Sample records for agreement kappa statistic

  1. Kappa statistic to measure agreement beyond chance in free-response assessments.

    PubMed

    Carpentier, Marc; Combescure, Christophe; Merlini, Laura; Perneger, Thomas V

    2017-04-19

    The usual kappa statistic requires that all observations be enumerated. However, in free-response assessments, only positive (or abnormal) findings are notified, but negative (or normal) findings are not. This situation occurs frequently in imaging or other diagnostic studies. We propose here a kappa statistic that is suitable for free-response assessments. We derived the equivalent of Cohen's kappa statistic for two raters under the assumption that the number of possible findings for any given patient is very large, as well as a formula for sampling variance that is applicable to independent observations (for clustered observations, a bootstrap procedure is proposed). The proposed statistic was applied to a real-life dataset, and compared with the common practice of collapsing observations within a finite number of regions of interest. The free-response kappa is computed from the total numbers of discordant (b and c) and concordant positive (d) observations made in all patients, as 2d/(b + c + 2d). In 84 full-body magnetic resonance imaging procedures in children that were evaluated by 2 independent raters, the free-response kappa statistic was 0.820. Aggregation of results within regions of interest resulted in overestimation of agreement beyond chance. The free-response kappa provides an estimate of agreement beyond chance in situations where only positive findings are reported by raters.

  2. Interrater reliability: the kappa statistic.

    PubMed

    McHugh, Mary L

    2012-01-01

    The kappa statistic is frequently used to test interrater reliability. The importance of rater reliability lies in the fact that it represents the extent to which the data collected in the study are correct representations of the variables measured. Measurement of the extent to which data collectors (raters) assign the same score to the same variable is called interrater reliability. While there have been a variety of methods to measure interrater reliability, traditionally it was measured as percent agreement, calculated as the number of agreement scores divided by the total number of scores. In 1960, Jacob Cohen critiqued use of percent agreement due to its inability to account for chance agreement. He introduced the Cohen's kappa, developed to account for the possibility that raters actually guess on at least some variables due to uncertainty. Like most correlation statistics, the kappa can range from -1 to +1. While the kappa is one of the most commonly used statistics to test interrater reliability, it has limitations. Judgments about what level of kappa should be acceptable for health research are questioned. Cohen's suggested interpretation may be too lenient for health related studies because it implies that a score as low as 0.41 might be acceptable. Kappa and percent agreement are compared, and levels for both kappa and percent agreement that should be demanded in healthcare studies are suggested.

  3. The disagreeable behaviour of the kappa statistic.

    PubMed

    Flight, Laura; Julious, Steven A

    2015-01-01

    It is often of interest to measure the agreement between a number of raters when an outcome is nominal or ordinal. The kappa statistic is used as a measure of agreement. The statistic is highly sensitive to the distribution of the marginal totals and can produce unreliable results. Other statistics such as the proportion of concordance, maximum attainable kappa and prevalence and bias adjusted kappa should be considered to indicate how well the kappa statistic represents agreement in the data. Each kappa should be considered and interpreted based on the context of the data being analysed. Copyright © 2014 John Wiley & Sons, Ltd.

  4. The kappa statistic in rehabilitation research: an examination.

    PubMed

    Tooth, Leigh R; Ottenbacher, Kenneth J

    2004-08-01

    The number and sophistication of statistical procedures reported in medical rehabilitation research is increasing. Application of the principles and methods associated with evidence-based practice has contributed to the need for rehabilitation practitioners to understand quantitative methods in published articles. Outcomes measurement and determination of reliability are areas that have experienced rapid change during the past decade. In this study, distinctions between reliability and agreement are examined. Information is presented on analytical approaches for addressing reliability and agreement with the focus on the application of the kappa statistic. The following assumptions are discussed: (1) kappa should be used with data measured on a categorical scale, (2) the patients or objects categorized should be independent, and (3) the observers or raters must make their measurement decisions and judgments independently. Several issues related to using kappa in measurement studies are described, including use of weighted kappa, methods of reporting kappa, the effect of bias and prevalence on kappa, and sample size and power requirements for kappa. The kappa statistic is useful for assessing agreement among raters, and it is being used more frequently in rehabilitation research. Correct interpretation of the kappa statistic depends on meeting the required assumptions and accurate reporting.

  5. High Agreement and High Prevalence: The Paradox of Cohen's Kappa.

    PubMed

    Zec, Slavica; Soriani, Nicola; Comoretto, Rosanna; Baldi, Ileana

    2017-01-01

    Cohen's Kappa is the most used agreement statistic in literature. However, under certain conditions, it is affected by a paradox which returns biased estimates of the statistic itself. The aim of the study is to provide sufficient information which allows the reader to make an informed choice of the correct agreement measure, by underlining some optimal properties of Gwet's AC1 in comparison to Cohen's Kappa, using a real data example. During the process of literature review, we have asked a panel of three evaluators to come up with a judgment on the quality of 57 randomized controlled trials assigning a score to each trial using the Jadad scale. The quality was evaluated according to the following dimensions: adopted design, randomization unit, type of primary endpoint. With respect to each of the above described features, the agreement between the three evaluators has been calculated using Cohen's Kappa statistic and Gwet's AC1 statistic and, finally, the values have been compared with the observed agreement. The values of the Cohen's Kappa statistic would lead to believe that the agreement levels for the variables Unit, Design and Primary Endpoints are totally unsatisfactory. The AC1 statistic, on the contrary, shows plausible values which are in line with the respective values of the observed concordance. We conclude that it would always be appropriate to adopt the AC1 statistic, thus bypassing any risk of incurring the paradox and drawing wrong conclusions about the results of agreement analysis.

  6. Nomogram for sample size calculation on a straightforward basis for the kappa statistic.

    PubMed

    Hong, Hyunsook; Choi, Yunhee; Hahn, Seokyung; Park, Sue Kyung; Park, Byung-Joo

    2014-09-01

    Kappa is a widely used measure of agreement. However, it may not be straightforward in some situation such as sample size calculation due to the kappa paradox: high agreement but low kappa. Hence, it seems reasonable in sample size calculation that the level of agreement under a certain marginal prevalence is considered in terms of a simple proportion of agreement rather than a kappa value. Therefore, sample size formulae and nomograms using a simple proportion of agreement rather than a kappa under certain marginal prevalences are proposed. A sample size formula was derived using the kappa statistic under the common correlation model and goodness-of-fit statistic. The nomogram for the sample size formula was developed using SAS 9.3. The sample size formulae using a simple proportion of agreement instead of a kappa statistic and nomograms to eliminate the inconvenience of using a mathematical formula were produced. A nomogram for sample size calculation with a simple proportion of agreement should be useful in the planning stages when the focus of interest is on testing the hypothesis of interobserver agreement involving two raters and nominal outcome measures. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Inequalities between Kappa and Kappa-Like Statistics for "k x k" Tables

    ERIC Educational Resources Information Center

    Warrens, Matthijs J.

    2010-01-01

    The paper presents inequalities between four descriptive statistics that can be expressed in the form [P-E(P)]/[1-E(P)], where P is the observed proportion of agreement of a "kappa x kappa" table with identical categories, and E(P) is a function of the marginal probabilities. Scott's "pi" is an upper bound of Goodman and Kruskal's "lambda" and a…

  8. The Problems with the Kappa Statistic as a Metric of Interobserver Agreement on Lesion Detection Using a Third-reader Approach When Locations Are Not Prespecified.

    PubMed

    Shih, Joanna H; Greer, Matthew D; Turkbey, Baris

    2018-03-16

    To point out the problems with Cohen kappa statistic and to explore alternative metrics to determine interobserver agreement on lesion detection when locations are not prespecified. Use of kappa and two alternative methods, namely index of specific agreement (ISA) and modified kappa, for measuring interobserver agreement on the location of detected lesions are presented. These indices of agreement are illustrated by application to a retrospective multireader study in which nine readers detected and scored prostate cancer lesions in 163 consecutive patients (n = 110 cases, n = 53 controls) using the guideline of Prostate Imaging Reporting and Data System version 2 on multiparametric magnetic resonance imaging. The proposed modified kappa, which properly corrects for the amount of agreement by chance, is shown to be approximately equivalent to the ISA. In the prostate cancer data, average kappa, modified kappa, and ISA equaled 30%, 55%, and 57%, respectively, for all lesions and 20%, 87%, and 87%, respectively, for index lesions. The application of kappa could result in a substantial downward bias in reader agreement on lesion detection when locations are not prespecified. ISA is recommended for assessment of reader agreement on lesion detection. Published by Elsevier Inc.

  9. Kappa statistic for clustered matched-pair data.

    PubMed

    Yang, Zhao; Zhou, Ming

    2014-07-10

    Kappa statistic is widely used to assess the agreement between two procedures in the independent matched-pair data. For matched-pair data collected in clusters, on the basis of the delta method and sampling techniques, we propose a nonparametric variance estimator for the kappa statistic without within-cluster correlation structure or distributional assumptions. The results of an extensive Monte Carlo simulation study demonstrate that the proposed kappa statistic provides consistent estimation and the proposed variance estimator behaves reasonably well for at least a moderately large number of clusters (e.g., K ≥50). Compared with the variance estimator ignoring dependence within a cluster, the proposed variance estimator performs better in maintaining the nominal coverage probability when the intra-cluster correlation is fair (ρ ≥0.3), with more pronounced improvement when ρ is further increased. To illustrate the practical application of the proposed estimator, we analyze two real data examples of clustered matched-pair data. Copyright © 2014 John Wiley & Sons, Ltd.

  10. A note on the kappa statistic for clustered dichotomous data.

    PubMed

    Zhou, Ming; Yang, Zhao

    2014-06-30

    The kappa statistic is widely used to assess the agreement between two raters. Motivated by a simulation-based cluster bootstrap method to calculate the variance of the kappa statistic for clustered physician-patients dichotomous data, we investigate its special correlation structure and develop a new simple and efficient data generation algorithm. For the clustered physician-patients dichotomous data, based on the delta method and its special covariance structure, we propose a semi-parametric variance estimator for the kappa statistic. An extensive Monte Carlo simulation study is performed to evaluate the performance of the new proposal and five existing methods with respect to the empirical coverage probability, root-mean-square error, and average width of the 95% confidence interval for the kappa statistic. The variance estimator ignoring the dependence within a cluster is generally inappropriate, and the variance estimators from the new proposal, bootstrap-based methods, and the sampling-based delta method perform reasonably well for at least a moderately large number of clusters (e.g., the number of clusters K ⩾50). The new proposal and sampling-based delta method provide convenient tools for efficient computations and non-simulation-based alternatives to the existing bootstrap-based methods. Moreover, the new proposal has acceptable performance even when the number of clusters is as small as K = 25. To illustrate the practical application of all the methods, one psychiatric research data and two simulated clustered physician-patients dichotomous data are analyzed. Copyright © 2014 John Wiley & Sons, Ltd.

  11. A Note on the Interpretation of Weighted Kappa and its Relations to Other Rater Agreement Statistics for Metric Scales

    ERIC Educational Resources Information Center

    Schuster, Christof

    2004-01-01

    This article presents a formula for weighted kappa in terms of rater means, rater variances, and the rater covariance that is particularly helpful in emphasizing that weighted kappa is an absolute agreement measure in the sense that it is sensitive to differences in rater's marginal distributions. Specifically, rater mean differences will decrease…

  12. Count on kappa.

    PubMed

    Czodrowski, Paul

    2014-11-01

    In the 1960s, the kappa statistic was introduced for the estimation of chance agreement in inter- and intra-rater reliability studies. The kappa statistic was strongly pushed by the medical field where it could be successfully applied via analyzing diagnoses of identical patient groups. Kappa is well suited for classification tasks where ranking is not considered. The main advantage of kappa is its simplicity and the general applicability to multi-class problems which is the major difference to receiver operating characteristic area under the curve. In this manuscript, I will outline the usage of kappa for classification tasks, and I will evaluate the role and uses of kappa in specifically machine learning and cheminformatics.

  13. Testing the Difference of Correlated Agreement Coefficients for Statistical Significance

    ERIC Educational Resources Information Center

    Gwet, Kilem L.

    2016-01-01

    This article addresses the problem of testing the difference between two correlated agreement coefficients for statistical significance. A number of authors have proposed methods for testing the difference between two correlated kappa coefficients, which require either the use of resampling methods or the use of advanced statistical modeling…

  14. Inter-Coder Agreement in One-to-Many Classification: Fuzzy Kappa.

    PubMed

    Kirilenko, Andrei P; Stepchenkova, Svetlana

    2016-01-01

    Content analysis involves classification of textual, visual, or audio data. The inter-coder agreement is estimated by making two or more coders to classify the same data units, with subsequent comparison of their results. The existing methods of agreement estimation, e.g., Cohen's kappa, require that coders place each unit of content into one and only one category (one-to-one coding) from the pre-established set of categories. However, in certain data domains (e.g., maps, photographs, databases of texts and images), this requirement seems overly restrictive. The restriction could be lifted, provided that there is a measure to calculate the inter-coder agreement in the one-to-many protocol. Building on the existing approaches to one-to-many coding in geography and biomedicine, such measure, fuzzy kappa, which is an extension of Cohen's kappa, is proposed. It is argued that the measure is especially compatible with data from certain domains, when holistic reasoning of human coders is utilized in order to describe the data and access the meaning of communication.

  15. Inter-Coder Agreement in One-to-Many Classification: Fuzzy Kappa

    PubMed Central

    Kirilenko, Andrei P.; Stepchenkova, Svetlana

    2016-01-01

    Content analysis involves classification of textual, visual, or audio data. The inter-coder agreement is estimated by making two or more coders to classify the same data units, with subsequent comparison of their results. The existing methods of agreement estimation, e.g., Cohen’s kappa, require that coders place each unit of content into one and only one category (one-to-one coding) from the pre-established set of categories. However, in certain data domains (e.g., maps, photographs, databases of texts and images), this requirement seems overly restrictive. The restriction could be lifted, provided that there is a measure to calculate the inter-coder agreement in the one-to-many protocol. Building on the existing approaches to one-to-many coding in geography and biomedicine, such measure, fuzzy kappa, which is an extension of Cohen’s kappa, is proposed. It is argued that the measure is especially compatible with data from certain domains, when holistic reasoning of human coders is utilized in order to describe the data and access the meaning of communication. PMID:26933956

  16. Measuring agreement of multivariate discrete survival times using a modified weighted kappa coefficient.

    PubMed

    Guo, Ying; Manatunga, Amita K

    2009-03-01

    Assessing agreement is often of interest in clinical studies to evaluate the similarity of measurements produced by different raters or methods on the same subjects. We present a modified weighted kappa coefficient to measure agreement between bivariate discrete survival times. The proposed kappa coefficient accommodates censoring by redistributing the mass of censored observations within the grid where the unobserved events may potentially happen. A generalized modified weighted kappa is proposed for multivariate discrete survival times. We estimate the modified kappa coefficients nonparametrically through a multivariate survival function estimator. The asymptotic properties of the kappa estimators are established and the performance of the estimators are examined through simulation studies of bivariate and trivariate survival times. We illustrate the application of the modified kappa coefficient in the presence of censored observations with data from a prostate cancer study.

  17. Some Paradoxical Results for the Quadratically Weighted Kappa

    ERIC Educational Resources Information Center

    Warrens, Matthijs J.

    2012-01-01

    The quadratically weighted kappa is the most commonly used weighted kappa statistic for summarizing interrater agreement on an ordinal scale. The paper presents several properties of the quadratically weighted kappa that are paradoxical. For agreement tables with an odd number of categories "n" it is shown that if one of the raters uses the same…

  18. Appropriate Statistics for Determining Chance-Removed Interpractitioner Agreement.

    PubMed

    Popplewell, Michael; Reizes, John; Zaslawski, Chris

    2018-05-31

    Fleiss' Kappa (FK) has been commonly, but incorrectly, employed as the "standard" for evaluating chance-removed inter-rater agreement with ordinal data. This practice may lead to misleading conclusions in inter-rater agreement research. An example is presented that demonstrates the conditions where FK produces inappropriate results, compared with Gwet's AC2, which is proposed as a more appropriate statistic. A novel format for recording a Chinese Medical (CM) diagnoses, called the Diagnostic System of Oriental Medicine (DSOM), was used to record and compare patient diagnostic data, which, unlike the contemporary CM diagnostic format, allows agreement by chance to be considered when evaluating patient data obtained with unrestricted diagnostic options available to diagnosticians. Five CM practitioners diagnosed 42 subjects drawn from an open population. Subjects' diagnoses were recorded using the DSOM format. All the available data were initially used to evaluate agreement. Then, the subjects were sorted into three groups to demonstrate the effects of differing data marginality on the calculated chance-removed agreement. Agreement between the practitioners for each subject was evaluated with linearly weighted simple agreement, FK and Gwet's AC2. In all cases, overall agreement was much lower with FK than Gwet's AC2. Larger differences occurred when the data were more free marginal. Inter-rater agreement determined with FK statistics is unlikely to be correct unless it can be shown that the data from which agreement is determined are, in fact, fixed marginal. It follows that results obtained on agreement between practitioners with FK are probably incorrect. It is shown that inter-rater agreement evaluated with AC2 statistic is an appropriate measure when fixed marginal data are neither expected nor guaranteed. The AC2 statistic should be used as the standard statistical approach for determining agreement between practitioners.

  19. Kappa statistic for clustered dichotomous responses from physicians and patients.

    PubMed

    Kang, Chaeryon; Qaqish, Bahjat; Monaco, Jane; Sheridan, Stacey L; Cai, Jianwen

    2013-09-20

    The bootstrap method for estimating the standard error of the kappa statistic in the presence of clustered data is evaluated. Such data arise, for example, in assessing agreement between physicians and their patients regarding their understanding of the physician-patient interaction and discussions. We propose a computationally efficient procedure for generating correlated dichotomous responses for physicians and assigned patients for simulation studies. The simulation result demonstrates that the proposed bootstrap method produces better estimate of the standard error and better coverage performance compared with the asymptotic standard error estimate that ignores dependence among patients within physicians with at least a moderately large number of clusters. We present an example of an application to a coronary heart disease prevention study. Copyright © 2013 John Wiley & Sons, Ltd.

  20. Kappa statistic for the clustered dichotomous responses from physicians and patients

    PubMed Central

    Kang, Chaeryon; Qaqish, Bahjat; Monaco, Jane; Sheridan, Stacey L.; Cai, Jianwen

    2013-01-01

    The bootstrap method for estimating the standard error of the kappa statistic in the presence of clustered data is evaluated. Such data arise, for example, in assessing agreement between physicians and their patients regarding their understanding of the physician-patient interaction and discussions. We propose a computationally efficient procedure for generating correlated dichotomous responses for physicians and assigned patients for simulation studies. The simulation result demonstrates that the proposed bootstrap method produces better estimate of the standard error and better coverage performance compared to the asymptotic standard error estimate that ignores dependence among patients within physicians with at least a moderately large number of clusters. An example of an application to a coronary heart disease prevention study is presented. PMID:23533082

  1. Interobserver agreement on Poser's and the new McDonald's diagnostic criteria for multiple sclerosis.

    PubMed

    Zipoli, V; Portaccio, E; Siracusa, G; Pracucci, G; Sorbi, S; Amato, M P

    2003-10-01

    We assessed the interobserver agreement on the diagnosis of multiple sclerosis (MS) in a study sample consisting of 41 MS (15 relapsing remitting, two secondary progressive, five primary progressive and 19 presenting their first clinical attack) and three non-MS cases. Clinical and paraclinical information was recorded in standardized forms. Four neurologists were asked to make a diagnosis using Poser's and McDonald's criteria and to assess MRI scans according to the McDonald's guidelines. In terms of the kappa statistic (kappa), we found a moderate agreement on the overall diagnosis using both Poser's and McDonald's criteria (kappa, respectively 0.57 and 0.52). As for distinct diagnostic categories, we observed a moderate to substantial agreement for the three McDonald categories (range of kappa values 0.49-0.64) and a fair to substantial agreement for the nine Poser categories (range of kappa values 0.37-0.67). Taking into account clinical information, the agreement on dissemination over time was substantially higher (kappa = 0.69) than that found on dissemination over space (kappa = 0.46). In contrast, for MRI assessment, the agreement for spatial dissemination was substantial (kappa = 0.74) compared with the fair agreement (kappa = 0.25) yielded by dissemination over time. The new McDonald's criteria yield a good overall diagnostic reliability, and compare favourably with Poser's classification in terms of agreement on distinct diagnostic categories.

  2. Measurement of Angle Kappa Using Ultrasound Biomicroscopy and Corneal Topography

    PubMed Central

    Yeo, Joon Hyung; Moon, Nam Ju

    2017-01-01

    Purpose To introduce a new convenient and accurate method to measure the angle kappa using ultrasound biomicroscopy (UBM) and corneal topography. Methods Data from 42 eyes (13 males and 29 females) were analyzed in this study. The angle kappa was measured using Orbscan II and calculated with UBM and corneal topography. The angle kappa of the dominant eye was compared with measurements by Orbscan II. Results The mean patient age was 36.4 ± 13.8 years. The average angle kappa measured by Orbscan II was 3.98° ± 1.12°, while the average angle kappa calculated with UBM and corneal topography was 3.19° ± 1.15°. The difference in angle kappa measured by the two methods was statistically significant (p < 0.001). The two methods showed good reliability (intraclass correlation coefficient, 0.671; p < 0.001). Bland-Altman plots were used to demonstrate the agreement between the two methods. Conclusions We designed a new method using UBM and corneal topography to calculate the angle kappa. This method is convenient to use and allows for measurement of the angle kappa without an expensive device. PMID:28471103

  3. Measurement of Angle Kappa Using Ultrasound Biomicroscopy and Corneal Topography.

    PubMed

    Yeo, Joon Hyung; Moon, Nam Ju; Lee, Jeong Kyu

    2017-06-01

    To introduce a new convenient and accurate method to measure the angle kappa using ultrasound biomicroscopy (UBM) and corneal topography. Data from 42 eyes (13 males and 29 females) were analyzed in this study. The angle kappa was measured using Orbscan II and calculated with UBM and corneal topography. The angle kappa of the dominant eye was compared with measurements by Orbscan II. The mean patient age was 36.4 ± 13.8 years. The average angle kappa measured by Orbscan II was 3.98° ± 1.12°, while the average angle kappa calculated with UBM and corneal topography was 3.19° ± 1.15°. The difference in angle kappa measured by the two methods was statistically significant (p < 0.001). The two methods showed good reliability (intraclass correlation coefficient, 0.671; p < 0.001). Bland-Altman plots were used to demonstrate the agreement between the two methods. We designed a new method using UBM and corneal topography to calculate the angle kappa. This method is convenient to use and allows for measurement of the angle kappa without an expensive device. © 2017 The Korean Ophthalmological Society

  4. Statistical properties of measures of association and the Kappa statistic for assessing the accuracy of remotely sensed data using double sampling

    Treesearch

    Mohammed A. Kalkhan; Robin M. Reich; Raymond L. Czaplewski

    1996-01-01

    A Monte Carlo simulation was used to evaluate the statistical properties of measures of association and the Kappa statistic under double sampling with replacement. Three error matrices representing three levels of classification accuracy of Landsat TM Data consisting of four forest cover types in North Carolina. The overall accuracy of the five indices ranged from 0.35...

  5. A Ratio Test of Interrater Agreement with High Specificity

    ERIC Educational Resources Information Center

    Cousineau, Denis; Laurencelle, Louis

    2015-01-01

    Existing tests of interrater agreements have high statistical power; however, they lack specificity. If the ratings of the two raters do not show agreement but are not random, the current tests, some of which are based on Cohen's kappa, will often reject the null hypothesis, leading to the wrong conclusion that agreement is present. A new test of…

  6. Inter-observer and intra-observer agreement on interpretation of uroflowmetry curves of kindergarten children.

    PubMed

    Chang, Shang-Jen; Yang, Stephen S D

    2008-12-01

    To evaluate the inter-observer and intra-observer agreement on the interpretation of uroflowmetry curves of children. Healthy kindergarten children were enrolled for evaluation of uroflowmetry. Uroflowmetry curves were classified as bell-shaped, tower, plateau, staccato and interrupted. Only the bell-shaped curves were regarded as normal. Two urodynamists evaluated the curves independently after reviewing the definitions of the different types of uroflowmetry curve. The senior urodynamist evaluated the curves twice 3 months apart. The final conclusion was made when consensus was reached. Agreement among observers was analyzed using kappa statistics. Of 190 uroflowmetry curves eligible for analysis, the intra-observer agreement in interpreting each type of curve and interpreting normalcy vs abnormality was good (kappa=0.71 and 0.68, respectively). Very good inter-observer agreement (kappa=0.81) on normalcy and good inter-observer agreement (kappa=0.73) on types of uroflowmetry were observed. Poor inter-observer agreement existed on the classification of specific types of abnormal uroflowmetry curves (kappa=0.07). Uroflowmetry is a good screening tool for normalcy of kindergarten children, while not a good tool to define the specific types of abnormal uroflowmetry.

  7. Log-Linear Modeling of Agreement among Expert Exposure Assessors

    PubMed Central

    Hunt, Phillip R.; Friesen, Melissa C.; Sama, Susan; Ryan, Louise; Milton, Donald

    2015-01-01

    Background: Evaluation of expert assessment of exposure depends, in the absence of a validation measurement, upon measures of agreement among the expert raters. Agreement is typically measured using Cohen’s Kappa statistic, however, there are some well-known limitations to this approach. We demonstrate an alternate method that uses log-linear models designed to model agreement. These models contain parameters that distinguish between exact agreement (diagonals of agreement matrix) and non-exact associations (off-diagonals). In addition, they can incorporate covariates to examine whether agreement differs across strata. Methods: We applied these models to evaluate agreement among expert ratings of exposure to sensitizers (none, likely, high) in a study of occupational asthma. Results: Traditional analyses using weighted kappa suggested potential differences in agreement by blue/white collar jobs and office/non-office jobs, but not case/control status. However, the evaluation of the covariates and their interaction terms in log-linear models found no differences in agreement with these covariates and provided evidence that the differences observed using kappa were the result of marginal differences in the distribution of ratings rather than differences in agreement. Differences in agreement were predicted across the exposure scale, with the likely moderately exposed category more difficult for the experts to differentiate from the highly exposed category than from the unexposed category. Conclusions: The log-linear models provided valuable information about patterns of agreement and the structure of the data that were not revealed in analyses using kappa. The models’ lack of dependence on marginal distributions and the ease of evaluating covariates allow reliable detection of observational bias in exposure data. PMID:25748517

  8. Origins and properties of kappa distributions in space plasmas

    NASA Astrophysics Data System (ADS)

    Livadiotis, George

    2016-07-01

    Classical particle systems reside at thermal equilibrium with their velocity distribution function stabilized into a Maxwell distribution. On the contrary, collisionless and correlated particle systems, such as the space and astrophysical plasmas, are characterized by a non-Maxwellian behavior, typically described by the so-called kappa distributions. Empirical kappa distributions have become increasingly widespread across space and plasma physics. However, a breakthrough in the field came with the connection of kappa distributions to the solid statistical framework of Tsallis non-extensive statistical mechanics. Understanding the statistical origin of kappa distributions was the cornerstone of further theoretical developments and applications, some of which will be presented in this talk: (i) The physical meaning of thermal parameters, e.g., temperature and kappa index; (ii) the multi-particle description of kappa distributions; (iii) the phase-space kappa distribution of a Hamiltonian with non-zero potential; (iv) the Sackur-Tetrode entropy for kappa distributions, and (v) the new quantization constant, h _{*}˜10 ^{-22} Js.

  9. Common pitfalls in statistical analysis: Measures of agreement.

    PubMed

    Ranganathan, Priya; Pramesh, C S; Aggarwal, Rakesh

    2017-01-01

    Agreement between measurements refers to the degree of concordance between two (or more) sets of measurements. Statistical methods to test agreement are used to assess inter-rater variability or to decide whether one technique for measuring a variable can substitute another. In this article, we look at statistical measures of agreement for different types of data and discuss the differences between these and those for assessing correlation.

  10. Compressed ultrasound video image-quality evaluation using a Likert scale and Kappa statistical analysis

    NASA Astrophysics Data System (ADS)

    Stewart, Brent K.; Carter, Stephen J.; Langer, Steven G.; Andrew, Rex K.

    1998-06-01

    Experiments using NASA's Advanced Communications Technology Satellite were conducted to provide an estimate of the compressed video quality required for preservation of clinically relevant features for the detection of trauma. Bandwidth rates of 128, 256 and 384 kbps were used. A five point Likert scale (1 equals no useful information and 5 equals good diagnostic quality) was used for a subjective preference questionnaire to evaluate the quality of the compressed ultrasound imagery at the three compression rates for several anatomical regions of interest. At 384 kbps the Likert scores (mean plus or minus SD) were abdomen (4.45 plus or minus 0.71), carotid artery (4.70 plus or minus 0.36), kidney (5.0 plus or minus 0.0), liver (4.67 plus or minus 0.58) and thyroid (4.03 plus or minus 0.74). Due to the volatile nature of the H.320 compressed digital video stream, no statistically significant results can be derived through this methodology. As the MPEG standard has at its roots many of the same intraframe and motion vector compression algorithms as the H.261 (such as that used in the previous ACTS/AMT experiments), we are using the MPEG compressed video sequences to best gauge what minimum bandwidths are necessary for preservation of clinically relevant features for the detection of trauma. We have been using an MPEG codec board to collect losslessly compressed video clips from high quality S- VHS tapes and through direct digitization of S-video. Due to the large number of videoclips and questions to be presented to the radiologists and for ease of application, we have developed a web browser interface for this video visual perception study. Due to the large numbers of observations required to reach statistical significance in most ROC studies, Kappa statistical analysis is used to analyze the degree of agreement between observers and between viewing assessment. If the degree of agreement amongst readers is high, then there is a possibility that the ratings (i

  11. Statistical mechanics in the context of special relativity.

    PubMed

    Kaniadakis, G

    2002-11-01

    In Ref. [Physica A 296, 405 (2001)], starting from the one parameter deformation of the exponential function exp(kappa)(x)=(sqrt[1+kappa(2)x(2)]+kappax)(1/kappa), a statistical mechanics has been constructed which reduces to the ordinary Boltzmann-Gibbs statistical mechanics as the deformation parameter kappa approaches to zero. The distribution f=exp(kappa)(-beta E+betamu) obtained within this statistical mechanics shows a power law tail and depends on the nonspecified parameter beta, containing all the information about the temperature of the system. On the other hand, the entropic form S(kappa)= integral d(3)p(c(kappa) f(1+kappa)+c(-kappa) f(1-kappa)), which after maximization produces the distribution f and reduces to the standard Boltzmann-Shannon entropy S0 as kappa-->0, contains the coefficient c(kappa) whose expression involves, beside the Boltzmann constant, another nonspecified parameter alpha. In the present effort we show that S(kappa) is the unique existing entropy obtained by a continuous deformation of S0 and preserving unaltered its fundamental properties of concavity, additivity, and extensivity. These properties of S(kappa) permit to determine unequivocally the values of the above mentioned parameters beta and alpha. Subsequently, we explain the origin of the deformation mechanism introduced by kappa and show that this deformation emerges naturally within the Einstein special relativity. Furthermore, we extend the theory in order to treat statistical systems in a time dependent and relativistic context. Then, we show that it is possible to determine in a self consistent scheme within the special relativity the values of the free parameter kappa which results to depend on the light speed c and reduces to zero as c--> infinity recovering in this way the ordinary statistical mechanics and thermodynamics. The statistical mechanics here presented, does not contain free parameters, preserves unaltered the mathematical and epistemological structure of

  12. Nutritional status of children and adolescents based on body mass index: agreement between World Health Organization and International Obesity Task Force

    PubMed Central

    Cavazzotto, Timothy Gustavo; Brasil, Marcos Roberto; Oliveira, Vinicius Machado; da Silva, Schelyne Ribas; Ronque, Enio Ricardo V.; Queiroga, Marcos Roberto; Serassuelo, Helio

    2014-01-01

    Objective: To investigate the agreement between two international criteria for classification of children and adolescents nutritional status. Methods: The study included 778 girls and 863 boys aged from six to 13 years old. Body mass and height were measured and used to calculate the body mass index. Nutritional status was classified according to the cut-off points defined by the World Health Organization and the International Obesity Task Force. The agreement was evaluated using Kappa statistic and weighted Kappa. Results: In order to classify the nutritional status, the agreement between the criteria was higher for the boys (Kappa 0.77) compared to girls (Kappa 0.61). The weighted Kappa was also higher for boys (0.85) in comparison to girls (0.77). Kappa index varied according to age. When the nutritional status was classified in only two categories - appropriate (thinness + accentuated thinness + eutrophy) and overweight (overweight + obesity + severe obesity) -, the Kappa index presented higher values than those related to the classification in six categories. Conclusions: A substantial agreement was observed between the criteria, being higher in males and varying according to the age. PMID:24676189

  13. Prospective assessment of interobserver agreement for defecography in fecal incontinence.

    PubMed

    Dobben, Annette C; Wiersma, Tjeerd G; Janssen, Lucas W M; de Vos, Rien; Terra, Maaike P; Baeten, Cor G; Stoker, Jaap

    2005-11-01

    The primary aim of our study was to determine the interobserver agreement of defecography in diagnosing enterocele, anterior rectocele, intussusception, and anismus in fecal-incontinent patients. The subsidiary aim was to evaluate the influence of level of experience on interpreting defecography. Defecography was performed in 105 consecutive fecal-incontinent patients. Observers were classified by level of experience and their findings were compared with the findings of an expert radiologist. The quality of the expert radiologist's findings was evaluated by an intraobserver agreement procedure. Intraobserver agreement was good to very good except for anismus: incomplete evacuation after 30 sec (kappa, 0.55) and puborectalis impression (kappa, 0.54). Interobserver agreement for enterocele and rectocele was good (kappa, 0.66 for both) and for intussusception, fair (kappa, 0.29). Interobserver agreement for anismus: incomplete evacuation after 30 sec was moderate (kappa, 0.47), and for anismus: puborectalis impression was fair (kappa, 0.24). Agreement in grading of enterocele and rectocele was good (kappa, 0.64 and 0.72, respectively) and for intussusception, fair (kappa, 0.39). Agreement separated by experience level was very good for rectocele (kappa, 0.83) and grading of rectoceles (kappa, 0.83) and moderate for intussusception (kappa, 0.44) at the most experienced level. For enterocele and grading, experience level did not influence the reproducibility. Reproducibility for enterocele, anterior rectocele, and severity grading is good, but for intussusception is fair to moderate. For anismus, the diagnosis of incomplete evacuation after 30 sec is more reproducible than puborectalis impression. The level of experience seems to play a role in diagnosing anterior rectocele and its grading and in diagnosing intussusception.

  14. Measures of Agreement Between Many Raters for Ordinal Classifications

    PubMed Central

    Nelson, Kerrie P.; Edwards, Don

    2015-01-01

    Screening and diagnostic procedures often require a physician's subjective interpretation of a patient's test result using an ordered categorical scale to define the patient's disease severity. Due to wide variability observed between physicians’ ratings, many large-scale studies have been conducted to quantify agreement between multiple experts’ ordinal classifications in common diagnostic procedures such as mammography. However, very few statistical approaches are available to assess agreement in these large-scale settings. Existing summary measures of agreement rely on extensions of Cohen's kappa [1 - 5]. These are prone to prevalence and marginal distribution issues, become increasingly complex for more than three experts or are not easily implemented. Here we propose a model-based approach to assess agreement in large-scale studies based upon a framework of ordinal generalized linear mixed models. A summary measure of agreement is proposed for multiple experts assessing the same sample of patients’ test results according to an ordered categorical scale. This measure avoids some of the key flaws associated with Cohen's kappa and its extensions. Simulation studies are conducted to demonstrate the validity of the approach with comparison to commonly used agreement measures. The proposed methods are easily implemented using the software package R and are applied to two large-scale cancer agreement studies. PMID:26095449

  15. Interobserver agreement in the histologic diagnosis of colorectal polyps. the experience of the multicenter adenoma colorectal study (SMAC).

    PubMed

    Costantini, Massimo; Sciallero, Stefania; Giannini, Augusto; Gatteschi, Beatrice; Rinaldi, Paolo; Lanzanova, Giuseppe; Bonelli, Luigina; Casetti, Tino; Bertinelli, Elisabetta; Giuliani, Orietta; Castiglione, Guido; Mantellini, Paola; Naldoni, Carlo; Bruzzi, Paolo

    2003-03-01

    Current clinical practice guidelines for patients with colorectal polyps are mainly based on the histologic characteristics of their lesions. However, interobserver variability in the assessment of specific polyp characteristics was evaluated in very few studies. The purpose of this study was to evaluate the interobserver agreement of four pathologists in the diagnosis of histologic type of colorectal polyps and in the degree of dysplasia and of infiltrating carcinoma in adenomas. A stratified random sample of 100 polyps was obtained from the 4,889 polyps resected within the Multicentre Adenoma Colorectal Study (SMAC), and the slides were blindly reviewed by the four pathologists. Agreement was analyzed using kappa statistics. A median kappa of 0.89 (range 0.79-1.0) was estimated for the interobserver agreement for the diagnosis of hyperplastic polyp vs. adenoma. The agreement in the diagnosis of tubular, tubulovillous, and villous type, was given by median kappa values of 0.50, 0.15, and 0.36, respectively. The median kappa for the diagnosis of infiltrating carcinoma was 0.78 (range 0.73-0.84). Agreement on diagnosis of adenoma histologic subtypes, degrees of dysplasia, or infiltrating carcinoma in adenoma was moderate. A simpler classifications might help to better identify patients at different risk of colorectal cancer.

  16. Cohen's Linearly Weighted Kappa Is a Weighted Average of 2 x 2 Kappas

    ERIC Educational Resources Information Center

    Warrens, Matthijs J.

    2011-01-01

    An agreement table with [n as an element of N is greater than or equal to] 3 ordered categories can be collapsed into n - 1 distinct 2 x 2 tables by combining adjacent categories. Vanbelle and Albert ("Stat. Methodol." 6:157-163, 2009c) showed that the components of Cohen's weighted kappa with linear weights can be obtained from these n - 1…

  17. Using Relative Improvement over Chance (RIOC) to Examine Agreement between Tests: Three Case Examples Using Studies of Developmental Coordination Disorder (DCD) in Children

    ERIC Educational Resources Information Center

    Cairney, John; Streiner, David L.

    2011-01-01

    Although statistics such as kappa and phi are commonly used to assess agreement between tests, in situations where the base rate of a disorder in a population is low or high, these statistics tend to underestimate actual agreement. This can occur even if the tests are good and the classification of subjects is adequate. Relative improvement over…

  18. Mechanisms generating kappa distributions in plasmas

    NASA Astrophysics Data System (ADS)

    Livadiotis, Georgios

    2017-10-01

    Kappa distributions have become increasingly widespread across plasma physics. Publication records reveal an exponential growth of papers relevant to kappa distributions. However, the vast majority of publications refer to statistical fits and applications of these distributions in plasmas. Up to date, there is no systematic analysis on the origin of kappa distributions, that is, the mechanisms that can generate kappa distributions in plasmas. The general scheme that characterizes these mechanisms is composed of two parts: (1) the generation of local correlations among particles, and (2) the thermalization, that is, the stabilization of the particle system into stationary states described by kappa distributions or combinations thereof. Several mechanisms are known in the literature, each characterized by a specific relationship between the plasma properties. These relationships serve as conditions that need to be fulfilled for the corresponding mechanisms to be applied in the plasma. Using these relationships, we identify three mechanisms that generate kappa distributions in the solar wind plasma: (i) Debye shielding, (ii) magnetic field binding, and (iii) thermal fluctuations, each one prevailing in different scales of the solar wind plasma and magnetic field properties. The work was supported in part by the project NNX17AB74G of NASA's HGI Program.

  19. Agreement analysis between three different short geriatric screening scales in patients undergoing chemotherapy for solid tumors.

    PubMed

    Joshi, Amit; Tandon, Nidhi; Patil, Vijay M; Noronha, Vanita; Gupta, Sudeep; Bhattacharjee, Atanu; Prabhash, Kumar

    2017-01-01

    Comprehensive geriatric assessment (CGA) in routine practice is not logistically feasible. Short geriatric screening tools are available for selecting patients for CGA. However none of them is validated in India. In this analysis we aim to compare the level of agreement between three commonly used short screening tools (Flemish version of TRST (fTRST), G8 and VES-13. Patients ≥65 years with a solid tumor malignancy undergoing cancer directed treatment were interviewed between March 2013 to July 2014. Geriatric screening with G8, fTRST and VES-13 tools was performed in these patients. G8 score ≤14, fTRST score ≥1 and VES-13 score ≥3 were taken as indicators for the presence of a high risk geriatric profile respectively. R version 3.1.2 was used for analysis. Cohen kappa agreement statistics was used to compare the agreement between the 3 tools. p value of 0.05 was taken as significant. The kappa statistics value for agreement between G8 score and fTRST, between VES-13 and fTRST and between VES-13 and G8 were 0.12 (P = 0.04), 0.16 (P = 0.07) and 0.05 (P = 0.45) respectively. It was found that maximum agreement was observed for VES-13 and fTRST. The agreement value of VES-13 and fTRST observed was 59.44 %(39.63% for high risk profile and 19.81% for low risk profile). The agreement value of G-8 and fTRST was 39.62% (2.83% only for high risk profile and 36.79% for low risk profile). The lowest agreement was between G8 and VES-13, 35.84% (7.54% for high risk detection and 28.30% for low risk detection). There was poor agreement (in view of kappa value been below 0.2) between the 3 short geriatric screening tools. Research needs to be directed to compare the agreement level between these 3 scales and CGA, so that the appropriate short screening tool can be selected for routine use.

  20. Scales of degree of facial paralysis: analysis of agreement.

    PubMed

    Fonseca, Kércia Melo de Oliveira; Mourão, Aline Mansueto; Motta, Andréa Rodrigues; Vicente, Laelia Cristina Caseiro

    2015-01-01

    It has become common to use scales to measure the degree of involvement of facial paralysis in phonoaudiological clinics. To analyze the inter- and intra-rater agreement of the scales of degree of facial paralysis and to elicit point of view of the appraisers regarding their use. Cross-sectional observational clinical study of the Chevalier and House & Brackmann scales performed by five speech therapists with clinical experience, who analyzed the facial expression of 30 adult subjects with impaired facial movements two times, with a one week interval between evaluations. The kappa analysis was employed. There was excellent inter-rater agreement for both scales (kappa>0.80), and on the Chevalier scale a substantial intra-rater agreement in the first assessment (kappa=0.792) and an excellent agreement in the second assessment (kappa=0.928). The House & Brackmann scale showed excellent agreement at both assessments (kappa=0.850 and 0.857). As for the appraisers' point of view, one appraiser thought prior training is necessary for the Chevalier scale and, four appraisers felt that training is important for the House & Brackmann scale. Both scales have good inter- and intra-rater agreement and most of the appraisers agree on the ease and relevance of the application of these scales. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  1. Kappa and Rater Accuracy: Paradigms and Parameters

    ERIC Educational Resources Information Center

    Conger, Anthony J.

    2017-01-01

    Drawing parallels to classical test theory, this article clarifies the difference between rater accuracy and reliability and demonstrates how category marginal frequencies affect rater agreement and Cohen's kappa. Category assignment paradigms are developed: comparing raters to a standard (index) versus comparing two raters to one another…

  2. Effect of patient age awareness on diagnostic agreement of chronic or aggressive periodontitis between clinicians; a pilot study.

    PubMed

    Oshman, Sarah; El Chaar, Edgard; Lee, Yoonjung Nicole; Engebretson, Steven

    2016-07-25

    The aim of this pilot study was to test whether diagnostic agreement of aggressive and chronic periodontitis amongst Board Certified Periodontists, is influenced by knowledge of a patient's age. In 1999 at the International World Workshop age was removed as a diagnostic criteria for aggressive periodontitis. The impact of this change on the diagnostic reliability amongst clinicians has not yet been assessed. Nine periodontal case reports were twice presented to sixteen board certified periodontists, once with age withheld and again with patient age provided. Participants were instructed to choose a diagnosis of Chronic Periodontitis or Aggressive Periodontitis. Diagnostic agreement was calculated using the Fleiss Kappa test. Including the patients' age in case report information increased diagnostic agreement (the kappa statistic) from 0.49 (moderate agreement) to 0.61 (substantial agreement). These results suggest that knowledge of a patients' age influenced clinical diagnosis, when distinguishing between aggressive periodontitis and chronic periodontitis, which may in turn impact treatment decision-making.

  3. Evaluating Random Error in Clinician-Administered Surveys: Theoretical Considerations and Clinical Applications of Interobserver Reliability and Agreement.

    PubMed

    Bennett, Rebecca J; Taljaard, Dunay S; Olaithe, Michelle; Brennan-Jones, Chris; Eikelboom, Robert H

    2017-09-18

    The purpose of this study is to raise awareness of interobserver concordance and the differences between interobserver reliability and agreement when evaluating the responsiveness of a clinician-administered survey and, specifically, to demonstrate the clinical implications of data types (nominal/categorical, ordinal, interval, or ratio) and statistical index selection (for example, Cohen's kappa, Krippendorff's alpha, or interclass correlation). In this prospective cohort study, 3 clinical audiologists, who were masked to each other's scores, administered the Practical Hearing Aid Skills Test-Revised to 18 adult owners of hearing aids. Interobserver concordance was examined using a range of reliability and agreement statistical indices. The importance of selecting statistical measures of concordance was demonstrated with a worked example, wherein the level of interobserver concordance achieved varied from "no agreement" to "almost perfect agreement" depending on data types and statistical index selected. This study demonstrates that the methodology used to evaluate survey score concordance can influence the statistical results obtained and thus affect clinical interpretations.

  4. Agreement Analysis: What He Said, She Said Versus You Said.

    PubMed

    Vetter, Thomas R; Schober, Patrick

    2018-06-01

    kappa statistic. Assessing the interrater agreement between observers, in the case of ordinal variables and data, also has important biomedical applicability. Typically, this situation calls for use of the Cohen weighted kappa. Questionnaires, psychometric scales, and diagnostic tests are widespread and increasingly used by not only researchers but also clinicians in their daily practice. It is essential that these questionnaires, scales, and diagnostic tests have a high degree of agreement between observers. It is therefore vital that biomedical researchers and clinicians apply the appropriate statistical measures of agreement to assess the reproducibility and quality of these measurement instruments and decision-making processes.

  5. Inter- and intraobserver agreement in 24-hour combined multiple intraluminal impedance and pH measurement in children.

    PubMed

    Pilic, Denisa; Höfs, Carolin; Weitmann, Sandra; Nöh, Frank; Fröhlich, Thorsten; Skopnik, Heino; Köhler, Henrik; Wenzl, Tobias G; Schmidt-Choudhury, Anjona

    2011-09-01

    Assessment of intra- and interobserver agreement in multiple intraluminal impedance (MII) measurement between investigators from different institutions. Twenty-four 18- to 24-hour MII tracings were randomly chosen from 4 different institutions (6 per center). Software-aided automatic analysis was performed. Each result was validated by 2 independent investigators from the 4 different centers (4 investigator combinations). For intraobserver agreement, 6 measurements were analyzed twice by the same investigator. Agreement between investigators was calculated using the Cohen kappa coefficient. Interobserver agreement: 13 measurements showed a perfect agreement (kappa > 0.8); 9 had a substantial (kappa 0.61-0.8), 1 a moderate (kappa coefficient 0.41 to 0.6), and 1 a fair agreement (kappa coefficient 0.11-0.4). Median kappa value was 0.83. Intraobserver agreement: 5 tracings showed perfect and 1 showed a substantial agreement. The median kappa value was 0.88. Most measurements showed substantial to perfect intra- and interobserver agreement. Still, we found a few outliers presumably caused by poorer signal quality in some tracings rather than being observer dependent. An improvement of analysis results may be achieved by using a standard analysis protocol, a standardized method for judging tracing quality, better training options for method users, and more interaction between investigators from different institutions.

  6. Agreement between Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the proposed DSM-V attention deficit hyperactivity disorder diagnostic criteria: an exploratory study.

    PubMed

    Ghanizadeh, Ahmad

    2013-01-01

    There is no empirical literature about the American Psychiatry Association proposed new diagnostic criteria for attention deficit hyperactivity disorder (ADHD). This study examined the agreement between ADHD diagnosis derived from Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and DSM-V diagnostic criteria. It also reports sensitivity, specificity, and agreement for ADHD diagnosis. A clinical sample of 246 children and adolescents were interviewed face to face using both ADHD diagnostic criteria for DSM-V and DSM-IV by interviewing clinician. Comorbid psychiatric disorders were screened using DSM-IV criteria. The rate of ADHD diagnosis using DSM-V was significantly higher than the rate detected by using DSM-IV diagnostic criteria. The sensitivity of DSM-V diagnostic criteria was 100%, while its specificity was 71.1%. The kappa agreement between DSM-IV and DSM-V was 0.75. In addition, positive predictive value was 85.1%. All the four newly added symptoms to ADHD diagnostic criteria are statistically more common in the children with ADHD than those in the comparison group. However, these symptoms are also very common in the children without ADHD. It is expected that the rate of ADHD would increase using the proposed ADHD DSM-V criteria. Moreover, the newly added symptoms have a low specificity for ADHD diagnosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Agreement between proband and parental self-report of smoking behavior and nicotine dependence.

    PubMed

    Marks, Judith L; Swan, Gary E; Pomerleau, Cynthia S; Pomerleau, Ovide F

    2003-08-01

    Although investigators have used family history methods to investigate familial clustering of disorders such as depressive disorder, alcoholism, coronary heart disease, and cancer, research of this type is relatively new to the field of smoking. We examined agreement between proband report of parental smoking behavior and parent's self-reported smoking behavior in 126 proband-parent pairs. Probands were either never, current, or exsmokers; parents were either current or exsmokers. Agreement between proband and parent was better for smoking behaviors when the parent was a current smoker. We found good proband-parent agreement for some smoking behaviors when the parent was a current smoker (e.g., age started smoking [mean (SD) difference between proband and parental report, 1.36 years (9.07 years)], and cigarettes per day and brand smoked [kappa=.49 and.56, respectively]) but poor agreement for items that may represent more complex or less observable indicators of nicotine dependence, regardless of parental smoking status. Reliability was excellent for probands of either current- or exsmoker parents for smoking status (kappa=.92). As a result of probands' difficulty in reliably answering several items that comprise the Fagerström Tolerance Questionnaire (FTQ) (e.g., number of minutes to parent's first cigarette of the day, whether parent smoked more in the morning than during the rest of the day) and the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) diagnosis (e.g., sleep difficulties and difficulty concentrating during nicotine withdrawal), reliability for an FTQ score >/=7 (kappa=.067) and the DSM-IV nicotine dependence diagnosis (kappa=.28) was poor. Our findings should aid investigators in defining the limits of proband reports of parental smoking behavior and identify opportunities for the development of better approaches for the assessment of familial nicotine dependence.

  8. Rating experiments in forestry: How much agreement is there in tree marking?

    PubMed Central

    Pallarés Ramos, Carlos; Kędziora, Wojciech; Haufe, Jens; Stoyan, Dietrich

    2018-01-01

    The process of selecting individual trees by humans for forest management purposes is the result of a plethora of factors and processes that are hard to disentangle. And yet in the past many textbooks and other publications have maintained that this selection leads to somewhat unanimous results. In this study, we analysed the data of 36 so-called marteloscope experiments from all over Britain, which are managed by the Ae Training Centre (Scotland, UK). Our objective was (1) to establish how much agreement there actually was when asking test persons (raters) to apply two different thinning methods, low and crown thinning. In addition we (2) were interested in understanding some of the processes leading to certain levels of agreement and in relationships between the agreement measures and characteristics of forest structure. Our analysis was based on multivariate statistics, particularly using Fleiss’ kappa. This was the first time that an analysis of rater behaviour was performed at such a large scale and it revealed that the general agreement in tree selection in Britain was only slight to fair, i.e. much lower than in medical experiments. The variability of selecting individual trees was considerable. We also found that agreement in tree selection was much stronger in low-thinning as opposed to crown-thinning experiments. As the latter is an important method of Continuous Cover Forestry and British forestry is increasingly adopting this forest management type, our results suggested that there is a need to provide more training. Interestingly the different levels of agreement as identified by Fleiss’ kappa could not be explained by measures of forest structure, however, the mean conformity number, a surrogate of Fleiss’ kappa, showed correlations and indicated that conformity increased with increasing complexity of tree stem diameter structure. PMID:29566076

  9. The Smile Esthetic Index (SEI): A method to measure the esthetics of the smile. An intra-rater and inter-rater agreement study.

    PubMed

    Rotundo, Roberto; Nieri, Michele; Bonaccini, Daniele; Mori, Massimiliano; Lamberti, Elena; Massironi, Domenico; Giachetti, Luca; Franchi, Lorenzo; Venezia, Piero; Cavalcanti, Raffaele; Bondi, Elena; Farneti, Mauro; Pinchi, Vilma; Buti, Jacopo

    2015-01-01

    To propose a method to measure the esthetics of the smile and to report its validation by means of an intra-rater and inter-rater agreement analysis. Ten variables were chosen as determinants for the esthetics of a smile: smile line and facial midline, tooth alignment, tooth deformity, tooth dischromy, gingival dischromy, gingival recession, gingival excess, gingival scars and diastema/missing papillae. One examiner consecutively selected seventy smile pictures, which were in the frontal view. Ten examiners, with different levels of clinical experience and specialties, applied the proposed assessment method twice on the selected pictures, independently and blindly. Intraclass correlation coefficient (ICC) and Fleiss' kappa) statistics were performed to analyse the intra-rater and inter-rater agreement. Considering the cumulative assessment of the Smile Esthetic Index (SEI), the ICC value for the inter-rater agreement of the 10 examiners was 0.62 (95% CI: 0.51 to 0.72), representing a substantial agreement. Intra-rater agreement ranged from 0.86 to 0.99. Inter-rater agreement (Fleiss' kappa statistics) calculated for each variable ranged from 0.17 to 0.75. The SEI was a reproducible method, to assess the esthetic component of the smile, useful for the diagnostic phase and for setting appropriate treatment plans.

  10. (Dis)agreement on Sight-Singing Assessment of Undergraduate Musicians

    PubMed Central

    Bortz, Graziela; Germano, Nayana G.; Cogo-Moreira, Hugo

    2018-01-01

    Assessment criteria for sight-singing abilities are similar to those used to judge music performances across music school programs. However, little evidence of agreement among judges has been provided in the literature. Fifty out of 152 participants were randomly selected and blindly assessed by three judges, who evaluated students based on given criteria. Participants were recorded while sight-singing 19 intervals and 10 tonal melodies. Interjudge agreement on melodic sight-singing was tested considering four items in a five-point Likert scale format as follows: (1) Intonation and pitch accuracy; (2) Tonal sense and memory; (3) Rhythmic precision, regularity of pulse and subdivisions; (4) Fluency and music direction. Intervals were scored considering a 3-point Likert scale. Agreement was conducted using weighted kappa. For melodic sight-singing considering the ten tonal melodies, on average, the weighted kappa (κw) were: κ1w = 0.296, κ2w = 0.487, κ3w = 0.224, and κ4w = 0.244, ranging from fair to moderate.. For intervals, the lowest agreement was kappa = 0.406 and the highest was kappa = 0.792 (on average, kappa = 0.637). These findings light up the discussion on the validity and reliability of models that have been taken for granted in assessing music performance in auditions and contests, and illustrate the need to better discuss evaluation criteria. PMID:29896144

  11. Inter-rater Agreement of End-of-shift Evaluations Based on a Single Encounter

    PubMed Central

    Warrington, Steven; Beeson, Michael; Bradford, Amber

    2017-01-01

    Introduction End-of-shift evaluation (ESE) forms, also known as daily encounter cards, represent a subset of encounter-based assessment forms. Encounter cards have become prevalent for formative evaluation, with some suggesting a potential for summative evaluation. Our objective was to evaluate the inter-rater agreement of ESE forms using a single scripted encounter at a conference of emergency medicine (EM) educators. Methods Following institutional review board exemption, we created a scripted video simulating an encounter between an intern and a patient with an ankle injury. That video was shown during a lecture at the Council of EM Residency Director’s Academic Assembly with attendees asked to evaluate the “resident” using one of eight possible ESE forms randomly distributed. Descriptive statistics were used to analyze the results with Fleiss’ kappa to evaluate inter-rater agreement. Results Most of the 324 respondents were leadership in residency programs (66%), with a range of 29–47 responses per evaluation form. Few individuals (5%) felt they were experts in assessing residents based on EM milestones. Fleiss’ kappa ranged from 0.157 – 0.308 and did not perform much better in two post-hoc subgroup analyses. Conclusion The kappa ranges found show only slight to fair inter-rater agreement and raise concerns about the use of ESE forms in assessment of EM residents. Despite limitations present in this study, these results and a lack of other studies on inter-rater agreement of encounter cards should prompt further studies of such methods of assessment. Additionally, EM educators should focus research on methods to improve inter-rater agreement of ESE forms or other evaluating other methods of assessment of EM residents. PMID:28435505

  12. Examining Agreement and Longitudinal Stability among Traditional and RTI-Based Definitions of Reading Disability Using the Affected-Status Agreement Statistic

    ERIC Educational Resources Information Center

    Waesche, Jessica S. Brown; Schatschneider, Christopher; Maner, Jon K.; Ahmed, Yusra; Wagner, Richard K.

    2011-01-01

    Rates of agreement among alternative definitions of reading disability and their 1- and 2-year stabilities were examined using a new measure of agreement, the affected-status agreement statistic. Participants were 288,114 first through third grade students. Reading measures were "Dynamic Indicators of Basic Early Literacy Skills" Oral…

  13. Porcine arterivirus activates the NF-{kappa}B pathway through I{kappa}B degradation

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

    Lee, Sang-Myeong; Kleiboeker, Steven B.

    2005-11-10

    Nuclear factor-kappaB (NF-{kappa}B) is a critical regulator of innate and adaptive immune function as well as cell proliferation and survival. The present study demonstrated for the first time that a virus belonging to the Arteriviridae family activates NF-{kappa}B in MARC-145 cells and alveolar macrophages. In porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells, NF-{kappa}B activation was characterized by translocation of NF-{kappa}B from the cytoplasm to the nucleus, increased DNA binding activity, and NF-{kappa}B-regulated gene expression. NF-{kappa}B activation was increased as PRRSV infection progressed and in a viral dose-dependent manner. UV-inactivation of PRRSV significantly reduced the level of NF-{kappa}B activation. Degradationmore » of I{kappa}B protein was detected late in PRRSV infection, and overexpression of the dominant negative form of I{kappa}B{alpha} (I{kappa}B{alpha}DN) significantly suppressed NF-{kappa}B activation induced by PRRSV. However, I{kappa}B{alpha}DN did not affect viral replication and viral cytopathic effect. PRRSV infection induced oxidative stress in cells by generating reactive oxygen species (ROS), and antioxidants inhibited NF-{kappa}B DNA binding activity in PRRSV-infected cells, suggesting ROS as a mechanism by which NF-{kappa}B was activated by PRRSV infection. Moreover, NF-{kappa}B-dependent expression of matrix metalloproteinase (MMP)-2 and MMP-9 was observed in PRRSV-infected cells, an observation which implies that NF-{kappa}B activation is a biologically significant aspect of PRRSV pathogenesis. The results presented here provide a basis for understanding molecular pathways of pathology and immune evasion associated with disease caused by PRRSV.« less

  14. Adiposity assessments: agreement between dual-energy X-ray absorptiometry and anthropometric measures in US children12-3

    PubMed Central

    Tuan, Nguyen T; Wang, Youfa

    2014-01-01

    Objectives To evaluate performance of anthropometric measures relative to percentage body fat (%BF) measured by dual-energy X-ray absorptiometry (DXA) in children. Design and Methods We used data from 8-19-y-old US children enrolled in a nationally representative cross-sectional survey in 2001-2004 (n=5,355) with measured %BF, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and triceps skinfold thickness (TSF). Agreement and prediction were evaluated based on standardized regression coefficients (β), kappa, and the area under the receiver-operating characteristic curves (AUC). Results The association between Z scores for %BF and anthropometric measures was strong (β of ~0.75-0.90, kappa of ~0.60-0.75, and AUC of ~0.87-0.98; P<0.001 for all), with only some variations by race-ethnicity, mostly in girls. In boys, TSF and WHtR Z-scores had stronger agreement with %BF than BMI (β of 0.91 and 0.86 vs. 0.79, kappa of 0.75 and 0.71 vs. 0.59, and AUC of 0.97 and 0.97 vs. 0.91; P<0.05 for all). In boys with BMI < median but %BF ≥ median, β value of TSF Z score was higher than those from BMI. In girls, TSF also provided a higher agreement than BMI, but was only statistically higher for kappa. Conclusions High agreement and small racial-ethnic variations in the association between percentage body fat and anthropometric measures support the use of anthropometric measures, especially waist-to-height ratio and triceps skinfold thickness, as proxy indicators for adiposity. PMID:24415710

  15. Parent and teen agreement on driving expectations prior to teen licensure.

    PubMed

    Hamann, Cara J; Ramirez, Marizen; Yang, Jingzhen; Chande, Vidya; Peek-Asa, Corinne

    2014-01-01

    To examine pre-licensure agreement on driving expectations and predictors of teen driving expectations among parent-teen dyads. Cross-sectional survey of 163 parent-teen dyads. Descriptive statistics, weighted Kappa coefficients, and linear regression were used to examine expectations about post-licensure teen driving. Teens reported high pre-licensure unsupervised driving (N = 79, 48.5%) and regular access to a car (N = 130, 81.8%). Parents and teens had low agreement on teen driving expectations (eg, after dark, κw = 0.23). Each time teens currently drove to/from school, their expectation of driving in risky conditions post-licensure increased (β = 0.21, p = .02). Pre-licensure improvement of parent-teen agreement on driving expectations are needed to have the greatest impact on preventing teens from driving in high risk conditions.

  16. Improving agreement in assessment of synovitis in rheumatoid arthritis.

    PubMed

    Cheung, Peter P; Dougados, Maxime; Andre, Vincent; Balandraud, Nathalie; Chales, Gérard; Chary-Valckenaere, Isabelle; Chatelus, Emmanuel; Dernis, Emmanuelle; Gill, Ghislaine; Gilson, Mélanie; Guis, Sandrine; Mouterde, Gael; Pavy, Stephan; Pouyol, François; Marhadour, Thierry; Richette, Pascal; Ruyssen-Witrand, Adeline; Soubrier, Martin; Gossec, Laure

    2013-03-01

    Synovitis assessment through evaluation of swollen joints is integral in steering treatment decisions in rheumatoid arthritis (RA). However, there is high inter-observer variation. The objective was to assess if a short collegiate consensus would improve swollen joint agreement between rheumatologists and whether this was affected by experience. Eighteen rheumatologists from French university rheumatology units participated in three 30 minutes rounds over a half day meeting evaluating joint counts of RA patients in small groups, followed by short consensus discussions. Agreement was evaluated at the end of each round as follows: (i) global agreement of swollen joints (ii) swollen joint agreement according to level of experience of the rheumatologist (iii) swollen joint count and (iv) agreement of disease activity state according to the Disease Activity Score (DAS28). Agreement was calculated using percentage agreement and kappa. Global agreement of swollen joints failed to improve (kappa 0.50 to 0.52) at the joint level. Agreement between seniors did not improve but agreement between newly qualified rheumatologists and their senior peer, which was initially poor (kappa 0.28), improved significantly (to 0.54) at the end of the consensus exercises. Concordance of DAS28 activity states improved from 71% to 87%. Consensus exercises for swollen joint assessment is worthwhile and may potentially improve agreement between clinicians in clinical synovitis and disease activity state, benefit was mostly observed in newly qualified rheumatologists. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  17. Evaluation of inter-observer agreement when using a clinical respiratory scoring system in pre-weaned dairy calves.

    PubMed

    Buczinski, S; Faure, C; Jolivet, S; Abdallah, A

    2016-07-01

    To determine inter-observer agreement for a clinical scoring system for the detection of bovine respiratory disease complex in calves, and the impact of classification of calves as sick or healthy based on different cut-off values. Two third-year veterinary students (Observer 1 and 2) and one post-graduate student (Observer 3) received 4 hours of training on scoring dairy calves for signs of respiratory disease, including rectal temperature, cough, eye and nasal discharge, and ear position. Observers 1 and 2 scored 40 pre-weaning dairy calves 24 hours apart (80 observations) over three visits to a calf-rearing facility, and Observers 1, 2 and 3 scored 20 calves on one visit. Inter-observer agreement was assessed using percentage of agreement (PA) and Kappa statistics for individual clinical signs, comparing Observers 1 and 2. Agreement between the three observers for total clinical score was assessed using cut-off values of ≥4, ≥5 and ≥6 to indicate unhealthy calves. Inter-observer PA for rectal temperature was 0.68, for cough 0.78, for nasal discharge 0.62, for eye discharge 0.63, and for ear position 0.85. Kappa values for all clinical signs indicated slight to fair agreement (<0.4), except temperature that had moderate agreement (0.6). The Fleiss' Kappa for total score, using cut-offs of ≥4, ≥5 and ≥6 to indicate unhealthy calves, was 0.35, 0.06 and 0.13, respectively, indicating slight to fair agreement. There was important inter-observer discrepancies in scoring clinical signs of respiratory disease, using relatively inexperienced observers. These disagreements may ultimately mean increased false negative or false positive diagnoses and incorrect treatment of cases. Visual assessment of clinical signs associated with bovine respiratory disease needs to be thoroughly validated when disease monitoring is based on the use of a clinical scoring system.

  18. Agreement Between VO2peak Predicted From PACER and One-Mile Run Time-Equated Laps.

    PubMed

    Saint-Maurice, Pedro F; Anderson, Katelin; Bai, Yang; Welk, Gregory J

    2016-12-01

    This study examined the agreement between estimated peak oxygen consumption (VO 2peak ) obtained from the Progressive Aerobic Cardiovascular Endurance Run (PACER) fitness test and equated PACER laps derived from One-Mile Run time (MR). A sample of 680 participants (324 boys and 356 girls) in Grades 7 through 12 completed both the PACER and the MR assessments. MR time was converted to PACER laps (PACER-MEQ) using previously developed conversion algorithms. Agreement between PACER and PACER-MEQ VO 2peak was examined using Pearson correlations, mean absolute percent error (MAPE), and equivalence testing procedures. Classification agreement based on health-related standards was examined using sensitivity, specificity, and Kappa statistics. Overall agreement between estimated VO 2peak obtained from the PACER and PACER-MEQ was high in boys, r(324) = .79, R 2  = .63, and moderate in girls, r(356) = .57, R 2  = .33. The MAPE for estimates obtained from PACER-MEQ was 10.3% and estimates were deemed equivalent to the PACER (43.1 ± 6.9 mL/kg/min vs. 44.6 ± 0.3 mL/kg/min). Classification agreement as illustrated by sensitivity and specificity ranged from 20.4% to 90.2% and was higher for classifications in the Healthy Fitness Zone (HFZ). Kappa statistics ranged from .14 to .51 and were also higher for the HFZ. Equated PACER laps can be used to obtain equivalent estimates of PACER VO 2peak in groups of adolescents, but some disparities can be found when students' scores are classified into the Needs Improvement Zone.

  19. Pharmacological characterization of the cloned kappa opioid receptor as a kappa 1b subtype.

    PubMed

    Lai, J; Ma, S W; Zhu, R H; Rothman, R B; Lentes, K U; Porreca, F

    1994-10-27

    Substantial pharmacological evidence in vitro and in vivo has suggested the existence of subtypes of the kappa opioid receptor. Quantitative radioligand binding techniques resolved the presence of two high affinity binding sites for the kappa 1 ligand [3H]U69,593 in mouse brain membranes, termed kappa 1a and kappa 1b, respectively. Whereas the kappa 1a site has high affinity for fedotozine and oxymorphindole and low affinity for bremazocine and alpha-neoendorphin, site kappa 1b has high affinity for bremazocine and alpha-neoendorphin and low affinity for fedotozine and oxymorphindole. CI-977 and U69,593 bind equally well at both sites. To determine the relationship between these kappa 1 receptor subtypes and the recently cloned mouse kappa 1 receptor (KOR), we examined [3H]U69,593 binding to the KOR in stably transfected cells (KORCHN-8). Competition of [3H]U69,593 binding to the KOR by bremazocine, alpha-neoendorphin, fedotozine and oxymorphindole resolved a single class of binding sites at which these agents had binding affinities similar to that of the kappa 1b site present in mouse brain. These results suggest that the cloned KOR corresponds to the kappa 1 site in mouse brain defined as kappa 1b.

  20. Agreement between admission and discharge diagnoses: Analysis by the groups of international classification of diseases, 10th revision.

    PubMed

    Mihailović, Nataša; Trajković, Goran; Simić-Vukomanović, Ivana; Ristić, Svetlana; Kocić, Sanja

    2016-12-01

    Admission diagnosis represents the diagnosis of an illness, injury or condition due to which a patient is referred to hospital to be admitted. Discharge diagnosis represents the main reason of illness or condition due to which a patient is admitted. The aim of this study was to analyze the agreement between admission diagnostic groups and discharge diagnostic groups of patients in the Clinical Center Kragujevac in the period from January 1, 2006 to December 31, 2013 on the basis of the hospitalization report. From the basic set of reports, 5% of random samples were singled out and they contained 20,422 reports. Out of the given number of reports, 18,173 hospitalization reports were complete and then further analyzed in the paper. Admission diagnostic groups given by the primary care doctor were compared with discharge diagnostic groups filled out by the practicing physician in the hospital ward from which a patient was discharged. The agreement of these two diagnostic groups was an indication of the high-quality performance of the primary care doctor. Agreement analysis was conducted using Cohen’s Kappa statistics. Agreement analysis showed that the values of the Kappa coefficient for the five leading admission diagnostic groups were in the range of κ = 0.61 to κ = 0.94. The values of the Kappa coefficient for the five most common discharge diagnostic groups were in the range of κ = 0.55 to κ = 0.81. Hospitalization report is a reliable individual report on inpatient care, so it could be used in determining the degree of agreement between admission diagnostic groups and discharge diagnostic groups.

  1. Inter-rater agreement for a retrospective exposure assessment of asbestos, chromium, nickel and welding fumes in a study of lung cancer and ionizing radiation.

    PubMed

    Seel, E A; Zaebst, D D; Hein, M J; Liu, J; Nowlin, S J; Chen, P

    2007-10-01

    A retrospective exposure assessment of asbestos, welding fumes, chromium and nickel (in welding fumes) was conducted at the Portsmouth Naval Shipyard for a nested case-control study of lung cancer risk from external ionizing radiation. These four contaminants were included because of their potential to confound or modify the effect of a lung cancer-radiation relationship. The exposure assessment included three experienced industrial hygienists from the shipyard who independently assessed exposures for 3519 shop/job/time period combinations. A consensus process was used to resolve estimates with large differences. Final exposure estimates were linked to employment histories of the 4388 study subjects to calculate their cumulative exposures. Inter-rater agreement analyses were performed on the original estimates to better understand the estimation process. Although concordance was good to excellent (78-99%) for intensity estimates and excellent (96-99%) for frequency estimates, overall simple kappa statistics indicated only slight agreement beyond chance (kappa < 0.2). Unbalanced distributions of exposure estimates partly contributed to the weak observed overall inter-rater agreement. Pairwise weighted kappa statistics revealed better agreement between two of the three panelists (kappa = 0.19-0.65). The final consensus estimates were similar to the estimates made by these same two panelists. Overall welding fume exposures were fairly stable across time at the shipyard while asbestos exposures were higher in the early years and fell in the mid-1970s. Mean cumulative exposure for all study subjects was 520 fiber-days cc(-1) for asbestos and 1000 mg-days m(-3) for welding fumes. Mean exposure was much lower for nickel (140 microg-days m(-3)) and chromium (45 microg-days m(-3)). Asbestos and welding fume exposure estimates were positively associated with lung cancer in the nested case-control study. The radiation-lung cancer relationship was attenuated by the inclusion

  2. Investigating Various Thresholds as Immunohistochemistry Cutoffs for Observer Agreement.

    PubMed

    Ali, Asif; Bell, Sarah; Bilsland, Alan; Slavin, Jill; Lynch, Victoria; Elgoweini, Maha; Derakhshan, Mohammad H; Jamieson, Nigel B; Chang, David; Brown, Victoria; Denley, Simon; Orange, Clare; McKay, Colin; Carter, Ross; Oien, Karin A; Duthie, Fraser R

    2017-10-01

    Clinical translation of immunohistochemistry (IHC) biomarkers requires reliable and reproducible cutoffs or thresholds for interpretation of immunostaining. Most IHC biomarker research focuses on the clinical relevance (diagnostic, prognostic, or predictive utility) of cutoffs, with less emphasis on observer agreement using these cutoffs. From the literature, we identified 3 commonly used cutoffs of 10% positive epithelial cells, 20% positive epithelial cells, and moderate to strong staining intensity (+2/+3 hereafter) to use for investigating observer agreement. A series of 36 images of microarray cores stained for 4 different IHC biomarkers, with variable staining intensity and percentage of positive cells, was used for investigating interobserver and intraobserver agreement. Seven pathologists scored the immunostaining in each image using the 3 cutoffs for positive and negative staining. Kappa (κ) statistic was used to assess the strength of agreement for each cutoff. The interobserver agreement between all 7 pathologists using the 3 cutoffs was reasonably good, with mean κ scores of 0.64, 0.59, and 0.62, respectively, for 10%, 20%, and +2/+3 cutoffs. A good agreement was observed for experienced pathologists using the 10% cutoff, and their agreement was statistically higher than for junior pathologists (P=0.02). In addition, the mean intraobserver agreement for all 7 pathologists using the 3 cutoffs was reasonably good, with mean κ scores of 0.71, 0.60, and 0.73, respectively, for 10%, 20%, and +2/+3 cutoffs. For all 3 cutoffs, a positive correlation was observed with perceived ease of interpretation (P<0.003). Finally, cytoplasmic-only staining achieved higher agreement using all 3 cutoffs than mixed staining patterns. All 3 cutoffs investigated achieve reasonable strength of agreement, modestly decreasing interobserver and intraobserver variability in IHC interpretation. These cutoffs have previously been used in cancer pathology, and this study provides

  3. Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

    PubMed

    Agrawal, Anil Kumar; Pielka, Ewa; Lipinski, Artur; Jelen, Michal; Kielan, Wojciech; Agrawal, Siddarth

    2018-01-01

    Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

  4. 40 CFR 721.10033 - Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Zinc, [ethanedioato(2-)-. kappa. O1... Specific Chemical Substances § 721.10033 Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as zinc...

  5. 40 CFR 721.10033 - Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Zinc, [ethanedioato(2-)-. kappa. O1... Specific Chemical Substances § 721.10033 Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as zinc...

  6. Measuring agreement between decision support reminders: the cloud vs. the local expert.

    PubMed

    Dixon, Brian Edward; Simonaitis, Linas; Perkins, Susan M; Wright, Adam; Middleton, Blackford

    2014-04-10

    A cloud-based clinical decision support system (CDSS) was implemented to remotely provide evidence-based guideline reminders in support of preventative health. Following implementation, we measured the agreement between preventive care reminders generated by an existing, local CDSS and the new, cloud-based CDSS operating on the same patient visit data. Electronic health record data for the same set of patients seen in primary care were sent to both the cloud-based web service and local CDSS. The clinical reminders returned by both services were captured for analysis. Cohen's Kappa coefficient was calculated to compare the two sets of reminders. Kappa statistics were further adjusted for prevalence and bias due to the potential effects of bias in the CDS logic and prevalence in the relative small sample of patients. The cloud-based CDSS generated 965 clinical reminders for 405 patient visits over 3 months. The local CDSS returned 889 reminders for the same patient visit data. When adjusted for prevalence and bias, observed agreement varied by reminder from 0.33 (95% CI 0.24 - 0.42) to 0.99 (95% CI 0.97 - 1.00) and demonstrated almost perfect agreement for 7 of the 11 reminders. Preventive care reminders delivered by two disparate CDS systems show substantial agreement. Subtle differences in rule logic and terminology mapping appear to account for much of the discordance. Cloud-based CDSS therefore show promise, opening the door for future development and implementation in support of health care providers with limited resources for knowledge management of complex logic and rules.

  7. Professional Practice and Innovation: Level of Agreement between Coding Sources of Percentage Total Body Surface Area Burnt (%TBSA).

    PubMed

    Watterson, Dina; Cleland, Heather; Picton, Natalie; Simpson, Pam M; Gabbe, Belinda J

    2011-03-01

    The percentage of total body surface area burnt (%TBSA) is a critical measure of burn injury severity and a key predictor of burn injury outcome. This study evaluated the level of agreement between four sources of %TBSA using 120 cases identified through the Victorian State Trauma Registry. Expert clinician, ICD-10-AM, Abbreviated Injury Scale, and burns registry coding were compared using measures of agreement. There was near-perfect agreement (weighted Kappa statistic 0.81-1) between all sources of data, suggesting that ICD-10-AM is a valid source of %TBSA and use of ICD-10-AM codes could reduce the resource used by trauma and burns registries capturing this information.

  8. Inter-radiologist agreement for CT scoring of pediatric splenic injuries and effect on an established clinical practice guideline.

    PubMed

    Leschied, Jessica R; Mazza, Michael B; Davenport, Matthew; Chong, Suzanne T; Smith, Ethan A; Hoff, Carrie N; Ladino-Torres, Maria F; Khalatbari, Shokoufeh; Ehrlich, Peter F; Dillman, Jonathan R

    2016-02-01

    The American Pediatric Surgical Association (APSA) advocates for the use of a clinical practice guideline to direct management of hemodynamically stable pediatric spleen injuries. The clinical practice guideline is based on the CT score of the spleen injury according to the American Association for the Surgery of Trauma (AAST) CT scoring system. To determine the potential effect of radiologist agreement for CT scoring of pediatric spleen injuries on an established APSA clinical practice guideline. We retrospectively analyzed blunt splenic injuries occurring in children from January 2007 to January 2012 at a single level 1 trauma center (n = 90). Abdominal CT exams performed at clinical presentation were reviewed by four radiologists who documented the following: (1) splenic injury grade (AAST system), (2) arterial extravasation and (3) pseudoaneurysm. Inter-rater agreement for AAST injury grade was assessed using the multi-rater Fleiss kappa and Kendall coefficient of concordance. Inter-rater agreement was assessed using weighted (AAST injury grade) or prevalence-adjusted bias-adjusted (binary measures) kappa statistics; 95% confidence intervals were calculated. We evaluated the hypothetical effect of radiologist disagreement on an established APSA clinical practice guideline. Inter-rater agreement was good for absolute AAST injury grade (kappa: 0.64 [0.59–0.69]) and excellent for relative AAST injury grade (Kendall w: 0.90). All radiologists agreed on the AAST grade in 52% of cases. Based on an established clinical practice guideline, radiologist disagreement could have changed the decision for intensive care management in 11% (10/90) of children, changed the length of hospital stay in 44% (40/90), and changed the time to return to normal activity in 44% (40/90). Radiologist agreement when assigning splenic AAST injury grades is less than perfect, and disagreements have the potential to change management in a substantial number of pediatric patients.

  9. Novel selective kappa-opioid ligands.

    PubMed

    Peeters, O M; Jamroz, D; Blaton, N M; De Ranter, C J

    1999-03-15

    The single-crystal X-ray structures of (-)-dimethyl[(2S)-1-(5,6,7,8- tetrahydro-5-oxonaphthalene-2-acetyl)piperidin-2-ylmethyl ]ammonium chloride, C20H29N2O2+.Cl-(BRL-53001A), and (-)-ethylmethyl[(2S)-1-(5,6,7,8-tetrahydro-5-oxonaphthalene- 2- acetyl)piperidin-2-ylmethyl]-ammonium chloride dihydrate, C21H31N2O2+.Cl-.2H2O (BRL-53188A), have been determined. The two molecules have different conformations in the 1-tetralon-6-ylacetyl residue but the same conformation in the 1-acetyl-2-(dialkylaminomethyl)piperidine moiety. The conformations found are in agreement with the required chemical features for kappa affinity and antinociceptive potency.

  10. Observer Agreement for Measurements in Videolaryngostroboscopy.

    PubMed

    Brunings, Jan Wouter; Vanbelle, Sophie; Akkermans, Annemarie; Heemskerk, Nienke M M; Kremer, Bernd; Stokroos, Robert J; Baijens, Laura W J

    2017-11-06

    This study evaluated the levels of intraobserver and interobserver agreement for measurements of visuoperceptual variables in videolaryngostroboscopic examinations and compared the observers' behavior during independent versus consensus panel rating. This is a retrospective study. This study was conducted in a single-center tertiary care facility. Sixty-four patients with dysphonia of heterogeneous etiology were included. All subjects underwent a standardized videolaryngostroboscopic examination. Two experienced and trained observers scored exactly the same examinations, first independently and then on a consensus panel. Specific visuoperceptual variables and the clinical diagnosis (as recommended by the Committee on Phoniatrics and the Phonosurgery Committee of the European Laryngological Society and advised by the American Speech-Language-Hearing Association) were scored. Descriptive and kappa statistics were used. In general, intraobserver agreement was better than agreement between observers for measurements of several variables. The intrapanel observer agreement levels were slightly higher than the intraobserver agreement levels on the independent rating task. When rating on the consensus panel, the observers deviated considerably from the scores they had previously given on the independent rating task. Observer agreement in videolaryngostroboscopic assessment has important implications not only for the diagnosis and treatment of dysphonic patients but also for the interpretation of the results of scientific studies using videolaryngostroboscopic outcome parameters. The identification of factors that can influence the levels of observer agreement can provide a better understanding of the rating process and its limitations. The results of this study suggest that future research could achieve better agreement levels by rating the visuoperceptual variables in a panel setting. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  11. Variance estimates and confidence intervals for the Kappa measure of classification accuracy

    Treesearch

    M. A. Kalkhan; R. M. Reich; R. L. Czaplewski

    1997-01-01

    The Kappa statistic is frequently used to characterize the results of an accuracy assessment used to evaluate land use and land cover classifications obtained by remotely sensed data. This statistic allows comparisons of alternative sampling designs, classification algorithms, photo-interpreters, and so forth. In order to make these comparisons, it is...

  12. The Orientation of Gastric Biopsy Samples Improves the Inter-observer Agreement of the OLGA Staging System.

    PubMed

    Cotruta, Bogdan; Gheorghe, Cristian; Iacob, Razvan; Dumbrava, Mona; Radu, Cristina; Bancila, Ion; Becheanu, Gabriel

    2017-12-01

    Evaluation of severity and extension of gastric atrophy and intestinal metaplasia is recommended to identify subjects with a high risk for gastric cancer. The inter-observer agreement for the assessment of gastric atrophy is reported to be low. The aim of the study was to evaluate the inter-observer agreement for the assessment of severity and extension of gastric atrophy using oriented and unoriented gastric biopsy samples. Furthermore, the quality of biopsy specimens in oriented and unoriented samples was analyzed. A total of 35 subjects with dyspeptic symptoms addressed for gastrointestinal endoscopy that agreed to enter the study were prospectively enrolled. The OLGA/OLGIM gastric biopsies protocol was used. From each subject two sets of biopsies were obtained (four from the antrum, two oriented and two unoriented, two from the gastric incisure, one oriented and one unoriented, four from the gastric body, two oriented and two unoriented). The orientation of the biopsy samples was completed using nitrocellulose filters (Endokit®, BioOptica, Milan, Italy). The samples were blindly examined by two experienced pathologists. Inter-observer agreement was evaluated using kappa statistic for inter-rater agreement. The quality of histopathology specimens taking into account the identification of lamina propria was analyzed in oriented vs. unoriented samples. The samples with detectable lamina propria mucosae were defined as good quality specimens. Categorical data was analyzed using chi-square test and a two-sided p value <0.05 was considered statistically significant. A total of 350 biopsy samples were analyzed (175 oriented / 175 unoriented). The kappa index values for oriented/unoriented OLGA 0/I/II/III and IV stages have been 0.62/0.13, 0.70/0.20, 0.61/0.06, 0.62/0.46, and 0.77/0.50, respectively. For OLGIM 0/I/II/III stages the kappa index values for oriented/unoriented samples were 0.83/0.83, 0.88/0.89, 0.70/0.88 and 0.83/1, respectively. No case of OLGIM IV

  13. Inter-observer agreement for diagnostic classification of esophageal motility disorders defined in high-resolution manometry.

    PubMed

    Fox, M R; Pandolfino, J E; Sweis, R; Sauter, M; Abreu Y Abreu, A T; Anggiansah, A; Bogte, A; Bredenoord, A J; Dengler, W; Elvevi, A; Fruehauf, H; Gellersen, S; Ghosh, S; Gyawali, C P; Heinrich, H; Hemmink, M; Jafari, J; Kaufman, E; Kessing, K; Kwiatek, M; Lubomyr, B; Banasiuk, M; Mion, F; Pérez-de-la-Serna, J; Remes-Troche, J M; Rohof, W; Roman, S; Ruiz-de-León, A; Tutuian, R; Uscinowicz, M; Valdovinos, M A; Vardar, R; Velosa, M; Waśko-Czopnik, D; Weijenborg, P; Wilshire, C; Wright, J; Zerbib, F; Menne, D

    2015-01-01

    High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤ 2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics. © 2014 International Society for Diseases of the Esophagus.

  14. Agreement Between Maternal Report and Medical Records During Pregnancy: Medications for Rheumatoid Arthritis and Asthma.

    PubMed

    Palmsten, Kristin; Hulugalle, Avanthi; Bandoli, Gretchen; Kuo, Grace M; Ansari, Shayda; Xu, Ronghui; Chambers, Christina D

    2018-01-01

    There are limited data regarding the comparability of medication exposure information during pregnancy from maternal report and medical records, including for rheumatoid arthritis and asthma-related medications. This study included pregnant women with rheumatoid arthritis (n = 216) and asthma (n = 172) enrolled in the MothertoBaby Pregnancy Studies (2009-2014). Women reported types and dates of medications used through semi-structured telephone interviews up to three times during pregnancy and once after delivery, and medical records were obtained. We calculated Cohen's kappa coefficients and 95% confidence intervals (CIs) and per cent agreement for agreement between report and records. For rheumatoid arthritis, prednisone was reported most frequently (53%). During pregnancy, kappa coefficients for rheumatoid arthritis medications ranged from 0.32 (95% CI 0.15, 0.50) for ibuprofen, with 84.3% agreement, to 0.90 (95% CI 0.84, 0.96) for etanercept with 95.4% agreement, and was 0.44 (95% CI 0.33, 0.55) for prednisone, with 71.3% agreement. For asthma, albuterol was reported most frequently (77.9%). During pregnancy, kappa coefficients for asthma medications ranged from 0.21 (95% CI 0.08, 0.35), with 64.5% agreement for albuterol to 0.84 (95% CI 0.71, 0.96) for budesonide/formoterol, with 96.5% agreement. Where kappas for any use during pregnancy were less than excellent (i.e. ≤0.80), medication use was more frequently captured by report than record. Agreement was higher for medications typically used continuously than sporadically. Information on medication use from medical records alone may not be adequate when studying the impact of intermittently used medications during pregnancy on perinatal outcomes. © 2017 John Wiley & Sons Ltd.

