effect replicated in Experiment 1 for categorization of object pictures. To some, this pattern suggests a dual-process mechanism, in which objects first activate basic-level…

Predicting Behavior Assessment System for Children-Second Edition Self-Report of Personality Child Form Results Using the Behavioral and Emotional Screening System Student Form: A Replication Study with an Urban, Predominantly Latino/a Sample

ERIC Educational Resources Information Center

Kiperman, Sarah; Black, Mary S.; McGill, Tia M.; Harrell-Williams, Leigh M.; Kamphaus, Randy W.

2014-01-01

This study assesses the ability of a brief screening form, the Behavioral and Emotional Screening System-Student Form (BESS-SF), to predict scores on the much longer form from which it was derived: the Behavior Assessment System for Children-Second Edition Self-Report of Personality-Child Form (BASC-2-SRP-C). The present study replicates a former…

Dimensions of self-leadership: a German replication and extension.

PubMed

Müller, Güonter F

2006-10-01

In a sample of 167 German students three dimensions of self-leadership, i.e., constructive thoughts, natural reward creation, and proactive behavior, were replicated as when scale values of a German self-leadership questionnaire were subjected to confirmatory factor analysis very satisfactory fit-indices were obtained. In addition, dimensions of self-leadership correlated with entrepreneurial trait disposition (multiple R=0.46, p < .01), and entrepreneurial job orientation (multiple R=0.23, p < .05). Conclusions for further research and practical applications are discussed.

Moment-to-Moment Transfer of Positive Emotions in Daily Life Predicts Future Course of Depression in Both General Population and Patient Samples

PubMed Central

Höhn, Petra; Menne-Lothmann, Claudia; Peeters, Frenk; Nicolson, Nancy A.; Jacobs, Nele; Derom, Catherine; Thiery, Evert; van Os, Jim; Wichers, Marieke

2013-01-01

Objective Positive affect (PA) is closely linked to prevention of, and recovery from, depression. Previous studies have investigated PA reactivity to pleasant situations with respect to its protective properties in relation to mood disorder. The purpose of this study was to examine, and replicate, whether moment-to-moment transfer of PA in daily life (PA persistence) is relevant to the prediction of future course of depression. Method Individuals from three different studies (one general population sample (n=540), and two patient samples (n=43 and n=50) with matching controls (n=39 and n=21, respectively)) participated in an Experience Sampling Method (ESM) study. Time-lagged multilevel analyses were used to assess the degree of transfer (or persistence) of momentary positive affective states over time, in relation to naturalistic outcome (study 1) or treatment outcome (studies 2 and 3). Depressive symptoms were measured using the Symptom Checklist (SCL-90R) in sample 1 and the Hamilton Depression Rating Scale (HDRS) in samples 2 and 3. Results In study 1, participants with greater momentary PA persistence were less likely to show depressive symptoms at follow-up. In study 2, patients were more likely to respond to treatment if they displayed greater momentary PA persistence, particularly in those with recurrent depression. In study 3, patients with greater momentary PA persistence were similarly more likely to respond to treatment, especially when treated with imipramine rather than placebo. Conclusion The ability to transfer PA from one moment to the next is an important factor in the prevention of and recovery from depressive symptoms. Patients with recurrent depression and those who receive antidepressants rather than placebo may benefit most from this effect. The results suggest that treatment-induced improvement in depression is mediated by increased levels of momentary transfer of PA in daily life, acquisition of which may be contingent on duration of exposure to depressive experience. PMID:24086602