  15. Measuring agreement between decision support reminders: the cloud vs. the local expert

    PubMed Central

    2014-01-01

    Background A cloud-based clinical decision support system (CDSS) was implemented to remotely provide evidence-based guideline reminders in support of preventative health. Following implementation, we measured the agreement between preventive care reminders generated by an existing, local CDSS and the new, cloud-based CDSS operating on the same patient visit data. Methods Electronic health record data for the same set of patients seen in primary care were sent to both the cloud-based web service and local CDSS. The clinical reminders returned by both services were captured for analysis. Cohen’s Kappa coefficient was calculated to compare the two sets of reminders. Kappa statistics were further adjusted for prevalence and bias due to the potential effects of bias in the CDS logic and prevalence in the relative small sample of patients. Results The cloud-based CDSS generated 965 clinical reminders for 405 patient visits over 3 months. The local CDSS returned 889 reminders for the same patient visit data. When adjusted for prevalence and bias, observed agreement varied by reminder from 0.33 (95% CI 0.24 – 0.42) to 0.99 (95% CI 0.97 – 1.00) and demonstrated almost perfect agreement for 7 of the 11 reminders. Conclusions Preventive care reminders delivered by two disparate CDS systems show substantial agreement. Subtle differences in rule logic and terminology mapping appear to account for much of the discordance. Cloud-based CDSS therefore show promise, opening the door for future development and implementation in support of health care providers with limited resources for knowledge management of complex logic and rules. PMID:24720863

  16. KAPPA -- Kernel Application Package

    NASA Astrophysics Data System (ADS)

    Currie, Malcolm J.; Berry, David. S.

    KAPPA is an applications package comprising about 180 general-purpose commands for image processing, data visualisation, and manipulation of the standard Starlink data format---the NDF. It is intended to work in conjunction with Starlink's various specialised packages. In addition to the NDF, KAPPA can also process data in other formats by using the `on-the-fly' conversion scheme. Many commands can process data arrays of arbitrary dimension, and others work on both spectra and images. KAPPA operates from both the UNIX C-shell and the ICL command language. This document describes how to use KAPPA and its features. There is some description of techniques too, including a section on writing scripts. This document includes several tutorials and is illustrated with numerous examples. The bulk of this document comprises detailed descriptions of each command as well as classified and alphabetical summaries.

  17. [Inter-observes agreement of Ishak and Metavir scores in histological evaluation of chronic viral hepatitis B and C].

    PubMed

    Rammeh, Soumaya; Khadra, Hajer Ben; Znaidi, Nadia Sabbegh; Romdhane, Neila Attia; Najjar, Taoufik; Bouzaidi, Slim; Zermani, Rachida

    2014-01-01

    Many classification systems are currently used for histological evaluation of the severity of chronic viral hepatitis, including the Ishak and Metavir scores, but there is not a consensus classification. The objective of this work was to study the intra and inter-observers agreement of these two scores in the histopathological analysis of liver biopsies in patients with chronic viral hepatitis B or C. Fifty nine patients were included in the study, 26 had chronic hepatitis C and 33 had chronic hepatitis B. To investigate the inter-observers agreement, the liver biopsies were analyzed separately by two pathologists without prior consensus reading. The two pathologists conducted then a consensual reading before reviewing all cases independently. Cohen's kappa coefficient was calculated and in case of asymmetry Spearman's rho coefficient. Before the consensus reading, the agreement was moderate for the analysis of histological activity with both scores (Metavir: kappa=0.41, Ishak: rho=0.58). For the analysis of fibrosis, the agreement was good with both scores (Metavir: kappa=0.61, Ishak: rho=0.86). The consensus reading has improved the reproducibility of the activity that has become good with both scores (Metavir: kappa=0.77, Ishak: rho=0.76). For fibrosis improvement was observed with the Ishak score which agreement became excellent (kappa=0.81). In conclusion, we recommend in routine practice, a combined score: Metavir for activity and Ishak for fibrosis and to make a double reading for each biopsy.

  18. Alternative Methods for Calculating Intercoder Reliability in Content Analysis: Kappa, Weighted Kappa and Agreement Charts Procedures.

    ERIC Educational Resources Information Center

    Kang, Namjun

    If content analysis is to satisfy the requirement of objectivity, measures and procedures must be reliable. Reliability is usually measured by the proportion of agreement of all categories identically coded by different coders. For such data to be empirically meaningful, a high degree of inter-coder reliability must be demonstrated. Researchers in…

  19. Agreement between questionnaire and medical records on some health and socioeconomic problems among poisoning cases

    PubMed Central

    Fathelrahman, Ahmed I

    2009-01-01

    Background The main objective of the present study was to evaluate the agreement between questionnaire and medical records on some health and socioeconomic problems among poisoning cases. Methods Cross-sectional sample of 100 poisoning cases consecutively admitted to the Hospital Pulau Pinang, Malaysia during the period from September 2003 to February 2004 were studied. Data on health and socioeconomic problems were collected both by self-administered questionnaire and from medical records. Agreement between the two sets of data was assessed by calculating the concordance rate, Kappa (k) and PABAK. McNemar statistic was used to test differences between categories. Results Data collected by questionnaire and medical records showed excellent agreement on the "marital status"; good agreements on "chronic illness", "psychiatric illness", and "previous history of poisoning"; and fair agreements on "at least one health problem", and "boy-girl friends problem". PABAK values suggest better agreements' measures. Conclusion There were excellent to good agreements between questionnaire and medical records on the marital status and most of the health problems and fair to poor agreements on the majority of socioeconomic problems. The implications of those findings were discussed. PMID:19751526

  20. Observers' Agreement on Measurements in Fiberoptic Endoscopic Evaluation of Swallowing.

    PubMed

    Pilz, Walmari; Vanbelle, Sophie; Kremer, Bernd; van Hooren, Michel R; van Becelaere, Tine; Roodenburg, Nel; Baijens, Laura W J

    2016-04-01

    This study analyzed the effect that dysphagia etiology, different observers, and bolus consistency might have on the level of agreement for measurements in FEES images reached by independent versus consensus panel rating. Sixty patients were included and divided into two groups according to dysphagia etiology: neurological or head and neck oncological. All patients underwent standardized FEES examination using thin and thick liquid consistencies. Two observers scored the same exams, first independently and then in a consensus panel. Four ordinal FEES variables were analyzed. Statistical analysis was performed using a linear weighted kappa coefficient and Bayesian multilevel model. Intra- and interobserver agreement on FEES measurements ranged from 0.76 to 0.93 and from 0.61 to 0.88, respectively. Dysphagia etiology did not influence observers' agreement level. However, bolus consistency resulted in decreased interobserver agreement for all measured FEES variables during thin liquid swallows. When rating on the consensus panel, the observers deviated considerably from the scores they had previously given on the independent rating task. Observer agreement on measurements in FEES exams was influenced by bolus consistency, not by dysphagia etiology. Therefore, observer agreement on FEES measurements should be analyzed by taking bolus consistency into account, as it might affect the interpretation of the outcome. Identifying factors that might influence agreement levels could lead to better understanding of the rating process and assist in developing a more precise measurement scale that would ensure higher levels of observer agreement for measurements in FEES exams.

  1. Assessment of Interradiologist Agreement Regarding Mammographic Breast Density Classification Using the Fifth Edition of the BI-RADS Atlas.

    PubMed

    Ekpo, Ernest U; Ujong, Ujong Peter; Mello-Thoms, Claudia; McEntee, Mark F

    2016-05-01

    The objective of the present study was to assess interradiologist agreement regarding mammographic breast density assessment performed using the rating scale outlined in the fifth edition of the BI-RADS atlas of the American College of Radiology. Breast density assessments of 1000 cases were conducted by five radiologists from the same institution who together had recently undergone retraining in mammographic breast density classification based on the fifth edition of BI-RADS. The readers assigned breast density grades (A-D) on the basis of the BI-RADS classification scheme. Repeat assessment of 100 cases was performed by all readers 1 month after the initial assessment. A weighted kappa was used to calculate intrareader and interreader agreement. Intrareader agreement ranged from a kappa value of 0.86 (95% CI, 0.77-0.93) to 0.89 (95% CI, 0.81-0.95) on a four-category scale (categories A-D) and from 0.89 (95% CI, 0.86-0.92) to 0.94 (95% CI, 0.89-0.97) on a two-category scale (category A-B vs category C-D). Interreader agreement ranged from substantial (κ = 0.76; 95% CI, 0.73-0.78) to almost perfect (κ = 0.87; 95% CI, 0.86-0.89) on a four-category scale, and the overall weighted kappa value was substantial (0.79; 95% CI, 0.78-0.83). Interreader agreement on a two-category scale ranged from a kappa value of 0.85 (95% CI, 0.83-0.86) to 0.91 (95% CI, 0.90-0.92), and the overall weighted kappa was 0.88 (95% CI, 0.87-0.89). Overall, with regard to mammographic breast density classification, radiologists had substantial interreader agreement when a four-category scale was used and almost perfect interreader agreement when a dichotomous scale was used.

  2. Heat shock protein 70 negatively regulates the heat-shock-induced suppression of the I{kappa}B/NF-{kappa}B cascade by facilitating I{kappa}B kinase renaturation and blocking its further denaturation

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

    Lee, Kyoung-Hee; Lee, Choon-Taek; Kim, Young Whan

    2005-07-01

    Heat shock (HS) treatment has been previously shown to suppress the I{kappa}B/nuclear factor-{kappa}B (NF-{kappa}B) cascade by denaturing, and thus inactivating I{kappa}B kinase (IKK). HS is characterized by the induction of a group of heat shock proteins (HSPs). However, their role in the HS-induced suppression of the I{kappa}B/NF-{kappa}B cascade is unclear. Adenovirus-mediated HSP70 overexpression was found not to suppress the TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway, thus suggesting that HSP70 is unlikely to suppress this pathway. When TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway was regained 24 h after HS, HSP70 was found to be highly up-regulated. Moreover, blocking HSP70 induction delayedmore » TNF-{alpha}-induced I{kappa}B{alpha} degradation and the resolubilization of IKK. In addition, HSP70 associated physically with IKK, suggesting that HSP70 is involved in the recovery process via molecular chaperone effect. Adenovirus-mediated HSP70 overexpression prior to HS blocked the I{kappa}B{alpha} stabilizing effect of HS by suppressing IKK insolubilization. Moreover, the up-regulation of endogenous HSP70 by preheating, suppressed this subsequent HS-induced IKK insolubilization, and this effect was abrogated by blocking HSP70 induction. These findings indicate that HSP70 accumulates during HS and negatively regulates the HS-induced suppression of the I{kappa}B/NF-{kappa}B cascade by facilitating the renaturation of IKK and blocking its further denaturation.« less

  3. Agreement between the caudal fold test and serological tests for the detection of Mycobacterium bovis infection in bison.

    PubMed

    Chapinal, Núria; Elkin, Brett T; Joly, Damien O; Schumaker, Brant A; Stephen, Craig

    2012-08-01

    The objective of this study was to estimate agreement between the caudal fold test (CFT) and different serological tests for the detection of Mycobacterium bovis infection in bison by using prevalence-adjusted bias-adjusted kappa (PABAK). A total of 212 of wild wood bison from Wood Buffalo National Park were tested with the CFT as well as several serological tests: fluorescent polarization assay (FPA), multiantigen print immunoassay (MAPIA), rapid lateral-flow test (RT) and dual path platform test (DPP). For RT, 3 variations were conducted using 30μl of serum (RT 30), 20μl of serum (RT 20) and 20μl of serum considering only a strong reaction as positive (RT 20 ST). The McNemar's χ(2) test was conducted to assess whether the proportion of positive test results to 2 different tests differed. Two measures of agreement between pair of tests were estimated: the Cohen's kappa statistic and PABAK. The apparent prevalence of tuberculosis in the sampled animals varied depending on the diagnostic test from 6.1% (FPA and DPP) to 47.2% (CFT). The prevalence estimated by CFT differed from the prevalence estimated by the other tests, whereas the prevalence estimated by FPA, MAPIA, RT 20 ST and DPP were not significantly different. The kappa and PABAK estimates calculated between CFT and the rest of the tests suggested poor to slight agreement between tests (k and PABAK<0.25 in all cases). The PABAK estimates for the pairwise combinations among serological tests were numerically greater than the kappa estimates (and significantly greater when FPA was compared to the rest of serological tests), and suggested substantial to almost perfect agreement (PABAK>0.75 in all cases). The disagreement between the skin and serological tests for the detection of M. bovis infection could be partly because the tests measure different immunological responses (cell-mediated vs. humoral) that are predominant at different stages of the infection, and partly due to inaccuracy of the tests

  4. Standardized assessment of tumor-infiltrating lymphocytes in breast cancer: an evaluation of inter-observer agreement between pathologists.

    PubMed

    Tramm, Trine; Di Caterino, Tina; Jylling, Anne-Marie B; Lelkaitis, Giedrius; Lænkholm, Anne-Vibeke; Ragó, Péter; Tabor, Tomasz P; Talman, Maj-Lis M; Vouza, Emmanouela

    2018-01-01

    In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new biomarker in the routine practice, and evaluation of the analytical validity is needed, including testing the reproducibility of decentralized assessment of TILs. The aim of this study was to evaluate the inter-observer agreement of TILs assessment using a standardized method, as proposed by the International TILs Working Group 2014, applied to a cohort of breast cancers reflecting an average breast cancer population. Stromal TILs were assessed using full slide sections from 124 breast cancers with varying histology, malignancy grade and ER- and HER2 status. TILs were estimated by nine dedicated breast pathologists using scanned hematoxylin-eosin stainings. TILs results were categorized using various cutoffs, and the inter-observer agreement was evaluated using the intraclass coefficient (ICC), Kappa statistics as well as individual overall agreements with the median value of TILs. Evaluation of TILs led to an ICC of 0.71 (95% CI: 0.65-0.77) corresponding to an acceptable agreement. Kappa values were in the range of 0.38-0.46 corresponding to a fair to moderate agreement. The individual agreements increased, when using only two categories ('high' vs. 'low' TILs) and a cutoff of 50-60%. The results of the present study are in accordance with previous studies, and shows that the proposed methodology for standardized evaluation of TILs renders an acceptable inter-observer agreement. The findings, however, indicate that assessment of TILs needs further refinement, and is in support of the latest St. Gallen Consensus, that routine reporting of TILs for early breast cancer is not ready for implementation in a clinical setting.

  5. Emergency Physicians Are Able to Detect Right Ventricular Dilation With Good Agreement Compared to Cardiology.

    PubMed

    Rutz, Matt A; Clary, Julie M; Kline, Jeffrey A; Russell, Frances M

    2017-07-01

    Focused cardiac ultrasound (FOCUS) is a useful tool in evaluating patients presenting to the emergency department (ED) with acute dyspnea. Prior work has shown that right ventricular (RV) dilation is associated with repeat hospitalizations and shorter life expectancy. Traditionally, RV assessment has been evaluated by cardiologist-interpreted comprehensive echocardiography. The primary goal of this study was to determine the inter-rater reliability between emergency physicians (EPs) and a cardiologist for determining RV dilation on FOCUS performed on ED patients with acute dyspnea. This was a prospective, observational study at two urban academic EDs; patients were enrolled if they had acute dyspnea and a computed tomographic pulmonary angiogram without acute disease. All patients had an EP-performed FOCUS to assess for RV dilation. RV dilation was defined as an RV to left ventricular ratio greater than 1. FOCUS interpretations were compared to a blinded cardiologist FOCUS interpretation using agreement and kappa statistics. Of 84 FOCUS examinations performed on 83 patients, 17% had RV dilation. Agreement and kappa, for EP-performed FOCUS for RV dilation were 89% (95% confidence interval [CI] 80-95%) and 0.68 (95% CI 0.48-0.88), respectively. Emergency physician sonographers are able to detect RV dilation with good agreement when compared to cardiology. These results support the wider use of EP-performed FOCUS to evaluate for RV dilation in ED patients with dyspnea. © 2017 by the Society for Academic Emergency Medicine.

  6. Inter-rater agreement on PIVC-associated phlebitis signs, symptoms and scales.

    PubMed

    Marsh, Nicole; Mihala, Gabor; Ray-Barruel, Gillian; Webster, Joan; Wallis, Marianne C; Rickard, Claire M

    2015-10-01

    Many peripheral intravenous catheter (PIVC) infusion phlebitis scales and definitions are used internationally, although no existing scale has demonstrated comprehensive reliability and validity. We examined inter-rater agreement between registered nurses on signs, symptoms and scales commonly used in phlebitis assessment. Seven PIVC-associated phlebitis signs/symptoms (pain, tenderness, swelling, erythema, palpable venous cord, purulent discharge and warmth) were observed daily by two raters (a research nurse and registered nurse). These data were modelled into phlebitis scores using 10 different tools. Proportions of agreement (e.g. positive, negative), observed and expected agreements, Cohen's kappa, the maximum achievable kappa, prevalence- and bias-adjusted kappa were calculated. Two hundred ten patients were recruited across three hospitals, with 247 sets of paired observations undertaken. The second rater was blinded to the first's findings. The Catney and Rittenberg scales were the most sensitive (phlebitis in >20% of observations), whereas the Curran, Lanbeck and Rickard scales were the most restrictive (≤2% phlebitis). Only tenderness and the Catney (one of pain, tenderness, erythema or palpable cord) and Rittenberg scales (one of erythema, swelling, tenderness or pain) had acceptable (more than two-thirds, 66.7%) levels of inter-rater agreement. Inter-rater agreement for phlebitis assessment signs/symptoms and scales is low. This likely contributes to the high degree of variability in phlebitis rates in literature. We recommend further research into assessment of infrequent signs/symptoms and the Catney or Rittenberg scales. New approaches to evaluating vein irritation that are valid, reliable and based on their ability to predict complications need exploration. © 2015 John Wiley & Sons, Ltd.

  7. Agreement in the assessment of metastatic spine disease using scoring systems.

    PubMed

    Arana, Estanislao; Kovacs, Francisco M; Royuela, Ana; Asenjo, Beatriz; Pérez-Ramírez, Ursula; Zamora, Javier

    2015-04-01

    To assess variability in the use of Tomita and modified Bauer scores in spine metastases. Clinical data and imaging from 90 patients with biopsy-proven spinal metastases, were provided to 83 specialists from 44 hospitals. Spinal levels involved and the Tomita and modified Bauer scores for each case were determined twice by each clinician, with a minimum of 6-week interval. Clinicians were blinded to every evaluation. Kappa statistic was used to assess intra and inter-observer agreement. Subgroup analyses were performed according to clinicians' specialty (medical oncology, neurosurgery, radiology, orthopedic surgery and radiation oncology), years of experience (⩽7, 8-13, ⩾14), and type of hospital (four levels). For metastases identification, intra-observer agreement was "substantial" (0.600.80) at the other levels. Inter-observer agreement was "almost perfect" at lumbar spine, and "substantial" at the other levels. Intra-observer agreement for the Tomita and Bauer scores was almost perfect. Inter-observer agreement was almost perfect for the Tomita score and substantial for the Bauer one. Results were similar across specialties, years of experience and type of hospital. Agreement in the assessment of metastatic spine disease is high. These scoring systems can improve communication among clinicians involved in oncology care. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Echocardiographic agreement in the diagnostic evaluation for infective endocarditis.

    PubMed

    Lauridsen, Trine Kiilerich; Selton-Suty, Christine; Tong, Steven; Afonso, Luis; Cecchi, Enrico; Park, Lawrence; Yow, Eric; Barnhart, Huiman X; Paré, Carlos; Samad, Zainab; Levine, Donald; Peterson, Gail; Stancoven, Amy Butler; Johansson, Magnus Carl; Dickerman, Stuart; Tamin, Syahidah; Habib, Gilbert; Douglas, Pamela S; Bruun, Niels Eske; Crowley, Anna Lisa

    2016-07-01

    Echocardiography is essential for the diagnosis and management of infective endocarditis (IE). However, the reproducibility for the echocardiographic assessment of variables relevant to IE is unknown. Objectives of this study were: (1) To define the reproducibility for IE echocardiographic variables and (2) to describe a methodology for assessing quality in an observational cohort containing site-interpreted data. IE reproducibility was assessed on a subset of echocardiograms from subjects enrolled in the International Collaboration on Endocarditis registry. Specific echocardiographic case report forms were used. Intra-observer agreement was assessed from six site readers on ten randomly selected echocardiograms. Inter-observer agreement between sites and an echocardiography core laboratory was assessed on a separate random sample of 110 echocardiograms. Agreement was determined using intraclass correlation (ICC), coverage probability (CP), and limits of agreement for continuous variables and kappa statistics (κweighted) and CP for categorical variables. Intra-observer agreement for LVEF was excellent [ICC = 0.93 ± 0.1 and all pairwise differences for LVEF (CP) were within 10 %]. For IE categorical echocardiographic variables, intra-observer agreement was best for aortic abscess (κweighted = 1.0, CP = 1.0 for all readers). Highest inter-observer agreement for IE categorical echocardiographic variables was obtained for vegetation location (κweighted = 0.95; 95 % CI 0.92-0.99) and lowest agreement was found for vegetation mobility (κweighted = 0.69; 95 % CI 0.62-0.86). Moderate to excellent intra- and inter-observer agreement is observed for echocardiographic variables in the diagnostic assessment of IE. A pragmatic approach for determining echocardiographic data reproducibility in a large, multicentre, site interpreted observational cohort is feasible.

  9. A Statistical Analysis of Reviewer Agreement and Bias in Evaluating Medical Abstracts 1

    PubMed Central

    Cicchetti, Domenic V.; Conn, Harold O.

    1976-01-01

    Observer variability affects virtually all aspects of clinical medicine and investigation. One important aspect, not previously examined, is the selection of abstracts for presentation at national medical meetings. In the present study, 109 abstracts, submitted to the American Association for the Study of Liver Disease, were evaluated by three “blind” reviewers for originality, design-execution, importance, and overall scientific merit. Of the 77 abstracts rated for all parameters by all observers, interobserver agreement ranged between 81 and 88%. However, corresponding intraclass correlations varied between 0.16 (approaching statistical significance) and 0.37 (p < 0.01). Specific tests of systematic differences in scoring revealed statistically significant levels of observer bias on most of the abstract components. Moreover, the mean differences in interobserver ratings were quite small compared to the standard deviations of these differences. These results emphasize the importance of evaluating the simple percentage of rater agreement within the broader context of observer variability and systematic bias. PMID:997596

  10. 40 CFR 721.10033 - Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-. 721.10033 Section 721.10033 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1003...

  11. 40 CFR 721.10033 - Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-. 721.10033 Section 721.10033 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1003...

  12. 40 CFR 721.10033 - Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-. 721.10033 Section 721.10033 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1003...

  13. Homologous kappa-neurotoxins exhibit residue-specific interactions with the alpha 3 subunit of the nicotinic acetylcholine receptor: a comparison of the structural requirements for kappa-bungarotoxin and kappa-flavitoxin binding.

    PubMed

    McLane, K E; Weaver, W R; Lei, S; Chiappinelli, V A; Conti-Tronconi, B M

    1993-07-13

    kappa-Flavotoxin (kappa-FTX), a snake neurotoxin that is a selective antagonist of certain neuronal nicotinic acetylcholine receptors (AChRs), has recently been isolated and characterized [Grant, G. A., Frazier, M. W., & Chiappinelli, V. A. (1988) Biochemistry 27, 1532-1537]. Like the related snake toxin kappa-bungarotoxin (kappa-BTX), kappa-FTX binds with high affinity to alpha 3 subtypes of neuronal AChRs, even though there are distinct sequence differences between the two toxins. To further characterize the sequence regions of the neuronal AChR alpha 3 subunit involved in formation of the binding site for this family of kappa-neurotoxins, we investigated kappa-FTX binding to overlapping synthetic peptides screening the alpha 3 subunit sequence. A sequence region forming a "prototope" for kappa-FTX was identified within residues alpha 3 (51-70), confirming the suggestions of previous studies on the binding of kappa-BTX to the alpha 3 subunit [McLane, K. E., Tang, F., & Conti-Tronconi, B. M. (1990) J. Biol. Chem. 265, 1537-1544] and alpha-bungarotoxin to the Torpedo AChR alpha subunit [Conti-Tronconi, B. M., Tang, F., Diethelm, B. M., Spencer, S. R., Reinhardt-Maelicke, S., & Maelicke, A. (1990) Biochemistry 29, 6221-6230] that this sequence region is involved in formation of a cholinergic site. Single residue substituted analogues, where each residue of the sequence alpha 3 (51-70) was sequentially replaced by a glycine, were used to identify the amino acid side chains involved in the interaction of this prototope with kappa-FTX.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Statistical methods for conducting agreement (comparison of clinical tests) and precision (repeatability or reproducibility) studies in optometry and ophthalmology.

    PubMed

    McAlinden, Colm; Khadka, Jyoti; Pesudovs, Konrad

    2011-07-01

    The ever-expanding choice of ocular metrology and imaging equipment has driven research into the validity of their measurements. Consequently, studies of the agreement between two instruments or clinical tests have proliferated in the ophthalmic literature. It is important that researchers apply the appropriate statistical tests in agreement studies. Correlation coefficients are hazardous and should be avoided. The 'limits of agreement' method originally proposed by Altman and Bland in 1983 is the statistical procedure of choice. Its step-by-step use and practical considerations in relation to optometry and ophthalmology are detailed in addition to sample size considerations and statistical approaches to precision (repeatability or reproducibility) estimates. Ophthalmic & Physiological Optics © 2011 The College of Optometrists.

  15. Agreement between TOAST and CCS ischemic stroke classification: the NINDS SiGN study.

    PubMed

    McArdle, Patrick F; Kittner, Steven J; Ay, Hakan; Brown, Robert D; Meschia, James F; Rundek, Tatjana; Wassertheil-Smoller, Sylvia; Woo, Daniel; Andsberg, Gunnar; Biffi, Alessandro; Brenner, David A; Cole, John W; Corriveau, Roderick; de Bakker, Paul I W; Delavaran, Hossein; Dichgans, Martin; Grewal, Raji P; Gwinn, Katrina; Huq, Mohammed; Jern, Christina; Jimenez-Conde, Jordi; Jood, Katarina; Kaplan, Robert C; Katschnig, Petra; Katsnelson, Michael; Labovitz, Daniel L; Lemmens, Robin; Li, Linxin; Lindgren, Arne; Markus, Hugh S; Peddareddygari, Leema R; Pedersén, Annie; Pera, Joanna; Redfors, Petra; Roquer, Jaume; Rosand, Jonathan; Rost, Natalia S; Rothwell, Peter M; Sacco, Ralph L; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie; Thijs, Vincent; Tiedt, Steffen; Valenti, Raffaella; Worrall, Bradford B

    2014-10-28

    The objective of this study was to assess the level of agreement between stroke subtype classifications made using the Trial of Org 10172 Acute Stroke Treatment (TOAST) and Causative Classification of Stroke (CCS) systems. Study subjects included 13,596 adult men and women accrued from 20 US and European genetic research centers participating in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN). All cases had independently classified TOAST and CCS stroke subtypes. Kappa statistics were calculated for the 5 major ischemic stroke subtypes common to both systems. The overall agreement between TOAST and CCS was moderate (agreement rate, 70%; κ = 0.59, 95% confidence interval [CI] 0.58-0.60). Agreement varied widely across study sites, ranging from 28% to 90%. Agreement on specific subtypes was highest for large-artery atherosclerosis (κ = 0.71, 95% CI 0.69-0.73) and lowest for small-artery occlusion (κ = 0.56, 95% CI 0.54-0.58). Agreement between TOAST and CCS diagnoses was moderate. Caution is warranted when comparing or combining results based on the 2 systems. Replication of study results, for example, genome-wide association studies, should utilize phenotypes determined by the same classification system, ideally applied in the same manner. © 2014 American Academy of Neurology.

  16. Inter-observer agreement improves with PERCIST 1.0 as opposed to qualitative evaluation in non-small cell lung cancer patients evaluated with F-18-FDG PET/CT early in the course of chemo-radiotherapy.

    PubMed

    Fledelius, Joan; Khalil, Azza; Hjorthaug, Karin; Frøkiær, Jørgen

    2016-12-01

    The purpose of this study is to determine whether a qualitative approach or a semi-quantitative approach provides the most robust method for early response evaluation with 2'-deoxy-2'-[(18)F]fluoro-D-glucose (F-18-FDG) positron emission tomography combined with whole body computed tomography (PET/CT) in non-small cell lung cancer (NSCLC). In this study eight Nuclear Medicine consultants analyzed F-18-FDG PET/CT scans from 35 patients with locally advanced NSCLC. Scans were performed at baseline and after 2 cycles of chemotherapy. Each observer used two different methods for evaluation: (1) PET response criteria in solid tumors (PERCIST) 1.0 and (2) a qualitative approach. Both methods allocate patients into one of four response categories (complete and partial metabolic response (CMR and PMR) and stable and progressive metabolic disease (SMD and PMD)). The inter-observer agreement was evaluated using Fleiss' kappa for multiple raters, Cohens kappa for comparison of the two methods, and intraclass correlation coefficients (ICC) for comparison of lean body mass corrected standardized uptake value (SUL) peak measurements. The agreement between observers when determining the percentage change in SULpeak was "almost perfect", with ICC = 0.959. There was a strong agreement among observers allocating patients to the different response categories with a Fleiss kappa of 0.76 (0.71-0.81). In 22 of the 35 patients, complete agreement was observed with PERCIST 1.0. The agreement was lower when using the qualitative method, moderate, having a Fleiss kappa of 0.60 (0.55-0.64). Complete agreement was achieved in only 10 of the 35 patients. The difference between the two methods was statistically significant (p < 0.005) (chi-squared). Comparing the two methods for each individual observer showed Cohen's kappa values ranging from 0.64 to 0.79, translating into a strong agreement between the two methods. PERCIST 1.0 provides a higher overall agreement between observers

  17. Porcine circovirus type 2 induces the activation of nuclear factor kappa B by I{kappa}B{alpha} degradation

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

    Wei Li; Kwang, Jimmy; Wang Jin

    The transcription factor NF-{kappa}B is commonly activated upon virus infection and a key player in the induction and regulation of the host immune response. The present study demonstrated for the first time that porcine circovirus type 2 (PCV2), which is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome, can activate NF-{kappa}B in PCV2-infected PK15 cells. In PCV2-infected cells, NF-{kappa}B was activated concomitantly with viral replication, which was characterized by increased DNA binding activity, translocation of NF-{kappa}B p65 from the cytoplasm to the nucleus, as well as degradation and phosphorylation of I{kappa}B{alpha} protein. We further demonstratedmore » PCV2-induced activation of NF-{kappa}B and colocalization of p65 nuclear translocation with virus replication in cultured cells. Treatment of cells with CAPE, a selective inhibitor of NF-{kappa}B activation, reduced virus protein expression and progeny production followed by decreasing PCV2-induced apoptotic caspase activity, indicating the involvement of this transcription factor in induction of cell death. Taken together, these data suggest that NF-{kappa}B activation is important for PCV2 replication and contributes to virus-mediated changes in host cells. The results presented here provide a basis for understanding molecular mechanism of PCV2 infection.« less

  18. Agreement between self-reported data on medicine use and prescription records vary according to method of analysis and therapeutic group.

    PubMed

    Nielsen, Merete Willemoes; Søndergaard, Birthe; Kjøller, Mette; Hansen, Ebba Holme

    2008-09-01

    This study compared national self-reported data on medicine use and national prescription records at the individual level. Data from the nationally representative Danish health survey conducted in 2000 (n=16,688) were linked at the individual level to national prescription records covering 1999-2000. Kappa statistics and 95% confidence intervals were calculated. Applying the legend time method to medicine groups used mainly on a chronic basis revealed good to very good agreement between the two data sources, whereas medicines used as needed showed fair to moderate agreement. When a fixed-time window was applied for analysis, agreement was unchanged for medicines used mainly on a chronic basis, whereas agreement increased somewhat compared to the legend time method when analyzing medicines used as needed. Agreement between national self-reported data and national prescription records differed according to method of analysis and therapeutic group. A fixed-time window is an appropriate method of analysis for most therapeutic groups.

  19. Kappa and Rater Accuracy: Paradigms and Parameters.

    PubMed

    Conger, Anthony J

    2017-12-01

    Drawing parallels to classical test theory, this article clarifies the difference between rater accuracy and reliability and demonstrates how category marginal frequencies affect rater agreement and Cohen's kappa (κ). Category assignment paradigms are developed: comparing raters to a standard (index) versus comparing two raters to one another (concordance), using both nonstochastic and stochastic category membership. Using a probability model to express category assignments in terms of rater accuracy and random error, it is shown that observed agreement (Po) depends only on rater accuracy and number of categories; however, expected agreement (Pe) and κ depend additionally on category frequencies. Moreover, category frequencies affect Pe and κ solely through the variance of the category proportions, regardless of the specific frequencies underlying the variance. Paradoxically, some judgment paradigms involving stochastic categories are shown to yield higher κ values than their nonstochastic counterparts. Using the stated probability model, assignments to categories were generated for 552 combinations of paradigms, rater and category parameters, category frequencies, and number of stimuli. Observed means and standard errors for Po, Pe, and κ were fully consistent with theory expectations. Guidelines for interpretation of rater accuracy and reliability are offered, along with a discussion of alternatives to the basic model.

  20. FBI-1 enhances transcription of the nuclear factor-kappaB (NF-kappaB)-responsive E-selectin gene by nuclear localization of the p65 subunit of NF-kappaB.

    PubMed

    Lee, Dong-Kee; Kang, Jae-Eun; Park, Hye-Jin; Kim, Myung-Hwa; Yim, Tae-Hee; Kim, Jung-Min; Heo, Min-Kyu; Kim, Kyu-Yeun; Kwon, Ho Jeong; Hur, Man-Wook

    2005-07-29

    The POZ domain is a highly conserved protein-protein interaction motif found in many regulatory proteins. Nuclear factor-kappaB (NF-kappaB) plays a key role in the expression of a variety of genes in response to infection, inflammation, and stressful conditions. We found that the POZ domain of FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) interacted with the Rel homology domain of the p65 subunit of NF-kappaB in both in vivo and in vitro protein-protein interaction assays. FBI-1 enhanced NF-kappaB-mediated transcription of E-selectin genes in HeLa cells upon phorbol 12-myristate 13-acetate stimulation and overcame gene repression by IkappaB alpha or IkappaB beta. In contrast, the POZ domain of FBI-1, which is a dominant-negative form of FBI-1, repressed NF-kappaB-mediated transcription, and the repression was cooperative with IkappaB alpha or IkappaB beta. In contrast, the POZ domain tagged with a nuclear localization sequence polypeptide of FBI-1 enhanced NF-kappaB-responsive gene transcription, suggesting that the molecular interaction between the POZ domain and the Rel homology domain of p65 and the nuclear localization by the nuclear localization sequence are important in the transcription enhancement mediated by FBI-1. Confocal microscopy showed that FBI-1 increased NF-kappaB movement into the nucleus and increased the stability of NF-kappaB in the nucleus, which enhanced NF-kappaB-mediated transcription of the E-selectin gene. FBI-1 also interacted with IkappaB alpha and IkappaB beta.

  1. Characterization of kappa 1 and kappa 2 opioid binding sites in frog (Rana esculenta) brain membrane preparation

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

    Benyhe, S.; Varga, E.; Hepp, J.

    1990-09-01

    The distribution and properties of frog brain kappa-opioid receptor subtypes differ not only from those of the guinea pig brain, but also from that of the rat brain. In guinea pig cerebellum the kappa 1 is the dominant receptor subtype, frog brain contains mainly the kappa 2 subtype, and the distribution of the rat brain subtypes is intermediate between the two others. In competition experiments it has been established that ethylketocyclazocine and N-cyclopropylmethyl-norazidomorphine, which are nonselective kappa-ligands, have relatively high affinities to frog brain membranes. The kappa 2 ligands (Met5)enkephalin-Arg6-Phe7 and etorphine also show high affinities to the frog brain.more » Kappa 1 binding sites measured in the presence of 5 microM/D-Ala2-Leu5/enkephalin represent 25-30% of (3H)ethylketocyclazocine binding in frog brain membranes. The kappa 2 subtype in frog brain resembles more to the mu subtype than the delta subtype of opioid receptors, but it differs from the mu subtype in displaying low affinity toward beta-endorphin and /D-Ala2-(Me)Phe4-Gly5-ol/enkephalin (DAGO). From our data it is evident that the opioid receptor subtypes are already present in the amphibian brain but the differences among them are less pronounced than in mammalian brain.« less

  2. High inter-observer agreement of observer-perceived pain assessment in the emergency department.

    PubMed

    Hangaard, Martin Høhrmann; Malling, Brian; Mogensen, Christian Backer

    2018-02-21

    Triage is used to prioritize the patients in the emergency department. The majority of the triage systems include the patients' pain score to assess their level of acuity by using a combination of patient reported pain and observer-perceived pain; the latter therefore requires a certain degree of inter-observer agreement. The aim of the present study was to assess the inter-observer agreement of perceived pain among emergency department nurses and to evaluate if it was influenced by predetermined factors like age and gender. A project assistant randomly recruited two nurses, who were not allowed to interact with each other, to assess patient pain intensity on the numeric ranking scale. The project assistant afterwards entered the pain scores in a predesigned electronic questionnaire. We used weighted Fleiss-Cohen (quadratic) kappa statistics, Bland-Altman statistics and logistic regression analysis to assess the inter-observer agreement. One hundred and sixty-two patients were included. They had a median age of 38 years and 45% were females. 30% of the patients were acute surgical patients and 70% acute orthopedic patients. The average time between the pain assessments were 1,7 min. The Bland Altman analysis found a mean difference in pain score of 0.2 and 95% limits of agreement of +/- 3 point. When the NRS scores were translated to commonly used pain categories (no, mild, moderate or severe pain) we found a 70% agreement with a mean difference in categories of 0.05 and 95% limits of agreement of +/- 1 category. Patient age, gender, localization of pain, examination room or presence of a significant other did not affect the inter-observer agreement. We found 70% agreement on pain category between the nurses and it is justified that nurse-perceived pain assessment is used for triage in the emergency department.

  3. Interobserver agreement in analysis of cardiotocograms recorded during trial of labor after cesarean.

    PubMed

    Caning, M M; Thisted, D L A; Amer-Wählin, I; Laier, G H; Krebs, L

    2018-05-17

    To examine interobserver agreement in intrapartum cardiotocography (CTG) classification in women undergoing trial of labor after a cesarean section (TOLAC) at term with or without complete uterine rupture. Nineteen blinded and independent Danish obstetricians assessed CTG tracings from 47 women (174 individual pages) with a complete uterine rupture during TOLAC and 37 women (133 individual pages) with no uterine rupture during TOLAC. Individual pages with CTG tracings lasting at least 20 min were evaluated by three different assessors and counted as an individual case. The tracings were analyzed according to the modified version of the Federation of Gynaecology and Obstetrics (FIGO) guidelines elaborated for the use of STAN (ST-analysis). Occurrence of defined abnormalities was recorded and the tracings were classified as normal, suspicious, pathological, or preterminal. The interobserver agreement was evaluated using Fleiss' kappa. Agreement on classification of a preterminal CTG was almost perfect. The interobserver agreement on normal, suspicious or pathological CTG was moderate to substantial. Regarding the presence of severe variable decelerations, the agreement was moderate. No statistical difference was found in the interobserver agreement between classification of tracings from women undergoing TOLAC with and without complete uterine rupture. The interobserver agreement on classification of CTG tracings from high-risk deliveries during TOLAC is best for assessment of a preterminal CTG and the poorest for the identification of severe variable decelerations.

  4. MicroRNA-22 and microRNA-140 suppress NF-{kappa}B activity by regulating the expression of NF-{kappa}B coactivators

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

    Takata, Akemi; Otsuka, Motoyuki, E-mail: otsukamo-tky@umin.ac.jp; Kojima, Kentaro

    2011-08-12

    Highlights: {yields} miRNAs were screened for their ability to regulate NF-{kappa}B activity. {yields} miRNA-22 and miRNA-140-3p suppress NF-{kappa}B activity by regulating coactivators. {yields} miRNA-22 targets nuclear receptor coactivator 1 (NCOA1). {yields} miRNA-140-3p targets nuclear receptor-interacting protein 1 (NRIP1). -- Abstract: Nuclear factor {kappa}B (NF-{kappa}B) is a transcription factor that regulates a set of genes that are critical to many biological phenomena, including liver tumorigenesis. To identify microRNAs (miRNAs) that regulate NF-{kappa}B activity in the liver, we screened 60 miRNAs expressed in hepatocytes for their ability to modulate NF-{kappa}B activity. We found that miRNA-22 and miRNA-140-3p significantly suppressed NF-{kappa}B activity bymore » regulating the expression of nuclear receptor coactivator 1 (NCOA1) and nuclear receptor-interacting protein 1 (NRIP1), both of which are NF-{kappa}B coactivators. Our results provide new information about the roles of miRNAs in the regulation of NF-{kappa}B activity.« less

  5. Intramodality and intermodality agreement in radiography and computed tomography of equine distal limb fractures.

    PubMed

    Crijns, C P; Martens, A; Bergman, H-J; van der Veen, H; Duchateau, L; van Bree, H J J; Gielen, I M V L

    2014-01-01

    Computed tomography (CT) is increasingly accessible in equine referral hospitals. To document the level of agreement within and between radiography and CT in characterising equine distal limb fractures. Retrospective descriptive study. Images from horses that underwent radiographic and CT evaluation for suspected distal limb fractures were reviewed, including 27 horses and 3 negative controls. Using Cohen's kappa and weighted kappa analysis, the level of agreement among 4 observers for a predefined set of diagnostic characteristics for radiography and CT separately and for the level of agreement between the 2 imaging modalities were documented. Both CT and radiography had very good intramodality agreement in identifying fractures, but intermodality agreement was lower. There was good intermodality and intramodality agreement for anatomical localisation and the identification of fracture displacement. Agreement for articular involvement, fracture comminution and fracture fragment number was towards the lower limit of good agreement. There was poor to fair intermodality agreement regarding fracture orientation, fracture width and coalescing cracks; intramodality agreement was higher for CT than for radiography for these features. Further studies, including comparisons with surgical and/or post mortem findings, are required to determine the sensitivity and specificity of CT and radiography in the diagnosis and characterisation of equine distal limb fractures. © 2013 EVJ Ltd.

  6. Agreement between diagnoses reached by clinical examination and available reference standards: a prospective study of 216 patients with lumbopelvic pain

    PubMed Central

    Laslett, Mark; McDonald, Barry; Tropp, Hans; Aprill, Charles N; Öberg, Birgitta

    2005-01-01

    Background The tissue origin of low back pain (LBP) or referred lower extremity symptoms (LES) may be identified in about 70% of cases using advanced imaging, discography and facet or sacroiliac joint blocks. These techniques are invasive and availability varies. A clinical examination is non-invasive and widely available but its validity is questioned. Diagnostic studies usually examine single tests in relation to single reference standards, yet in clinical practice, clinicians use multiple tests and select from a range of possible diagnoses. There is a need for studies that evaluate the diagnostic performance of clinical diagnoses against available reference standards. Methods We compared blinded clinical diagnoses with diagnoses based on available reference standards for known causes of LBP or LES such as discography, facet, sacroiliac or hip joint blocks, epidurals injections, advanced imaging studies or any combination of these tests. A prospective, blinded validity design was employed. Physiotherapists examined consecutive patients with chronic lumbopelvic pain and/or referred LES scheduled to receive the reference standard examinations. When diagnoses were in complete agreement regardless of complexity, "exact" agreement was recorded. When the clinical diagnosis was included within the reference standard diagnoses, "clinical agreement" was recorded. The proportional chance criterion (PCC) statistic was used to estimate agreement on multiple diagnostic possibilities because it accounts for the prevalence of individual categories in the sample. The kappa statistic was used to estimate agreement on six pathoanatomic diagnoses. Results In a sample of chronic LBP patients (n = 216) with high levels of disability and distress, 67% received a patho-anatomic diagnosis based on available reference standards, and 10% had more than one tissue origin of pain identified. For 27 diagnostic categories and combinations, chance clinical agreement (PCC) was estimated at 13

  7. Tooth shade measurements under standard and nonstandard illumination and their agreement with skin color.

    PubMed

    Al-Dwairi, Ziad; Shaweesh, Ashraf; Kamkarfar, Sohrab; Kamkarfar, Shahrzad; Borzabadi-Farahani, Ali; Lynch, Edward

    2014-01-01

    The purpose of this study was to examine the relationship between skin color (shade) and tooth shade under standard and nonstandard illumination sources. Four hundred Jordanian participants (200 males, 200 females, 20 to 50 years of age) were studied. Skin colors were assessed and categorized using the L'Oreal and Revlon foundation shade guides (light, medium, dark). The Vita Pan Classical Shade Guide (VPCSG; Vident) and digital Vita EasyShade Intraoral Dental Spectrophotometer (VESIDS; Vident) were used to select shades in the middle thirds of maxillary central incisors; tooth shades were classified into four categories (highest, high, medium, low). Significant gender differences were observed for skin colors (P = .000) and tooth shade guide systems (P = .001 and .050 for VPCSG and VESIDS, respectively). The observed agreement was 100% and 93% for skin and tooth shade guides, respectively. The corresponding kappa statistic values were 1.00 and 0.79, respectively (substantial agreement, P < .001). The observed agreement between skin color and tooth shades (VPCSG and VESIDS) was approximately 50%. The digital tooth shade guide system can be a satisfactory substitute for classical tooth shade guides and clinical shade matching. There was only moderate agreement between skin color and tooth shade.

  8. Agreement between hysterosalpingography and laparoscopic chromopertubation in assessment of tubal patency.

    PubMed

    Matorras, R; Rodriguez, F; Pêrez, C; Pijoan, J I; Echanojauregui, A; Rodriguez-Escudero, F J

    1998-01-01

    To assess the agreement between tubal patency assessed by laparoscopy with chromopertubation and by hysterosalpingography using contrast media. University Medical School. 314 consecutive women subjected to laparoscopy and hysterosalpingography for an infertility study. Prospective study. Chromopertubation using Methylen blue dye, performed on days 20-24. Hysterosalpingography performed on days 7-10 with water soluble contrast. Kappa coefficient calculation. Kappa coefficient ranged from 0.40 to 0.36, depending on the categories analyzed, corresponding to a fair agreement. The diagnosis of tubal factor requires that both tubal patency tests (Hysterosalpingography and laparoscopy) show an abnormal patency. When one of the aforementioned tests is normal, performing the second one has little clinical advantage. However, it is suggested that when there is a discordant patency the pregnancy rates could be somewhat reduced.

  9. The effects of dexamethasone on rat brain cortical nuclear factor kappa B (NF-{kappa}B) in endotoxic shock

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

    Wang Zhi; Kang Jinsong; Li Yang

    2006-08-01

    To explore the molecular mechanism of brain tissue injury induced by lipopolysaccharide (LPS), we studied the effects of endotoxic shock on rat brain cortex NF-{kappa}B and the effects of dexamethasone on these changes. Rats were randomly divided into LPS, LPS + dexamethasone, and control groups. The DNA-binding activity of NF-{kappa}B was observed using electrophoretic mobility shift assay (EMSA). Protein expression in nuclear extracts was studied using Western blots, and nuclear translocation was observed using immunohistochemistry. These indices were assayed at 1 h and 4 h after intravenous injection of LPS (4 mg.kg{sup -1}). EMSA showed significantly increased NF-{kappa}B DNA-binding activitymore » in nuclear extracts from the LPS group at both 1 h and 4 h after LPS injection, compared with the control group (P < 0.01). For the LPS group, the NF-{kappa}B DNA-binding activity was greater at 1 h than at 4 h (P < 0.05). The expression of p65 and p50 protein in the nuclear extracts was also increased, as compared with the control group. However, the expression of p65 and p50 protein from cytosolic extracts did not show any significant change. Dexamethasone down-regulated not only NF-{kappa}B DNA-binding activity but also the expression of p65 protein in the nuclear extracts. From these data, we have concluded that NF-{kappa}B activation and nuclear translocation of NF-{kappa}B play a key role in the molecular mechanism of brain tissue injury in endotoxic shock. Dexamethasone may alleviate brain injury by inhibiting NF-{kappa}B activation.« less

  10. Preliminary Estimation of Kappa Parameter in Croatia

    NASA Astrophysics Data System (ADS)

    Stanko, Davor; Markušić, Snježana; Ivančić, Ines; Mario, Gazdek; Gülerce, Zeynep

    2017-12-01

    Spectral parameter kappa κ is used to describe spectral amplitude decay “crash syndrome” at high frequencies. The purpose of this research is to estimate spectral parameter kappa for the first time in Croatia based on small and moderate earthquakes. Recordings of local earthquakes with magnitudes higher than 3, epicentre distances less than 150 km, and focal depths less than 30 km from seismological stations in Croatia are used. The value of kappa was estimated from the acceleration amplitude spectrum of shear waves from the slope of the high-frequency part where the spectrum starts to decay rapidly to a noise floor. Kappa models as a function of a site and distance were derived from a standard linear regression of kappa-distance dependence. Site kappa was determined from the extrapolation of the regression line to a zero distance. The preliminary results of site kappa across Croatia are promising. In this research, these results are compared with local site condition parameters for each station, e.g. shear wave velocity in the upper 30 m from geophysical measurements and with existing global shear wave velocity - site kappa values. Spatial distribution of individual kappa’s is compared with the azimuthal distribution of earthquake epicentres. These results are significant for a couple of reasons: to extend the knowledge of the attenuation of near-surface crust layers of the Dinarides and to provide additional information on the local earthquake parameters for updating seismic hazard maps of studied area. Site kappa can be used in the re-creation, and re-calibration of attenuation of peak horizontal and/or vertical acceleration in the Dinarides area since information on the local site conditions were not included in the previous studies.

  11. Comparison of intra-oral and study cast measurements in the assessment of malocclusion.

    PubMed

    Ovsenik, Maja; Farcnik, Franc M; Verdenik, Ivan

    2004-06-01

    Malocclusion assessment methods are based on registrations and measurements made on study casts, which requires that impressions be taken. In addition to being costly and time-consuming, this process can be unpleasant for very young children. Therefore, the aim of this study was to evaluate the reliability of intra-oral measurements that compute a malocclusion index score to determine malocclusion severity in the mixed dentition. The research was part of a longitudinal study in Slovenia on a sample of 530 3-year-old children. At 8 years of age (mean 8.5 years, standard deviation 0.2), a cohort of 101 children (44 boys, 57 girls) was randomly selected in a cross-sectional study. Quantitative registrations of space and occlusal anomalies were performed intra-orally as well as on study casts. Kappa (kappa) statistics were used to evaluate the agreement between clinical and study cast malocclusion assessments. Systematic bias of measurements was tested using Wilcoxon's signed rank test. The results showed complete agreement between the two measurements for anterior crossbite, anterior open bite and overjet scores (kappa = 1); excellent reliability for the buccal segment relationship (kappa = 0.93), transverse occlusion of posterior teeth (kappa = 0.87); and substantial agreement for overbite (kappa = 0.79) and midline deviation (kappa = 0.71). For the remainder of the traits the agreement was moderate: rotation of incisors (kappa = 0.58), crowding of upper incisors (kappa = 0.51), axial inclination of teeth (kappa = 0.44) and lower incisor crowding (kappa = 0.41). Intra-orally small, but statistically significant scoring of lower incisor rotation and crowding was identified. On the study casts the most favourable axial inclination was found for buccal segment occlusion. Overall classification into severity grades, based on the total malocclusion score, showed excellent agreement between the two methods (kappa = 0.89), without statistically significant bias

  12. Statistical Validation for Clinical Measures: Repeatability and Agreement of Kinect™-Based Software

    PubMed Central

    Tello, Emanuel; Rodrigo, Alejandro; Valentinuzzi, Max E.

    2018-01-01

    Background The rehabilitation process is a fundamental stage for recovery of people's capabilities. However, the evaluation of the process is performed by physiatrists and medical doctors, mostly based on their observations, that is, a subjective appreciation of the patient's evolution. This paper proposes a tracking platform of the movement made by an individual's upper limb using Kinect sensor(s) to be applied for the patient during the rehabilitation process. The main contribution is the development of quantifying software and the statistical validation of its performance, repeatability, and clinical use in the rehabilitation process. Methods The software determines joint angles and upper limb trajectories for the construction of a specific rehabilitation protocol and quantifies the treatment evolution. In turn, the information is presented via a graphical interface that allows the recording, storage, and report of the patient's data. For clinical purposes, the software information is statistically validated with three different methodologies, comparing the measures with a goniometer in terms of agreement and repeatability. Results The agreement of joint angles measured with the proposed software and goniometer is evaluated with Bland-Altman plots; all measurements fell well within the limits of agreement, meaning interchangeability of both techniques. Additionally, the results of Bland-Altman analysis of repeatability show 95% confidence. Finally, the physiotherapists' qualitative assessment shows encouraging results for the clinical use. Conclusion The main conclusion is that the software is capable of offering a clinical history of the patient and is useful for quantification of the rehabilitation success. The simplicity, low cost, and visualization possibilities enhance the use of the software Kinect for rehabilitation and other applications, and the expert's opinion endorses the choice of our approach for clinical practice. Comparison of the new measurement

  13. Statistical Validation for Clinical Measures: Repeatability and Agreement of Kinect™-Based Software.

    PubMed

    Lopez, Natalia; Perez, Elisa; Tello, Emanuel; Rodrigo, Alejandro; Valentinuzzi, Max E

    2018-01-01

    The rehabilitation process is a fundamental stage for recovery of people's capabilities. However, the evaluation of the process is performed by physiatrists and medical doctors, mostly based on their observations, that is, a subjective appreciation of the patient's evolution. This paper proposes a tracking platform of the movement made by an individual's upper limb using Kinect sensor(s) to be applied for the patient during the rehabilitation process. The main contribution is the development of quantifying software and the statistical validation of its performance, repeatability, and clinical use in the rehabilitation process. The software determines joint angles and upper limb trajectories for the construction of a specific rehabilitation protocol and quantifies the treatment evolution. In turn, the information is presented via a graphical interface that allows the recording, storage, and report of the patient's data. For clinical purposes, the software information is statistically validated with three different methodologies, comparing the measures with a goniometer in terms of agreement and repeatability. The agreement of joint angles measured with the proposed software and goniometer is evaluated with Bland-Altman plots; all measurements fell well within the limits of agreement, meaning interchangeability of both techniques. Additionally, the results of Bland-Altman analysis of repeatability show 95% confidence. Finally, the physiotherapists' qualitative assessment shows encouraging results for the clinical use. The main conclusion is that the software is capable of offering a clinical history of the patient and is useful for quantification of the rehabilitation success. The simplicity, low cost, and visualization possibilities enhance the use of the software Kinect for rehabilitation and other applications, and the expert's opinion endorses the choice of our approach for clinical practice. Comparison of the new measurement technique with established

  14. A Population-Based Assessment of the Agreement Between Grading of Goniophotographic Images and Gonioscopy in the Chinese-American Eye Study (CHES)

    PubMed Central

    Murakami, Yohko; Wang, Dandan; Burkemper, Bruce; Lin, Shan C.; Varma, Rohit

    2016-01-01

    Purpose To compare grading of goniophotographic images and gonioscopy in assessing the iridocorneal angle. Methods In a population-based, cross-sectional study, participants underwent gonioscopy and goniophotographic imaging during the same visit. The iridocorneal angle was classified as closed if the posterior trabecular meshwork could not be seen. A single masked observer graded the goniophotographic images, and each eye was classified as having angle closure based on the number of closed quadrants. Agreement between the methods was analyzed by calculating kappa (κ) and first-order agreement coefficient (AC1) statistics and comparison of area under receiver operating characteristic curves (AUC). Results A total of 4149 Chinese Americans (3994 eyes) were included in this study. The agreement for angle closure diagnosis between gonioscopy and EyeCam was moderate to excellent (κ = 0.60, AC1 0.90, AUC 0.76–0.80). Conclusions Detection of iridocorneal angle closure based on goniophotographic imaging shows moderate to very good agreement with angle closure assessment using gonioscopy. PMID:27571018

  15. A Population-Based Assessment of the Agreement Between Grading of Goniophotographic Images and Gonioscopy in the Chinese-American Eye Study (CHES).

    PubMed

    Murakami, Yohko; Wang, Dandan; Burkemper, Bruce; Lin, Shan C; Varma, Rohit

    2016-08-01

    To compare grading of goniophotographic images and gonioscopy in assessing the iridocorneal angle. In a population-based, cross-sectional study, participants underwent gonioscopy and goniophotographic imaging during the same visit. The iridocorneal angle was classified as closed if the posterior trabecular meshwork could not be seen. A single masked observer graded the goniophotographic images, and each eye was classified as having angle closure based on the number of closed quadrants. Agreement between the methods was analyzed by calculating kappa (κ) and first-order agreement coefficient (AC1) statistics and comparison of area under receiver operating characteristic curves (AUC). A total of 4149 Chinese Americans (3994 eyes) were included in this study. The agreement for angle closure diagnosis between gonioscopy and EyeCam was moderate to excellent (κ = 0.60, AC1 0.90, AUC 0.76-0.80). Detection of iridocorneal angle closure based on goniophotographic imaging shows moderate to very good agreement with angle closure assessment using gonioscopy.

  16. Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

    PubMed

    Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

    2018-01-20

    The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

  17. Inter-rater and intra-rater agreement on the Nordic Orofacial Test--Screening examination in children, adolescents and young adults with cerebral palsy.

    PubMed

    Edvinsson, Siv Elisabet; Lundqvist, Lars-Olov

    2014-02-01

    To evaluate inter-rater and intra-rater agreement on the Nordic Orofacial Test-Screening (NOT-S) examination applied to children, adolescents and young adults with cerebral palsy (CP). Using the NOT-S examination, two speech and language pathologists independently assessed video recordings of 48 subjects with CP aged 5-22 years and representing all CP sub-diagnoses and levels of gross motor function and manual ability. Thirty-one subjects were reassessed. Fifteen out of 17 items in the NOT-S examination domains (1) Face at rest, (2) Nose breathing, (3) Facial expression, (4) Masticatory muscle and jaw function, (5) Oral motor function and (6) Speech were rated using a 'yes' (dysfunction observed)/'no' format, generating an overall score of 0-6. Inter-rater agreement: Twelve out of 15 items and five out of six domains showed acceptable unweighted kappa values (κ = 0.46-1.00). The lowest kappa value was found for domain 4 (κ = -0.04), although it had high inter-rater agreement (92%). The linear weighted kappa value for the overall NOT-S examination score was 0.65 (95% CI = 0.49-0.82). Intra-rater agreement: All items and domains showed acceptable unweighted kappa values (items 0.58-1.00 and 0.59-1.00, domains 0.81-1.00 and 0.62-0.89) for both raters. The linear weighted kappa value for the overall NOT-S examination score was 0.81 (95% CI = 0.63-0.99) for rater A and 0.54 (95% CI = 0.25-0.82) for rater B. The NOT-S examination has acceptable inter-rater and intra-rater agreement when used in young individuals with CP.

  18. Methodological review: measured and reported congruence between preferred and actual place of death.

    PubMed

    Bell, C L; Somogyi-Zalud, E; Masaki, K H

    2009-09-01

    Congruence between preferred and actual place of death is an important palliative care outcome reported in the literature. We examined methods of measuring and reporting congruence to highlight variations impairing cross-study comparisons. Medline, PsychInfo, CINAHL, and Web of Science were systematically searched for clinical research studies examining patient preference and congruence as an outcome. Data were extracted into a matrix, including purpose, reported congruence, and method for eliciting preference. Studies were graded for quality. Using tables of preferred versus actual places of death, an overall congruence (total met preferences out of total preferences) and a kappa statistic of agreement were determined for each study. Twelve studies were identified. Percentage of congruence was reported using four different definitions. Ten studies provided a table or partial table of preferred versus actual deaths for each place. Three studies provided kappa statistics. No study achieved better than moderate agreement when analysed using kappa statistics. A study which elicited ideal preference reported the lowest agreement, while longitudinal studies reporting final preferred place of death yielded the highest agreement (moderate agreement). Two other studies of select populations also yielded moderate agreement. There is marked variation in methods of eliciting and reporting congruence, even among studies focused on congruence as an outcome. Cross-study comparison would be enhanced by the use of similar questions to elicit preference, tables of preferred versus actual places of death, and kappa statistics of agreement.

  19. Agreement between coding schemas used to identify bleeding-related hospitalizations in claims analyses of nonvalvular atrial fibrillation patients.

    PubMed

    Coleman, Craig I; Vaitsiakhovich, Tatsiana; Nguyen, Elaine; Weeda, Erin R; Sood, Nitesh A; Bunz, Thomas J; Schaefer, Bernhard; Meinecke, Anna-Katharina; Eriksson, Daniel

    2018-01-01

    Schemas to identify bleeding-related hospitalizations in claims data differ in billing codes used and coding positions allowed. We assessed agreement across bleeding-related hospitalization coding schemas for claims analyses of nonvalvular atrial fibrillation (NVAF) patients on oral anticoagulation (OAC). We hypothesized that prior coding schemas used to identify bleeding-related hospitalizations in claim database studies would provide varying levels of agreement in incidence rates. Within MarketScan data, we identified adults, newly started on OAC for NVAF from January 2012 to June 2015. Billing code schemas developed by Cunningham et al., the US Food and Drug Administration (FDA) Mini-Sentinel program, and Yao et al. were used to identify bleeding-related hospitalizations as a surrogate for major bleeding. Bleeds were subcategorized as intracranial hemorrhage (ICH), gastrointestinal (GI), or other. Schema agreement was assessed by comparing incidence, rates of events/100 person-years (PYs), and Cohen's kappa statistic. We identified 151 738 new-users of OAC with NVAF (CHA2DS2-VASc score = 3, [interquartile range = 2-4] and median HAS-BLED score = 3 [interquartile range = 2-3]). The Cunningham, FDA Mini-Sentinel, and Yao schemas identified any bleeding-related hospitalizations in 1.87% (95% confidence interval [CI]: 1.81-1.94), 2.65% (95% CI: 2.57-2.74), and 4.66% (95% CI: 4.55-4.76) of patients (corresponding rates = 3.45, 4.90, and 8.65 events/100 PYs). Kappa agreement across schemas was weak-to-moderate (κ = 0.47-0.66) for any bleeding hospitalization. Near-perfect agreement (κ = 0.99) was observed with the FDA Mini-Sentinel and Yao schemas for ICH-related hospitalizations, but agreement was weak when comparing Cunningham to FDA Mini-Sentinel or Yao (κ = 0.52-0.53). FDA Mini-Sentinel and Yao agreement was moderate (κ = 0.62) for GI bleeding, but agreement was weak when comparing Cunningham to FDA Mini-Sentinel or Yao (κ

  20. Nonplanar ion acoustic waves with kappa-distributed electrons

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

    Sahu, Biswajit

    2011-06-15

    Using the standard reductive perturbation technique, nonlinear cylindrical and spherical Kadomtsev-Petviashvili equations are derived for the propagation of ion acoustic solitary waves in an unmagnetized collisionless plasma with kappa distributed electrons and warm ions. The influence of kappa-distributed electrons and the effects caused by the transverse perturbation on cylindrical and spherical ion acoustic waves (IAWs) are investigated. It is observed that increase in the kappa distributed electrons (i.e., decreasing {kappa}) decreases the amplitude of the solitary electrostatic potential structures. The numerical results are presented to understand the formation of ion acoustic solitary waves with kappa-distributed electrons in nonplanar geometry. Themore » present investigation may have relevance in the study of propagation of IAWs in space and laboratory plasmas.« less

  1. Are photographic records reliable for orthodontic screening?

    PubMed

    Mandall, N A

    2002-06-01

    The aim of the study was to evaluate the reliability of a panel of orthodontists for accepting new patient referrals based on clinical photographs. Eight orthodontists from Greater Manchester, Lancashire, Chester, and Derbyshire observed clinical photographs of 40 consecutive new patients attending the orthodontic department, Hope Hospital, Salford. They recorded whether or not they would accept the patient, as a new patient referral, in their department. Each consultant was asked to take into account factors, such as oral hygiene, dental development, and severity of the malocclusion. Kappa statistic for multiple-rater agreement and kappa statistic for intra-observer reliability were calculated. Inter-observer panel agreement for accepting new patient referrals based on photographic information was low (multiple rater kappa score 0.37). Intra-examiner agreement was better (kappa range 0.34-0.90). Clinician agreement for screening and accepting orthodontic referrals based on clinical photographs is comparable to that previously reported for other clinical decision making.

  2. Poor-to-moderate agreement between self and proxy interviews of mobile phone use.

    PubMed

    Hutter, Hans-Peter; Ehrenhöfer, Lisa; Freuis, Edith; Hartl, Patrik; Kundi, Michael

    2012-10-01

    In epidemiological studies, cases cannot always be interviewed due to them being too ill or already deceased. Under these circumstances, proxy interviews are often conducted; however, the veridicality of information about mobile phone use gained by proxy interviews has been doubted. The issue is undecided due to the lack of empirical data. We conducted a study of 119 heterosexual couples. Both partners answered two questionnaires about mobile phone use, one about their own use and one about their partner's use. Overall agreement assessed using Cohen's kappa, Passing and Bablok regression, and concordance coefficients between self and proxy data was poor to moderate (e.g., concordance coefficients of 0.55 for duration of use). The only item with good agreement was whether or not a prepaid phone was used (Cohen's kappa 0.78 and 0.63 for male and female estimates, respectively), and to a lesser degree, the onset of mobile phone use (concordance coefficients of 0.66 and 0.61). Poorest agreement was obtained for the side of the head the mobile phone was held during calls (kappa coefficients of 0.20 and 0.24 for female and male estimates, respectively). We conclude that the assessment of mobile phone use by proxy data cannot be relied on except for information about onset of mobile phone use, use of prepaid or contract phones, and, to a lesser degree, duration of daily use. Agreement concerning the important information about side of the head the mobile phone is held during calls was poorest and only slightly better than chance. Copyright © 2012 Wiley Periodicals, Inc.

  3. A pilot study of clinical agreement in cardiovascular preparticipation examinations: how good is the standard of care?

    PubMed

    O'Connor, Francis G; Johnson, Jeremy D; Chapin, Mark; Oriscello, Ralph G; Taylor, Dean C

    2005-05-01

    To evaluate the interobserver agreement between physicians regarding a abnormal cardiovascular assessment on athletic preparticipation examinations. Cross-sectional clinical survey. Outpatient Clinic, United States Military Academy, West Point, NY. We randomly selected 101 out of 539 cadet-athletes presenting for a preparticipation examination. Two primary care sports medicine fellows and a cardiologist examined the cadets. After obtaining informed consent from all participants, all 3 physicians separately evaluated all 101 cadets. The physicians recorded their clinical findings and whether they thought further cardiovascular evaluation (echocardiography) was indicated. Rate of referral for further cardiovascular evaluation, clinical agreement between sports medicine fellows, and clinical agreement between sports medicine fellows and the cardiologist. Each fellow referred 6 of the 101 evaluated cadets (5.9%). The cardiologist referred none. Although each fellow referred 6 cadets, only 1 cadet was referred by both. The kappa statistic for clinical agreement between fellows is 0.114 (95% CI, -0.182 to 0.411). There was no clinical agreement between the fellows and the cardiologist. This pilot study reveals a low level of agreement between physicians regarding which athletes with an abnormal examination deserved further testing. It challenges the standard of care and questions whether there is a need for improved technologies or improved training in cardiovascular clinical assessment.

  4. Characterizing Cometary Electrons with Kappa Distributions

    NASA Technical Reports Server (NTRS)

    Broiles, T. W.; Livadiotis, G.; Burch, J. L.; Chae, K.; Clark, G.; Cravens, T. E.; Davidson, R.; Eriksson, A.; Frahm, R. A.; Fuselier, S. A.; hide

    2016-01-01

    The Rosetta spacecraft has escorted comet 67P/Churyumov-Gerasimenko since 6 August 2014 and has offered an unprecedented opportunity to study plasma physics in the coma. We have used this opportunity to make the first characterization of cometary electrons with kappa distributions. Two three-dimensional kappa functions were fit to the observations, which we interpret as two populations of dense and warm (density 10 cubic centimeters, temperature 2 times 10 (sup 5) degrees Kelvin, invariant kappa index 10 to 1000), and rarefied and hot (density equals 0.005 cubic centimeters, temperature 5 times 10 (sup 5) degrees Kelvin, invariant kappa index equals 1 to 10) electrons. We fit the observations on 30 October 2014 when Rosetta was 20 kilometers from 67P, and 3 Astronomical Units from the Sun. We repeated the analysis on 15 August 2015 when Rosetta was 300 kilometers from the comet and 1.3 Astronomical Units from the Sun. Comparing the measurements on both days gives the first comparison of the cometary electron environment between a nearly inactive comet far from the Sun and an active comet near perihelion. We find that the warm population density increased by a factor of 3, while the temperature cooled by a factor of 2, and the invariant kappa index was unaffected. We find that the hot population density increased by a factor of 10, while the temperature and invariant kappa index were unchanged. We conclude that the hot population is likely the solar wind halo electrons in the coma. The warm population is likely of cometary origin, but its mechanism for production is not known.

  5. Agreement between the skin prick test and specific serum IgE for egg white and cow's milk allergens in young infant with atopic dermatitis.

    PubMed

    Yang, Hyeon-Jong; Park, Min-Ju; Youn, Seo Young; Yoo, Sangsoo; Min, Taek Ki; Jeon, You Hoon; Lee, Hae Won; Lee, Ji Sung; Pyun, Bok Yang

    2014-06-01

    The skin prick test (SPT) for detecting atopic sensitization is not preferred in young infants with atopic dermatitis (AD) because of concerns about poor skin reactivity. This study aimed to evaluate whether the results of SPT agreed well with those of specific serum immunoglobulin E (sIgE) antibody test in young infants with AD. This study included 2,077 eligible infants (age, <12 months) with AD who were tested by either SPT or sIgE between 2007 and 2011. Among them, 199 infants tested for egg white (EW) and 192 infants tested for cow's milk (CM), by both SPT and sIgE on the same day were identified and reviewed retrospectively. Kappa statistics and tests for equal kappa statistics were used to evaluate the agreement between the SPT and sIgE. The mean wheal diameter and the allergen-to-histamine ratio of SPT showed substantial agreement with those of sIgE for EW (κ = 0.62, 0.69) and CM (κ = 0.34, 0.47). The agreement for EW was significantly higher <6-month-old than in ≥6-month-old infants (κ = 0.79 vs. 0.54, P = 0.02), and that for CM was similar (P = 0.60). The mean wheal diameters for EW and CM were evenly distributed, and did not show increasing trends regardless of age in months (Ptrend = 0.13 and 0.06, respectively). The results of SPT agreed well with those of sIgE. This finding provides a rationale for using SPT, and suggests that SPT can be used along with sIgE to detect food sensitization in young infants with AD.

  6. Reliability and One-Year Stability of the PIN3 Neighborhood Environmental Audit in Urban and Rural Neighborhoods.

    PubMed

    Porter, Anna K; Wen, Fang; Herring, Amy H; Rodríguez, Daniel A; Messer, Lynne C; Laraia, Barbara A; Evenson, Kelly R

    2018-06-01

    Reliable and stable environmental audit instruments are needed to successfully identify the physical and social attributes that may influence physical activity. This study described the reliability and stability of the PIN3 environmental audit instrument in both urban and rural neighborhoods. Four randomly sampled road segments in and around a one-quarter mile buffer of participants' residences from the Pregnancy, Infection, and Nutrition (PIN3) study were rated twice, approximately 2 weeks apart. One year later, 253 of the year 1 sampled roads were re-audited. The instrument included 43 measures that resulted in 73 item scores for calculation of percent overall agreement, kappa statistics, and log-linear models. For same-day reliability, 81% of items had moderate to outstanding kappa statistics (kappas ≥ 0.4). Two-week reliability was slightly lower, with 77% of items having moderate to outstanding agreement using kappa statistics. One-year stability had 68% of items showing moderate to outstanding agreement using kappa statistics. The reliability of the audit measures was largely consistent when comparing urban to rural locations, with only 8% of items exhibiting significant differences (α < 0.05) by urbanicity. The PIN3 instrument is a reliable and stable audit tool for studies assessing neighborhood attributes in urban and rural environments.

  7. Statistical methods used to test for agreement of medical instruments measuring continuous variables in method comparison studies: a systematic review.

    PubMed

    Zaki, Rafdzah; Bulgiba, Awang; Ismail, Roshidi; Ismail, Noor Azina

    2012-01-01

    Accurate values are a must in medicine. An important parameter in determining the quality of a medical instrument is agreement with a gold standard. Various statistical methods have been used to test for agreement. Some of these methods have been shown to be inappropriate. This can result in misleading conclusions about the validity of an instrument. The Bland-Altman method is the most popular method judging by the many citations of the article proposing this method. However, the number of citations does not necessarily mean that this method has been applied in agreement research. No previous study has been conducted to look into this. This is the first systematic review to identify statistical methods used to test for agreement of medical instruments. The proportion of various statistical methods found in this review will also reflect the proportion of medical instruments that have been validated using those particular methods in current clinical practice. Five electronic databases were searched between 2007 and 2009 to look for agreement studies. A total of 3,260 titles were initially identified. Only 412 titles were potentially related, and finally 210 fitted the inclusion criteria. The Bland-Altman method is the most popular method with 178 (85%) studies having used this method, followed by the correlation coefficient (27%) and means comparison (18%). Some of the inappropriate methods highlighted by Altman and Bland since the 1980s are still in use. This study finds that the Bland-Altman method is the most popular method used in agreement research. There are still inappropriate applications of statistical methods in some studies. It is important for a clinician or medical researcher to be aware of this issue because misleading conclusions from inappropriate analyses will jeopardize the quality of the evidence, which in turn will influence quality of care given to patients in the future.

  8. Statistical Methods Used to Test for Agreement of Medical Instruments Measuring Continuous Variables in Method Comparison Studies: A Systematic Review

    PubMed Central

    Zaki, Rafdzah; Bulgiba, Awang; Ismail, Roshidi; Ismail, Noor Azina

    2012-01-01

    Background Accurate values are a must in medicine. An important parameter in determining the quality of a medical instrument is agreement with a gold standard. Various statistical methods have been used to test for agreement. Some of these methods have been shown to be inappropriate. This can result in misleading conclusions about the validity of an instrument. The Bland-Altman method is the most popular method judging by the many citations of the article proposing this method. However, the number of citations does not necessarily mean that this method has been applied in agreement research. No previous study has been conducted to look into this. This is the first systematic review to identify statistical methods used to test for agreement of medical instruments. The proportion of various statistical methods found in this review will also reflect the proportion of medical instruments that have been validated using those particular methods in current clinical practice. Methodology/Findings Five electronic databases were searched between 2007 and 2009 to look for agreement studies. A total of 3,260 titles were initially identified. Only 412 titles were potentially related, and finally 210 fitted the inclusion criteria. The Bland-Altman method is the most popular method with 178 (85%) studies having used this method, followed by the correlation coefficient (27%) and means comparison (18%). Some of the inappropriate methods highlighted by Altman and Bland since the 1980s are still in use. Conclusions This study finds that the Bland-Altman method is the most popular method used in agreement research. There are still inappropriate applications of statistical methods in some studies. It is important for a clinician or medical researcher to be aware of this issue because misleading conclusions from inappropriate analyses will jeopardize the quality of the evidence, which in turn will influence quality of care given to patients in the future. PMID:22662248

  9. Provider Agreement in the Assessment of Glaucoma Progression within a Team Model.

    PubMed

    Shah, Saumya; Choo, Clara; Odden, Jamie; Zhao, Bingying; Fang, Chengbo; Schornack, Muriel; Stalboerger, Gina; Bennett, Jeffrey R; Khanna, Cheryl L

    2018-06-04

    Glaucoma specialists and optometrists who work in a team model at a single institution utilize a common definition of glaucoma progression and treatment algorithm. The purpose of this study was to assess the consistency of agreement in identifying glaucoma progression among glaucoma specialists and optometrists of one team. 399 eyes of 200 patients age 18 or older with glaucoma were enrolled over two years. Clinical data, disc photographs, OCT, and visual fields were independently reviewed by two masked optometrists and two masked fellowship-trained glaucoma specialists. Each eye was judged as progression or no-progression of glaucomatous disease. The following were assessed: (1) agreement among optometrists; (2) agreement among glaucoma specialists; and (3) agreement among optometrists and glaucoma specialists. The frequency of use of testing modality to determine progression was also studied. Kappa statistics were used to evaluate agreements. Optometrists agreed with each other for 74.2% of the eyes assessed (κ=0.42), whereas glaucoma specialists agreed with each other for 78.7% of eyes (κ=0.39). All four providers agreed with each other for 54.4% of the eyes evaluated (κ=0.37). Providers had the highest agreement when the progression decision was based on disc hemorrhage (92%) and the lowest agreement when based on OCT progression analysis (36%). Compared to optometrists, glaucoma specialists used OCT (P= <0.01) more frequently to determine disease progression. Fair to moderate agreement levels were found among providers in their assessment of glaucoma progression, suggesting that a team approach to glaucoma management may be effective. Further work is needed to investigate ways to optimize consistency within the glaucoma team.

  10. PIC simulations of a three component plasma described by Kappa distribution functions as observed in Saturn's magnetosphere

    NASA Astrophysics Data System (ADS)

    Barbosa, Marcos; Alves, Maria Virginia; Simões Junior, Fernando

    2016-04-01

    In plasmas out of thermodynamic equilibrium the particle velocity distribution can be described by the so called Kappa distribution. These velocity distribution functions are a generalization of the Maxwellian distribution. Since 1960, Kappa velocity distributions were observed in several regions of interplanetary space and astrophysical plasmas. Using KEMPO1 particle simulation code, modified to introduce Kappa distribution functions as initial conditions for particle velocities, the normal modes of propagation were analyzed in a plasma containing two species of electrons with different temperatures and densities and ions as a third specie.This type of plasma is usually found in magnetospheres such as in Saturn. Numerical solutions for the dispersion relation for such a plasma predict the presence of an electron-acoustic mode, besides the Langmuir and ion-acoustic modes. In the presence of an ambient magnetic field, the perpendicular propagation (Bernstein mode) also changes, as compared to a Maxwellian plasma, due to the Kappa distribution function. Here results for simulations with and without external magnetic field are presented. The parameters for the initial conditions in the simulations were obtained from the Cassini spacecraft data. Simulation results are compared with numerical solutions of the dispersion relation obtained in the literature and they are in good agreement.

  11. Agreement between calcaneal quantitative ultrasound and osteoporosis self-assessment tool for Asians in identifying individuals at risk of osteoporosis

    PubMed Central

    Chin, Kok-Yong; Low, Nie Yen; Kamaruddin, Alia Annessa Ain; Dewiputri, Wan Ilma; Soelaiman, Ima-Nirwana

    2017-01-01

    Background Calcaneal quantitative ultrasound (QUS) is a useful tool in osteoporosis screening. However, QUS device may not be available at all primary health care settings. Osteoporosis self-assessment tool for Asians (OSTA) is a simple algorithm for osteoporosis screening that does not require any sophisticated instruments. This study explored the possibility of replacing QUS with OSTA by determining their agreement in identifying individuals at risk of osteoporosis. Methods A cross-sectional study was conducted to recruit Malaysian men and women aged ≥50 years. Their bone health status was measured using a calcaneal QUS device and OSTA. The association between OSTA and QUS was determined using Spearman’s correlation and their agreement was assessed using Cohen Kappa and receiver-operating curve. Results All QUS indices correlated significantly with OSTA (p<0.05). The agreement between QUS and OSTA was minimal but statistically significant (p<0.05). The performance of OSTA in identifying subjects at risk of osteoporosis according to QUS was poor-to-fair in women (p<0.05), but not statistically significant for men (p>0.05). Changing the cut-off values improved the performance of OSTA in women but not in men. Conclusion The agreement between QUS and OSTA is minimal in categorizing individuals at risk of osteoporosis. Therefore, they cannot be used interchangeably in osteoporosis screening. PMID:29070951

  12. Generation of Kappa Distributions in Solar Wind at 1 au

    NASA Astrophysics Data System (ADS)

    Livadiotis, G.; Desai, M. I.; Wilson, L. B., III

    2018-02-01

    We examine the generation of kappa distributions in the solar wind plasma near 1 au. Several mechanisms are mentioned in the literature, each characterized by a specific relationship between the solar wind plasma features, the interplanetary magnetic field (IMF), and the kappa index—the parameter that governs the kappa distributions. This relationship serves as a signature condition that helps the identification of the mechanism in the plasma. In general, a mechanism that generates kappa distributions involves a single or a series of stochastic or physical processes that induces local correlations among particles. We identify three fundamental solar wind plasma conditions that can generate kappa distributions, noted as (i) Debye shielding, (ii) frozen IMF, and (iii) temperature fluctuations, each one prevailing in different scales of solar wind plasma and magnetic field properties. Moreover, our findings show that the kappa distributions, and thus, their generating mechanisms, vary significantly with solar wind features: (i) the kappa index has different dependence on the solar wind speed for slow and fast modes, i.e., slow wind is characterized by a quasi-constant kappa index, κ ≈ 4.3 ± 0.7, while fast wind exhibits kappa indices that increase with bulk speed; (ii) the dispersion of magnetosonic waves is more effective for lower kappa indices (i.e., further from thermal equilibrium); and (iii) the kappa and polytropic indices are positively correlated, as it was anticipated by the theory.

  13. Obliquely Propagating Waves in Bi-Kappa Plasmas

    NASA Astrophysics Data System (ADS)

    Gaelzer, R.; Ziebell, L. F.; Meneses, A. R.

    2016-12-01

    The effects of kappa velocity distribution functions (VDFs) have been the subjectof intense research. Such functions have beenfound to provide a better fitting to the VDFs measured by spacecraftin the solar wind. An anisotropic VDF contains free energy that can excite wavesin the plasma. The induced turbulence also determines the observed shape of the VDF.The general treatment for waves excited by (bi-)Maxwellian plasmas is well-established.However, for kappa distributions (isotropic or anisotropic), the majority of the studieswere restricted to the limiting cases of purely parallel or perpendicular propagation.Contributions to the general case of obliquely-propagating waves have been scarcely reported.The absence of a general treatment prevents a complete analysis of the wave-particle interactionin kappa plasmas, since some instabilities can operate both in the parallel and oblique directions.A series of papers published by the authors begin to remedy this situation. In a first work [1],we have obtained the dielectric tensor and dispersion relations for quasi-perpendicular dispersive Alfvén waves resulting from a kappa VDF. This approach was later generalized by [2],where the formalism was extended to the general case of electrostatic/electromagnetic waves propagatingin an isotropic kappa plasma in any frequency range and for arbitrary angles.In the present work [3], we generalize even further the formalism by the derivation of thegeneral dielectric tensor of an anisotropic bi-kappa plasma. We present the state-of-the-art of theformalism and show how it enables a systematic study of waves and instabilities propagating inarbitrary directions and frequencies in a bi-kappa plasma.[1] R. Gaelzer, L. F. Ziebell, J. Geophys. Res. 119, 9334 (2014), doi: 10.1002/2014JA020667.[2] R. Gaelzer, L. F. Ziebell, Phys. Plasmas 23, 022110 (2016), doi: 10.1063/1.4941260.[3] R. Gaelzer et al., Phys. Plasmas 23, 062108 (2016), doi: 10.1063/1.4953430.

  14. Interobserver variability when employing the IUGA/ICS classification system for complications related to prostheses and grafts in female pelvic floor surgery.

    PubMed

    Gowda, Meghana; Kit, Laura Chang; Stuart Reynolds, W; Wang, Li; Dmochowski, Roger R; Kaufman, Melissa R

    2013-10-01

    To unify and organize reporting, an International Urogynecological Association (IUGA)/International Continence Society (ICS) expert consortium published terminology guidelines with a classification system for complications related to implants used in female pelvic surgery. We hypothesize that the complexity of the codification system may be a hindrance to precision, especially with decreasing levels of postgraduate expertise. Residents, fellows, and attending physicians were asked to code seven test cases taken from published literature. Category, timing, and site components of the classification system were assessed independently and according to the level of training. Interobserver reliability was calculated as percent agreement and Fleiss' kappa statistic. A total of 24 participants (6 attending physicians, 3 fellows, and 15 residents) were tested. The percent agreement showed significant variation when classified by level of training. In all categories, attending physicians had the greatest percentage agreement and largest kappa. The most agreement was seen when attending physicians classified mesh complications by time, 71% agreement with kappa 0.73 [95% confidence interval (CI) 0.58-0.88]. For the same task, the percentage agreement for fellows was 57%, kappa 0.55 (95% CI 0.23-0.87) and with residents 57%, kappa 0.71([95% CI 0.64-0.78). Interestingly, the site component of the classification system had the least overall agreement and lowest kappa [0%, kappa 0.29 (95% CI 0.26-0.32)] followed by the category component [14%, kappa 0.48 (95% CI 0.46-0.5)]. The IUGA/ICS mesh complication classification system has poor interobserver reliability. This trended downward with decreasing postgraduate level; however, we did not have sufficient statistical power to show an association when stratifying by all training levels. This highlights the complex nature of the classification system in its current form and its limitation for widespread clinical and research

  15. AGREEMENT AND COVERAGE OF INDICATORS OF RESPONSE TO INTERVENTION: A MULTI-METHOD COMPARISON AND SIMULATION

    PubMed Central

    Fletcher, Jack M.; Stuebing, Karla K.; Barth, Amy E.; Miciak, Jeremy; Francis, David J.; Denton, Carolyn A.

    2013-01-01

    Purpose Agreement across methods for identifying students as inadequate responders or as learning disabled is often poor. We report (1) an empirical examination of final status (post-intervention benchmarks) and dual-discrepancy growth methods based on growth during the intervention and final status for assessing response to intervention; and (2) a statistical simulation of psychometric issues that may explain low agreement. Methods After a Tier 2 intervention, final status benchmark criteria were used to identify 104 inadequate and 85 adequate responders to intervention, with comparisons of agreement and coverage for these methods and a dual-discrepancy method. Factors affecting agreement were investigated using computer simulation to manipulate reliability, the intercorrelation between measures, cut points, normative samples, and sample size. Results Identification of inadequate responders based on individual measures showed that single measures tended not to identify many members of the pool of 104 inadequate responders. Poor to fair levels of agreement for identifying inadequate responders were apparent between pairs of measures In the simulation, comparisons across two simulated measures generated indices of agreement (kappa) that were generally low because of multiple psychometric issues inherent in any test. Conclusions Expecting excellent agreement between two correlated tests with even small amounts of unreliability may not be realistic. Assessing outcomes based on multiple measures, such as level of CBM performance and short norm-referenced assessments of fluency may improve the reliability of diagnostic decisions. PMID:25364090

  16. Spine Instability Neoplastic Score: agreement across different medical and surgical specialties.

    PubMed

    Arana, Estanislao; Kovacs, Francisco M; Royuela, Ana; Asenjo, Beatriz; Pérez-Ramírez, Úrsula; Zamora, Javier

    2016-05-01

    Spinal instability is an acknowledged complication of spinal metastases; in spite of recent suggested criteria, it is not clearly defined in the literature. This study aimed to assess intra and interobserver agreement when using the Spine Instability Neoplastic Score (SINS) by all physicians involved in its management. Independent multicenter reliability study for the recently created SINS, undertaken with a panel of medical oncologists, neurosurgeons, radiologists, orthopedic surgeons, and radiation oncologists, was carried out. Ninety patients with biopsy-proven spinal metastases and magnetic resonance imaging, reviewed at the multidisciplinary tumor board of our institution, were included. Intraclass correlation coefficient (ICC) was used for SINS score agreement. Fleiss kappa statistic was used to assess agreement on the location of the most affected vertebral level; agreement on the SINS category ("stable," "potentially stable," or "unstable"); and overall agreement with the classification established by tumor board. Clinical data and imaging were provided to 83 specialists in 44 hospitals across 14 Spanish regions. No assessment criteria were pre-established. Each clinician assessed the SINS score twice, with a minimum 6-week interval. Clinicians were blinded to assessments made by other specialists and to their own previous assessment. Subgroup analyses were performed by clinicians' specialty, experience (≤7, 8-13, ≥14 years), and hospital category (four levels according to size and complexity). This study was supported by Kovacs Foundation. Intra and interobserver agreement on the location of the most affected levels was "almost perfect" (κ>0.94). Intra-observer agreement on the SINS score was "excellent" (ICC=0.77), whereas interobserver agreement was "moderate" (ICC=0.55). Intra-observer agreement in SINS category was "substantial" (k=0.61), whereas interobserver agreement was "moderate" (k=0.42). Overall agreement with the tumor board classification

  17. Ambiguities and conflicting results: the limitations of the kappa statistic in establishing the interrater reliability of the Irish nursing minimum data set for mental health: a discussion paper.

    PubMed

    Morris, Roisin; MacNeela, Padraig; Scott, Anne; Treacy, Pearl; Hyde, Abbey; O'Brien, Julian; Lehwaldt, Daniella; Byrne, Anne; Drennan, Jonathan

    2008-04-01

    In a study to establish the interrater reliability of the Irish Nursing Minimum Data Set (I-NMDS) for mental health difficulties relating to the choice of reliability test statistic were encountered. The objective of this paper is to highlight the difficulties associated with testing interrater reliability for an ordinal scale using a relatively homogenous sample and the recommended kw statistic. One pair of mental health nurses completed the I-NMDS for mental health for a total of 30 clients attending a mental health day centre over a two-week period. Data was analysed using the kw and percentage agreement statistics. A total of 34 of the 38 I-NMDS for mental health variables with lower than acceptable levels of kw reliability scores achieved acceptable levels of reliability according to their percentage agreement scores. The study findings implied that, due to the homogeneity of the sample, low variability within the data resulted in the 'base rate problem' associated with the use of kw statistic. Conclusions point to the interpretation of kw in tandem with percentage agreement scores. Suggestions that kw scores were low due to chance agreement and that one should strive to use a study sample with known variability are queried.

  18. Resampling probability values for weighted kappa with multiple raters.

    PubMed

    Mielke, Paul W; Berry, Kenneth J; Johnston, Janis E

    2008-04-01

    A new procedure to compute weighted kappa with multiple raters is described. A resampling procedure to compute approximate probability values for weighted kappa with multiple raters is presented. Applications of weighted kappa are illustrated with an example analysis of classifications by three independent raters.

  19. Kappa-Electrons Downstream of the Solar Wind Termination Shock

    NASA Astrophysics Data System (ADS)

    Fahr, H. J.

    2017-12-01

    A theoretical description of the solar wind electron distribution function downstream of the termination shock under the influence of the shock-induced injection of overshooting KeV-energetic electrons will be presented. A kinetic phasespace transport equation in the bulk frame of the heliosheath plasma flow is developed for the solar wind electrons, taking into account shock-induced electron injection, convective changes, magnetic cooling processes and whistler wave-induced energy diffusion. Assuming that the local electron distribution under the prevailing Non-LTE conditions can be represented by a local kappa function with a local kappa parameter that varies with the streamline coordinates, we determine the parameters of the resulting, initial kappa distribution for the downstream electrons. From this initial function spectral electron fluxes can be derived and can be compared with those measured by the VOYAGER-1 spacecraft in the range between 40 to 70 KeV. It can then be shown that with kappa values around kappa = 6 one can in fact fit these data very satisfactorily. In addition it is shown that for isentropic electron flows kappa-distributed electrons have to undergo simultaneous changes of both parameters, i.e. kappa and theta, of the electron kappa function. It is also shown then that under the influence of energy sinks and sources the electron flux becomes non-isentropic with electron entropies changing along the streamline.

  20. Are distal radius fracture classifications reproducible? Intra and interobserver agreement.

    PubMed

    Belloti, João Carlos; Tamaoki, Marcel Jun Sugawara; Franciozi, Carlos Eduardo da Silveira; Santos, João Baptista Gomes dos; Balbachevsky, Daniel; Chap Chap, Eduardo; Albertoni, Walter Manna; Faloppa, Flávio

    2008-05-01

    Various classification systems have been proposed for fractures of the distal radius, but the reliability of these classifications is seldom addressed. For a fracture classification to be useful, it must provide prognostic significance, interobserver reliability and intraobserver reproducibility. The aim here was to evaluate the intraobserver and interobserver agreement of distal radius fracture classifications. This was a validation study on interobserver and intraobserver reliability. It was developed in the Department of Orthopedics and Traumatology, Universidade Federal de São Paulo - Escola Paulista de Medicina. X-rays from 98 cases of displaced distal radius fracture were evaluated by five observers: one third-year orthopedic resident (R3), one sixth-year undergraduate medical student (UG6), one radiologist physician (XRP), one orthopedic trauma specialist (OT) and one orthopedic hand surgery specialist (OHS). The radiographs were classified on three different occasions (times T1, T2 and T3) using the Universal (Cooney), Arbeitsgemeinschaft für Osteosynthesefragen/Association for the Study of Internal Fixation (AO/ASIF), Frykman and Fernández classifications. The kappa coefficient (kappa) was applied to assess the degree of agreement. Among the three occasions, the highest mean intraobserver k was observed in the Universal classification (0.61), followed by Fernández (0.59), Frykman (0.55) and AO/ASIF (0.49). The interobserver agreement was unsatisfactory in all classifications. The Fernández classification showed the best agreement (0.44) and the worst was the Frykman classification (0.26). The low agreement levels observed in this study suggest that there is still no classification method with high reproducibility.

  1. Patient-clinician agreement on signs and symptoms of 'strep throat': a MetroNet study.

    PubMed

    Xu, Jinping; Schwartz, Kendra; Monsur, Joseph; Northrup, Justin; Neale, Anne Victoria

    2004-12-01

    Despite substantial use of the telephone in health care, only a few studies have formally evaluated the appropriateness of telephone-based management for acute medical problems. The accuracy of patients' report of signs and symptoms remains unknown. We compared the agreement between patient self-assessment and clinician assessment on the typical signs and symptoms of group A beta-haemolytic Streptococcus (GABHS) to investigate the potential difficulties of using patient self-report to triage sore throat patients. In this cross-sectional study, each of 200 adult pharyngitis patients was instructed to examine him/herself and to record the symptoms and physical findings. Two clinicians independently interviewed and examined each patient and recorded their findings. Each patient then had a rapid GABHS antigen test, the results of which were blinded to both clinicians and patients. Each patient self-assessment was compared with the findings of each clinician, and the agreement and disagreement between them computed. We found varying levels of agreement (kappa=-0.05 to 0.71) between patients and clinicians on sore throat history and physical assessments. Importantly, there was fair to substantial agreement (kappa=0.20-0.71) on the key signs and symptoms used in GABHS clinical prediction rules. As expected, history items had the highest agreement (kappa=0.52-0.71). Patients were more likely than clinicians to report rather than deny a specific physical sign. Adult sore throat patients may reliably report their symptoms, but may not be able to assess and report accurately on relevant physical signs of pharyngitis. Patients have a tendency to over-report physical signs. This study indicates the potential difficulties associated with telephone triage of sore throat patients, or other illnesses that require assessment of physical signs.

  2. Nonequilibrium approach regarding metals from a linearised kappa distribution

    NASA Astrophysics Data System (ADS)

    Domenech-Garret, J. L.

    2017-10-01

    The widely used kappa distribution functions develop high-energy tails through an adjustable kappa parameter. The aim of this work is to show that such a parameter can itself be regarded as a function, which entangles information about the sources of disequilibrium. We first derive and analyse an expanded Fermi-Dirac kappa distribution. Later, we use this expanded form to obtain an explicit analytical expression for the kappa parameter of a heated metal on which an external electric field is applied. We show that such a kappa index causes departures from equilibrium depending on the physical magnitudes. Finally, we study the role of temperature and electric field on such a parameter, which characterises the electron population of a metal out of equilibrium.

  3. Aortitis in giant cell arteritis: diagnosis with FDG PET/CT and agreement with CT angiography.

    PubMed

    Hommada, Mona; Mekinian, Arsène; Brillet, Pierre-Yves; Abad, Sébastien; Larroche, Claire; Dhôte, Robin; Fain, Olivier; Soussan, Michael

    2017-11-01

    To assess the detection rate of aortitis in giant cell arteritis (GCA) with fluorodeoxyglucose positron emission tomography/computed tomography (PET) and to compare the findings with CT angiography (CTA). Fifty-two GCA patients and 27 controls were included. GCA patients had a PET scan at diagnosis (35/52) or during relapse (17/52). Concomitant CTA was performed in 35/52 patients. Aortitis was defined as FDG uptake higher than the liver for PET and wall thickness≥3mm for CTA. Agreement between PET and CTA was evaluated by the kappa coefficient and Spearman correlation coefficient. Aortitis was diagnosed using PET in 40% (14/35) of patients at diagnosis and in 0% of controls (0/27). Agreement was perfect between PET and CT at a patient-based level, and very good at a vascular segment-based level (kappa: 0.72 to 1). PET was positive in 35% (6/17) of patients scanned during GCA relapse, showing aortitis (n=4) and/or articular uptake (n=4). Discrepancies between PET and CT were observed only in relapsing GCA (n=3). Correlation between the maximum standardized uptake value and wall thickness was moderate at diagnosis (r: 0.57 to 0.7) and not statistically significant during relapse. The detection rate of aortitis in GCA patients using PET is 40%, approximately in the range of CTA rates, suggesting that the two techniques have similar sensitivity. PET seems valuable in relapsing GCA, allowing the detection of vascular and articular activities. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. [Evaluation of agreement and correlation of three occlusal indices in an assessment of orthodontic treatment need].

    PubMed

    Djordjević, Jelena; Sćepan, Ivana; Glisić, Branislav

    2011-02-01

    Occlusal indices are quantitative diagnostic indicators of malocclusion severity, orthodontic treatment need, complexity and outcome. The aim of this study was to determine correlations and agreement among three occlusal indices: the Index of Orthodontic Treatment Need (IOTN), the Peer Assessment Rating Index (PAR) and the Index of Complexity, Outcome and Need (ICON) in evaluating orthodontic treatment need. A total eighty study models of patients referred to the Department of Orthodontics, School of Dentistry, Belgrade, were assessed in this retrospective study. Malocclusions of various types and severity in the permanent dentition were included. The Aesthetic and the Dental Health Component of IOTN determined orthodontic treatment need in 25% and 51% of the patients, respectively. PAR determined orthodontic treatment need in 59% and ICON in 53% of patients. The Aesthetic Component of IOTN and ICON had the highest correlation (Spearman's correlation coefficient 0.95, p < 0.01). Correlations between indices were 0.44 to 0.61 with statistical significance (p < 0.01). The agreement between indices, calculated using Kappa statistics, was 0.22 to 0.63. The most critical in malocclusion assessment was PAR. The Aesthetic Component of IOTN and ICON correlated highly (p < 0.01). Correlations between other pairs of indices were moderate (p < 0.01). The Aesthetic Component of IOTN and ICON had substantial agreement, whereas agreement between other indices was fair or moderate. ICON could replace PAR and IOTN. Application of occlusal indices enables objective evaluation of orthodontic treatment need and easier determination of the treatment priorities.

  5. Suboptimal Agreement Among Cytopathologists in Diagnosis of Malignancy Based on Endoscopic Ultrasound Needle Aspirates of Solid Pancreatic Lesions: A Validation Study.

    PubMed

    Marshall, Carrie; Mounzer, Rawad; Hall, Matt; Simon, Violette; Centeno, Barbara; Dennis, Katie; Dhillon, Jasreman; Fan, Fang; Khazai, Laila; Klapman, Jason; Komanduri, Srinadh; Lin, Xiaoqi; Lu, David; Mehrotra, Sanjana; Muthusamy, V Raman; Nayar, Ritu; Paintal, Ajit; Rao, Jianyu; Sams, Sharon; Shah, Janak; Watson, Rabindra; Rastogi, Amit; Wani, Sachin

    2018-07-01

    Despite the widespread use of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to sample pancreatic lesions and the standardization of pancreaticobiliary cytopathologic nomenclature, there are few data on inter-observer agreement among cytopathologists evaluating pancreatic cytologic specimens obtained by EUS-FNA. We developed a scoring system to assess agreement among cytopathologists in overall diagnosis and quantitative and qualitative parameters, and evaluated factors associated with agreement. We performed a prospective study to validate results from our pilot study that demonstrated moderate to substantial inter-observer agreement among cytopathologists for the final cytologic diagnosis. In the first phase, 3 cytopathologists refined criteria for assessment of quantity and quality measures. During phase 2, EUS-FNA specimens of solid pancreatic lesions from 46 patients were evaluated by 11 cytopathologists at 5 tertiary care centers using a standardized scoring tool. Individual quantitative and qualitative measures were scored and an overall cytologic diagnosis was determined. Clinical and EUS parameters were assessed as predictors of unanimous agreement. Inter-observer agreement (IOA) was calculated using multi-rater kappa (κ) statistics and a logistic regression model was created to identify factors associated with unanimous agreement. The IOA for final diagnoses, based on cytologic analysis, was moderate (κ = 0.56; 95% CI, 0.43-0.70). Kappa values did not increase when categories of suspicious for malignancy, malignant, and neoplasm were combined. IOA was slight to moderate for individual quantitative (κ = 0.007; 95% CI, -0.03 to -0.04) and qualitative parameters (κ = 0.5; 95% CI, 0.47-0.53). Jaundice was the only factor associated with agreement among all cytopathologists on multivariate analysis (odds ratio for unanimous agreement, 5.3; 95% CI, 1.1-26.89). There is a suboptimal level of agreement among cytopathologists in the diagnosis

  6. NF-kappaB modulators from Valeriana officinalis.

    PubMed

    Jacobo-Herrera, Nadia J; Vartiainen, Nina; Bremner, Paul; Gibbons, Simon; Koistinaho, Jari; Heinrich, Michael

    2006-10-01

    Valeriana officinalis (Valerianaceae) has been of great interest for its therapeutic uses for treating mild nervous tension and temporary sleeping problems. In traditional European medicine it has been also reported as an antiinflammatory remedy. This study reports that the EtOAc extract of the underground parts of V. officinalis showed inhibitory activity against NF-kappaB at 100 microg/mL in the IL-6/Luc assay on HeLa cells and provided protection against excitotoxicity in primary brain cell cultures at micromolar concentrations. Bioassay-guided fractionation of the EtOAc extract led to the isolation of three known sesquiterpenes: acetylvalerenolic acid (1), valerenal (2) and valerenic acid (3), 1 and 3 were active as inhibitors of NF-kappaB at a concentration of 100 microg/mL. Acetylvalerenolic acid (1) reduced NF-kappaB activity to 4%, whereas valerenic acid (3) reduced NF-kappaB activity to 25%. Copyright 2006 John Wiley & Sons, Ltd.

  7. NF-kappaB mediates FGF signal regulation of msx-1 expression.

    PubMed

    Bushdid, P B; Chen, C L; Brantley, D M; Yull, F; Raghow, R; Kerr, L D; Barnett, J V

    2001-09-01

    The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-kappaB activity is necessary for both chicken and mouse limb development. We report here that the NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene expression. Copyright 2001 Academic Press.

  8. Intra- and inter-observer agreement when using a descriptive classification scale for clinical assessment of faecal consistency in growing pigs.

    PubMed

    Pedersen, Ken Steen; Toft, Nils

    2011-03-01

    The objective of the current study was to evaluate intra- and inter-observer agreement using a descriptive classification scale with four categories, descriptive text and pictures for assessment of consistency in faecal samples from pigs post weaning. The four consistency categories were score one=firm and shaped, score two=soft and shaped, score three=loose and score four=watery. Five observers from the same veterinary practice examined 100 faecal samples using the scale with four categories. Four of the observers examined the 100 faecal samples twice within the same day. Within observers the difference in proportions for the individual consistency categories between two examinations was on average 0.04 (range: 0-0.10). The mean intra-observer agreement was 0.82 (range: 0.72-0.91) with a mean kappa value of 0.76 (range: 0.61-0.88). For inter-observer agreement overall kappa was 0.64. For the 10 pair-wise comparisons the mean inter-observer agreement was 0.73 (range: 0.61-0.90) with a mean kappa value of 0.64 (range: 0.48-0.87). The difference in proportions for the individual consistency categories was on average 0.08 (range: 0-0.17). In conclusion, the agreement observed for the descriptive classification scale with four categories, descriptive text and pictures may be categorized as a substantial to almost perfect intra-observer agreement and a moderate to almost perfect inter-observer agreement. However, more objective measures than clinical scales may still be needed to improve intra- and inter-observer agreement in research studies. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Measuring agreement between cervical vertebrae and hand-wrist maturation in determining skeletal age: reassessing the theory in patients with short stature.

    PubMed

    Danaei, Shahla Momeni; Karamifar, Amirali; Sardarian, Ahmadreza; Shahidi, Shoaleh; Karamifar, Hamdollah; Alipour, Abbas; Ghodsi Boushehri, Sahar

    2014-09-01

    The objective of this study was to determine the degree of agreement between hand-wrist radiography and cervical vertebral maturation analysis in patients diagnosed with short stature. A cross-sectional study was designed; 178 patients (90 girls, 88 boys) diagnosed with short stature and seeking treatment were selected. The patients were divided into 2 groups (76 with familial short stature, 102 with nonfamilial short stature). Hand-wrist and lateral cephalometric radiographs were obtained from the patients. The hand-wrist radiographs were analyzed using the Fishman method, and the lateral cephalometric views were categorized according to the method of Hassel and Farman. The degree of agreement between the 2 methods of predicting skeletal maturation was measured by calculating the contingency coefficient and the weighted kappa statistic. A high degree of agreement was observed between the 2 methods of analyzing skeletal maturation. It was also observed that agreement was higher in girls in the familial short-stature group, whereas boys had higher agreement in the nonfamilial short-stature group. Cervical vertebral maturation can be a valuable substitute for hand-wrist radiography in patients with short stature. Copyright © 2014 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  10. Depletion of the cellular levels of Bag-1 proteins attenuates phorbol ester-induced downregulation of I{kappa}B{alpha} and nuclear accumulation of NF-{kappa}B

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

    Maier, Jana V., E-mail: Jana.maier@kit.edu; Volz, Yvonne; Berger, Caroline

    2010-10-22

    Research highlights: {yields}Bag-1 depletion only marginally affects the action of the glucocorticoid receptor but strongly regulates the activity of NF-{kappa}B. {yields}Bag-1 depletion attenuates phosphorylation and degradation of I{kappa}B{alpha} and nuclear accumulation of NF-{kappa}B p65 and p50. {yields}Bag-1 interacts with I{kappa}B{alpha} and partially restores I{kappa}B{alpha} and NF-{kappa}B activation in Bag-1 depleted cells. -- Abstract: Bag-1 consists in humans of four isoforms generated from the same RNA by alternative translation. Overexpression of single Bag-1 isoforms has identified Bag-1 as a negative regulator of action of many proteins including the glucocorticoid receptor (GR). Here we have analysed the ability of Bag-1 to regulatemore » the transrepression function of the GR. Silencing Bag-1 expression only marginally affects the transrepression action of the GR but decreased the action of the transcription factor NF-{kappa}B. Furthermore phosphorylation and degradation of the inhibitor protein I{kappa}B{alpha} and nuclear accumulation of p65 and p50 NF-{kappa}B proteins in response to phorbol ester was attenuated following Bag-1 depletion in HeLa cells. Reconstitution of Bag-1 in depleted cells partially restored I{kappa}B{alpha} and NF-{kappa}B activation. Knock-down of Bag-1 expression also did not significantly alter GR-mediated transactivation but affected the basal transcription of some of the target genes. Thus Bag-1 proteins function as regulators of the action of selective transcription factors.« less

  11. Verification of a computer-aided replica technique for evaluating prosthesis adaptation using statistical agreement analysis.

    PubMed

    Mai, Hang-Nga; Lee, Kyeong Eun; Lee, Kyu-Bok; Jeong, Seung-Mi; Lee, Seok-Jae; Lee, Cheong-Hee; An, Seo-Young; Lee, Du-Hyeong

    2017-10-01

    The purpose of this study was to evaluate the reliability of computer-aided replica technique (CART) by calculating its agreement with the replica technique (RT), using statistical agreement analysis. A prepared metal die and a metal crown were fabricated. The gap between the restoration and abutment was replicated using silicone indicator paste (n = 25). Gap measurements differed in the control (RT) and experimental (CART) groups. In the RT group, the silicone replica was manually sectioned, and the marginal and occlusal gaps were measured using a microscope. In the CART group, the gap was digitized using optical scanning and image superimposition, and the gaps were measured using a software program. The agreement between the measurement techniques was evaluated by using the 95% Bland-Altman limits of agreement and concordance correlation coefficients (CCC). The least acceptable CCC was 0.90. The RT and CART groups showed linear association, with a strong positive correlation in gap measurements, but without significant differences. The 95% limits of agreement between the paired gap measurements were 3.84% and 7.08% of the mean. The lower 95% confidence limits of CCC were 0.9676 and 0.9188 for the marginal and occlusal gap measurements, respectively, and the values were greater than the allowed limit. The CART is a reliable digital approach for evaluating the fit accuracy of fixed dental prostheses.

  12. NF-{kappa}B regulates Lef1 gene expression in chondrocytes

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

    Yun, Kangsun; Choi, Yoo Duk; Nam, Jong Hee

    The relation of Wnt/{beta}-catenin signaling to osteoarthritis progression has been revealed with little information on the underlying molecular mechanism. In this study we found overexpression of Lef1 in cartilage tissue of osteoarthritic patients and elucidated molecular mechanism of NF-{kappa}B-mediated Lef1 gene regulation in chondrocytes. Treatment of IL-1{beta} augmented Lef1 upregulation and nuclear translocation of NF-{kappa}B in chondrocytes. Under IL-1{beta} signaling, treatment of NF-{kappa}B nuclear translocation inhibitor SN-50 reduced Lef1 expression. A conserved NF-{kappa}B-binding site between mouse and human was selected through bioinformatic analysis and mapped at the 14 kb upstream of Lef1 transcription initiation site. NF-{kappa}B binding to the sitemore » was confirmed by chromatin immunoprecipitation assay. Lef1 expression was synergistically upregulated by interactions of NF-{kappa}B with Lef1/{beta}-catenin in chondrocytes. Our results suggest a pivotal role of NF-{kappa}B in Lef1 expression in arthritic chondrocytes or cartilage degeneration.« less

  13. IKK{epsilon} modulates RSV-induced NF-{kappa}B-dependent gene transcription

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

    Bao Xiaoyong; Indukuri, Hemalatha; Liu Tianshuang

    2010-12-20

    Respiratory syncytial virus (RSV), a negative-strand RNA virus, is the most common cause of epidemic respiratory disease in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-{kappa}B (NF-{kappa}B). In this study we have investigated the role of the non canonical I{kappa}B kinase (IKK){epsilon} in modulating RSV-induced NF-{kappa}B activation. Our results show that inhibition of IKK{epsilon} activation results in significant impairment of viral-induced NF-{kappa}B-dependent gene expression, through a reduction in NF-{kappa}B transcriptional activity, without changes in nuclear translocation or DNA-binding activity. Absencemore » of IKK{epsilon} results in a significant decrease of RSV-induced NF-{kappa}B phosphorylation on serine 536, a post-translational modification important for RSV-induced NF-{kappa}B-dependent gene expression, known to regulate NF-{kappa}B transcriptional activity without affecting nuclear translocation. This study identifies a novel mechanism by which IKK{epsilon} regulates viral-induced cellular signaling.« less

  14. Agreement between parent and child report on parental practices regarding dietary, physical activity and sedentary behaviours: the ENERGY cross-sectional survey.

    PubMed

    Rebholz, Cornelia E; Chinapaw, Mai J M; van Stralen, Maartje M; Bere, Elling; Bringolf, Bettina; De Bourdeaudhuij, Ilse; Jan, Nataša; Kovacs, Eva; Maes, Lea; Manios, Yannis; Moreno, Luis; Singh, Amika S; Brug, Johannes; te Velde, Saskia J

    2014-09-05

    Parents and their parenting practices play an important role in shaping their children's environment and energy-balance related behaviours (EBRBs). Measurement of parenting practices can be parent- or child-informed, however not much is known about agreement between parent and child perspectives. This study aimed to assess agreement between parent and child reports on parental practices regarding EBRBs across different countries in Europe and to identify correlates of agreement. Within the ENERGY-project, a cross-sectional survey was conducted among 10-12 year old children and their parents in eight European countries. Both children and parents filled in a questionnaire on 14 parental practices regarding five different EBRBs (i.e. soft drink, fruit juice and breakfast consumption, sports activity and watching TV) and socio-demographic characteristics. Children's anthropometric measurements were taken at school. We calculated percentages of agreement between children and their parents and weighted kappa statistics (for ordinal variables) per practice and country and assessed factors associated with agreement using multilevel linear regression. Reports of 6425 children and their parents were available for analysis. Overall mean agreement between parent and child reports was 43% and varied little among countries. The lowest agreement was found for questions assessing joint parent-child activities, such as sports (27%; Kappa (κ) = 0.14) or watching TV (30%; κ = 0.17), and for parental allowance of the child to have soft drinks (32%; κ = 0.24) or fruit juices (32%; κ = 0.19), or to watch TV (27%; κ = 0.17). Having breakfast products available at home or having a TV in the child's bedroom were the only practices with moderate to good agreement (>60%; κ = 0.06 and 0.77, respectively). In general, agreement was lower for boys, younger children, younger parents, parents with less than 14 years of education, single parents, parents with a higher self-reported body

  15. Agreement between pedometer and accelerometer in measuring physical activity in overweight and obese pregnant women.

    PubMed

    Kinnunen, Tarja I; Tennant, Peter W G; McParlin, Catherine; Poston, Lucilla; Robson, Stephen C; Bell, Ruth

    2011-06-27

    Inexpensive, reliable objective methods are needed to measure physical activity (PA) in large scale trials. This study compared the number of pedometer step counts with accelerometer data in pregnant women in free-living conditions to assess agreement between these measures. Pregnant women (n = 58) with body mass index ≥25 kg/m(2) at median 13 weeks' gestation wore a GT1M Actigraph accelerometer and a Yamax Digi-Walker CW-701 pedometer for four consecutive days. The Spearman rank correlation coefficients were determined between pedometer step counts and various accelerometer measures of PA. Total agreement between accelerometer and pedometer step counts was evaluated by determining the 95% limits of agreement estimated using a regression-based method. Agreement between the monitors in categorising participants as active or inactive was assessed by determining Kappa. Pedometer step counts correlated moderately (r = 0.36 to 0.54) with most accelerometer measures of PA. Overall step counts recorded by the pedometer and the accelerometer were not significantly different (medians 5961 vs. 5687 steps/day, p = 0.37). However, the 95% limits of agreement ranged from -2690 to 2656 steps/day for the mean step count value (6026 steps/day) and changed substantially over the range of values. Agreement between the monitors in categorising participants to active and inactive varied from moderate to good depending on the criteria adopted. Despite statistically significant correlations and similar median step counts, the overall agreement between pedometer and accelerometer step counts was poor and varied with activity level. Pedometer and accelerometer steps cannot be used interchangeably in overweight and obese pregnant women.

  16. Kappa angles in different positions in patients with myopia during LASIK

    PubMed Central

    Qi, Hui; Jiang, Jing-Jing; Jiang, Yan-Ming; Wang, Li-Qiang; Huang, Yi-Fei

    2016-01-01

    AIM To investigate the difference in kappa angle between sitting and supine positions during laser-assisted in situ keratomileusis (LASIK). METHODS A retrospective study was performed on 395 eyes from 215 patients with myopia that received LASIK. Low, moderate, and high myopia groups were assigned according to diopters. The horizontal and vertical components of kappa angle in sitting position were measured before the operation, and in supine position during the operation. The data from the two positions were compared and the relationship between kappa angle and diopters were analyzed. RESULTS Two hundred and twenty-three eyes (56.5%) in sitting position and 343 eyes (86.8%) in supine position had positive kappa angles. There were no significant differences in horizontal and vertical components of kappa angle in the sitting position or horizontal components of kappa angle in the supine position between the three groups (P>0.05). A significant difference in the vertical components of kappa angle in the supine position was seen in the three groups (P<0.01). Differences in both horizontal and vertical components of kappa angles were significant between the sitting and supine positions. Positive correlations in both horizontal and vertical components of kappa angles (P<0.05) were found and vertical components of kappa angle in sitting and supine positions were negatively correlated with the degree of myopia (sitting position: r=-0.109; supine position: r=-0.172; P<0.05). CONCLUSION There is a correlation in horizontal and vertical components of kappa angle in sitting and supine positions. Positive correlations in both horizontal and vertical components of kappa angle in sitting and supine positions till the end of the results. This result still needs further observation. Clinicians should take into account different postures when excimer laser surgery needs to be performed. PMID:27162734

  17. Antiinflammatory effects of glucocorticoids in brain cells, independent of NF-kappa B.

    PubMed

    Bourke, E; Moynagh, P N

    1999-08-15

    Glucocorticoids are potent antiinflammatory drugs. They inhibit the expression of proinflammatory cytokines and adhesion molecules. It has recently been proposed that the underlying basis to such inhibition is the induction of the protein I kappa B, which inhibits the transcription factor NF-kappa B. The latter is a key activator of the genes encoding cytokines and adhesion molecules. The present study shows that the synthetic glucocorticoid, dexamethasone, inhibits the induction of the proinflammatory cytokine IL-8 and the adhesion molecules VCAM-1 and ICAM-1 in human 1321N1 astrocytoma and SK.N.SH neuroblastoma cells. However, dexamethasone failed to induce I kappa B or inhibit activation of NF-kappa B by IL-1 in the two cell types. EMSA confirmed the identity of the activated NF-kappa B by demonstrating that an oligonucleotide, containing the wild-type NF-kappa B-binding motif, inhibited formation of the NF-kappa B-DNA complexes whereas a mutated form of the NF-kappa B-binding motif was ineffective. In addition, supershift analysis showed that the protein subunits p50 and p65 were prevalent components in the activated NF-kappa B complexes. The lack of effect of dexamethasone on the capacity of IL-1 to activate NF-kappa B correlated with its inability to induce I kappa B and the ability of IL-1 to cause degradation of I kappa B, even in the presence of dexamethasone. The results presented in this paper strongly suggest that glucocorticoids may exert antiinflammatory effects in cells of neural origin by a mechanism(s) independent of NF-kappa B.

  18. Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast.

    PubMed

    Gomes, Douglas S; Porto, Simone S; Balabram, Débora; Gobbi, Helenice

    2014-06-19

    This study aimed to assess inter-observer variability between the original diagnostic reports and later review by a specialist in breast pathology considering lobular neoplasias (LN), columnar cell lesions (CCL), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) of the breast. A retrospective, observational, cross-sectional study was conducted. A total of 610 breast specimens that had been formally sent for consultation and/or second opinions to the Breast Pathology Laboratory of Federal University of Minas Gerais were analysed between January 2005 and December 2010. The inter-observer variability between the original report and later review was compared regarding the diagnoses of LN, CCL, ADH, and DCIS. Statistical analyses were conducted using the Kappa index. Weak correlations were observed for the diagnoses of columnar cell change (CCC; Kappa=0.38), columnar cell hyperplasia (CCH; Kappa=0.32), while a moderate agreement (Kappa=0.47) was observed for the diagnoses of flat epithelial atypia (FEA). Good agreement was observed in the diagnoses of atypical lobular hyperplasia (ALH; Kappa=0.62) and lobular carcinoma in situ (LCIS; Kappa=0.66). However, poor agreement was observed for the diagnoses of pleomorphic LCIS (Kappa=0.22). Moderate agreement was observed for the diagnoses of ADH (Kappa=0.44), low-grade DCIS (Kappa=0.47), intermediate-grade DCIS (Kappa=0.45), and DCIS with microinvasion (Kappa=0.56). Good agreement was observed between the diagnoses of high-grade DCIS (Kappa=0.68). According to our data, the best diagnostic agreements were observed for high-grade DCIS, ALH, and LCIS. CCL without atypia and pleomorphic LCIS had the worst agreement indices. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1640072350119725.

  19. Inter-rater agreement of the Quality of Life-Alzheimer's Disease (QoL-AD) self-rating and proxy rating scale: secondary analysis of RightTimePlaceCare data.

    PubMed

    Römhild, Josephine; Fleischer, Steffen; Meyer, Gabriele; Stephan, Astrid; Zwakhalen, Sandra; Leino-Kilpi, Helena; Zabalegui, Adelaida; Saks, Kai; Soto-Martin, Maria; Sutcliffe, Caroline; Rahm Hallberg, Ingalill; Berg, Almuth

    2018-06-28

    To assess the quality of life of people with dementia, measures are required for self-rating by the person with dementia, and for proxy rating by others. The Quality of Life in Alzheimer's Disease scale (QoL-AD) is available in two versions, QoL-AD-SR (self-rating) and QoL-AD-PR (proxy rating). The aim of our study was to analyse the inter-rater agreement between self- and proxy ratings, in terms of both the total score and the items, including an analysis specific to care setting, and to identify factors associated with this agreement. Cross-sectional QoL-AD data from the 7th Framework European RightTimePlaceCare study were analysed. A total of 1330 cases were included: n = 854 receiving home care and n = 476 receiving institutional long-term nursing care. The proxy raters were informal carers (home care) and best-informed professional carers (institutional long-term nursing care). Inter-rater agreement was investigated using Bland-Altman plots for the QoL-AD total score and by weighted kappa statistics for single items. Associations were investigated by regression analysis. The overall QoL-AD assessment of those with dementia revealed a mean value of 33.2 points, and the proxy ratings revealed a mean value of 29.8 points. The Bland-Altman plots revealed a poor agreement between self- and proxy ratings for the overall sample and for both care settings. With one exception (item 'Marriage' weighted kappa 0.26), the weighted kappa values for the single QoL-AD items were below 0.20, indicating poor agreement. Home care setting, dementia-related behavioural and psychological symptoms, and the functional status of the person with dementia, along with the caregiver burden, were associated with the level of agreement. Only the home care setting was associated with an increase larger than the predefined acceptable difference between self- and proxy ratings. Proxy quality of life ratings from professional and informal carers appear to be lower than the self

  20. A Simulation Study of Rater Agreement Measures with 2x2 Contingency Tables

    ERIC Educational Resources Information Center

    Ato, Manuel; Lopez, Juan Jose; Benavente, Ana

    2011-01-01

    A comparison between six rater agreement measures obtained using three different approaches was achieved by means of a simulation study. Rater coefficients suggested by Bennet's [sigma] (1954), Scott's [pi] (1955), Cohen's [kappa] (1960) and Gwet's [gamma] (2008) were selected to represent the classical, descriptive approach, [alpha] agreement…

  1. Ion-cyclotron instability in plasmas described by product-bi-kappa distributions

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

    Santos, M. S. dos; Ziebell, L. F., E-mail: luiz.ziebell@ufrgs.br; Gaelzer, R., E-mail: rudi.gaelzer@ufrgs.br

    The dispersion relation for parallel propagating waves in the ion-cyclotron branch is investigated numerically by considering that the velocity distribution of the ion population is a function of type product-bi-kappa. We investigate the effects of the non-thermal features and of the anisotropy associated with this type of distribution on the ion-cyclotron instability, as well as the influence of different forms of the electron distribution, by considering Maxwellian distributions, bi-kappa distributions, and product-bi-kappa distributions. The cases of ions described by either Maxwellian or bi-kappa distributions are also considered, for comparison. The results of the numerical analysis show that the increase inmore » the non-thermal character associated with the anisotropic kappa distributions for ions contributes to enhance the instability as compared to that obtained in the Maxwellian case, in magnitude and in wave number range, with more significant enhancement for the case of ion product-bi-kappa distributions than for the case of ion bi-kappa distributions. It is also shown that the ion-cyclotron instability is decreased if the electrons are described by product-bi-kappa distributions, while electrons described by bi-kappa distributions lead to growth rates which are very similar to those obtained considering a Maxwellian distribution for the electron population.« less

  2. Intra- and interobserver agreement among obstetric experts in court regarding the review of abnormal fetal heart rate tracings and obstetrical management.

    PubMed

    Sabiani, Laura; Le Dû, Renaud; Loundou, Anderson; d'Ercole, Claude; Bretelle, Florence; Boubli, Léon; Carcopino, Xavier

    2015-12-01

    The objective of the study was to evaluate the intra- and interobserver agreement among obstetric experts in court regarding the retrospective review of abnormal fetal heart rate tracings and obstetrical management of patients with abnormal fetal heart rate during labor. A total of 22 French obstetric experts in court reviewed 30 cases of term deliveries of singleton pregnancies diagnosed with at least 1 hour of abnormal fetal heart rate, including 10 cases with adverse neonatal outcome. The experts reviewed all cases twice within a 3-month interval, with the first review being blinded to neonatal outcome. For each case reviewed, the experts were provided with the obstetric data and copies of the complete fetal heart rate recording and the partogram. The experts were asked to classify the abnormal fetal heart rate tracing and to express whether they agreed with the obstetrical management performed. When they disagreed, the experts were asked whether they concluded that an error had been made and whether they considered the obstetrical management as the cause of cerebral palsy in children if any. Compared with blinded review, the experts were significantly more likely to agree with the obstetric management performed (P < .001) and with the mode of delivery (P < .001) when informed about the neonatal outcome and were less likely to conclude that an error had been made (P < .001) or to establish a link with potential cerebral palsy (P = .003). The experts' intraobserver agreement for the review of abnormal fetal heart rate tracing and obstetrical management were both mediocre (kappa = 0.46-0.51 and kappa = 0.48-0.53, respectively). The interobserver agreement for the review of abnormal fetal heart rate tracing was low and was not improved by knowledge of the neonatal outcome (kappa = 0.11-0.18). The interobserver agreement for the interpretation of obstetrical management was also low (kappa = 0.08-0.19) but appeared to be improved by knowledge of the neonatal outcome

  3. The Correlation between Angle Kappa and Ocular Biometry in Koreans

    PubMed Central

    Choi, Se Rang

    2013-01-01

    Purpose To investigate normative angle kappa data and to examine whether correlations exist between angle kappa and ocular biometric measurements (e.g., refractive error, axial length) and demographic features in Koreans. Methods Data from 436 eyes (213 males and 223 females) were analyzed in this study. The angle kappa was measured using Orbscan II. We used ocular biometric measurements, including refractive spherical equivalent, interpupillary distance and axial length, to investigate the correlations between angle kappa and ocular biometry. The IOL Master ver. 5.02 was used to obtain axial length. Results The mean patient age was 57.5 ± 12.0 years in males and 59.4 ± 12.4 years in females (p = 0.11). Angle kappa averaged 4.70 ± 2.70 degrees in men and 4.89 ± 2.14 degrees in women (p = 0.48). Axial length and spherical equivalent were correlated with angle kappa (r = -0.342 and r = 0.197, respectively). The correlation between axial length and spherical equivalent had a negative correlation (r = -0.540, p < 0.001). Conclusions Angle kappa increased with spherical equivalent and age. Thus, careful manipulation should be considered in older and hyperopic patients when planning refractive or strabismus surgery. PMID:24311927

  4. Inhibition of single Shaker K channels by kappa-conotoxin-PVIIA.

    PubMed Central

    Naranjo, David

    2002-01-01

    kappa-Conotoxin-PVIIA (kappa-PVIIA) is a 27-residue basic (+4) peptide from the venom of the predator snail Conus purpurascens. A single kappa-PVIIA molecule interrupts ion conduction by binding to the external mouth of Shaker K channels. The blockade of Shaker by kappa-PVIIA was studied at the single channel level in membrane patches from Xenopus oocytes. The amplitudes of blocked and closed events were undistinguishable, suggesting that the toxin interrupts ion conduction completely. Between -20 and 40 mV kappa-PVIIA increased the latency to the first opening by one order of magnitude in a concentration-independent fashion. Because kappa-PVIIA has higher affinity for the closed channels at high enough concentration to block >90% of the resting channels, the dissociation rate could be estimated from the analysis of the first latency. At 0 mV, the dissociation rate was 20 s(-1) and had an effective valence of 0.64. The apparent closing rate increased linearly with [kappa-PVIIA] indicating an association rate of 56 microM(-1) s(-1). The toxin did not modify the fraction of null traces. This result suggests that the structural rearrangements in the external mouth contributing to the slow inactivation preserve the main geometrical features of the toxin-receptor interaction. PMID:12023223

  5. c-rel activates but v-rel suppresses transcription from kappa B sites.

    PubMed Central

    Inoue, J; Kerr, L D; Ransone, L J; Bengal, E; Hunter, T; Verma, I M

    1991-01-01

    We show that the product of the protooncogene c-rel is a constituent of an NF-kappa B-like complex that binds to the kappa B site originally identified in the enhancer of immunoglobulin kappa light chain gene. c-rel protein synthesized in bacteria binds to the kappa B site in a sequence-specific manner. The rel-kappa B complex can be disrupted by incubation with anti-rel antibodies. The rel protein can form oligomers. The c-rel protein can activate transcription from promoters containing kappa B sites; v-rel, on the other hand, suppresses the transcription of genes linked to kappa B sites. Thus, v-rel may interfere with the normal transcriptional machinery of the cell by acting as a dominant negative mutant. Images PMID:2023921

  6. The META score for differentiating metastatic from osteoporotic vertebral fractures: an independent agreement assessment.

    PubMed

    Besa, Pablo; Urrutia, Julio; Campos, Mauricio; Mobarec, Sebastián; Cruz, Juan Pablo; Cikutovic, Pablo; Diaz, Gonzalo

    2018-04-27

    Differentiating osteoporotic vertebral fractures (OVFs) from metastatic vertebral fractures (MVFs) is an important clinical challenge. A novel magnetic resonance imaging (MRI)-based score (the META score) was described, aiming to differentiate OVF from MVF. This score showed an almost perfect agreement by the group developing it, but an independent agreement evaluation is pending. We aimed to perform an independent inter- and intraobserver agreement evaluation of the META score and to test the score's capability of differentiating OVF from MVF. This is an agreement study of the META score. Sixty-four patients with confirmed OVF or MVF were assessed by six independent evaluators (three spine surgeons and three fellowship-trained radiologists) using the META score. We used the intraclass correlation coefficient (ICC) to determine the overall inter-and intraobserver agreement, and the kappa statistic (κ) to express the agreement for each individual score criterion. The score accuracy was determined by calculating the area under the receiver operating characteristic curve. Finally, we used κ to evaluate the agreement among raters to determine whether the fracture was OVF or MVF. The overall interobserver agreement was poor [ICC=0.10 (0.02-0.20)]; spine surgeons [ICC=0.75 (0.66-0.83)] had better agreement than radiologists did [ICC=0.05 (-0.08 to 0.21)]. The intraobserver agreement was poor [ICC=0.17 (0.01-0.32)]; both spine surgeons [ICC=0.21 (0.05-0.41)] and radiologists had a poor agreement [ICC=0.03 (-0.29 to 0.27)]. The agreement for each specific criterion varied from κ=0.24 to κ=0.60. The area under the receiver operating characteristic curve was 0.58 (0.64 for spine surgeons and 0.52 for radiologists, p<.01). The interobserver agreement using the META score was adequate for spine surgeons but not for other potential users (radiologists); the intraobserver agreement was poor. Further studies are thus necessary before the use of this score is recommended

  7. Particle-in-cell Simulations of Waves in a Plasma Described by Kappa Velocity Distribution as Observed in the Saturńs Magnetosphere

    NASA Astrophysics Data System (ADS)

    Alves, M. V.; Barbosa, M. V. G.; Simoes, F. J. L., Jr.

    2016-12-01

    Observations have shown that several regions in space plasmas exhibit non-Maxwellian distributions with high energy superthermal tails. Kappa velocity distribution functions can describe many of these regions and have been used since the 60's. They suit well to represent superthermal tails in solar wind as well as to obtain plasma parameters of plasma within planetary magnetospheres. A set of initial velocities following kappa distribution functions is used in KEMPO1 particle simulation code to analyze the normal modes of wave propagation. Initial conditions are determined using observed characteristics for Saturńs magnetosphere. Two electron species with different temperatures and densities and ions as a third species are used. Each electron population is described by a different kappa index. Particular attention is given to perpendicular propagation, Bernstein modes, and parallel propagation, Langmuir and electron-acoustic modes. The dispersion relation for the Bernstein modes is strongly influenced by the shape of the velocity distribution and consequently by the value of kappa index. Simulation results are compared with numerical solutions of the dispersion relation obtained in the literature and they are in good agreement.

  8. A Pilot Study Comparing Observational and Questionnaire Surrogate Measures of Pesticide Exposure Among Residents Impacted by the Ecuadorian Flower Industry.

    PubMed

    Handal, Alexis J; McGough-Maduena, Alison; Páez, Maritza; Skipper, Betty; Rowland, Andrew S; Fenske, Richard A; Harlow, Siobán D

    2015-01-01

    Self-reported measures of residential pesticide exposure are commonly used in epidemiological studies, especially when financial and logistical resources are limited. However, self-reporting is prone to misclassification bias. This pilot study assesses the agreement between self-report of residential pesticide exposure with direct observation measures, in an agricultural region of Ecuador, as a cross-validation method in 26 participants (16 rose workers and 10 controls), with percent agreement and kappa statistics calculated. Proximity of homes to nearby flower farms was found to have only fair agreement (kappa =.35). The use of discarded plastics (kappa =.06) and wood (kappa =.13) were found to have little agreement. Results indicate that direct observation or measurement may provide more accurate appraisals of residential exposures, such as proximity to industrial farmland and the use of discarded materials obtained from the flower farms.

  9. Interrater and intrarater agreements of magnetic resonance imaging findings in the lumbar spine: significant variability across degenerative conditions.

    PubMed

    Fu, Michael C; Buerba, Rafael A; Long, William D; Blizzard, Daniel J; Lischuk, Andrew W; Haims, Andrew H; Grauer, Jonathan N

    2014-10-01

    Magnetic resonance imaging (MRI) is frequently used in the evaluation of degenerative conditions in the lumbar spine. The relative interrater and intrarater agreements of MRI findings across different pathologic conditions are underexplored, as most studies are focused on specific findings. The purpose of this study was to characterize the interrater and intrarater agreements of MRI findings used to assess the degenerative lumbar spine. A retrospective diagnostic study at a large academic medical center was undertaken with a panel of orthopedic surgeons and musculoskeletal radiologists to assess lumbar MRIs using standardized criteria. Seventy-five subjects who underwent routine lumbar spine MRI at our institution were included. Each MRI study was assessed for 10 lumbar degenerative findings using standardized criteria. Lumbar vertebral levels were assessed independently, where applicable, for a total of 52 data points collected per study. T2-weighted axial and sagittal MRI sequences were presented in random order to the four reviewers (two orthopedic spine surgeons and two musculoskeletal radiologists) independently to determine interrater agreement. The first 10 studies were reevaluated at the end to determine intrarater agreement. Images were assessed using standardized and pilot-tested criteria to assess disc degeneration, stenosis, and other degenerative changes. Interrater and intrarater absolute percent agreements were calculated. To highlight the most clinically important MRI disagreements, a modified agreement analysis was also performed (in which disagreements between the lowest two severity grades for applicable conditions were ignored). Fleiss kappa coefficients for interrater agreement were determined. The overall absolute and modified interrater agreements were 76.9% and 93.5%, respectively. The absolute and modified intrarater agreements were 81.3% and 92.7%, respectively. Average Fleiss kappa coefficient was 0.431, suggesting moderate overall

  10. Interobserver agreement for post mortem renal histopathology and diagnosis of acute tubular necrosis in critically ill patients.

    PubMed

    Glassford, Neil J; Skene, Alison; Guardiola, Maria B; Chan, Matthew J; Bagshaw, Sean M; Bellomo, Rinaldo; Solez, Kim

    2017-12-01

    The renal histopathology of critically ill patients dying with acute kidney injury (AKI) in intensive care units of high income countries remains uncertain. Retrospective observational assessment of interobserver agreement in the reporting of renal post mortem histopathology, and the ability of pathologists blinded to the clinical context to independently identify the presence of pre-mortem AKI from digital images of histological sections from 34 critically ill patients dying in teaching hospitals in Australia and Canada. We identified a heterogeneous cohort with a median age of 65 years (interquartile range [IQR], 56.5-77), APACHE II score of 27 (IQR, 19-33), and sepsis as the most common admission diagnosis (12/34; 35%). The most common proximate causes of death were cardiovascular (19/34; 56%) and respiratory (7/34; 21%) failure. AKI was common, with 23 patients (68%) developing RIFLE-F AKI, and 21 patients (62%) receiving renal replacement therapy. Structured reporting for tubular inflammation showed excellent agreement (kappa = 1), but no other subdomain demonstrated better than moderate agreement (kappa < 0.6). Only fair agreement (55.9% of cases; kappa = 0.23) was demonstrated on the diagnosis of moderate to severe acute tubular necrosis (ATN). Pathologist A predicted RIFLE-I or worse AKI with the diagnosis of ATN, with an overall accuracy of 61.8%; pathologist B predicted AKI with an accuracy of 35.3%. Post mortem assessment of the renal histopathology in critically ill patients is neither robust nor reproducible; independent pathologists agree poorly on the diagnosis of ATN, and their structural assessment appears dissociated from ante-mortem renal function.

  11. Agreement between a self-administered questionnaire on musculoskeletal disorders of the neck-shoulder region and a physical examination

    PubMed Central

    Perreault, Nathalie; Brisson, Chantal; Dionne, Clermont E; Montreuil, Sylvie; Punnett, Laura

    2008-01-01

    Background In epidemiological studies on neck-shoulder disorders, physical examination by health professionals, although more expensive, is usually considered a better method of data collection than self-administered questionnaires on symptoms. However, little is known on the comparison of these two methods of data collection. The agreement between self-administered questionnaires and the physical examination on the presence of neck-shoulders disorders was assessed in the present study. Methods This study was conducted among clerical workers using video display units. Prevalent cases were workers for whom neck-shoulder symptoms were present for at least 3 days during the previous 7 days and for whom pain intensity was greater than 50 mm on a 100 mm visual analogue scale. All 85 workers meeting this definition and a random sample of 102 workers who did not meet this definition were selected. Physical examination included measures of active range of motion and musculoskeletal strength. Cohen's kappa and global percent agreement were calculated to compare the two methods of data collection. The effect on the agreement of different question and physical examination definitions and the importance of the time interval elapsed between the administrations of the tests were also evaluated. Results Kappa coefficients ranged from 0.19 to 0.54 depending on the definitions used to ascertain disorders. The agreement was highest when the two instruments were administered 21 days apart or less (Kappa = 0.54, global agreement = 77%). It was not substantially improved by the addition of criteria related to functional limitations or when comparisons were made with alternative physical examination definitions. Pain intensity recorded during physical examination maneuvers was an important element of the agreement between questionnaire and physical examination findings. Conclusion These results suggest a fair to good agreement between the presence of musculoskeletal disorders

  12. Agreement between allergen-specific IgE assays and ensuing immunotherapy recommendations from four commercial laboratories in the USA

    PubMed Central

    Plant, Jon D; Neradelik, Moni B; Polissar, Nayak L; Fadok, Valerie A; Scott, Brian A

    2014-01-01

    Background Canine allergen-specific IgE assays in the USA are not subjected to an independent laboratory reliability monitoring programme. Hypothesis/Objectives The aim of this study was to evaluate the agreement of diagnostic results and treatment recommendations of four serum IgE assays commercially available in the USA. Methods Replicate serum samples from 10 atopic dogs were submitted to each of four laboratories for allergen-specific IgE assays (ACTT®, VARL Liquid Gold, ALLERCEPT® and Greer® Aller-g-complete®). The interlaboratory agreement of standard, regional panels and ensuing treatment recommendations were analysed with the kappa statistic (κ) to account for agreement that might occur merely by chance. Six comparisons of pairs of laboratories and overall agreement among laboratories were analysed for ungrouped allergens (as tested) and also with allergens grouped according to reported cross-reactivity and taxonomy. Results The overall chance-corrected agreement of the positive/negative test results for ungrouped and grouped allergens was slight (κ = 0.14 and 0.13, respectively). Subset analysis of the laboratory pair with the highest level of diagnostic agreement (κ = 0.36) found slight agreement (κ = 0.13) for ungrouped plants and fungi, but substantial agreement (κ = 0.71) for ungrouped mites. The overall agreement of the treatment recommendations was slight (κ = 0.11). Altogether, 85.1% of ungrouped allergen treatment recommendations were unique to one laboratory or another. Conclusions and clinical importance Our study indicated that the choice of IgE assay may have a major influence on the positive/negative results and ensuing treatment recommendations. PMID:24461034

  13. Bis(acesulfamato-kappaO4)diaquabis(3-methylpyridine-kappaN)nickel(II).

    PubMed

    Dege, Necmi; Içbudak, Hasan; Adiyaman, Elif

    2007-01-01

    In the crystal structure of the title compound [systematic name: diaquabis(6-methyl-2,2-dioxo-1,2,3-oxathiazin-4-olato-kappaO4)bis(3-methylpyridine-kappaN)nickel(II)], [Ni(C4H4NO4S)2(C6H7N)2(H2O)2], the Ni(II) centre resides on a centre of symmetry and has a distorted octahedral geometry. The basal plane is formed by two carbonyl O atoms of two monodentate trans-oriented acesulfamate ligands and two trans aqua ligands. The axial positions in the octahedron are occupied by two N atoms of two trans pyridine ligands. Molecules are stacked in columns running along the a axis. There are pi-pi stacking interactions between the molecules in each column, with a distance of 3.623 (2) A between the centroids of the pyridine rings. There are also O-H...O interactions between the columns.

  14. Kappa Agonists as a Novel Therapy for Menopausal Hot Flashes

    PubMed Central

    Oakley, Amy E.; Steiner, Robert A.; Chavkin, Charles; Clifton, Donald K.; Ferrara, Laura K.; Reed, Susan D.

    2015-01-01

    Objective Postmenopausal hot flash etiology is poorly understood, making it difficult to develop and target ideal therapies. A network of hypothalamic estrogen-sensitive neurons producing Kisspeptin, Neurokinin B, and Dynorphin (KNDy neurons), located adjacent to the thermoregulatory center, regulate pulsatile secretion of GnRH and LH. Dynorphin may inhibit this system by binding kappa opioid receptors within the vicinity of KNDy neurons. We hypothesize that hot flashes are reduced by KNDy neuron manipulation. Methods A double-blind, cross-over, placebo-controlled pilot study evaluated the effect of a kappa agonist (KA).Hot flash frequency was the primary outcome. Twelve healthy postmenopausal women with moderate-severe hot flashes, ages 48-60 years, were randomized. Eight women with sufficient baseline hot flashes for statistical analysis completed all 3 interventions: placebo, standard Pentazocine/Naloxone (50/0.5 mg) or low-dose Pentazocine/Naloxone (25/0.25 mg). In an inpatient research setting, each participant received the 3 interventions, in randomized order, on 3 separate days. On each day, an intravenous catheter was inserted for luteinizing hormone (LH) blood sampling, and skin conductance and Holter monitors were placed. Subjective hot flash frequency and severity were recorded. Results Mean hot flash frequency 2-7 hours following therapy initiation was lower than that for placebo (KA standard-dose: 4.75 ± 0.67; KA low-dose: 4.50 ± 0.57; and placebo: 5.94 ± 0.78 hot flashes/5 hours; p =0.025). Hot flash intensity did not vary between interventions. LH pulsatility mirrored objective hot flashes in some, but not all women. Conclusions This pilot suggests that kappa agonists may affect menopausal vasomotor symptoms. PMID:25988798

  15. Total knee arthroplasty: good agreement of clinical severity scores between patients and consultants.

    PubMed

    Ebinesan, Ananthan D; Sarai, Bhupinder S; Walley, Gayle; Bridgman, Stephen; Maffulli, Nicola

    2006-07-31

    Nearly 20,000 patients per year in the UK receive total knee arthroplasty (TKA). One of the problems faced by the health services of many developed countries is the length of time patients spend waiting for elective treatment. We therefore report the results of a study in which the Salisbury Priority Scoring System (SPSS) was used by both the surgeon and their patients to ascertain whether there were differences between the surgeon generated and patient generated Salisbury Priority Scores. The Salisbury Priority Scoring System (SPSS) was used to assign relative priority to patients with knee osteoarthritis as part of a randomised controlled trial comparing the standard medial parapatellar approach versus the sub-vastus approach in TKA. The operating surgeons and each patient completed the SPSS at the same pre-assessment clinic. The SPSS assesses four criteria, namely progression of disease, pain or distress, disability or dependence on others, and loss of usual occupation. Crosstabs and agreement measures (Cohen's kappa) were performed. Overall, the four SPSS criteria showed a kappa value of 0.526, 0.796, 0.813, and 0.820, respectively, showing moderate to very good agreement between the patient and the operating consultant. Male patients showed better agreement than female patients. The Salisbury Priority Scoring System is a good means of assessing patients' needs in relation to elective surgery, with high agreement between the patient and the operating surgeon.

  16. Nuclear factor kappa B: a potential target for anti-HIV chemotherapy.

    PubMed

    Pande, V; Ramos, M J

    2003-08-01

    The Nuclear Factor Kappa B (NF-kappaB) is a lymphoid-specific transcription factor, which is sequestered in the cytoplasm by the protein IkappaB. NF-kappaB plays a major role in the regulation of HIV-1 gene expression. Upon activation, NF-kappaB is released from IkappaB, moves to the nucleus, and binds to its sites on the HIV long terminal repeat to start transcription of integrated HIV genome. The present review focuses on the NF-kappaB as a potential target for the development of chemotherapy against HIV-1. Beginning from the viral-binding to reverse transcription, integration, and gene expression, to the virion maturation, the life cycle of HIV presents drug-targets at all the stages. As a result, many drugs have been developed and have entered clinical trials. Some of the most important of these are reverse transcriptase and protease inhibitors, which have been used mostly in clinical studies in the form of combined therapy. But, this combined therapy has presented the problem of resistance, due to mutations in the virus. However, targeting NF-kappaB for the suppression of virus does not present the problem of resistance, as NF-kappaB is a normal part of the human T-4 cell, and is not subject to mutations, as is the virus. An overview of the NF-kappaB system and its role in HIV-1 is presented, followed by a critical review of its current and potential synthetic inhibitors. The drugs studied against NF-kappaB fall mainly into three categories: (1) Antioxidants, against oxidative stress conditions, which aid in NF-kappaB activation, (2) IkappaB phosphorylation and degradation inhibitors (the phosphorylation and degradation of IkappaB is necessary to make NF-kappaB free and move to the nucleus), and (3) NF-kappaB DNA binding inhibitors. The antioxidants include N-Acetyl-L-cysteine (NAC), alpha-Lipoic acid, glutathione monoester, pyrrolidine dithiocarbamate, and tepoxalin, of which NAC is the best studied. The IkappaB phosphorylation and degradation inhibitors

  17. Correlation and agreement of self-assessed and objective skin disease severity in a cross-sectional study of patients with acne, psoriasis, and atopic eczema.

    PubMed

    Magin, Parker J; Pond, C Dimity; Smith, Wayne T; Watson, Alan B; Goode, Susan M

    2011-12-01

    Previous studies have shown variable correlation of patients' self-assessed skin severity measures and clinician-assessed objective measures of severity. But, generally, correlation has not been as good as might be expected for conditions in which the objective physical extent of skin disease is apparent to the sufferer to an extent that is not applicable in many other diseases. This paper reports agreement and correlation of self-assessed and objective severity measures in a study of 108 subjects with acne, psoriasis, or atopic eczema. The study was a cross-sectional study examining psychological associations of these skin diseases. Objective severity was assessed with the Leeds technique (acne), the Psoriasis Area and Severity Index, and Six Area Six Sign Atopic Dermatitis instruments. Agreement is a more appropriate measure than correlation in this situation and was measured with weighted kappa, while correlation was measured with Spearman's rank correlation. There was a modest correlation of ρ = 0.46 and similarly very modest agreement of 0.35 (weighted kappa) of self-assessed and clinician-assessed disease severity. Furthermore, self-assessed (but not clinician-assessed) severity was statistically associated with psychological morbidity in this study; i.e. - depression, anxiety, and overall psychological morbidity. Clinicians should consider psychological sequelae of skin disease, not only in those with objectively more severe disease but in patients across the severity spectrum. Both observational and interventional studies of skin disease should include both clinician-assessed and self-assessed measures of severity among assessed variables. © 2011 The International Society of Dermatology.

  18. Involvement of nuclear factor {kappa}B in platelet CD40 signaling

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

    Hachem, Ahmed; Yacoub, Daniel; Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1

    Highlights: Black-Right-Pointing-Pointer sCD40L induces TRAF2 association to CD40 and NF-{kappa}B activation in platelets. Black-Right-Pointing-Pointer I{kappa}B{alpha} phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. Black-Right-Pointing-Pointer I{kappa}B{alpha} is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-{kappa}B). Givenmore » that platelets contain NF-{kappa}B, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of I{kappa}B{alpha}, which are abolished by CD40L blockade. Inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced I{kappa}B{alpha} phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on I{kappa}B{alpha} phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-{kappa}B activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against

  19. Agreement between pedometer and accelerometer in measuring physical activity in overweight and obese pregnant women

    PubMed Central

    2011-01-01

    Background Inexpensive, reliable objective methods are needed to measure physical activity (PA) in large scale trials. This study compared the number of pedometer step counts with accelerometer data in pregnant women in free-living conditions to assess agreement between these measures. Methods Pregnant women (n = 58) with body mass index ≥25 kg/m2 at median 13 weeks' gestation wore a GT1M Actigraph accelerometer and a Yamax Digi-Walker CW-701 pedometer for four consecutive days. The Spearman rank correlation coefficients were determined between pedometer step counts and various accelerometer measures of PA. Total agreement between accelerometer and pedometer step counts was evaluated by determining the 95% limits of agreement estimated using a regression-based method. Agreement between the monitors in categorising participants as active or inactive was assessed by determining Kappa. Results Pedometer step counts correlated moderately (r = 0.36 to 0.54) with most accelerometer measures of PA. Overall step counts recorded by the pedometer and the accelerometer were not significantly different (medians 5961 vs. 5687 steps/day, p = 0.37). However, the 95% limits of agreement ranged from -2690 to 2656 steps/day for the mean step count value (6026 steps/day) and changed substantially over the range of values. Agreement between the monitors in categorising participants to active and inactive varied from moderate to good depending on the criteria adopted. Conclusions Despite statistically significant correlations and similar median step counts, the overall agreement between pedometer and accelerometer step counts was poor and varied with activity level. Pedometer and accelerometer steps cannot be used interchangeably in overweight and obese pregnant women. PMID:21703033

  20. Interobserver agreement between primary graders and an expert grader in the Bristol and Weston diabetic retinopathy screening programme: a quality assurance audit.

    PubMed

    Patra, S; Gomm, E M W; Macipe, M; Bailey, C

    2009-08-01

    To assess the quality and accuracy of primary grading in the Bristol and Weston diabetic retinopathy screening programme and to set standards for future interobserver agreement reports. A prospective audit of 213 image sets from six fully trained primary graders in the Bristol and Weston diabetic retinopathy screening programme was carried out over a 4-week period. All the images graded by the primary graders were regraded by an expert grader blinded to the primary grading results and the identity of the primary grader. The interobserver agreement between primary graders and the blinded expert grader and the corresponding Kappa coefficient was determined for overall grading, referable, non-referable and ungradable disease. The audit standard was set at 80% for interobserver agreement with a Kappa coefficient of 0.7. The interobserver agreement bettered the audit standard of 80% in all the categories. The Kappa coefficient was substantial (0.7) for the overall grading results and ranged from moderate to substantial (0.59-0.65) for referable, non-referable and ungradable disease categories. The main recommendation of the audit was to provide refresher training for the primary graders with focus on ungradable disease. The audit demonstrated an acceptable level of quality and accuracy of primary grading in the Bristol and Weston diabetic retinopathy screening programme and provided a standard against which future interobserver agreement can be measured for quality assurance within a screening programme. Diabet. Med. 26, 820-823 (2009).

  1. Direct covalent modification as a strategy to inhibit nuclear factor-kappa B.

    PubMed

    Pande, Vineet; Sousa, Sérgio F; Ramos, Maria João

    2009-01-01

    Nuclear Factor-KkappaB (NF-kappaB) is a transcription factor whose inappropriate activation may result in the development of a number of diseases including cancer, inflammation, neurodegeneration and AIDS. Recent studies on NF-kappaB mediated pathologies, made therapeutic interventions leading to its inhibition an emerging theme in pharmaceutical research. NF-kappaB resides in the cytoplasm and is activated by several time-dependent factors, leading to proteasome-dependent degradation of its inhibitory protein (IkappaB), resulting in free NF-kappaB (p50 and p65 subunits, involved in disease states), which binds to target DNA sites, further resulting in enhanced transcription of several disease associated proteins. The complex pathway of NF-kappaB, finally leading to its DNA binding, has attracted several approaches interfering with this pathway. One such approach is that of a direct covalent modification of NF-kappaB. In this article, we present a critical review on the pharmacological agents that have been studied as inhibitors of NF-kappaB by covalently modifying redox-regulated cysteine residues in its subunits, ultimately resulting in the inhibition of kappaB DNA recognition and binding. Beginning with a general overview of NF-kappaB pathway and several possibilities of chemical interventions, the significance of redox-regulation in NF-kappaB activation and DNA binding is presented. Further, protein S-thiolation, S-nitrosylation and irreversible covalent modification are described as regular biochemical events in the cell, having provided a guideline for the development of NF-kappaB inhibitors discussed further. Although just a handful of inhibitors, with most of them being alkylating agents have been studied in the present context, this approach presents potential for the development of a new class of NF-kappaB-inhibitors.

  2. Influence of true within-herd prevalence of small ruminant lentivirus infection in goats on agreement between serological immunoenzymatic tests.

    PubMed

    Czopowicz, Michał; Szaluś-Jordanow, Olga; Mickiewicz, Marcin; Moroz, Agata; Witkowski, Lucjan; Markowska-Daniel, Iwona; Bagnicka, Emilia; Kaba, Jarosław

    2017-09-01

    The study was conducted to evaluate influence of the true within-herd prevalence of small ruminant lentivirus (SRLV) infection on agreement beyond chance between three different types of commercial serological ELISAs. Blood samples were collected from 865 goats from 12 dairy goat herds. Serum samples were tested using three commercial ELISA kits: whole-virus indirect ELISA (wELISA), indirect ELISA based on recombined TM and CA antigens (TM/CA-ELISA), and competitive-inhibition ELISA based on SU antigen (SU-ELISA). Herds were classed into three prevalence strata of high (>50%), moderate (10-50%) and low (<10%) true within-herd prevalence of SRLV infection. The latter was estimated on the basis of results of wELISA adjusted by its sensitivity and specificity. Agreement beyond chance between the three ELISAs was assessed at two levels. First, the general agreement was determined using two coefficients corrected for chance-agreement: Cohen's kappa and Gwet's AC 1 . Then, agreement between tests was evaluated using Gwet's AC 1 separately in the three prevalence strata and compared between them by computing 95% confidence intervals for differences with a Bonferroni correction for multiple comparisons. The general agreement between the three tests was very good: wELISA and TM/CA-ELISA - Cohen's kappa of 81.8% (CI 95%: 77.9% to 85.7%), Gwet's AC 1 of 82.7% (CI 95%: 79.0% to 86.4%); wELISA and SU-ELISA - Cohen's kappa of 83.2% (CI 95%: 79.4% to 86.9%), Gwet's AC 1 of 83.9% (CI 95%: 80.4% to 87.5%); TM/CA-ELISA and SU-ELISA - Cohen's kappa of 86.0% (CI 95%: 82.6% to 89.5%), Gwet's AC 1 of 86.9% (CI 95%: 83.6% to 90.1%). However, agreement between ELISAs was significantly related to the within-herd true prevalence - it was significantly lower (although still high) when within-herd true prevalence was moderate (Gwet's AC 1 between 67.2% and 78.7%), whereas remained very high, when true within-herd prevalence was either >50% (Gwet's AC 1 between 91.9% and 98.8%) or <10% (Gwet

  3. Agreement between core laboratory and study investigators for imaging scores in a thrombectomy trial.

    PubMed

    Fahed, Robert; Ben Maacha, Malek; Ducroux, Célina; Khoury, Naim; Blanc, Raphaël; Piotin, Michel; Lapergue, Bertrand

    2018-05-14

    We aimed to assess the agreement between study investigators and the core laboratory (core lab) of a thrombectomy trial for imaging scores. The Alberta Stroke Program Early CT Score (ASPECTS), the European Collaborative Acute Stroke Study (ECASS) hemorrhagic transformation (HT) classification, and the Thrombolysis In Cerebral Infarction (TICI) scores as recorded by study investigators were compared with the core lab scores in order to assess interrater agreement, using Cohen's unweighted and weighted kappa statistics. There were frequent discrepancies between study sites and core lab for all the scores. Agreement for ASPECTS and ECASS HT classification was less than substantial, with disagreement occurring in more than one-third of cases. Agreement was higher on MRI-based scores than on CT, and was improved after dichotomization on both CT and MRI. Agreement for TICI scores was moderate (with disagreement occurring in more than 25% of patients), and went above the substantial level (less than 10% disagreement) after dichotomization (TICI 0/1/2a vs 2b/3). Discrepancies between scores assessed by the imaging core lab and those reported by study sites occurred in a significant proportion of patients. Disagreement in the assessment of ASPECTS and day 1 HT scores was more frequent on CT than on MRI. The agreement for the dichotomized TICI score (the trial's primary outcome) was substantial, with less than 10% of disagreement between study sites and core lab. NCT02523261, Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Kappa Distribution in a Homogeneous Medium: Adiabatic Limit of a Super-diffusive Process?

    NASA Astrophysics Data System (ADS)

    Roth, I.

    2015-12-01

    The classical statistical theory predicts that an ergodic, weakly interacting system like charged particles in the presence of electromagnetic fields, performing Brownian motions (characterized by small range deviations in phase space and short-term microscopic memory), converges into the Gibbs-Boltzmann statistics. Observation of distributions with a kappa-power-law tails in homogeneous systems contradicts this prediction and necessitates a renewed analysis of the basic axioms of the diffusion process: characteristics of the transition probability density function (pdf) for a single interaction, with a possibility of non-Markovian process and non-local interaction. The non-local, Levy walk deviation is related to the non-extensive statistical framework. Particles bouncing along (solar) magnetic field with evolving pitch angles, phases and velocities, as they interact resonantly with waves, undergo energy changes at undetermined time intervals, satisfying these postulates. The dynamic evolution of a general continuous time random walk is determined by pdf of jumps and waiting times resulting in a fractional Fokker-Planck equation with non-integer derivatives whose solution is given by a Fox H-function. The resulting procedure involves the known, although not frequently used in physics fractional calculus, while the local, Markovian process recasts the evolution into the standard Fokker-Planck equation. Solution of the fractional Fokker-Planck equation with the help of Mellin transform and evaluation of its residues at the poles of its Gamma functions results in a slowly converging sum with power laws. It is suggested that these tails form the Kappa function. Gradual vs impulsive solar electron distributions serve as prototypes of this description.

  5. Assessment of the agreement between the Framingham and DAD risk equations for estimating cardiovascular risk in adult Africans living with HIV infection: a cross-sectional study.

    PubMed

    Noumegni, Steve Raoul; Ama, Vicky Jocelyne Moor; Assah, Felix K; Bigna, Jean Joel; Nansseu, Jobert Richie; Kameni, Jenny Arielle M; Katte, Jean-Claude; Dehayem, Mesmin Y; Kengne, Andre Pascal; Sobngwi, Eugene

    2017-01-01

    The Absolute cardiovascular disease (CVD) risk evaluation using multivariable CVD risk models is increasingly advocated in people with HIV, in whom existing models remain largely untested. We assessed the agreement between the general population derived Framingham CVD risk equation and the HIV-specific Data collection on Adverse effects of anti-HIV Drugs (DAD) CVD risk equation in HIV-infected adult Cameroonians. This cross-sectional study involved 452 HIV infected adults recruited at the HIV day-care unit of the Yaoundé Central Hospital, Cameroon. The 5-year projected CVD risk was estimated for each participant using the DAD and Framingham CVD risk equations. Agreement between estimates from these equations was assessed using the spearman correlation and Cohen's kappa coefficient. The mean age of participants (80% females) was 44.4 ± 9.8 years. Most participants (88.5%) were on antiretroviral treatment with 93.3% of them receiving first-line regimen. The most frequent cardiovascular risk factors were abdominal obesity (43.1%) and dyslipidemia (33.8%). The median estimated 5-year CVD risk was 0.6% (25th-75th percentiles: 0.3-1.3) using the DAD equation and 0.7% (0.2-2.0) with the Framingham equation. The Spearman correlation between the two estimates was 0.93 ( p  < 0.001). The kappa statistic was 0.61 (95% confident interval: 0.54-0.67) for the agreement between the two equations in classifying participants across risk categories defined as low, moderate, high and very high. Most participants had a low-to-moderate estimated CVD risk, with acceptable level of agreement between the general and HIV-specific equations in ranking CVD risk.

  6. The active movement scale: an evaluative tool for infants with obstetrical brachial plexus palsy.

    PubMed

    Curtis, Christine; Stephens, Derek; Clarke, Howard M; Andrews, David

    2002-05-01

    Newborns with peripheral nerve lesions involving the upper extremity are difficult to evaluate. The reliability of the Active Movement Scale (AMS), a tool for assessing motor function in infants with obstetrical brachial plexus palsy (OBPP), was examined in 2 complementary studies. Part A was an interrater reliability study in which 63 infants younger than 1 year with OBPP were independently evaluated by 2 physical therapists using the AMS. The scores were compared for reliability and controlled for chance agreement by using kappa statistics. Overall kappa analysis of the 15 tested movements showed a moderate strength of score agreement (kappa = 0.51). Quadratic-weighted kappa (kappa(quad)) statistics showed that 8 of the 15 movements tested were in the highest strength of agreement category (kappa(quad) = 0.81-1.00). Five movements showed substantial agreement (kappa(quad) = 0.61-0.80), and 2 movements had moderate agreement (kappa(quad) = 0.41- 0.60). The overall kappa(quad) was 0.89. Part B was a variability study designed to examine the dispersion of scores when infants with OBPP were evaluated with the AMS by multiple raters. Ten pediatric physical therapists with varying degrees of experience using the scale attended a 1(1/2)-hour instructional workshop on administration of the tool for infants with OBPP. A chain-block study design was used to obtain 30 assessments of 10 infants by 10 raters. A 2-way analysis of variance indicated that the variability of scores due to rater factors was low compared with the variability due to patient factors and that variation in scores due to rater experience was minimal. The results of part A indicate that the AMS is a reliable tool for the assessment of infants with OBPP when raters familiar with the scale are compared. The results of part B suggest that, with minimal training, raters with a range of experience using the AMS are able to reliably evaluate infants with upper-extremity paralysis.

  7. Pre-folding IkappaBalpha alters control of NF-kappaB signaling.

    PubMed

    Truhlar, Stephanie M E; Mathes, Erika; Cervantes, Carla F; Ghosh, Gourisankar; Komives, Elizabeth A

    2008-06-27

    Transcription complex components frequently show coupled folding and binding but the functional significance of this mode of molecular recognition is unclear. IkappaBalpha binds to and inhibits the transcriptional activity of NF-kappaB via its ankyrin repeat (AR) domain. The beta-hairpins in ARs 5-6 in IkappaBalpha are weakly-folded in the free protein, and their folding is coupled to NF-kappaB binding. Here, we show that introduction of two stabilizing mutations in IkappaBalpha AR 6 causes ARs 5-6 to fold cooperatively to a conformation similar to that in NF-kappaB-bound IkappaBalpha. Free IkappaBalpha is degraded by a proteasome-dependent but ubiquitin-independent mechanism, and this process is slower for the pre-folded mutants both in vitro and in cells. Interestingly, the pre-folded mutants bind NF-kappaB more weakly, as shown by both surface plasmon resonance and isothermal titration calorimetry in vitro and immunoprecipitation experiments from cells. One consequence of the weaker binding is that resting cells containing these mutants show incomplete inhibition of NF-kappaB activation; they have significant amounts of nuclear NF-kappaB. Additionally, the weaker binding combined with the slower rate of degradation of the free protein results in reduced levels of nuclear NF-kappaB upon stimulation. These data demonstrate clearly that the coupled folding and binding of IkappaBalpha is critical for its precise control of NF-kappaB transcriptional activity.

  8. Agreement Between Responses From Community-Dwelling Persons With Stroke and Their Proxies on the NIH Neurological Quality of Life (Neuro-QoL) Short Forms.

    PubMed

    Kozlowski, Allan J; Singh, Ritika; Victorson, David; Miskovic, Ana; Lai, Jin-Shei; Harvey, Richard L; Cella, David; Heinemann, Allen W

    2015-11-01

    To examine agreement between patient and proxy responses on the Quality of Life in Neurological Disorders (Neuro-QoL) instruments after stroke. Cross-sectional observational substudy of the longitudinal, multisite, multicondition Neuro-QoL validation study. In-person, interview-guided, patient-reported outcomes. Convenience sample of dyads (N=86) of community-dwelling persons with stroke and their proxy respondents. Not applicable. Dyads concurrently completed short forms of 8 or 9 items for the 13 Neuro-QoL adult domains using the patient-proxy perspective. Agreement was examined at the scale-level with difference scores, intraclass correlation coefficients (ICCs), effect size statistics, and Bland-Altman plots, and at the item-level with kappa coefficients. We found no mean differences between patients and proxies on the Applied Cognition-General Concerns, Depression, Satisfaction With Social Roles and Activities, Stigma, and Upper Extremity Function (Fine Motor, activities of daily living) short forms. Patients rated themselves more favorably on the Applied Cognition-Executive Function, Ability to Participate in Social Roles and Activities, Lower Extremity Function (Mobility), Positive Affect and Well-Being, Anxiety, Emotional and Behavioral Dyscontrol, and Fatigue short forms. The largest mean patient-proxy difference observed was 3 T-score points on the Lower Extremity Function (Mobility). ICCs ranged from .34 to .59. However, limits of agreement showed dyad differences exceeding ±20 T-score points, and item-level agreement ranged from not significant to weighted kappa=.34. Proxy responses on Neuro-QoL short forms can complement responses of moderate- to high-functioning community-dwelling persons with stroke and augment group-level analyses, but do not substitute for individual patient ratings. Validation is needed for other stroke populations. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  9. Digital assessment of the fetal alcohol syndrome facial phenotype: reliability and agreement study.

    PubMed

    Tsang, Tracey W; Laing-Aiken, Zoe; Latimer, Jane; Fitzpatrick, James; Oscar, June; Carter, Maureen; Elliott, Elizabeth J

    2017-01-01

    To examine the three facial features of fetal alcohol syndrome (FAS) in a cohort of Australian Aboriginal children from two-dimensional digital facial photographs to: (1) assess intrarater and inter-rater reliability; (2) identify the racial norms with the best fit for this population; and (3) assess agreement with clinician direct measures. Photographs and clinical data for 106 Aboriginal children (aged 7.4-9.6 years) were sourced from the Lililwan Project . Fifty-eight per cent had a confirmed prenatal alcohol exposure and 13 (12%) met the Canadian 2005 criteria for FAS/partial FAS. Photographs were analysed using the FAS Facial Photographic Analysis Software to generate the mean PFL three-point ABC-Score, five-point lip and philtrum ranks and four-point face rank in accordance with the 4-Digit Diagnostic Code. Intrarater and inter-rater reliability of digital ratings was examined in two assessors. Caucasian or African American racial norms for PFL and lip thickness were assessed for best fit; and agreement between digital and direct measurement methods was assessed. Reliability of digital measures was substantial within (kappa: 0.70-1.00) and between assessors (kappa: 0.64-0.89). Clinician and digital ratings showed moderate agreement (kappa: 0.47-0.58). Caucasian PFL norms and the African American Lip-Philtrum Guide 2 provided the best fit for this cohort. In an Aboriginal cohort with a high rate of FAS, assessment of facial dysmorphology using digital methods showed substantial inter- and intrarater reliability. Digital measurement of features has high reliability and until data are available from a larger population of Aboriginal children, the African American Lip-Philtrum Guide 2 and Caucasian (Strömland) PFL norms provide the best fit for Australian Aboriginal children.

  10. Agreement between allergen-specific IgE assays and ensuing immunotherapy recommendations from four commercial laboratories in the USA.

    PubMed

    Plant, Jon D; Neradelik, Moni B; Polissar, Nayak L; Fadok, Valerie A; Scott, Brian A

    2014-02-01

    Canine allergen-specific IgE assays in the USA are not subjected to an independent laboratory reliability monitoring programme. The aim of this study was to evaluate the agreement of diagnostic results and treatment recommendations of four serum IgE assays commercially available in the USA. Replicate serum samples from 10 atopic dogs were submitted to each of four laboratories for allergen-specific IgE assays (ACTT(®) , VARL Liquid Gold, ALLERCEPT(®) and Greer(®) Aller-g-complete(®) ). The interlaboratory agreement of standard, regional panels and ensuing treatment recommendations were analysed with the kappa statistic (κ) to account for agreement that might occur merely by chance. Six comparisons of pairs of laboratories and overall agreement among laboratories were analysed for ungrouped allergens (as tested) and also with allergens grouped according to reported cross-reactivity and taxonomy. The overall chance-corrected agreement of the positive/negative test results for ungrouped and grouped allergens was slight (κ = 0.14 and 0.13, respectively). Subset analysis of the laboratory pair with the highest level of diagnostic agreement (κ = 0.36) found slight agreement (κ = 0.13) for ungrouped plants and fungi, but substantial agreement (κ = 0.71) for ungrouped mites. The overall agreement of the treatment recommendations was slight (κ = 0.11). Altogether, 85.1% of ungrouped allergen treatment recommendations were unique to one laboratory or another. Our study indicated that the choice of IgE assay may have a major influence on the positive/negative results and ensuing treatment recommendations. © 2014 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and the ACVD.

  11. Synergistic activation of NF-{kappa}B by nontypeable H. influenzae and S. pneumoniae is mediated by CK2, IKK{beta}-I{kappa}B{alpha}, and p38 MAPK

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

    Kweon, Soo-Mi; Wang, Beinan; Rixter, Davida

    2006-12-15

    In review of the past studies on NF-{kappa}B regulation, most of them have focused on investigating how NF-{kappa}B is activated by a single inducer at a time. Given the fact that, in mixed bacterial infections in vivo, multiple inflammation inducers, including both nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae, are present simultaneously, a key issue that has yet to be addressed is whether NTHi and S. pneumoniae simultaneously activate NF-{kappa}B and the subsequent inflammatory response in a synergistic manner. Here, we show that NTHi and S. pneumoniae synergistically induce NF-{kappa}B-dependent inflammatory response via activation of multiple signaling pathways in vitromore » and in vivo. The classical IKK{beta}-I{kappa}B{alpha} and p38 MAPK pathways are involved in synergistic activation of NF-{kappa}B via two distinct mechanisms, p65 nuclear translocation-dependent and -independent mechanisms. Moreover, casein kinase 2 (CK2) is involved in synergistic induction of NF-{kappa}B via a mechanism dependent on phosphorylation of p65 at both Ser536 and Ser276 sites. These studies bring new insights into the molecular mechanisms underlying the NF-{kappa}B-dependent inflammatory response in polymicrobial infections and may lead to development of novel therapeutic strategies for modulating inflammation in mixed infections for patients with otitis media and chronic obstructive pulmonary diseases.« less

  12. Research diagnostic criteria for temporomandibular disorders (RDC/TMD): development of image analysis criteria and examiner reliability for image analysis.

    PubMed

    Ahmad, Mansur; Hollender, Lars; Anderson, Quentin; Kartha, Krishnan; Ohrbach, Richard; Truelove, Edmond L; John, Mike T; Schiffman, Eric L

    2009-06-01

    As part of the Multisite Research Diagnostic Criteria For Temporomandibular Disorders (RDC/TMD) Validation Project, comprehensive temporomandibular joint diagnostic criteria were developed for image analysis using panoramic radiography, magnetic resonance imaging (MRI), and computerized tomography (CT). Interexaminer reliability was estimated using the kappa (kappa) statistic, and agreement between rater pairs was characterized by overall, positive, and negative percent agreement. Computerized tomography was the reference standard for assessing validity of other imaging modalities for detecting osteoarthritis (OA). For the radiologic diagnosis of OA, reliability of the 3 examiners was poor for panoramic radiography (kappa = 0.16), fair for MRI (kappa = 0.46), and close to the threshold for excellent for CT (kappa = 0.71). Using MRI, reliability was excellent for diagnosing disc displacements (DD) with reduction (kappa = 0.78) and for DD without reduction (kappa = 0.94) and good for effusion (kappa = 0.64). Overall percent agreement for pairwise ratings was >or=82% for all conditions. Positive percent agreement for diagnosing OA was 19% for panoramic radiography, 59% for MRI, and 84% for CT. Using MRI, positive percent agreement for diagnoses of any DD was 95% and of effusion was 81%. Negative percent agreement was >or=88% for all conditions. Compared with CT, panoramic radiography and MRI had poor and marginal sensitivity, respectively, but excellent specificity in detecting OA. Comprehensive image analysis criteria for the RDC/TMD Validation Project were developed, which can reliably be used for assessing OA using CT and for disc position and effusion using MRI.

  13. Agreement in electrocardiogram interpretation in patients with septic shock.

    PubMed

    Mehta, Sangeeta; Granton, John; Lapinsky, Stephen E; Newton, Gary; Bandayrel, Kristofer; Little, Anjuli; Siau, Chuin; Cook, Deborah J; Ayers, Dieter; Singer, Joel; Lee, Terry C; Walley, Keith R; Storms, Michelle; Cooper, Jamie; Holmes, Cheryl L; Hebert, Paul; Gordon, Anthony C; Presneill, Jeff; Russell, James A

    2011-09-01

    The reliability of electrocardiogram interpretation to diagnose myocardial ischemia in critically ill patients is unclear. In adults with septic shock, we assessed intra- and inter-rater agreement of electrocardiogram interpretation, and the effect of knowledge of troponin values on these interpretations. Prospective substudy of a randomized trial of vasopressin vs. norepinephrine in septic shock. Nine Canadian intensive care units. Adults with septic shock requiring at least 5 μg/min of norepinephrine for 6 hrs. Twelve-lead electrocardiograms were recorded before study drug, and 6 hrs, 2 days, and 4 days after study drug initiation. Two physician readers, blinded to patient data and group, independently interpreted electrocardiograms on three occasions (first two readings were blinded to patient data; third reading was unblinded to troponin). To calibrate and refine definitions, both readers initially reviewed 25 trial electrocardiograms representing normal to abnormal. Cohen's Kappa and the φ statistic were used to analyze intra- and inter-rater agreement. One hundred twenty-one patients (62.2 ± 16.5 yrs, Acute Physiology and Chronic Health Evaluation II 28.6 ± 7.7) had 373 electrocardiograms. Blinded to troponin, readers 1 and 2 interpreted 46.4% and 30.0% of electrocardiograms as normal, and 15.3% and 12.3% as ischemic, respectively. Intrarater agreement was moderate for overall ischemia (κ 0.54 and 0.58), moderate/good for "normal" (κ 0.69 and 0.55), fair to good for specific signs of ischemia (ST elevation, T inversion, and Q waves, reader 1 κ 0.40 to 0.69; reader 2 κ 0.56 to 0.70); and good/very good for atrial arrhythmias (κ 0.84 and 0.79) and bundle branch block (κ 0.88 and 0.79). Inter-rater agreement was fair for ischemia (κ 0.29), moderate for ST elevation (κ 0.48), T inversion (κ 0.52), and Q waves (κ 0.44), good for bundle branch block (κ 0.78), and very good for atrial arrhythmias (κ 0.83). Inter-rater agreement for ischemia improved

  14. Interobserver agreement in retrospective chart reviews for factors associated with cervical spine injuries in children.

    PubMed

    Olsen, Cody S; Kuppermann, Nathan; Jaffe, David M; Brown, Kathleen; Babcock, Lynn; Mahajan, Prashant V; Leonard, Julie C

    2015-04-01

    The objective was to describe the interobserver agreement between trained chart reviewers and physician reviewers in a multicenter retrospective chart review study of children with cervical spine injuries (CSIs). Medical records of children younger than 16 years old with cervical spine radiography from 17 Pediatric Emergency Care Applied Research Network (PECARN) hospitals from years 2000 through 2004 were abstracted by trained reviewers for a study aimed to identify predictors of CSIs in children. Independent physician-reviewers abstracted patient history and clinical findings from a random sample of study patient medical records at each hospital. Interobserver agreement was assessed using percent agreement and the weighted kappa (κ) statistic, with lower 95% confidence intervals. Moderate or better agreement (κ > 0.4) was achieved for most candidate CSI predictors, including altered mental status (κ = 0.87); focal neurologic findings (κ = 0.74); posterior midline neck tenderness (κ = 0.74); any neck tenderness (κ = 0.89); torticollis (κ = 0.79); complaint of neck pain (κ = 0.83); history of loss of consciousness (κ = 0.89); nonambulatory status (κ = 0.74); and substantial injuries to the head (κ = 0.50), torso/trunk (κ = 0.48), and extremities (κ = 0.59). High-risk mechanisms showed near-perfect agreement (diving, κ = 1.0; struck by car, κ = 0.93; other motorized vehicle crash, κ = 0.93; fall, κ = 0.92; high-risk motor vehicle collision, κ = 0.89; hanging, κ = 0.80). Fair agreement was found for clotheslining mechanisms (κ = 0.36) and substantial face injuries (κ = 0.40). Most retrospectively assessed variables thought to be predictive of CSIs in blunt trauma-injured children had at least moderate interobserver agreement, suggesting that these data are sufficiently valid for use in identifying potential predictors of CSI. © 2015 by the Society for Academic Emergency Medicine.

  15. Glaucoma progression detection: agreement, sensitivity, and specificity of expert visual field evaluation, event analysis, and trend analysis.

    PubMed

    Antón, Alfonso; Pazos, Marta; Martín, Belén; Navero, José Manuel; Ayala, Miriam Eleonora; Castany, Marta; Martínez, Patricia; Bardavío, Javier

    2013-01-01

    To assess sensitivity, specificity, and agreement among automated event analysis, automated trend analysis, and expert evaluation to detect glaucoma progression. This was a prospective study that included 37 eyes with a follow-up of 36 months. All had glaucomatous disks and fields and performed reliable visual fields every 6 months. Each series of fields was assessed with 3 different methods: subjective assessment by 2 independent teams of glaucoma experts, glaucoma/guided progression analysis (GPA) event analysis, and GPA (visual field index-based) trend analysis. Kappa agreement coefficient between methods and sensitivity and specificity for each method using expert opinion as gold standard were calculated. The incidence of glaucoma progression was 16% to 18% in 3 years but only 3 cases showed progression with all 3 methods. Kappa agreement coefficient was high (k=0.82) between subjective expert assessment and GPA event analysis, and only moderate between these two and GPA trend analysis (k=0.57). Sensitivity and specificity for GPA event and GPA trend analysis were 71% and 96%, and 57% and 93%, respectively. The 3 methods detected similar numbers of progressing cases. The GPA event analysis and expert subjective assessment showed high agreement between them and moderate agreement with GPA trend analysis. In a period of 3 years, both methods of GPA analysis offered high specificity, event analysis showed 83% sensitivity, and trend analysis had a 66% sensitivity.

  16. The relationship between kappa and temperature in energetic ion spectra at Jupiter

    NASA Technical Reports Server (NTRS)

    Collier, Michael R.; Hamilton, D. C.

    1995-01-01

    A universal energy per charge kappa function fit is simultaneously applied to the spectra of Voyager 2 Low Energy Charged Particle (LECP) proton, helium, oxygen, sulfur, and carbon ions during 33 Jovian plasma sheet crossings from 26 to 160 R(sub J). The fits yield an approximately linear relationship between high energy spectral index, kappa, and core proton temperature of the form kappa (T(sub H)) approximately = eta dot T(sub H) + kappa(sub 0) with eta = 0.080 ke/V, kappa(sub 0) = 2.86, and T(sub H) measured in keV. Core proton temperatures range from 5 to 35 keV with spectral indices ranging from 3 to 6.

  17. Phi Delta Kappa Viewpoint.

    ERIC Educational Resources Information Center

    Phi Delta Kappa, Trenton, NJ. Trenton Area Chapter.

    This collection of articles on aspects of educational research, service, and leadership, are all written by members the Trenton (New Jersey) Area Chapter of Phi Delta Kappa. "Extra Year Programs: The K-1 Transition," by Richard Graja, reports on a study of 210 families regarding the Extra Year program, an opportunity for children to…

  18. Bullying at school: Agreement between caregivers' and children's perception.

    PubMed

    Durán, Lucas G; Scherñuk Schroh, Jordán C; Panizoni, Estefanía P; Jouglard, Ezequiel F; Serralunga, M Gabriela; Esandi, M Eugenia

    2017-02-01

    Bullying at school is usually kept secret from adults, making them unaware of the situation. To describe caregivers' and children's perception and assess their agreement in terms of bullying situations. Cross-sectional study in children aged 8-12 years old attending public schools and their caregivers. The questionnaire on preconceptions of intimidation and bullying among peers (PRECONCIMEI) (child/caregiver version) was used. Studied outcome measures: Scale of bullying, causes of bullying, child involvement in bullying, communication in bullying situations. Univariate and bivariate analyses were done and agreement was estimated using the Kappa index. A total of 529 child/caregiver dyads participated. Among caregivers, 35% stated that bullying occurred in their children's schools. Among children, 133 (25%) admitted to being involved: 70 (13%) were victims of bullying, 40 (8%) were bullies, and 23 (4%) were bullied and perpetrated bullying. Among the 63 caregivers of children who admitted to be bullies, 78% did not consider their children capable of perpetrating bullying. Among children who were bullied or who both suffered bullying and bullied others, 69.9% (65/93) indicated that "if they were the victims of bullying, they would tell their family." However, 89.2% (83/93) of caregivers considered that their children would tell them if they were ever involved in these situations. Agreement was observed in terms of a positive communication (Kappa = -0.04) between 62.6% (57/91) of the child/caregiver dyads school bullying. Disagreement was observed between children and their caregivers in relation to the frequency and communication of bullying situations. Few caregivers whose children admitted to being involved in these situations believed it was a possibility. Sociedad Argentina de Pediatría

  19. 40 CFR 721.10688 - Copper, chloro[tris(2-chloroethyl) phosphite-.kappa.P]-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) phosphite-.kappa.P]-. 721.10688 Section 721.10688 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10688 Copper, chloro[tris(2-chloroethyl) phosphite-.kappa.P]-. (a... copper, chloro[tris(2-chloroethyl) phosphite-.kappa.P]- (PMN P-13-221; CAS No. 24484-01-3) is subject to...

  20. TRIM45 negatively regulates NF-{kappa}B-mediated transcription and suppresses cell proliferation

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

    Shibata, Mio; Sato, Tomonobu; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer NF-{kappa}B plays an important role in cell survival and carcinogenesis. Black-Right-Pointing-Pointer TRIM45 negatively regulates TNF{alpha}-induced NF-{kappa}B-mediated transcription. Black-Right-Pointing-Pointer TRIM45 overexpression suppresses cell growth. Black-Right-Pointing-Pointer TRIM45 acts as a repressor for the NF-{kappa}B signal and regulates cell growth. -- Abstract: The NF-{kappa}B signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-{kappa}B is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-{kappa}B signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin-proteasome system. It has been reported that overexpression of TRIM45, one ofmore » the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNF{alpha}-induced NF-{kappa}B-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-{kappa}B signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-{kappa}B signal and regulates cell growth.« less

  1. Internal Passage Heat Transfer Prediction Using Multiblock Grids and a Kappa-Omega Turbulence Model

    NASA Technical Reports Server (NTRS)

    Rigby, David L.; Ameri, Ali A.; Steinthorsson, Erlendur

    1996-01-01

    Numerical simulations of the three-dimensional flow and heat transfer in a rectangular duct with a 180 C bend were performed. Results are presented for Reynolds numbers of 17,000 and 37,000 and for aspect ratios of 0.5 and I.O. A kappa-omega turbulence model with no reference to distance to a wall is used. Direct comparison between single block and multiblock grid calculations are made. Heat transfer and velocity distributions are compared to available literature with good agreement. The multi-block grid system is seen to produce more accurate results compared to a single-block grid with the same number of cells.

  2. Agreement between computed tomography, magnetic resonance imaging, and surgical findings in dogs with degenerative lumbosacral stenosis.

    PubMed

    Suwankong, Niyada; Voorhout, George; Hazewinkel, Herman A W; Meij, Björn P

    2006-12-15

    To assess the extent of agreement between computed tomography (CT), magnetic resonance imaging (MRI), and surgical findings in dogs with degenerative lumbosacral stenosis. Observational study. 35 dogs with degenerative lumbosacral stenosis. Results of preoperative CT and MRI were compared with surgical findings with respect to degree and location of disk protrusion, position of the dural sac, amount of epidural fat, and swelling of spinal nerve roots. A lumbosacral step was seen on radiographic images from 22 of 32 (69%) dogs, on CT images from 23 of 35 (66%) dogs, and on MR images from 21 of 35 (60%) dogs. Most dogs had slight or moderate disk protrusion that was centrally located. There was substantial or near perfect agreement between CT and MRI findings in regard to degree of disk protrusion (kappa, 0.88), location of disk protrusion (0.63), position of the dural sac (0.89), amount of epidural fat (0.72), and swelling of spinal nerve roots (0.60). The degree of agreement between CT and surgical findings and between MRI and surgical findings was moderate in regard to degree and location of disk protrusion (kappa, 0.44 to 0.56) and swelling of spinal nerve roots (0.40 and 0.50). Results indicate that there is a high degree of agreement between CT and MRI findings in dogs with degenerative lumbosacral stenosis but that the degree of agreement between diagnostic imaging findings and surgical findings is lower.

  3. AGREEMENT BETWEEN MEASURED AND PERCEIVED NUTRITIONAL STATUS REPORTED BY PRESCHOOL CHILDREN’S MOTHERS

    PubMed Central

    Pedraza, Dixis Figueroa; Sousa, Carolina Pereira da Cunha; de Olinda, Ricardo Alves

    2017-01-01

    ABSTRACT Objective: To verify the agreement between nutritional status perceived by mothers and that diagnosed in preschool children, by providing the differences according to children’s sex and age. Methods: Study with data from a cohort of 269 preschool children assisted in public daycare centers of Campina Grande, Paraíba (Northeast Brazil). Children’s information about their date of birth, sex and nutritional status (weight/stature Z scores) was collected. Furthermore, the mothers were asked about their perception of children’s weight. The diagnostic agreement between the measured nutritional status and that perceived by mothers was assessed through the weighted Kappa test, with a 5% significance level. Results: The percentage of disagreement between the measured nutritional status and that perceived by mothers was 32.7%, with Kappa of 0.122, which is considered insignificant. There was a remarkable overweight underestimation (69.6%). Agreement between maternal perception of overweight and the diagnosed nutritional status was higher for older children (36-59 months versus 24-35 months) and for girls. Conclusions: The study regarding maternal perception of preschool children’s nutritional status showed the difficulty that mothers face in recognizing the real nutritional status of their children, especially the underestimation of overweight. Maternal perception of overweight in children is misrepresented in boys and in younger children with more importance. PMID:28977296

  4. Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NF{kappa}B

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

    Eliseev, Roman A.; Schwarz, Edward M.; Zuscik, Michael J.

    2006-01-01

    The transcription factor NF{kappa}B is constitutively activated in various tumor cells where it promotes proliferation and represses apoptosis. The bone morphogenetic proteins (BMPs) delay cell proliferation and promote differentiation and apoptosis of bone cells through activation of Smad downstream effectors and via Smad-independent mechanisms. Thus, NF{kappa}B and BMP pathways play opposing roles in regulating osteoblastic cell fate. Here, we show that in osteosarcoma Saos2 osteoblasts, NF{kappa}B regulates the activity of the BMP/Smad signaling. Inhibition of NF{kappa}B by overexpression of mI{kappa}B leads to the induction of osteoblast differentiation. Saos2 cells overexpressing mI{kappa}B (Saos2-mI{kappa}B) exhibit higher expression of osteoblast phenotypic genes suchmore » as alkaline phosphatase, Runx2 and osteocalcin and are more responsive to BMP2 in comparison to wild-type cells (Saos2-wt) or empty vector infected controls (Saos2-EV). Furthermore, BMP-2 signaling and Smad phosphorylation are significantly increased in Saos2-mI{kappa}B cells in comparison to Saos2-EV cells. Inhibition of NF{kappa}B signaling in Saos2-mI{kappa}B cells is associated with decreased expression of the BMP signaling inhibitor Smad7. While gain of Smad7 function in Saos2-mI{kappa}B cells results in inhibition of BMP signaling, anti-sense knockdown of Smad7 in Saos2-EV cells leads to upregulation of BMP signaling. We therefore conclude that in osteosarcoma Saos2 cells, NF{kappa}B represses BMP/Smad signaling and BMP2-induced differentiation through Smad7.« less

  5. Screening for anti-inflammatory activity of 12 Arnica (Asteraceae) species assessed by inhibition of NF-kappaB and release of human neutrophil elastase.

    PubMed

    Ekenäs, Catarina; Zebrowska, Anna; Schuler, Barbara; Vrede, Tobias; Andreasen, Katarina; Backlund, Anders; Merfort, Irmgard; Bohlin, Lars

    2008-12-01

    Several species in the genus Arnica have been used in traditional medicine to treat inflammatory-related disorders. Extracts of twelve Arnica species and two species closely related to arnica ( Layia hieracioides and Madia sativa) were investigated for inhibition of human neutrophil elastase release and inhibition of transcription factor NF-kappaB. Statistical analyses reveal significant differences in inhibitory capacities between extracts. Sesquiterpene lactones of the helenanolide type, of which some are known inhibitors of human neutrophil elastase release and NF-kappaB, are present in large amounts in the very active extracts of A. montana and A. chamissonis. Furthermore, A. longifolia, which has previously not been investigated, shows a high activity similar to that of A. montana and A. chamissonis in both bioassays. Sesquiterpene lactones of the xanthalongin type are present in large amounts in A. longifolia and other active extracts and would be interesting to evaluate further. COX-2:cyclooxygenase 2 EMSA:electrophoretic mobility shift assay fMLP: N-formyl-methionyl-leucyl-phenylalanine HaCaT:human keratinocyte HNE:human neutrophil elastase IkappaB:inhibitory subunit of kappaB iNOS:inducible nitric oxide synthase NF-kappaB:nuclear factor kappaB PAF:platelet activating factor STL:sesquiterpene lactone TNF-alpha:tumor necrosis factor alpha.

  6. NF-kappaB transcription factor is required for inhibitory avoidance long-term memory in mice.

    PubMed

    Freudenthal, Ramiro; Boccia, Mariano M; Acosta, Gabriela B; Blake, Mariano G; Merlo, Emiliano; Baratti, Carlos M; Romano, Arturo

    2005-05-01

    Although it is generally accepted that memory consolidation requires regulation of gene expression, only a few transcription factors (TFs) have been clearly demonstrated to be specifically involved in this process. Increasing research data point to the participation of the Rel/nuclear factor-kappaB (NF-kappaB) family of TFs in memory and neural plasticity. Here we found that two independent inhibitors of NF-kappaB induced memory impairment in the one-trial step-through inhibitory avoidance paradigm in mice: post-training administration of the drug sulfasalazine and 2 h pretraining administration of a double-stranded DNA oligonucleotide containing the NF-kappaB consensus sequence (kappaB decoy). Conversely, one base mutation of the kappaB decoy (mut-kappaB decoy) injection did not affect long-term memory. Accordingly, the kappaB decoy inhibited NF-kappaB in hippocampus 2 h after injection but no inhibition was found with mut-kappaB decoy administration. A temporal course of hippocampal NF-kappaB activity after training was determined. Unexpectedly, an inhibition of NF-kappaB was found 15 min after training in shocked and unshocked groups when compared with the naïve group. Hippocampal NF-kappaB was activated 45 min after training in both shocked and unshocked groups, decreasing 1 h after training and returning to basal levels 2 and 4 h after training. On the basis of the latter results, we propose that activation of NF-kappaB in hippocampus is part of the molecular mechanism involved in the storage of contextual features that constitute the conditioned stimulus representation. The results presented here provide the first evidence to support NF-kappaB activity being regulated in hippocampus during consolidation, stressing the role of this TF as a conserved molecular mechanism for memory storage.

  7. I did eat my vegetables. Agreement between parent and child food intake diaries.

    PubMed

    Rangelov, Natalie; Suggs, L Suzanne; Marques-Vidal, Pedro

    2016-12-01

    To assess the level of agreement between children and their parents when reporting a child's food consumption. Cross-sectional study in which children and parents independently completed 7 d food diaries describing the foods and drinks the child consumed at every meal and snack. The association between child and parent reporting was assessed for nineteen food groups using Kendall's tau-b non-parametric correlations, Spearman's rank correlations, kappa coefficients and Lin's concordance measure of agreement. Results were also stratified by gender of the child and his/her grade at school. Households in Ticino, Switzerland, April-June 2014. Two hundred and ninety-nine children aged 6-12 years and one of their parents participated, with 264 providing complete data (35 % completion rate). Results showed a high level of agreement between child and parent reporting. Spearman correlations ranged from 0·55 (sauces) and 0·57 (fatty meat) to 0·80 (fruit), 0·83 (starchy foods) and 0·84 (pastries). All nineteen Spearman correlations were significant at the 0·001 level. Kendall's tau-b correlations ranged from 0·44 (fat meat) to 0·81 (puff pastry). Kappa values showed low to high levels of agreement, ranging from 0·15 (sweets) to 0·77 (puff pastry). Lin's concordance correlation coefficients ranged from 0·39 (whole grains) to 0·86 (puff pastry). When assessing the eating behaviour of children using a 7 d food diary, children's reports might be as reliable as their parents'.

  8. Purinergic signaling is required for fluid shear stress-induced NF-{kappa}B translocation in osteoblasts

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

    Genetos, Damian C., E-mail: dgenetos@ucdavis.edu; Karin, Norman J.; Geist, Derik J.

    2011-04-01

    Fluid shear stress regulates gene expression in osteoblasts, in part by activation of the transcription factor NF-{kappa}B. We examined whether this process was under the control of purinoceptor activation. MC3T3-E1 osteoblasts under static conditions expressed the NF-{kappa}B inhibitory protein I{kappa}B{alpha} and exhibited cytosolic localization of NF-{kappa}B. Under fluid shear stress, I{kappa}B{alpha} levels decreased, and concomitant nuclear localization of NF-{kappa}B was observed. Cells exposed to fluid shear stress in ATP-depleted medium exhibited no significant reduction in I{kappa}B{alpha}, and NF-{kappa}B remained within the cytosol. Similar results were found using oxidized ATP or Brilliant Blue G, P2X{sub 7} receptor antagonists, indicating that themore » P2X{sub 7} receptor is responsible for fluid shear-stress-induced I{kappa}B{alpha} degradation and nuclear accumulation of NF-{kappa}B. Pharmacologic blockage of the P2Y6 receptor also prevented shear-induced I{kappa}B{alpha} degradation. These phenomena involved neither ERK1/2 signaling nor autocrine activation by P2X{sub 7}-generated lysophosphatidic acid. Our results suggest that fluid shear stress regulates NF-{kappa}B activity through the P2Y{sub 6} and P2X{sub 7} receptor.« less

  9. NF-kappaB activation in cancer: a challenge for ubiquitination- and proteasome-based therapeutic approach.

    PubMed

    Amit, Sharon; Ben-Neriah, Yinon

    2003-02-01

    Nuclear factor-kappa B (NF-kappaB) activation relies primarily on ubiquitin-mediated degradation of its inhibitor IkappaB. NF-kappaB plays an important role in many aspects of tumor development, progression, and therapy. Some types of cancer are characterized by constitutive NF-kappaB activity, whereas in others such activity is induced following chemotherapy. NF-kappaB-harboring tumors are generally resistant to chemotherapy and their eradication requires NF-kappaB inhibition. Here we describe the mechanisms of NF-kappaB activation in normal and tumor cells, review prevalent notions regarding the factor's contribution to tumorigenicity and discuss present and future options for NF-kappaB inhibition in cancer. The ubiquitination-mediated activation of NF-kappaB is intersected by another cancer-associated protein, beta-catenin. We, therefore, compare the related activation pathways and discuss the possibility of differential targeting of the involved ubiquitination machinery. Copyright 2002 Elsevier Science Ltd.

  10. Systematic reviews need to consider applicability to disadvantaged populations: inter-rater agreement for a health equity plausibility algorithm

    PubMed Central

    2012-01-01

    Background Systematic reviews have been challenged to consider effects on disadvantaged groups. A priori specification of subgroup analyses is recommended to increase the credibility of these analyses. This study aimed to develop and assess inter-rater agreement for an algorithm for systematic review authors to predict whether differences in effect measures are likely for disadvantaged populations relative to advantaged populations (only relative effect measures were addressed). Methods A health equity plausibility algorithm was developed using clinimetric methods with three items based on literature review, key informant interviews and methodology studies. The three items dealt with the plausibility of differences in relative effects across sex or socioeconomic status (SES) due to: 1) patient characteristics; 2) intervention delivery (i.e., implementation); and 3) comparators. Thirty-five respondents (consisting of clinicians, methodologists and research users) assessed the likelihood of differences across sex and SES for ten systematic reviews with these questions. We assessed inter-rater reliability using Fleiss multi-rater kappa. Results The proportion agreement was 66% for patient characteristics (95% confidence interval: 61%-71%), 67% for intervention delivery (95% confidence interval: 62% to 72%) and 55% for the comparator (95% confidence interval: 50% to 60%). Inter-rater kappa, assessed with Fleiss kappa, ranged from 0 to 0.199, representing very low agreement beyond chance. Conclusions Users of systematic reviews rated that important differences in relative effects across sex and socioeconomic status were plausible for a range of individual and population-level interventions. However, there was very low inter-rater agreement for these assessments. There is an unmet need for discussion of plausibility of differential effects in systematic reviews. Increased consideration of external validity and applicability to different populations and settings is

  11. Systematic reviews need to consider applicability to disadvantaged populations: inter-rater agreement for a health equity plausibility algorithm.

    PubMed

    Welch, Vivian; Brand, Kevin; Kristjansson, Elizabeth; Smylie, Janet; Wells, George; Tugwell, Peter

    2012-12-19

    Systematic reviews have been challenged to consider effects on disadvantaged groups. A priori specification of subgroup analyses is recommended to increase the credibility of these analyses. This study aimed to develop and assess inter-rater agreement for an algorithm for systematic review authors to predict whether differences in effect measures are likely for disadvantaged populations relative to advantaged populations (only relative effect measures were addressed). A health equity plausibility algorithm was developed using clinimetric methods with three items based on literature review, key informant interviews and methodology studies. The three items dealt with the plausibility of differences in relative effects across sex or socioeconomic status (SES) due to: 1) patient characteristics; 2) intervention delivery (i.e., implementation); and 3) comparators. Thirty-five respondents (consisting of clinicians, methodologists and research users) assessed the likelihood of differences across sex and SES for ten systematic reviews with these questions. We assessed inter-rater reliability using Fleiss multi-rater kappa. The proportion agreement was 66% for patient characteristics (95% confidence interval: 61%-71%), 67% for intervention delivery (95% confidence interval: 62% to 72%) and 55% for the comparator (95% confidence interval: 50% to 60%). Inter-rater kappa, assessed with Fleiss kappa, ranged from 0 to 0.199, representing very low agreement beyond chance. Users of systematic reviews rated that important differences in relative effects across sex and socioeconomic status were plausible for a range of individual and population-level interventions. However, there was very low inter-rater agreement for these assessments. There is an unmet need for discussion of plausibility of differential effects in systematic reviews. Increased consideration of external validity and applicability to different populations and settings is warranted in systematic reviews to meet this

  12. Mechanisms for kappa reduction and color removal by xylanases

    Treesearch

    Thomas W. Jeffries; Mark Davis; Brian Rosin; Larry L. Landucci

    1998-01-01

    Xylanases reduce kappa and release UV- and visibly absorptive materials from kraft pulps. The extents of these actions depend on the origin and processing of the pulp, access of enzymes to the substrate, and the natures of the enzymes. Hexeneuronic acid (HexA) is a component of kraft pulp xylans that accounts for a fraction of the kappa content. It absorbs strongly in...

  13. Ion and electron Kappa distribution functions in the plasma sheet.

    NASA Astrophysics Data System (ADS)

    Moya, P. S.; Stepanova, M. V.; Espinoza, C.; Antonova, E. E.; Valdivia, J. A.

    2017-12-01

    We present a study of ion and electron flux spectra in the Earth's plasma sheet using kappa distribution functions. Satellite data from the THEMIS mission were collected for thousands of crossings through the plasma sheet, between 7 and 35 Re and during the years 2008-2009. The events were separated according to the geomagnetic activity at the time. Our results show the distribution of the kappa index and characteristic energies across the plasma sheet and its evolution with distance to Earth for quiet times and for the substorm expansion and recovery phases. For the ions, it is observed that the kappa values tend to decrease outwards and that this effect is more significant in the dusk sector, where the smallest values are found for distances beyond 15 Re. The main effect of the substorms appears as an enhancement of this behavior. The electrons show a much more homogeneous distribution in quiet times, with a mild tendency for larger kappa values at larger distances. During substorms, the kappa values tend to equalize and appear very homogenous during expansion. However, they exhibit a significant increase in the dusk sector during the recovery substorm phase. Finally, we observe that the characteristic energy of the particles during substorms increases and concentrate at distances less than 15 Re.

  14. Inter-observer and intra-observer agreement between embryologists during selection of a single Day 5 embryo for transfer: a multicenter study.

    PubMed

    Storr, Ashleigh; Venetis, Christos A; Cooke, Simon; Kilani, Suha; Ledger, William

    2017-02-01

    What is the inter-observer and intra-observer agreement between embryologists when selecting a single Day 5 embryo for transfer? The inter-observer and intra-observer agreement between embryologists when selecting a single Day 5 embryo for transfer was generally good, although not optimal, even among experienced embryologists. Previous research on the morphological assessment of early stage (two pronuclei to Day 3) embryos has shown varying levels of inter-observer and intra-observer agreement. However, single blastocyst transfer is now becoming increasingly popular and there are no published data that assess inter-observer and intra-observer agreement when selecting a single embryo for Day 5 transfer. This was a prospective study involving 10 embryologists working at five different IVF clinics within a single organization between July 2013 and November 2015. The top 10 embryologists were selected based on their yearly Quality Assurance Program scores for blastocyst grading and were asked to morphologically grade all Day 5 embryos and choose a single embryo for transfer in a survey of 100 cases using 2D images. A total of 1000 decisions were therefore assessed. For each case, Day 5 images were shown, followed by a Day 3 and Day 5 image of the same embryo. Subgroup analyses were also performed based on the following characteristics of embryologists: the level of clinical embryology experience in the laboratory; amount of research experience; number of days per week spent grading embryos. The agreement between these embryologists and the one that scored the embryos on the actual day of transfer was also evaluated. Inter-observer and intra-observer variability was assessed using the kappa coefficient to evaluate the extent of agreement. This study showed that all 10 embryologists agreed on the embryo chosen for transfer in 50 out of 100 cases. In 93 out of 100 cases, at least 6 out of the 10 embryologists agreed. The inter-observer and intra-observer agreement among

  15. Receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in gingival crevicular fluid

    PubMed Central

    Sarlati, Fatemeh; Sattari, Mandana; Razzaghi, Shilan; Nasiri, Malihe

    2012-01-01

    Background: Osteoclastogenesis is coordinated by the interaction of three members of the tumor necrosis factor (TNF) superfamily: Osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK). The aim of this study was to investigate RANKL and OPG levels, and their relative ratio in gingival crevicular fluid (GCF) of patients with chronic and aggressive periodontitis, as well as healthy controls. Materials and Methods: In this analytical study, GCF was obtained from healthy (n = 10), mild chronic periodontitis (n = 18), moderate chronic periodontitis (n = 18), severe chronic periodontitis (n = 20), and generalized aggressive periodontitis (n = 20) subjects. RANKL and OPG concentrations were measured by enzyme-linked immunosorbent assay. Statistical tests used were Kruskal–Wallis test, Mann–Whitney U rank sum test, and Spearman's rank correlation analysis. The level of statistical significance was set at P < 0.05. Results: Mean RANKL concentration showed no statistically significant differences between groups (P = 0.58). There were also no significant differences between mean OPG concentration in the five groups (P = 0.0.56). Moreover, relative RANKL/OPG ratio did not reveal a significant difference between the three study group subjects: healthy, chronic periodontitis (mild, moderate, severe), and aggressive periodontitis (P = 0.41). There was statistically significant correlation between the concentration of sRANKL and Clinical Attachment Level (CAL) in moderate chronic periodontitis patients (R = 0.48, P = 0.04). There was also negative correlation between OPG concentration and CAL in moderate chronic periodontitis patients, although not significant (R = −0.13). Conclusion: RANKL was prominent in periodontitis sites, especially in moderate periodontitis patients, whereas OPG was not detectable in some diseased sites with bleeding on probing, supporting the role of these two molecules in

  16. Agreement between T2 and haste sequences in the evaluation of thoracolumbar intervertebral disc disease in dogs.

    PubMed

    Mankin, Joseph M; Hecht, Silke; Thomas, William B

    2012-01-01

    The purpose of this study was to compare half-Fourier-acquisition single-shot turbo spin-echo (HASTE) and T2-weighted (T2-W) sequences in dogs with thoracolumbar disc extrusion. MRI studies in 60 dogs (767 individual intervertebral disc spaces) were evaluated. Agreement between T2-W and HASTE sequences was assessed for two criteria: presence of an extradural lesion and treatment recommendation. There was moderate agreement between T2-W and HASTE sequences as to presence of an extradural lesion (kappa = 0.575). HASTE was in agreement in 96.1% of the sites where no extradural lesion was identified on T2-W images, but only in 58.1% of the sites where extradural lesions were identified on T2-W images. There was also moderate agreement between T2-W and HASTE sequences as to treatment recommendations (kappa = 0.476). HASTE was in agreement in 98.4% of the sites where a lesion was considered nonsurgical on T2 but only 82.1% of sites a lesion was considered surgical on T2. In 1.0% of sites considered not surgical and in 9.8% of sites considered equivocal based on T2-W images, a surgical lesion was identified on HASTE. Acquisition of a HASTE sequence in addition to conventional sequences may be beneficial in determining the severity of spinal cord compression in some cases when evaluating the canine spine.

  17. Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls.

    PubMed

    Baud, Véronique; Karin, Michael

    2009-01-01

    Nuclear factor kappaB (NF-kappaB) transcription factors have a key role in many physiological processes such as innate and adaptive immune responses, cell proliferation, cell death, and inflammation. It has become clear that aberrant regulation of NF-kappaB and the signalling pathways that control its activity are involved in cancer development and progression, as well as in resistance to chemotherapy and radiotherapy. This article discusses recent evidence from cancer genetics and cancer genome studies that support the involvement of NF-kappaB in human cancer, particularly in multiple myeloma. The therapeutic potential and benefit of targeting NF-kappaB in cancer, and the possible complications and pitfalls of such an approach, are explored.

  18. Kappa2 opioid receptor subtype binding requires the presence of the DOR-1 gene.

    PubMed

    Ansonoff, Michael A; Wen, Ting; Pintar, John E

    2010-01-01

    Over the past several years substantial evidence has documented that opioid receptor homo- and heterodimers form in cell lines expressing one or more of the opioid receptors. We used opioid receptor knockout mice to determine whether in vivo pharmacological characteristics of kappa1 and kappa2 opioid receptors changed following knockout of specific opioid receptors. Using displacement of the general opioid ligand diprenorphine, we observed that occupancy or knockout of the DOR-1 gene increases the binding density of kappa1 receptors and eliminates kappa2 receptors in crude membrane preparations while the total density of kappa opioid binding sites is unchanged. Further, the analgesic potency of U69,593 in cumulative dose response curves is enhanced in mice lacking the DOR-1 gene. These results demonstrate that the DOR-1 gene is required for the expression of the kappa2 opioid receptor subtype and are consistent with the possibility that a KOR-1/DOR-1 heterodimer mediates kappa2 pharmacology.

  19. The Treatment of Brain Arteriovenous Malformation Study (TOBAS): A preliminary inter- and intra-rater agreement study on patient management.

    PubMed

    Fahed, Robert; Batista, André L; Darsaut, Tim E; Gentric, Jean-Christophe; Ducroux, Célina; Chaalala, Chiraz; Roberge, David; Bojanowski, Michel W; Weill, Alain; Roy, Daniel; Magro, Elsa; Raymond, Jean

    2017-07-01

    The best management of brain arteriovenous malformation (bAVM) patients remains unknown. Randomized allocation may be more readily accepted when there is uncertainty and disagreement regarding the management of potential participants. In planning for a trial, we aimed to assess variability and agreement among physicians managing bAVM patients. A portfolio composed of 35 patients was sent to 47 clinicians of various specialties managing bAVM patients. For each patient, physicians were asked their best management decision (surgery/embolization/radiosurgery/conservative), their confidence level, and whether they would include the patient in a randomized trial comparing conservative and curative management. Seven physicians, who had access to all images of each patient, independently responded twice, to assess inter and intra-rater agreement using kappa statistics. The inter-rater agreement (30 raters, including 16 neuroradiologists) for best management decision was only "fair" (κ [95%CI]=0.210[0.157; 0.295]). Agreement remained below 'substantial' (κ<.6) between physicians of the same specialty, and when no distinctions were made between various treatments (when responses were dichotomized as conservative versus curative). With access to all images the inter-rater agreement remained fair. The intra-rater agreement reached "substantial" only for the dichotomized decisions. Responding clinicians were willing to include 54.4% of patients (mainly unruptured bAVMs) in a randomized trial. There is a lack of agreement among clinicians involved in the management of bAVM patients. In this study a substantial proportion of clinicians were willing to offer randomized allocation of management options to a substantial number of patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Pitfalls in the statistical examination and interpretation of the correspondence between physician and patient satisfaction ratings and their relevance for shared decision making research

    PubMed Central

    2011-01-01

    Background The correspondence of satisfaction ratings between physicians and patients can be assessed on different dimensions. One may examine whether they differ between the two groups or focus on measures of association or agreement. The aim of our study was to evaluate methodological difficulties in calculating the correspondence between patient and physician satisfaction ratings and to show the relevance for shared decision making research. Methods We utilised a structured tool for cardiovascular prevention (arriba™) in a pragmatic cluster-randomised controlled trial. Correspondence between patient and physician satisfaction ratings after individual primary care consultations was assessed using the Patient Participation Scale (PPS). We used the Wilcoxon signed-rank test, the marginal homogeneity test, Kendall's tau-b, weighted kappa, percentage of agreement, and the Bland-Altman method to measure differences, associations, and agreement between physicians and patients. Results Statistical measures signal large differences between patient and physician satisfaction ratings with more favourable ratings provided by patients and a low correspondence regardless of group allocation. Closer examination of the raw data revealed a high ceiling effect of satisfaction ratings and only slight disagreement regarding the distributions of differences between physicians' and patients' ratings. Conclusions Traditional statistical measures of association and agreement are not able to capture a clinically relevant appreciation of the physician-patient relationship by both parties in skewed satisfaction ratings. Only the Bland-Altman method for assessing agreement augmented by bar charts of differences was able to indicate this. Trial registration ISRCTN: ISRCT71348772 PMID:21592337

  1. 40 CFR 721.10356 - Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-. 721.10356 Section 721.10356 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific...

  2. 40 CFR 721.10356 - Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-. 721.10356 Section 721.10356 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific...

  3. 40 CFR 721.10356 - Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-. 721.10356 Section 721.10356 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific...

  4. Salicylates inhibit flavivirus replication independently of blocking nuclear factor kappa B activation.

    PubMed

    Liao, C L; Lin, Y L; Wu, B C; Tsao, C H; Wang, M C; Liu, C I; Huang, Y L; Chen, J H; Wang, J P; Chen, L K

    2001-09-01

    Flaviviruses comprise a positive-sense RNA genome that replicates exclusively in the cytoplasm of infected cells. Whether flaviviruses require an activated nuclear factor(s) to complete their life cycle and trigger apoptosis in infected cells remains elusive. Flavivirus infections quickly activate nuclear factor kappa B (NF-kappaB), and salicylates have been shown to inhibit NF-kappaB activation. In this study, we investigated whether salicylates suppress flavivirus replication and virus-induced apoptosis in cultured cells. In a dose-dependent inhibition, we found salicylates within a range of 1 to 5 mM not only restricted flavivirus replication but also abrogated flavivirus-triggered apoptosis. However, flavivirus replication was not affected by a specific NF-kappaB peptide inhibitor, SN50, and a proteosome inhibitor, lactacystin. Flaviviruses also replicated and triggered apoptosis in cells stably expressing IkappaBalpha-DeltaN, a dominant-negative mutant that antagonizes NF-kappaB activation, as readily as in wild-type BHK-21 cells, suggesting that NF-kappaB activation is not essential for either flavivirus replication or flavivirus-induced apoptosis. Salicylates still diminished flavivirus replication and blocked apoptosis in the same IkappaBalpha-DeltaN cells. This inhibition of flaviviruses by salicylates could be partially reversed by a specific p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Together, these results show that the mechanism by which salicylates suppress flavivirus infection may involve p38 MAP kinase activity but is independent of blocking the NF-kappaB pathway.

  5. Relationship and inter observer agreement of tooth and face forms in a Saudi subpopulation.

    PubMed

    Habib, Syed Rashid; Shiddi, Ibraheem Al; Al-Sufyani, Mohammed D; Althobaiti, Fahad A

    2015-04-01

    To determine the relationship of tooth form with the face form by different observers and further investigate the inter observer agreement on tooth forms, face forms, their relationship among male Saudis. A comparative cross-sectional study. Department of Prosthodontics, College of Dentistry, King Saud University, Riyadh, KSA, from February till August 2013. Ninety four male participants aged 18 - 35 years were randomly recruited for the study. Full-face and anterior teeth (intraoral) digital photographs in the frontal plane were recorded. The outline tracings of the face and the tooth were obtained using Autocad (version 2010) software. The outline of the tooth was enlarged proportionately, without altering the length to width ratio to fit the face outline. The outlines were then evaluated visually by 6 prosthodontists and results were tabulated. The most common type of face form (49.65%) and tooth form (56.38%) was square tapering. Using the visual method, a good relationship (31.41%), moderate relationship (35.31%), weak relationship (19.68%) and no relationship (13.65%) between the tooth form and face form was found by the observers. Overall kappa for inter observer agreement on face form, tooth form and their relationship was 0.24, 0.17 and 0.26 respectively. The kappa values showed a fair agreement between the observers. The study results indicated that there was no highly defined relationship between the tooth form and face form in the studied Saudi subpopulation. A fair agreement was found between the observers for classifying the tooth forms, face froms and their relationship.

  6. Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

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

    Baldini, Elizabeth H., E-mail: ebaldini@partners.org; Abrams, Ross A.; Bosch, Walter

    Purpose: The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials: Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneousmore » truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions: For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.« less

  7. Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

    PubMed Central

    Baldini, Elizabeth H.; Abrams, Ross A.; Bosch, Walter; Roberge, David; Haas, Rick L.M.; Catton, Charles N.; Indelicato, Daniel J.; Olsen, Jeffrey R.; Deville, Curtiland; Chen, Yen-Lin; Finkelstein, Steven E.; DeLaney, Thomas F.; Wang, Dian

    2015-01-01

    Purpose The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed. PMID:26194680

  8. Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

    NASA Technical Reports Server (NTRS)

    Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

    1999-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

  9. MRMC analysis of agreement studies

    NASA Astrophysics Data System (ADS)

    Gallas, Brandon D.; Anam, Amrita; Chen, Weijie; Wunderlich, Adam; Zhang, Zhiwei

    2016-03-01

    The purpose of this work is to present and evaluate methods based on U-statistics to compare intra- or inter-reader agreement across different imaging modalities. We apply these methods to multi-reader multi-case (MRMC) studies. We measure reader-averaged agreement and estimate its variance accounting for the variability from readers and cases (an MRMC analysis). In our application, pathologists (readers) evaluate patient tissue mounted on glass slides (cases) in two ways. They evaluate the slides on a microscope (reference modality) and they evaluate digital scans of the slides on a computer display (new modality). In the current work, we consider concordance as the agreement measure, but many of the concepts outlined here apply to other agreement measures. Concordance is the probability that two readers rank two cases in the same order. Concordance can be estimated with a U-statistic and thus it has some nice properties: it is unbiased, asymptotically normal, and its variance is given by an explicit formula. Another property of a U-statistic is that it is symmetric in its inputs; it doesn't matter which reader is listed first or which case is listed first, the result is the same. Using this property and a few tricks while building the U-statistic kernel for concordance, we get a mathematically tractable problem and efficient software. Simulations show that our variance and covariance estimates are unbiased.

  10. Multi-rater Agreement in the Assessment of Anterior Cruciate Ligament Reconstruction Failure. A Radiographic and Video Analysis of the MARS Cohort

    PubMed Central

    Matava, Matthew J.; Arciero, Robert A.; Baumgarten, Keith M.; Carey, James L.; DeBerardino, Thomas M.; Hame, Sharon L.; Hannafin, Jo A.; Miller, Bruce S.; Nissen, Carl W.; Taft, Timothy N.; Wolf, Brian R.; Wright, Rick W.

    2015-01-01

    Background ACL reconstruction failure occurs in up to 10% of cases. Technical errors are considered the most common cause of graft failure despite the absence of validated studies. There is limited data regarding the agreement among orthopedic surgeons in terms of the etiology of primary ACL reconstruction failure and accuracy of graft tunnel placement. Purpose The purpose of this study is to test the hypothesis that experienced knee surgeons have a high level of inter-observer reliability in the agreement of the etiology of the primary ACL reconstruction failure, anatomical graft characteristics, tunnel placement. Methods Twenty cases of revision ACL reconstruction were randomly selected from the MARS database. Each case included the patient's history, standardized radiographs, and a concise 30-second arthroscopic video taken at the time of revision demonstrating the graft remnant and location of the tunnel apertures. 10 MARS surgeons not involved with the primary surgery reviewed all 20 cases. Each surgeon completed a two-part questionnaire dealing with each surgeon's training and practice as well as the placement of the femoral and tibial tunnels, condition of the primary graft, and the surgeon's opinion as to the etiology of graft failure. Inter-rater agreement was determined for each question. Inter-rater agreement was determined for each question with the kappa coefficient and prevalence adjusted bias adjusted kappa (PABAK). Results The 10 reviewers were in practice an average of 14 years. All performed at least 25 ACL reconstructions per year and 9 were fellowship-trained in sports medicine. There was wide variability in agreement among knee experts as to the specific etiology of ACL graft failure. When specifically asked about technical error as the cause for failure, inter-observer agreement was only slight (prevalence adjusted bias adjusted kappa [PABAK]: 0.26). There was fair overall agreement on ideal femoral tunnel placement (PABAK: 0.55), but only

  11. Chronic intermittent hypoxia activates nuclear factor-{kappa}B in cardiovascular tissues in vivo

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

    Greenberg, Harly; Ye Xiaobing; Wilson, David

    2006-05-05

    Obstructive sleep apnea (OSA) is an important risk factor for cardiovascular morbidity and mortality. The mechanisms through which OSA promotes the development of cardiovascular disease are poorly understood. In this study, we tested the hypotheses that chronic exposure to intermittent hypoxia and reoxygenation (CIH) is a major pathologic factor causing cardiovascular inflammation, and that CIH-induces cardiovascular inflammation and pathology by activating the NF-{kappa}B pathway. We demonstrated that exposure of mice to CIH activated NF-{kappa}B in cardiovascular tissues, and that OSA patients had markedly elevated monocyte NF-{kappa}B activity, which was significantly decreased when obstructive apneas and their resultant CIH were eliminatedmore » by nocturnal CPAP therapy. The elevated NF-{kappa}B activity induced by CIH is accompanied by and temporally correlated to the increased expression of iNOS protein, a putative and important NF-{kappa}B-dependent gene product. Thus, CIH-mediated NF-{kappa}B activation may be a molecular mechanism linking OSA and cardiovascular pathologies seen in OSA patients.« less

  12. Agreement between ethnicity recorded in two New Zealand health databases: effects of discordance on cardiovascular outcome measures (PREDICT CVD3).

    PubMed

    Marshall, Roger J; Zhang, Zhongqian; Broad, Joanna B; Wells, Sue

    2007-06-01

    To assess agreement between ethnicity as recorded by two independent databases in New Zealand, PREDICT and the National Health Index (NHI), and to assess sensitivity of ethnic-specific measures of health outcomes to either ethnicity record. Patients assessed using PREDICT form the study cohort. Ethnicity was recorded for PREDICT and an associated NHI ethnicity code was identified by merge-match linking on an encrypted NHI number. Agreement between ethnicity measures was assessed by kappa scores and scaled rectangle diagrams. A cohort of 18,239 individuals was linked in both PREDICT and NHI databases. The agreement between ethnicity classifications was reasonably good, with overall kappa coefficient of 0.82. There was better agreement for women than men and agreement improved with age and with time since the PREDICT system has been operational. Ethnic-specific cardiovascular (CVD) hospital admission rates were sensitive to ethnicity coding by NHI or PREDICT; rate ratios for ethnic groups, relative to European, based on PREDICT were attenuated towards the null relative to the NHI classification. Agreement between ethnicity was moderately good. Discordances that do exist do not have a substantial effect on prevalence-based measures of effect; however, they do on measurement of the admission of CVD. Different categorisations of ethnicity data from routine (and other) databases can lead to different ethnic-specific estimates of epidemiological effects. There is an imperative to record ethnicity in a rational, systematic and consistent way.

  13. EWS-FLI1 inhibits TNF{alpha}-induced NF{kappa}B-dependent transcription in Ewing sarcoma cells

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

    Lagirand-Cantaloube, Julie, E-mail: julie.cantaloube@crbm.cnrs.fr; Laud, Karine, E-mail: karine.laud@curie.fr; Institut Curie, Genetique et biologie des cancers, Paris

    2010-09-03

    Research highlights: {yields} EWS-FLI1 interferes with TNF-induced activation of NF{kappa}B in Ewing sarcoma cells. {yields} EWS-FLI1 knockdown in Ewing sarcoma cells increases TNF-induced NF{kappa}B binding to DNA. {yields} EWS-FLI1 reduces TNF-stimulated NF{kappa}B-dependent transcriptional activation. {yields} Constitutive NF{kappa}B activity is not affected by EWS-FLI1. {yields} EWS-FLI1 physically interacts with NF{kappa}B p65 in vivo. -- Abstract: Ewing sarcoma is primarily caused by a t(11;22) chromosomal translocation encoding the EWS-FLI1 fusion protein. To exert its oncogenic function, EWS-FLI1 acts as an aberrant transcription factor, broadly altering the gene expression profile of tumor cells. Nuclear factor-kappaB (NF{kappa}B) is a tightly regulated transcription factor controllingmore » cell survival, proliferation and differentiation, as well as tumorigenesis. NF{kappa}B activity is very low in unstimulated Ewing sarcoma cells, but can be induced in response to tumor necrosis factor (TNF). We wondered whether NF{kappa}B activity could be modulated by EWS-FLI1 in Ewing sarcoma. Using a knockdown approach in Ewing sarcoma cells, we demonstrated that EWS-FLI1 has no influence on NF{kappa}B basal activity, but impairs TNF-induced NF{kappa}B-driven transcription, at least in part through inhibition of NF{kappa}B binding to DNA. We detected an in vivo physical interaction between the fusion protein and NF{kappa}B p65, which could mediate these effects. Our findings suggest that, besides directly controlling the activity of its primary target promoters, EWS-FLI1 can also indirectly influence gene expression in tumor cells by modulating the activity of key transcription factors such as NF{kappa}B.« less

  14. Regulation of NF-{kappa}B activity in astrocytes: effects of flavonoids at dietary-relevant concentrations

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

    Spilsbury, Alison; Vauzour, David; Spencer, Jeremy P.E.

    Highlights: Black-Right-Pointing-Pointer We tested the hypothesis that low concentrations of flavonoids inhibit NF-{kappa}B in astrocytes. Black-Right-Pointing-Pointer Primary cultured astrocytes possess a functional {kappa}B-system, measured using luciferase assays. Black-Right-Pointing-Pointer Seven flavonoids (100 nM-1 {mu}M) failed to reduce NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer Four flavonoids (100 nM-1 {mu}M) failed to reduce TNFa-stimulated NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer (-)-Epicatechin did not regulate nuclear translocation of the NF-{kappa}B subunit, p65. -- Abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Sustained activation of nuclear transcription factor {kappa}B (NF-{kappa}B) is thought to play an importantmore » role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-{kappa}B signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNF{alpha}, 150 ng/ml) increased NF-{kappa}B-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative I{kappa}B{alpha} construct. In addition, TNF{alpha} increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-{kappa}B activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((-)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1-1 {mu}M) for 18 h. None of the flavonoids modulated constitutive or

  15. Transcription factor NF-kappaB participates in regulation of epithelial cell turnover in the colon.

    PubMed

    Inan, M S; Tolmacheva, V; Wang, Q S; Rosenberg, D W; Giardina, C

    2000-12-01

    The transcription factor nuclear factor (NF)-kappaB regulates the expression of genes that can influence cell proliferation and death. Here we analyze the contribution of NF-kappaB to the regulation of epithelial cell turnover in the colon. Immunohistochemical, immunoblot, and DNA binding analyses indicate that NF-kappaB complexes change as colonocytes mature: p65-p50 complexes predominate in proliferating epithelial cells of the colon, whereas the p50-p50 dimer is prevalent in mature epithelial cells. NF-kappaB1 (p50) knockout mice were used to study the role of NF-kappaB in regulating epithelial cell turnover. Knockout animals lacked detectable NF-kappaB DNA binding activity in isolated epithelial cells and had significantly longer crypts with a more extensive proliferative zone than their wild-type counterparts (as determined by proliferating cell nuclear antigen staining and in vivo bromodeoxyuridine labeling). Gene expression profiling reveals that the NF-kappaB1 knockout mice express the potentially growth-enhancing tumor necrosis factor (TNF)-alpha and nerve growth factor-alpha genes at elevated levels, with in situ hybridization localizing some of the TNF-alpha expression to epithelial cells. TNF-alpha is NF-kappaB regulated, and its upregulation in NF-kappaB1 knockouts may result from an alleviation of p50-p50 repression. NF-kappaB complexes may therefore influence cell proliferation in the colon through their ability to selectively activate and/or repress gene expression.

  16. Level of Agreement and Factors Associated With Discrepancies Between Nationwide Medical History Questionnaires and Hospital Claims Data.

    PubMed

    Kim, Yeon-Yong; Park, Jong Heon; Kang, Hee-Jin; Lee, Eun Joo; Ha, Seongjun; Shin, Soon-Ae

    2017-09-01

    The objectives of this study were to investigate the agreement between medical history questionnaire data and claims data and to identify the factors that were associated with discrepancies between these data types. Data from self-reported questionnaires that assessed an individual's history of hypertension, diabetes mellitus, dyslipidemia, stroke, heart disease, and pulmonary tuberculosis were collected from a general health screening database for 2014. Data for these diseases were collected from a healthcare utilization claims database between 2009 and 2014. Overall agreement, sensitivity, specificity, and kappa values were calculated. Multiple logistic regression analysis was performed to identify factors associated with discrepancies and was adjusted for age, gender, insurance type, insurance contribution, residential area, and comorbidities. Agreement was highest between questionnaire data and claims data based on primary codes up to 1 year before the completion of self-reported questionnaires and was lowest for claims data based on primary and secondary codes up to 5 years before the completion of self-reported questionnaires. When comparing data based on primary codes up to 1 year before the completion of self-reported questionnaires, the overall agreement, sensitivity, specificity, and kappa values ranged from 93.2 to 98.8%, 26.2 to 84.3%, 95.7 to 99.6%, and 0.09 to 0.78, respectively. Agreement was excellent for hypertension and diabetes, fair to good for stroke and heart disease, and poor for pulmonary tuberculosis and dyslipidemia. Women, younger individuals, and employed individuals were most likely to under-report disease. Detailed patient characteristics that had an impact on information bias were identified through the differing levels of agreement.

  17. Analysis of agreement between cardiac risk stratification protocols applied to participants of a center for cardiac rehabilitation

    PubMed Central

    Santos, Ana A. S.; Silva, Anne K. F.; Vanderlei, Franciele M.; Christofaro, Diego G. D.; Gonçalves, Aline F. L.; Vanderlei, Luiz C. M.

    2016-01-01

    ABSTRACT Background Cardiac risk stratification is related to the risk of the occurrence of events induced by exercise. Despite the existence of several protocols to calculate risk stratification, studies indicating that there is similarity between these protocols are still unknown. Objective To evaluate the agreement between the existing protocols on cardiac risk rating in cardiac patients. Method The records of 50 patients from a cardiac rehabilitation program were analyzed, from which the following information was extracted: age, sex, weight, height, clinical diagnosis, medical history, risk factors, associated diseases, and the results from the most recent laboratory and complementary tests performed. This information was used for risk stratification of the patients in the protocols of the American College of Sports Medicine, the Brazilian Society of Cardiology, the American Heart Association, the protocol designed by Frederic J. Pashkow, the American Association of Cardiovascular and Pulmonary Rehabilitation, the Société Française de Cardiologie, and the Sociedad Española de Cardiología. Descriptive statistics were used to characterize the sample and the analysis of agreement between the protocols was calculated using the Kappa coefficient. Differences were considered with a significance level of 5%. Results Of the 21 analyses of agreement, 12 were considered significant between the protocols used for risk classification, with nine classified as moderate and three as low. No agreements were classified as excellent. Different proportions were observed in each risk category, with significant differences between the protocols for all risk categories. Conclusion The agreements between the protocols were considered low and moderate and the risk proportions differed between protocols. PMID:27556385

  18. Agreement in cardiovascular risk rating based on anthropometric parameters

    PubMed Central

    Dantas, Endilly Maria da Silva; Pinto, Cristiane Jordânia; Freitas, Rodrigo Pegado de Abreu; de Medeiros, Anna Cecília Queiroz

    2015-01-01

    Objective To investigate the agreement in evaluation of risk of developing cardiovascular diseases based on anthropometric parameters in young adults. Methods The study included 406 students, measuring weight, height, and waist and neck circumferences. Waist-to-height ratio and the conicity index. The kappa coefficient was used to assess agreement in risk classification for cardiovascular diseases. The positive and negative specific agreement values were calculated as well. The Pearson chi-square (χ2) test was used to assess associations between categorical variables (p<0.05). Results The majority of the parameters assessed (44%) showed slight (k=0.21 to 0.40) and/or poor agreement (k<0.20), with low values of negative specific agreement. The best agreement was observed between waist circumference and waist-to-height ratio both for the general population (k=0.88) and between sexes (k=0.93 to 0.86). There was a significant association (p<0.001) between the risk of cardiovascular diseases and females when using waist circumference and conicity index, and with males when using neck circumference. This resulted in a wide variation in the prevalence of cardiovascular disease risk (5.5%-36.5%), depending on the parameter and the sex that was assessed. Conclusion The results indicate variability in agreement in assessing risk for cardiovascular diseases, based on anthropometric parameters, and which also seems to be influenced by sex. Further studies in the Brazilian population are required to better understand this issue. PMID:26466060

  19. Marginal instability threshold of magnetosonic waves in kappa distributed plasma

    NASA Astrophysics Data System (ADS)

    Bashir, M. F.; Manzoor, M. Z.; Ilie, R.; Yoon, P. H.; Miasli, M. S.

    2017-12-01

    The dispersion relation of magnetosonic wave is studied taking the non-extensive anisotropic counter-streaming distribution which follows the Tsallis statistics. The effects of non-extensivity parameter (q), counter-streaming parameter (P) and the wave-particle interaction is analyzed on the growth rate and the marginal instability threshold condition of Magnetosonic (MS) mode to provide the possible explanation of different regions the Bale-diagram obtained from the solar wind data at 1 AU as represented by the temperature anisotropy ( ) vs plasma beta ( ) solar wind data plot. It is shown that the most of the regions of Bale-diagram is bounded by the MS instability under different condition and best fitted by the non-extesnive distribution. The results for the bi-kappa distribution and bi- Maxwellian distribution are also obtained in the limits and respectively.

  20. 48 CFR 31.109 - Advance agreements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Advance agreements. 31.109... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Applicability 31.109 Advance agreements. (a) The extent of... contractors should seek advance agreement on the treatment of special or unusual costs and on statistical...

  1. 48 CFR 31.109 - Advance agreements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Advance agreements. 31.109... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Applicability 31.109 Advance agreements. (a) The extent of... contractors should seek advance agreement on the treatment of special or unusual costs and on statistical...

  2. 48 CFR 31.109 - Advance agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Advance agreements. 31.109... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Applicability 31.109 Advance agreements. (a) The extent of... contractors should seek advance agreement on the treatment of special or unusual costs and on statistical...

  3. Agreement between Internet-based self- and proxy-reported health care resource utilization and administrative health care claims.

    PubMed

    Palmer, Liisa; Johnston, Stephen S; Rousculp, Matthew D; Chu, Bong-Chul; Nichol, Kristin L; Mahadevia, Parthiv J

    2012-05-01

    Although Internet-based surveys are becoming more common, little is known about agreement between administrative claims data and Internet-based survey self- and proxy-reported health care resource utilization (HCRU) data. This analysis evaluated the level of agreement between self- and proxy-reported HCRU data, as recorded through an Internet-based survey, and administrative claims-based HCRU data. The Child and Household Influenza-Illness and Employee Function study collected self- and proxy-reported HCRU data monthly between November 2007 and May 2008. Data included the occurrence and number of visits to hospitals, emergency departments, urgent care centers, and outpatient offices for a respondent's and his or her household members' care. Administrative claims data from the MarketScan® Databases were assessed during the same time and evaluated relative to survey-based metrics. Only data for individuals with employer-sponsored health care coverage linkable to claims were included. The Kappa (κ) statistic was used to evaluate visit concordance, and the intraclass correlation coefficient was used to describe frequency consistency. Agreement for presence of a health care visit and the number of visits were similar for self- and proxy-reported HCRU data. There was moderate to substantial agreement related to health care visit occurrence between survey-based and claims-based HCRU data for inpatient, emergency department, and office visits (κ: 0.47-0.77). There was less agreement on health care visit frequencies, with intraclass correlation coefficient values ranging from 0.14 to 0.71. This study's agreement values suggest that Internet-based surveys are an effective method to collect self- and proxy-reported HCRU data. These results should increase confidence in the use of the Internet for evaluating disease burden. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  4. Evaluation of Mother-Child Agreement and Factorial Structures of the SCARED Questionnaire in an Italian Clinical Sample

    PubMed Central

    Scaini, Simona; Ogliari, Anna; De Carolis, Ludovica; Bellodi, Laura; Di Serio, Clelia; Brombin, Chiara

    2017-01-01

    Background: A great part of the literature has confirmed the importance of both child and parents reports as source of factual information, especially for childhood emotional syndromes. In our study we aimed at: (i) calculating mother-child agreement and (ii) evaluating factorial structure of the Screen for Child Anxiety Related Emotional Disorders (SCARED) questionnaire in an Italian clinical sample. The novelty of this contribution is two-fold: first, from a clinical point of view, we investigated the parent-child agreement level and examined separately the factorial structures of both parent and child versions of the SCARED for the first time in an Italian clinical sample. Second, unlike previous studies, we used statistical approaches specifically suited to account for the ordinal nature of the collected variables. Method: In a clinical sample of 171 children and adolescents aged 8–18 and their mothers we evaluated inter-rater agreement using weighted kappa indices to assess agreement for each item belonging to a certain SCARED subscale. Exploratory factor analysis for ordinal data was then performed on the polychoric correlation matrix calculated on SCARED items. Differences in the numbers of symptoms reported by children and parents were evaluated as well. Results and Conclusions: Our results reveal moderate to strong mother-child agreement. A significant age effect is present. Two different factorial solutions emerged for parent and child SCARED versions (a 5 factor structure for parents and a 6 factor solution in the child version, including a new factor “Worry about Parents”). This study confirmed the importance of evaluating both child and parent reports in assessment protocols for anxiety disorders. Our findings could help clinicians to determine which information, and from which rater, must be accounted for in evaluating treatment decisions. Moreover, we find that patients characteristics, such as gender and age, should be taken into account when

  5. Agreement between the SCORE and D’Agostino Scales for the Classification of High Cardiovascular Risk in Sedentary Spanish Patients

    PubMed Central

    Gómez-Marcos, Manuel A.; Grandes, Gonzalo; Iglesias-Valiente, José A.; Sánchez, Alvaro; Montoya, Imanol; García-Ortiz, Luis

    2009-01-01

    Background: To evaluate agreement between cardiovascular risk in sedentary patients as estimated by the new Framingham-D’Agostino scale and by the SCORE chart, and to describe the patient characteristics associated with the observed disagreement between the scales. Design: A cross-sectional study was undertaken involving a systematic sample of 2,295 sedentary individuals between 40–65 years of age seen for any reason in 56 primary care offices. An estimation was made of the Pearson correlation coefficient and kappa statistic for the classification of high risk subjects (≥20% according to the Framingham-D’Agostino scale, and ≥5% according to SCORE). Polytomous logistic regression models were fitted to identify the variables associated with the discordance between the two scales. Results: The mean risk in males (35%) was 19.5% ± 13% with D’Agostino scale, and 3.2% ± 3.3% with SCORE. Among females, they were 8.1% ± 6.8% and 1.2% ± 2.2%, respectively. The correlation between the two scales was 0.874 in males (95% CI: 0.857–0.889) and 0.818 in females (95% CI: 0.800–0.834), while the kappa index was 0.50 in males (95% CI: 0.44%–0.56%) and 0.61 in females (95% CI: 0.52%–0.71%). The most frequent disagreement, characterized by high risk according to D’Agostino scale but not according to SCORE, was much more prevalent among males and proved more probable with increasing age and increased LDL-cholesterol, triglyceride and systolic blood pressure values, as well as among those who used antihypertensive drugs and smokers. Conclusions: The quantitative correlation between the two scales is very high. Patient categorization as corresponding to high risk generates disagreements, mainly among males, where agreement between the two classifications is only moderate. PMID:20049225

  6. Indices of agreement between neurosurgeons and a radiologist in interpreting tomography scans in an emergency department.

    PubMed

    Dourado, Jules Carlos; Pereira, Júlio Leonardo Barbosa; Albuquerque, Lucas Alverne Freitas de; Carvalho, Gervásio Teles Cardos de; Dias, Patrícia; Dias, Laura; Bicalho, Marcos; Magalhães, Pollyana; Dellaretti, Marcos

    2015-08-01

    The power of interpretation in the analysis of cranial computed tomography (CCT) among neurosurgeons and radiologists has rarely been studied. This study aimed to assess the rate of agreement in the interpretation of CCTs between neurosurgeons and a radiologist in an emergency department. 227 CCT were independently analyzed by two neurosurgeons (NS1 and NS2) and a radiologist (RAD). The level of agreement in interpreting the examination was studied. The Kappa values obtained between NS1 and NS2 and RAD were considered nearly perfect and substantial agreement. The highest levels of agreement when evaluating abnormalities were observed in the identification of tumors, hydrocephalus and intracranial hematomas. The worst levels of agreement were observed for leukoaraiosis and reduced brain volume. For diseases in which the emergency room procedure must be determined, agreement in the interpretation of CCTs between the radiologist and neurosurgeons was satisfactory.

  7. Reliability and validity of a nutrition and physical activity environmental self-assessment for child care

    PubMed Central

    Benjamin, Sara E; Neelon, Brian; Ball, Sarah C; Bangdiwala, Shrikant I; Ammerman, Alice S; Ward, Dianne S

    2007-01-01

    Background Few assessment instruments have examined the nutrition and physical activity environments in child care, and none are self-administered. Given the emerging focus on child care settings as a target for intervention, a valid and reliable measure of the nutrition and physical activity environment is needed. Methods To measure inter-rater reliability, 59 child care center directors and 109 staff completed the self-assessment concurrently, but independently. Three weeks later, a repeat self-assessment was completed by a sub-sample of 38 directors to assess test-retest reliability. To assess criterion validity, a researcher-administered environmental assessment was conducted at 69 centers and was compared to a self-assessment completed by the director. A weighted kappa test statistic and percent agreement were calculated to assess agreement for each question on the self-assessment. Results For inter-rater reliability, kappa statistics ranged from 0.20 to 1.00 across all questions. Test-retest reliability of the self-assessment yielded kappa statistics that ranged from 0.07 to 1.00. The inter-quartile kappa statistic ranges for inter-rater and test-retest reliability were 0.45 to 0.63 and 0.27 to 0.45, respectively. When percent agreement was calculated, questions ranged from 52.6% to 100% for inter-rater reliability and 34.3% to 100% for test-retest reliability. Kappa statistics for validity ranged from -0.01 to 0.79, with an inter-quartile range of 0.08 to 0.34. Percent agreement for validity ranged from 12.9% to 93.7%. Conclusion This study provides estimates of criterion validity, inter-rater reliability and test-retest reliability for an environmental nutrition and physical activity self-assessment instrument for child care. Results indicate that the self-assessment is a stable and reasonably accurate instrument for use with child care interventions. We therefore recommend the Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC

  8. Immunoglobulin kappa light chain gene promoter and enhancer are not responsible for B-cell restricted gene rearrangement.

    PubMed Central

    Goodhardt, M; Babinet, C; Lutfalla, G; Kallenbach, S; Cavelier, P; Rougeon, F

    1989-01-01

    We have produced transgenic mice which synthesize chimeric mouse-rabbit immunoglobulin (Ig) kappa light chains following in vivo recombination of an injected unrearranged kappa gene. The exogenous gene construct contained a mouse germ-line kappa variable (V kappa) gene segment, the mouse germ-line joining (J kappa) locus including the enhancer, and the rabbit b9 constant (C kappa) region. A high level of V-J recombination of the kappa transgene was observed in spleen of the transgenic mice. Surprisingly, a particularly high degree of variability in the exact site of recombination and the presence of non germ-line encoded nucleotides (N-regions) were found at the V-J junction of the rearranged kappa transgene. Furthermore, unlike endogenous kappa genes, rearrangement of the exogenous gene occurred in T-cells of the transgenic mice. These results show that additional sequences, other than the heptamer-nonamer signal sequences and the promoter and enhancer elements, are required to obtain stage- and lineage- specific regulation of Ig kappa light chain gene rearrangement in vivo. Images PMID:2508061

  9. Nuclear factor-kappaB activation correlates with better prognosis and Akt activation in human gastric cancer.

    PubMed

    Lee, Byung Lan; Lee, Hye Seung; Jung, Jieun; Cho, Sung Jin; Chung, Hee-Yong; Kim, Woo Ho; Jin, Young-Woo; Kim, Chong Soon; Nam, Seon Young

    2005-04-01

    Because the biological significance of constitutive nuclear factor-kappaB (NF-kappaB) activation in human gastric cancer is unclear, we undertook this study to clarify the regulatory mechanism of NF-kappaB activation and its clinical significance. Immunohistochemistry for NF-kappaB/RelA was done on 290 human gastric carcinoma specimens placed on tissue array slides. The correlations between NF-kappaB activation and clinicopathologic features, prognosis, Akt activation, tumor suppressor gene expression, or Bcl-2 expression were analyzed. We also did luciferase reporter assay, Western blot analysis, and reverse transcription-PCR using the SNU-216 human gastric cancer cell line transduced with retroviral vectors containing constitutively active Akt or the NF-kappaB repressor mutant of IkappaBalpha. Nuclear expression of RelA was found in 18% of the gastric carcinomas and was higher in early-stage pathologic tumor-node-metastasis (P = 0.019). A negative correlation was observed between NF-kappaB activation and lymphatic invasion (P = 0.034) and a positive correlation between NF-kappaB activation and overall survival rate of gastric cancer patients (P = 0.0228). In addition, NF-kappaB activation was positively correlated with pAkt (P = 0.047), p16 (P = 0.004), adenomatous polyposis coli (P < 0.001), Smad4 (P = 0.002), and kangai 1 (P < 0.001) expression. An in vitro study showed that NF-kappaB activity in gastric cancer cells is controlled by and controls Akt. NF-kappaB activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis and Akt activation. These findings suggest that NF-kappaB activation is a valuable prognostic variable in gastric carcinoma.

  10. Different effects of antisense RelA p65 and NF-kappaB1 p50 oligonucleotides on the nuclear factor-kappaB mediated expression of ICAM-1 in human coronary endothelial and smooth muscle cells.

    PubMed

    Voisard, R; Huber, N; Baur, R; Susa, M; Ickrath, O; Both, A; Koenig, W; Hombach, V

    2001-01-01

    Activation of nuclear factor-kappaB (NF-kappaB) is one of the key events in early atherosclerosis and restenosis. We hypothesized that tumor necrosis factor-alpha (TNF-alpha) induced and NF-kappaB mediated expression of intercellular adhesion molecule-1 (ICAM-1) can be inhibited by antisense RelA p65 and NF-kappaB1 p50 oligonucleotides (RelA p65 and NF-kappaB1 p50). Smooth muscle cells (SMC) from human coronary plaque material (HCPSMC, plaque material of 52 patients), SMC from the human coronary media (HCMSMC), human endothelial cells (EC) from umbilical veins (HUVEC), and human coronary EC (HCAEC) were successfully isolated (HCPSMC, HUVEC), identified and cultured (HCPSMC, HCMSMC, HUVEC, HCAEC). 12 hrs prior to TNF-alpha stimulus (20 ng/mL, 6 hrs) RelA p65 and NF-kappaB1 p50 (1, 2, 4, 10, 20, and 30 microM) and controls were added for a period of 18 hrs. In HUVEC and HCAEC there was a dose dependent inhibition of ICAM-1 expression after adding of both RelA p65 and NF-kappaB1 p50. No inhibitory effect was seen after incubation of HCMSMC with RelA p65 and NF-kappaB1 p50. A moderate inhibition of ICAM-1 expression was found after simultaneous addition of RelA p65 and NF-kappaB1 p50 to HCPSMC, no inhibitory effect was detected after individual addition of RelA p65 and NF-kappaB1 p50. The data point out that differences exist in the NF-kappaB mediated expression of ICAM-1 between EC and SMC. Experimental antisense strategies directed against RelA p65 and NF-kappaB1 p50 in early atherosclerosis and restenosis are promising in HCAEC but will be confronted with redundant pathways in HCMSMC and HCPSMC.

  11. Test-Retest Reliability, Agreement and Responsiveness of Productivity Loss (iPCQ-VR) and Healthcare Utilization (TiCP-VR) Questionnaires for Sick Workers with Chronic Musculoskeletal Pain.

    PubMed

    Beemster, Timo T; van Velzen, Judith M; van Bennekom, Coen A M; Reneman, Michiel F; Frings-Dresen, Monique H W

    2018-03-16

    The purpose of this study was to assess test-retest reliability, agreement, and responsiveness of questionnaires on productivity loss (iPCQ-VR) and healthcare utilization (TiCP-VR) for sick-listed workers with chronic musculoskeletal pain who were referred to vocational rehabilitation. Methods Test-retest reliability and agreement was assessed with a 2-week interval. Responsiveness was assessed at discharge after a 15-week vocational rehabilitation (VR) program. Data was obtained from six Dutch VR centers. Test-retest reliability was determined with intraclass correlation coefficient (ICC) and Cohen's kappa. Agreement was determined by Standard Error of Measurement (SEM), smallest detectable changes (on group and individual level), and percentage observed, positive and negative agreement. Responsiveness was determined with area under the curve (AUC) obtained from receiver operation characteristic (ROC). Results A sample of 52 participants on test-retest reliability and agreement, and a sample of 223 on responsiveness were included in the analysis. Productivity loss (iPCQ-VR): ICCs ranged from 0.52 to 0.90, kappa ranged from 0.42 to 0.96, and AUC ranged from 0.55 to 0.86. Healthcare utilization (TiCP-VR): ICC was 0.81, and kappa values of the single healthcare utilization items ranged from 0.11 to 1.00. Conclusions The iPCQ-VR showed good measurement properties on working status, number of hours working per week and long-term sick leave, and low measurement properties on short-term sick leave and presenteeism. The TiCP-VR showed adequate reliability on all healthcare utilization items together and medication use, but showed low measurement properties on the single healthcare utilization items.

  12. Assessing food selection in a health promotion program: validation of a brief instrument for American Indian children in the southwest United States.

    PubMed

    Koehler, K M; Cunningham-Sabo, L; Lambert, L C; McCalman, R; Skipper, B J; Davis, S M

    2000-02-01

    Brief dietary assessment instruments are needed to evaluate behavior changes of participants in dietary intervention programs. The purpose of this project was to design and validate an instrument for children participating in Pathways to Health, a culturally appropriate, cancer prevention curriculum. Validation of a brief food selection instrument, Yesterday's Food Choices (YFC), which contained 33 questions about foods eaten the previous day with response choices of yes, no, or not sure. Reference data for validation were 24-hour dietary recalls administered individually to 120 students selected randomly. The YFC and 24-hour dietary recalls were administered to American Indian children in fifth- and seventh-grade classes in the Southwest United States. Dietary recalls were coded for food items in the YFC and results were compared for each item using percentage agreement and the kappa statistic. Percentage agreement for all items was greater than 60%; for most items it was greater than 70%, and for several items it was greater than 80%. The amount of agreement beyond that explained by chance (kappa statistic) was generally small. Three items showed substantial agreement beyond chance (kappa > or = 0.6); 2 items showed moderate agreement (kappa = 0.40 to 0.59) most items showed fair agreement (kappa = 0.20 to 0.39). The food items showing substantial agreement were hot or cold cereal, low-fat milk, and mutton or chile stew. Fried or scrambled eggs and deep-fried foods showed moderate agreement beyond chances. Previous development and validation of brief food selection instruments for children participating in health promotion programs has had limited success. In this study, instrument-related factors that apparently contributed to poor agreement between data from the YFC and 24-hour dietary recall were inclusion of categories of foods vs specific foods; food knowledge, preparation, and vocabulary, item length, and overreporting of attractive foods. Collecting and

  13. The radiant ephemerides of kappa-Cygnids from the IMO video database

    NASA Astrophysics Data System (ADS)

    Triglav-Cekada, Mihaela

    2006-08-01

    The analysis of single-station IMO video network data of the July and August period with 36 576 meteors in search of kappa-Cygnid, alpha-Lyrid and zeta-Draconid meteor showers was made using the program Radiant. These showers will be named kappa-Cygnid meteor complex radiants. The detailed analysis of the whole August period from 1993-2004 included the behavior of radiants in different magnitude ranges and different years from 2000 on. Detailed radiant calculations for different velocities for 5g and 10g solar longitude intervals were also done. In 10g solar longitude intervals also the calculations for different magnitude ranges were conducted. The activity of the kappa-Cygnid radiant and the alpha-Lyrid radiant was proven, unlike the zeta-Draconid radiant, where no activity could be confirmed. For the whole August period also the behavior of radiants in separate years 2000-2004, when day-to-day meteor coverage is available, was made. From that it can be hinted on alternating bigger activity of the kappa-Cygnid and alpha-Lyrid radiants. In the years 2000 and 2001 the alpha-Lyrid radiant is more active, when on the contrary in 2002, 2003 and 2004 the kappa-Cygnid radiant is more active. The year 2003 is interesting from another aspect, as three radiants can be seen. If the third radiant is the zeta-Draconid radiant, a few years more video observations will have to be gathered and the radiant calculations repeated. For the day of the kappa-Cygnid meteor complex maximum, on August 18, the mean radiant positions were deduced: the more active kappa-Cygnid radiant lies at alpha=280 deg and delta=+58 deg with an area of the maximum probability of 10 deg x 15 deg, and the less active alpha-Lyrid radiant is placed at alpha=292 deg and delta=+52 deg with a radius of maximum probability of 2 deg. The radiant drift was not possible to obtain as in the 5 deg and 10 deg solar longitude interval calculations the positions of both radiants apparently oscillate. As no change can

  14. A new structural class of proteasome inhibitors that prevent NF-kappa B activation.

    PubMed

    Lum, R T; Kerwar, S S; Meyer, S M; Nelson, M G; Schow, S R; Shiffman, D; Wick, M M; Joly, A

    1998-05-01

    The multicatalytic proteinase or proteasome is a highly conserved cellular structure that is responsible for the ATP-dependent proteolysis of many proteins involved in important regulatory cellular processes. We have identified a novel class of inhibitors of the chymotrypsin-like proteolytic activity of the 20S proteasome that exhibit IC50 values ranging from 0.1 to 0.5 microgram/mL (0.1 to 1 microM). In cell proliferation assays, these compounds inhibit growth with an IC50 ranging from 5 to 10 micrograms/mL (10-20 microM). A representative member of this class of inhibitors was tested in other biological assays. CVT-634 (5-methoxy-1-indanone-3-acetyl-leu-D-leu-1-indanylamide) prevented lipopolysaccharide (LPS), tumor necrosis factor (TNF)-, and phorbol ester-induced activation of nuclear factor kappa B (NF-kappa B) in vitro by preventing signal-induced degradation of I kappa B-alpha. In these studies, the I kappa B-alpha that accumulated was hyperphosphorylated, indicating that CVT-634 did not inhibit I kappa B-alpha kinase, the enzyme responsible for signal-induced phosphorylation of I kappa B-alpha. In vivo studies indicated that CVT-634 prevented LPS-induced TNF synthesis in a murine macrophage cell line. In addition, in mice pretreated with CVT-634 at 25 and 50 mg/kg and subsequently treated with LPS, serum TNF levels were significantly lower (225 +/- 59 and 83 +/- 41 pg/mL, respectively) than in those mice that were treated only with LPS (865 +/- 282 pg/mL). These studies suggest that specific inhibition of the chymotrypsin-like activity of the proteasome is sufficient to prevent signal-induced NF-kappa B activation and that the proteasome is a novel target for the identification of agents that may be useful in the treatment of diseases whose etiology is dependent upon the activation of NF-kappa B.

  15. Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B

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

    Reimers, Kerstin; Buchholz, Katja; Werchau, Hermann

    2005-01-20

    Respiratory syncytial virus (RSV) induces the production of a number of cytokines and chemokines by activation of nuclear factor kappa B (NF-{kappa}B). The activation of NF-{kappa}B has been shown to depend on viral replication in the infected cells. In this study, we demonstrate that expression of RSV M2-1 protein, a transcriptional processivity and anti-termination factor, is sufficient to activate NF-{kappa}B in A549 cells. Electromobility shift assays show increased NF-{kappa}B complexes in the nuclei of M2-1-expressing cells. M2-1 protein is found in nuclei of M2-1-expressing cells and in RSV-infected cells. Co-immunoprecipitations of nuclear extracts of M2-1-expressing cells and of RSV-infected cellsmore » revealed an association of M2-1 with Rel A protein. Furthermore, the activation of NF-{kappa}B depends on the C-terminus of the RSV M2-1 protein, as shown by NF-{kappa}B-induced gene expression of a reporter gene construct.« less

  16. BFV activates the NF-kappaB pathway through its transactivator (BTas) to enhance viral transcription

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

    Wang Jian; Tan Juan; Zhang Xihui

    2010-05-10

    Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-kappaB (NF-kappaB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-kappaB pathway through the action of its transactivator, BTas. Both cellular IKKbeta and IkappaBalpha also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-kappaB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKalpha and IKKbeta), which may bemore » responsible for regulation of IKK kinase activity and persistent NF-kappaB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-kappaB. Together, this study suggests that BFV activates the NF-kappaB pathway through BTas to enhance viral transcription.« less

  17. BFV activates the NF-kappaB pathway through its transactivator (BTas) to enhance viral transcription.

    PubMed

    Wang, Jian; Tan, Juan; Zhang, Xihui; Guo, Hongyan; Zhang, Qicheng; Guo, Tingting; Geng, Yunqi; Qiao, Wentao

    2010-05-10

    Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-kappaB (NF-kappaB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-kappaB pathway through the action of its transactivator, BTas. Both cellular IKKbeta and IkappaBalpha also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-kappaB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKalpha and IKKbeta), which may be responsible for regulation of IKK kinase activity and persistent NF-kappaB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-kappaB. Together, this study suggests that BFV activates the NF-kappaB pathway through BTas to enhance viral transcription. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Recall of past use of mobile phone handsets.

    PubMed

    Parslow, R C; Hepworth, S J; McKinney, P A

    2003-01-01

    Previous studies investigating health effects of mobile phones have based their estimation of exposure on self-reported levels of phone use. This UK validation study assesses the accuracy of reported voice calls made from mobile handsets. Data collected by postal questionnaire from 93 volunteers was compared to records obtained prospectively over 6 months from four network operators. Agreement was measured for outgoing calls using the kappa statistic, log-linear modelling, Spearman correlation coefficient and graphical methods. Agreement for number of calls gained moderate classification (kappa = 0.39) with better agreement for duration (kappa = 0.50). Log-linear modelling produced similar results. The Spearman correlation coefficient was 0.48 for number of calls and 0.60 for duration. Graphical agreement methods demonstrated patterns of over-reporting call numbers (by a factor of 1.7) and duration (by a factor of 2.8). These results suggest that self-reported mobile phone use may not fully represent patterns of actual use. This has implications for calculating exposures from questionnaire data.

  19. The kappa-opiate receptor impacts the pathophysiology and behavior of substance use.

    PubMed

    Mysels, David; Sullivan, Maria A

    2009-01-01

    There is increasing evidence that the kappa-opiate receptor, in addition to the mu-opiate receptor, plays an important role in substance use pathophysiology and behavior. As dopamine activity is upregulated through chronic substance use, kappa receptor activity, mediated through the peptide dynorphin, is upregulated in parallel. Dynorphin causes dysphoria and decreased locomotion, and the upregulation of its activity on the kappa receptor likely dampens the excitation caused by increased dopaminergic activity. This feedback mechanism may have significant clinical implications for treating drug dependent patients in various stages of their pathology.

  20. Inter-rater agreement in the assessment of abnormal chest X-ray findings for tuberculosis between two Asian countries

    PubMed Central

    2012-01-01

    Background Inter-rater agreement in the interpretation of chest X-ray (CXR) films is crucial for clinical and epidemiological studies of tuberculosis. We compared the readings of CXR films used for a survey of tuberculosis between raters from two Asian countries. Methods Of the 11,624 people enrolled in a prevalence survey in Hanoi, Viet Nam, in 2003, we studied 258 individuals whose CXR films did not exclude the possibility of active tuberculosis. Follow-up films obtained from accessible individuals in 2006 were also analyzed. Two Japanese and two Vietnamese raters read the CXR films based on a coding system proposed by Den Boon et al. and another system newly developed in this study. Inter-rater agreement was evaluated by kappa statistics. Marginal homogeneity was evaluated by the generalized estimating equation (GEE). Results CXR findings suspected of tuberculosis differed between the four raters. The frequencies of infiltrates and fibrosis/scarring detected on the films significantly differed between the raters from the two countries (P < 0.0001 and P = 0.0082, respectively, by GEE). The definition of findings such as primary cavity, used in the coding systems also affected the degree of agreement. Conclusions CXR findings were inconsistent between the raters with different backgrounds. High inter-rater agreement is a component necessary for an optimal CXR coding system, particularly in international studies. An analysis of reading results and a thorough discussion to achieve a consensus would be necessary to achieve further consistency and high quality of reading. PMID:22296612

  1. Agreement Between the JCDCG, Revised NCEP-ATPIII, and IDF Definitions of Metabolic Syndrome in a Northwestern Chinese Population.

    PubMed

    Sun, Fei; Gao, Bin; Wang, Li; Xing, Ying; Ming, Jie; Zhou, Jie; Fu, Jianfang; Li, Xiaomiao; Xu, Shaoyong; Liu, Guocai; Ji, Qiuhe

    2018-05-28

    The Joint Committee for Developing Chinese Guidelines (JCDCG) introduced the Chinese definition for metabolic syndrome (MS), which has been verified in southern Chinese people but not in northwestern Chinese people. We evaluated the MS definition proposed by the JCDCG in a northwestern Chinese population, in comparison with those of the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) and the International Diabetes Federation (IDF). This population-based cross-sectional study was a part of the China National Diabetes and Metabolic Disorders Study conducted in Shaanxi province. We included 3243 participants aged ≥ 20 years. The age-adjusted MS prevalence was assessed per the 2007 Chinese population structure. The agreement between different definitions was assessed by the kappa statistic. The standardized prevalence of JCDCG-MS, revised ATPIII-MS, and IDF-MS was 22.4%, 29.4%, and 24.9%, respectively. Among women, the agreement of the JCDCG definition with the revised ATPIII and the IDF definition was not good (κ = 0.599 and 0.601, respectively); 54.6% of the revised ATPIII-MS and 56% of the IDF-MS were defined as MS according to the JCDCG definition. Among men, the agreement of JCDCG definition with the revised ATPIII and IDF definitions was very good (κ = 0.863) and substantial (κ = 0.741), respectively. The agreement of the JCDCG definition with the revised ATPIII and IDF definitions was insufficient in women. Compared with the other two definitions, the JCDCG definition underestimates MS prevalence in northwestern women.

  2. Polycystin-1 promotes PKC{alpha}-mediated NF-{kappa}B activation in kidney cells

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

    Banzi, Manuela; Aguiari, Gianluca; Trimi, Viky

    2006-11-17

    Polycystin-1 (PC1), the PKD1 gene product, is a membrane receptor which regulates many cell functions, including cell proliferation and apoptosis, both typically increased in cyst lining cells in autosomal dominant polycystic kidney disease. Here we show that PC1 upregulates the NF-{kappa}B signalling pathway in kidney cells to prevent cell death. Human embryonic kidney cell lines (HEK293{sup CTT}), stably expressing a PC1 cytoplasmic terminal tail (CTT), presented increased NF-{kappa}B nuclear levels and NF-{kappa}B-mediated luciferase promoter activity. This, consistently, was reduced in HEK293 cells in which the endogenous PC1 was depleted by RNA interference. CTT-dependent NF-{kappa}B promoter activation was mediated by PKC{alpha}more » because it was blocked by its specific inhibitor Ro-320432. Furthermore, it was observed that apoptosis, which was increased in PC1-depleted cells, was reduced in HEK293{sup CTT} cells and in porcine kidney LtTA cells expressing a doxycycline-regulated CTT. Staurosporine, a PKC inhibitor, and parthenolide, a NF-{kappa}B inhibitor, significantly reduced the CTT-dependent antiapoptotic effect. These data reveal, therefore, a novel pathway by which polycystin-1 activates a PKC{alpha}-mediated NF-{kappa}B signalling and cell survival.« less

  3. NF-{kappa}B inhibition is involved in tobacco smoke-induced apoptosis in the lungs of rats

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

    Zhong Caiyun; Zhou Yamei; Pinkerton, Kent E.

    2008-07-15

    Apoptosis is a vital mechanism for the regulation of cell turnover and plays a critical role in tissue homeostasis and development of many disease processes. Previous studies have demonstrated the apoptotic effect of tobacco smoke; however, the molecular mechanisms by which tobacco smoke triggers apoptosis remain unclear. In the present study we investigated the effects of tobacco smoke on the induction of apoptosis in the lungs of rats and modulation of nuclear factor-kappa B (NF-{kappa}B) in this process. Exposure of rats to 80 mg/m{sup 3} tobacco smoke significantly induced apoptosis in the lungs. Tobacco smoke resulted in inhibition of NF-{kappa}Bmore » activity, noted by suppression of inhibitor of {kappa}B (I{kappa}B) kinase (IKK), accumulation of I{kappa}B{alpha}, decrease of NF-{kappa}B DNA binding activity, and downregulation of NF-{kappa}B-dependent anti-apoptotic proteins, including Bcl-2, Bcl-xl, and inhibitors of apoptosis. Initiator caspases for the death receptor pathway (caspase 8) and the mitochondrial pathway (caspase 9) as well as effector caspase 3 were activated following tobacco smoke exposure. Tobacco smoke exposure did not alter the levels of p53 and Bax proteins. These findings suggest the role of NF-{kappa}B pathway in tobacco smoke-induced apoptosis.« less

  4. Corrective recombination of mouse immunoglobulin kappa alleles in Abelson murine leukemia virus-transformed pre-B cells.

    PubMed Central

    Feddersen, R M; Van Ness, B G

    1990-01-01

    Previous characterization of mouse immunoglobulin kappa gene rearrangement products cloned from murine plasmacytomas has indicated that two recombination events can take place on a single kappa allele (R. M. Feddersen and B. G. Van Ness, Proc. Natl. Acad. Sci. USA 82:4792-4797, 1985; M. A. Shapiro and M. Weigert, J. Immunol. 139:3834-3839, 1987). To determine whether multiple recombinations on a single kappa allele can contribute to the formation of productive V-J genes through corrective recombinations, we have examined several Abelson murine leukemia virus-transformed pre-B-cell clones which rearrange the kappa locus during cell culture. Clonal cell lines which had rearranged one kappa allele nonproductively while maintaining the other allele in the germ line configuration were grown, and secondary subclones, which subsequently expressed kappa protein, were isolated and examined for further kappa rearrangement. A full spectrum of rearrangement patterns was observed in this sequential cloning, including productive and nonproductive recombinations of the germ line allele and secondary recombinations of the nonproductive allele. The results show that corrective V-J recombinations, with displacement of the nonproductive kappa gene, occur with a significant frequency (6 of 17 kappa-producing subclones). Both deletion and maintenance of the primary (nonfunctional) V-J join, as a reciprocal product, were observed. Images PMID:2153918

  5. [Interobserver agreement on electrocardiographic diagnosis of left ventricular hypertrophy in hypertensive patients in Andalusia. PREHVIA study].

    PubMed

    Martín-Rioboó, Enrique; López Granados, Amador; Cea Calvo, Luis; Pérula De Torres, Luis Angel; García Criado, Emilio; Anguita Sánchez, Manuel P; García Matarín, Lisardo; Molina Díaz, Rafael; Ureña Fernández, Tomas

    2009-05-01

    To assess the agreement between Primary Care (PC) doctors and a cardiology specialist in diagnosing left ventricular hypertrophy in the electrocardiograph (LVH-ECG) in hypertensive patients. Cross-sectional, multicentre study. Andalusian Primary Care Centres. A total of 120 PC doctors who using a random sample selected patients of 35 years or more with AHT of at least 6 months of progression. PRIMARY VARIABLES: Demographic data, risk factors and cardiovascular diseases were recorded. The LVH-ECG was evaluated by applying Cornell voltage criteria, Cornell and Sokolow-Lyon product. The PC researchers read the ECG first and the cardiologist made a second reading blind. A total of 570 patients (mean +/- SD of age, 65 +/- 11 years; 54.5% females); the LVH-ECG prevalence was 13.7% (95% CI, 10.8-16.6; 12.6% by Cornell and 1.6% by Sokolow-Lyon). The agreement in the diagnosis between the PC doctors and the cardiologist was 0.378 (95% CI, 0.272-0.486; disagreements in 15.5% of cases). The PC doctors slightly underestimated the LVH-ECG prevalence by Cornell and slightly overestimated it by the Sokolow-Lyon criteria. The agreement was also low for all of them (kappa = 0.367; 95% CI, 0.252-0.482, for Cornell, and kappa = 0.274; 95% CI: 0.093-0.454 for Sokolow-Lyon). The agreement between the diagnosis by the PC doctors and the cardiologist was low. The implications of this study suggest the need to improve the reading of ECG among PC doctors. The use of computerised systems could be a good option.

  6. Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2.

    PubMed

    Van Huffel, S; Delaei, F; Heyninck, K; De Valck, D; Beyaert, R

    2001-08-10

    The nuclear factor kappaB (NF-kappaB) plays a central role in the regulation of genes implicated in immune responses, inflammatory processes, and apoptotic cell death. The zinc finger protein A20 is a cellular inhibitor of NF-kappaB activation by various stimuli and plays a critical role in terminating NF-kappaB responses. The underlying mechanism for NF-kappaB inhibition by A20 is still unknown. A20 has been shown to interact with several proteins including tumor necrosis factor (TNF) receptor-associated factors 2 and 6, as well as the inhibitory protein of kappaB kinase (IKK) gamma protein. Here we report the cloning and characterization of ABIN-2, a previously unknown protein that binds to the COOH-terminal zinc finger domain of A20. NF-kappaB activation induced by TNF and interleukin-1 is inhibited by overexpression of ABIN-2. The latter also inhibits NF-kappaB activation induced by overexpression of receptor-interacting protein or TNF receptor-associated factor 2. In contrast, NF-kappaB activation by overexpression of IKKbeta or direct activators of the IKK complex, such as Tax, cannot be inhibited by ABIN-2. These results indicate that ABIN-2 interferes with NF-kappaB activation upstream of the IKK complex and that it might contribute to the NF-kappaB-inhibitory function of A20.

  7. Validity and reliability of a method for assessment of cervical vertebral maturation.

    PubMed

    Zhao, Xiao-Guang; Lin, Jiuxiang; Jiang, Jiu-Hui; Wang, Qingzhu; Ng, Sut Hong

    2012-03-01

    To evaluate the validity and reliability of the cervical vertebral maturation (CVM) method with a longitudinal sample. Eighty-six cephalograms from 18 subjects (5 males and 13 females) were selected from the longitudinal database. Total mandibular length was measured on each film; an increased rate served as the gold standard in examination of the validity of the CVM method. Eleven orthodontists, after receiving intensive training in the CVM method, evaluated all films twice. Kendall's W and the weighted kappa statistic were employed. Kendall's W values were higher than 0.8 at both times, indicating strong interobserver reproducibility, but interobserver agreement was documented twice at less than 50%. A wide range of intraobserver agreement was noted (40.7%-79.1%), and substantial intraobserver reproducibility was proved by kappa values (0.53-0.86). With regard to validity, moderate agreement was reported between the gold standard and observer staging at the initial time (kappa values 0.44-0.61). However, agreement seemed to be unacceptable for clinical use, especially in cervical stage 3 (26.8%). Even though the validity and reliability of the CVM method proved statistically acceptable, we suggest that many other growth indicators should be taken into consideration in evaluating adolescent skeletal maturation.

  8. Reliability of psychiatric diagnosis in hospitalized adolescents. Interrater agreement using DSM-III.

    PubMed

    Strober, M; Green, J; Carlson, G

    1981-02-01

    To determine the reliability of psychiatric diagnosis in hospitalized adolescents, 95 consecutively admitted patients were diagnosed independently by two experienced clinicians using DSM-III criteria. Diagnostic judgments were based on joint interview of the patient via a structured mental-status examination, nursing observations, and referral materials. Concordance was analyzed by the kappa coefficient. A total of 13 DSM-III categories were used to classify this cohort, with the majority of categories representing traditional syndromes of functional psychopathology. There was complete agreement between the raters for more than three fourths of the patients. Levels of agreement for the categories of schizophrenia and major affective disorder were similar to values obtained in recent studies of adult patients. The results are discussed in relation to historical conceptions of adolescent psychopathology.

  9. Regulation of the nuclear factor (NF)-kappaB pathway by ISGylation.

    PubMed

    Minakawa, Miki; Sone, Takayuki; Takeuchi, Tomoharu; Yokosawa, Hideyoshi

    2008-12-01

    Post-translational modification with ISG15 (interferon-stimulated gene 15 kDa) (ISGylation) is mediated by a sequential reaction similar to ubiquitination, and various target proteins for ISGylation have been identified. We previously reported that ISGylation of the E2 ubiquitin-conjugating enzyme Ubc13 suppresses its E2 activity. Ubc13 forms a heterodimer with Uev1A, a ubiquitin-conjugating enzyme variant, and the Ubc13-Uev1A complex catalyzes the assembly of a Lys63-linked polyubiquitin chain, which plays a non-proteolytic role in the nuclear factor (NF)-kappaB pathway. In this study, we examined the effect of ISGylation on tumor necrosis factor receptor-associated factor (TRAF)-6/transforming growth factor beta-activated kinase (TAK)-1-dependent NF-kappaB activation. We found that expression of the ISGylation system suppresses NF-kappaB activation via TRAF6 and TAK1 and that the level of polyubiquitinated TRAF6 is reduced by expression of the ISGylation system. Taken together, the results suggest that the NF-kappaB pathway is negatively regulated by ISGylation.

  10. Graphical aids for visualizing and interpreting patterns in departures from agreement in ordinal categorical observer agreement data.

    PubMed

    Bangdiwala, Shrikant I

    2017-01-01

    When studying the agreement between two observers rating the same n units into the same k discrete ordinal categories, Bangdiwala (1985) proposed using the "agreement chart" to visually assess agreement. This article proposes that often it is more interesting to focus on the patterns of disagreement and visually understanding the departures from perfect agreement. The article reviews the use of graphical techniques for descriptively assessing agreement and disagreements, and also reviews some of the available summary statistics that quantify such relationships.

  11. RRM2 induces NF-{kappa}B-dependent MMP-9 activation and enhances cellular invasiveness

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

    Duxbury, Mark S.; Whang, Edward E.

    2007-03-02

    Ribonucleotide reductase is a dimeric enzyme that catalyzes conversion of ribonucleotide 5'-diphosphates to their 2'-deoxynucleotide forms, a rate-limiting step in the production of 2'-deoxyribonucleoside 5'-triphosphates required for DNA synthesis. The ribonucleotide reductase M2 subunit (RRM2) is a determinant of malignant cellular behavior in a range of human cancers. We examined the effect of RRM2 overexpression on pancreatic adenocarcinoma cellular invasiveness and nuclear factor-{kappa}B (NF-{kappa}B) transcription factor activity. RRM2 overexpression increases pancreatic adenocarcinoma cellular invasiveness and MMP-9 expression in a NF-{kappa}B-dependent manner. RNA interference (RNAi)-mediated silencing of RRM2 expression attenuates cellular invasiveness and NF-{kappa}B activity. NF-{kappa}B is a key mediator ofmore » the invasive phenotypic changes induced by RRM2 overexpression.« less

  12. Agreement between hospital discharge diagnosis codes and medical records to identify metastatic colorectal cancer and associated comorbidities in elderly patients.

    PubMed

    Gouverneur, A; Dolatkhani, D; Rouyer, M; Grelaud, A; Francis, F; Gilleron, V; Fourrier-Réglat, A; Noize, P

    2017-08-01

    Quality of coding to identify cancers and comorbidities through the French hospital diagnosis database (Programme de médicalisation des systèmes d'information, PMSI) has been little investigated. Agreement between medical records and PMSI database was evaluated regarding metastatic colorectal cancer (mCRC) and comorbidities. From 01/01/2013 to 06/30/2014, 74 patients aged≥65years at mCRC diagnosis were identified in Bordeaux teaching hospital. Data on mCRC and comorbidities were collected from medical records. All diagnosis codes (main, related and associated) registered into the PMSI were extracted. Agreement between sources was evaluated using the percent agreement for mCRC and the kappa (κ) statistic for comorbidities. Agreement for primary CRC and mCRC was higher using all types of diagnosis codes instead of the main one exclusively (respectively 95% vs. 53% for primary CRC and 91% vs. 24% for mCRC). Agreement was substantial (κ 0.65) for cardiovascular diseases, notably atrial fibrillation (κ 0.77) and hypertension (κ 0.68). It was moderate for psychiatric disorders (κ 0.49) and respiratory diseases (κ 0.48), although chronic obstructive pulmonary disease had a good agreement (κ 0.75). Within the class of endocrine, nutritional and metabolic diseases (κ 0.55), agreement was substantial for diabetes (κ 0.91), obesity (κ 0.82) and hypothyroidism (κ 0.72) and moderate for hypercholesterolemia (κ 0.51) and malnutrition (κ 0.42). These results are reassuring with regard to detection through PMSI of mCRC if all types of diagnosis codes are considered and useful to better choose comorbidities in elderly mCRC patients that could be well identified through hospital diagnosis codes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Agreement Rate of Rapid Urease Test, Conventional PCR, and Scorpion Real-Time PCR in Detecting Helicobacter Pylori from Tonsillar Samples of Patients with Chronic Tonsillitis

    PubMed Central

    Najafipour, Reza; Farivar, Taghi Naserpour; Pahlevan, Ali Akbar; Johari, Pouran; Safdarian, Farshid; Asefzadeh, Mina

    2012-01-01

    Background: Helicobacter pylori is capable of inducing systemic inflammatory reactions through immunological processes. There are several methods to identify the presence of H. pylori in clinical samples including rapid urease test (RUT), conventional polymerase chain reaction (PCR), and the Scorpion real-time PCR. Aim: The aim of the present study is to compare the agreement rate of these tests in identifying H. pylori in tonsillar biopsy specimens collected from patients with chronic tonsillitis. Materials and Methods: A total of 103 tonsil biopsy samples from patients with clinical signs of chronic tonsillitis were examined with RUT, PCR, and Scorpion real-time PCR. The degree of agreement between the three tests was later calculated. Results: There was a poor degree of agreement between RUT and PCR and also RUT and Scorpion real-time PCR (Kappa=0.269 and 0.249, respectively). In contrast with RUT, there was a strong degree of agreement between PCR and Scorpion real-time PCR (Kappa=0.970). Conclusion: The presence of a strong agreement between the Scorpion real-time PCR and PCR as well as its technical advantage over the conventional PCR assay, made the Scorpion real-time PCR an appropriate laboratory test to investigate the presence of H. pylori in tonsillar biopsy specimens in patients suffering from chronic tonsillitis. PMID:22754245

  14. African swine fever virus IAP-like protein induces the activation of nuclear factor kappa B.

    PubMed

    Rodríguez, Clara I; Nogal, María L; Carrascosa, Angel L; Salas, María L; Fresno, Manuel; Revilla, Yolanda

    2002-04-01

    African swine fever virus (ASFV) encodes a homologue of the inhibitor of apoptosis (IAP) that promotes cell survival by controlling the activity of caspase-3. Here we show that ASFV IAP is also able to activate the transcription factor NF-kappaB. Thus, transient transfection of the viral IAP increases the activity of an NF-kappaB reporter gene in a dose-responsive manner in Jurkat cells. Similarly, stably transfected cells expressing ASFV IAP have elevated basal levels of c-rel, an NF-kappaB-dependent gene. NF-kappaB complexes in the nucleus were increased in A224L-expressing cells compared with control cells upon stimulation with phorbol myristate acetate (PMA) plus ionomycin. This resulted in greater NF-kappaB-dependent promoter activity in ASFV IAP-expressing than in control cells, both in basal conditions and after PMA plus ionophore stimulation. The elevated NF-kappaB activity seems to be the consequence of higher IkappaB kinase (IKK) basal activity in these cells. The NF-kappaB-inducing activity of ASFV IAP was abrogated by an IKK-2 dominant negative mutant and enhanced by expression of tumor necrosis factor receptor-associated factor 2.

  15. NF-kappaB activation in hypothalamic pro-opiomelanocortin neurons is essential in illness- and leptin-induced anorexia.

    PubMed

    Jang, Pil-Geum; Namkoong, Cherl; Kang, Gil Myoung; Hur, Man-Wook; Kim, Seung-Whan; Kim, Geun Hyang; Kang, Yeoungsup; Jeon, Min-Jae; Kim, Eun Hee; Lee, Myung-Shik; Karin, Michael; Baik, Ja-Hyun; Park, Joong-Yeol; Lee, Ki-Up; Kim, Young-Bum; Kim, Min-Seon

    2010-03-26

    Anorexia and weight loss are prevalent in infectious diseases. To investigate the molecular mechanisms underlying these phenomena, we established animal models of infection-associated anorexia by administrating bacterial and viral products, lipopolysaccharide (LPS) and human immunodeficiency virus-1 transactivator protein (Tat). In these models, we found that the nuclear factor-kappaB (NF-kappaB), a pivotal transcription factor for inflammation-related proteins, was activated in the hypothalamus. In parallel, administration of LPS and Tat increased hypothalamic pro-inflammatory cytokine production, which was abrogated by inhibition of hypothalamic NF-kappaB. In vitro, NF-kappaB activation directly stimulated the transcriptional activity of pro-opiomelanocortin (POMC), a precursor of anorexigenic melanocortin, and mediated the stimulatory effects of LPS, Tat, and pro-inflammatory cytokines on POMC transcription, implying the involvement of NF-kappaB in controlling feeding behavior. Consistently, hypothalamic injection of LPS and Tat caused a significant reduction in food intake and body weight, which was prevented by blockade of NF-kappaB and melanocortin. Furthermore, disruption of I kappaB kinase-beta, an upstream kinase of NF-kappaB, in POMC neurons attenuated LPS- and Tat-induced anorexia. These findings suggest that infection-associated anorexia and weight loss are mediated via NF-kappaB activation in hypothalamic POMC neurons. In addition, hypothalamic NF-kappaB was activated by leptin, an important anorexigenic hormone, and mediates leptin-stimulated POMC transcription, indicating that hypothalamic NF-kappaB also serves as a downstream signaling pathway of leptin.

  16. Phi Delta Kappa at the Threshold

    ERIC Educational Resources Information Center

    Walling, Donovan R.

    2006-01-01

    Since its fraternal origins a century ago, Phi Delta Kappa (PDK) International has been foremost a society of individuals joined together in professional collegiality and dedicated to tenets of leadership, service, and research in education. As PDK crosses the threshold into its second century, that early spirit of association lit in 1906, like…

  17. Persistent tumor necrosis factor signaling in normal human fibroblasts prevents the complete resynthesis of I kappa B-alpha.

    PubMed

    Poppers, D M; Schwenger, P; Vilcek, J

    2000-09-22

    Transcription factor NF-kappa B is normally sequestered in the cytoplasm, complexed with I kappa B inhibitory proteins. Tumor necrosis factor (TNF) and interleukin-1 induce I kappa B-alpha phosphorylation, leading to I kappa B-alpha degradation and translocation of NF-kappa B to the nucleus where it activates genes important in inflammatory and immune responses. TNF and interleukin-1 actions are typically terminated by desensitization, and I kappa B-alpha reappearance normally occurs within 30-60 min. We found that in normal human FS-4 fibroblasts maintained in the presence of TNF, I kappa B-alpha protein failed to return to base-line levels for up to 15 h. Removal of TNF at any time during the 15-h period resulted in complete I kappa B-alpha resynthesis, suggesting that I kappa B-alpha reappearance was prevented by continued TNF signaling. Long term exposure of FS-4 fibroblasts to TNF led to a persistent presence of I kappa B-alpha mRNA, sustained I kappa B kinase activation, continuous proteasome-mediated degradation of I kappa B-alpha, and sustained nuclear localization of NF-kappa B. Continuous exposure of FS-4 cells to TNF did not lead to a sustained activation of p38 or ERK mitogen-activated protein kinases, suggesting that not all TNF-induced signaling pathways are persistently activated. These findings challenge the notion that all cytokine-mediated signals are rapidly terminated by desensitization and illustrate the need to elucidate the process of deactivation of TNF-induced signaling.

  18. Interrater agreement in visual scoring of neonatal seizures based on majority voting on a web-based system: The Neoguard EEG database.

    PubMed

    Dereymaeker, Anneleen; Ansari, Amir H; Jansen, Katrien; Cherian, Perumpillichira J; Vervisch, Jan; Govaert, Paul; De Wispelaere, Leen; Dielman, Charlotte; Matic, Vladimir; Dorado, Alexander Caicedo; De Vos, Maarten; Van Huffel, Sabine; Naulaers, Gunnar

    2017-09-01

    To assess interrater agreement based on majority voting in visual scoring of neonatal seizures. An online platform was designed based on a multicentre seizure EEG-database. Consensus decision based on 'majority voting' and interrater agreement was estimated using Fleiss' Kappa. The influences of different factors on agreement were determined. 1919 Events extracted from 280h EEG of 71 neonates were reviewed by 4 raters. Majority voting was applied to assign a seizure/non-seizure classification. 44% of events were classified with high, 36% with moderate, and 20% with poor agreement, resulting in a Kappa value of 0.39. 68% of events were labelled as seizures, and in 46%, all raters were convinced about electrographic seizures. The most common seizure duration was <30s. Raters agreed best for seizures lasting 60-120s. There was a significant difference in electrographic characteristics of seizures versus dubious events, with seizures having longer duration, higher power and amplitude. There is a wide variability in identifying rhythmic ictal and non-ictal EEG events, and only the most robust ictal patterns are consistently agreed upon. Database composition and electrographic characteristics are important factors that influence interrater agreement. The use of well-described databases and input of different experts will improve neonatal EEG interpretation and help to develop uniform seizure definitions, useful for evidence-based studies of seizure recognition and management. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  19. ICI 204448: a kappa-opioid agonist with limited access to the CNS.

    PubMed Central

    Shaw, J. S.; Carroll, J. A.; Alcock, P.; Main, B. G.

    1989-01-01

    1. A number of compounds were evaluated in an attempt to identify a kappa-opioid receptor agonist with limited access to the central nervous system. 2. Quaternary derivatives of the kappa-opioid agonists tifluadom, U-50488H and ethylketocyclazocine were essentially devoid of opioid activity in a range of isolated tissue preparations. 3. A novel compound - ICI 204448 - is described which produced a potent and naloxone-reversible inhibition of electrically-evoked contraction of the guinea-pig ileum, mouse vas deferens and rabbit vas deferens preparations. ICI 204448 was shown to displace the binding of the kappa-opioid ligand [3H]-bremazocine from guinea-pig cerebellum membranes. 4. Ex vivo binding studies in mice showed ICI 204448 to be well absorbed following subcutaneous administration. The brain levels achieved by ICI 20448 were substantially lower than those produced by kappa-agonists such as U-50488H and tifluadom. 5. A good correlation was found for a range of opioids between lipophilicity and degree of CNS penetration. PMID:2568146

  20. Large-scale production of kappa-carrageenan droplets for gel-bead production: theoretical and practical limitations of size and production rate.

    PubMed

    Hunik, J H; Tramper, J

    1993-01-01

    Immobilization of biocatalysts in kappa-carrageenan gel beads is a widely used technique nowadays. Several methods are used to produce the gel beads. The gel-bead production rate is usually sufficient to make the relatively small quantities needed for bench-scale experiments. The droplet diameter can, within limits, be adjusted to the desired size, but it is difficult to predict because of the non-Newtonian fluid behavior of the kappa-carrageenan solution. Here we present the further scale-up of the extrusion technique with the theory to predict the droplet diameters for non-Newtonian fluids. The emphasis is on the droplet formation, which is the rate-limiting step in this extrusion technique. Uniform droplets were formed by breaking up a capillary jet with a sinusoidal signal of a vibration exciter. At the maximum production rate of 27.6 dm3/h, uniform droplets with a diameter of (2.1 +/- 0.12) x 10(-3) m were obtained. This maximum flow rate was limited by the power transfer of the vibration exciter to the liquid flow. It was possible to get a good prediction of the droplet diameter by estimating the local viscosity from shear-rate calculations and an experimental relation between the shear rate and viscosity. In this way the theory of Newtonian fluids could be used for the non-Newtonian kappa-carrageenan solution. The calculated optimal break-up frequencies and droplet sizes were in good agreement with those found in the experiments.

  1. Validating Smoking Data From the Veteran’s Affairs Health Factors Dataset, an Electronic Data Source

    PubMed Central

    Brandt, Cynthia A.; Skanderson, Melissa; Justice, Amy C.; Shahrir, Shahida; Butt, Adeel A.; Brown, Sheldon T.; Freiberg, Matthew S.; Gibert, Cynthia L.; Goetz, Matthew Bidwell; Kim, Joon Woo; Pisani, Margaret A.; Rimland, David; Rodriguez-Barradas, Maria C.; Sico, Jason J.; Tindle, Hilary A.; Crothers, Kristina

    2011-01-01

    Introduction: We assessed smoking data from the Veterans Health Administration (VHA) electronic medical record (EMR) Health Factors dataset. Methods: To assess the validity of the EMR Health Factors smoking data, we first created an algorithm to convert text entries into a 3-category smoking variable (never, former, and current). We compared this EMR smoking variable to 2 different sources of patient self-reported smoking survey data: (a) 6,816 HIV-infected and -uninfected participants in the 8-site Veterans Aging Cohort Study (VACS-8) and (b) a subset of 13,689 participants from the national VACS Virtual Cohort (VACS-VC), who also completed the 1999 Large Health Study (LHS) survey. Sensitivity, specificity, and kappa statistics were used to evaluate agreement of EMR Health Factors smoking data with self-report smoking data. Results: For the EMR Health Factors and VACS-8 comparison of current, former, and never smoking categories, the kappa statistic was .66. For EMR Health Factors and VACS-VC/LHS comparison of smoking, the kappa statistic was .61. Conclusions: Based on kappa statistics, agreement between the EMR Health Factors and survey sources is substantial. Identification of current smokers nationally within the VHA can be used in future studies to track smoking status over time, to evaluate smoking interventions, and to adjust for smoking status in research. Our methodology may provide insights for other organizations seeking to use EMR data for accurate determination of smoking status. PMID:21911825

  2. The inter-rater reliability of the incontinence-associated dermatitis intervention tool-D (IADIT-D) between two independent registered nurses of nursing home residents in long-term care facilities.

    PubMed

    Braunschmidt, Brigitte; Müller, Gerhard; Jukic-Puntigam, Margareta; Steininger, Alfred

    2013-01-01

    Incontinence-associated dermatitis (IAD) is the clinical manifestation of moisture related skin damage (Beeckman, Woodward, & Gray, 2011). Valid assessment instruments are needed for risk assessment and classification of IAD. Aim of the quantitative-descriptive cross-sectional study was to determine the inter-rater reliability of the item scores of the German Incontinence Associated Dermatitis Intervention Tool (IADIT-D) between two independent assessors of nursing home residents (n = 381) in long-term care facilities. The 19 pairs of assessors consisted of registered nurses. The data analysis was computed first with the calculation of the total percentage of agreement. Because this value is not randomly adjusted, the calculation of the Kappa-coefficients and AC1-Statistic was done as well. The total percentage of the inter-rater agreement was 84% (n = 319). In a second step of analysis, the calculation of all items determined high (kappa = .70) and very high agreement (AC1 = .83) levels, respectively. For the risk assessment (kappa = .82; AC1 = .94), the values amounted to very high agreement levels and for the classification (kappa(w) = .70; AC1 = .76) to high agreement levels. The high to very high agreement values of IADIT-D demonstrate that the items can be regarded as stable in regards to the inter-rater reliability for the use in long-term care facilities. In addition, further validation studies are needed.

  3. The LIM-homeodomain transcription factor LMX1B regulates expression of NF-kappa B target genes

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

    Rascle, Anne; Neumann, Tanja; Raschta, Anne-Sarah

    2009-01-01

    LMX1B is a LIM-homeodomain transcription factor essential for development. Putative LMX1B target genes have been identified through mouse gene targeting studies, but their identity as direct LMX1B targets remains hypothetical. We describe here the first molecular characterization of LMX1B target gene regulation. Microarray analysis using a tetracycline-inducible LMX1B expression system in HeLa cells revealed that a subset of NF-{kappa}B target genes, including IL-6 and IL-8, are upregulated in LMX1B-expressing cells. Inhibition of NF-{kappa}B activity by short interfering RNA-mediated knock-down of p65 impairs, while activation of NF-{kappa}B activity by TNF-{alpha} synergizes induction of NF-{kappa}B target genes by LMX1B. Chromatin immunoprecipitation demonstratedmore » that LMX1B binds to the proximal promoter of IL-6 and IL-8 in vivo, in the vicinity of the characterized {kappa}B site, and that LMX1B recruitment correlates with increased NF-{kappa}B DNA association. IL-6 promoter-reporter assays showed that the {kappa}B site and an adjacent putative LMX1B binding motif are both involved in LMX1B-mediated transcription. Expression of NF-{kappa}B target genes is affected in the kidney of Lmx1b{sup -/-} knock-out mice, thus supporting the biological relevance of our findings. Together, these data demonstrate for the first time that LMX1B directly regulates transcription of a subset of NF-{kappa}B target genes in cooperation with nuclear p50/p65 NF-{kappa}B.« less

  4. A new gene in A. rubens: A sea star Ig kappa gene.

    PubMed

    Vincent, Nadine; Osteras, Magne; Otten, Patricia; Leclerc, Michel

    2014-12-01

    The sea star Asterias rubens reacts specifically to the antigen:HRP (horse-radish peroxydase) and produces an antibody anti-HRP. We previously identified a candidate Ig kappa gene corresponding to this manuscript. We show now the gene referred to as: "sea star Ig kappa gene in its specificity".

  5. NF-kappaB mediates mitogen-activated protein kinase pathway-dependent iNOS expression in human melanoma.

    PubMed

    Uffort, Deon G; Grimm, Elizabeth A; Ellerhorst, Julie A

    2009-01-01

    Tumor expression of inducible nitric oxide synthase (iNOS) predicts poor outcomes for melanoma patients. We have reported the regulation of melanoma iNOS by the mitogen-activated protein kinase (MAPK) pathway. In this study, we test the hypothesis that NF-kappaB mediates this regulation. Western blotting of melanoma cell lysates confirmed the constitutive expression of iNOS. Western blot detected baseline levels of activated nuclear extracellular signal-regulated kinase and NF-kappaB. Indirect immunofluorescence confirmed the presence of NF-kappaB p50 and p65 in melanoma cell nuclei, with p50 being more prevalent. Electrophoretic mobility shift assay demonstrated baseline NF-kappaB activity, the findings confirmed by supershift analysis. Treatment of melanoma cells with the MEK inhibitor U0126 decreased NF-kappaB binding to its DNA recognition sequence, implicating the MAPK pathway in NF-kappaB activation. Two specific NF-kappaB inhibitors suppressed iNOS expression, demonstrating regulation of iNOS by NF-kappaB. Several experiments indicated the presence of p50 homodimers, which lack a transactivation domain and rely on the transcriptional coactivator Bcl-3 to carry out this function. Bcl-3 was detected in melanoma cells and co-immunoprecipitated with p50. These data suggest that the constitutively activated melanoma MAPK pathway stimulates activation of NF-kappaB hetero- and homodimers, which, in turn, drive iNOS expression and support melanoma tumorigenesis.

  6. [Comparison of anterior chamber angle examination by UBM, SL-OCT and gonioscopy].

    PubMed

    Liu, Rui-jue; Wang, Men; Xia, Wen-tao; Yu, Xiao-ying; Chen, Jie-min; Zhou, Shu; Peng, Shu-ya; Liu, Dong-mei

    2014-08-01

    To compare the agreement of anterior chamber angle examination by ultrasound biomicroscope (UBM), slit lamp optical coherence tomography (SL-OCT), and gonioscopy in angle recession and angle closure. The anterior chamber angle was measured with UBM, SL-OCT and gonioscopy in turns for temporal, nasal, superior and inferior quadrant in the same dark room. The results were compared with the agreement of the three methods in angle recession and angle closure by χ2 test and Kappa test. There were no statistically significant differences of the three methods in testing angle closure and angle recession (P>0.05). The consistency of UBM and gonioscopy was better (Kappa value of 0.882) than that of SL-OCT and gonioscopy (Kappa value of 0.624). When testing angle recession, UBM is better than SL-OCT with gonioscopy as the standard. When testing angle closure, UBM, SL-OCT and gonioscopy have good agreement.

  7. Retroperitoneal sarcoma (RPS) high risk gross tumor volume boost (HR GTV boost) contour delineation agreement among NRG sarcoma radiation and surgical oncologists.

    PubMed

    Baldini, Elizabeth H; Bosch, Walter; Kane, John M; Abrams, Ross A; Salerno, Kilian E; Deville, Curtiland; Raut, Chandrajit P; Petersen, Ivy A; Chen, Yen-Lin; Mullen, John T; Millikan, Keith W; Karakousis, Giorgos; Kendrick, Michael L; DeLaney, Thomas F; Wang, Dian

    2015-09-01

    Curative intent management of retroperitoneal sarcoma (RPS) requires gross total resection. Preoperative radiotherapy (RT) often is used as an adjuvant to surgery, but recurrence rates remain high. To enhance RT efficacy with acceptable tolerance, there is interest in delivering "boost doses" of RT to high-risk areas of gross tumor volume (HR GTV) judged to be at risk for positive resection margins. We sought to evaluate variability in HR GTV boost target volume delineation among collaborating sarcoma radiation and surgical oncologist teams. Radiation planning CT scans for three cases of RPS were distributed to seven paired radiation and surgical oncologist teams at six institutions. Teams contoured HR GTV boost volumes for each case. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. HRGTV boost volume contour agreement between the seven teams was "substantial" or "moderate" for all cases. Agreement was best on the torso wall posteriorly (abutting posterior chest abdominal wall) and medially (abutting ipsilateral para-vertebral space and great vessels). Contours varied more significantly abutting visceral organs due to differing surgical opinions regarding planned partial organ resection. Agreement of RPS HRGTV boost volumes between sarcoma radiation and surgical oncologist teams was substantial to moderate. Differences were most striking in regions abutting visceral organs, highlighting the importance of collaboration between the radiation and surgical oncologist for "individualized" target delineation on the basis of areas deemed at risk and planned resection.

  8. Utility of physical examination and comparison to echocardiography for cardiac diagnosis.

    PubMed

    Patel, Ashish; Tomar, Nitin Singh; Bharani, Anil

    To find out the accuracy of cardiac auscultation using non-digital stethoscope in physical diagnosis of cardiac diseases. We enrolled 104 consecutive patients with abnormal cardiac auscultatory findings attending cardiology clinic and not previously evaluated by echocardiography. One time detailed cardiac physical examination followed by echocardiography within 1 month was undertaken. Agreement between two methods was calculated using mean pair percentage agreement, kappa statistics (κ) and calculation of 95% confidence interval (CI) for kappa statistics. Using kappa statistics, there was almost perfect agreement between cardiac auscultation and echocardiography for the detection of mitral stenosis (κ=0.865; CI 0.76-0.97) and ventricular septal defect (κ=0.872; CI=0.73-1.01). Substantial agreement was noted for aortic stenosis (κ=0.752; CI=0.56-0.94), pulmonary stenosis (κ=0.647; CI=0.33-0.97) and atrial septal defect (κ=0.646; CI=0.32-0.97), while moderate agreement was found for mitral regurgitation (κ=0.470; CI=0.30-0.64), aortic regurgitation (κ=0.456; CI=0.25-0.66) and tricuspid regurgitation (κ=0.575; CI=0.38-0.77). For combined mitral stenosis and mitral regurgitation lesions, almost perfect agreement was found for mitral stenosis (κ=0.842; CI=0.691-0.993) while fair agreement noted for mitral regurgitation (κ=0.255; CI=-0.008 to 0.518). Careful clinical auscultation using a stethoscope remains a valuable tool for cardiac diagnosis. Decision on initial diagnosis and management of valvular and congenital heart diseases should be based on clinical examination and integrating such information with echocardiography as required. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  9. Spectral geometry of {kappa}-Minkowski space

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

    D'Andrea, Francesco

    After recalling Snyder's idea [Phys. Rev. 71, 38 (1947)] of using vector fields over a smooth manifold as 'coordinates on a noncommutative space', we discuss a two-dimensional toy-model whose 'dual' noncommutative coordinates form a Lie algebra: this is the well-known {kappa}-Minkowski space [Phys. Lett. B 334, 348 (1994)]. We show how to improve Snyder's idea using the tools of quantum groups and noncommutative geometry. We find a natural representation of the coordinate algebra of {kappa}-Minkowski as linear operators on an Hilbert space (a major problem in the construction of a physical theory), study its 'spectral properties', and discuss how tomore » obtain a Dirac operator for this space. We describe two Dirac operators. The first is associated with a spectral triple. We prove that the cyclic integral of Dimitrijevic et al. [Eur. Phys. J. C 31, 129 (2003)] can be obtained as Dixmier trace associated to this triple. The second Dirac operator is equivariant for the action of the quantum Euclidean group, but it has unbounded commutators with the algebra.« less

  10. Chlamydia pneumoniae activates IKK/I kappa B-mediated signaling, which is inhibited by 4-HNE and following primary exposure.

    PubMed

    Donath, Bernadette; Fischer, Claudia; Page, Sharon; Prebeck, Sigrid; Jilg, Nikolaus; Weber, Marion; da Costa, Clarissa; Neumeier, Dieter; Miethke, Thomas; Brand, Korbinian

    2002-11-01

    Chlamydia pneumoniae may be involved in atherosclerosis by inducing inflammation as well as LDL oxidation. The transcription factor NF-kappa B is found in an active state in atherosclerotic lesions. This study examined the effect of C. pneumoniae exposure on the NF-kappa B system in human monocytic lineage cells. Short exposure to C. pneumoniae as well as chlamydial heat shock protein 60 activated NF-kappa B, accompanied by increased cytokine production. Incubation with C. pneumoniae-induced depletion of I kappa B-alpha and later I kappa B-epsilon which was preceded by I kappa B kinase complex activation. 4-Hydroxynonenal, an aldehyde LDL oxidation product, was shown to inhibit C. pneumoniae induced NF-kappa B activation by preventing I kappa B phosphorylation/proteolysis. During long-term incubation with C. pneumoniae I kappa B-alpha returned to baseline, whereas the levels of I kappa B-epsilon and p65 were upregulated. Interestingly, long-term preincubation with C. pneumoniae selectively prevented restimulation by this microorganism, which appears to be at least partly facilitated by inhibition of I kappa B proteolysis. C. pneumoniae-induced NF-kappa B activation as well as the inhibition of that effect under certain conditions may contribute to chronic inflammation with potential relevance to vascular disease.

  11. Reinstatement of cocaine place-conditioning prevented by the peptide kappa-opioid receptor antagonist arodyn.

    PubMed

    Carey, A N; Borozny, K; Aldrich, J V; McLaughlin, J P

    2007-08-13

    Stress contributes to the reinstatement of cocaine-seeking behavior in abstinent subjects. Kappa-opioid receptor antagonists attenuate the behavioral effects of stress, potentially providing therapeutic value in treating cocaine abuse. Presently, the peptide arodyn produced long-lasting kappa-opioid receptor antagonism, suppressing kappa-opioid receptor agonist-induced antinociception at least 3 days after intracerebroventricular administration of 0.3 nmol. C57Bl/6J mice demonstrated cocaine-conditioned place preference, extinction over 3 weeks, and a subsequent reinstatement of place preference. Arodyn pretreatment suppressed stress-induced, but not cocaine-exposed, reinstatement of cocaine place preference. These results verify that arodyn and other kappa-opioid receptor antagonists may be useful therapeutics for cocaine abuse.

  12. Agreement Between 35 Published Frailty Scores in the General Population

    PubMed Central

    Aguayo, Gloria A.; Donneau, Anne-Françoise; Vaillant, Michel T.; Schritz, Anna; Franco, Oscar H.; Stranges, Saverio; Malisoux, Laurent; Guillaume, Michèle; Witte, Daniel R.

    2017-01-01

    Abstract In elderly populations, frailty is associated with higher mortality risk. Although many frailty scores (FS) have been proposed, no single score is considered the gold standard. We aimed to evaluate the agreement between a wide range of FS in the English Longitudinal Study of Ageing (ELSA). Through a literature search, we identified 35 FS that could be calculated in ELSA wave 2 (2004–2005). We examined agreement between each frailty score and the mean of 35 FS, using a modified Bland-Altman model and Cohen's kappa (κ). Missing data were imputed. Data from 5,377 participants (ages ≥60 years) were analyzed (44.7% men, 55.3% women). FS showed widely differing degrees of agreement with the mean of all scores and between each pair of scores. Frailty classification also showed a very wide range of agreement (Cohen's κ = 0.10–0.83). Agreement was highest among “accumulation of deficits”-type FS, while accuracy was highest for multidimensional FS. There is marked heterogeneity in the degree to which various FS estimate frailty and in the identification of particular individuals as frail. Different FS are based on different concepts of frailty, and most pairs cannot be assumed to be interchangeable. Research results based on different FS cannot be compared or pooled. PMID:28633404

  13. Effect of clinical information and previous exam execution on observer agreement and reliability in the analysis of hysteroscopic video-recordings.

    PubMed

    Martinho, Margarida Suzel Lopes; da Costa Santos, Cristina Maria Nogueira; Silva Carvalho, João Luís Mendonça; Bernardes, João Francisco Montenegro Andrade Lima

    2018-02-01

    Inter-observer agreement and reliability in hysteroscopic image assessment remain uncertain and the type of factors that may influence it has only been studied in relation to the experience of hysteroscopists. We aim to assess the effect of clinical information and previous exam execution on observer agreement and reliability in the analysis of hysteroscopic video-recordings. Ninety hysteroscopies were video-recorded and randomized into a group without (Group 1) and with clinical information (Group 2). The videos were independently analyzed by three hysteroscopists, regarding lesion location, dimension, and type, as well as decision to perform a biopsy. One of the hysteroscopists had executed all the exams before. Proportions of agreement (PA) and kappa statistics (κ) with 95% confidence intervals (95% CI) were used. In Group 2, there was a higher proportion of a normal diagnosis (p < 0.001) and a lower proportion of biopsies recommended (p = 0.027). Observer agreement and reliability were better in Group 2, with the PA and κ ranging, respectively, from 0.73 (95% CI 0.62, 0.83) and 0.44 (95% CI 0.26, 0.63), for image quality, to 0.94 (95% CI 0.88, 0.99) and 0.85 (95% CI 0.65, 0.95), for the decision to perform a biopsy. Execution of the exams before the analysis of the video-recordings did not significantly affect the results. With clinical information, agreement and reliability in the overall analysis of hysteroscopic video-recordings may reach almost perfect results and this was not significantly affected by the execution of the exams before the analysis. However, there is still uncertainty in the analysis of specific endometrial cavity abnormalities.

  14. Human placenta: relative content of antibodies of different classes and subclasses (IgG1-IgG4) containing lambda- and kappa-light chains and chimeric lambda-kappa-immunoglobulins.

    PubMed

    Lekchnov, Evgenii A; Sedykh, Sergey E; Dmitrenok, Pavel S; Buneva, Valentina N; Nevinsky, Georgy A

    2015-06-01

    The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Affinity chromatography, ELISA, SDS-PAGE and matrix-assisted laser desorption ionization mass spectrometry were used. Using 10 intact human placentas deprived of blood, a quantitative analysis of average relative content [% of total immunoglobulins (Igs)] was carried out for the first time: (92.7), IgA (2.4), IgM (2.5), kappa-antibodies (51.4), lambda-antibodies (48.6), IgG1 (47.0), IgG2 (39.5), IgG3 (8.8) and IgG4 (4.3). It was shown for the first time that placenta contains sIgA (2.5%). In the classic paradigm, Igs represent products of clonal B-cell populations, each producing antibodies recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, similarly to human milk Igs, placenta antibodies undergo extensive half-molecule exchange and the IgG pool consists of 43.5 ± 15.0% kappa-kappa-IgGs and 41.6 ± 17.0% lambda-lambda-IgGs, while 15.0 ± 4.0% of the IgGs contained both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained, respectively (%): IgG1 (47.7 and 34.4), IgG2 (36.3 and 44.5), IgG3 (7.4 and 11.8) and IgG4 (7.5 and 9.1), while chimeric kappa-lambda-IgGs consisted of (%): 43.5 IgG1, 41.0 IgG2, 5.6 IgG3 and 7.9 IgG4. Our data are indicative of the possibility of half-molecule exchange between placenta IgGs of various subclasses, raised against different antigens, which explains a very well-known polyspecificity and cross-reactivity of different human IgGs. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Degree of agreement among sepsis diagnosis criteria in adult emergency room patients with infection

    NASA Astrophysics Data System (ADS)

    Sinto, R.; Chandra, A. T.; Lie, K. C.; Suwarto, S.

    2018-03-01

    The study on the degree of agreement among three established sepsis diagnosis criteria become the necessity to investigate the best sepsis diagnosis criteria in Indonesia further. A cross-sectional study of adult Emergency Room patients hospitalized with a diagnosis of infection in CiptoMangunkusumo Hospital, Indonesia was conducted during March and April 2017. We recorded diagnosis, gender, age, comorbidities, infection source, and origin. Every subject was classified into sepsis and non-sepsis based on 1991, 2001 and sepsis-3 criteria. Raw % and Kappa agreement coefficients (κ) were calculated according to previously established formula to measure the degree of agreement among three diagnostic criteria. As many as 278 subjects were included in this study. The raw % agreement and κ between 1991 and 2001 criteria is 69.07% and 0.34 respectively. The raw % agreement and κ between 2001 and sepsis-3 criteria is 56.12% and 0.15 respectively. The raw % agreement and κ between 1991 and sepsis-3 criteria is 48.19% and -0.02. In conclusions, there is afair agreement between 1991 and 2001 criteria, poor agreement between 2001 and sepsis-3 criteria, and poor disagreement between 1991 and sepsis-3 criteria. This necessitates further Indonesian study of the best diagnosis criteria to diagnose an infected patient with sepsis.

  16. Inverse expression of estrogen receptor-beta and nuclear factor-kappaB in urinary bladder carcinogenesis.

    PubMed

    Kontos, Stylianos; Kominea, Athina; Melachrinou, Maria; Balampani, Eleni; Sotiropoulou-Bonikou, Georgia

    2010-09-01

    To investigate the expression of nuclear factor-kappaB (NF-kappaB) and estrogen receptor-beta (ER-beta) signalling pathways in bladder urothelial carcinoma according to clinicopathological features, in order to elucidate their role during carcinogenesis. Immunohistochemical methodology was carried out on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females) who underwent transurethral resection of bladder neoplasms. Correlations between ER-beta and NF-kappaB, and tumor grade and T-stage were evaluated, along with demographic data, sex and age. A significant decrease in ER-beta expression in the nucleus of bladder cells during loss of cell differentiation (r(s) = -0.61, P-value < 0.001, test of trend P-value = 0.003) and in muscle invasive carcinomas (T2-T4; test of trend P-value < 0.001) was found. p65 Subunit of NF-kappaB was expressed in the nucleus and in the cytoplasm of bladder epithelial cells. A strong positive association between tumor grade and nuclear expression of NF-kappaB was shown. No correlation between NF-kappaB, nuclear or cytoplasmic staining, with T-stage was observed. An inverse correlation between ER-beta and nuclear p65 immunoreactivity was observed (r(s) = -0.45, P-value < 0.001). There was no correlation with demographic data. Our immunohistochemical study suggests the possible inverse regulation of NF-kappaB and ER-beta transcription factor during bladder carcinogenesis. Selective ER-beta agonists and agents, inhibitors of NF-kappaB, might represent a possible new treatment strategy for bladder urothelial tumors.

  17. NF-{kappa}B p65 represses {beta}-catenin-activated transcription of cyclin D1

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

    Hwang, Injoo; Choi, Yong Seok; Jeon, Mi-Ya

    2010-12-03

    Research highlights: {yields} Cyclin D1 transcription is directly activated by {beta}-catenin; however, {beta}-catenin-induced cyclin D1 transcription is reduced by NF-{kappa}B p65. {yields} Protein-protein interaction between NF-{kappa}B p65 and {beta}-catenin might be responsible for p65-mediated repression of cyclin D1. {yields} One of five putative binding sites, located further upstream of other sites, is the major {beta}-catenin binding site in the cyclin D1 promoter. {yields} NF-{kappa}B binding site in cyclin D1 is occupied not only by p65 but also by {beta}-catenin, which is dynamically regulated by the signal. -- Abstract: Signaling crosstalk between the {beta}-catenin and NF-{kappa}B pathways represents a functional network.more » To test whether the crosstalk also occurs on their common target genes, the cyclin D1 promoter was used as a model because it contains binding sites for both proteins. {beta}-catenin activated transcription from the cyclin D1 promoter, while co-expression of NF-{kappa}B p65 reduced {beta}-catenin-induced transcription. Chromatin immunoprecipitation revealed lithium chloride-induced binding of {beta}-catenin on one of the T-cell activating factor binding sites. More interestingly, {beta}-catenin binding was greatly reduced by NF-{kappa}B p65, possibly by the protein-protein interaction between the two proteins. Such a dynamic and complex binding of {beta}-catenin and NF-{kappa}B on promoters might contribute to the regulated expression of their target genes.« less

  18. Peripheral kappa-opioid agonist, ICI 204448, evokes hypothermia in cold-exposed rats.

    PubMed

    Rawls, Scott M; Ding, Zhe; Gray, Alex M; Cowan, Alan

    2005-05-01

    ICI 204448, a selective kappa-opioid agonist with limited CNS access, can be used to discriminate central and peripheral opioid actions on physiological systems such as pain and thermoregulation. Therefore, we investigated the effect of ICI 204448 (2.5, 5, and 10 mg/kg, s.c.) on male Sprague-Dawley rats exposed to ambient temperatures of 5, 20, or 32 degrees C. ICI 204448 did not alter the body temperature of rats maintained at 20 or 32 degrees C. However, 5 and 10 mg/kg of ICI 204448 evoked significant hypothermia in rats exposed to 5 degrees C. The i.c.v. administration of nor-BNI, a kappa-opioid antagonist, did not affect the hypothermia produced by the systemic injection of ICI 204448. Thus, an involvement of brain kappa-opioid receptors in ICI 204448-evoked hypothermia is unlikely. The present data demonstrate for the first time that ICI 204448 produces hypothermia in cold-exposed rats and suggest that the role of peripheral kappa-opioid receptors in thermoregulation becomes more significant at cold ambient temperatures. Copyright (c) 2005 S. Karger AG, Basel.

  19. Low agreement between the fitnessgram criterion references for adolescents

    PubMed Central

    Coledam, Diogo Henrique Constantino; Batista, João Pedro; Glaner, Maria Fátima

    2015-01-01

    OBJECTIVE: To analyze the association and agreement of fitnessgram reference criteria (RC) for cardiorespiratory fitness, body mass index (BMI) and strength in youth. METHODS: The study included 781 youth, 386 females, aged 10 to 18 years of Londrina-PR. It were performed cardiorespiratory fitness and muscular strength tests and was calculated body mass index. The association between the tests was analyzed using Poisson regression to obtain prevalence ratio (PR) and confidence intervals of 95%, while agreement of the reference criteria was tested by Kappa index. RESULTS: Significant associations were found between cardiorespiratory fitness and BMI (PR=1,49, 1,27-1,75), muscle strength and BMI (PR=1,55, 1,17-2,08), cardiorespiratory fitness and muscle strength (PR=1,81, 1,47-2,24). The agreement between reference criteria ranged from weak to fair, 48.8% (k=0.05, p=0.10) for cardiorespiratory fitness and BMI, 52.9% (k=0.09, p=0.001) for muscle strength and BMI and 38.4% (k=0.22, p<0.001) for cardiorespiratory fitness and muscle strength. CONCLUSIONS: Although RC for cardiorespiratory fitness, muscle strength and BMI are associated, the agreement between them ranged from weak to fair. To evaluate health related physical fitness it is suggest the execution of all tests, since each test has specific characteristics. PMID:25649383

  20. Colloidal gas-liquid condensation of polystyrene latex particles with intermediate kappa a values (5 to 160, a > kappa(-1)).

    PubMed

    Ishikawa, Masamichi; Kitano, Ryota

    2010-02-16

    Polystyrene latex particles showed gas-liquid condensation under the conditions of large particle radius (a > kappa(-1)) and intermediate kappa a, where kappa is the Debye-Hückel parameter and a is the particle radius. The particles were dissolved in deionized water containing ethanol from 0 to 77 vol %, settled to the bottom of the glass plate within 1 h, and then laterally moved toward the center of a cell over a 20 h period in reaching a state of equilibrium condensation. All of the suspensions that were 1 and 3 microm in diameter and 0.01-0.20 vol % in concentration realized similar gas-liquid condensation with clear gas-liquid boundaries. In 50 vol % ethanol solvent, additional ethanol was added to enhance the sedimentation force so as to restrict the particles in a monoparticle layer thickness. The coexistence of gas-liquid-solid (crystalline solid) was microscopically recognized from the periphery to the center of the condensates. A phase diagram of the gas-liquid condensation was created as a function of KCl concentration at a particle diameter of 3 microm, 0.10 vol % concentration, and 50:50 water/ethanol solvent at room temperature. The miscibility gap was observed in the concentration range from 1 to 250 microM. There was an upper limit of salt concentration where the phase separation disappeared, showing nearly critical behavior of macroscopic density fluctuation from 250 microM to 1 mM. These results add new experimental evidence to the existence of colloidal gas-liquid condensation and specify conditions of like-charge attraction between particles.

  1. GS143, an I{kappa}B ubiquitination inhibitor, inhibits allergic airway inflammation in mice

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

    Hirose, Koichi; Wakashin, Hidefumi; Oki, Mie

    2008-09-26

    Asthma is characterized by airway inflammation with intense eosinophil infiltration and mucus hyper-production, in which antigen-specific Th2 cells play critical roles. Nuclear factor-{kappa}B (NF-{kappa}B) pathway has been demonstrated to be essential for the production of Th2 cytokines and chemokines in the airways in murine asthma models. In the present study, we examined the effect of GS143, a novel small-molecule inhibitor of I{kappa}B ubiquitination, on antigen-induced airway inflammation and Th2 cytokine production in mice. Intranasal administration of GS143 prior to antigen challenge suppressed antigen-induced NF-{kappa}B activation in the lung of sensitized mice. Intranasal administration of GS143 also inhibited antigen-induced eosinophil andmore » lymphocyte recruitment into the airways as well as the expression of Th2 cytokines and eotaxin in the airways. Moreover, GS143 inhibited antigen-induced differentiation of Th2 cells but not of Th1 cells in vitro. Taken together, these results suggest that I{kappa}B ubiquitination inhibitor may have therapeutic potential against asthma.« less

  2. Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions.

    PubMed

    Townsend, Catherine L; Laffy, Julie M J; Wu, Yu-Chang Bryan; Silva O'Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K

    2016-01-01

    Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  3. Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions

    PubMed Central

    Townsend, Catherine L.; Laffy, Julie M. J.; Wu, Yu-Chang Bryan; Silva O’Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K.

    2016-01-01

    Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response. PMID:27729912

  4. Method for rapidly determining a pulp kappa number using spectrophotometry

    DOEpatents

    Chai, Xin-Sheng; Zhu, Jun Yong

    2002-01-01

    A system and method for rapidly determining the pulp kappa number through direct measurement of the potassium permanganate concentration in a pulp-permanganate solution using spectrophotometry. Specifically, the present invention uses strong acidification to carry out the pulp-permanganate oxidation reaction in the pulp-permanganate solution to prevent the precipitation of manganese dioxide (MnO.sub.2). Consequently, spectral interference from the precipitated MnO.sub.2 is eliminated and the oxidation reaction becomes dominant. The spectral intensity of the oxidation reaction is then analyzed to determine the pulp kappa number.

  5. 28 CFR 22.24 - Information transfer agreement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STATISTICAL INFORMATION § 22.24 Information transfer agreement. Prior to the transfer of any identifiable... identifiable to a private person will be used only for research and statistical purposes. (b) Information...-know basis for research or statistical purposes, provided that such transfer is approved by the person...

  6. Low frequency electromagnetic fluctuations in Kappa magnetized plasmas

    NASA Astrophysics Data System (ADS)

    Kim, Sunjung; Lazar, M.; Schlickeiser, R.; López, R. A.; Yoon, P. H.

    2018-07-01

    The present paper provides a theoretical approach for the evaluation of the low frequency spontaneously emitted electromagnetic (EM) fluctuations in Kappa magnetized plasmas, which include the kinetic Alfvén, fast magnetosonic/whistler, kinetic slow mode, ion Bernstein cyclotron modes, and higher-order modes. The model predictions are consistent with particle-in-cell simulations. Effects of suprathermal particles on low frequency fluctuations are studied by varying the power index, either for ions (κ i) or for electrons (κ e). Computations for an arbitrary wave vector orientation and wave polarization provide the intensity of spontaneous emissions to be enhanced in the presence of suprathermal populations. These results strongly suggest that spontaneous fluctuations may significantly contribute to the EM fluctuations observed in space plasmas, where suprathermal Kappa distributed particles are ubiquitous.

  7. Lenke and King classification systems for adolescent idiopathic scoliosis: interobserver agreement and postoperative results

    PubMed Central

    Hosseinpour-Feizi, Hojjat; Soleimanpour, Jafar; Sales, Jafar Ganjpour; Arzroumchilar, Ali

    2011-01-01

    Purpose The aim of this study was to investigate the interobserver agreement of the Lenke and King classifications for adolescent idiopathic scoliosis, and to compare the results of surgery performed based on classification of the scoliosis according to each of these classification systems. Methods The study was conducted in Shohada Hospital in Tabriz, Iran, between 2009 and 2010. First, a reliability assessment was undertaken to assess interobserver agreement of the Lenke and King classifications for adolescent idiopathic scoliosis. Second, postoperative efficacy and safety of surgery performed based on the Lenke and King classifications were compared. Kappa coefficients of agreement were calculated to assess the agreement. Outcomes were compared using bivariate tests and repeated measures analysis of variance. Results A low to moderate interobserver agreement was observed for the King classification; the Lenke classification yielded mostly high agreement coefficients. The outcome of surgery was not found to be substantially different between the two systems. Conclusion Based on the results, the Lenke classification method seems advantageous. This takes into consideration the Lenke classification’s priority in providing details of curvatures in different anatomical surfaces to explain precise intensity of scoliosis, that it has higher interobserver agreement scores, and also that it leads to noninferior postoperative results compared with the King classification method. PMID:22267934

  8. Lenke and King classification systems for adolescent idiopathic scoliosis: interobserver agreement and postoperative results.

    PubMed

    Hosseinpour-Feizi, Hojjat; Soleimanpour, Jafar; Sales, Jafar Ganjpour; Arzroumchilar, Ali

    2011-01-01

    The aim of this study was to investigate the interobserver agreement of the Lenke and King classifications for adolescent idiopathic scoliosis, and to compare the results of surgery performed based on classification of the scoliosis according to each of these classification systems. The study was conducted in Shohada Hospital in Tabriz, Iran, between 2009 and 2010. First, a reliability assessment was undertaken to assess interobserver agreement of the Lenke and King classifications for adolescent idiopathic scoliosis. Second, postoperative efficacy and safety of surgery performed based on the Lenke and King classifications were compared. Kappa coefficients of agreement were calculated to assess the agreement. Outcomes were compared using bivariate tests and repeated measures analysis of variance. A low to moderate interobserver agreement was observed for the King classification; the Lenke classification yielded mostly high agreement coefficients. The outcome of surgery was not found to be substantially different between the two systems. Based on the results, the Lenke classification method seems advantageous. This takes into consideration the Lenke classification's priority in providing details of curvatures in different anatomical surfaces to explain precise intensity of scoliosis, that it has higher interobserver agreement scores, and also that it leads to noninferior postoperative results compared with the King classification method.

  9. Evaluation of data obtained from military disability medical administrative databases for service members with schizophrenia or bipolar disorder.

    PubMed

    Millikan, Amy M; Weber, Natalya S; Niebuhr, David W; Torrey, E Fuller; Cowan, David N; Li, Yuanzhang; Kaminski, Brenda

    2007-10-01

    We are studying associations between selected biomarkers and schizophrenia or bipolar disorder among military personnel. To assess potential diagnostic misclassification and to estimate the date of illness onset, we reviewed medical records for a subset of cases. Two psychiatrists independently reviewed 182 service medical records retrieved from the Department of Veterans Affairs. Data were evaluated for diagnostic concordance between database diagnoses and reviewers. Interreviewer variability was measured by using proportion of agreement and the kappa statistic. Data were abstracted to estimate date of onset. High levels of agreement existed between database diagnoses and reviewers (proportion, 94.7%; kappa = 0.88) and between reviewers (proportion, 92.3%; kappa = 0.87). The median time between illness onset and initiation of medical discharge was 1.6 and 1.1 years for schizophrenia and bipolar disorder, respectively. High levels of agreement between investigators and database diagnoses indicate that diagnostic misclassification is unlikely. Discharge procedure initiation date provides a suitable surrogate for disease onset.

  10. A method for reducing misclassification in the extended Glasgow Outcome Score.

    PubMed

    Lu, Juan; Marmarou, Anthony; Lapane, Kate; Turf, Elizabeth; Wilson, Lindsay

    2010-05-01

    The eight-point extended Glasgow Outcome Scale (GOSE) is commonly used as the primary outcome measure in traumatic brain injury (TBI) clinical trials. The outcome is conventionally collected through a structured interview with the patient alone or together with a caretaker. Despite the fact that using the structured interview questionnaires helps reach agreement in GOSE assessment between raters, significant variation remains among different raters. We introduce an alternate GOSE rating system as an aid in determining GOSE scores, with the objective of reducing inter-rater variation in the primary outcome assessment in TBI trials. Forty-five trauma centers were randomly assigned to three groups to assess GOSE scores on sample cases, using the alternative GOSE rating system coupled with central quality control (Group 1), the alternative system alone (Group 2), or conventional structured interviews (Group 3). The inter-rater variation between an expert and untrained raters was assessed for each group and reported through raw agreement and with weighted kappa (kappa) statistics. Groups 2 and 3 without central review yielded inter-rater agreements of 83% (weighted kappa = 0.81; 95% CI 0.69, 0.92) and 83% (weighted kappa = 0.76, 95% CI 0.63, 0.89), respectively, in GOS scores. In GOSE, the groups had an agreement of 76% (weighted kappa = 0.79; 95% CI 0.69, 0.89), and 63% (weighted kappa = 0.70; 95% CI 0.60, 0.81), respectively. The group using the alternative rating system coupled with central monitoring yielded the highest inter-rater agreement among the three groups in rating GOS (97%; weighted kappa = 0.95; 95% CI 0.89, 1.00), and GOSE (97%; weighted kappa = 0.97; 95% CI 0.91, 1.00). The alternate system is an improved GOSE rating method that reduces inter-rater variations and provides for the first time, source documentation and structured narratives that allow a thorough central review of information. The data suggest that a collective effort can be made to

  11. Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the cytoplasm through nuclear export.

    PubMed

    Chen, Yao; Li, Hong Hai; Fu, Jing; Wang, Xue Feng; Ren, Yi Bin; Dong, Li Wei; Tang, Shan Hua; Liu, Shu Qing; Wu, Meng Chao; Wang, Hong Yang

    2007-12-01

    p28(GANK) (also known as PSMD10, p28 and gankyrin) is an ankyrin repeat anti-apoptotic oncoprotein that is commonly overexpressed in hepatocellular carcinomas and increases the degradation of p53 and Rb. NF-kappaB (nuclear factor-kappaB) is known to be sequestered in the cytoplasm by I kappaB (inhibitor of NF-kappaB) proteins, but much less is known about the cytoplasmic retention of NF-kappaB by other cellular proteins. Here we show that p28(GANK) inhibits NF-kappaB activity. As a nuclear-cytoplasmic shuttling protein, p28(GANK) directly binds to NF-kappaB/RelA and exports RelA from nucleus through a chromosomal region maintenance-1 (CRM-1) dependent pathway, which results in the cytoplasmic retention of NF-kappaB/RelA. We demonstrate that all the ankyrin repeats of p28(GANK) are required for the interaction with RelA and that the N terminus of p28(GANK), which contains the nuclear export sequence (NES), is responsible for suppressing NF-kappaB/RelA nuclear translocation. These results suggest that overexpression of p28(GANK) prevents the nuclear localization and inhibits the activity of NF-kappaB/RelA.

  12. Agreement among orthodontists experienced with cone-beam computed tomography on the need for follow-up and the clinical impact of craniofacial findings from multiplanar and 3-dimensional reconstructed views.

    PubMed

    Edwards, Ryan; Alsufyani, Noura; Heo, Giseon; Flores-Mir, Carlos

    2015-08-01

    In this study, we aimed to assess interrater and intrarater agreement among orthodontic clinicians in their assessments of reported incidental findings in regard to both the need for additional follow-up and the impact on future orthodontic treatment in large-field maxillofacial cone-beam computed tomography (CBCT) imaging. The study sample consisted of 18 nonrandomly selected large-field maxillofacial CBCT volumes containing a reported total of 88 radiographic findings. All scans were associated with formal radiologic reports. However, the suggestions of further follow-up were removed from the radiologic reports so as to not bias the 3 evaluating orthodontists in their subsequent decision making. The evaluators had on average 7.6 years of CBCT usage and self-interpretation experience. Reliability was determined by quantifying the level of agreement between the evaluators' assessments for both research questions for all 88 findings using a binary response (yes/no) as the outcome measure. The Cohen kappa statistic was calculated to quantify intrarater and interrater agreement globally for both statements. Although interrater agreement was considerable, potential decisions with clinical impact were not consistent. This needs to be considered when interpreting maxillofacial incidental findings. Evaluators demonstrated higher levels of agreement for dentoalveolar findings compared with all other extragnathic regions when assessing clinical significance. Among the evaluators who were considered experienced in CBCT, "fair-to-good" interrater agreement and "excellent" intrarater agreement were demonstrated in terms of the need for further follow-up and their potential impact on future orthodontic treatment. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  13. Analysis and Quantitation of NF-[kappa]B Nuclear Translocation in Tumor Necrosis Factor Alpha (TNF-[alpha]) Activated Vascular Endothelial Cells

    NASA Astrophysics Data System (ADS)

    Fuseler, John W.; Merrill, Dana M.; Rogers, Jennifer A.; Grisham, Matthew B.; Wolf, Robert E.

    2006-07-01

    Nuclear factor kappa B (NF-[kappa]B) is a heterodimeric transcription factor typically composed of p50 and p65 subunits and is a pleiotropic regulator of various inflammatory and immune responses. In quiescent cells, p50/p65 dimers are sequestered in the cytoplasm bound to its inhibitors, the I-[kappa]Bs, which prevent entry into the nucleus. Following cellular stimulation, the I-[kappa]Bs are rapidly degraded, activating NF-[kappa]B. The active form of NF-[kappa]B rapidly translocates into the nucleus, binding to consensus sequences in the promoter/enhancer region of various genes, promoting their transcription. In human vascular endothelial cells activated with tumor necrosis factor-alpha, the activation and translocation of NF-[kappa]B is rapid, reaching maximal nuclear localization by 30 min. In this study, the appearance of NF-[kappa]B (p65 subunit, p65-NF-[kappa]B) in the nucleus visualized by immunofluorescence and quantified by morphometric image analysis (integrated optical density, IOD) is compared to the appearance of activated p65-NF-[kappa]B protein in the nucleus determined biochemically. The appearance of p65-NF-[kappa]B in the nucleus measured by fluorescence image analysis and biochemically express a linear correlation (R2 = 0.9477). These data suggest that localization and relative protein concentrations of NF-[kappa]B can be reliably determined from IOD measurements of the immunofluorescent labeled protein.

  14. Agreement on Reporting of Physical, Psychological and Sexual Violence Among White, Black and Hispanic Couples in the U.S.

    PubMed Central

    Caetano, Raul; Field, Craig; Ramisetty-Mikler, Susie; Lipsky, Sherry

    2008-01-01

    This paper examines agreement on reports of male-to-female (MFPV) and female-to-male (FMPV) psychological, physical and sexual violence among White, Black and Hispanic couples in the U.S. Using a probability sample, separate face-to-face interviews were conducted in respondents’ homes with both members of 1,025 intact couples living in the 48 contiguous states. The overall survey response rate was 72%. Results indicate that agreement on each of the three types of violence is low, independent of perpetrator’s gender and ethnicity. Kappa coefficients of agreement ranged from .07 to .48. Higher agreement is obtained for psychological violence, followed by physical and sexual violence. Depending on the type of violence, between 30% (psychological aggression) and 90% (sexual coercion) of events would not have been identified if identification required agreement between partners. Logistic analysis shows that the severity of violence is the only variable that increases the likelihood of agreement across the three types of violence. PMID:18768744

  15. Comparison of the tuberculin skin test and the QuantiFERON-TB Gold test in detecting latent tuberculosis in health care workers in Iran

    PubMed Central

    2016-01-01

    OBJECTIVES: The tuberculin skin test (TST) and the QuantiFERON-TB Gold test (QFT) are used to identify latent tuberculosis infections (LTBIs). The aim of this study was to determine the agreement between these two tests among health care workers in Iran. METHODS: This cross-sectional study included 177 tuberculosis (TB) laboratory staff and 67 non-TB staff. TST indurations of 10 mm or more were considered positive. The Student’s t-test and the chi-square test were used to compare the mean score and proportion of variables between the TB laboratory staff and the non-TB laboratory staff. Kappa statistics were used to evaluate the agreement between these tests, and logistic regression was used to assess the risk factors associated with positive results for each test. RESULTS: The prevalence of LTBIs according to both the QFT and the TST was 17% (95% confidence interval [CI], 12% to 21%) and 16% (95% CI, 11% to 21%), respectively. The agreement between the QFT and the TST was 77.46%, with a kappa of 0.19 (95% CI, 0.04 to 0.34). CONCLUSIONS: Although the prevalence of LTBI based on the QFT and the TST was not significantly different, the kappa statistic was low between these two tests for the detection of LTBIs. PMID:27457062

  16. Inter-physician agreement on the readiness of sick-listed employees to return to work.

    PubMed

    Schreuder, Jolanda A H; Roelen, Corné A M; de Boer, Mintje; Brouwer, Sandra; Groothoff, Johan W

    2012-01-01

    To determine the agreement between occupational physician (OP) ratings of an employee's readiness to return to work (RRTW). Anonymized written vignettes of 132 employees, sick-listed for at least 3 weeks, were reviewed by 5 OPs. The OPs intuitively rated RRTW as the ability (knowledge and skills) and willingness (motivation and confidence) of sick-listed employees to resume work. Inter-OP percentages of agreement were calculated and Cohen's kappas (κ) were determined to correct for agreement by chance. The percentage of agreement between OPs was 57% (range 39-89%) on the ability and 63% (range 48-87%) on the willingness of sick-listed employees to resume work. The mean κ was 0.14 (range from -0.21 to 0.79) for ability and 0.25 (range from -0.11 to 0.74) for willingness. The OP-rating of RRTW of employees sick-listed with mental disorders did not differ from the OP-rating of RRTW of employees with musculoskeletal disorders. The inter-OP agreement on intuitively rated RRTW showed a wide variability, which accentuates the need for instruments to establish an employee's RRTW and for training in giving well founded return to work recommendations.

  17. Agreement of Tracing and Direct Viewing Techniques for Cervical Vertebral Maturation Assessment.

    PubMed

    Wiwatworakul, Opas; Manosudprasit, Montian; Pisek, Poonsak; Chatrchaiwiwatana, Supaporn; Wangsrimongkol, Tasanee

    2015-08-01

    This study aimed to evaluate agreement among three methods for cervical vertebral maturation (CVM) assessment, comprising direct viewing, tracing only, and tracing with digitized points. Two examiners received training and tests of reliability with each CVM method before evaluation of agreement among methods. The subjects were 96 female-cleft lateral cephalometric radiographs (films of eight subjects for each age ranged from seven to 18 years). The examiners interpreted CVM stages of the subjects with four-week interval between uses of each method. The range of weighted kappa values for paired comparisons among the three methods were: 0.96-0.98 for direct viewing and tracing only comparison; 0.93-0.94 for direct viewing and tracing with digitized points comparison; and 0.96-0.97 for tracing only and tracing with digitized points comparison. The intraclass correlation coefficient (ICC) value among the three methods was 0.95. These results indicated very good agreement among methods. Use of direct viewing is suitable for CVM assessment without spending more time for tracing. However, the three methods might be used interchangeably.

  18. IgA-kappa type multiple myeloma affecting proximal and distal renal tubules.

    PubMed

    Minemura, K; Ichikawa, K; Itoh, N; Suzuki, N; Hara, M; Shigematsu, S; Kobayashi, H; Hiramatsu, K; Hashizume, K

    2001-09-01

    A 45-year-old male was admitted because of chest pain, lumbago, and bilateral ankle pain. Examination disclosed hypophosphatemic osteomalacia, acquired Fanconi syndrome, and abnormalities in distal nephron such as distal renal tubular acidosis and renal diabetes insipidus. Further exploration revealed IgA kappa multiple myeloma excreting urinary Bence Jones protein (kappa-light chain). Renal biopsy revealed thick basement membranes and elec-tron-dense crystals in proximal tubular epithelial cells. Immunofluorescent studies revealed deposition of kappa-light chain in renal tubular epithelial cells that caused the renal tubular damage. Although the osteomalacia was relieved by medical treatment, the urinary Bence Jones protein and the renal tubular defects were not improved by the chemotherapy for the myeloma. The patient died of exacerbation of multiple myeloma at 50 years of age.

  19. Cationization of kappa- and iota-carrageenan--Characterization and properties of amphoteric polysaccharides.

    PubMed

    Barahona, Tamara; Prado, Héctor J; Bonelli, Pablo R; Cukierman, Ana L; Fissore, Eliana L; Gerschenson, Lia N; Matulewicz, María C

    2015-08-01

    Commercial kappa- and iota carrageenans were cationized with 3-chloro-2-hydroxypropyltrimethylammonium chloride in aqueous sodium hydroxide solution. For kappa-carrageenan three derivatives with different degrees of substitution were obtained. Native and amphoteric kappa-carrageenans were characterized by NMR and infrared spectroscopy, scanning electron and atomic force microscopy; methanolysis products were studied by electrospray ionization mass spectrometry. Young moduli and the strain at break of films, differential scanning calorimetry, rheological and flocculation behavior were also evaluated; the native and the amphoteric derivatives showed different and interesting properties. Cationization of iota-carrageenan was more difficult, indicating as it was previously observed for agarose, that substitution starts preferentially on the 2-position of 3,6-anhydrogalactose residues; in iota-carrageenan this latter unit is sulfated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Reciprocal inhibition of p53 and nuclear factor-kappaB transcriptional activities determines cell survival or death in neurons.

    PubMed

    Culmsee, Carsten; Siewe, Jan; Junker, Vera; Retiounskaia, Marina; Schwarz, Stephanie; Camandola, Simonetta; El-Metainy, Shahira; Behnke, Hagen; Mattson, Mark P; Krieglstein, Josef

    2003-09-17

    The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses, and activation of p53 precedes apoptosis in many cell types. Controversial reports exist on the role of the transcription factor nuclear factor-kappaB (NF-kappaB) in p53-mediated apoptosis, depending on the cell type and experimental conditions. Therefore, we sought to elucidate the role of NF-kappaB in p53-mediated neuron death. In cultured neurons DNA damaging compounds induced activation of p53, whereas NF-kappaB activity declined significantly. The p53 inhibitor pifithrin-alpha (PFT) preserved NF-kappaB activity and protected neurons against apoptosis. Immunoprecipitation experiments revealed enhanced p53 binding to the transcriptional cofactor p300 after induction of DNA damage, whereas binding of p300 to NF-kappaB was reduced. In contrast, PFT blocked the interaction of p53 with the cofactor, whereas NF-kappaB binding to p300 was enhanced. Most interestingly, similar results were observed after oxygen glucose deprivation in cultured neurons and in ischemic brain tissue. Ischemia-induced repression of NF-kappaB activity was prevented and brain damage was reduced by the p53 inhibitor PFT in a dose-dependent manner. It is concluded that a balanced competitive interaction of p53 and NF-kappaB with the transcriptional cofactor p300 exists in neurons. Exposure of neurons to lethal stress activates p53 and disrupts NF-kappaB binding to p300, thereby blocking NF-kappaB-mediated survival signaling. Inhibitors of p53 provide pronounced neuroprotective effects because they block p53-mediated induction of cell death and concomitantly enhance NF-kappaB-induced survival signaling.

  1. Induction of oncogene addiction shift to NF-{kappa}B by camptothecin in solid tumor cells

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

    Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko

    2009-12-04

    The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-{kappa}B activity driven by I{kappa}B kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-{kappa}B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in thismore » study present an example of the shift in signals that support the survival of solid tumor cells to NF-{kappa}B during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-{kappa}B inhibitors.« less

  2. NMR study on the network structure of a mixed gel of kappa and iota carrageenans.

    PubMed

    Hu, Bingjie; Du, Lei; Matsukawa, Shingo

    2016-10-05

    The temperature dependencies of the (1)H T2 and diffusion coefficient (D) of a mixed solution of kappa-carrageenan and iota-carrageenan were measured by NMR. Rheological and NMR measurements suggested an exponential formation of rigid aggregates of kappa-carrageenan and a gradual formation of fine aggregates of iota-carrageenan during two step increases of G'. The results also suggested that longer carrageenan chains are preferentially involved in aggregation, thus resulting in a decrease in the average Mw of solute carrageenans. The results of diffusion measurements for poly(ethylene oxide) (PEO) suggested that kappa-carrageenan formed thick aggregates that decreased hindrance to PEO diffusion by decreasing the solute kappa-carrageenan concentration in the voids of the aggregated chains, and that iota-carrageenan formed fine aggregates that decreased the solute iota-carrageenan concentration less. DPEO in a mixed solution of kappa-carrageenan and iota-carrageenan suggested two possibilities for the microscopic network structure: an interpenetrating network structure, or micro-phase separation. Copyright © 2016. Published by Elsevier Ltd.

  3. Identification of known drugs that act as inhibitors of NF-kappaB signaling and their mechanism of action.

    PubMed

    Miller, Susanne C; Huang, Ruili; Sakamuru, Srilatha; Shukla, Sunita J; Attene-Ramos, Matias S; Shinn, Paul; Van Leer, Danielle; Leister, William; Austin, Christopher P; Xia, Menghang

    2010-05-01

    Nuclear factor-kappa B (NF-kappaB) is a transcription factor that plays a critical role across many cellular processes including embryonic and neuronal development, cell proliferation, apoptosis, and immune responses to infection and inflammation. Dysregulation of NF-kappaB signaling is associated with inflammatory diseases and certain cancers. Constitutive activation of NF-kappaB signaling has been found in some types of tumors including breast, colon, prostate, skin and lymphoid, hence therapeutic blockade of NF-kappaB signaling in cancer cells provides an attractive strategy for the development of anticancer drugs. To identify small molecule inhibitors of NF-kappaB signaling, we screened approximately 2800 clinically approved drugs and bioactive compounds from the NIH Chemical Genomics Center Pharmaceutical Collection (NPC) in a NF-kappaB mediated beta-lactamase reporter gene assay. Each compound was tested at fifteen different concentrations in a quantitative high throughput screening format. We identified nineteen drugs that inhibited NF-kappaB signaling, with potencies as low as 20 nM. Many of these drugs, including emetine, fluorosalan, sunitinib malate, bithionol, narasin, tribromsalan, and lestaurtinib, inhibited NF-kappaB signaling via inhibition of IkappaBalpha phosphorylation. Others, such as ectinascidin 743, chromomycin A3 and bortezomib utilized other mechanisms. Furthermore, many of these drugs induced caspase 3/7 activity and had an inhibitory effect on cervical cancer cell growth. Our results indicate that many currently approved pharmaceuticals have previously unappreciated effects on NF-kappaB signaling, which may contribute to anticancer therapeutic effects. Comprehensive profiling of approved drugs provides insight into their molecular mechanisms, thus providing a basis for drug repurposing. Published by Elsevier Inc.

  4. NIK and IKKbeta interdependence in NF-kappaB signalling--flux analysis of regulation through metabolites.

    PubMed

    Kim, Hong-Bum; Evans, Iona; Smallwood, Rod; Holcombe, Mike; Qwarnstrom, Eva E

    2010-02-01

    Activation of the transcription factor NF-kappaB is central to control of immune and inflammatory responses. Cytokine induced activation through the classical or canonical pathway relies on degradation of the inhibitor, IkappaBalpha and regulation by the IKKbeta kinase. In addition, the NF-kappaB is activated through the NF-kappaB-inducing kinase, NIK. Analysis of the IKK/NIK inter-relationship and its impact on NF-kappaB control, were analysed by mathematical modelling, using matrix formalism and stoichiometrically balanced reactions. The analysis considered a range of bio-reactions and core metabolites and their role in relation to kinase activation and in control of specific steps of the NF-kappaB pathway. The model predicts a growth-rate and time-dependent transfer of the primary kinase activity from IKKbeta to NIK. In addition, it suggests that NIK/IKKbeta interdependence is controlled by intermediates of phosphoribosylpyrophosphate (PRPP) within the glycolysis pathway, and thus, identifies a link between specific metabolic events and kinase activation in inflammatory signal transduction. Subsequent in vitro experiments, carried out to validate the impact of IKK/NIK interdependence, confirmed signal amplification at the level of the NF-kappaB/IkappaBalpha complex control in the presence of both kinases. Further, they demonstrate that the induced potentiation is due to synergistic enhancement of relA-dependent activation. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  5. Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft Tissue Sarcoma of the Extremity

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

    Bahig, Houda; Roberge, David, E-mail: david.roberge.chum@ssss.gouv.qc.ca; Bosch, Walter

    Purpose: Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Methods and Materials: Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a singlemore » observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm{sup 3} (7-413 cm{sup 3}), 280 cm{sup 3} and 360 cm{sup 3}. The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm{sup 3} (24-565 cm{sup 3}) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm{sup 3} (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm{sup 3}, respectively. There were 3 large tumors with >30 cm{sup 3} of SE not included in the CTV3cm volume. Conclusion: Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant

  6. Agreement among RTOG sarcoma radiation oncologists in contouring suspicious peritumoral edema for preoperative radiation therapy of soft tissue sarcoma of the extremity.

    PubMed

    Bahig, Houda; Roberge, David; Bosch, Walter; Levin, William; Petersen, Ivy; Haddock, Michael; Freeman, Carolyn; Delaney, Thomas F; Abrams, Ross A; Indelicato, Danny J; Baldini, Elizabeth H; Hitchcock, Ying; Kirsch, David G; Kozak, Kevin R; Wolfson, Aaron; Wang, Dian

    2013-06-01

    Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm(3) (7-413 cm(3)), 280 cm(3) and 360 cm(3). The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm(3) (24-565 cm(3)) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm(3) (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm(3), respectively. There were 3 large tumors with >30 cm(3) of SE not included in the CTV3cm volume. Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE. Copyright © 2013 Elsevier Inc. All rights

  7. Curcumin Regulates Low-Linear Energy Transfer {gamma}-Radiation-Induced NF{kappa}B-Dependent Telomerase Activity in Human Neuroblastoma Cells

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

    Aravindan, Natarajan, E-mail: naravind@ouhsc.ed; Veeraraghavan, Jamunarani; Madhusoodhanan, Rakhesh

    2011-03-15

    Purpose: We recently reported that curcumin attenuates ionizing radiation (IR)-induced survival signaling and proliferation in human neuroblastoma cells. Also, in the endothelial system, we have demonstrated that NF{kappa}B regulates IR-induced telomerase activity (TA). Accordingly, we investigated the effect of curcumin in inhibiting IR-induced NF{kappa}B-dependent hTERT transcription, TA, and cell survival in neuroblastoma cells. Methods and Materials: SK-N-MC or SH-SY5Y cells exposed to IR and treated with curcumin (10-100 nM) with or without IR were harvested after 1 h through 24 h. NF{kappa}B-dependent regulation was investigated either by luciferase reporter assays using pNF{kappa}B-, pGL3-354-, pGL3-347-, or pUSE-I{kappa}B{alpha}-Luc, p50/p65, or RelA siRNA-transfectedmore » cells. NF{kappa}B activity was analyzed using an electrophoretic mobility shift assay and hTERT expression using the quantitative polymerase chain reaction. TA was determined using the telomerase repeat amplification protocol assay and cell survival using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium bromide and clonogenic assay. Results: Curcumin profoundly inhibited IR-induced NF{kappa}B. Consequently, curcumin significantly inhibited IR-induced TA and hTERT mRNA at all points investigated. Furthermore, IR-induced TA is regulated at the transcriptional level by triggering telomerase reverse transcriptase (TERT) promoter activation. Moreover, NF{kappa}B becomes functionally activated after IR and mediates TA upregulation by binding to the {kappa}B-binding region in the promoter region of the TERT gene. Consistently, elimination of the NF{kappa}B-recognition site on the telomerase promoter or inhibition of NF{kappa}B by the I{kappa}B{alpha} mutant compromises IR-induced telomerase promoter activation. Significantly, curcumin inhibited IR-induced TERT transcription. Consequently, curcumin inhibited hTERT mRNA and TA in NF{kappa}B overexpressed cells. Furthermore, curcumin

  8. Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens.

    PubMed

    Rose, Jamie H; Karkhanis, Anushree N; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F; Becker, Howard C; McCool, Brian A; Jones, Sara R

    2016-05-01

    Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. These data suggest that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety

  9. Over-expression of Flt3 induces NF-kappaB pathway and increases the expression of IL-6.

    PubMed

    Takahashi, Shinichiro; Harigae, Hideo; Ishii, Keiko Kumura; Inomata, Mitsue; Fujiwara, Tohru; Yokoyama, Hisayuki; Ishizawa, Kenichi; Kameoka, Junichi; Licht, Jonathan D; Sasaki, Takeshi; Kaku, Mitsuo

    2005-08-01

    Activating mutations or over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), associated with activation of Ras/MAP kinase and other signaling pathways. In this study, we addressed the role of Flt3 in the activation of nuclear factor-kappa B (NF-kappaB), which is a target molecule of these kinase pathways. In BaF3 cells stably expressing Flt3, a NF-kappaB-responsive reporter was upregulated and its target gene, IL-6, was increased by the involvement of Flt3-ERK/MAPK-NF-kappaB pathway. Furthermore, we found a modest positive correlation (r=0.35, p=0.096) between Flt3 and IL-6 mRNA expression in 24 AML specimens. These results suggest a role of Flt3 over-expression in NF-kappaB pathway.

  10. Agreement between hopelessness/helplessness and Montgomery-Asberg Depression Rating Scale in healthy individuals and in patients with benign breast disease and breast cancer: a prospective case-control study in Finland.

    PubMed

    Eskelinen, Matti; Korhonen, Riika; Selander, Tuomas; Ollonen, Paula

    2015-04-01

    The relation between scoring for hopelessness/helplessness and the Montgomery-Asberg Depression Rating Scale (MADRS) in healthy study subjects (HSS) and in patients with benign breast disease (BBD) and breast cancer (BC) has not been compared in a prospective study. We, therefore, investigated hopelessness and helplessness scores versus the MADRS in 115 patients. In the Kuopio Breast Cancer Study, 115 women with breast symptoms were evaluated for hopelessness and helplessness, and for the MADRS before any diagnostic procedures were carried out. In the self-rating score (SRS), hopelessness/helplessness versus the MADRS were highly significantly positively correlated in the HSS, BBD and BC groups. In the SRS, the weighted kappa values for hopelessness/helplessness versus the MADRS in the HSS, BBD and BC groups were also statistically significant. There was also a significant positive correlation in the examiner-rating score (ERS) for hopelessness versus the MADRS in the HSS, BBD and BC groups and for helplessness versus the MADRS in the HSS, BBD and BC groups. The unweighted kappa values in the ERS for hopelessness versus the MADRS were statistically highly significant for the HSS, BBD and BC groups and those for helplessness versus the MADRS in the HSS and BBD groups were statistically significant. A new finding with clinical relevance in the present work is the agreement between hopelessness/helplessness scores and MADRS in the SRS and ERS. In the breast cancer diagnostic unit, the identification of hopeless/helpless persons is essential in suicide prevention and it is important to assess and treat hopelessness/helplessness even though an individual may report few depressive symptoms. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. Angle Kappa Measurements: Normal Values in Healthy Iranian Population Obtained With the Orbscan II

    PubMed Central

    Gharaee, Hamid; Shafiee, Masoud; Hoseini, Rafie; Abrishami, Mojtaba; Abrishami, Yalda; Abrishami, Mostafa

    2014-01-01

    Background: The angle kappa is important in proper centration of corneal ablation in keratorefractive surgery. Orbscan II device is widely used preoperatively in photoablation surgeries and can be used to measure the angle kappa. Objectives: This study aimed to determine the mean angle kappa and its intercepts in healthy young Iranian adults. Patients and Methods: In this cross-sectional study, orthotropic patients (age range, 18-35 years) who were referred to the Khatam Eye Hospital (Mashhad, Iran) were included. Exclusion criteria were as follows: history of any eye deviation or strabismus with or without orthoptic or surgical treatment; any intraocular, corneal, or keratorefractive surgery; contact lens use; any corneal anomaly; any ophthalmic or systemic drug consumption; and hyperopic spherical refraction > + 3.00 diopters (D), spherical refraction > -5.00 D, or cylindrical refraction > 2.00 D. All of the parameters were measured by the same operator through an Orbscan II device. Results: A total of 977 healthy participants who aged 18 to 45 years were included consecutively. The study population consisted of 614 females and 363 males. The average angle kappa was 5.00º ± 1.36º at 240.21º ± 97.17º in males and 4.97º ± 1.30º at 244.22º ± 94.39º in females (P = 0.63). The average horizontal (x-axis) angle kappa was -0.02º ± 0.49º, with a mean of -0.02º ± 0.50º in males and -0.02º ± 0.49º in females (P = 0.93). The average vertical (y-axis) angle kappa was -0.09º ± 0.32º, with a mean of -0.09º ± 0.33º in males and -0.09º ± 0.32º in females (P = 0.74). Conclusions: By using the normal angle kappa determined in this study, pseudodeviations can be identified more precisely in those who might undergo keratorefractive surgery. PMID:25763261

  12. Agreement between patients and general practitioners on quality deviations during the cancer diagnostic pathway and associations with time to diagnosis.

    PubMed

    Jensen, Henry; Sperling, Cecilie; Sandager, Mette; Vedsted, Peter

    2015-06-01

    High quality and minimal delay are crucial and anticipated elements in the diagnostic cancer pathway as delay in the diagnosis may worsen the prognosis and cause lower patient satisfaction. The aim of this study was to describe agreement in reported quality deviations (QDs) between general practitioners (GPs) and cancer patients during the diagnostic pathway in primary care and to estimate the association between length of diagnostic interval and level of agreement on reported QDs. The study was carried out as a Danish cross-sectional study of incident cancer patients identified in the Danish National Patient Registry. Data were collected by independent questionnaires from patients (response rate: 53.0%) and their GPs (response rate: 73.8%), and 2177 pairs of questionnaires were subsequently combined. Agreement between GP- and patient-reported QDs was estimated using Cohen's Kappa, whereas the association between level of agreement and time to diagnosis was estimated using quantile regression. Patients reported QDs in 29.0% and GPs in 28.5% of the cases, but agreed only slightly on QD presence (Kappas between -0.08 and 0.26). Agreement on 'QD presence' was associated with a 54-day (95%CI: 44-64) longer time to diagnosis than agreement on 'no QD presence'. The association with a longer diagnostic interval was stronger when only GP reported a QD the association than when only patient reported a QD. Included GPs and patients agreed only slightly on QD presence although they reported the same amount of QDs; this suggests that GPs and patients see QDs as two different concepts. QD presence had a stronger impact on time to diagnosis when reported by the GP (alone or in agreement with the patient) than when reported by the patient alone. The GP may thus be the most important source of information on QD and diagnostic interval, while the patient information tends to underpin this assessment. © The Author 2015. Published by Oxford University Press. All rights reserved. For

  13. Agreement between Gonioscopic Examination and Swept Source Fourier Domain Anterior Segment Optical Coherence Tomography Imaging

    PubMed Central

    Nguyen, Donna; Minnal, Vandana R.

    2016-01-01

    Purpose. To evaluate interobserver, intervisit, and interinstrument agreements for gonioscopy and Fourier domain anterior segment optical coherence tomography (FD ASOCT) for classifying open and narrow angle eyes. Methods. Eighty-six eyes with open or narrow anterior chamber angles were included. The superior angle was classified open or narrow by 2 of 5 glaucoma specialists using gonioscopy and imaged by FD ASOCT in the dark. The superior angle of each FD ASOCT image was graded as open or narrow by 2 masked readers. The same procedures were repeated within 6 months. Kappas for interobserver and intervisit agreements for each instrument and interinstrument agreements were calculated. Results. The mean age was 50.9 (±18.4) years. Interobserver agreements were moderate to good for both gonioscopy (0.57 and 0.69) and FD ASOCT (0.58 and 0.75). Intervisit agreements were moderate to excellent for both gonioscopy (0.53 to 0.86) and FD ASOCT (0.57 and 0.85). Interinstrument agreements were fair to good (0.34 to 0.63), with FD ASOCT classifying more angles as narrow than gonioscopy. Conclusions. Both gonioscopy and FD ASOCT examiners were internally consistent with similar interobserver and intervisit agreements for angle classification. Agreement between instruments was fair to good, with FD ASOCT classifying more angles as narrow than gonioscopy. PMID:27990300

  14. Selection and Reporting of Statistical Methods to Assess Reliability of a Diagnostic Test: Conformity to Recommended Methods in a Peer-Reviewed Journal

    PubMed Central

    Park, Ji Eun; Han, Kyunghwa; Sung, Yu Sub; Chung, Mi Sun; Koo, Hyun Jung; Yoon, Hee Mang; Choi, Young Jun; Lee, Seung Soo; Kim, Kyung Won; Shin, Youngbin; An, Suah; Cho, Hyo-Min

    2017-01-01

    Objective To evaluate the frequency and adequacy of statistical analyses in a general radiology journal when reporting a reliability analysis for a diagnostic test. Materials and Methods Sixty-three studies of diagnostic test accuracy (DTA) and 36 studies reporting reliability analyses published in the Korean Journal of Radiology between 2012 and 2016 were analyzed. Studies were judged using the methodological guidelines of the Radiological Society of North America-Quantitative Imaging Biomarkers Alliance (RSNA-QIBA), and COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) initiative. DTA studies were evaluated by nine editorial board members of the journal. Reliability studies were evaluated by study reviewers experienced with reliability analysis. Results Thirty-one (49.2%) of the 63 DTA studies did not include a reliability analysis when deemed necessary. Among the 36 reliability studies, proper statistical methods were used in all (5/5) studies dealing with dichotomous/nominal data, 46.7% (7/15) of studies dealing with ordinal data, and 95.2% (20/21) of studies dealing with continuous data. Statistical methods were described in sufficient detail regarding weighted kappa in 28.6% (2/7) of studies and regarding the model and assumptions of intraclass correlation coefficient in 35.3% (6/17) and 29.4% (5/17) of studies, respectively. Reliability parameters were used as if they were agreement parameters in 23.1% (3/13) of studies. Reproducibility and repeatability were used incorrectly in 20% (3/15) of studies. Conclusion Greater attention to the importance of reporting reliability, thorough description of the related statistical methods, efforts not to neglect agreement parameters, and better use of relevant terminology is necessary. PMID:29089821

  15. Inter-Rater Agreement of Auscultation, Palpable Fremitus, and Ventilator Waveform Sawtooth Patterns Between Clinicians.

    PubMed

    Berry, Marc P; Martí, Joan-Daniel; Ntoumenopoulos, George

    2016-10-01

    Clinicians often use numerous bedside assessments for secretion retention in participants who are receiving invasive mechanical ventilation. This study aimed to evaluate inter-rater agreement between clinicians when using standard clinical assessments of secretion retention and whether differences in clinician experience influenced inter-rater agreement. Seventy-one mechanically ventilated participants were assessed by a research clinician and by one of 13 ICU clinicians. Each clinician conducted a standardized assessment of lung auscultation, palpation for chest-wall (rhonchal) fremitus, and ventilator inspiratory/expiratory flow-time waveforms for the sawtooth pattern. On the presence of breath sounds, agreement ranged from absolute to moderate in the upper zones and the lower zones, respectively. Kappa values for abnormal and adventitious lung sounds achieved moderate agreement in the upper zones, less than chance agreement to substantial agreement in the middle zones, and moderate agreement to almost perfect agreement in the lower zones. Moderate to almost perfect agreement was established for palpable fremitus in the upper zones, moderate to substantial agreement in the middle zones, and less than chance to moderate agreement in the lower zones. Inter-rater agreement on the presence of expiratory sawtooth pattern identification showed moderate agreement. The level of percentage agreement between the research and ICU clinicians for each respiratory assessment studied did not relate directly to level of clinical experience. Inter-rater agreement for all assessments showed variability between lung regions but maintained reasonable percentage agreement in mechanically ventilated participants. The level of percentage agreement achieved between clinicians did not directly relate to clinical experience for all respiratory assessments. Therefore, these respiratory assessments should not necessarily be viewed in isolation but interpreted within the context of a full

  16. Falls documentation in nursing homes: agreement between the minimum data set and chart abstractions of medical and nursing documentation.

    PubMed

    Hill-Westmoreland, Elizabeth E; Gruber-Baldini, Ann L

    2005-02-01

    To assess the agreement between falls as recorded in the Minimum Data Set (MDS) and fall events abstracted from chart documentation of elderly nursing home (NH) residents. Secondary analysis of data from a longitudinal panel study. Fifty-six randomly selected NHs in Maryland stratified by facility size and geographic region. Four hundred sixty-two NH residents, aged 65 and older, in NHs for 1 year. Falls were abstracted from resident charts and compared with MDS fall variables. Fall events data obtained from other sources of chart documentation were matched for the corresponding periods of 30 and 180 days before the 1-year MDS assessment date. For a 30-day period, concordance between the MDS and chart abstractions of falls occurred in 65% of cases, with a kappa coefficient of 0.29 (P<.001), indicating fair agreement. Concordance occurred between the sources for 75% of cases for a 180-day period, with a kappa of 0.50 (P<.001), indicating moderate agreement. During the 180-day period, chart abstractions showed that 49% of the sample fell, whereas the MDS revealed that only 28% fell. An analysis of residents whose falls the MDS missed indicated that these residents had significantly more activity of daily living impairment and significantly less unsteady gait and cane/walker use. The MDS underreported falls. Nurses completing MDS assessments must carefully review residents' medical records for falls documentation. Future studies should use caution when employing MDS data as the only indicator of falls.

  17. Agreement studies in radiology research.

    PubMed

    Farzin, B; Gentric, J-C; Pham, M; Tremblay-Paquet, S; Brosseau, L; Roy, C; Jamali, S; Chagnon, M; Darsaut, T E; Guilbert, F; Naggara, O; Raymond, J

    2017-03-01

    The goal of this study was to estimate the frequency and the quality of agreement studies published in diagnostic imaging journals. All studies published between January 2011 and December 2012 in four radiology journals were reviewed. Four trained readers evaluated agreement studies using a 24-item form that included the 15 items of the Guidelines for Reporting Reliability and Agreement Studies criteria. Of 2229 source titles, 280 studies (13%) reported agreement. The mean number of patients per study was 81±99 (SD) (range, 0-180). Justification for sample size was found in 9 studies (3%). The number of raters was≤2 in 226 studies (81%). No intra-observer study was performed in 212 (76%) articles. Confidence intervals and interpretation of statistical estimates were provided in 98 (35%) and 147 (53%) of the studies, respectively. In 168 studies (60%), the agreement study was not mentioned in the discussion section. In 8 studies (3%), reporting of the agreement study was judged to be adequate. Twenty studies (7%) were dedicated to agreement. Agreement studies are preliminary and not adequately reported. Studies dedicated to agreement are infrequent. They are research opportunities that should be promoted. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  18. TAK1 regulates NF-{Kappa}B and AP-1 activation in airway epithelial cells following RSV infection

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

    Dey, Nilay; Liu Tianshuang; Garofalo, Roberto P.

    2011-09-30

    Respiratory syncytial virus (RSV) is the most common cause of epidemic respiratory diseases in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-{kappa}B (NF-{kappa}B) and AP-1. In this study, we have investigated the signaling pathway leading to activation of these two transcription factors in response to RSV infection. Our results show that IKK{beta} plays a key role in viral-induced NF-{kappa}B activation, while JNK regulates AP-1-dependent gene transcription, as demonstrated by using kinase inactive proteins and chemical inhibitors of the two kinases.more » Inhibition of TAK1 activation, by overexpression of kinase inactive TAK1 or using cells lacking TAK1 expression, significantly reduced RSV-induced NF-{kappa}B and AP-1 nuclear translocation and DNA-binding activity, as well as NF-{kappa}B-dependent gene expression, identifying TAK1 as an important upstream signaling molecule regulating RSV-induced NF-{kappa}B and AP-1 activation. - Highlights: > IKK{beta} is a major kinase involved in RSV-induced NF-{kappa}B activation. > JNK regulates AP-1-dependent gene transcription in RSV infection. > TAK1 is a critical upstream signaling molecule for both pathways in infected cells.« less

  19. Prevalence of mutations in hepatitis C virus core protein associated with alteration of NF-kappaB activation.

    PubMed

    Mann, Elizabeth A; Stanford, Sandra; Sherman, Kenneth E

    2006-10-01

    The hepatitis C virus (HCV) core protein is a key structural element of the virion but also affects a number of cellular pathways, including nuclear factor kappaB (NF-kappaB) signaling. NF-kappaB is a transcription factor that regulates both anti-apoptotic and pro-inflammatory genes and its activation may contribute to HCV-mediated pathogenesis. Amino acid sequence divergence in core is seen at the genotype level as well as within patient isolates. Recent work has implicated amino acids 9-11 of core in the modulation of NF-kappaB activation. We report that the sequence RKT is highly conserved (93%) at this position across all HCV genotypes, based on sequences collected in the Los Alamos HCV database. Of the 13 types of variants present in the database, the two most prevalent substitutions are RQT and RKP. We further show that core encoding RKP fails to activate NF-kappaB signaling in vitro while NF-kappaB activation by core encoding RQT does not differ from control RKT core. The effect of RKP core is specific to NF-kappaB signaling as activator protein 1 (AP-1) activity is not altered. Further studies are needed to assess potential associations between specific amino acid substitutions at positions 9-11 and liver disease progression and/or response to treatment in individual patients.

  20. Relationship between carbachol hyperstimulation-induced pancreatic intracellular trypsinogen and NF-kappa B activation in rats in vitro.

    PubMed

    Jiang, Chunfang; Zheng, Hai; Liu, Sunan; Fang, Kaifeng

    2008-02-01

    The relationship between intracellular trypsinogen activation and NF-kappa B activation in rat pancreatic acinar cells induced by M3 cholinergic receptor agonist (carbachol) hyperstimulation was studied. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, the active protease inhibitor (pefabloc) and NF-kappa B inhibitor (PDTC) in vitro. Intracellular trypsin activity was measured by using a fluorogenic substrate. The activity of NF-kappa B was monitored by using electrophoretic mobility shift assay. The results showed that after pretreatment with 2 mmol/L pefabloc, the activities of trypsin and NF-kappa B in pancreatic acinar cells treated with high concentrations of carbachol (10(-3) mol/L) in vitro was significantly decreased as compared with control group (P<0.01). The addition of 10(-2) mol/L PDTC resulted in a significant decrease of NF-kappa B activities in pancreatic acinar cells after treated with high concentrations of carbachol (10(-3) mol/L) in vitro, but the intracellular trypsinogen activity was not obviously inhibited (P>0.05). It was concluded that intracellular trypsinogen activation is likely involved in the regulation of high concentrations of carbachol-induced NF-kappa B activation in pancreatic acinar cells in vitro. NF-kappa B activation is likely not necessary for high concentrations of carbachol-induced trypsinogen activation in pancreatic acinar cells in vitro.

  1. 40 CFR 721.1880 - Borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...)hydro-, sodium, (T-4)-. 721.1880 Section 721.1880 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.1880 Borate(1-), tris(acetato-.kappa.O)hydro-, sodium... substance identified as borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)- (PMN P-00-0922; CAS No...

  2. 40 CFR 721.1880 - Borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...)hydro-, sodium, (T-4)-. 721.1880 Section 721.1880 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.1880 Borate(1-), tris(acetato-.kappa.O)hydro-, sodium... substance identified as borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)- (PMN P-00-0922; CAS No...

  3. Agreement between PRE2DUP register data modeling method and comprehensive drug use interview among older persons

    PubMed Central

    Taipale, Heidi; Tanskanen, Antti; Koponen, Marjaana; Tolppanen, Anna-Maija; Tiihonen, Jari; Hartikainen, Sirpa

    2016-01-01

    Background PRE2DUP is a modeling method that generates drug use periods (ie, when drug use started and ended) from drug purchases recorded in dispensing-based register data. It is based on the evaluation of personal drug purchasing patterns and considers hospital stays, possible stockpiling of drugs, and package information. Objective The objective of this study was to investigate person-level agreement between self-reported drug use in the interview and drug use modeled from dispensing data with PRE2DUP method for various drug classes used by older persons. Methods Self-reported drug use was assessed from the GeMS Study including a random sample of persons aged ≥75 years from the city of Kuopio, Finland, in 2006. Drug purchases recorded in the Prescription register data of these persons were modeled to determine drug use periods with PRE2DUP modeling method. Agreement between self-reported drug use on the interview date and drug use calculated from register-based data was compared in order to find the frequently used drugs and drug classes, which was evaluated by Cohen’s kappa. Kappa values 0.61–0.80 were considered to represent good and 0.81–1.00 as very good agreement. Results Among 569 participants with mean age of 82 years, the agreement between interview and register data was very good for 75% and very good or good for 93% of the studied drugs or drug classes. Good or very good agreement was observed for drugs that are typically used on regular bases, whereas “as needed” drugs represented poorer results. Conclusion PRE2DUP modeling method validly describes regular drug use among older persons. For most of drug classes investigated, PRE2DUP-modeled register data described drug use as well as interview-based data which are more time-consuming to collect. Further studies should be conducted by comparing it with other methods and in different drug user populations. PMID:27785101

  4. The stimulation of central kappa opioid receptors decreases male sexual behavior and locomotor activity.

    PubMed

    Leyton, M; Stewart, J

    1992-10-23

    Systemic injections of the kappa (kappa) opioid receptor agonist U-50,488H decreased male sexual behavior, locomotor activity, body temperature and bodily grooming, and induced body flattening. The U-50,488H-induced inhibitions of male sexual behavior were prevented by systemic injections of naloxone and by intra-cranial injections of the kappa opioid antagonist nor-binaltorphimine (NBNI). Injections of NBNI to either the ventral tegmental area (VTA) or the nucleus accumbens septi (NAS) increased female-directed behavior, and prevented the U-50,488H-induced decreases in female-directed behavior. Intra-VTA NBNI prevented U-50,488H-induced decreases in the mean number of ejaculations, intra-NAS NBNI prevented U-50,488H-induced increases in copulation latencies. Intra-medial preoptic area (mPOA) injections of NBNI increased female-directed behavior, and attenuated U-50,488H-induced decreases in female-directed behavior as well as U-50,488H-induced increases in both copulation and ejaculation latencies. Injections of NBNI dorsal to the mPOA were ineffective. Two of 26 days following the central injection of NBNI, systemic injections of U-50,488H remained behaviorally ineffective, leaving both sexual behavior and locomotor activity undiminished. These results suggest that the stimulation of central kappa opioid receptors inhibits sexual behavior in the male rat; perhaps endogenous kappa opioid agonists induce sexual refractory periods.

  5. Agreement of glaucoma specialists and experienced optometrists in gonioscopy and optic disc evaluation

    PubMed Central

    Kumar, Addepalli U.; Jonnadula, Ganesh B.; Garudadri, Chandrasekhar; Rao, Harsha L.; Senthil, Sirisha; Papas, Eric B.; Sankaridurg, Padmaja; Khanna, Rohit C.

    2013-01-01

    Purpose To compare the diagnostic performance of glaucoma specialists and experienced optometrists in gonioscopy and optic disc assessment. Methods This study was done to validate the diagnostic performance of two experienced optometrists for using their skills of detecting glaucoma using gonioscopy and optic disc assessment in a major epidemiological study, the L V Prasad Eye Institute Glaucoma Epidemiology and Molecular Genetics Study (LVPEI-GLEAMS). Gonioscopic findings for 150 eyes were categorized as 0, 1 and 2 for open angle, primary angle closure suspect (PACS) and primary angle closure (PAC) respectively. Optic disc findings for 200 eyes were categorized as 0, 1 and 2 for normal, suspects and glaucomatous respectively. Weighted kappa (κ) and diagnostic accuracy parameters were calculated. Two optometrists (#1 and #2) participated in the study. Results Agreement between glaucoma specialists and optometrist for interpretation of gonioscopy to discriminate PACS and PAC from open angles and for interpretation of optic disc to discriminate glaucomatous and suspicious discs from normal, the kappa (κ) was 0.92 and 0.84 and 0.90 and 0.89 for optometrists #1 and #2 respectively. Sensitivities and specificities were above 90% for gonioscopy. Optic disc evaluation had specificities greater than 95% to discriminate normal from glaucomatous discs while the sensitivities were 83% and 93% for optometrists #1 and #2 respectively. Conclusion Agreement between optometrists and glaucoma specialists, in diagnostic performance of gonioscopy and optic assessment was excellent with high sensitivity and specificity. Hence, we conclude that the experienced optometrists can detect glaucoma accurately in the LVPEI-GLEAMS.

  6. Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

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

    Zhong, Xia, E-mail: zhongxia1977@126.com; Li, Xiaonan; Liu, Fuli

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibitedmore » TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.« less

  7. Curcumin Modulates the Radiosensitivity of Colorectal Cancer Cells by Suppressing Constitutive and Inducible NF-{kappa}B Activity

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

    Sandur, Santosh K.; Deorukhkar, Amit; Pandey, Manoj K.

    2009-10-01

    Purpose: Radiation therapy is an integral part of the preoperative treatment of rectal cancers. However, only a minority of patients achieve a complete pathologic response to therapy because of resistance of these tumors to radiation therapy. This resistance may be mediated by constitutively active pro-survival signaling pathways or by inducible/acquired mechanisms in response to radiation therapy. Simultaneous inhibition of these pathways can sensitize these tumors to radiation therapy. Methods and Materials: Human colorectal cancer cells were exposed to clinically relevant doses of gamma rays, and the mechanism of their radioresistance was investigated. We characterized the transcription factor nuclear factor-{kappa}B (NF-{kappa}B)more » activation as a mechanism of inducible radioresistance in colorectal cancer and used curcumin, the active ingredient in the yellow spice turmeric, to overcome this resistance. Results: Curcumin inhibited the proliferation and the post-irradiation clonogenic survival of multiple colorectal cancer cell lines. Radiation stimulated NF-{kappa}B activity in a dose- and time-dependent manner, whereas curcumin suppressed this radiation-induced NF-{kappa}B activation via inhibition of radiation-induced phosphorylation and degradation of inhibitor of {kappa}B alpha, inhibition of inhibitor of {kappa}B kinase activity, and inhibition of Akt phosphorylation. Curcumin also suppressed NF-{kappa}B-regulated gene products (Bcl-2, Bcl-x{sub L}, inhibitor of apoptosis protein-2, cyclooxygenase-2, and cyclin D1). Conclusions: Our results suggest that transient inducible NF-{kappa}B activation provides a prosurvival response to radiation that may account for development of radioresistance. Curcumin blocks this signaling pathway and potentiates the antitumor effects of radiation therapy.« less

  8. Application of the kappa-omega Turbulence Model to Quasi-Three-Dimensional Turbomachinery Flows

    NASA Technical Reports Server (NTRS)

    Chima, Rodrick V.

    1996-01-01

    Many computational fluid dynamics codes for turbomachinery use the Baldwin-Lomax (B-L) turbulence model. It is easy to implement in two dimensions and works well for predicting overall turbomachinery performance. However, it is awkward to implement in three dimensions, often has difficulty finding the length scale, has a crude transition model, and neglects freestream turbulence, surface roughness, and mass injection. The kappa-omega model developed by Wilcox is an appealing alternative for several reasons. First, it is the only two-equation model that can be integrated to the wall without requiring damping functions or the distance to the wall, and hence, should behave well numerically. Second, the effects of freestream turbulence, surface roughness, and mass injection are easily included in the model. Finally, transition can be simulated using the low Reynolds number version of the model. Menter applied the kappa-model to external flows and showed very good results for flows with adverse pressure gradients. Liu and Zheng described their implementation of the kappa-model in a cascade code that included an area change term to account for endwall convergence. They validated the model for a flat plate, and compared the B-L and kappa-models to measured surface pressures for a low-pressure turbine cascade. Since they did not use the low Reynolds number version of the model, their results showed problems resulting from early transition. In this Note the low Reynolds number kappa-model was incorporated in the author's quasi-three-dimensional turbomachinery analysis code. The code includes the effects of rotation, radius change, and stream-surface thickness variation, and also includes the B-L turbulence model. The kappa-omega model was implemented using many of Menter's recommendations and an implicit approximate-factorization scheme described by Baldwin and Barth. The model was tested for a transonic compressor with rotation and variable stream-surface radius and height

  9. Pim-2 activates API-5 to inhibit the apoptosis of hepatocellular carcinoma cells through NF-kappaB pathway.

    PubMed

    Ren, Ke; Zhang, Wei; Shi, Yujun; Gong, Jianping

    2010-06-01

    Pim-2 is proved to be relevant to the tumorigenesis of hepatocellular carcinoma (HCC), but the mechanism is unclear. We studied the relationship among Pim-2, NF-kappaB and API-5. In our experiment, expression level of the three factors and phosphorylation level of API-5, as well as NF-kappaB activity, were detected in HCC tissues and the nontumorous controls. Then Pim-2 gene was transfected into nontumorous liver cells L02, and Pim-2 SiRNA was transfected into hepatoblastoma cell line HepG2. Parthenolide was added as NF-kappaB inhibitor. The same detections as above were repeated in the cells, along with the apoptosis analysis. We found the levels of Pim-2, NF-kappaB and API-5, as well as NF-kappaB activity, were significantly higher in HCC tissues. Pim-2 level was increased in L02 cells after the transfection of Pim-2 gene, but decreased in HepG2 cells after the transfection of Pim-2 SiRNA. The levels of NF-kappaB and API-5, as well as NF-kappaB activity and API-5 phosphorylation level, were in accordance with Pim-2 level, but could be reversed by Parthenolide. Cell apoptosis rates were negatively correlated with API-5 phosphorylation level. Therefore, we infer that Pim-2 could activate API-5 to inhibit the apoptosis of liver cells, and NF-kappaB is the key regulator.

  10. The consistency of experts' evaluation of obstetric claims for compensation.

    PubMed

    Andreasen, S; Backe, B; Lydersen, S; Øvrebø, K; Øian, P

    2015-06-01

    The aim of this study was to investigate the consistency of experts' evaluation of different types of obstetric claims for compensation. Inter-rater reliability study of obstetric claims for compensation. Medical experts' evaluation in The Norwegian System of Compensation to Patients, a no-blame system. The 15 most frequently used medical experts were asked to evaluate 12 obstetric claims applied for compensation. Inter-rater agreement was assessed by absolute agreement, Fleiss' kappa statistic and Gwet's AC1. Consistency in the evaluation of negligence (carelessness without intention to harm) and causality (relation between care and injury) between negligence and patient injury. The experts demonstrated moderate consistency in their evaluation of negligence (Fleiss' kappa = 0.53/AC1 = 0.54) and causality (Fleiss' kappa = 0.41/AC1 = 0.54). There was a higher level of agreement in clinical scenarios with well-documented diagnostic criteria and guidelines, including shoulder dystocia and asphyxia with low Apgar score and metabolic acidosis. We found a moderate level of agreement in experts' evaluation of negligence and causality between the injury and provided health care, the two most important questions to be answered in obstetric claims for compensation. © 2014 Royal College of Obstetricians and Gynaecologists.

  11. (/sup 3/H)Ethylketocyclazocine binding to mouse brain membranes: evidence for a kappa opioid receptor type

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

    Garzon, J.; Sanchez-Blazquez, P.; Lee, N.M.

    1984-10-01

    The binding of the putative kappa agonist ethylketocyclazocine (EKC) to synaptosomal membranes of mouse brain was studied. This benzomorphan was able to bind to different opioid receptors. A portion of this binding was not inhibited by the agonist naloxone, even at high concentrations (10 microM). This population of receptors, to which opioate alkaloids and opiod peptides display very low affinity, is probably the sigma receptor. Another class of binding sites was identified by the simultaneous addition of the selective agonists Sandoz FK-33824 and D-Ala2-D-Leu5-enkephalin, which blocked the access of EKC to mu and delta opioid receptors, respectively, leaving a portionmore » of naloxone-displaceable benzomorphan binding still detectable. Analysis of this remaining binding revealed a small population of receptors of high affinity, the kappa receptor. Therefore, EKC binds to the mu, delta, kappa and sigma receptors in the mouse brain, with similar affinities for the mu and kappa (0.22 and 0.15 nM). These results confirm the existence of a kappa opioid receptor type in the mouse brain.« less

  12. Exfoliated cells of the oral mucosa for HPV typing by SPF10 in head and neck cancer.

    PubMed

    Morbini, Patrizia; Dal Bello, Barbara; Alberizzi, Paola; Mannarini, Laura; Mevio, Niccolò; Bertino, Giulia; Benazzo, Marco

    2012-12-01

    HPV infection in the superficial cells of the oral mucosa could reflect the presence of HPV in head and neck cancer cells. Due mostly to the use of heterogeneous analytical methods, discordant data exist in the literature regarding the agreement between the presence of HPV in non-neoplastic oral mucosa and in tumour tissue from the same patient. The presence of HPV DNA and viral types were compared in paired cytological and biopsy samples from 56 patients with head and neck neoplastic and preneoplastic lesions using the highly sensitive SPF10 LiPA Extra assay, which has been validated recently for formalin-fixed paraffin-embedded tissue using paired cervical cytology and biopsy samples. Kappa statistics were used to measure the inter-rater agreement. The overall agreement with respect to HPV infection was 96.43% (kappa=0.8367). For 76.79% of subjects (kappa=0.6937), the same number of HPV types was detected in cytological and biopsy specimens. The overall positive typing agreement was 90.90%, comprising 130 out of 143 individual HPV type analyses. The agreement shown was good for HPV 18, 44, 45, 54 and 66 (kappa=0.6585-0. 7321), excellent for HPV 6, 16, 40, and 54 (kappa=0.8108-0.8679), and absolute for HPV 11, 31, 33, 35, 39, 51, 52, 53, 59, 74, and 69-71 (kappa=1.0000). The high sensitivity of the SPF10 LiPA and its excellent performance both for recognising HPV infection and for identifying the viral types present in tumour tissue and in oral exfoliated cells make it a useful method for the assessment of HPV infection in patients with head and neck cancer. The excellent agreement for HPV infection and genotyping in paired samples suggests that oral exfoliated cells can be used for HPV detection in the head and neck region. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. The Role of the Noncanonical NF-KappaB Pathway in Colon Cancer

    DTIC Science & Technology

    2016-08-01

    AWARD NUMBER: W81XWH-13-1-0321 TITLE: The Role of the Noncanonical NF -KappaB Pathway in Colon Cancer PRINCIPAL INVESTIGATOR: Yatrik Shah...2013 - 29 May 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0321 The Role of the Noncanonical NF -KappaB Pathway in Colon Cancer 5b...inflammatory bowel disease samples that the non-canonical NF -κB2 signaling cascade is highly activated in intestinal epithelial cells compared to normal

  14. Substantial observer variability in the differentiation between primary intracerebral hemorrhage and hemorrhagic transformation of infarction on CT brain imaging.

    PubMed

    Lovelock, Caroline E; Anslow, Philip; Molyneux, Andrew J; Byrne, James V; Kuker, Wilhelm; Pretorius, Pieter M; Coull, Andrew; Rothwell, Peter M

    2009-12-01

    CT remains the most commonly used imaging technique in acute stroke but is often delayed after minor stroke. Interobserver reliability in distinguishing hemorrhagic transformation of infarction from intracerebral hemorrhage may depend on delays to CT but has not been reported previously despite the clinical importance of this distinction. Initial CT scans with intraparenchymal hematoma from the first 1000 patients with stroke in the Oxford Vascular Study were independently categorized as intracerebral hemorrhage or hemorrhagic transformation of infarction by 5 neuroradiologists, both blinded and unblinded to clinical history. Thirty scans were reviewed twice. Agreement was quantified by the kappa statistic. Seventy-eight scans showed intraparenchymal hematoma. Blinded pairwise interrater agreements for a diagnosis of intracerebral hemorrhage ranged from kappa=0.15 to 0.48 with poor overall agreement (kappa=0.35; 95% CI, 0.15 to 0.54) even after unblinding (kappa=0.41; 0.21 to 0.60). Blinded intrarater agreements ranged from kappa=0.21 to 0.92. Lack of consensus after unblinding was greatest in patients scanned >or=24 hours after stroke onset (67% versus 25%, P=0.001) and in minor stroke (National Institutes of Health Stroke Scale or=24 hours after minor stroke and in 48% of all 30-day stroke survivors in whom reliable diagnosis would be expected to influence long-term management. Reliability of diagnosis of intraparenchymal hematoma on CT brain scan in minor stroke is poor, particularly if scanning is delayed. Immediate brain imaging is justified in patients with minor stroke.

  15. Diagnosing central lesions of the triangular fibrocartilage as traumatic or degenerative: a review of clinical accuracy.

    PubMed

    Löw, S; Erne, H; Pillukat, T; Mühldorfer-Fodor, M; Unglaub, F; Spies, C K

    2017-05-01

    This study examined the reliability of surgeons' estimations as to whether central lesions of the triangular fibrocartilage complex were traumatic or degenerative. A total of 50 consecutive central triangular fibrocartilage complex lesions were independently rated by ten experienced wrist surgeons viewing high-quality arthroscopy videos. The videos were reassessed after intervals of 3 months; at the second assessment surgeons were given the patient's history, radiographs and both, each in a randomized order. Finally, the surgeons assessed the histories and radiographs without the videos. Kappa statistics revealed fair interrater agreement when the histories were added to the videos. The other four modalities demonstrated moderate agreement, with lower Kappa values for the assessment without videos. Intra-rater reliability showed fair agreement for three surgeons, moderate agreement for two surgeons and substantial agreement for five surgeons. It appears that classification of central triangular fibrocartilage complex lesions depends on the information provided upon viewing the triangular fibrocartilage complex at arthroscopy. II.

  16. Tumor necrosis factor alpha induces gamma-glutamyltransferase expression via nuclear factor-kappaB in cooperation with Sp1.

    PubMed

    Reuter, Simone; Schnekenburger, Michael; Cristofanon, Silvia; Buck, Isabelle; Teiten, Marie-Hélène; Daubeuf, Sandrine; Eifes, Serge; Dicato, Mario; Aggarwal, Bharat B; Visvikis, Athanase; Diederich, Marc

    2009-02-01

    Gamma-glutamyltransferase (GGT) cleaves the gamma-glutamyl moiety of glutathione (GSH), an endogenous antioxidant, and is involved in mercapturic acid metabolism and in cancer drug resistance when overexpressed. Moreover, GGT converts leukotriene (LT) C4 into LTD4 implicated in various inflammatory pathologies. So far the effect of inflammatory stimuli on regulation of GGT expression and activity remained to be addressed. We found that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) induced GGT promoter transactivation, mRNA and protein synthesis, as well as enzymatic activity. Remicade, a clinically used anti-TNFalpha antibody, small interfering RNA (siRNA) against p50 and p65 nuclear factor-kappaB (NF-kappaB) isoforms, curcumin, a well characterized natural NF-kappaB inhibitor, as well as a dominant negative inhibitor of kappaB alpha (IkappaBalpha), prevented GGT activation at various levels, illustrating the involvement of this signaling pathway in TNFalpha-induced stimulation. Over-expression of receptor of TNFalpha-1 (TNFR1), TNFR-associated factor-2 (TRAF2), TNFR-1 associated death domain (TRADD), dominant negative (DN) IkappaBalpha or NF-kappaB p65 further confirmed GGT promoter activation via NF-kappaB. Linker insertion mutagenesis of 536 bp of the proximal GGT promoter revealed NF-kappaB and Sp1 binding sites at -110 and -78 relative to the transcription start site, responsible for basal GGT transcription. Mutation of the NF-kappaB site located at -110 additionally inhibited TNFalpha-induced promoter induction. Chromatin immunoprecipitation (ChIP) assays confirmed mutagenesis results and further demonstrated that TNFalpha treatment induced in vivo binding of both NF-kappaB and Sp1, explaining increased GGT expression, and led to RNA polymerase II recruitment under inflammatory conditions.

  17. Interrater and intrarater reliability of FDI criteria applied to photographs of posterior tooth-colored restorations.

    PubMed

    Kim, Dohyun; Ahn, So-Yeon; Kim, Junyoung; Park, Sung-Ho

    2017-07-01

    Since 2007, the FDI World Dental Federation (FDI) criteria have been used for the clinical evaluation of dental restorations. However, the reliability of the FDI criteria has not been sufficiently addressed. The purpose of this study was to assess and compare the interrater and intrarater reliability of the FDI criteria by evaluating posterior tooth-colored restorations photographically. A total of 160 clinical photographs of posterior tooth-colored restorations were evaluated independently by 5 raters with 9 of the FDI criteria suitable for photographic evaluation. The raters recorded the score of each restoration by using 5 grades, and the score was dichotomized into the clinical evaluation scores. After 1 month, 2 of the raters reevaluated the same set of 160 photographs in random order. To estimate the interrater reliability among the 5 raters, the proportion of agreement was calculated, and the Fleiss multirater kappa statistic was used. For the intrarater reliability, the proportion of agreement was calculated, and the Cohen standard kappa statistic was used for each of the 2 raters. The interrater proportion of agreement was 0.41 to 0.57, and the kappa value was 0.09 to 0.39. Overall, the intrarater reliability was higher than the interrater reliability, and rater 1 demonstrated higher intrarater reliability than rater 2. The proportion of agreement and kappa values increased when the 5 scores were dichotomized. The reliability was relatively lower for the esthetic properties compared with the functional or biological properties. Within the limitations of this study, the FDI criteria presented slight to fair interrater reliability and fair to excellent intrarater reliability in the photographic evaluation of posterior tooth-colored restorations. The reliability was improved by simplifying the evaluation scores. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  18. A Korean rheumatic diseases screening questionnaire.

    PubMed Central

    Lee, Hye-Soon; Oh, Kwang-Taek; Kim, Tae-Hwan; Jung, Sungsoo; Yoo, Dae-Hyun; Bae, Sang-Cheol

    2003-01-01

    The aim of our study was to develop a Korean rheumatic diseases-screening questionnaire. The questionnaire was constructed based on American College of Rheumatology criteria for rheumatic diseases and a connective tissue diseases screening questionnaire. Two groups of patients were selected and completed the questionnaire: (i) those with osteoarthritis (n=46), rheumatoid arthritis (n=52), systemic lupus erythematosus (n=50), scleroderma (n=8), polymyositis or dermatomyositis (n=7), Sjogren's disease (n=4), and mixed connective-tissue disease (n=9) as case subjects; and (ii) those with fibromyalgia (n=8) and general disease without evidence of any rheumatic disease (n=72) as controls. Laboratory results were analyzed for correlation with actual data using kappa (kappa) statistics. Test-retest reliability was performed in 12 patients, and showed strong agreement between the first and second interviews (kappa=0.91). The sensitivity of the questionnaire ranged from 77.8 to 100%, and specificity ranged from 68.8 to 95.0%. Negative predictive values were very high in the general population, from 98.4 to 99.99%. The kappa statistic for agreement between laboratory items was 0.22-0.56, except for rheumatoid factor, antinuclear antibody test, and muscle enzyme level. We have developed a simple and sensitive Korean rheumatic diseases-screening questionnaire for the epidemiologic study of rheumatic diseases in Korea. PMID:12692412

  19. Agreement between histopathological results in clinically diagnosed cases of indeterminate leprosy in São Paulo, Brazil.

    PubMed

    Lombardi, C; Cohen, S; Leiker, D L; Souza, J M; Cunha, P R; Martelli, C M; Andrade, A L; Zicker, F

    1994-01-01

    Histopathological slides from skin biopsies of fifty-seven self-reporting patients diagnosed as indeterminate leprosy by the Leprosy Control Programme in São Paulo, were sent to three independent histopathologists. Agreement between the reports were based on the following diagnosis: "indeterminate leprosy", "suggestive leprosy" or "no leprosy". A great variation was observed in the interpretation of the histopathological examination. The three pathologists reported "indeterminate leprosy" respectively in 7.0%, 54.4% and 84.2%, of the cases studied. A kappa index of agreement between any two pathologists ranged from 0.08 to 0.32, showing poor agreement between observers. Agreement improved by pooling together the reports "suggestive leprosy" and "indeterminate leprosy". The three pathologists agreed in the results of 24 biopsies of the 27 classified as leprosy by any one of the three observers. Eight cases were considered as "no leprosy" by all pathologists. Higher agreement indices were obtained for positive and negative proportionate concordance between any two examiners. The implications of the variation in the diagnosis of indeterminate leprosy and early leprosy are discussed in the context of public health and case-management.

  20. Measurement agreement of the self-administered questionnaire of the Belgian Health Interview Survey: Paper-and-pencil versus web-based mode.

    PubMed

    Braekman, Elise; Berete, Finaba; Charafeddine, Rana; Demarest, Stefaan; Drieskens, Sabine; Gisle, Lydia; Molenberghs, Geert; Tafforeau, Jean; Van der Heyden, Johan; Van Hal, Guido

    2018-01-01

    Before organizing mixed-mode data collection for the self-administered questionnaire of the Belgian Health Interview Survey, measurement effects between the paper-and-pencil and the web-based questionnaire were evaluated. A two-period cross-over study was organized with a sample of 149 employees of two Belgian research institutes (age range 22-62 years, 72% female). Measurement agreement was assessed for a diverse range of health indicators related to general health, mental and psychosocial health, health behaviors and prevention with kappa coefficients and intraclass correlation (ICC). The quality of the data collected by both modes was evaluated by quantifying the missing, 'don't know' and inconsistent values and data entry mistakes. Good to very good agreement was found for all categorical indicators with kappa coefficients superior to 0.60, except for two mental and psychosocial health indicators namely the presence of a sleeping disorder and of a depressive disorder (kappa≥0.50). For the continuous indicators high to acceptable agreement was observed with ICC superior to 0.70. Inconsistent answers and data-entry mistakes were only occurring in the paper-and-pencil mode. There were no less missing values in the web-based mode compared to the paper-and-pencil mode. The study supports the idea that web-based modes provide, in general, equal responses to paper-and-pencil modes. However, health indicators based upon factual and objective items tend to have higher measurement agreement than indicators requiring an assessment of personal subjective feelings. A web-based mode greatly facilitates the data-entry process and guides the completing of a questionnaire. However, item non-response was not positively affected.

  1. Neutrality of the canonical NF-kappaB-dependent pathway for human and murine cytomegalovirus transcription and replication in vitro.

    PubMed

    Benedict, Chris A; Angulo, Ana; Patterson, Ginelle; Ha, Sukwon; Huang, Huang; Messerle, Martin; Ware, Carl F; Ghazal, Peter

    2004-01-01

    Cytomegalovirus (CMV) is known to rapidly induce activation of nuclear factor kappaB (NF-kappaB) after infection of fibroblast and macrophage cells. NF-kappaB response elements are present in the enhancer region of the CMV major immediate-early promoter (MIEP), and activity of the MIEP is strongly upregulated by NF-kappaB in transient-transfection assays. Here we investigate whether the NF-kappaB-dependent pathway is required for initiating or potentiating human and murine CMV replication in vitro. We show that expression of a dominant negative mutant of the inhibitor of NF-kappaB-alpha (IkappaBalphaM) does not alter the replication kinetics of human or mouse CMV in cultured cells. In addition, mouse embryo fibroblasts genetically deficient for p65/RelA actually showed elevated levels of MCMV replication. Mutation of all NF-kappaB response elements within the enhancer of the MIEP in a recombinant mouse CMV containing the human MIEP (hMCMV-ES), which we have previously shown to replicate in murine fibroblasts with kinetics equivalent to that of wild-type mouse CMV, did not negatively affect replication in fibroblasts. Taken together, these data show that, for CMV replication in cultured fibroblasts activation of the canonical NF-kappaB pathway and binding of NF-kappaB to the MIEP are dispensable, and in the case of p65 may even interfere, thus uncovering a previously unrecognized level of complexity in the host regulatory network governing MIE gene expression in the context of a viral infection.

  2. Threshold level for measurement of UV sensitivity: reproducibility of phototest.

    PubMed

    Lock-Andersen, J; Wulf, H C

    1996-08-01

    The ultraviolet (UV) sensitivity is determined by a phototest where the skin is exposed to well-defined doses of UV radiation and the resulting erythema is graded by visual scoring after 20-24 h. In this study we wanted to estimate the reproducibility of erythema assessment in phototesting. Twenty-one healthy Caucasians with skin types I to IV were phototested on UV un-exposed buttock skin using a xenon lamp solar simulator. Twenty-four hours after UV exposure eight physicians independently graded the erythema reactions two times. Data were analysed using inter- and intra-observer agreement and kappa statistics, which adjusts for agreement that could be caused by chance alone. Observed agreement and kappa statistics were found to decrease with increasing intensity of erythema and to be lower for skin types III and IV compared to skin types I and II. Intra-observer agreement was uniformly better than inter-observer agreement. The difference between observers assessment could be as much as three clinical erythema grades. Physicians's previous experience with phototesting only had a minor influence on agreement. In conclusion, phototesting is based on subjective assessment of erythema and is not as precise and reproducible as expected. Agreement was better for barely perceptible erythema than for erythema with a well-defined border and we therefore recommend that the barely perceptible erythema reaction should be used for measurement of the minimal erythema dose.

  3. Inhibition of IL-1{beta}-mediated inflammatory responses by the I{kappa}B{alpha} super-repressor in human fibroblast-like synoviocytes

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

    Lee, Young-Rae; Kweon, Suc-Hyun; Kwon, Kang-Beom

    The IL-1{beta}-NF-{kappa}B axis is a key pathway in the pathogenesis of rheumatoid arthritis (RA) and is central in the production of proinflammatory mediators in the inflamed synovium. Therefore, we examined whether fibroblast-like synoviocytes (FLS) could be spared from IL-1{beta}-induced toxicity by an overexpressing I{kappa}B super-repressor. Infection of FLS with Ad-I{kappa}B{alpha} (S32A, S36A), an adenovirus-containing mutant I{kappa}B{alpha}, inhibited IL-1{beta}-induced nuclear translocation and DNA binding of NF-{kappa}B. In addition, Ad-I{kappa}B{alpha} (S32A, S36A) prevented IL-1{beta}-induced inflammatory responses; namely, the production of chemokines, such as ENA-78 and RANTES, and activation of MMP-1 and MMP-3. Finally, increased cellular proliferation of FLS after IL-1{beta} treatment wasmore » significantly reduced by Ad-I{kappa}B{alpha} (S32A, S36A). However, Ad-I{kappa}B{beta} (S19A, S23A), the I{kappa}B{beta} mutant, was not effective in preventing IL-1{beta} toxicity. These results suggest that inhibition of I{kappa}B{alpha} degradation is a potential target for the prevention of joint destruction in patients with RA.« less

  4. Transcription factor NF-kappaB regulates inducible CD83 gene expression in activated T lymphocytes.

    PubMed

    McKinsey, T A; Chu, Z; Tedder, T F; Ballard, D W

    2000-01-01

    The immunoglobulin superfamily member CD83 is expressed on the surface of mature dendritic cells that present processed antigens to T lymphocytes. In addition, T cells acquire CD83 expression following mitogenic stimulation in vitro. Here we report two lines of evidence demonstrating that this inducible lymphocyte response is genetically programmed by transcription factor NF-kappaB and contingent upon proteolytic breakdown of its cytoplasmic inhibitor IkappaBalpha. First, signal-dependent induction of CD83 mRNA expression is blocked in both transformed and primary T cells harboring a degradation-resistant mutant of IkappaBalpha that constitutively represses NF-kappaB. Second, as revealed in gel retardation assays, the IkappaBalpha constitutive repressor prevents the inducible interaction of NF-kappaB with consensus recognition sites identified in the CD83 promoter. Given that IkappaBalpha is functionally coupled to the T-cell antigen receptor, these findings suggest that the downstream transcription unit for CD83 is triggered by NF-kappaB during an adaptive immune response.

  5. Effects of Cot expression on the nuclear translocation of NF-kappaB in RBL-2H3 cells.

    PubMed

    Chikamatsu, Satomi; Furuno, Tadahide; Kinoshita, Yosuke; Inoh, Yoshikazu; Hirashima, Naohide; Teshima, Reiko; Nakanishi, Mamoru

    2007-03-01

    Cot is a serine/threonine protein kinase and is classified as a mitogen-activated protein (MAP) kinase kinase kinase. Overexpression of this protein has been shown to activate the extracellular signal-regulated kinase, the c-Jun N-terminal kinase, and the p38 MAP kinase pathways and to stimulate NF-AT and NF-kappaB-dependent transcription. Here we have shown that Cot kinase activity is intimately involved in the high affinity receptor for IgE (FcvarepsilonRI)-mediated nuclear translocation of NF-kappaB1 independent of NF-kappaB-inducing kinase (NIK) in rat basophilic leukemia (RBL-2H3) cells. A transfected green fluorescent protein-tagged NF-kappaB1 (GFP-NF-kappaB1) resided in the cytoplasm in RBL-2H3 cells and it remained in the cytoplasm even when Cot tagged with red fluorescent protein (Cot-RFP) was co-expressed. Western blotting analysis showed that IkappaB kinases (IKKs) were expressed in RBL-2H3 cells but NIK was not. GFP-NF-kappaB1 translocated from the cytoplasm to the nucleus after the aggregation of FcvarepsilonRI in Cot-transfected cells but not in kinase-deficient Cot-transfected cells. This finding gives a new insight into the role of Cot in the FcvarepsilonRI-mediated NF-kappaB activation in mast cells.

  6. An essential complementary role of NF-kappaB pathway to microbicidal oxidants in Drosophila gut immunity.

    PubMed

    Ryu, Ji-Hwan; Ha, Eun-Mi; Oh, Chun-Taek; Seol, Jae-Hong; Brey, Paul T; Jin, Ingnyol; Lee, Dong Gun; Kim, Jaesang; Lee, Daekee; Lee, Won-Jae

    2006-08-09

    In the Drosophila gut, reactive oxygen species (ROS)-dependent immunity is critical to host survival. This is in contrast to the NF-kappaB pathway whose physiological function in the microbe-laden epithelia has yet to be convincingly demonstrated despite playing a critical role during systemic infections. We used a novel in vivo approach to reveal the physiological role of gut NF-kappaB/antimicrobial peptide (AMP) system, which has been 'masked' in the presence of the dominant intestinal ROS-dependent immunity. When fed with ROS-resistant microbes, NF-kappaB pathway mutant flies, but not wild-type flies, become highly susceptible to gut infection. This high lethality can be significantly reduced by either re-introducing Relish expression to Relish mutants or by constitutively expressing a single AMP to the NF-kappaB pathway mutants in the intestine. These results imply that the local 'NF-kappaB/AMP' system acts as an essential 'fail-safe' system, complementary to the ROS-dependent gut immunity, during gut infection with ROS-resistant pathogens. This system provides the Drosophila gut immunity the versatility necessary to manage sporadic invasion of virulent pathogens that somehow counteract or evade the ROS-dependent immunity.

  7. Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2.

    PubMed Central

    Duckett, C S; Gedrich, R W; Gilfillan, M C; Thompson, C B

    1997-01-01

    CD30 is a lymphoid cell-specific surface receptor which was originally identified as an antigen expressed on Hodgkin's lymphoma cells. Activation of CD30 induces the nuclear factor kappaB (NF-kappaB) transcription factor. In this study, we define the domains in CD30 which are required for NF-kappaB activation. Two separate elements of the cytoplasmic domain which were capable of inducing NF-kappaB independently of one another were identified. The first domain (domain 1) mapped to a approximately 120-amino-acid sequence in the membrane-proximal region of the CD30 cytoplasmic tail, between residues 410 and 531. A second, more carboxy-terminal region (domain 2) was identified between residues 553 and 595. Domain 2 contains two 5- to 10-amino-acid elements which can mediate the binding of CD30 to members of the tumor necrosis factor receptor-associated factor (TRAF) family of signal transducing proteins. Coexpression of CD30 with TRAF1 or TRAF2 but not TRAF3 augmented NF-kappaB activation through domain 2 but not domain 1. NF-kappaB induction through domain 2 was inhibited by coexpression of either full-length TRAF3 or dominant negative forms of TRAF1 or TRAF2. In contrast, NF-kappaB induction by domain 1 was not affected by alterations in TRAF protein levels. Together, these data support a model in which CD30 can induce NF-kappaB by both TRAF-dependent and -independent mechanisms. TRAF-dependent induction of NF-kappaB appears to be regulated by the relative levels of individual TRAF proteins in the cell. PMID:9032281

  8. Convulsions may alter the specificity of kappa-opiate receptors.

    PubMed

    Mansour, A; Valenstein, E S

    1986-06-01

    Morphine, a mu-opiate agonist, and ethylketazocine, a kappa-opiate agonist, produce distinct behavioral, pharmacologic, and biochemical effects. In the mouse, large doses of morphine produce convulsions that are usually lethal and that cannot be blocked by naltrexone, whereas ethylketazocine produces nonlethal clonic convulsions that can be blocked by naltrexone. Moreover, mice made tolerant to morphine failed to show cross-tolerance to ethylketazocine, suggesting that the convulsions induced by these drugs are not mediated via a common opioid mechanism. Following a series of electroconvulsive shocks, both morphine and ethylketazocine produced clonic convulsions that were not lethal and that could be blocked by naltrexone. Furthermore, electroconvulsive shock-treated animals made tolerant to morphine-induced convulsions showed cross-tolerance to ethylketazocine. These data suggest that electroconvulsive shock may alter kappa-opioid systems in such a way as to allow mu-agonists to be functional at these sites.

  9. Endodontic radiography: who is reading the digital radiograph?

    PubMed

    Tewary, Shalini; Luzzo, Joseph; Hartwell, Gary

    2011-07-01

    Digital radiographic imaging systems have undergone tremendous improvements since their introduction. Advantages of digital radiographs over conventional films include lower radiation doses compared with conventional films, instantaneous images, archiving and sharing images easily, and manipulation of several radiographic properties that might help in diagnosis. A total of 6 observers including 2 endodontic residents, 3 endodontists, and 1 oral radiologist evaluated 150 molar digital periapical radiographs to determine which of the following conditions existed: normal periapical tissue, widened periodontal ligament, or presence of periapical radiolucency. The evaluators had full control over the radiograph's parameters of the Planmeca Dimaxis software program. All images were viewed on the same computer monitor with ideal vie-wing conditions. The same 6 observers evaluated the same 150 digital images 3 months later. The data were analyzed to determine how well the evaluators agreed with each other (interobserver agreement) for 2 rounds of observations and with themselves (intraobserver agreement). Fleiss kappa statistical analysis was used to measure the level of agreement among multiple raters. The overall Fleiss kappa value for interobserver agreement for the first round of interpretation was 0.34 (P < .001). The overall Fleiss kappa value for interobserver agreement for the second round of interpretation was 0.35 (P < .001). This resulted in fair (0.2-0.4) agreement among the 6 raters at both observation periods. A weighted kappa analysis was used to determine intraobserver agreement, which showed on average a moderate agreement. The results indicate that the interpretation of a dental radiograph is subjective, irrespective of whether conventional or digital radiographs are used. The factors that appeared to have the most impact were the years of experience of the examiner and familiarity of the operator with a given digital system. Copyright © 2011 American

  10. TLR3-mediated NF-{kappa}B signaling in human esophageal epithelial cells.

    PubMed

    Lim, Diana M; Narasimhan, Sneha; Michaylira, Carmen Z; Wang, Mei-Lun

    2009-12-01

    Despite its position at the front line against ingested pathogens, very little is presently known about the role of the esophageal epithelium in host innate immune defense. As a key player in the innate immune response, Toll-like receptor (TLR) signaling has not been well characterized in human esophageal epithelial cells. In the present study, we investigated the inflammatory response and signaling pathways activated by TLR stimulation of human esophageal cells in vitro. Using quantitative RT-PCR, we profiled the expression pattern of human TLRs 1-10 in primary esophageal keratinocytes (EPC2), immortalized nontransformed esophageal keratinocytes (EPC2-hTERT), and normal human esophageal mucosal biopsies and found that TLRs 1, 2, 3, and 5 were expressed both in vivo and in vitro. Using the cytokine IL-8 as a physiological read out of the inflammatory response, we found that TLR3 is the most functional of the expressed TLRs in both primary and immortalized esophageal epithelial cell lines in response to its synthetic ligand polyinosinic polycytidylic acid [poly(I:C)]. Through reporter gene studies, we show that poly(I:C)-induced NF-kappaB activation is critical for the transactivation of the IL-8 promoter in vitro and that nuclear translocation of NF-kappaB occurs at an early time point following poly(I:C) stimulation of esophageal epithelial cells. Importantly, we also show that poly(I:C) stimulation induces the NF-kappaB-dependent esophageal epithelial expression of TLR2, leading to enhanced epithelial responsiveness of EPC2-hTERT cells to TLR2 ligand stimulation, suggesting an important regulatory role for TLR3-mediated NF-kappaB signaling in the innate immune response of esophageal epithelial cells. Our findings demonstrate for the first time that TLR3 is highly functional in the human esophageal epithelium and that TLR3-mediated NF-kappaB signaling may play an important regulatory role in esophageal epithelial homeostasis.

  11. Quantitation of IgG kappa and IgG lambda in the cerebrospinal fluid by sandwich ELISA method.

    PubMed

    Zeman, David; Kušnierová, Pavlína; Bojková, Jana; Všianský, František; Zapletalová, Olga

    2017-01-01

    IgG kappa and IgG lambda concentrations were quantified in 96 paired CSF and sera using Hevylite™ antibodies in an in-house developed sandwich ELISA method. In 56 of these samples, the results were compared with a qualitative isoelectric focusing/affinity-mediated immunoblotting assay for oligoclonal IgG kappa and IgG lambda. Normal IgG kappa/lambda ratio in the CSF was the same as in serum. In 19/33 patients with intrathecal oligoclonal IgG synthesis, skewed IgG kappa/lambda ratio was observed (increased in 16 and decreased in 3 cases). The analysis of light chain composition of intrathecally synthesised immunoglobulins could contribute to our understanding of intrathecal humoral immune response, although its diagnostic utility is limited.

  12. CoMFA analyses of C-2 position salvinorin A analogs at the kappa-opioid receptor provides insights into epimer selectivity.

    PubMed

    McGovern, Donna L; Mosier, Philip D; Roth, Bryan L; Westkaemper, Richard B

    2010-04-01

    The highly potent and kappa-opioid (KOP) receptor-selective hallucinogen Salvinorin A and selected analogs have been analyzed using the 3D quantitative structure-affinity relationship technique Comparative Molecular Field Analysis (CoMFA) in an effort to derive a statistically significant and predictive model of salvinorin affinity at the KOP receptor and to provide additional statistical support for the validity of previously proposed structure-based interaction models. Two CoMFA models of Salvinorin A analogs substituted at the C-2 position are presented. Separate models were developed based on the radioligand used in the kappa-opioid binding assay, [(3)H]diprenorphine or [(125)I]6 beta-iodo-3,14-dihydroxy-17-cyclopropylmethyl-4,5 alpha-epoxymorphinan ([(125)I]IOXY). For each dataset, three methods of alignment were employed: a receptor-docked alignment derived from the structure-based docking algorithm GOLD, another from the ligand-based alignment algorithm FlexS, and a rigid realignment of the poses from the receptor-docked alignment. The receptor-docked alignment produced statistically superior results compared to either the FlexS alignment or the realignment in both datasets. The [(125)I]IOXY set (Model 1) and [(3)H]diprenorphine set (Model 2) gave q(2) values of 0.592 and 0.620, respectively, using the receptor-docked alignment, and both models produced similar CoMFA contour maps that reflected the stereoelectronic features of the receptor model from which they were derived. Each model gave significantly predictive CoMFA statistics (Model 1 PSET r(2)=0.833; Model 2 PSET r(2)=0.813). Based on the CoMFA contour maps, a binding mode was proposed for amine-containing Salvinorin A analogs that provides a rationale for the observation that the beta-epimers (R-configuration) of protonated amines at the C-2 position have a higher affinity than the corresponding alpha-epimers (S-configuration). (c) 2010. Published by Elsevier Inc.

  13. Corneal NF-kappaB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice.

    PubMed

    Alexander, George; Carlsen, Harald; Blomhoff, Rune

    2006-04-01

    To determine the dynamics of Nuclear Factor-kappaB (NF-kappaB) in murine corneal pathology and the role of NF-kappaB in maintaining corneal clarity after ultraviolet B radiation insult, transgenic mice containing NF-kappaB-luciferase reporter were exposed to LPS (bacterial lipopolysaccharide), TNF-alpha (Tumor Necrosis Factor-alpha) or 4 kJ m(-2) UV-B radiation. NF-kappaB decoy oligonucleotides were also administered in some of the UV-B experiments. Following various exposure times, the mice were sacrificed and whole eyes or corneal tissues were obtained. Whole eyes were examined for scattering using a point-source optical imaging technique. Tissue homogenates were examined for luciferase activity using a luminometer. TNF-alpha and LPS-injected NF-kappaB-luciferase transgenic mice demonstrated 3-10-fold increases in cornea NF-kappaB with peak activities at 4 and 6 hr post-injection, respectively. Mice exposed to 4 kJ m(-2) UV-B exhibited a 3-fold increase in NF-kappaB activity 4 hr post-exposure. The administration of NF-kappaB-decoy oligonucleotides to mice had the effect of reducing UV-B-induced NF-kappaB activity in the cornea and significantly increasing the amount of light scattering in UV-B exposed corneas 7 days post-UV-B exposure when compared to sham injected mice. These results indicate that NF-kappaB is activated in cornea in pathologies that involves increased plasma levels of LPS and TNF-alpha, as well as direct UV-B exposure, and suggest that NF-kappaB activation play an essential part in the corneal healing process.

  14. T cell-intrinsic requirement for NF-kappa B induction in postdifferentiation IFN-gamma production and clonal expansion in a Th1 response.

    PubMed

    Corn, Radiah A; Aronica, Mark A; Zhang, Fuping; Tong, Yingkai; Stanley, Sarah A; Kim, Se Ryoung Agnes; Stephenson, Linda; Enerson, Ben; McCarthy, Susan; Mora, Ana; Boothby, Mark

    2003-08-15

    NF-kappaB/Rel transcription factors are linked to innate immune responses and APC activation. Whether and how the induction of NF-kappaB signaling in normal CD4(+) T cells regulates effector function are not well-understood. The liberation of NF-kappaB dimers from inhibitors of kappaB (IkappaBs) constitutes a central checkpoint for physiologic regulation of most forms of NF-kappaB. To investigate the role of NF-kappaB induction in effector T cell responses, we targeted inhibition of the NF-kappaB/Rel pathway specifically to T cells. The Th1 response in vivo is dramatically weakened when T cells defective in their NF-kappaB induction (referred to as IkappaBalpha(DeltaN) transgenic cells) are activated by a normal APC population. Analyses in vivo, and IL-12-supplemented T cell cultures in vitro, reveal that the mechanism underlying this T cell-intrinsic requirement for NF-kappaB involves activation of the IFN-gamma gene in addition to clonal expansion efficiency. The role of NF-kappaB in IFN-gamma gene expression includes a modest decrease in Stat4 activation, T box expressed in T cell levels, and differentiation efficiency along with a more prominent postdifferentiation step. Further, induced expression of Bcl-3, a trans-activating IkappaB-like protein, is decreased in T cells as a consequence of NF-kappaB inhibition. Together, these findings indicate that NF-kappaB induction in T cells regulates efficient clonal expansion, Th1 differentiation, and IFN-gamma production by Th1 lymphocytes at a control point downstream from differentiation.

  15. Lymphotoxin activation by human T-cell leukemia virus type I-infected cell lines: role for NF-kappa B.

    PubMed

    Paul, N L; Lenardo, M J; Novak, K D; Sarr, T; Tang, W L; Ruddle, N H

    1990-11-01

    Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of biologically active lymphotoxin (LT; tumor necrosis factor-beta) protein and LT mRNA. To understand the regulation of LT transcription by HTLV-I, we analyzed the ability of a series of deletions of the LT promoter to drive the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I-positive MT-2 cells. The smallest LT promoter fragment (-140 to +77) that was able to drive CAT activity contained a site that was similar to the immunoglobulin kappa-chain NF-kappa B-binding site. Since the HTLV-I tax gene activates the nuclear form of NF-kappa B, this finding suggested a possible means of HTLV-I activation of LT production. We found that the LT kappa B-like site specifically formed a complex with NF-kappa B-containing nuclear extract from MT-2, C81-66-45, and other activated T cells. Mutation of the LT kappa B site in the context of the LT promoter (-293 to +77) (mutant M1) reduced the ability of the promoter to drive the CAT gene in HTLV-I-infected and noninfected human T-cell lines. These data suggest a general role for NF-kappa B activation in the induction of LT gene transcription. Activation of LT in HTLV-I-infected cells may explain the pathology associated with HTLV-I infection, including the hypercalcemia that is prevalent in adult T-cell leukemia.

  16. Evaluation of dental therapists undertaking dental examinations in a school setting in Scotland.

    PubMed

    O'Keefe, Emma J; McMahon, Alex D; Jones, Colwyn M; Curnow, Morag M; Macpherson, Lorna M D

    2016-12-01

    To measure agreement between dental therapists and the Scottish gold-standard dentist undertaking National Dental Inspection Programme (NDIP) examinations. A study of interexaminer agreement between 19 dental therapists and the national gold-standard dentist was carried out. Pre-calibration training used the caries diagnostic criteria and examination techniques agreed by the British Association for the Study of Community Dentistry (BASCD). Twenty-three 5-year-old children (Primary 1) and 17 11-year-old children (Primary 7) children were examined. Agreement was assessed using kappa statistics on d 3 mft and D 3 MFT for P1 and P7 children, sensitivity and specificity values, and kappa statistics on d 3 t/D 3 T and ft/FT. Calibration data on P1 and P7 children from 2009-2012 involving dentists as examiners were used for comparison. Economic evaluation was undertaken using a cost minimization analysis approach. The mean kappa score was 0.84 (SD 0.07) ranging from 0.69 to 0.94. All dental therapists scored good or very good agreement with the gold-standard dentist. This compares with historic NDIP calibration data with dentists, against the same gold-standard dentist, where the mean kappa value was 0.68 (SD 0.22) with a range of 0.35-1.00. The mean sensitivity score was 0.98 (SD 0.04) (range 0.88-1.0) and mean specificity score was 0.90 (SD 0.06) (range 0.78-0.96). Health economic analysis estimated that salary costs would be 33.6% lower if dental therapists were substituted for dentists in the year 2013, with an estimated saving of approximately £103 646 per annum on the national budget. We conclude that dental therapists show a high level of interexaminer agreement, and with the appropriate annual training and calibration, they could undertake dental examinations as part of the NDIP programme. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Reactive oxygen species mediate liver injury through parenchymal nuclear factor-kappaB inactivation in prolonged ischemia/reperfusion.

    PubMed

    Llacuna, Laura; Marí, Montserrat; Lluis, Josep M; García-Ruiz, Carmen; Fernández-Checa, José C; Morales, Albert

    2009-05-01

    Nuclear factor (NF)-kappaB participates in ischemia/reperfusion (I/R) hepatic signaling, stimulating both protective mechanisms and the generation of inflammatory cytokines. After analyzing NF-kappaB activation during increasing times of ischemia in murine I/R, we observed that the nuclear translocation of p65 paralleled Src and IkappaB tyrosine phosphorylation, which peaked after 60 minutes of ischemia. After extended ischemic periods (90 to 120 minutes) however, nuclear p65 levels were inversely correlated with the progressive induction of oxidative stress. Despite this profile of NF-kappaB activation, inflammatory genes, such as tumor necrosis factor (TNF) and interleukin (IL)-1beta, predominantly induced by Kupffer cells, increased throughout time during ischemia (30 to 120 minutes), whereas protective NF-kappaB-dependent genes, such as manganese superoxide dismutase (Mn-SOD), expressed in parenchymal cells, decreased. Consistent with this behavior, gadolinium chloride pretreatment abolished TNF/IL-1beta up-regulation during ischemia without affecting Mn-SOD levels. Interestingly, specific glutathione (GSH) up-regulation in hepatocytes by S-adenosylmethionine increased Mn-SOD expression and protected against I/R-mediated liver injury despite TNF/IL-1beta induction. Similar protection was achieved by administration of the SOD mimetic MnTBAP. In contrast, indiscriminate hepatic GSH depletion by buthionine-sulfoximine before I/R potentiated oxidative stress and decreased both nuclear p65 and Mn-SOD expression levels, increasing TNF/IL-1beta up-regulation and I/R-induced liver damage. Thus, the divergent role of NF-kappaB activation in selective liver cell populations underlies the dichotomy of NF-kappaB in hepatic I/R injury, illustrating the relevance of specifically maintaining NF-kappaB activation in parenchymal cells.

  18. p38 mitogen-activated protein kinase up-regulates NF-{kappa}B transcriptional activation through RelA phosphorylation during stretch-induced myogenesis

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

    Ji, Guoping; Liu, Dongxu; Liu, Jing

    2010-01-01

    p38 MAPK and nuclear factor-B (NF-B) signaling pathways play an indispensable role in the control of skeletal myogenesis. The specific contribution of these signaling pathways to the response of myoblast to the mechanical stimulation and the molecular mechanisms underlying this response remain unresolved. Using an established in vitro model, we now show that p38 MAP kinase activity regulates the transcriptional activation of NF-{kappa}B in response to mechanical stimulation of myoblasts. Furthermore, SB203580 blocked stretch-induced NF-{kappa}B activation during myogenesis, not through down-regulation of degradation of I{kappa}B-{alpha}, and consequent translocation of the p65 subunit of NF-{kappa}B to the nucleus. It is likelymore » that stretch-induced NF-{kappa}B activation by phosphorylation of p65 NF-{kappa}B. Moreover, depletion of p38{alpha} using siRNA significantly reduces stretch-induced phosphorylation of RelA and NF-{kappa}B activity. These results provides the first evidence of a cross-talk between p38 MAPK and NF-{kappa}B signaling pathways during stretch-induced myogenesis, with phosphorylation of RelA being one of the effectors of this promyogenic mechanism. The {alpha} isoform of p38MAP kinase regulates the transcriptional activation of NF-{kappa}B following stimulation with cyclic stretch.« less

  19. NF-kappaB signaling blockade by Bay 11-7085 during early cardiac morphogenesis induces alterations of the outflow tract in chicken heart.

    PubMed

    Hernández-Gutierrez, S; García-Peláez, I; Zentella-Dehesa, A; Ramos-Kuri, M; Hernández-Franco, P; Hernández-Sánchez, F; Rojas, E

    2006-07-01

    Nuclear factor kappaB (NF-kappaB) is a pleiotropic transcription factor implicated in the regulation of diverse morphologic cardiac alterations, for which the p50 and p65 subunits form the most prevalent dimeric form in the heart. NF-kappaB is inactivated by proteins of the IkappaB family, which trap it in the cytoplasm. It is not known whether NF-kappaB influences cardiac development. Here we investigated the role of NF-kappaB in regulating transcription in chicken heart morphogenesis. Specifically, we tested whether NF-kappaB activation is required for normal formation of the outflow tract (OFT) during a critical stage of heart development. We designed a reporter vector with kappaB binding sites for Rel family members in the promoter, upstream from the cDNA of Green Fluorescent Protein (GFP). This construct was injected directly into the developing heart of chicken embryos. NF-kappaB activation was subsequently inhibited by administration of the specific pharmacological agent Bay 11-7085. We found that forced NF-kappaB expression was associated with multiple congenital cardiac alterations of the OFT (mainly IVC, DORV and great arteries stenosis). These findings indicate that blockade of NF-kappaB induces apoptosis and is an important factor in the development of OFT during cardiogenesis. However, it remains unknown which members of the Rel family are relevant in this process.

  20. Activation of kappa opioid receptors in the dorsal raphe have sex dependent effects on social behavior in California mice.

    PubMed

    Wright, Emily C; Parks, Tiffany V; Alexander, Jonathon O; Supra, Rajesh; Trainor, Brian C

    2018-06-06

    Kappa opioid receptor activation has been linked to stress and anxiety behavior, thus leading to kappa antagonists being popularized in research as potential anxiolytics. However, while these findings may hold true in standard models, the neuromodulatory effects of social defeat may change the behavioral outcome of kappa opioid receptor activation. Previous research has shown that social defeat can lead to hyperactivity of serotonergic neurons in the dorsal raphe nucleus, and that inhibition of this increase blocks the social deficits caused by defeat. Kappa opioid receptor activation in the dorsal raphe nucleus works to decrease serotonergic activity. We injected the kappa opioid receptor U50,488 directly into the dorsal raphe nucleus of male and female, defeat and control adult California mice. Here we show evidence that U50,488 induces anxiety behavior in control male California mice, but helps relieve it in defeated males. Consistent with previous literature, we find little effect in females adding evidence that there are marked and important sex differences in the kappa opioid system. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Agreement between patient interview data on prescription medication use and pharmacy records in those aged older than 50 years varied by therapeutic group and reporting of indicated health conditions.

    PubMed

    Richardson, Kathryn; Kenny, Rose Anne; Peklar, Jure; Bennett, Kathleen

    2013-11-01

    To estimate the agreement between interview-ascertained medication use and pharmacy records among the population aged older than 50 years, and to identify patient-level predictors of discordance. The Irish Longitudinal study on Ageing is representative of community-dwelling adults aged 50 years and older in Ireland. Interview-ascertained medication data from 2,621 participants were linked to pharmacy dispensing records. The kappa statistics measured the agreement between the two sources for 19 therapeutic classes. Logistic regression assessed the effect of patient-level characteristics on survey under- and overreporting of regularly dispensed medications. Agreement was good or very good (κ=0.64-0.86) for 15 medication classes, and moderate or poor for antiinflammatory and antirheumatic products (κ=0.54), analgesics (κ=0.50), psycholeptics (κ=0.59), and ophthalmologicals (κ=0.37). Not reporting an indicated health condition, less frequent dispensing, older age, and more medications regularly dispensed were associated with survey underreporting, but results varied by therapeutic class. Memory and cognition were not associated with discordance. Ascertaining medication use via patient interview seems a valid method for most medication classes and also captures nonprescription and supplement use. However, medications applied topically and as needed may be underreported. The source of medication data should be carefully considered when performing pharmacoepidemiological studies. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Phenotyping polyclonal kappa and lambda light chain molecular mass distributions in patient serum using mass spectrometry.

    PubMed

    Barnidge, David R; Dasari, Surendra; Ramirez-Alvarado, Marina; Fontan, Adrian; Willrich, Maria A V; Tschumper, Renee C; Jelinek, Diane F; Snyder, Melissa R; Dispenzieri, Angela; Katzmann, Jerry A; Murray, David L

    2014-11-07

    We previously described a microLC-ESI-Q-TOF MS method for identifying monoclonal immunoglobulins in serum and then tracking them over time using their accurate molecular mass. Here we demonstrate how the same methodology can be used to identify and characterize polyclonal immunoglobulins in serum. We establish that two molecular mass distributions observed by microLC-ESI-Q-TOF MS are from polyclonal kappa and lambda light chains using a combination of theoretical molecular masses from gene sequence data and the analysis of commercially available purified polyclonal IgG kappa and IgG lambda from normal human serum. A linear regression comparison of kappa/lambda ratios for 74 serum samples (25 hypergammaglobulinemia, 24 hypogammaglobulinemia, 25 normal) determined by microflowLC-ESI-Q-TOF MS and immunonephelometry had a slope of 1.37 and a correlation coefficient of 0.639. In addition to providing kappa/lambda ratios, the same microLC-ESI-Q-TOF MS analysis can determine the molecular mass for oligoclonal light chains observed above the polyclonal background in patient samples. In 2 patients with immune disorders and hypergammaglobulinemia, we observed a skewed polyclonal molecular mass distribution which translated into biased kappa/lambda ratios. Mass spectrometry provides a rapid and simple way to combine the polyclonal kappa/lambda light chain abundance ratios with the identification of dominant monoclonal as well as oligoclonal light chain immunoglobulins. We anticipate that this approach to evaluating immunoglobulin light chains will lead to improved understanding of immune deficiencies, autoimmune diseases, and antibody responses.

  3. Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy, inhibit the proinflammatory transcription factor NF-kappaB.

    PubMed

    Riehemann, K; Behnke, B; Schulze-Osthoff, K

    1999-01-08

    Activation of transcription factor NF-kappaB is elevated in several chronic inflammatory diseases and is responsible for the enhanced expression of many proinflammatory gene products. Extracts from leaves of stinging nettle (Urtica dioica) are used as antiinflammatory remedies in rheumatoid arthritis. Standardized preparations of these extracts (IDS23) suppress cytokine production, but their mode of action remains unclear. Here we demonstrate that treatment of different cells with IDS23 potently inhibits NF-kappaB activation. An inhibitory effect was observed in response to several stimuli, suggesting that IDS23 suppressed a common NF-kappaB pathway. Inhibition of NF-kappaB activation by IDS23 was not mediated by a direct modification of DNA binding, but rather by preventing degradation of its inhibitory subunit IkappaB-alpha. Our results suggests that part of the antiinflammatory effect of Urtica extract may be ascribed to its inhibitory effect on NF-kappaB activation.

  4. Hypnotics use in children 0-18 months: moderate agreement between mother-reported survey data and prescription registry data.

    PubMed

    Holdø, Ingvild; Bramness, Jørgen G; Handal, Marte; Torgersen, Leila; Reichborn-Kjennerud, Ted; Ystrøm, Eivind; Nordeng, Hedvig; Skurtveit, Svetlana

    2017-01-01

    Different methods in pharmacoepidemiology can be used to study hypnotic use in children. But neither questionnaire-based data nor prescription records can be considered a "gold standard". This study aimed to investigate the agreement between mother-reported questionnaire-based data and prescription record data for hypnotic drugs in children aged 0-18 months. The agreement was compared to the agreement for a group of antiepileptic drugs. Prescription record data were collected from the Norwegian prescription database for 47,413 children also surveyed in the Norwegian mother and child cohort between 2005 and 2009. Agreement between in the two data sources was calculated using Cohens Kappa. Multinomial logistic regression was used to calculate the effect of sociodemographic variables on discrepancies in data sources. The agreement between mother-reported and dispensed hypnotics was less than 50% for all hypnotics. Sensitivity of reporting increased with number of filled prescriptions. The agreement of antiepileptic drugs was 92.9% in the same population. Of several sociodemographic factors only paternal educational level and maternal work situation was significantly related to agreement between prescription record and survey data. There was a moderate agreement between reported use and dispensed hypnotic drugs for infants and toddlers. Results indicate that sociodemographic factors play only a minor role in explaining discrepancy.

  5. Radiographic classifications in Perthes disease

    PubMed Central

    Huhnstock, Stefan; Svenningsen, Svein; Merckoll, Else; Catterall, Anthony; Terjesen, Terje; Wiig, Ola

    2017-01-01

    Background and purpose Different radiographic classifications have been proposed for prediction of outcome in Perthes disease. We assessed whether the modified lateral pillar classification would provide more reliable interobserver agreement and prognostic value compared with the original lateral pillar classification and the Catterall classification. Patients and methods 42 patients (38 boys) with Perthes disease were included in the interobserver study. Their mean age at diagnosis was 6.5 (3–11) years. 5 observers classified the radiographs in 2 separate sessions according to the Catterall classification, the original and the modified lateral pillar classifications. Interobserver agreement was analysed using weighted kappa statistics. We assessed the associations between the classifications and femoral head sphericity at 5-year follow-up in 37 non-operatively treated patients in a crosstable analysis (Gamma statistics for ordinal variables, γ). Results The original lateral pillar and Catterall classifications showed moderate interobserver agreement (kappa 0.49 and 0.43, respectively) while the modified lateral pillar classification had fair agreement (kappa 0.40). The original lateral pillar classification was strongly associated with the 5-year radiographic outcome, with a mean γ correlation coefficient of 0.75 (95% CI: 0.61–0.95) among the 5 observers. The modified lateral pillar and Catterall classifications showed moderate associations (mean γ correlation coefficient 0.55 [95% CI: 0.38–0.66] and 0.64 [95% CI: 0.57–0.72], respectively). Interpretation The Catterall classification and the original lateral pillar classification had sufficient interobserver agreement and association to late radiographic outcome to be suitable for clinical use. Adding the borderline B/C group did not increase the interobserver agreement or prognostic value of the original lateral pillar classification. PMID:28613966

  6. Agreement and Predictive Validity Using Less Conservative FNIH Sarcopenia Project Weakness Cutpoints

    PubMed Central

    Shaffer, Nancy Chiles; Ferrucci, Luigi; Shardell, Michelle; Simonsick, Eleanor M.; Studenski, Stephanie

    2016-01-01

    OBJECTIVES The FNIH Sarcopenia Project derived conservative definitions for weakness and low lean mass, resulting in low prevalence and low agreement with prior definitions. The FNIH Project also estimated a less conservative cutpoint for low grip strength, potentially yielding a cutpoint for low lean mass more consistent with the European Working Group on Sarcopenia in Older People (EWGSOP). We derived lean mass cutpoints based on the less conservative cutpoint for grip strength (WeakI), and assessed agreement with EWGSOP and prediction of incident slow walking and mortality. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS Longitudinal analysis of 287 men and 258 women from the Baltimore Longitudinal Study of Aging aged >65 years, with 2–10 years followup. Weakness was determined via hand dynamometer, appendicular lean mass (ALM) via DEXA, and slow walking by 6m usual pace walk <0.8m/s. Analyses used classification and regression tree analysis, Cohen’s Kappa, and Cox models. RESULTS Cutpoints derived from WeakI for ALM (ALMI) and ALM adjusted for body mass index (ALM/BMII) were (ALMI) <21.4kg (men) and <14.1kg (women); and (ALM/BMII) <0.725 (men) and <0.591 (women). Kappas with EWGSOP were (ALMI); 0.65 (men) and 0.75 (women) and ALM/BMII; 0.34 (men) and 0.47 (women). In men, the hazard ratio for incident slow walking by WeakI + ALMI was 2.44 (95% CI:1.02–5.82) versus 2.91 (95% CI:1.11–7.62) by EWGSOP. Neither approach predicted incident slow walking in women. CONCLUSION The ALMI cutpoints agree with EWGSOP and predict slow walking in men. Future studies should explore sex differences in the relationship between body composition and physical function and the impact of change in muscle mass on muscle strength and physical function. PMID:28024092

  7. Prospective cohort study of ultrasound-ultrasound and ultrasound-MR enterography agreement in the evaluation of pediatric small bowel Crohn disease.

    PubMed

    Dillman, Jonathan R; Smith, Ethan A; Sanchez, Ramon; DiPietro, Michael A; Dehkordy, Soudabeh Fazeli; Adler, Jeremy; DeMatos-Maillard, Vera; Khalatbari, Shokoufeh; Davenport, Matthew S

    2016-04-01

    There is a paucity of published literature describing ultrasound (US)-US and US-MR enterography (MRE) inter-radiologist agreement in pediatric small bowel Crohn disease. To prospectively assess US-US and US-MRE inter-radiologist agreement in pediatric small bowel Crohn disease. Institutional Review Board approval and informed consent/assent were obtained for this HIPAA-compliant prospective cohort study of children with newly diagnosed distal small bowel Crohn disease (July 2012 to December 2014). Enrolled subjects (n = 29) underwent two small bowel US examinations performed by blinded independent radiologists both before and at multiple time points after initiation of medical therapy (231 unique US examinations, in total); 134 US examinations were associated with concurrent MRE. The MRE examination was interpreted by a third blinded radiologist. The following was documented on each examination: involved length of ileum (cm); maximum bowel wall thickness (mm); amount of bowel wall and mesenteric Doppler signal, and presence of stricture, penetrating disease and/or abscess. Inter-radiologist agreement was assessed with single-measure, three-way, mixed-model intra-class correlation coefficients (ICC) and prevalence-adjusted, bias-adjusted kappa statistics (κ). Numbers in brackets are 95% confidence intervals. Ultrasound-US agreement was moderate for involved length (ICC: 0.41 [0.35-0.49]); substantial for maximum bowel wall thickness (ICC: 0.67 [0.64-0.70]); moderate for bowel wall Doppler signal (ICC: 0.53 [0.48-0.59]); slight for mesenteric Doppler signal (ICC: 0.25 [0.18-0.42]), and moderate to almost perfect for stricture (κ: 0.54), penetrating disease (κ: 0.80), and abscess (κ: 0.96). US-MRE agreement was moderate for involved length (ICC: 0.42 [0.37-0.49]); substantial for maximum bowel wall thickness (ICC: 0.66 [0.65-0.69]), and substantial to almost perfect for stricture (κ: 0.61), penetrating disease (κ: 0.72) and abscess (κ: 0.88). Ultrasound

  8. NIK and Cot cooperate to trigger NF-kappaB p65 phosphorylation.

    PubMed

    Wittwer, Tobias; Schmitz, M Lienhard

    2008-06-27

    The serine/threonine kinase Cot triggers NF-kappaB-dependent transactivation and activation of various MAPKinases. Here we identify Cot as a novel p65 interacting protein kinase. Cot expression induces p65 phosphorylation at serines 536 and 468 in dependence from its kinase function. Accordingly, shRNA-mediated knockdown of Cot expression interferes with TNF-induced NF-kappaB-dependent gene expression. Also the C-terminally truncated, oncogenic form of Cot is able to trigger p65 phosphorylation. In vitro kinase assays and dominant negative mutants revealed that NIK functions downstream of Cot to mediate p65 phosphorylation.

  9. Terminally Ill Taiwanese Cancer Patients' and Family Caregivers' Agreement on Patterns of Life-Sustaining Treatment Preferences Is Poor to Fair and Declines Over a Decade: Results From Two Independent Cross-Sectional Studies.

    PubMed

    Liu, Tsang-Wu; Wen, Fur-Hsing; Wang, Cheng-Hsu; Hong, Ruey-Long; Chow, Jyh-Ming; Chen, Jen-Shi; Chiu, Chang-Fang; Tang, Siew Tzuh

    2017-07-01

    Temporal changes have not been examined in patient-caregiver agreement on life-sustaining treatment (LST) preferences at end of life (EOL). We explored the extent of and changes in patient-caregiver agreement on LST-preference patterns for two independent cohorts of Taiwanese cancer patient-family caregiver dyads recruited a decade apart. We surveyed preferences for cardiopulmonary resuscitation, intensive care unit care, cardiac massage, intubation with mechanical ventilation, intravenous nutritional support, tube feeding, and dialysis among 1049 and 1901 dyads in 2003-2004 and 2011-2012, respectively. LST-preference patterns were examined by multi-group latent class analysis. Extent of patient-caregiver agreement on LST-preference patterns was determined by percentage agreement and kappa coefficients. For both patients and family caregivers, we identified seven distinct LST-preference classes. Patient-caregiver agreement on LST-preference patterns was poor to fair across both study cohorts, indicated by 24.4%-43.5% agreement and kappa values of 0.06 (95% CI: 0.04, 0.09) to 0.27 (0.23, 0.30), and declined significantly over time. Agreement on LST-preference patterns was most likely when both patients and caregivers uniformly rejected LSTs. When patients disagreed with caregivers on LST-preference patterns, discrepancies were most likely when patients totally rejected LSTs but caregivers uniformly preferred LSTs or preferred nutritional support but rejected other treatments. Patients and family caregivers had poor-to-fair agreement on LST-preference patterns, and agreement declined significantly over a decade. Encouraging an open dialogue between patients and their family caregivers about desired EOL care would facilitate patient-caregiver agreement on LST-preference patterns, thus honoring terminally ill cancer patients' wishes when they cannot make EOL-care decisions. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc

  10. NBBA, a synthetic small molecule, inhibits TNF-{alpha}-induced angiogenesis by suppressing the NF-{kappa}B signaling pathway

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

    Kim, Nam Hee; Jung, Hye Jin; Shibasaki, Futoshi

    2010-01-15

    Nuclear factor-{kappa}B (NF-{kappa}B) is a crucial transcription factor that contributes to cancer development by regulating a number of genes involved in angiogenesis and tumorigenesis. Here, we describe (Z)-N-(3-(7-nitro-3-oxobenzo[d][1,2]selenazol-2(3H)-yl)benzylidene) propan-2-amine oxide (NBBA) as a new anti-angiogenic small molecule that targets NF-{kappa}B activity. NBBA showed stronger growth inhibition on human umbilical vein endothelial cells (HUVECs) than on the cancer cell lines we tested. Moreover, NBBA inhibited tumor necrosis factor-alpha (TNF-{alpha})-induced tube formation and invasion of HUVECs. In addition, NBBA suppressed the neovascularization of chorioallantonic membrane from growing chick embryos in vivo. To address the mode of action of the compound, the effectmore » of NBBA on TNF-{alpha}-induced NF-{kappa}B transcription activity was investigated. NBBA suppressed TNF-{alpha}-induced c-Jun N-terminal kinase phosphorylation, which resulted in suppression of transcription of NF-{kappa}B and its target genes, including interleukin-8, interleukin-1{alpha}, and epidermal growth factor. Collectively, these results demonstrated that NBBA is a new anti-angiogenic small molecule that targets the NF-{kappa}B signaling pathway.« less

  11. Are parents and adolescents in agreement on reporting of recurrent non-specific low back pain in adolescents? A cross-sectional descriptive study.

    PubMed

    Chiwaridzo, Matthew; Naidoo, Nirmala

    2015-12-08

    Non-specific low back pain is a prevalent symptom in adolescents and is recurrent in some instances. Recent studies have highlighted the marked impact the condition has on daily life of adolescents. However, it is unclear if parents of adolescents reporting recurrent non-specific low back pain know about their child's status. The purpose of the study was to determine the level of agreement between adolescents and their parents in reporting recurrent non-specific low back pain in Harare, Zimbabwe. This cross-sectional study formed part of a large study carried out to ascertain the prevalence of non-specific low back pain in Zimbabwean adolescents. Six hundred and twenty (n = 620) Medical Health Questionnaires were sent to parents. School-children with returned questionnaires and informed consents signed were subsequently eligible to participate. A reliable and validated low back pain study questionnaire was administered to 544 adolescents between the ages of 13 and 19 years randomly selected from government-administered schools. The questionnaire sought to determine adolescents with recurrent NSLBP. The Kappa statistic (k) was used to analyse agreement between adolescents and parental reports on recurrent NSLBP status. Parental and school-children response rates were acceptable (90.3 and 97.8 %, respectively). The prevalence of recurrent NSLBP was 28.8 % [95 % Confidence Interval, CI = 26.0-31.6]. Both sexes were equally affected [χ (2) (1) =0.19, p = 0.67]. The prevalence increased with age in both sexes [χ (2) trend =90.9, p < 0.001]. Parental reports agreed in 16.3 and 98.7 % for the adolescents with and without recurrent NSLBP respectively. The value of kappa (k) was 0.20 [SE = 0.04; 95 % CI, 0.13-0.27] with a prevalence index and bias index of -0.65 and 0.23, respectively. These results suggest poor strength of the agreement. Recurrent non-specific low back pain is relatively common among Zimbabwean adolescents. Most of the parents of

  12. Thalidomide suppresses NF-kappa B activation induced by TNF and H2O2, but not that activated by ceramide, lipopolysaccharides, or phorbol ester.

    PubMed

    Majumdar, Sekhar; Lamothe, Betty; Aggarwal, Bharat B

    2002-03-15

    Thalidomide ([+]-alpha-phthalimidoglutarimide), a psychoactive drug that readily crosses the blood-brain barrier, has been shown to exhibit anti-inflammatory, antiangiogenic, and immunosuppressive properties through a mechanism that is not fully established. Due to the central role of NF-kappaB in these responses, we postulated that thalidomide mediates its effects through suppression of NF-kappaB activation. We investigated the effects of thalidomide on NF-kappaB activation induced by various inflammatory agents in Jurkat cells. The treatment of these cells with thalidomide suppressed TNF-induced NF-kappaB activation, with optimum effect occurring at 50 microg/ml thalidomide. These effects were not restricted to T cells, as other hematopoietic and epithelial cell types were also inhibited. Thalidomide suppressed H(2)O(2)-induced NF-kappaB activation but had no effect on NF-kappaB activation induced by PMA, LPS, okadaic acid, or ceramide, suggesting selectivity in suppression of NF-kappaB. The suppression of TNF-induced NF-kappaB activation by thalidomide correlated with partial inhibition of TNF-induced degradation of an inhibitory subunit of NF-kappaB (IkappaBalpha), abrogation of IkappaBalpha kinase activation, and inhibition of NF-kappaB-dependent reporter gene expression. Thalidomide abolished the NF-kappaB-dependent reporter gene expression activated by overexpression of TNFR1, TNFR-associated factor-2, and NF-kappaB-inducing kinase, but not that activated by the p65 subunit of NF-kappaB. Overall, our results clearly demonstrate that thalidomide suppresses NF-kappaB activation specifically induced by TNF and H(2)O(2) and that this may contribute to its role in suppression of proliferation, inflammation, angiogenesis, and the immune system.

  13. The reliability of endoscopic examination in assessment of arytenoid cartilage movement in horses. Part I: Subjective and objective laryngeal evaluation.

    PubMed

    Hackett, R P; Ducharme, N G; Fubini, S L; Erb, H N

    1991-01-01

    Videorecordings of the laryngeal activity of 108 unsedated horses were obtained at rest by passing a flexible videoendoscope into the nasopharynx through the right ventral meatus. All videotaped images were reviewed once, and 72 were reviewed twice, by three veterinarians. Laryngeal cartilage movement was assessed subjectively with a five-tier grading system. The mean intraobserver agreement was 83.3% (range, 75.0%-90.2%) with a kappa statistic of .65 to .98. The mean interobserver agreement was 79.0% (range, 70.4%-80.6%) with a kappa statistic of .51 to .90. A computer program was developed to measure the left:right ratio of the rima glottidis. The mean left:right ratio for horses assigned a median laryngeal grade of I was 0.84 (range, 0.55-1.03); for grade II, 0.82 (0.50-1.12); for grade III, 0.59 (0.39-0.91); and for grade IV, 0.24 (0.07-0.35).

  14. Agreement between Results of Home Sleep Testing for Obstructive Sleep Apnea with and without a Sleep Specialist

    PubMed Central

    Aurora, R. Nisha; Putcha, Nirupama; Swartz, Rachel; Punjabi, Naresh M.

    2016-01-01

    Background Obstructive sleep apnea is a prevalent yet underdiagnosed condition associated with cardiovascular morbidity and mortality. Home sleep testing offers an efficient means for diagnosing obstructive sleep apnea but has primarily been deployed in clinical samples with a high pretest probability. The current study sought to assess if obstructive sleep apnea can be diagnosed with home sleep testing in a non-referred sample without involvement of a sleep medicine specialist. Methods A study of community-based adults with untreated obstructive sleep apnea was undertaken. Misclassification of disease severity based on home sleep testing with and without involvement of a sleep medicine specialist was assessed, and agreement was characterized using scatter plots, Pearson's correlation coefficient, Bland-Altman analysis, and the kappa statistic. Analyses were also conducted to assess whether any observed differences varied as a function of pretest probability of obstructive sleep apnea or subjective sleepiness. Results The sample consisted of 191 subjects with over half (56.5%) having obstructive sleep apnea. Without involvement of a sleep medicine specialist, obstructive sleep apnea was not identified in only 5.8% of the sample. Analyses comparing the categorical assessment of disease severity with and without a sleep medicine specialist showed that in total, 32 subjects (16.8%) were misclassified. Agreement in the disease severity with and without a sleep medicine specialist was not influenced by the pretest probability or daytime sleep tendency. Conclusion Obstructive sleep apnea can be reliably identified with home sleep testing in a non-referred sample irrespective of the pretest probability of the disease. PMID:26968467

  15. Kappa and Hirschberg ratio measured with an automated video gaze tracker.

    PubMed

    Schaeffel, Frank

    2002-05-01

    To develop a fast automated procedure to measure kappa and the Hirschberg ratio for immediate use in a video gaze tracker. Using the hardware platform of the PowerRefractor and a 200 mm lens, the pupil was imaged with a resolution of 57 pixels/mm, at a camera distance of 90 cm. Both the positions of the first Purkinje image and the edges of the pupil were located at 25 Hz sampling rate with subpixel resolution using video image processing software developed under Borland C++. Subjects fixated on a red spot on the left side of the monitor. If their fixation was stable (standard deviation <0.2 degrees in 25 subsequent measurements evaluated in 1 s), the fixation spot appeared automatically on the right side, and the procedure was repeated. Data on the angular position of the optical axis for both targets were stored and provided kappa and the Hirschberg ratio with a standard deviation of about 0.2 degrees or better. This enabled the system to track fixation with a resolution of about 0.2 degrees. (1) Kappa was +3.91+/-2.73 degrees (right eyes), -3.93+/-2.68 degrees (left eyes, mean +/- SD from 24 young adults). Kappa was highly correlated in both eyes (r = 0.8996), but there were significant asymmetries between both eyes in three subjects (delta up to 3 degrees). (2) The Hirschberg ratios were 12.93+/-1.23 degrees/mm = 22.56 delta/mm (right eyes) and 12.82+/-1.49 degrees/mm = 22.38 delta/mm (left eyes). They were also highly correlated in both eyes (r = 0.931). (3) Neither kappa nor the Hirschberg ratios were correlated to refractive errors (range +0.50 to -7.75 D, mean -1.73+/-2.29 D [spherical equivalents]). (1) The video gaze tracker measured fixation with an angular resolution high enough to display the eye position during reading of individual words on the computer screen. (2) The applicable Hirschberg ratio changed with the power of the spectacles of the subjects by about 3% per diopter. (3) In some subjects, there were significant differences in the geometry

  16. Diagnosing Nodular Regenerative Hyperplasia of the Liver Is Thwarted by Low Interobserver Agreement.

    PubMed

    Jharap, Bindia; van Asseldonk, Dirk P; de Boer, Nanne K H; Bedossa, Pierre; Diebold, Joachim; Jonker, A Mieke; Leteurtre, Emmanuelle; Verheij, Joanne; Wendum, Dominique; Wrba, Fritz; Zondervan, Pieter E; Colombel, Jean-Frédéric; Reinisch, Walter; Mulder, Chris J J; Bloemena, Elisabeth; van Bodegraven, Adriaan A

    2015-01-01

    Nodular regenerative hyperplasia (NRH) of the liver is associated with several diseases and drugs. Clinical symptoms of NRH may vary from absence of symptoms to full-blown (non-cirrhotic) portal hypertension. However, diagnosing NRH is challenging. The objective of this study was to determine inter- and intraobserver agreement on the histopathologic diagnosis of NRH. Liver specimens (n=48) previously diagnosed as NRH, were reviewed for the presence of NRH by seven pathologists without prior knowledge of the original diagnosis or clinical background. The majority of the liver specimens were from thiopurine using inflammatory bowel disease patients. Histopathologic features contributing to NRH were also assessed. Criteria for NRH were modified by consensus and subsequently validated. Interobserver agreement was evaluated by using the standard kappa index. After review, definite NRH, inconclusive NRH and no NRH were found in 35% (23-40%), 21% (13-27%) and 44% (38-56%), respectively (median, IQR). The median interobserver agreement for NRH was poor (κ = 0.20, IQR 0.14-0.28). The intraobserver variability on NRH ranged between 14% and 71%. After modification of the criteria and exclusion of biopsies with technical shortcomings, the interobserver agreement on the diagnosis NRH was fair (κ = 0.45). The interobserver agreement on the histopathologic diagnosis of NRH was poor, even when assessed by well-experienced liver pathologists. Modification of the criteria of NRH based on consensus effort and exclusion of biopsies of poor quality led to a fairly increased interobserver agreement. The main conclusion of this study is that NRH is a clinicopathologic diagnosis that cannot reliably be based on histopathology alone.

  17. Dental Hygiene Faculty Calibration Using Two Accepted Standards for Calculus Detection: A Pilot Study.

    PubMed

    Santiago, Lisa J; Freudenthal, Jacqueline J; Peterson, Teri; Bowen, Denise M

    2016-08-01

    Faculty calibration studies for calculus detection use two different standards for examiner evaluation, yet the only therapeutic modality that can be used for nonsurgical periodontal treatment is scaling/root debridement or planing. In this study, a pretest-posttest design was used to assess the feasibility of faculty calibration for calculus detection using two accepted standards: that established by the Central Regional Dental Testing Service, Inc. (CRDTS; readily detectible calculus) and the gold standard for scaling/root debridement (root roughness). Four clinical dental hygiene faculty members out of five possible participants at Halifax Community College agreed to participate. The participants explored calculus on the 16 assigned teeth (64 surfaces) of four patients. Calculus detection scores were calculated before and after training. Kappa averages using CRDTS criteria were 0.561 at pretest and 0.631 at posttest. Kappa scores using the scaling/root debridement or planing standard were 0.152 at pretest and 0.271 at posttest. The scores indicated improvement from moderate (Kappa=0.41-0.60) to substantial agreement (Kappa=0.61-0.80) following training using the CRDTS standard. Although this result differed qualitatively and Kappas were significantly different from 0, the differences for pre- to post-Kappas for patient-rater dyads using CRDTS were not statistically significant (p=0.778). There was no difference (p=0.913) in Kappa scores pre- to post-training using the scaling/root debridement standard. Despite the small number of participants in this study, the results indicated that training to improve interrater reliability to substantial agreement was feasible using the CRDTS standard but not using the gold standard. The difference may have been due to greater difficulty in attaining agreement regarding root roughness. Future studies should include multiple training sessions with patients using the same standard for scaling/root debridement used for

  18. Lymphotoxin activation by human T-cell leukemia virus type I-infected cell lines: role for NF-kappa B.

    PubMed Central

    Paul, N L; Lenardo, M J; Novak, K D; Sarr, T; Tang, W L; Ruddle, N H

    1990-01-01

    Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of biologically active lymphotoxin (LT; tumor necrosis factor-beta) protein and LT mRNA. To understand the regulation of LT transcription by HTLV-I, we analyzed the ability of a series of deletions of the LT promoter to drive the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I-positive MT-2 cells. The smallest LT promoter fragment (-140 to +77) that was able to drive CAT activity contained a site that was similar to the immunoglobulin kappa-chain NF-kappa B-binding site. Since the HTLV-I tax gene activates the nuclear form of NF-kappa B, this finding suggested a possible means of HTLV-I activation of LT production. We found that the LT kappa B-like site specifically formed a complex with NF-kappa B-containing nuclear extract from MT-2, C81-66-45, and other activated T cells. Mutation of the LT kappa B site in the context of the LT promoter (-293 to +77) (mutant M1) reduced the ability of the promoter to drive the CAT gene in HTLV-I-infected and noninfected human T-cell lines. These data suggest a general role for NF-kappa B activation in the induction of LT gene transcription. Activation of LT in HTLV-I-infected cells may explain the pathology associated with HTLV-I infection, including the hypercalcemia that is prevalent in adult T-cell leukemia. Images PMID:1976820

  19. Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor {kappa}B p65 activation

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

    Xue, Xia; Center for New Drugs Evaluation, Shandong University, Jinan 250012; Qu, Xian-Jun

    Research highlights: {yields} Permanent NF-{kappa}B p65 activation contributes to the infarction after ischemia-reperfusion injury in rats. {yields} Baicalin can markedly inhibit the nuclear NF-{kappa}B p65 expression and m RNA levels after ischemia-reperfusion injury in rats. {yields} Baicalin decreased the cerebral infarction area via inhibiting the activation of nuclear NF-{kappa}B p65. -- Abstract: Baicalin is a flavonoid compound purified from plant Scutellaria baicalensis Georgi. We aimed to evaluate the neuroprotective effects of baicalin against cerebral ischemic reperfusion injury. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. Baicalin at dosesmore » of 50, 100 and 200 mg/kg was intravenously injected after ischemia onset. Twenty-four hours after reperfusion, the neurological deficit was scored and infarct volume was measured. Hematoxylin and eosin (HE) staining was performed to analyze the histopathological changes of cortex and hippocampus neurons. We examined the levels of NF-{kappa}B p65 in ischemic cortexes by Western blot analysis and RT-PCR assay. The results showed that the neurological deficit scores were significantly decreased from 2.0 {+-} 0.7 to 1.2 {+-} 0.4 and the volume of infarction was reduced by 25% after baicalin injection. Histopathological examination showed that the increase of neurons with pycnotic shape and condensed nuclear in cortex and hippocampus were not observed in baicalin treated animals. Further examination showed that NF-{kappa}B p65 in cortex was increased after ischemia reperfusion injury, indicating the molecular mechanism of ischemia reperfusion injury. The level of NF-{kappa}B p65 was decreased by 73% after baicalin treatment. These results suggest that baicalin might be useful as a potential neuroprotective agent in stroke therapy. The neuroprotective effects of baicalin may relate to inhibition of NF-{kappa}B p65.« less

  20. Reliability of medical record abstraction by non-physicians for orthopedic research.

    PubMed

    Mi, Michael Y; Collins, Jamie E; Lerner, Vladislav; Losina, Elena; Katz, Jeffrey N

    2013-06-09

    Medical record review (MRR) is one of the most commonly used research methods in clinical studies because it provides rich clinical detail. However, because MRR involves subjective interpretation of information found in the medical record, it is critically important to understand the reproducibility of data obtained from MRR. Furthermore, because medical record review is both technically demanding and time intensive, it is important to establish whether trained research staff with no clinical training can abstract medical records reliably. We assessed the reliability of abstraction of medical record information in a sample of patients who underwent total knee replacement (TKR) at a referral center. An orthopedic surgeon instructed two research coordinators (RCs) in the abstraction of inpatient medical records and operative notes for patients undergoing primary TKR. The two RCs and the surgeon each independently reviewed 75 patients' records and one RC reviewed the records twice. Agreement was assessed using the proportion of items on which reviewers agreed and the kappa statistic. The kappa for agreement between the surgeon and each RC ranged from 0.59 to 1 for one RC and 0.49 to 1 for the other; the percent agreement ranged from 82% to 100% for one RC and 70% to 100% for the other. The repeated abstractions by the same RC showed high intra-rater agreement, with kappas ranging from 0.66 to 1 and percent agreement ranging from 97% to 100%. Inter-rater agreement between the two RCs was moderate with kappa ranging from 0.49 to 1 and percent agreement ranging from 76% to 100%. The MRR method used in this study showed excellent reliability for abstraction of information that had low technical complexity and moderate to good reliability for information that had greater complexity. Overall, these findings support the use of non-surgeons to abstract surgical data from operative notes.

  1. Incensole acetate, a novel anti-inflammatory compound isolated from Boswellia resin, inhibits nuclear factor-kappa B activation.

    PubMed

    Moussaieff, Arieh; Shohami, Esther; Kashman, Yoel; Fride, Ester; Schmitz, M Lienhard; Renner, Florian; Fiebich, Bernd L; Munoz, Eduardo; Ben-Neriah, Yinon; Mechoulam, Raphael

    2007-12-01

    Boswellia resin is a major anti-inflammatory agent in herbal medical tradition, as well as a common food supplement. Its anti-inflammatory activity has been attributed to boswellic acid and its derivatives. Here, we re-examined the anti-inflammatory effect of the resin, using inhibitor of nuclear factor-kappaB alpha (IkappaB alpha) degradation in tumor necrosis factor (TNF) alpha-stimulated HeLa cells for a bioassay-guided fractionation. We thus isolated two novel nuclear factor-kappaB (NF-kappaB) inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its nonacetylated form, incensole (IN). IA inhibited TAK/TAB-mediated IkappaB kinase (IKK) activation loop phosphorylation, resulting in the inhibition of cytokine and lipopolysaccharide-mediated NF-kappaB activation. It had no effect on IKK activity in vitro, and it did not suppress IkappaB alpha phosphorylation in costimulated T-cells, indicating that the kinase inhibition is neither direct nor does it affect all NF-kappaB activation pathways. The inhibitory effect seems specific; IA did not interfere with TNFalpha-induced activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. IA treatment had a robust anti-inflammatory effect in a mouse inflamed paw model. Cembrenoid diterpenoids, specifically IA and its derivatives, may thus constitute a potential novel group of NF-kappaB inhibitors, originating from an ancient anti-inflammatory herbal remedy.

  2. Intra- and inter-observer agreement in histological assessment of canine soft tissue sarcoma.

    PubMed

    Yap, F W; Rasotto, R; Priestnall, S L; Parsons, K J; Stewart, J

    2017-12-01

    The diagnosis of canine soft tissue sarcoma (STS) is based on histological assessment. Assessment of criteria such as, degree of differentiation, necrosis score and mitotic score, gives rise to a final tumour grade, which is important in the recommendation of treatment and prognosis of patients. Previously diagnosed cases of STS were independently assessed by three board-certified veterinary pathologists. Participating pathologists were blinded to the original results. For the intra-observer study, the cases were assessed by a single pathologist six months apart and slides were randomized between readings. For the inter-observer study, the whole case series was assessed by a single pathologist before being passed onto the next pathologist. Intraclass correlation coefficient (ICC) and Fleiss's Kappa (ƙ) for the intra- (single observer) and inter-observer agreement. Strong agreement was observed for the intra-observer assessment in necrosis score, mitotic score, total score and tumour grading (ICC between 0.78 to 0.91). The intra-observer agreement for differentiation score was rated perfect (ICC 1.00). The agreement between pathologists for the diagnosis and grading of canine STS was moderate (ƙ = 0.60 and 0.43 respectively). Histological assessment of canine STS had high reproducibility by an individual pathologist. The agreement of diagnosis and grading of canine STS was moderate between pathologists. Future studies are required to investigate further assessment criteria to improve the specificity of STS diagnosis and the accuracy of the STS grading in dogs. © 2017 John Wiley & Sons Ltd.

  3. Application of iota and kappa carrageenans to traditional several food using modified cassava flour

    NASA Astrophysics Data System (ADS)

    Al-Baarri, A. N.; Legowo, A. M.; Rizqiati, H.; Widayat; Septianingrum, A.; Sabrina, H. N.; Arganis, L. M.; Saraswati, R. O.; Mochtar, Rr C. P. R.

    2018-01-01

    Carrageenan has been known well as hydrocolloids that forming viscous dispersions and gels when dispersed in water. The carrageenan has not been widely applied to traditional foods. Therefore, the aim of this research was to determine the effect of kappa and iota carrageenans in traditional food models using modified cassava flour, sugar, and coconut milk. The textural properties, i.e. hardness, cohesiveness, springiness and adhesiveness have been measured using texture analyzer. The study indicated that traditional food models added kappa carrageenan at 2% generated remarkably higher in the hardness, cohesiveness, and springiness than those added iota carrageenan. On the other hand, the reserve result were found in the adhesiveness parameter. As conclusion, kappa carrageenan scan be potentially used for producing traditional foods based on the hard-texture-oriented foods whereas iota carrageenan can be used for the traditional foods with better adhesiveness.

  4. Comparing Visual and Statistical Analysis of Multiple Baseline Design Graphs.

    PubMed

    Wolfe, Katie; Dickenson, Tammiee S; Miller, Bridget; McGrath, Kathleen V

    2018-04-01

    A growing number of statistical analyses are being developed for single-case research. One important factor in evaluating these methods is the extent to which each corresponds to visual analysis. Few studies have compared statistical and visual analysis, and information about more recently developed statistics is scarce. Therefore, our purpose was to evaluate the agreement between visual analysis and four statistical analyses: improvement rate difference (IRD); Tau-U; Hedges, Pustejovsky, Shadish (HPS) effect size; and between-case standardized mean difference (BC-SMD). Results indicate that IRD and BC-SMD had the strongest overall agreement with visual analysis. Although Tau-U had strong agreement with visual analysis on raw values, it had poorer agreement when those values were dichotomized to represent the presence or absence of a functional relation. Overall, visual analysis appeared to be more conservative than statistical analysis, but further research is needed to evaluate the nature of these disagreements.

  5. Understanding parent-teacher agreement of the Strengths and Difficulties Questionnaire (SDQ): Comparison across seven European countries.

    PubMed

    Cheng, Sabrina; Keyes, Katherine M; Bitfoi, Adina; Carta, Mauro Giovanni; Koç, Ceren; Goelitz, Dietmar; Otten, Roy; Lesinskiene, Sigita; Mihova, Zlatka; Pez, Ondine; Kovess-Masfety, Viviane

    2018-03-01

    Assessments of child psychopathology are often derived from parental and teacher reports, yet there is substantial disagreement. This study utilized data from 7 European countries to examine parent-teacher agreement and possible explanatory factors for parent-teacher disagreement such as child and family characteristics, parenting dimensions, and maternal distress were explored. Parent-teacher agreement of the Strengths and Difficulties Questionnaire were assessed using a cross-sectional survey of 4,894 school aged children 6-11 from the School Children Mental Health Europe Project. Parent-teacher agreement was low to moderate (Pearson correlation ranging from .24 (Prosocial) to .48 (Hyperactivity) for the 5 subscales across 7 countries); kappa coefficient ranged from .01 (Turkey) to .44 (Italy) for internalizing problems and .19(Romania) to .44(Italy) for externalizing problems. Child's gender and age, mother's employment status, single parent home, number of children in household, and selected parenting dimension were found to be explanatory of informant disagreement. This study not only serves to advance our understanding of parent-teacher agreement of the Strengths and Difficulties Questionnaire in 7 European countries but provides a novel approach to examining the factors that contribute to informant disagreement. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Prevalence of constipation: agreement among several criteria and evaluation of the diagnostic accuracy of qualifying symptoms and self-reported definition in a population-based survey in Spain.

    PubMed

    Garrigues, Vicente; Gálvez, Consuelo; Ortiz, Vicente; Ponce, Marta; Nos, Pilar; Ponce, Julio

    2004-03-01

    The aims of this study were to estimate the prevalence of chronic constipation and to evaluate the diagnostic accuracy of the symptoms and the self-reported definition of constipation. A cross-sectional survey was conducted in the general community in 1999. A questionnaire comprising 21 items was developed and mailed to a random sample of 489 subjects who were aged between 18 and 65 years and who belonged to a Spanish population. In the 349 subjects (71%) responding to the questionnaire, the prevalence of self-reported constipation was 29.5% (95% confidence interval (CI): 24.9, 34.3) versus 19.2% (95% CI: 15.1, 23.3) and 14.0% (95% CI: 10.4, 17.7) based on Rome I and Rome II criteria, respectively. Agreement was good between self-reported and Rome I criteria (kappa: 0.68) and between Rome I and Rome II criteria (kappa: 0.71), and it was moderate between self-reported and Rome II criteria (kappa: 0.55). Female gender was identified to be a risk factor for constipation; fiber intake and physical exercise were found to be protective factors. Likelihood ratios were higher for the presence of anal blockage and straining and for the absence of hard stools. Chronic constipation is a highly prevalent problem, especially in women. Different prevalence estimates of constipation were observed using different criteria, although agreement between them was acceptable. Anal blockage, straining, and hard stools show the greatest accuracy for the diagnosis of constipation.

  7. Manipulation of NF-KappaBetta Activity in the Macrophage Lineage as a Novel Therapeutic Approach

    DTIC Science & Technology

    2007-05-01

    Sadikot, J. W. Christman, and T. S. Blackwell. 2003. Bioluminescent detection of endotoxin effects on HIV-1 LTR-driven transcription in vivo. J...differences in proliferation rates, expression of downstream gene expression and effects mediated by altered macrophages on associated epithelial...kappaB activity within macrophages has significant effects on mammary ductal development. 15. SUBJECT TERMS NF-kappaB, macrophages, mammary ductal

  8. Identifying walking trips from GPS and accelerometer data in adolescent females

    PubMed Central

    Rodriguez, Daniel; Cho, GH; Elder, John; Conway, Terry; Evenson, Kelly R; Ghosh-Dastidar, Bonnie; Shay, Elizabeth; Cohen, Deborah A; Veblen-Mortenson, Sarah; Pickrell, Julie; Lytle, Leslie

    2013-01-01

    Background Studies that have combined accelerometers and global positioning systems (GPS) to identify walking have done so in carefully controlled conditions. This study tested algorithms for identifying walking trips from accelerometer and GPS data in free-living conditions. The study also assessed the accuracy of the locations where walking occurred compared to what participants reported in a diary. Methods A convenience sample of high school females was recruited (N=42) in 2007. Participants wore a GPS unit and an accelerometer, and recorded their out-of-school travel for six days. Split-sample validation was used to examine agreement in the daily and total number of walking trips with Kappa statistics and count regression models, while agreement in locations visited by walking was examined with geographic information systems. Results Agreement varied based on the parameters of the algorithm, with algorithms exhibiting moderate to substantial agreement with self-reported daily (Kappa = 0.33–0.48) and weekly (Kappa = 0.41–0.64) walking trips. Comparison of reported locations reached by walking and GPS data suggest that reported locations are accurate. Conclusions The use of GPS and accelerometers is promising for assessing the number of walking trips and the walking locations of adolescent females. PMID:21934163

  9. Agreement of label information of cardiovascular drugs in pregnancy among Korea, the USA, the UK, and Japan.

    PubMed

    Lee, Shin Haeng; Shin, Ju-Young; Park, Mi-Ju; Park, Byung-Joo

    2014-04-01

    Drug label is a common source of information; however, the content varies widely. This study aims to evaluate label information on cardiovascular drugs regarding pregnancy for their similarities in Korea, USA, UK, and Japan. Study drugs were selected as following (1) cardiovascular drugs according to the WHO ATC code (C01-C09) and (2) drugs currently marketed in all four countries were included. Evidence level was classified into five categories ('Definite', 'Probable', 'Possible', 'Unlikely', and 'Unclassified') and recommendation level was classified into four categories ('Contraindicated', 'Cautious', 'Compatible', and 'Unclassified'). Frequency and proportion were presented. Percent agreement and kappa coefficient with 95% confidence interval (CI) were calculated using SAS ver. 9.3. Total of 50 cardiovascular drugs were included. 'Unclassified' was represented the most in Korea, followed by Japan and UK (58%, 54%, and 46%, p<0.05). For recommendation level, the majority of drugs in all four countries were classified as 'contraindicated' or 'cautious'. Japanese labels had the largest proportion of 'contraindicated' level (62%), and Korea and UK followed (58%, 44%, p<0.05). Only in the USA, 10.0% of the drugs were 'compatible' whereas, there were none in Korea, UK, and Japan (p<0.01). Korea and Japan showed a substantial agreement in evidence and recommendation level (kappa=0.69, 0.67). Labels of cardiovascular drugs in pregnancy differed widely. Reliable safety information in pregnancy should be provided through regular updates. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Patient-family agreement on values and preferences for life-sustaining treatment: results of a multicentre observational study.

    PubMed

    Abdul-Razzak, Amane; Heyland, Daren K; Simon, Jessica; Ghosh, Sunita; Day, Andrew G; You, John J

    2017-07-22

    To quantify agreement between patients and their family members on their own values and preferences for use or non-use of life-sustaining treatments for the patient. Hospitalised patients aged 55 years or older with advanced pulmonary, cardiac, liver disease or metastatic cancer or aged 80 years or older from medical wards at 16 Canadian hospitals and their family members completed a questionnaire including eight items about values related to life-sustaining treatment and a question about preferences for life-sustaining treatments. We recruited a total of 313 patient-family member dyads. Crude agreement between patients and family members about values related to life-sustaining treatment was 42% across all eight items but varied widely: 20% when asking how important it was for the patient to respect the wishes of family members regarding their care; 72% when asking how important it was for the patient to be kept comfortable and suffer as little as possible. Crude agreement on preferences for life-sustaining treatment was 91% (kappa 0.60; 95%CI 0.45 to 0.75) when looking at preferences for cardiopulmonary resuscitation (CPR) versus no CPR but fell to 56% when including all five response options with varying degrees of resuscitative, medical or comfort options (kappa 0.39; 95%CI 0.31 to 0.47). There is appreciable disagreement between seriously ill hospitalised patients and family members in their values and preferences for life-sustaining treatment. Strategies are needed to improve the quality of advance care planning, so that surrogates are better able to honour patient's wishes at the end of life. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Comparison between the International Physical Activity Questionnaire and the American College of Sports Medicine/American Heart Association criteria to classify the physical activity profile in adults.

    PubMed

    de Moraes, Suzana Alves; Suzuki, Cláudio Shigueki; de Freitas, Isabel Cristina Martins

    2013-01-01

    the study aims to evaluate the reproducibility between the International Physical Activity Questionnaire and the American College of Sports Medicine/American Heart Association criteria to classify the physical activity profile in an adult population living in Ribeirão Preto, SP, Brazil. population-based cross-sectional study, including 930 adults of both genders. The reliability was evaluated by Kappa statistics, estimated according to socio-demographic strata. the kappa estimates showed good agreement between the two criteria in all strata. However, higher prevalence of "actives" was found by using the American College of Sports Medicine/American Heart Association. although the estimates have indicated good agreement, the findings suggest caution in choosing the criteria to classify physical activity profile mainly when "walking" is the main modality of physical activity.

  12. Evidence for activation of nuclear factor kappaB in obstructive sleep apnea.

    PubMed

    Yamauchi, Motoo; Tamaki, Shinji; Tomoda, Koichi; Yoshikawa, Masanori; Fukuoka, Atsuhiko; Makinodan, Kiyoshi; Koyama, Noriko; Suzuki, Takahiro; Kimura, Hiroshi

    2006-12-01

    Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis, and atherosclerosis evolves from activation of the inflammatory cascade. We propose that activation of the nuclear factor kappaB (NF-kappaB), a key transcription factor in the inflammatory cascade, occurs in OSA. Nine age-matched, nonsmoking, and non-hypertensive men with OSA symptoms and seven similar healthy subjects were recruited for standard polysomnography followed by the collection of blood samples for monocyte nuclear p65 concentrations (OSA and healthy groups). In the OSA group, p65 and of monocyte production of tumor necrosis factor alpha (TNF-alpha) were measured at the same time and after the next night of continuous positive airway pressure (CPAP). p65 Concentrations in the OSA group were significantly higher than in the control group [median, 0.037 ng/microl (interquartile range, 0.034 to 0.051) vs 0.019 ng/microl (interquartile range, 0.013 to 0.032); p = 0.008], and in the OSA group were significantly correlated with apnea-hypopnea index and time spent below an oxygen saturation of 90% (r = 0.77 and 0.88, respectively) after adjustment for age and BMI. One night of CPAP resulted in a reduction in p65 [to 0.020 ng/mul (interquartile range, 0.010 to 0.036), p = 0.04] and levels of TNF-alpha production in cultured monocytes [16.26 (interquartile range, 7.75 to 24.85) to 7.59 ng/ml (interquartile range, 5.19 to 12.95), p = 0.01]. NF-kappaB activation occurs with sleep-disordered breathing. Such activation of NF-kappaB may contribute to the pathogenesis of atherosclerosis in OSA patients.

  13. Agreement among health care professionals in diagnosing case Vignette-based surgical site infections.

    PubMed

    Lepelletier, Didier; Ravaud, Philippe; Baron, Gabriel; Lucet, Jean-Christophe

    2012-01-01

    To assess agreement in diagnosing surgical site infection (SSI) among healthcare professionals involved in SSI surveillance. Case-vignette study done in 2009 in 140 healthcare professionals from seven specialties (20 in each specialty, Anesthesiologists, Surgeons, Public health specialists, Infection control physicians, Infection control nurses, Infectious diseases specialists, Microbiologists) in 29 University and 36 non-University hospitals in France. We developed 40 case-vignettes based on cardiac and gastrointestinal surgery patients with suspected SSI. Each participant scored six randomly assigned case-vignettes before and after reading the SSI definition on an online secure relational database. The intraclass correlation coefficient (ICC) was used to assess agreement regarding SSI diagnosis on a seven-point Likert scale and the kappa coefficient to assess agreement for superficial or deep SSI on a three-point scale. Based on a consensus, SSI was present in 21 of 40 vignettes (52.5%). Intraspecialty agreement for SSI diagnosis ranged across specialties from 0.15 (95% confidence interval, 0.00-0.59) (anesthesiologists and infection control nurses) to 0.73 (0.32-0.90) (infectious diseases specialists). Reading the SSI definition improved agreement in the specialties with poor initial agreement. Intraspecialty agreement for superficial or deep SSI ranged from 0.10 (-0.19-0.38) to 0.54 (0.25-0.83) (surgeons) and increased after reading the SSI definition only among the infection control nurses from 0.10 (-0.19-0.38) to 0.41 (-0.09-0.72). Interspecialty agreement for SSI diagnosis was 0.36 (0.22-0.54) and increased to 0.47 (0.31-0.64) after reading the SSI definition. Among healthcare professionals evaluating case-vignettes for possible surgical site infection, there was large disagreement in diagnosis that varied both between and within specialties.

  14. Transcriptional regulation of NADPH oxidase isoforms, Nox1 and Nox4, by nuclear factor-{kappa}B in human aortic smooth muscle cells

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

    Manea, Adrian, E-mail: adrian.manea@icbp.ro; Tanase, Laurentia I.; Raicu, Monica

    Inflammation-induced changes in the activity and expression of NADPH oxidases (Nox) play a key role in atherogenesis. The molecular mechanisms of Nox regulation are scantily elucidated. Since nuclear factor-{kappa}B (NF-{kappa}B) controls the expression of many genes associated to inflammation-related diseases, in this study we have investigated the role of NF-{kappa}B signaling in the regulation of Nox1 and Nox4 transcription in human aortic smooth muscle cells (SMCs). Cultured cells were exposed to tumor necrosis factor-{alpha} (TNF{alpha}), a potent inducer of both Nox and NF-{kappa}B, up to 24 h. Lucigenin-enhanced chemiluminescence and dichlorofluorescein assays, real-time polymerase chain reaction, and Western blot analysismore » showed that inhibition of NF-{kappa}B pathway reduced significantly the TNF{alpha}-dependent up-regulation of Nox-derived reactive oxygen species production, Nox1 and Nox4 expression. In silico analysis indicated the existence of typical NF-{kappa}B elements in the promoters of Nox1 and Nox4. Transient overexpression of p65/NF-{kappa}B significantly increased the promoter activities of both isoforms. Physical interaction of p65/NF-{kappa}B proteins with the predicted sites was demonstrated by chromatin immunoprecipitation assay. These findings demonstrate that NF-{kappa}B is an essential regulator of Nox1- and Nox4-containing NADPH oxidase in SMCs. Elucidation of the complex relationships between NF-{kappa}B and Nox enzymes may lead to a novel pharmacological strategy to reduce both inflammation and oxidative stress in atherosclerosis and its associated complications.« less

  15. Coordination of NF-kappaB and NFAT antagonism by the forkhead transcription factor Foxd1.

    PubMed

    Lin, Ling; Peng, Stanford L

    2006-04-15

    Forkhead transcription factors play critical roles in the maintenance of immune homeostasis. In this study, we demonstrate that this regulation most likely involves intricate interactions between the forkhead family members and inflammatory transcription factors: the forkhead member Foxd1 coordinates the regulation of the activity of two key inflammatory transcription factors, NF-AT and NF-kappaB, with Foxd1 deficiency resulting in multiorgan, systemic inflammation, exaggerated Th cell-derived cytokine production, and T cell proliferation in autologous MLRs. Foxd1-deficient T cells possess increased activity of both NF-AT and NF-kappaB: the former correlates with the ability of Foxd1 to regulate casein kinase 1, an NF-AT inhibitory kinase; the latter with the ability of Foxd1 to regulate Foxj1, which regulates the NF-kappaB inhibitory subunit IkappaB beta. Thus, Foxd1 modulates inflammatory reactions and prevents autoimmunity by directly regulating anti-inflammatory regulators of the NF-AT pathway, and by coordinating the suppression of the NF-kappaB pathway via Foxj1. These findings indicate the presence of a general network of forkhead proteins that enforce T cell quiescence.

  16. The lymphotoxin promoter is stimulated by HTLV-I tax activation of NF-kappa B in human T-cell lines.

    PubMed

    Paul, N L; Millet, I; Ruddle, N H

    1993-07-01

    The HTLV-I transcriptional activator tax was used to gain insight into the mechanism of lymphotoxin (LT; TNF-beta) gene induction. Tax-expressing cell lines produce LT biologic activity. An LT promoter (LT-293) CAT construct that contained an NF-kappa B site was active in the LT-producing C81-66-45 cell line, which contains defective HTLV-I but expresses tax. The observation that a mutated LT-kappa B construct (M1-CAT) was inactive in C81-66-45, confirmed the importance of NF-kappa B in LT gene expression. Tax was transfected into HTLV-I-negative human T-cell lines. Jurkat T cells stably expressing tax contained elevated levels of NF-kappa B that directly bound to the LT-kappa B site. Tax co-transfected with reporter constructs into Jurkat cells maximally activated HTLV-I-LTR-CAT and kappa B-fos-CAT and also activated LT-293 to a lesser extent. In JM T cells, tax induced LT-293 activity by two- to four-fold, though there was no induction of M1-CAT. The increase in LT-293 CAT activity mirrored the increase in LT biologic activity seen under these conditions. These studies, the first to demonstrate induction of LT promoter activity over basal levels, indicate that HTLV-I tax causes low-level activation of both endogenous LT and the LT promoter, at least in part through activation of NF-kappa B.

  17. Alpha Kappa Alpha Sorority's Reading Improvement Program for Minorities.

    ERIC Educational Resources Information Center

    Marable, June Morehead

    This document discusses the founding and establishment of Alpha Kappa Alpha Sorority's reading experience pilot project. The efforts of this project were aligned with those of Right to Read and Reading Is Fundamental (RIF). Because of the response from parents and children, plans are being made to increase present operations within the next…

  18. Site-directed mutagenesis study on DNA binding regions of the mouse homologue of Suppressor of Hairless, RBP-J kappa.

    PubMed Central

    Chung, C N; Hamaguchi, Y; Honjo, T; Kawaichi, M

    1994-01-01

    To map regions important for DNA binding of the mouse homologue of Suppressor of Hairless or RBP-J kappa protein, mutated mouse RBP-J kappa cDNAs were made by insertion of oligonucleotide linkers or base replacement. DNA binding assays using the mutated proteins expressed in COS cells showed that various mutations between 218 Arg and 227 Arg decreased the DNA binding activity drastically. The DNA binding activity was not affected by amino acid replacements within the integrase motif of the RBP-J kappa protein (230His-269His). Replacements between 291Arg and 323Tyr affected the DNA binding activity slightly but reproducibly. These results indicate that the region encompassing 218Arg-227Arg is critical for the DNA binding activity of RBP-J kappa. This region did not show any significant homology to motifs or domains of the previously described DNA binding proteins. Using a truncation mutant protein RBP-J kappa was shown to associate with DNA as a monomer. Images PMID:8065905

  19. The validity and reliability of a simple semantic classification of foot posture.

    PubMed

    Cross, Hugh A; Lehman, Linda

    2008-12-01

    The Simple Semantic Classification (SSC) is described as a pragmatic method to assist in the assessment of the weight bearing foot. It was designed for application by therapists and technicians working in underdeveloped situations, after they have had basic orientation in foot function. To present evidence of the validity and inter observer reliability of the SSC. 13 physiotherapists from LEPRA India projects and 12 physical therapists functioning within the National Programme for the Elimination of Hansen's Disease (PNEH), Brazil, participated in an inter-observer exercise. Inter-observer agreement was gauged using the Kappa statistic. The results of the inter-observer exercise were dependent on observations of foot posture made from photographs. This was necessary to ensure that the procedure was standardised for participants in different countries. The method had limitations which were partly reflected in the results. The level of agreement between the principle investigator and Indian physiotherapists was Kappa = 058. The level of agreement between Brazilian physical therapists and the principle investigator was Kappa = 0.70. The authors opine that the results were sufficiently compelling to suggest that the Simple Semantic Classification can be used as a field method to identify people at increased risk of foot pathologies.

  20. An articulated rotating brush for office endometrial evaluation of climacteric outpatients.

    PubMed

    Bocanera, A R; Roncoroni, E C; Schlaen, I; Ben, J; Monteverde, R; González García, M; Puche, R C; Tozzini, R

    1994-05-01

    This paper reports the experience obtained in the last 8 years with an instrument (articulated rotative brush) that allows access to the entire endometrial surface, obtaining material for both histological and cytological study. The latter has the advantage of reducing the number of cases in which insufficient material frustrates endometrial assessment. In addition to the overall experience gained with this instrument, the proportion of agreement with anatomo-pathological diagnosis after hysterectomy in 61 patients was high (96%) and the unweighted kappa statistic (0.862) indicated very good accordance between these techniques. Comparison between the present method and hysteroscopic observations in 84 patients with perimenopausal bleeding revealed a general conformity of 0.65 and an unweighted kappa statistic of 0.368 (fair agreement). In a group of 72 cases with postmenopausal bleeding a general conformity value of 0.92 was obtained, with an unweighted kappa statistic of 0.84 (very good agreement). In 90% of the cases the procedure was well accepted. In 57.3% of the cases, no difficulties were encountered using the brushing technique; in 25.9% slight dilatation was deemed necessary, whereas in 16.8% technical difficulties could not be overcome and general anesthesia was indicated. A total of 769 outpatients were investigated, 75.3% of which had normal endometria, 12.7% benign hyperplasias, 2.6% precursor lesions, 1.7% suspect carcinoma, and 4.2% carcinomas. Insufficient material for diagnosis occurred in 3.5% of cases tested. The combined cytohistological and hysteroscopic assessment of the endometrium provides satisfactory results in the etiological diagnosis of peri and postmenopausal bleeding, and in the follow up of patients undergoing hormonal replacement therapy (HRT).

  1. Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trials.

    PubMed

    Press, Michael F; Sauter, Guido; Bernstein, Leslie; Villalobos, Ivonne E; Mirlacher, Martina; Zhou, Jian-Yuan; Wardeh, Rooba; Li, Yong-Tian; Guzman, Roberta; Ma, Yanling; Sullivan-Halley, Jane; Santiago, Angela; Park, Jinha M; Riva, Alessandro; Slamon, Dennis J

    2005-09-15

    To critically assess the accuracy and reproducibility of human epidermal growth factor receptor type 2 (HER-2) testing in outside/local community-based hospitals versus two centralized reference laboratories and its effect on selection of women for trastuzumab (Herceptin)-based clinical trials. Breast cancer specimens from 2,600 women were prospectively evaluated by fluorescence in situ hybridization (FISH) for entry into Breast Cancer International Research Group (BCIRG) clinical trials for HER-2-directed therapies. HER-2 gene amplification by FISH was observed in 657 of the 2,502 (26%) breast cancers successfully analyzed. Among 2,243 breast cancers with central laboratory immunohistochemistry (10H8-IHC) analysis, 504 (22.54%) showed overexpression (2+ or 3+). Outside/local laboratories assessed HER-2 status by immunohistochemistry in 1,536 of these cases and by FISH in 131 cases. Overall, the HER-2 alteration status determined by outside/local immunohistochemistry showed a 79% agreement rate [kappa statistic, 0.56; 95% confidence interval (95% CI), 0.52-0.60], with FISH done by the central laboratories. The agreement rate comparing BCIRG central laboratory 10H8-IHC and outside/local laboratory immunohistochemistry was 77.5% (kappa statistic, 0.51; 95% CI, 0.46-0.55). Finally, HER-2 status, determined by unspecified FISH assay methods at outside/local laboratories, showed a 92% agreement rate (kappa statistic, 0.83; 95% CI, 0.73-0.93), with FISH done at the BCIRG central laboratories. Compared with the HER-2 status determined at centralized BCIRG reference laboratories, these results indicate superiority of FISH to accurately and reproducibly assess tumors for the HER-2 alteration at outside/local laboratories for entry to clinical trials.

  2. Mechanisms of Kappa Opioid Receptor Potentiation of Dopamine D2 Receptor Function in Quinpirole-Induced Locomotor Sensitization in Rats.

    PubMed

    Escobar, Angélica P; González, Marcela P; Meza, Rodrigo C; Noches, Verónica; Henny, Pablo; Gysling, Katia; España, Rodrigo A; Fuentealba, José A; Andrés, María E

    2017-08-01

    Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of quinpirole, a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist. The mechanism underlying kappa opioid receptor potentiation of quinpirole-induced locomotor sensitization remains to be elucidated. Immunofluorescence anatomical studies were undertaken in mice brain slices and rat presynaptic synaptosomes to reveal kappa opioid receptor and D2R pre- and postsynaptic colocalization in the nucleus accumbens. Tonic and phasic dopamine release in the nucleus accumbens of rats repeatedly treated with U69593 and quinpirole was assessed by microdialysis and fast scan cyclic voltammetry. Anatomical data show that kappa opioid receptor and D2R colocalize postsynaptically in medium spiny neurons of the nucleus accumbens and the highest presynaptic colocalization occurs on the same dopamine terminals. Significantly reduced dopamine levels were observed in quinpirole, and U69593-quinpirole treated rats, explaining sensitization of D2R. Presynaptic inhibition induced by kappa opioid receptor and D2R of electrically evoked dopamine release was faster in U69593-quinpirole compared with quinpirole-repeatedly treated rats. Pre- and postsynaptic colocalization of kappa opioid receptor and D2R supports a role for kappa opioid receptor potentiating both the D2R inhibitory autoreceptor function and the inhibitory action of D2R on efferent medium spiny neurons. Kappa opioid receptor co-activation accelerates D2R sensitization by contributing to decrease dopamine release in the nucleus accumbens. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  3. Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis.

    PubMed

    Oakley, Fiona; Meso, Muriel; Iredale, John P; Green, Karen; Marek, Carylyn J; Zhou, Xiaoying; May, Michael J; Millward-Sadler, Harry; Wright, Matthew C; Mann, Derek A

    2005-01-01

    Resolution of liver fibrosis is associated with clearance of hepatic myofibroblasts by apoptosis; development of strategies that promote this process in a selective way is therefore important. The aim of this study was to determine whether the inhibitor of kappaB kinase suppressor sulfasalazine stimulates hepatic myofibroblast apoptosis and recovery from fibrosis. Hepatic myofibroblasts were generated by culture activation of rat and human hepatic stellate cells. Fibrosis was established in rat livers by chronic injury with carbon tetrachloride followed by recovery with or without sulfasalazine (150 mg/kg) treatment. Treatment of hepatic stellate cells with sulfasalazine (0.5-2.0 mmol/L) induced apoptosis of activated rat and human hepatic stellate cells. A single in vivo administration of sulfasalazine promoted accelerated recovery from fibrosis as assessed by improved fibrosis score, selective clearance of smooth muscle alpha-actin-positive myofibroblasts, reduced hepatic procollagen I and tissue inhibitor of metalloproteinase 1 messenger RNA expression, and increased matrix metalloproteinase 2 activity. Mechanistic studies showed that sulfasalazine selectively blocks nuclear factor-kappaB-dependent gene transcription, inhibits hepatic stellate cell expression of Gadd45beta, stimulates phosphorylation of Jun N-terminal kinase 2, and promotes apoptosis by a mechanism that is prevented by the Jun N-terminal kinase inhibitor SP600125. As further evidence for a survival role for the inhibitor of kappaB kinase/nuclear factor-kappaB pathway in activated hepatic stellate cells, a highly selective cell-permeable peptide inhibitor of kappaB kinase activation also stimulated hepatic stellate cell apoptosis via a Jun N-terminal kinase-dependent mechanism. Inhibition of the inhibitor of kappaB kinase/nuclear factor-kappaB pathway is sufficient to increase the rate at which activated hepatic stellate cells undergo apoptosis both in vitro and in vivo, and drugs that

  4. Highly condensed fluorinated methacrylate hybrid material for transparent low-kappa passivation layer in LCD-TFT.

    PubMed

    Oh, Ji-Hoon; Kwak, Seung-Yeon; Yang, Seung-Cheol; Bae, Byeong-Soo

    2010-03-01

    Photocurable and highly condensed fluorinated methacrylate oligosiloxane, with a low dielectric constant (kappa = 2.54), was prepared by a nonhydrolytic sol-gel condensation reaction. The oligosiloxane resin was then spin-coated, photocured, and thermally baked in order to fabricate a fluorinated methacrylate hybrid material (FM hybrimer) thin film. This study investigated the application of this FM hybrimer film as a low-kappa passivation layer in LCD-based thin film transistors (TFT). It was found that a dielectric constant as low as kappa = 2.54 could be obtained, without introducing pores in the dense FM hybrimer films. This study compares FM hybrimer film characteristics with those required for passivation layers in LCD-TFTs, including thermal stability, optical transmittance, hydrophobicity, gap fill, and planarization effects as well as electrical insulation.

  5. Liquid-liquid extraction of ethanol from aqueous solutions with amyl acetate, benzyl alcohol, and methyl isobutyl ketone at 298. 15. Kappa

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

    Solimo, H.N.; Martinez, H.E.; Riggio, R.

    1989-04-01

    Experimental mutual solubility and tie-line data were determined for three ternary liquid-liquid systems containing water, ethanol, and amyl acetate, benzyl alcohol, and methyl isobutyl ketone at 298.15{Kappa} in order to obtain their complete phase diagrams and to determine which is the most suitable solvent for extraction of ethanol from aqueous solutions. Tie lines were determined correlating the density of the binodal curve as a function of composition and the plait points using the Othmer and Tobias method. The experimental data were also correlated with the UNIFAC group contribution method. A qualitative agreement was obtained. Experimental results show that amyl acetatemore » is a better solvent than methyl isobutyl ketone and benzyl alcohol.« less

  6. Correlation and agreement: overview and clarification of competing concepts and measures.

    PubMed

    Liu, Jinyuan; Tang, Wan; Chen, Guanqin; Lu, Yin; Feng, Changyong; Tu, Xin M

    2016-04-25

    Agreement and correlation are widely-used concepts that assess the association between variables. Although similar and related, they represent completely different notions of association. Assessing agreement between variables assumes that the variables measure the same construct, while correlation of variables can be assessed for variables that measure completely different constructs. This conceptual difference requires the use of different statistical methods, and when assessing agreement or correlation, the statistical method may vary depending on the distribution of the data and the interest of the investigator. For example, the Pearson correlation, a popular measure of correlation between continuous variables, is only informative when applied to variables that have linear relationships; it may be non-informative or even misleading when applied to variables that are not linearly related. Likewise, the intraclass correlation, a popular measure of agreement between continuous variables, may not provide sufficient information for investigators if the nature of poor agreement is of interest. This report reviews the concepts of agreement and correlation and discusses differences in the application of several commonly used measures.

  7. Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

    PubMed

    Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

    2008-09-14

    PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.

  8. Agreement among healthcare professionals in ten European countries in diagnosing case-vignettes of surgical-site infections.

    PubMed

    Birgand, Gabriel; Lepelletier, Didier; Baron, Gabriel; Barrett, Steve; Breier, Ann-Christin; Buke, Cagri; Markovic-Denic, Ljiljana; Gastmeier, Petra; Kluytmans, Jan; Lyytikainen, Outi; Sheridan, Elizabeth; Szilagyi, Emese; Tacconelli, Evelina; Troillet, Nicolas; Ravaud, Philippe; Lucet, Jean-Christophe

    2013-01-01

    Although surgical-site infection (SSI) rates are advocated as a major evaluation criterion, the reproducibility of SSI diagnosis is unknown. We assessed agreement in diagnosing SSI among specialists involved in SSI surveillance in Europe. Twelve case-vignettes based on suspected SSI were submitted to 100 infection-control physicians (ICPs) and 86 surgeons in 10 European countries. Each participant scored eight randomly-assigned case-vignettes on a secure online relational database. The intra-class correlation coefficient (ICC) was used to assess agreement for SSI diagnosis on a 7-point Likert scale and the kappa coefficient to assess agreement for SSI depth on a three-point scale. Intra-specialty agreement for SSI diagnosis ranged across countries and specialties from 0.00 (95%CI, 0.00-0.35) to 0.65 (0.45-0.82). Inter-specialty agreement varied from 0.04 (0.00-0.62) in to 0.55 (0.37-0.74) in Germany. For all countries pooled, intra-specialty agreement was poor for surgeons (0.24, 0.14-0.42) and good for ICPs (0.41, 0.28-0.61). Reading SSI definitions improved agreement among ICPs (0.57) but not surgeons (0.09). Intra-specialty agreement for SSI depth ranged across countries and specialties from 0.05 (0.00-0.10) to 0.50 (0.45-0.55) and was not improved by reading SSI definition. Among ICPs and surgeons evaluating case-vignettes of suspected SSI, considerable disagreement occurred regarding the diagnosis, with variations across specialties and countries.

  9. Agreement among Healthcare Professionals in Ten European Countries in Diagnosing Case-Vignettes of Surgical-Site Infections

    PubMed Central

    Birgand, Gabriel; Lepelletier, Didier; Baron, Gabriel; Barrett, Steve; Breier, Ann-Christin; Buke, Cagri; Markovic-Denic, Ljiljana; Gastmeier, Petra; Kluytmans, Jan; Lyytikainen, Outi; Sheridan, Elizabeth; Szilagyi, Emese; Tacconelli, Evelina; Troillet, Nicolas; Ravaud, Philippe; Lucet, Jean-Christophe

    2013-01-01

    Objective Although surgical-site infection (SSI) rates are advocated as a major evaluation criterion, the reproducibility of SSI diagnosis is unknown. We assessed agreement in diagnosing SSI among specialists involved in SSI surveillance in Europe. Methods Twelve case-vignettes based on suspected SSI were submitted to 100 infection-control physicians (ICPs) and 86 surgeons in 10 European countries. Each participant scored eight randomly-assigned case-vignettes on a secure online relational database. The intra-class correlation coefficient (ICC) was used to assess agreement for SSI diagnosis on a 7-point Likert scale and the kappa coefficient to assess agreement for SSI depth on a three-point scale. Results Intra-specialty agreement for SSI diagnosis ranged across countries and specialties from 0.00 (95%CI, 0.00–0.35) to 0.65 (0.45–0.82). Inter-specialty agreement varied from 0.04 (0.00–0.62) in to 0.55 (0.37–0.74) in Germany. For all countries pooled, intra-specialty agreement was poor for surgeons (0.24, 0.14–0.42) and good for ICPs (0.41, 0.28–0.61). Reading SSI definitions improved agreement among ICPs (0.57) but not surgeons (0.09). Intra-specialty agreement for SSI depth ranged across countries and specialties from 0.05 (0.00–0.10) to 0.50 (0.45–0.55) and was not improved by reading SSI definition. Conclusion Among ICPs and surgeons evaluating case-vignettes of suspected SSI, considerable disagreement occurred regarding the diagnosis, with variations across specialties and countries. PMID:23874690

  10. Plasma Dispersion Function for the Kappa Distribution

    NASA Technical Reports Server (NTRS)

    Podesta, John J.

    2004-01-01

    The plasma dispersion function is computed for a homogeneous isotropic plasma in which the particle velocities are distributed according to a Kappa distribution. An ordinary differential equation is derived for the plasma dispersion function and it is shown that the solution can be written in terms of Gauss' hypergeometric function. Using the extensive theory of the hypergeometric function, various mathematical properties of the plasma dispersion function are derived including symmetry relations, series expansions, integral representations, and closed form expressions for integer and half-integer values of K.

  11. The upregulation of receptor activator NF-kappaB ligand expression by interleukin-1alpha and Porphyromonas endodontalis in human osteoblastic cells.

    PubMed

    Chen, S-C; Huang, F-M; Lee, S-S; Li, M-Z; Chang, Y-C

    2009-04-01

    To investigate the receptor activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL) in osteoblastic cells stimulated with inflammatory mediators. The expression of RANKL in human osteoblastic cell line U2OS stimulated by pro-inflammatory cytokine interleukin (IL)-1alpha and black-pigmented bacteria Porphyromonas endodontalis was investigated by Western blot and enzyme-linked immunosorbent assay (ELISA). The significance of the results obtained from control and treated groups was statistically analysed by the paired Student's t-test. IL-1alpha was found to upregulate RANKL production in U2OS cells (P < 0.05). Investigations of the time dependence of RANKL expression in IL-1alpha-treated cells revealed a rapid accumulation of RANKL protein after 1 h of exposure; it remained elevated throughout the 24-h incubation period shown by Western blot and ELISA. In addition, P. endodontalis also increased RANKL expression in U2OS cells after 4-h incubation period demonstrated by Western blot and ELISA (P < 0.05). IL-1alpha and P. endodontalis may be involved in developing apical periodontitis through the stimulation of RANKL production.

  12. A comparison of physicians and medical assistants in interpreting verbal autopsy interviews for allocating cause of neonatal death in Matlab, Bangladesh: can medical assistants be considered an alternative to physicians?

    PubMed Central

    2010-01-01

    Objective This study assessed the agreement between medical physicians in their interpretation of verbal autopsy (VA) interview data for identifying causes of neonatal deaths in rural Bangladesh. Methods The study was carried out in Matlab, a rural sub-district in eastern Bangladesh. Trained persons conducted the VA interview with the mother or another family member at the home of the deceased. Three physicians and a medical assistant independently reviewed the VA interviews to assign causes of death using the International Classification of Diseases - Tenth Revision (ICD-10) codes. A physician assigned cause was decided when at least two physicians agreed on a cause of death. Cause-specific mortality fraction (CSMF), kappa (k) statistic, sensitivity, specificity, and positive predictive values were applied to compare agreement between the reviewers. Results Of the 365 neonatal deaths reviewed, agreement on a direct cause of death was reached by at least two physicians in 339 (93%) of cases. Physician and medical assistant reviews of causes of death demonstrated the following levels of diagnostic agreement for the main causes of deaths: for birth asphyxia the sensitivity was 84%, specificity 93%, and kappa 0.77. For prematurity/low birth weight, the sensitivity, specificity, and kappa statistics were, respectively, 53%, 96%, and 0.55, for sepsis/meningitis they were 48%, 98%, and 0.53, and for pneumonia they were 75%, 94%, and 0.51. Conclusion This study revealed a moderate to strong agreement between physician- assigned and medical assistant- assigned major causes of neonatal death. A well-trained medical assistant could be considered an alternative for assigning major causes of neonatal deaths in rural Bangladesh and in similar settings where physicians are scarce and their time costs more. A validation study with medically confirmed diagnosis will improve the performance of VA for assigning cause of neonatal death. PMID:20712906

  13. Impact of specimen adequacy on the assessment of renal allograft biopsy specimens.

    PubMed

    Cimen, S; Geldenhuys, L; Guler, S; Imamoglu, A; Molinari, M

    2016-01-01

    The Banff classification was introduced to achieve uniformity in the assessment of renal allograft biopsies. The primary aim of this study was to evaluate the impact of specimen adequacy on the Banff classification. All renal allograft biopsies obtained between July 2010 and June 2012 for suspicion of acute rejection were included. Pre-biopsy clinical data on suspected diagnosis and time from renal transplantation were provided to a nephropathologist who was blinded to the original pathological report. Second pathological readings were compared with the original to assess agreement stratified by specimen adequacy. Cohen's kappa test and Fisher's exact test were used for statistical analyses. Forty-nine specimens were reviewed. Among these specimens, 81.6% were classified as adequate, 6.12% as minimal, and 12.24% as unsatisfactory. The agreement analysis among the first and second readings revealed a kappa value of 0.97. Full agreement between readings was found in 75% of the adequate specimens, 66.7 and 50% for minimal and unsatisfactory specimens, respectively. There was no agreement between readings in 5% of the adequate specimens and 16.7% of the unsatisfactory specimens. For the entire sample full agreement was found in 71.4%, partial agreement in 20.4% and no agreement in 8.2% of the specimens. Statistical analysis using Fisher's exact test yielded a P value above 0.25 showing that - probably due to small sample size - the results were not statistically significant. Specimen adequacy may be a determinant of a diagnostic agreement in renal allograft specimen assessment. While additional studies including larger case numbers are required to further delineate the impact of specimen adequacy on the reliability of histopathological assessments, specimen quality must be considered during clinical decision making while dealing with biopsy reports based on minimal or unsatisfactory specimens.

  14. Agreement between underlying cause and preventability of infant deaths before and after the investigation in Recife, Pernambuco State, Brazil, 2014.

    PubMed

    Marques, Lays Janaina Prazeres; Pimentel, Dayane da Rocha; Oliveira, Conceição Maria de; Vilela, Mirella Bezerra Rodrigues; Frias, Paulo Germano; Bonfim, Cristine Vieira do

    2018-01-01

    to assess the agreement and describe the causes and preventability of infant deaths before and after the investigation. investigation files and death certificates of infants under one year, of mothers living in Recife, Brazil, in 2014 were used; the Cohen kappa index was adopted for agreement analysis of the underlying causes of death; the list of preventable causes of deaths by interventions of the Brazilian National Health System was also adopted. 183 infant deaths were analyzed, of which 117 (63.9%) had the underlying cause revised; before the investigation, 170 (92.2%) deaths were considered preventable, and after investigation, 178 (97.3%); there was reasonable agreement (0.338) regarding the underlying causes of death, and moderate (0.439) for preventability. infant mortality surveillance enabled the improvement of vital events information, contributing to the progress in the specification of underlying causes of death and in the preventability of infant death.

  15. Nuclear IL-33 is a transcriptional regulator of NF-{kappa}B p65 and induces endothelial cell activation

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

    Choi, Yeon-Sook; Park, Jeong Ae; Kim, Jihye

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer IL-33 as nuclear factor regulated expression of ICAM-1 and VCAM-1. Black-Right-Pointing-Pointer Nuclear IL-33 increased the transcription of NF-{kappa}B p65 by binding to the p65 promoter. Black-Right-Pointing-Pointer Nuclear IL-33 controls NF-{kappa}B-dependent inflammatory responses. -- Abstract: Interleukin (IL)-33, an IL-1 family member, acts as an extracellular cytokine by binding its cognate receptor, ST2. IL-33 is also a chromatin-binding transcriptional regulator highly expressed in the nuclei of endothelial cells. However, the function of IL-33 as a nuclear factor is poorly defined. Here, we show that IL-33 is a novel transcriptional regulator of the p65 subunit of the NF-{kappa}B complex and ismore » involved in endothelial cell activation. Quantitative reverse transcriptase PCR and Western blot analyses indicated that IL-33 mediates the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in endothelial cells basally and in response to tumor necrosis factor-{alpha}-treatment. IL-33-induced ICAM-1/VCAM-1 expression was dependent on the regulatory effect of IL-33 on the nuclear factor (NF)-{kappa}B pathway; NF-{kappa}B p65 expression was enhanced by IL-33 overexpression and, conversely, reduced by IL-33 knockdown. Moreover, NF-{kappa}B p65 promoter activity and chromatin immunoprecipitation analysis revealed that IL-33 binds to the p65 promoter region in the nucleus. Our data provide the first evidence that IL-33 in the nucleus of endothelial cells participates in inflammatory reactions as a transcriptional regulator of NF-{kappa}B p65.« less

  16. CARMA3 is overexpressed in colon cancer and regulates NF-{kappa}B activity and cyclin D1 expression

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

    Miao, Zhifeng; Zhao, Tingting; Wang, Zhenning

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer CARMA3 expression is elevated in colon cancers. Black-Right-Pointing-Pointer CARMA3 promotes proliferation and cell cycle progression in colon cancer cells. Black-Right-Pointing-Pointer CARMA3 upregulates cyclinD1 through NF-{kappa}B activation. -- Abstract: CARMA3 was recently reported to be overexpressed in cancers and associated with the malignant behavior of cancer cells. However, the expression of CARMA3 and its biological roles in colon cancer have not been reported. In the present study, we analyzed the expression pattern of CARMA3 in colon cancer tissues and found that CARMA3 was overexpressed in 30.8% of colon cancer specimens. There was a significant association between CARMA3 overexpression andmore » TNM stage (p = 0.0383), lymph node metastasis (p = 0.0091) and Ki67 proliferation index (p = 0.0035). Furthermore, knockdown of CARMA3 expression in HT29 and HCT116 cells with high endogenous expression decreased cell proliferation and cell cycle progression while overexpression of CARMA3 in LoVo cell line promoted cell proliferation and facilitated cell cycle transition. Further analysis showed that CARMA3 knockdown downregulated and its overexpression upregulated cyclin D1 expression and phospho-Rb levels. In addition, we found that CARMA3 depletion inhibited p-I{kappa}B levels and NF-{kappa}B activity and its overexpression increased p-I{kappa}B expression and NF-{kappa}B activity. NF-{kappa}B inhibitor BAY 11-7082 reversed the role of CARMA3 on cyclin D1 upregulation. In conclusion, our study found that CARMA3 is overexpressed in colon cancers and contributes to malignant cell growth by facilitating cell cycle progression through NF-{kappa}B mediated upregulation of cyclin D1.« less

  17. Development of a Walking-Safety Scale for Older Adults, Part II: Interrater and Test–Retest Agreement of the GEM Scale

    PubMed Central

    Rousseau, Jacqueline; Kaegi, Christine; Boudreault, Renée; Nadeau, Sylvie

    2008-01-01

    Purpose: The GEM scale is an objective assessment tool, specifically developed for older adults, to evaluate walking safety using standardized tasks. The purpose of this study was to estimate the interrater and test–retest agreement of the GEM scale. Method: Participants (n = 41; ≥ 65 years) were recruited from geriatric units and assessed independently and simultaneously by three raters on two occasions using the GEM scale. Kappa coefficients and percentage agreement were calculated for each item of the scale. Results: A majority of walking items (n = 22) showed fair to substantial interrater agreement (κ ≥ 0.25) and substantial to almost perfect test–retest agreement (κ ≥ 0.60). Mean percentage agreement was high for both interrater and test–retest agreement (79% ± 15% and 83% ± 16% respectively). Moreover, detailed analyses demonstrated that the relatively low agreement of some items resulted from changes in the performance of some participants and the low variability of scores. Although some walking items showed less agreement, the final decision regarding the participants’ ability to walk safely resulted in moderate to substantial interrater and test–retest agreement. Conclusion: The GEM scale is a new assessment tool that can now be used with estimated interrater and test–retest properties to allow therapists to objectively evaluate walking safety among the elderly. PMID:20145760

  18. Influence of deoxynivalenol on NF-kappaB activation and IL-8 secretion in human intestinal Caco-2 cells.

    PubMed

    Van De Walle, Jacqueline; Romier, Béatrice; Larondelle, Yvan; Schneider, Yves-Jacques

    2008-04-01

    Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. In human intestinal Caco-2 cells, DON activates the mitogen-activated protein kinases (MAPKs). We hypothesized a link between DON ingestion and intestinal inflammation, and used Caco-2 cells to assess the effects of DON, at plausible intestinal concentrations (250-10,000 ng/ml), on inflammatory mediators acting downstream the MAPKs cascade i.e. activation of nuclear factor-kappaB (NF-kappaB) and interleukin-8 (IL-8) secretion. In addition, Caco-2 cells were co-exposed to pro-inflammatory stimuli in order to mimic an inflamed intestinal epithelium. Dose-dependent increases in NF-kappaB activity and IL-8 secretion were observed, reaching 1.4- and 7.6-fold, respectively using DON at 10 microg/ml. Phosphorylation of inhibitor-kappaB (IkappaB) increased (1.6-fold) at DON levels <0.5 microg/ml. Exposure of Caco-2 cells to pro-inflammatory agents, i.e. 25 ng/ml interleukin-1beta, 100 ng/ml tumor necrosis factor-alpha or 10 microg/ml lipopolysaccharides, activated NF-kappaB and increased IL-8 secretion. Synergistic interactions between these stimuli and DON were observed. These data show that DON induces NF-kappaB activation and IL-8 secretion dose-dependently in Caco-2 cells, and this effect was accentuated upon pro-inflammatory stimulation, suggesting DON exposure could cause or exacerbate intestinal inflammation.

  19. Interrater agreement in the interpretation of neonatal electroencephalography in hypoxic-ischemic encephalopathy.

    PubMed

    Wusthoff, Courtney J; Sullivan, Joseph; Glass, Hannah C; Shellhaas, Renée A; Abend, Nicholas S; Chang, Taeun; Tsuchida, Tammy N

    2017-03-01

    Research using neonatal electroencephalography (EEG) has been limited by a lack of a standardized classification system and interpretation terminology. In 2013, the American Clinical Neurophysiology Society (ACNS) published a guideline for standardized terminology and categorization in the description of continuous EEG in neonates. We sought to assess interrater agreement for this neonatal EEG categorization system as applied by a group of pediatric neurophysiologists. A total of 60 neonatal EEG studies were collected from three institutions. All EEG segments were from term neonates with hypoxic-ischemic encephalopathy. Three pediatric neurophysiologists independently reviewed each record using the ACNS standardized scoring system. Unweighted kappa values were calculated for interrater agreement of categorical data across multiple observers. Interrater agreement was very good for identification of seizures (κ = 0.93, p < 0.001), with perfect agreement in 95% of records (57 of 60). Interrater agreement was moderate for classifying records as normal or having any abnormality (κ = 0.49, p < 0.001), with perfect agreement in 78% of records (47 of 60). Interrater agreement was good in classifying EEG backgrounds on a 5-category scale (normal, excessively discontinuous, burst suppression, status epilepticus, or electrocerebral inactivity) (κ = 0.70, p < 0.001), with perfect agreement in 72% of records (43 of 60). Other specific background features had lower agreement, including voltage (κ = 0.41, p < 0.001), variability (κ = 0.35, p < 0.001), symmetry (κ = 0.18, p = 0.01), presence of abnormal sharp waves (κ < 0.20, p < 0.05), and presence of brief rhythmic discharges (κ < 0.20, p < 0.05). We found good or very good interrater agreement applying the ACNS system for identification of seizures and classification of EEG background. Other specific EEG features showed limited interrater agreement. Of importance to both clinicians and

  20. Proteasome and NF-kappaB inhibiting phaeophytins from the green alga Cladophora fascicularis.

    PubMed

    Huang, Xinping; Li, Min; Xu, Bo; Zhu, Xiaobin; Deng, Zhiwei; Lin, Wenhan

    2007-03-21

    Chemical examination of the green alga Cladophora fascicularis resulted in the isolation and characterization of a new porphyrin derivative, porphyrinolactone (1), along with five known phaeophytins 2-6 and fourteen sterols and cycloartanes. The structure of 1 was determined on the basis of spectroscopic analyses and by comparison of its NMR data with those of known phaeophytins. Compounds 1-6 displayed moderate inhibition of tumor necrosis factor alpha (TNF-alpha) induced nuclear factor-kappaB (NF-kappaB) activation, while 2 and 4 displayed potential inhibitory activity toward proteasome chymotripsin-like activation. The primary structure-activity relationship was also discussed.

  1. Diagnosing Nodular Regenerative Hyperplasia of the Liver Is Thwarted by Low Interobserver Agreement

    PubMed Central

    Jharap, Bindia; van Asseldonk, Dirk P.; de Boer, Nanne K. H.; Bedossa, Pierre; Diebold, Joachim; Jonker, A. Mieke; Leteurtre, Emmanuelle; Verheij, Joanne; Wendum, Dominique; Wrba, Fritz; Zondervan, Pieter E.; Colombel, Jean-Frédéric; Reinisch, Walter; Mulder, Chris J. J.; Bloemena, Elisabeth; van Bodegraven, Adriaan A.

    2015-01-01

    Background and Aims Nodular regenerative hyperplasia (NRH) of the liver is associated with several diseases and drugs. Clinical symptoms of NRH may vary from absence of symptoms to full-blown (non-cirrhotic) portal hypertension. However, diagnosing NRH is challenging. The objective of this study was to determine inter- and intraobserver agreement on the histopathologic diagnosis of NRH. Methods Liver specimens (n=48) previously diagnosed as NRH, were reviewed for the presence of NRH by seven pathologists without prior knowledge of the original diagnosis or clinical background. The majority of the liver specimens were from thiopurine using inflammatory bowel disease patients. Histopathologic features contributing to NRH were also assessed. Criteria for NRH were modified by consensus and subsequently validated. Interobserver agreement was evaluated by using the standard kappa index. Results After review, definite NRH, inconclusive NRH and no NRH were found in 35% (23-40%), 21% (13-27%) and 44% (38-56%), respectively (median, IQR). The median interobserver agreement for NRH was poor (κ = 0.20, IQR 0.14-0.28). The intraobserver variability on NRH ranged between 14% and 71%. After modification of the criteria and exclusion of biopsies with technical shortcomings, the interobserver agreement on the diagnosis NRH was fair (κ = 0.45). Conclusions The interobserver agreement on the histopathologic diagnosis of NRH was poor, even when assessed by well-experienced liver pathologists. Modification of the criteria of NRH based on consensus effort and exclusion of biopsies of poor quality led to a fairly increased interobserver agreement. The main conclusion of this study is that NRH is a clinicopathologic diagnosis that cannot reliably be based on histopathology alone. PMID:26054009

  2. Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men.

    PubMed

    Buford, Thomas W; Cooke, Matthew B; Manini, Todd M; Leeuwenburgh, Christiaan; Willoughby, Darryn S

    2010-05-01

    Nuclear factor kappa B (NF-kappaB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. The present study examined lean mass, maximal force production, and skeletal muscle NF-kappaB signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 +/- 6.59 year), physically active (OA, N = 14, 60.71 +/- 5.54 year), or young and sedentary (YS, N = 14, 21.35 +/- 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the beta subunit of IkB kinase (IKKbeta), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBalpha), and nuclear content of NF-kappaB subunits p50 and p65. When compared with YS, OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBalpha than OA and 61% more pIKBalpha than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of IKKbeta. These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBalpha. A sedentary lifestyle appears to play some role in increased IKBalpha; however, further research is needed to identify downstream effects of this increase.

  3. Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

    PubMed

    Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

    2007-04-01

    Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

  4. Daily peer review of abnormal cervical smears in the assessment of individual practice as an additional method of internal quality control.

    PubMed

    Confortini, M; Di Stefano, C; Biggeri, A; Bulgaresi, P; Di Claudio, G; Grisotto, L; Maddau, C; Matucci, M; Petreschi, C; Troni, G M; Turco, P; Foxi, P

    2016-02-01

    An important internal quality control system used in the Cancer Prevention and Research Institute cytopathology laboratory in Florence is the peer review procedure, based on the review of all abnormal cytological smears which routinely emerge. Peer review is an important training opportunity for all cytologists, especially for those with less experience. This article shows the results of the peer review procedure. Of the 63 754 Papanicolaou (Pap) smears screened in 2011, 1086 were considered to be abnormal [at least atypical squamous cells of undetermined significance (ASC-US+)] on primary screening (selected by a single cytologist) and were subjected to the peer review procedure. The overall performance of the laboratory's cytologists was evaluated using a multiple rater analysis and the comparison of each cytologist with the final diagnosis. Further, the agreement was assessed by means of Cohen's kappa and weighted kappa statistics. In general, a moderate/substantial level of agreement between the ten cytologists and the final diagnoses was evident. Kappa values for each reader compared with the final diagnosis ranged from 0.54 to 0.69. The overall kappa value was 0.62 [95% confidence interval (CI), 0.58-0.66] and overall weighted kappa value was 0.76 (95% CI, 0.74-0.79). The category-specific agreement showed the lowest values for atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). In summary, peer review represents an important internal quality control in the evaluation and improvement of inter-observer agreement and of the functioning of the laboratory as a whole. Multi-head microscope sessions may improve particularly the reproducibility of borderline diagnoses and, above all, can be an important training contribution for cytologists. © 2014 John Wiley & Sons Ltd.

  5. Cervical vertebrae maturation index estimates on cone beam CT: 3D reconstructions vs sagittal sections.

    PubMed

    Bonfim, Marco A E; Costa, André L F; Fuziy, Acácio; Ximenez, Michel E L; Cotrim-Ferreira, Flávio A; Ferreira-Santos, Rívea I

    2016-01-01

    The aim of this study was to evaluate the performance of CBCT three-dimensional (3D) reconstructions and sagittal sections for estimates of cervical vertebrae maturation index (CVMI). The sample consisted of 72 CBCT examinations from patients aged 8-16 years (45 females and 27 males) selected from the archives of two private clinics. Two calibrated observers (kappa scores: ≥0.901) interpreted the CBCT settings twice. Intra- and interobserver agreement for both imaging exhibition modes was analyzed by kappa statistics, which was also used to analyze the agreement between 3D reconstructions and sagittal sections. Correlations between cervical vertebrae maturation estimates and chronological age, as well as between the assessments by 3D reconstructions and sagittal sections, were analyzed using gamma Goodman-Kruskal coefficients (α = 0.05). The kappa scores evidenced almost perfect agreement between the first and second assessments of the cervical vertebrae by 3D reconstructions (0.933-0.983) and sagittal sections (0.983-1.000). Similarly, the agreement between 3D reconstructions and sagittal sections was almost perfect (kappa index: 0.983). In most divergent cases, the difference between 3D reconstructions and sagittal sections was one stage of CVMI. Strongly positive correlations (>0.8, p < 0.001) were found not only between chronological age and CVMI but also between the estimates by 3D reconstructions and sagittal sections (p < 0.001). Although CBCT imaging must not be used exclusively for this purpose, it may be suitable for skeletal maturity assessments.

  6. Cervical vertebrae maturation index estimates on cone beam CT: 3D reconstructions vs sagittal sections

    PubMed Central

    Bonfim, Marco A E; Costa, André L F; Ximenez, Michel E L; Cotrim-Ferreira, Flávio A; Ferreira-Santos, Rívea I

    2016-01-01

    Objectives: The aim of this study was to evaluate the performance of CBCT three-dimensional (3D) reconstructions and sagittal sections for estimates of cervical vertebrae maturation index (CVMI). Methods: The sample consisted of 72 CBCT examinations from patients aged 8–16 years (45 females and 27 males) selected from the archives of two private clinics. Two calibrated observers (kappa scores: ≥0.901) interpreted the CBCT settings twice. Intra- and interobserver agreement for both imaging exhibition modes was analyzed by kappa statistics, which was also used to analyze the agreement between 3D reconstructions and sagittal sections. Correlations between cervical vertebrae maturation estimates and chronological age, as well as between the assessments by 3D reconstructions and sagittal sections, were analyzed using gamma Goodman–Kruskal coefficients (α = 0.05). Results: The kappa scores evidenced almost perfect agreement between the first and second assessments of the cervical vertebrae by 3D reconstructions (0.933–0.983) and sagittal sections (0.983–1.000). Similarly, the agreement between 3D reconstructions and sagittal sections was almost perfect (kappa index: 0.983). In most divergent cases, the difference between 3D reconstructions and sagittal sections was one stage of CVMI. Strongly positive correlations (>0.8, p < 0.001) were found not only between chronological age and CVMI but also between the estimates by 3D reconstructions and sagittal sections (p < 0.001). Conclusions: Although CBCT imaging must not be used exclusively for this purpose, it may be suitable for skeletal maturity assessments. PMID:26509559

  7. Effects of kappa opioid agonists alone and in combination with cocaine on heart rate and blood pressure in conscious squirrel monkeys.

    PubMed

    Schindler, Charles W; Graczyk, Zofi; Gilman, Joanne P; Negus, S Stevens; Bergman, Jack; Mello, Nancy K; Goldberg, Steven R

    2007-12-08

    As kappa agonists have been proposed as treatments for cocaine abuse, the cardiovascular effects of the kappa opioid receptor agonists ethylketocyclazocine (EKC) and enadoline were investigated in conscious squirrel monkeys. Both EKC and enadoline increased heart rate with little effect on blood pressure. This effect appeared to be specific for kappa receptors as the mu opioid agonist morphine did not mimic the effects of the kappa agonists. The opioid antagonist naltrexone, at a dose of 1.0 mg/kg, blocked the effect of EKC. An action at both central and peripheral receptors may be responsible for the heart rate increase following kappa agonist treatment. The ganglionic blocker chlorisondamine partially antagonized the effect of EKC on heart rate, suggesting central involvement, while the peripherally-acting agonist ICI 204,448 ((+/-)-1-[2,3- (Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) also increased heart rate, supporting a peripheral site of action. When given in combination with cocaine, EKC produced effects that were sub-additive, suggesting that the kappa agonists may be used safely as cocaine abuse treatments.

  8. High-level replication of human immunodeficiency virus in thymocytes requires NF-kappaB activation through interaction with thymic epithelial cells.

    PubMed

    Chêne, L; Nugeyre, M T; Barré-Sinoussi, F; Israël, N

    1999-03-01

    We have previously demonstrated that interaction of infected thymocytes with autologous thymic epithelial cells (TEC) is a prerequisite for a high level of human immunodeficiency virus type 1 (HIV-1) replication in thymocytes (M. Rothe, L. Chêne, M. Nugeyre, F. Barré-Sinoussi, and N. Israël, J. Virol. 72:5852-5861, 1998). We report here that this activation of HIV replication takes place at the transcriptional level through activation of the Rel/NF-kappaB transcription factors. We first demonstrate that an HIV-1 provirus (SF-2 strain) very effectively replicates in thymocytes cocultured with TEC whereas this provirus, with kappaB sites deleted, fails to replicate. We provide evidence that several NF-kappaB complexes are constitutively found in the nuclei of thymocytes either freshly isolated from the thymus or maintained in coculture with autologous or heterologous TEC. The prevalent complex is the heterodimer p50-p65. NF-kappaB activity is tightly correlated with the transcriptional activity of a long terminal repeat (LTR) of HIV-1 transfected in thymocytes. The cotransfection of this LTR with a mutated IkappaBalpha molecule formally demonstrates that LTR transactivation is regulated by members of the Rel/NF-kappaB family in thymocytes. We also showed that tumor necrosis factor (TNF) and to a lesser extent interleukin-1 (IL-1), secreted within the coculture, induce NF-kappaB activity and a correlative LTR transactivation. However IL-7, a crucial factor for thymopoiesis that is secreted mainly by TEC, is a necessary cofactor for NF-kappaB activation elicited by TNF or IL-1. Together, these data indicate that NF-kappaB activation, required for a high level of HIV replication in thymocytes, is regulated in a specific manner in the thymic microenvironment which provides the necessary cytokines: TNF, IL-1, and IL-7.

  9. NF-{kappa}B signaling is activated and confers resistance to apoptosis in three-dimensionally cultured EGFR-mutant lung adenocarcinoma cells

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

    Sakuma, Yuji, E-mail: ysakuma@gancen.asahi.yokohama.jp; Yamazaki, Yukiko; Nakamura, Yoshiyasu

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer EGFR-mutant cells in 3D culture resist EGFR inhibition compared with suspended cells. Black-Right-Pointing-Pointer Degradation of I{kappa}B and activation of NF-{kappa}B are observed in 3D-cultured cells. Black-Right-Pointing-Pointer Inhibiting NF-{kappa}B enhances the efficacy of the EGFR inhibitor in 3D-cultured cells. -- Abstract: Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells in suspension undergo apoptosis to a greater extent than adherent cells in a monolayer when EGFR autophosphorylation is inhibited by EGFR tyrosine kinase inhibitors (TKIs). This suggests that cell adhesion to a culture dish may activate an anti-apoptotic signaling pathway other than the EGFR pathway. Since the microenvironment of cellsmore » cultured in a monolayer are substantially different to that of cells existing in three-dimension (3D) in vivo, we assessed whether two EGFR-mutant lung adenocarcinoma cell lines, HCC827 and H1975, were more resistant to EGFR TKI-induced apoptosis when cultured in a 3D extracellular matrix (ECM) as compared with in suspension. The ECM-adherent EGFR-mutant cells in 3D were significantly less sensitive to treatment with WZ4002, an EGFR TKI, than the suspended cells. Further, a marked degradation of I{kappa}B{alpha}, the inhibitor of nuclear factor (NF)-{kappa}B, was observed only in the 3D-cultured cells, leading to an increase in the activation of NF-{kappa}B. Moreover, the inhibition of NF-{kappa}B with pharmacological inhibitors enhanced EGFR TKI-induced apoptosis in 3D-cultured EGFR-mutant cells. These results suggest that inhibition of NF-{kappa}B signaling would render ECM-adherent EGFR-mutant lung adenocarcinoma cells in vivo more susceptible to EGFR TKI-induced cell death.« less

  10. Improved inter-observer agreement of an expert review panel in an oncology treatment trial--Insights from a structured interventional process.

    PubMed

    Nestle, Ursula; Rischke, Hans Christian; Eschmann, Susanne Martina; Holl, Gabriele; Tosch, Marco; Miederer, Matthias; Plotkin, Michail; Essler, Markus; Puskas, Cornelia; Schimek-Jasch, Tanja; Duncker-Rohr, Viola; Rühl, Friederike; Leifert, Anja; Mix, Michael; Grosu, Anca-Ligia; König, Jochem; Vach, Werner

    2015-11-01

    Oncologic imaging is a key for successful cancer treatment. While the quality assurance (QA) of image acquisition protocols has already been focussed, QA of reading and reporting offers still room for improvement. The latter was addressed in the context of a prospective multicentre trial on fluoro-deoxyglucose (FDG)-positron-emission tomography (PET)/CT-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). An expert panel was prospectively installed performing blinded reviews of mediastinal NSCLC involvement in FDG-PET/CT. Due to a high initial reporting inter-observer disagreement, the independent data monitoring committee (IDMC) triggered an interventional harmonisation process, which overall involved 11 experts uttering 6855 blinded diagnostic statements. After assessing the baseline inter-observer agreement (IOA) of a blinded re-review (phase 1), a discussion process led to improved reading criteria (phase 2). Those underwent a validation study (phase 3) and were then implemented into the study routine. After 2 months (phase 4) and 1 year (phase 5), the IOA was reassessed. The initial overall IOA was moderate (kappa 0.52 CT; 0.53 PET). After improvement of reading criteria, the kappa values improved substantially (kappa 0.61 CT; 0.66 PET), which was retained until the late reassessment (kappa 0.71 CT; 0.67 PET). Subjective uncertainty was highly predictive for low IOA. The IOA of an expert panel was significantly improved by a structured interventional harmonisation process which could be a model for future clinical trials. Furthermore, the low IOA in reporting nodal involvement in NSCLC may bear consequences for individual patient care. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. NF-kappaB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro.

    PubMed

    Feng, Jian Q; Xing, Lianping; Zhang, Jiang-Hong; Zhao, Ming; Horn, Diane; Chan, Jeannie; Boyce, Brendan F; Harris, Stephen E; Mundy, Gregory R; Chen, Di

    2003-08-01

    Bone morphogenetic protein-2 (BMP-2) regulates growth plate chondrogenesis during development and postnatal bone growth, but the control mechanisms of BMP-2 expression in growth plate chondrocytes are unknown. Here we have used both in vitro and in vivo approaches to demonstrate that transcription factor, NF-kappaB, regulates BMP-2 gene expression in chondrocytes. Two putative NF-kappaB response elements were found in the -2712/+165 region of the BMP-2 gene. Cotransfection of mutant I-kappaBalpha expression plasmids with BMP-2 promoter-luciferase reporters into TMC-23 chondrocyte cell line suppressed BMP-2 transcription. Mutations in NF-kappaB response elements in the BMP-2 gene lead to decreases in BMP-2 promoter activity. Electrophoretic mobility shift assay using nuclear extracts from TMC-23 chondrocytic cells revealed that the NF-kappaB subunits p50 and p65 bound to the NF-kappaB response elements of the BMP-2 gene. Thus, NF-kappaB may positively regulate BMP-2 gene transcription. Consistent with these findings, expression of BMP-2 mRNA was significantly reduced in growth plate chondrocytes in NF-kappaB p50/p52 dKO mice, which associated with decreased numbers of 5-bromo-2'-deoxyuridine (BrdUrd)-positive cells in the proliferating zone of growth plate in these mice. Therefore, in postnatal growth plate chondrocytes, expression of BMP-2 is regulated by NF-kappaB, which may play an important role in chondrogenesis.

  12. The discriminative effects of the kappa-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects.

    PubMed

    Butelman, Eduardo R; Rus, Szymon; Prisinzano, Thomas E; Kreek, Mary Jeanne

    2010-06-01

    The widely available hallucinogen salvinorin A is a unique example of a plant-derived compound selective for kappa-opioid receptors and may produce effects distinct from those of other compounds with classic hallucinogenic or dissociative properties which are also abused in humans. The objective of this study is to characterize the salvinorin A discriminative cue in nonhuman primates with high kappa-receptor genetic homology to humans. Adult rhesus monkeys (n = 3) were trained to discriminate salvinorin A (0.015 mg/kg, s.c.) from vehicle, in a food-reinforced operant discrimination assay. Parallel studies, using unconditioned behavioral endpoints (facial relaxation and ptosis) also evaluated the kappa-opioid receptor mediation of salvinorin A in vivo function. Monkeys trained to discriminate salvinorin A generalized structurally diverse, centrally penetrating kappa-agonists (bremazocine, U69,593, and U50,488). By contrast, mu- and delta-opioid agonists (fentanyl and SNC80, respectively) were not generalized, nor were the serotonergic 5HT2 hallucinogen psilocybin or the dissociative N-methyl-D-aspartic acid antagonist, ketamine. The discriminative effects of salvinorin A were blocked by the opioid antagonist quadazocine (0.32 mg/kg), but not by the 5HT2 antagonist ketanserin (0.1 mg/kg). Consistent with these findings, salvinorin and kappa-agonists (e.g., U69,593) produce effects in the unconditioned endpoints (e.g., ptosis), whereas psilocybin was inactive. These findings support the conclusion that the interoceptive/discriminative cue produced by salvinorin A is mediated by agonism at kappa-receptors and is mechanistically distinct from that produced by a classic serotonergic hallucinogen.

  13. Presynaptic inhibition of diverse afferents to the locus ceruleus by kappa-opiate receptors: a novel mechanism for regulating the central norepinephrine system.

    PubMed

    Kreibich, Arati; Reyes, Beverly A S; Curtis, Andre L; Ecke, Laurel; Chavkin, Charles; Van Bockstaele, Elisabeth J; Valentino, Rita J

    2008-06-18

    The norepinephrine nucleus, locus ceruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAAs), corticotropin-releasing factor (CRF), and endogenous opioids acting at mu-opiate receptors. Because the LC is also innervated by the endogenous kappa-opiate receptor (kappa-OR) ligand dynorphin and expresses kappa-ORs, this study investigated kappa-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of kappa-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the kappa-OR agonist (trans)-3,4-dichloro-N-methyl-N-[2-1-pyrrolidinyl)-cyclo-hexyl] benzeneacetamide (U50488) into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the kappa-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that kappa-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-norepinephrine system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate kappa-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders, or disorders characterized by abnormal sensory responses, such as autism.

  14. Escherichia coli K1 inhibits proinflammatory cytokine induction in monocytes by preventing NF-kappaB activation.

    PubMed

    Selvaraj, Suresh K; Prasadarao, Nemani V

    2005-08-01

    Phagocytes are well-known effectors of the innate immune system to produce proinflammatory cytokines and chemokines such as tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-8 during infections. Here, we show that infection of monocytes with wild-type Escherichia coli K1, which causes meningitis in neonates, suppresses the production of cytokines and chemokines (TNF-alpha, regulated on activation, normal T expressed and secreted, macrophage-inflammatory protein-1beta, IL-1beta, and IL-8). In contrast, infection of monocytes with a mutant E. coli, which lacks outer membrane protein A (OmpA- E. coli) resulted in robust production of cytokines and chemokines. Wild-type E. coli K1 (OmpA+ E. coli) prevented the phosphorylation and its degradation of inhibitor of kappaB, thereby blocking the translocation of nuclear factor (NF)-kappaB to the nucleus. OmpA+ E. coli-infected cells, subsequently subjected to lipopolysaccharide challenge, were crippled severely in their ability to activate NF-kappaB to induce cytokine/chemokine production. Selective inhibitors of the extracellular signal-regulated kinase (ERK) 1/2 pathway and p38 mitogen-activated protein kinase (MAPK), but not Jun N-terminal kinase, significantly reduced the activation of NF-kappaB and the production of cytokines and chemokines induced by OmpA- E. coli, indicating a role for these kinases in the NF-kappaB/cytokine pathway. It is interesting that the phosphorylation of ERK 1/2 and p38 MAPK was notably reduced in monocytes infected with OmpA+ E. coli when compared with monocytes infected with OmpA- E. coli, suggesting that the modulation of upstream events common for NF-kappaB and MAPKs by the bacterium is possible. The ability of OmpA+ E. coli K1 to inhibit the macrophage response temporarily may enable bacterial survival and growth within the host for the onset of meningitis by E. coli K1.

  15. The suppression of radiation-induced NF-{kappa}B activity by dexamethasone correlates with increased cell death in vivo

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

    Nam, Seon Young; Chung, Hee-Yong

    2005-10-21

    In this study, we show that dexamethasone treatment increases ionizing radiation-induced cell death by inducing the inhibitory {kappa}B{alpha} (I{kappa}B{alpha}) pathway in mice. The effect of dexamethasone on radiation-induced cell death was assessed by changes in total spleen cellularity and bone marrow colony-forming unit-granulocyte-macrophage (CFU-GM) contents after total body irradiation. While in vivo treatment of mice with dexamethasone alone (1 mg/kg/day, for 2 days) failed to elicit cell death in spleen cells, the combined treatment with dexamethasone (1 mg/kg/day, for 2 days) and {gamma}-rays (1 or 5 Gy) caused a 50-80% reduction in total cellularity in spleen and CFU-GM contents inmore » bone marrow. These results demonstrate that dexamethasone has a synergistic effect on radiation-induced cellular damages in vivo. Immunoblot analysis showed that dexamethasone treatment significantly increases I{kappa}B{alpha} expression in the spleens of irradiated mice. In addition, the dexamethasone treatment significantly reduced radiation-induced nuclear translocation of the nucleus factor-{kappa}B in the spleens of irradiated mice. These results indicate that dexamethasone treatment in vivo may increase radiation-induced cell damages by increasing I{kappa}B{alpha} expression in hematopoietic organs such as spleen and bone marrow.« less

  16. Styrene induces an inflammatory response in human lung epithelial cells via oxidative stress and NF-{kappa}B activation

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

    Roeder-Stolinski, Carmen; Fischaeder, Gundula; Oostingh, Gertie Janneke

    2008-09-01

    Styrene is a volatile organic compound (VOC) that is widely used as a solvent in many industrial settings. Chronic exposure to styrene can result in irritation of the mucosa of the upper respiratory tract. Contact of styrene with epithelial cells stimulates the expression of a variety of inflammatory mediators, including the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). To characterise the underlying mechanisms of the induction of inflammatory signals by styrene, we investigated the influence of this compound on the induction of oxidative stress and the activation of the nuclear factor-kappa B (NF-{kappa}B) signalling pathway in human lung epithelial cells (A549).more » The results demonstrate that styrene-induced MCP-1 expression, as well as the expression of the oxidative stress marker glutathione S-transferase (GST), is associated with a concentration dependent pattern of NF-{kappa}B activity. An inhibitor of NF-{kappa}B, IKK-NBD, and the anti-inflammatory antioxidant N-acetylcysteine (NAC) were both effective in suppressing styrene-induced MCP-1 secretion. In addition, NAC was capable of inhibiting the upregulation of GST expression. Our findings suggest that the activation of the NF-{kappa}B signalling pathway by styrene is mediated via a redox-sensitive mechanism.« less

  17. Moderate Resolution Spectroscopy of Substellar Companion Kappa Andromeda B

    NASA Astrophysics Data System (ADS)

    Wilcomb, Kielan; Konopacky, Quinn; Barman, Travis; Brown, Jessie; Brock, Laci; Macintosh, Bruce; Ruffio, Jean-Baptiste; Marois, Christian

    2018-01-01

    Recent direct imaging of exoplanets has revealed a population of Jupiter-like objects that orbit at large separations (~10-100 AU) from their host stars. These planets, with masses of ~2-14 MJup and temperatures of ~500-2000 K, remain a problem for the two main planet formation models—core accretion and gravitational instability. OSIRIS observations of directly imaged planets have expanded our understanding of their atmospheres, alluded to their formation, and uncovered individual molecular lines. Here, we present OSIRIS K band spectra of the “super-Jupiter,” Kappa Andromeda b. Kappa Andromeda b has a lower mass limit at the deuterium burning limit, but also has an uncertain age which may indicate the source is a higher mass brown dwarf. The spectra reveal resolved molecular lines from water and CO. We will present atmospheric properties of this object derived from comparison to PHOENIX atmosphere models, and measure a best fit C/O ratio for the source. We will compare our results to atmospheric properties of other brown dwarfs and gas giant planets in an effort to improve our knowledge of intricate atmospheres of young, substellar objects.

  18. Inhibition of NF-kappaB-mediated transcription and induction of apoptosis in human breast cancer cells by epoxypseudoisoeugenol-2-methyl butyrate.

    PubMed

    Ma, Guoyi; Tabanca, Nurhayat; Husnu Can Baser, K; Kirimer, Nese; Pasco, David S; Khan, Ikhlas A; Khan, Shabana I

    2009-03-01

    Breast cancer is one of the most prevalent woman cancers. Genomic instability, accumulative mutations, and subsequent changes in intracellular signaling cascades play key roles in the development of human breast cancers. Activation of nuclear factor-kappaB (NF-kappaB) has been implicated in oncogenesis of breast cancers and is known to be associated with resistance to anticancer agents and apoptosis. Blocking NF-kappaB signaling may represent a therapeutic strategy in breast cancer therapy. The objective of this study is to investigate the in vitro effects of epoxypseudoisoeugenol-2-methyl butyrate (EPB), a phenylpropranoid isolated from Pimpinella corymbosa, on the activation of NF-kappaB, cell growth, cell cycle progression and apoptosis in MCF-7 (estrogen-dependent) and BT-549 (estrogen-independent) breast cancer cells. Transcriptional activity of NF-kappaB was measured by cell based reporter gene assay. Cell proliferation was determined by MTT assay. Cell cycle analysis was carried out by flow cytometry and apoptosis was observed by DAPI staining assy. EPB inhibited the NF-kappaB-mediated transcription activity induced by tumor necrosis factor-alpha (TNF-alpha) and phorbol myristate acetate (PMA) in MCF-7 cells. EPB also inhibited constitutive NF-kappaB transcriptional activity in BT-549 cells. EPB inhibited the proliferation of both MCF-7 and BT-549 cells in a concentration- and time-dependent manner. EPB induced cell cycle arrest in G(1)/G(0) phase and apoptosis in both MCF-7 and BT 549 cells. These in vitro results indicated that EPB has a potential for use against both hormone-dependent and hormone-independent breast cancers and its effects seem to be mediated by inhibiting the NF-kappaB activity.

  19. Evidence for nucleotide receptor modulation of cross talk between MAP kinase and NF-kappa B signaling pathways in murine RAW 264.7 macrophages.

    PubMed

    Aga, Mini; Watters, Jyoti J; Pfeiffer, Zachary A; Wiepz, Gregory J; Sommer, Julie A; Bertics, Paul J

    2004-04-01

    Extracellular nucleotides such as ATP are present in abundance at sites of inflammation and tissue damage, and these agents exert a potent modulatory effect on macrophage/monocyte function via the nucleotide receptor P2X(7). In this regard, after exposure to bacterial LPS, P2X(7) activation augments expression of the inducible nitric oxide (NO) synthase and production of NO in macrophages. Because P2X(7) has been reported to stimulate certain members of the MAP kinase family (ERK1/2) and can enhance the DNA-binding activity of NF-kappa B, we tested the hypothesis that LPS and nucleotides regulate NF-kappa B-dependent inflammatory events via cross talk with MAPK-associated pathways. In this regard, the present studies revealed that cotreatment of macrophages with LPS and the P2X(7)-selective ligand 2'-3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) results in the cooperative activation of NF-kappa B DNA-binding activity and a sustained attenuation of levels of the NF-kappa B inhibitory protein I kappa B alpha. Interestingly, a persistent reduction in I kappa B alpha levels is also observed when the MEK1/2 inhibitor U0126 is coadministered with LPS, suggesting that components of the MEK/ERK pathway are involved in regulating I kappa B alpha protein expression and/or turnover. The observation that U0126 and BzATP exhibit overlapping actions with respect to LPS-induced changes in I kappa B alpha levels is supported by the finding that Ras activation, which is upstream of MEK/ERK activation, is reduced upon macrophage cotreatment with BzATP and LPS compared with the effects of BzATP treatment alone. These data are consistent with the concept that the Ras/MEK/ERK pathways are involved in regulating NF-kappa B/I kappa B-dependent inflammatory mediator production and suggest a previously unidentified mechanism by which nucleotides can modulate LPS-induced action via cross talk between NF-kappa B and Ras/MEK/MAPK-associated pathways.

  20. Low Reynolds number kappa-epsilon and empirical transition models for oscillatory pipe flow and heat transfer. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Bauer, Christopher

    1993-01-01

    Stirling engine heat exchangers are shell-and-tube type with oscillatory flow (zero-mean velocity) for the inner fluid. This heat transfer process involves laminar-transition turbulent flow motions under oscillatory flow conditions. A low Reynolds number kappa-epsilon model, (Lam-Bremhorst form), was utilized in the present study to simulate fluid flow and heat transfer in a circular tube. An empirical transition model was used to activate the low Reynolds number k-e model at the appropriate time within the cycle for a given axial location within the tube. The computational results were compared with experimental flow and heat transfer data for: (1) velocity profiles, (2) kinetic energy of turbulence, (3) skin friction factor, (4) temperature profiles, and (5) wall heat flux. The experimental data were obtained for flow in a tube (38 mm diameter and 60 diameter long), with the maximum Reynolds number based on velocity being Re(sub max) = 11840, a dimensionless frequency (Valensi number) of Va = 80.2, at three axial locations X/D = 16, 30 and 44. The agreement between the computations and the experiment is excellent in the laminar portion of the cycle and good in the turbulent portion. Moreover, the location of transition was predicted accurately. The Low Reynolds Number kappa-epsilon model, together with an empirical transition model, is proposed herein to generate the wall heat flux values at different operating parameters than the experimental conditions. Those computational data can be used for testing the much simpler and less accurate one dimensional models utilized in 1-D Stirling Engine design codes.

  1. Estimation of occupational cosmic radiation exposure among airline personnel: Agreement between a job-exposure matrix, aggregate, and individual dose estimates.

    PubMed

    Talibov, Madar; Salmelin, Raili; Lehtinen-Jacks, Susanna; Auvinen, Anssi

    2017-04-01

    Job-exposure matrices (JEM) are used for exposure assessment in occupational studies, but they can involve errors. We assessed agreement between the Nordic Occupational Cancer Studies JEM (NOCCA-JEM) and aggregate and individual dose estimates for cosmic radiation exposure among Finnish airline personnel. Cumulative cosmic radiation exposure for 5,022 airline crew members was compared between a JEM and aggregate and individual dose estimates. The NOCCA-JEM underestimated individual doses. Intraclass correlation coefficient was 0.37, proportion of agreement 64%, kappa 0.46 compared with individual doses. Higher agreement was achieved with aggregate dose estimates, that is annual medians of individual doses and estimates adjusted for heliocentric potentials. The substantial disagreement between NOCCA-JEM and individual dose estimates of cosmic radiation may lead to exposure misclassification and biased risk estimates in epidemiological studies. Using aggregate data may provide improved estimates. Am. J. Ind. Med. 60:386-393, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Molecular basis for the unique deubiquitinating activity of the NF-kappaB inhibitor A20.

    PubMed

    Lin, Su-Chang; Chung, Jee Y; Lamothe, Betty; Rajashankar, Kanagalaghatta; Lu, Miao; Lo, Yu-Chih; Lam, Amy Y; Darnay, Bryant G; Wu, Hao

    2008-02-15

    Nuclear factor kappaB (NF-kappaB) activation in tumor necrosis factor, interleukin-1, and Toll-like receptor pathways requires Lys63-linked nondegradative polyubiquitination. A20 is a specific feedback inhibitor of NF-kappaB activation in these pathways that possesses dual ubiquitin-editing functions. While the N-terminal domain of A20 is a deubiquitinating enzyme (DUB) for Lys63-linked polyubiquitinated signaling mediators such as TRAF6 and RIP, its C-terminal domain is a ubiquitin ligase (E3) for Lys48-linked degradative polyubiquitination of the same substrates. To elucidate the molecular basis for the DUB activity of A20, we determined its crystal structure and performed a series of biochemical and cell biological studies. The structure reveals the potential catalytic mechanism of A20, which may be significantly different from papain-like cysteine proteases. Ubiquitin can be docked onto a conserved A20 surface; this interaction exhibits charge complementarity and no steric clash. Surprisingly, A20 does not have specificity for Lys63-linked polyubiquitin chains. Instead, it effectively removes Lys63-linked polyubiquitin chains from TRAF6 without dissembling the chains themselves. Our studies suggest that A20 does not act as a general DUB but has the specificity for particular polyubiquitinated substrates to assure its fidelity in regulating NF-kappaB activation in the tumor necrosis factor, interleukin-1, and Toll-like receptor pathways.

  3. Diagnosing comorbidity in psychiatric hospital: challenging the validity of administrative registers.

    PubMed

    Oiesvold, Terje; Nivison, Mary; Hansen, Vidje; Skre, Ingunn; Ostensen, Line; Sørgaard, Knut W

    2013-01-08

    This study will explore the validity of psychiatric diagnoses in administrative registers with special emphasis on comorbid anxiety and substance use disorders. All new patients admitted to psychiatric hospital in northern Norway during one year were asked to participate. Of 477 patients found eligible, 272 gave their informed consent. 250 patients (52%) with hospital diagnoses comprised the study sample. Expert diagnoses were given on the basis of a structured diagnostic interview (M.I.N.I.PLUS) together with retrospective checking of the records. The hospital diagnoses were blind to the expert. The agreement between the expert's and the clinicians' diagnoses was estimated using Cohen's kappa statistics. The expert gave a mean of 3.4 diagnoses per patient, the clinicians gave 1.4. The agreement ranged from poor to good (schizophrenia). For anxiety disorders (F40-41) the agreement is poor (kappa = 0.12). While the expert gave an anxiety disorder diagnosis to 122 patients, the clinicians only gave it to 17. The agreement is fair concerning substance use disorders (F10-19) (kappa = 0.27). Only two out of 76 patients with concurrent anxiety and substance use disorders were identified by the clinicians. The validity of administrative registers in psychiatry seems dubious for research purposes and even for administrative and clinical purposes. The diagnostic process in the clinic should be more structured and treatment guidelines should include comorbidity.

  4. Exploring precarious employment and women's health within the context of U.S. microenterprise using focus groups.

    PubMed

    Salt, Rebekah; Lee, Jongwon

    2014-01-01

    Nursing has been a leader in exploring social determinants of health within the context of U.S. microenterprise and women's health. The purpose of this study was to explore precarious employment within the context of microenterprise and women's health using focus groups with clientele from New Mexico (NM). The specific aims were to identify (1) the health concerns of low-income women who utilized resources from Women's Economic Self-Sufficiency Team (WESST), and (2) the meaning of precarious employment in low-income women's lives. Fourteen women, ranging in age from 21-65 years, who were affiliated with regional WESST sites around NM participated in focus groups and completed a demographic questionnaire. Focus group data were analyzed using content analysis. The degree of interrater agreement was determined by calculating the Cohen's kappa, percentage agreement, and prevalence-adjusted and bias-adjusted kappa (PABAK). Two broad themes emerged from these data: (1) Working for Yourself and (2) Strategies. Although the women identified concerns about participation in microenterprise, flexibility, freedom, and feeling purposeful were motivators to pursue a small business. The kappa statistics on the five transcripts revealed poor inter-rater agreement, yet PABAK, which is a more sophisticated inter-rater reliability index, indicated that inter-rater agreement between the two raters was satisfactory. Despite the challenges associated with microenterprise in the US, women found value in working for themselves. © 2014 Wiley Periodicals, Inc.

  5. Statistical characteristics of storm interevent time, depth, and duration for eastern New Mexico, Oklahoma, and Texas

    USGS Publications Warehouse

    Asquith, William H.; Roussel, Meghan C.; Cleveland, Theodore G.; Fang, Xing; Thompson, David B.

    2006-01-01

    The design of small runoff-control structures, from simple floodwater-detention basins to sophisticated best-management practices, requires the statistical characterization of rainfall as a basis for cost-effective, risk-mitigated, hydrologic engineering design. The U.S. Geological Survey, in cooperation with the Texas Department of Transportation, has developed a framework to estimate storm statistics including storm interevent times, distributions of storm depths, and distributions of storm durations for eastern New Mexico, Oklahoma, and Texas. The analysis is based on hourly rainfall recorded by the National Weather Service. The database contains more than 155 million hourly values from 774 stations in the study area. Seven sets of maps depicting ranges of mean storm interevent time, mean storm depth, and mean storm duration, by county, as well as tables listing each of those statistics, by county, were developed. The mean storm interevent time is used in probabilistic models to assess the frequency distribution of storms. The Poisson distribution is suggested to model the distribution of storm occurrence, and the exponential distribution is suggested to model the distribution of storm interevent times. The four-parameter kappa distribution is judged as an appropriate distribution for modeling the distribution of both storm depth and storm duration. Preference for the kappa distribution is based on interpretation of L-moment diagrams. Parameter estimates for the kappa distributions are provided. Separate dimensionless frequency curves for storm depth and duration are defined for eastern New Mexico, Oklahoma, and Texas. Dimension is restored by multiplying curve ordinates by the mean storm depth or mean storm duration to produce quantile functions of storm depth and duration. Minimum interevent time and location have slight influence on the scale and shape of the dimensionless frequency curves. Ten example problems and solutions to possible applications are

  6. Evaluating the appropriateness of antimicrobial treatment in hospitalized patients: a comparison of three methods.

    PubMed

    Reisfeld, S; Assaly, M; Tannous, E; Amarney, K; Stein, M

    2018-06-01

    Approximately 20-50% of antimicrobial therapy in hospitalized patients is considered inappropriate, which may be associated with increased morbidity and mortality. The best method for evaluation of appropriateness is not well defined. To evaluate the rate of appropriate antimicrobial therapy in a secondary hospital using three different methods, and determine the rate of agreement between the different methods. A point prevalence study included all adult hospitalized patients receiving systemic antimicrobial therapy during 2016, screened on a single day. Clinical, laboratory and therapeutic data were collected from patient files, and appropriateness was rated with a qualitative evaluation by expert opinion. In addition, a quantitative evaluation was performed according to 11 quality indicators (QIs) rated for each patient. A strict definition of appropriateness was fulfilled if six essential QIs were met, and a lenient definition was fulfilled if at least five QIs were met. Agreement between methods was analysed using kappa statistic. Among 106 patients included, rates of appropriateness of antimicrobial therapy ranged from 20% to 75%, depending on the method of evaluation. Very low agreement was found between the strict definition and expert opinion (kappa=0.068), and medium agreement was found between the lenient definition and expert opinion (kappa=0.45). Rates of appropriateness of antimicrobial therapy varied between evaluation methods, with low to moderate agreement between the different methods. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  7. Multiparametric MRI of the prostate: diagnostic performance and interreader agreement of two scoring systems.

    PubMed

    Lin, Wei-Ching; Muglia, Valdair F; Silva, Gyl E B; Chodraui Filho, Salomão; Reis, Rodolfo B; Westphalen, Antonio C

    2016-06-01

    To compare the diagnostic accuracies and interreader agreements of the Prostate Imaging Reporting and Data System (PI-RADS) v. 2 and University of California San Francisco (UCSF) multiparametric prostate MRI scale for diagnosing clinically significant prostate cancer. This institutional review board-approved retrospective study included 49 males who had 1.5 T endorectal MRI and prostatectomy. Two radiologists scored suspicious lesions on MRI using PI-RADS v. 2 and the UCSF scale. Percent agreement, 2 × 2 tables and the area under the receiver operating characteristic curves (Az) were used to assess and compare the individual and overall scores of these scales. Interreader agreements were estimated with kappa statistics. Reader 1 (R1) detected 78 lesions, and Reader 2 (R2) detected 80 lesions. Both identified 52 of 65 significant cancers. The Az for PI-RADS v. 2 and UCSF scale for R1 were 0.68 and 0.69 [T2 weighted imaging (T2WI)], 0.75 and 0.68 [diffusion-weighted imaging (DWI)] and 0.64 and 0.72 (overall score), respectively, and were 0.72 and 0.75 (T2WI), 0.73 and 0.67 (DWI) and 0.66 and 0.75 (overall score) for R2. The dynamic contrast-enhanced percent agreements between scales were 100% (R1) and 95% (R2). PI-RADS v. 2 DWI of R1 performed better than UCSF DWI (Az = 0.75 vs Az = 0.68; p = 0.05); no other differences were found. The interreader agreements were higher for PI-RADS v. 2 (T2WI: 0.56 vs 0.42; DWI: 0.60 vs 0.46; overall: 0.61 vs 0.42). The UCSF approach to derive the overall PI-RADS v. 2 scores increased the Az for the identification of significant cancer (R1 to 0.76, p < 0.05; R2 to 0.71, p = 0.35). Although PI-RADS v. 2 DWI score may have a higher discriminatory performance than the UCSF scale counterpart to diagnose clinically significant cancer, the utilization of the UCSF scale weighing system for the integration of PI-RADS v. 2 individual parameter scores improved the accuracy its overall score. PI-RADS v. 2 is

  8. Comparison of two commonly used clinical cognitive screening tests to diagnose mild cognitive impairment in heart failure with the golden standard European Consortium Criteria.

    PubMed

    Alagiakrishnan, Kannayiram; Mah, Darren; Dyck, Jason R B; Senthilselvan, Ambikaipakan; Ezekowitz, Justin

    2017-02-01

    This study on mild cognitive impairment (MCI) in heart failure (HF) compares the utility of Montreal Cognitive Assessment (MoCA) to the Mini-Mental Status Exam (MMSE) for diagnosing MCI in a HF population when compared to the golden standard European Consortium Criteria (ECC). Participants were recruited from the Alberta HEART study at the Mazankowski Alberta Heart Institute in Edmonton and St. Mary's hospital in Camrose. This study enrolled 53 community adults aged>50years: 33 HF and 20 controls. Participants were assessed using both the MMSE and MoCA for MCI. MCI was diagnosed using the golden standard, European Consortium Criteria. Sensitivity and specificity analysis, positive and negative predictive values, likelihood ratios and kappa statistic were calculated. The mean age was 72.8years (SD 8.4), 60.4% were females and 34% had underlying ischemic heart disease. Overall, two thirds of patients (22/33, 66%) with HF had MCI. In comparison to European Consortium Criteria, the sensitivity and specificity of MoCA were 82% and 91% in identifying individuals with MCI, and MMSE were 9% and 91%, respectively. The positive and negative predictive values for MoCA were 95% and 71%, and for MMSE were 67% and 33%, respectively. Kappa statistics showed good agreement between MoCA and consortium criteria (kappa=0.68) and a low agreement between MMSE and consortium criteria (kappa=0.07). Cognitive dysfunction is common in patients with HF. Overall, the MoCA seems to be a better screening tool than MMSE for MCI in HF patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Breast lesion shape and margin evaluation: BI-RADS based metrics understate radiologists' actual levels of agreement.

    PubMed

    Rawashdeh, Mohammad; Lewis, Sarah; Zaitoun, Maha; Brennan, Patrick

    2018-05-01

    While there is much literature describing the radiologic detection of breast cancer, there are limited data available on the agreement between experts when delineating and classifying breast lesions. The aim of this work is to measure the level of agreement between expert radiologists when delineating and classifying breast lesions as demonstrated through Breast Imaging Reporting and Data System (BI-RADS) and quantitative shape metrics. Forty mammographic images, each containing a single lesion, were presented to nine expert breast radiologists using a high specification interactive digital drawing tablet with stylus. Each reader was asked to manually delineate the breast masses using the tablet and stylus and then visually classify the lesion according to the American College of Radiology (ACR) BI-RADS lexicon. The delineated lesion compactness and elongation were computed using Matlab software. Intraclass Correlation Coefficient (ICC) and Cohen's kappa were used to assess inter-observer agreement for delineation and classification outcomes, respectively. Inter-observer agreement was fair for BI-RADS shape (kappa = 0.37) and moderate for margin (kappa = 0.58) assessments. Agreement for quantitative shape metrics was good for lesion elongation (ICC = 0.82) and excellent for compactness (ICC = 0.93). Fair to moderate levels of agreement was shown by radiologists for shape and margin classifications of cancers using the BI-RADS lexicon. When quantitative shape metrics were used to evaluate radiologists' delineation of lesions, good to excellent inter-observer agreement was found. The results suggest that qualitative descriptors such as BI-RADS lesion shape and margin understate the actual level of expert radiologist agreement. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. The Pfirrmann classification of lumbar intervertebral disc degeneration: an independent inter- and intra-observer agreement assessment.

    PubMed

    Urrutia, Julio; Besa, Pablo; Campos, Mauricio; Cikutovic, Pablo; Cabezon, Mario; Molina, Marcelo; Cruz, Juan Pablo

    2016-09-01

    Grading inter-vertebral disc degeneration (IDD) is important in the evaluation of many degenerative conditions, including patients with low back pain. Magnetic resonance imaging (MRI) is considered the best imaging instrument to evaluate IDD. The Pfirrmann classification is commonly used to grade IDD; the authors describing this classification showed an adequate agreement using it; however, there has been a paucity of independent agreement studies using this grading system. The aim of this study was to perform an independent inter- and intra-observer agreement study using the Pfirrmann classification. T2-weighted sagittal images of 79 patients consecutively studied with lumbar spine MRI were classified using the Pfirrmann grading system by six evaluators (three spine surgeons and three radiologists). After a 6-week interval, the 79 cases were presented to the same evaluators in a random sequence for repeat evaluation. The intra-class correlation coefficient (ICC) and the weighted kappa (wκ) were used to determine the inter- and intra-observer agreement. The inter-observer agreement was excellent, with an ICC = 0.94 (0.93-0.95) and wκ = 0.83 (0.74-0.91). There were no differences between spine surgeons and radiologists. Likewise, there were no differences in agreement evaluating the different lumbar discs. Most differences among observers were only of one grade. Intra-observer agreement was also excellent with ICC = 0.86 (0.83-0.89) and wκ = 0.89 (0.85-0.93). In this independent study, the Pfirrmann classification demonstrated an adequate agreement among different observers and by the same observer on separate occasions. Furthermore, it allows communication between radiologists and spine surgeons.

  11. 2008 Niday Perinatal Database quality audit: report of a quality assurance project.

    PubMed

    Dunn, S; Bottomley, J; Ali, A; Walker, M

    2011-12-01

    This quality assurance project was designed to determine the reliability, completeness and comprehensiveness of the data entered into Niday Perinatal Database. Quality of the data was measured by comparing data re-abstracted from the patient record to the original data entered into the Niday Perinatal Database. A representative sample of hospitals in Ontario was selected and a random sample of 100 linked mother and newborn charts were audited for each site. A subset of 33 variables (representing 96 data fields) from the Niday dataset was chosen for re-abstraction. Of the data fields for which Cohen's kappa statistic or intraclass correlation coefficient (ICC) was calculated, 44% showed substantial or almost perfect agreement (beyond chance). However, about 17% showed less than 95% agreement and a kappa or ICC value of less than 60% indicating only slight, fair or moderate agreement (beyond chance). Recommendations to improve the quality of these data fields are presented.

  12. Validation of Spanish versions of the Pelvic Floor Distress Inventory (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ): a multicenter validation randomized study.

    PubMed

    Omotosho, Tola B; Hardart, Anne; Rogers, Rebecca G; Schaffer, Joseph I; Kobak, William H; Romero, Audrey A

    2009-06-01

    The purpose of this study is to validate Spanish versions of the Pelvic Floor Distress Inventory (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ). Spanish versions were developed using back translation and validation was performed by randomizing bilingual women to complete the Spanish or English versions of the questionnaires first. Weighted kappa statistics assessed agreement for individual questions; interclass correlation coefficients (ICC) compared primary and subscale scores. Cronbach's alpha assessed internal consistency of Spanish versions. To detect a 2.7 point difference in scores with 80% power and alpha of 0.05, 44 bilingual subjects were required. Individual questions showed good to excellent agreement (kappa > 0.6) for all but eight questions on the PFIQ. ICCs of primary and subscale scores for both questionnaires showed excellent agreement. (All ICC > 0.79). All Cronbach's alpha values were excellent (>0.84) for the primary scales of both questionnaires. Valid and reliable Spanish versions of the PFIQ and PFDI have been developed.

  13. TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for activation of NF-kappaB.

    PubMed

    Garrison, J B; Samuel, T; Reed, J C

    2009-04-02

    Marginal zone mucosa-associated lymphoid tissue (MALT) B-cell lymphoma is the most common extranodal non-Hodgkin lymphoma. The t(11;18)(q21;q21) translocation occurs frequently in MALT lymphomas and creates a chimeric NF-kappaB-activating protein containing the baculoviral IAP repeat (BIR) domains of c-IAP2 (inhibitor of apoptosis protein 2) fused with portions of the MALT1 protein. The BIR1 domain of c-IAP2 interacts directly with TRAF2 (TNFalpha-receptor-associated factor-2), but its role in NF-kappaB activation is still unclear. Here, we investigated the role of TRAF2 in c-IAP2/MALT1-induced NF-kappaB activation. We show the BIR1 domain of c-IAP2 is essential for NF-kappaB activation, whereas BIR2 and BIR3 domains are not. Studies of c-IAP2/MALT1 BIR1 mutant (E47A/R48A) that fails to activate NF-kappaB showed loss of TRAF2 binding, but retention of TRAF6 binding, suggesting that interaction of c-IAP2/MALT1 with TRAF6 is insufficient for NF-kappaB induction. In addition, a dominant-negative TRAF2 mutant or downregulation of TRAF2 achieved by small interfering RNA inhibited NF-kappaB activation by c-IAP2/MALT1 showing that TRAF2 is indispensable. Comparisons of the bioactivity of intact c-IAP2/MALT1 oncoprotein and BIR1 E47A/R48A c-IAP2/MALT1 mutant that cannot bind TRAF2 in a lymphoid cell line provided evidence that TRAF2 interaction is critical for c-IAP2/MALT1-mediated increases in the NF-kappaB activity, increased expression of endogenous NF-kappaB target genes (c-FLIP, TRAF1), and resistance to apoptosis.

  14. SIRT1 overexpression decreases cisplatin-induced acetylation of NF-{kappa}B p65 subunit and cytotoxicity in renal proximal tubule cells

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

    Jung, Yu Jin; Lee, Jung Eun; Lee, Ae Sin

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Cisplatin increases acetylation of NF-{kappa}B p65 subunit in HK2 cells. Black-Right-Pointing-Pointer SIRT1 overexpression decreases cisplatin-induced p65 acetylation and -cytotoxicity. Black-Right-Pointing-Pointer Resveratrol decreased cisplatin-induced cell viability through deacetylation of p65. -- Abstract: As the increased acetylation of p65 is linked to nuclear factor-{kappa}B (NF-{kappa}B) activation, the regulation of p65 acetylation can be a potential target for the treatment of inflammatory injury. Cisplatin-induced nephrotoxicity is an important issue in chemotherapy of cancer patients. SIRT1, nicotinamide adenine dinucleotide (NAD{sup +})-dependent protein deacetylase, has been implicated in a variety of cellular processes such as inflammatory injury and the control of multidrug resistancemore » in cancer. However, there is no report on the effect of SIRT1 overexpression on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury. To investigate the effect of SIRT1 in on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury, HK2 cells were exposed with SIRT1 overexpression, LacZ adenovirus or dominant negative adenovirus after treatment with cisplatin. While protein expression of SIRT1 was decreased by cisplatin treatment compared with control buffer treatment, acetylation of NF-{kappa}B p65 subunit was significantly increased after treatment with cisplatin. Overexpression of SIRT1 ameliorated the increased acetylation of p65 of NF-{kappa}B during cisplatin treatment and cisplatin-induced cytotoxicity. Further, treatment of cisplatin-treated HK2 cells with resveratrol, a SIRT1 activator, also decreased acetylation of NF-{kappa}B p65 subunit and cisplatin-induced increase of the cell viability in HK2 cells. Our findings suggests that the regulation of acetylation of p65 of NF-{kappa}B through SIRT1 can be a possible target to attenuate cisplatin-induced renal cell damage.« less

  15. Agreement between aggregate and individual-level measures of income and education: a comparison across three patient groups.

    PubMed

    Marra, Carlo A; Lynd, Larry D; Harvard, Stephanie S; Grubisic, Maja

    2011-03-31

    The association between lower socioeconomic status and poorer health outcomes has been observed using both individual-level and aggregate-level measures of income and education. While both are predictive of health outcomes, previous research indicates poor agreement between individual-level and aggregate-level measures. The purpose of this study was to determine the level of agreement between aggregate-level and individual-level measures of income and education among three distinct patient groups, specifically asthma, diabetes, and rheumatoid patients. Individual-level measures of annual household income and education were derived from three separate surveys conducted among patients with asthma (n = 359), diabetes (n = 281) and rheumatoid arthritis (n = 275). Aggregate-level measures of income and education were derived from the 2001 Canadian census, including both census tract-and dissemination area-level measures. Cross-tabulations of individual-level income by aggregate-level income were used to determine the percentage of income classifications in agreement. The kappa statistic (simple and weighted), Spearman's rank correlations, and intra-class correlation coefficient (ICC) were also calculated. Individual-level and aggregate-level education was compared using Chi-Square tests within patient groups. Point biserial correlation coefficients between individual-level and aggregate-level education were computed. Individual-level income was poorly correlated with aggregate-level measures, which provided the worst estimations of income among patients in the lowest income category at the individual-level. Both aggregate-level measures were best at approximating individual-level income in patients with diabetes, in whom aggregate-level estimates were only significantly different from individual-level measures for patients in the lowest income category. Among asthma patients, the proportion of patients classified by aggregate-level measures as having a university degree

  16. Ordovician and Silurian Phi Kappa and Trail Creek formations, Pioneer Mountains, central Idaho; stratigraphic and structural revisions, and new data on graptolite faunas

    USGS Publications Warehouse

    Dover, James H.; Berry, William B.N.; Ross, Reuben James

    1980-01-01

    Recent geologic mapping in the northern Pioneer Mountains combined with the identification of graptolites from 116 new collections indicate that the Ordovician and Silurian Phi Kappa and Trail Creek Formations occur in a series of thrust-bounded slices within a broad zone of imbricate thrust faulting. Though confirming a deformational style first reported in a 1963 study by Michael Churkin, our data suggest that the complexity and regional extent of the thrust zone were not previously recognized. Most previously published sections of the Phi Kappa and Trail Creek Formations were measured across unrecognized thrust faults and therefore include not only structural repetitions of graptolitic Ordovician and Silurian rocks but also other tectonically juxtaposed lithostratigraphic units of diverse ages as well. Because of this discovery, the need to reconsider the stratigraphic validity of these formations and their lithology, nomenclature, structural distribution, facies relations, and graptolite faunas has arisen. The Phi Kappa Formation in most thrust slices has internal stratigraphic continuity despite the intensity of deformation to which it was subjected. As revised herein, the Phi Kappa Formation is restricted to a structurally repeated succession of predominantly black, carbonaceous, graptolitic argillite and shale. Some limy, light-gray-weathering shale occurs in the middle part of the section, and fine-grained locally pebbly quartzite is present at the base. The basal quartzite is here named the Basin Gulch Quartzite Member of the Phi Kappa. The Phi Kappa redefined on a lithologic basis represents the span of Ordovician time from W. B. N. Berry's graptolite zones 2-4 through 15 and also includes approximately 17 m of lithologically identical shale of Early and Middle Silurian age at the top. The lower contact of the formation as revised is tectonic. The Phi Kappa is gradationally overlain by the Trail Creek Formation as restricted herein. Most of the coarser

  17. Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

    PubMed Central

    Teodorov, E.; Ferrari, M.F.R.; Fior-Chadi, D.R.; Camarini, R.; Felício, L.F.

    2012-01-01

    The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of U69593 group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female

  18. Predictive value of bone scintigraphy for the detection of joint involvement in Behçet's disease: Dermatologists' perspectives.

    PubMed

    Seo, Jimyung; Lee, Minseok; Choi, Min Ju; Zheng, Zhenlong; Cho, Arthur; Bang, Dongsik; Kim, Do Young

    2015-01-01

    Behçet's disease (BD) is a multisystemic inflammatory disease with articular involvement. Non-specific arthralgia without objective signs of arthritis, such as swelling or effusion, is common in such patients. Thus, an accurate diagnosis of joint involvement may be challenging for dermatologists. To evaluate the validity of (99m)Tc-methylene diphosphonate (Tc-99m-MDP) bone scintigraphy for joint involvement assessment in patients with BD. In 211 patients with BD who had scintigraphic evaluations due to joint symptoms, agreement between bone scintigraphy findings and clinically evaluated joint complaints was retrospectively assessed using Cohen's kappa (κ) statistic. A patient subset (n = 104) showing agreement between joint complaints and scintigraphy results was re-evaluated by a rheumatologist to determine the level of diagnostic specificity attained by combining bone scintigraphy with clinical examinations of dermatologists. The total kappa value (211 patients) was 0.604, indicating fair agreement between joint complaints and scintigraphy results. Individual analysis of eleven joint categories revealed statistically significant correlations for wrist (κ = 0.677), shoulder (κ = 0.661), and foot joints (κ = 0.618). Of the 104 referrals to a rheumatologist, 95 (91.34%) were confirmed as having BD-associated articular involvement. Joint acral areas (e.g., foot, hand, wrist and shoulder) that had the highest kappa value correlations also ranked highest in diagnostic specificity. Bone scintigraphy presents a simple and useful option for dermatologists to assess joint involvement in BD patients, especially for specific anatomic sites.

  19. Parent-child agreement regarding children's acute stress: the role of parent acute stress reactions.

    PubMed

    Kassam-Adams, Nancy; García-España, J Felipe; Miller, Victoria A; Winston, Flaura

    2006-12-01

    We examined parent-child agreement regarding child acute stress disorder (ASD) and the relationship between parent ASD symptoms and parent ratings of child ASD. Parent-child dyads (N = 219; child age 8-17 years) were assessed within 1 month of child injury. Parent-child agreement was examined regarding child ASD presence, severity, and specific symptoms. Relationships among parent ASD and parent- and child-reported child ASD were examined using regression analysis and generalized estimating equations (GEE). Parent-child agreement was low for presence of child ASD (kappa = 0.22) and for individual symptoms. Parent and child ratings of child ASD severity were moderately correlated (r = 0.35). Parent ASD was independently associated with parent-rated child ASD, after accounting for child self-rating (beta =.65). Generalized estimating equations indicated that parents with ASD overestimated child ASD and parents without ASD underestimated child ASD, compared to the child's self-rating. Parents' own responses to a potentially traumatic event appear to influence their assessment of child symptoms. Clinicians should obtain child self-report of ASD whenever possible and take parent symptoms into account when interpreting parent reports. Helping parents to assess a child's needs following a potentially traumatic event may be a relevant target for clinical attention.

  20. Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells.

    PubMed Central

    Niederman, T M; Garcia, J V; Hastings, W R; Luria, S; Ratner, L

    1992-01-01

    Human immunodeficiency virus type 1 (HIV-1) can establish a persistent and latent infection in CD4+ T lymphocytes (W. C. Greene, N. Engl. J. Med. 324:308-317, 1991; S. M. Schnittman, M. C. Psallidopoulos, H. C. Lane, L. Thompson, M. Baseler, F. Massari, C. H. Fox, N. P. Salzman, and A. S. Fauci, Science 245:305-308, 1989). Production of HIV-1 from latently infected cells requires host cell activation by T-cell mitogens (T. Folks, D. M. Powell, M. M. Lightfoote, S. Benn, M. A. Martin, and A. S. Fauci, Science 231:600-602, 1986; D. Zagury, J. Bernard, R. Leonard, R. Cheynier, M. Feldman, P. S. Sarin, and R. C. Gallo, Science 231:850-853, 1986). This activation is mediated by the host transcription factor NF-kappa B [G. Nabel and D. Baltimore, Nature (London) 326:711-717, 1987]. We report here that the HIV-1-encoded Nef protein inhibits the induction of NF-kappa B DNA-binding activity by T-cell mitogens. However, Nef does not affect the DNA-binding activity of other transcription factors implicated in HIV-1 regulation, including SP-1, USF, URS, and NF-AT. Additionally, Nef inhibits the induction of HIV-1- and interleukin 2-directed gene expression, and the effect on HIV-1 transcription depends on an intact NF-kappa B-binding site. These results indicate that defective recruitment of NF-kappa B may underlie Nef's negative transcriptional effects on the HIV-1 and interleukin 2 promoters. Further evidence suggests that Nef inhibits NF-kappa B induction by interfering with a signal derived from the T-cell receptor complex. Images PMID:1527859

  1. High-frequency expression of a conserved kappa light-chain variable-region gene in chronic lymphocytic leukemia

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

    Kipps, T.J.; Fong, S.; Tomhave, E.

    Malignant B lymphocytes from several patients with chronic lymphocytic leukemia (CLL) were examined for reactivity with murine monoclonal antibody 17.109. This antibody, prepared against the rheumatoid factor (RF) paraprotein Sie, recognizes a cross reactive idiotype on 48% of human IgM RF paraproteins, but does not react with IgM paraproteins without RF activity or substantially with normal pooled immunoglobulin. The 17.109-reactive idiotype is a marker for a kappa III variable-region gene, designated V/sub kappa/RF, that is conserved in outbred human populations. In a limited study of 31 CLL patients, the leukemic cells from 5 of 20 patients with kappa light chain-expressingmore » CLL were recognized by the 17.109 monoclonal antibody. Despite having malignant cells specifically reactive with this antibody, patients with 17.109-positive CLL did not have elevated serum levels of circulating antibody bearing 17.109-reactive determinants. Total RNAs isolated from the CLL B lymphocytes, or from hybridomas produced by fusing the CLL cells with the WI-L2-729-HF/sub 2/ cell line, were fractionated electrophoretically and examined by blot hybridization. Under stringent hybridization conditions capable of discerning a single base-pair mismatch, RNA from the 17.109-idiotype-positive CLL cells hybridized to synthetic oligonucleotide probes corresponding to framework and complementary-determining regions in the V/sub kappa/RF gene. The high frequency of the 17.109-associated idiotype and the V/sub kappa/RF gene in CLL suggests that the disease may arise from B lymphocytes that express a restricted set of inherited immunoglobulin variable-region genes with little or no somatic mutation.« less

  2. Prospective monitoring and self-report of previous falls among older women at high risk of falls and fractures: a study of comparison and agreement

    PubMed Central

    Garcia, Patrícia A.; Dias, João M. D.; Silva, Silvia L. A.; Dias, Rosângela C.

    2015-01-01

    Background: The identification of the occurrence of falls is an important step for screening and for rehabilitation processes for the elderly. The methods of monitoring these events are susceptible to recording biases, and the choice of the most accurate method remains challenging. Objectives: (i) To investigate the agreement between retrospective self-reporting and prospective monitoring of methods of recording falls, and (ii) to compare the retrospective self-reporting of falls and the prospective monitoring of falls and recurrent falls over a 12-month period among older women at high risk of falls and fractures. Method: A total of 118 community-dwelling older women with low bone density were recruited. The incidence of falls was monitored prospectively in 116 older women (2 losses) via monthly phone calls over the course of a year. At the end of this monitoring period, the older women were asked about their recall of falls in the same 12-month period. The agreement between the two methods was analyzed, and the sensitivity and specificity of self-reported previous falls in relation to the prospective monitoring were calculated. Results: There was moderate agreement between the prospective monitoring and the retrospective self-reporting of falls in classifying fallers (Kappa=0.595) and recurrent fallers (Kappa=0.589). The limits of agreement were 0.35±1.66 falls. The self-reporting of prior falls had a 67.2% sensitivity and a 94.2% specificity in classifying fallers among older women and a 50% sensitivity and a 98.9% specificity in classifying recurrent fallers. Conclusion: Self-reporting of falls over a 12-month period underestimated 32.8% of falls and 50% of recurrent falls. The findings recommend caution if one is considering replacing monthly monitoring with annual retrospective questioning. PMID:26083603

  3. Elimination of endogenous aberrant kappa chain transcripts from sp2/0-derived hybridoma cells by specific ribozyme cleavage: utility in genetic therapy of HIV-1 infections.

    PubMed Central

    Duan, L; Pomerantz, R J

    1994-01-01

    The pooled degenerate-primer polymerase chain reaction (PCR) technology is now widely used in the amplification and cloning of murine hybridoma-specific immunoglobulin gene cDNAs. The design of primers is mainly based on the highly conserved 5' terminus of immunoglobulin gene variable regions and the constant region in the 3' terminus. Of note, most murine hybridoma cell lines are derived from the Sp2/0 cell line, which is demonstrated to express endogenous aberrant kappa chains (abV kappa). This high-level endogenous abV kappa mixes with specific kappa chains in the hybridomas and interferes with the efficiency of the reverse transcriptase (RT)-PCR cloning strategy. In this report, during the cloning of murine anti-human immunodeficiency virus type I (HIV-1) hybridoma immunoglobulin cDNAs, a specific primer-PCR screening system was developed, based on the abV kappa complementarity-defining region (CDR), to eliminate abV kappa-carrying plasmids. Furthermore, an abV kappa sequence-specific derived ribozyme was developed and packaged in a retroviral expression vector system. This abV kappa ribozyme can be transduced into different murine hybridomas, and expressed intracellularly to potently eliminate endogenous abV kappa RNA. Images PMID:7816635

  4. Time-dependent modulation of thioredoxin reductase activity might contribute to sulforaphane-mediated inhibition of NF-kappaB binding to DNA.

    PubMed

    Heiss, Elke; Gerhäuser, Clarissa

    2005-01-01

    The chemopreventive agent sulforaphane (SFN) exerts anti-inflammatory activity by thiol-dependent inhibition of nuclear factor kappaB (NF-kappaB) DNA binding. To further analyze the underlying mechanisms, we focused on the thioredoxin/thioredoxin reductase (TrxR) system as a key redox mechanism regulating NF-kappaB DNA binding. Using cultured Raw 264.7 mouse macrophages as a model, 1-chloro-2,4-dinitrobenzene (CDNB), a known inhibitor of TrxR, was identified as an inhibitor of lipopolysaccharide (LPS)-mediated nitric oxide (NO) production and of NF-kappaB DNA binding. CDNB and SFN acted synergistically with respect to inhibition of LPS-induced NO release, and we consequently identified SFN as a novel inhibitor of TrxR enzymatic activity in vitro. Short-term treatment of Raw macrophages with SFN or CDNB resulted in the inhibition of TrxR activity in vivo with half-maximal inhibitory concentration of 25.0 +/- 3.5 microM and 9.4 +/- 3.7 microM, respectively, whereas after a 24-h treatment with 25 microM SFN, TrxR activity was >1.5-fold elevated. In additional experiments, we could exclude that inhibition of trans-activating activity of NF-kappaB contributed to the reduced expression of pro-inflammatory proteins by SFN, based on transient transfection experiments with a (kappaB)(2)- chloramphenicol acetyltransferase construct and a lack of inhibition of protein kinase A activity. These findings further emphasize the importance of redox modulation or thiol reactivity for the regulation of NF-kappaB-dependent transcription by SFN. Antioxid. Redox Signal. 7, 1601-1611. Antioxid. Redox Signal. 7, 1601-1611.

  5. Novel pharmacology: asimadoline, a kappa-opioid agonist, and visceral sensation.

    PubMed

    Camilleri, M

    2008-09-01

    Asimadoline is a potent kappa-opioid receptor agonist with a diaryl acetamide structure. It has high affinity for the kappa receptor, with IC(50) of 5.6 nmol L(-1) (guinea pig) and 1.2 nmol L(-1) (human recombinant), and high selectively with kappa : micro : delta binding ratios of 1 : 501 : 498 in human recombinant receptors. It acts as a complete agonist in in vitro assay. Asimadoline reduced sensation in response to colonic distension at subnoxious pressures in healthy volunteers and in irritable bowel syndrome (IBS) patients without alteration of colonic compliance. Asimadoline reduced satiation and enhanced the postprandial gastric volume (in female volunteers). However, there were no significant effects on gastrointestinal transit, colonic compliance, fasting or postprandial colonic tone. In a clinical trial in 40 patients with functional dyspepsia (Rome II), asimadoline did not significantly alter satiation or symptoms over 8 weeks. However, asimadoline, 0.5 mg, significantly decreased satiation in patients with higher postprandial fullness scores, and daily postprandial fullness severity (over 8 weeks); the asimadoline 1.0 mg group was borderline significant. In a clinical trial in patients with IBS, average pain 2 h post-on-demand treatment with asimadoline was not significantly reduced. Post hoc analyses suggest that asimadoline was effective in mixed IBS. In a 12-week study in 596 patients, chronic treatment with 0.5 mg and 1.0 mg asimadoline was associated with adequate relief of pain and discomfort, improvement in pain score and number of pain-free days in patients with IBS-D. The 1.0 mg dose was also efficacious in IBS-alternating. There were also weeks with significant reduction in bowel frequency and urgency. Asimadoline has been well tolerated in human trials to date.

  6. Myricetin down-regulates phorbol ester-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking activation of nuclear factor kappa B.

    PubMed

    Lee, Kyung Mi; Kang, Nam Joo; Han, Jin Hee; Lee, Ki Won; Lee, Hyong Joo

    2007-11-14

    Abnormal expression of cyclooxygenase-2 (COX-2) has been implicated in the development of cancer. There are multiple lines of evidence that red wine exerts chemopreventive effects, and 3,5,4'-trihydroxy- trans-stilbene (resveratrol), which is a non-flavonoid polyphenol found in red wine, has been reported to be a natural chemopreventive agent. However, other phytochemicals might contribute to the cancer-preventive activities of red wine, and the flavonol content of red wines is about 30 times higher than that of resveratrol. Here we report that 3,3',4',5,5',7-hexahydroxyflavone (myricetin), one of the major flavonols in red wine, inhibits 12-O-tetradecanoylphorbol-13-acetate (phorbol ester)-induced COX-2 expression in JB6 P+ mouse epidermal (JB6 P+) cells by suppressing activation of nuclear factor kappa B (NF-kappaB). Myricetin at 10 and 20 microM inhibited phorbol ester-induced upregulation of COX-2 protein, while resveratrol at the same concentration did not exert significant effects. The phorbol ester-induced production of prostaglandin E 2 was also attenuated by myricetin treatment. Myricetin inhibited both COX-2 and NF-kappaB transactivation in phorbol ester-treated JB6 P+ cells, as determined using a luciferase assay. Myricetin blocked the phorbol ester-stimulated DNA binding activity of NF-kappaB, as determined using an electrophoretic mobility shift assay. Moreover, TPCK (N-tosyl-l-phenylalanine chloromethyl ketone), a NF-kappaB inhibitor, significantly attenuated COX-2 expression and NF-kappaB promoter activity in phorbol ester-treated JB6 P+ cells. In addition, red wine extract inhibited phorbol ester-induced COX-2 expression and NF-kappaB transactivation in JB6 P+ cells. Collectively, these data suggest that myricetin contributes to the chemopreventive effects of red wine through inhibition of COX-2 expression by blocking the activation of NF-kappaB.

  7. An Independent Inter- and Intraobserver Agreement Evaluation of the AOSpine Subaxial Cervical Spine Injury Classification System.

    PubMed

    Urrutia, Julio; Zamora, Tomas; Yurac, Ratko; Campos, Mauricio; Palma, Joaquin; Mobarec, Sebastian; Prada, Carlos

    2017-03-01

    An agreement study. The aim of this study was to perform an independent interobserver and intraobserver agreement assessment of the AOSpine subaxial cervical spine injury classification system. The AOSpine subaxial cervical spine injury classification system was recently described. It showed substantial inter- and intraobserver agreement in the study describing it; however, an independent evaluation has not been performed. Anteroposterior and lateral radiographs, computed tomography scans, and magnetic resonance imaging of 65 patients with acute traumatic subaxial cervical spine injuries were selected and classified using the morphologic grading of the subaxial cervical spine injury classification system by 6 evaluators (3 spine surgeons and 3 orthopedic surgery residents). After a 6-week interval, the 65 cases were presented to the same evaluators in a random sequence for repeat evaluation. The kappa coefficient (κ) was used to determine the inter- and intraobserver agreement. The interobserver agreement was substantial when considering the fracture main types (A, B, C, or F), with κ = 0.61 (0.57-0.64), but moderate when considering the subtypes: κ = 0.57 (0.54-0.60). The intraobserver agreement was substantial considering the fracture types, with κ = 0.68 (0.62-0.74) and considering subtypes, κ = 0.62 (0.57-0.66). No significant differences were observed between spine surgeons and orthopedic residents in the overall inter- and intraobserver agreement, or in the inter- and intraobserver agreement of specific A, B, C, or F type of injuries. This classification allows adequate agreement among different observers and by the same observer on separate occasions. Future prospective studies should determine whether this classification allows surgeons to decide the best treatment for patients with subaxial cervical spine injuries. 3.

  8. Myocardial perfusion in patients with suspected coronary artery disease: comparison between 320-MDCT and rubidium-82 PET.

    PubMed

    Dantas, Roberto Nery; Assuncao, Antonildes Nascimento; Marques, Ismar Aguiar; Fahel, Mateus Guimaraes; Nomura, Cesar Higa; Avila, Luiz Francisco Rodrigues; Giorgi, Maria Clementina Pinto; Soares, Jose; Meneghetti, Jose Claudio; Parga, Jose Rodrigues

    2018-06-01

    Despite advances in non-invasive myocardial perfusion imaging (MPI) evaluation, computed tomography (CT) multiphase MPI protocols have not yet been compared with the highly accurate rubidium-82 positron emission tomography ( 82 RbPET) MPI. Thus, this study aimed to evaluate agreement between 82 RbPET and 320-detector row CT (320-CT) MPI using a multiphase protocol in suspected CAD patients. Forty-four patients referred for MPI evaluation were prospectively enrolled and underwent dipyridamole stress 82 RbPET and multiphase 320-CT MPI (five consecutive volumetric acquisitions during stress). Statistical analyses were performed using the R software. There was high agreement for recognizing summed stress scores ≥ 4 (kappa 0.77, 95% CI 0.55-0.98, p < 0.001) and moderate for detecting SDS ≥ 2 (kappa 0.51, 95% CI 0.23-0.80, p < 0.001). In a per segment analysis, agreement was high for the presence of perfusion defects during stress and rest (kappa 0.75 and 0.82, respectively) and was moderate for impairment severity (kappa 0.58 and 0.65, respectively). The 320-CT protocol was safe, with low radiation burden (9.3 ± 2.4 mSv). There was a significant agreement between dipyridamole stress 320-CT MPI and 82 RbPET MPI in the evaluation of suspected CAD patients of intermediate risk. The multiphase 320-CT MPI protocol was feasible, diagnostic and with relatively low radiation exposure. • Rubidium-82 PET and 320-MDCT can perform MPI studies for CAD investigation. • There is high agreement between rubidium-82 PET and 320-MDCT for MPI assessment. • Multiphase CT perfusion protocols are feasible and with low radiation. • Multiphase CT perfusion protocols can identify image artefacts.

  9. Validating the food behavior questions from the elementary school SPAN questionnaire.

    PubMed

    Thiagarajah, Krisha; Fly, Alyce D; Hoelscher, Deanna M; Bai, Yeon; Lo, Kaman; Leone, Angela; Shertzer, Julie A

    2008-01-01

    The School Physical Activity and Nutrition (SPAN) questionnaire was developed as a surveillance instrument to measure physical activity, nutrition attitudes, and dietary and physical activity behaviors in children and adolescents. The SPAN questionnaire has 2 versions. This study was conducted to evaluate the validity of food consumption items from the elementary school version of the SPAN questionnaire. Validity was assessed by comparing food items selected on the questionnaire with food items reported from a single 24-hour recall covering the same reference period. 5 elementary schools in Indiana. Fourth-grade student volunteers (N = 121) from 5 elementary schools. Agreement between responses to SPAN questionnaire items and reference values obtained through 24-hour dietary recall. The agreement between the questionnaire and the 24-hour recall was measured using Spearman correlation, percentage agreement, and kappa statistic. Correlation between SPAN item responses and recall data ranged from .25 (bread and related products) to .67 (gravy). The percentage agreement ranged from 26% (bread and related products) to 90% (gravy). The kappa statistic varied from .06 (chocolate candy) to .60 (beans). Results from this study indicate that the SPAN questionnaire can be administered in the classroom quickly and easily to measure many previous day dietary behaviors of fourth graders. However, questions addressing consumption of "vegetables," "candy," and "snacks" need further investigation.

  10. Improving the Validity and Reliability of a Health Promotion Survey for Physical Therapists

    PubMed Central

    Stephens, Jaca L.; Lowman, John D.; Graham, Cecilia L.; Morris, David M.; Kohler, Connie L.; Waugh, Jonathan B.

    2013-01-01

    Purpose Physical therapists (PTs) have a unique opportunity to intervene in the area of health promotion. However, no instrument has been validated to measure PTs’ views on health promotion in physical therapy practice. The purpose of this study was to evaluate the content validity and test-retest reliability of a health promotion survey designed for PTs. Methods An expert panel of PTs assessed the content validity of “The Role of Health Promotion in Physical Therapy Survey” and provided suggestions for revision. Item content validity was assessed using the content validity ratio (CVR) as well as the modified kappa statistic. Therapists then participated in the test-retest reliability assessment of the revised health promotion survey, which was assessed using a weighted kappa statistic. Results Based on feedback from the expert panelists, significant revisions were made to the original survey. The expert panel reached at least a majority consensus agreement for all items in the revised survey and the survey-CVR improved from 0.44 to 0.66. Only one item on the revised survey had substantial test-retest agreement, with 55% of the items having moderate agreement and 43% poor agreement. Conclusions All items on the revised health promotion survey demonstrated at least fair validity, but few items had reasonable test-retest reliability. Further modifications should be made to strengthen the validity and improve the reliability of this survey. PMID:23754935

  11. Dose-rate effects of protons on in vivo activation of nuclear factor-kappa B and cytokines in mouse bone marrow cells

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

    Rithidech, K.N.; Rusek, A.; Reungpatthanaphong, P.

    2010-05-28

    The objective of this study was to determine the kinetics of nuclear factor-kappa B (NF-{kappa}B) activation and cytokine expression in bone marrow (BM) cells of exposed mice as a function of the dose rate of protons. The cytokines included in this study are pro-inflammatory [i.e., tumor necrosis factor-alpha (TNF-{alpha}), interleukin-1beta (IL-1{beta}), and IL-6] and anti-inflammatory cytokines (i.e., IL-4 and IL-10). We gave male BALB/cJ mice a whole-body exposure to 0 (sham-controls) or 1.0 Gy of 100 MeV protons, delivered at 5 or 10 mGy min{sup -1}, the dose and dose rates found during solar particle events in space. As amore » reference radiation, groups of mice were exposed to 0 (sham-controls) or 1 Gy of {sup 137}Cs {gamma} rays (10 mGy min{sup -1}). After irradiation, BM cells were collected at 1.5, 3, 24 h, and 1 month for analyses (five mice per treatment group per harvest time). The results indicated that the in vivo time course of effects induced by a single dose of 1 Gy of 100 MeV protons or {sup 137}Cs {gamma} rays, delivered at 10 mGy min{sup -1}, was similar. Although statistically significant levels of NF-{kappa}B activation and pro-inflammatory cytokines in BM cells of exposed mice when compared to those in the corresponding sham controls (Student's t-test, p < 0.05 or < 0.01) were induced by either dose rate, these levels varied over time for each protein. Further, only a dose rate of 5 mGy min{sup -1} induced significant levels of anti-inflammatory cytokines. The results indicate dose-rate effects of protons.« less

  12. Further Evidence of the Association of the Diacylglycerol Kinase Kappa (DGKK) Gene With Hypospadias.

    PubMed

    Hozyasz, Kamil Konrad; Mostowska, Adrianna; Kowal, Andrzej; Mydlak, Dariusz; Tsibulski, Alexander; Jagodzinski, Pawel P

    2018-02-18

    Hypospadias is a common developmental anomaly of the male external genitalia. In previous studies conducted on West European, Californian, and Han Chinese populations the relationship between polymorphic variants of the diacylglycerol kinase kappa (DGKK) gene and hypospadias have been reported. The aim was to study the possible associations between polymorphic variants of the DGKK gene and hypospadias using an independent sample of the Polish population. Ten single nucleotide polymorphisms in DGKK, which were reported to have an impact on the risk of hypospadias in other populations, were genotyped using high-resolution melting curve analysis in a group of 166 boys with isolated anterior (66%) and middle (34%) forms of hypospadias and 285 properly matched controls without congenital anomalies. Two DGKK variants rs11091748 and rs12171755 were associated with increased risk of hypospadias in the Polish population. These results were statistically significant, even after applying the Bonferroni correction for multiple comparisons (P < .005). All the tested nucleotide variants were involved in haplotype combinations associated with hypospadias. The global p-values for haplotypes comprising of rs4143304-rs11091748, rs11091748-rs17328236, rs1934179-rs4554617, rs1934183-rs1934179-rs4554617 and rs12171755-rs1934183-rs1934179-rs4554617 were statistically significant, even after the permutation test correction. Our study provides strong evidence of an association between DGKK nucleotide variants, haplotypes and hypospadias susceptibility.

  13. Reliability of cervical vertebral maturation staging.

    PubMed

    Rainey, Billie-Jean; Burnside, Girvan; Harrison, Jayne E

    2016-07-01

    Growth and its prediction are important for the success of many orthodontic treatments. The aim of this study was to determine the reliability of the cervical vertebral maturation (CVM) method for the assessment of mandibular growth. A group of 20 orthodontic clinicians, inexperienced in CVM staging, was trained to use the improved version of the CVM method for the assessment of mandibular growth with a teaching program. They independently assessed 72 consecutive lateral cephalograms, taken at Liverpool University Dental Hospital, on 2 occasions. The cephalograms were presented in 2 different random orders and interspersed with 11 additional images for standardization. The intraobserver and interobserver agreement values were evaluated using the weighted kappa statistic. The intraobserver and interobserver agreement values were substantial (weighted kappa, 0.6-0.8). The overall intraobserver agreement was 0.70 (SE, 0.01), with average agreement of 89%. The interobserver agreement values were 0.68 (SE, 0.03) for phase 1 and 0.66 (SE, 0.03) for phase 2, with average interobserver agreement of 88%. The intraobserver and interobserver agreement values of classifying the vertebral stages with the CVM method were substantial. These findings demonstrate that this method of CVM classification is reproducible and reliable. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  14. Korteweg-deVries-Burgers (KdVB) equation in a five component cometary plasma with kappa described electrons and ions

    NASA Astrophysics Data System (ADS)

    Michael, Manesh; Willington, Neethu T.; Jayakumar, Neethu; Sebastian, Sijo; Sreekala, G.; Venugopal, Chandu

    2016-12-01

    We investigate the existence of ion-acoustic shock waves in a five component cometary plasma consisting of positively and negatively charged oxygen ions, kappa described hydrogen ions, hot solar electrons, and slightly colder cometary electrons. The KdVB equation has been derived for the system, and its solution plotted for different kappa values, oxygen ion densities, as well as the temperature ratios for the ions. It is found that the amplitude of the shock wave decreases with increasing kappa values. The strength of the shock profile decreases with increasing temperatures of the positively charged oxygen ions and densities of negatively charged oxygen ions.

  15. Confirmation of linear system theory prediction: Rate of change of Herrnstein's kappa as a function of response-force requirement.

    PubMed

    McDowell, J J; Wood, H M

    1985-01-01

    Four human subjects worked on all combinations of five variable-interval schedules and five reinforcer magnitudes ( cent/reinforcer) in each of two phases of the experiment. In one phase the force requirement on the operandum was low (1 or 11 N) and in the other it was high (25 or 146 N). Estimates of Herrnstein's kappa were obtained at each reinforcer magnitude. The results were: (1) response rate was more sensitive to changes in reinforcement rate at the high than at the low force requirement, (2) kappa increased from the beginning to the end of the magnitude range for all subjects at both force requirements, (3) the reciprocal of kappa was a linear function of the reciprocal of reinforcer magnitude for seven of the eight data sets, and (4) the rate of change of kappa was greater at the high than at the low force requirement by an order of magnitude or more. The second and third findings confirm predictions made by linear system theory, and replicate the results of an earlier experiment (McDowell & Wood, 1984). The fourth finding confirms a further prediction of the theory and supports the theory's interpretation of conflicting data on the constancy of Herrnstein's kappa.

  16. Oxidized ultrashort nanotubes as carbon scaffolds for the construction of cell-penetrating NF-kappaB decoy molecules.

    PubMed

    Crinelli, Rita; Carloni, Elisa; Menotta, Michele; Giacomini, Elisa; Bianchi, Marzia; Ambrosi, Gianluca; Giorgi, Luca; Magnani, Mauro

    2010-05-25

    Oligonucleotide (ODN) decoys are synthetic ODNs containing the DNA binding sequence of a transcription factor. When delivered to cells, these molecules can compete with endogenous sequences for binding the transcription factor, thus inhibiting its ability to activate the expression of target genes. Modulation of gene expression by decoy ODNs against nuclear factor-kappaB (NF-kappaB), a transcription factor regulating many genes involved in immunity, has been achieved in a variety of immune/inflammatory disorders. However, the successful use of transcription factor decoys depends on an efficient means to bring the synthetic DNA to target cells. It is known that single-walled carbon nanotubes (SWCNTs), under certain conditions, are able to cross the cell membrane. Thus, we have evaluated the possibility to functionalize SWCNTs with decoy ODNs against NF-kappaB in order to improve their intracellular delivery. To couple ODNs to CNTs, we have exploited the carbodiimide chemistry which allows covalent binding of amino-modified ODNs to carboxyl groups introduced onto SWCNTs through oxidation. The effective binding of ODNs to nanotubes has been demonstrated by a combination of microscopic, spectroscopic, and electrophoretic techniques. The uptake and subcellular distribution of ODN decoys bound to SWCNTs was analyzed by fluorescence microscopy. ODNs were internalized into macrophages and accumulated in the cytosol. Moreover, no cytotoxicity associated with SWCNT administration was observed. Finally, NF-kappaB-dependent gene expression was significantly reduced in cells receiving nanomolar concentrations of SWCNT-NF-kappaB decoys compared to cells receiving SWCNTs or SWCNTs functionalized with a nonspecific ODN sequence, demonstrating both efficacy and specificity of the approach.

  17. Hantaan virus nucleocapsid protein binds to importin alpha proteins and inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappa B.

    PubMed

    Taylor, Shannon L; Frias-Staheli, Natalia; García-Sastre, Adolfo; Schmaljohn, Connie S

    2009-02-01

    Hantaviruses such as Hantaan virus (HTNV) and Andes virus cause two human diseases, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, respectively. For both, disease pathogenesis is thought to be immunologically mediated and there have been numerous reports of patients with elevated levels of proinflammatory and inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), in their sera. Multiple viruses have developed evasion strategies to circumvent the host cell inflammatory process, with one of the most prevalent being the disruption of nuclear factor kappa B (NF-kappaB) activation. We hypothesized that hantaviruses might also moderate host inflammation by interfering with this pathway. We report here that the nucleocapsid (N) protein of HTNV was able to inhibit TNF-alpha-induced activation of NF-kappaB, as measured by a reporter assay, and the activation of endogenous p65, an NF-kappaB subunit. Surprisingly, there was no defect in the degradation of the inhibitor of NF-kappaB (IkappaB) protein, nor was there any alteration in the level of p65 expression in HTNV N-expressing cells. However, immunofluorescence antibody staining demonstrated that cells expressing HTNV N protein and a green fluorescent protein-p65 fusion had limited p65 nuclear translocation. Furthermore, we were able to detect an interaction between HTNV N protein and importin alpha, a nuclear import molecule responsible for shuttling NF-kappaB to the nucleus. Collectively, our data suggest that HTNV N protein can sequester NF-kappaB in the cytoplasm, thus inhibiting NF-kappaB activity. These findings, which were obtained using cells transfected with cDNA representing the HTNV N gene, were confirmed using HTNV-infected cells.

  18. 'Ease of interpretation' of cytological smears stained with modified ultrafast papanicolaou stain: Interobserver agreement and reproducibility.

    PubMed

    Uthamalingam, Preithy; Sathish Kumar, Thabasum; Venus, Albina; Sekar, Preethi; Muthusamy, Rajeshwari K; Mehta, Sangita

    2018-04-01

    Since its inception in 1995, the Ultrafast Papanicoloau (UFPAP) cytological stain has undergone a number of modifications to suit the local availability of reagents and cost in different set ups. However, the reported results have been uniformly encouraging. We designed a study to investigate the inter-observer agreement in 'perceived ease of interpretation' of cytological smears stained with Modified Ultrafast Papanicoloau stain (MUFPAP). After a small pilot study, we prospectively stained air-dried fine needle aspirate smears (FNACs) and Body Fluid smears with the standardized MUFPAP stain. The MUFPAP stained slides were evaluated in tandem with other routine cytological stains as well as independently by two pathologists. Two rater kappa was used to determine the agreement. The study included 93 fluids and 34 FNACs. A vast majority of the cases stained with MUFPAP were rated 'better' than the routine stains in terms of 'overall ease of interpretation' with considerable agreement. The agreement tended to be better for FNACs than fluid specimens. Cases with malignant pathology demonstrated a perfect agreement (kappa = 1) between the raters in terms of 'overall ease of interpretation' (91.7% cases were rated 'very good' by each pathologist) when compared to cases with benign pathology (kappa = 0.52). Nuclear characteristics were appreciated with a better agreement than other parameters. Modified UFPAP stain appears to be quick, reliable, cost-effective alternative in cytology, especially for detecting malignant cells in smears with low cellularity. Its specific advantage is robust nuclear staining against a clear background. © 2018 Wiley Periodicals, Inc.

  19. Kappa-receptor selective binding of opioid ligands with a heterocyclic bicyclo[3.3.1]nonan-9-one structure.

    PubMed

    Benyhe, S; Márki, A; Nachtsheim, Corina; Holzgrabe, Ulrike; Borsodi, Anna

    2003-01-01

    Previous pharmacological results have suggested that members of the heterocyclic bicyclo[3.3.1]nonan-9-one-like compounds are potent kappa-opioid receptor specific agonists. One lead molecule of this series. called compound 1 (dimethyl 7-methyl-2,4-di-2-pyridyl-3.7-diazabicyclo[3.3.1]nonan-9-one-1,5-dicarboxylate) exhibited high affinity for [3H]ethylketocyclazocine and [3H]U-69.593 binding sites in guinea pig cerebellar membranes which known to be a good source for kappa1 receptors. It was shown by molecular modelling that heterocyclic bicyclo[3.3.1]nonan-9-ones fit very well with the structure of ketazocine, a prototypic kappa-selective benzomorphan compound; when compared to the arylacetamide structure of U-69.593, a specific kappa1-receptor agonist, a similar geometry was found with a slightly different distribution of the charges. It is postulated, that the essential structural skeleton involved in the opioid activity is an aryl-propyl-amine element distributed along the N7-C6-C5-C4-aryl bonds.

  20. Kinetic study of ion acoustic twisted waves with kappa distributed electrons

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

    Arshad, Kashif, E-mail: kashif.arshad.butt@gmail.com; Aman-ur-Rehman, E-mail: amansadiq@gmail.com; Mahmood, Shahzad, E-mail: shahzadm100@gmail.com

    2016-05-15

    The kinetic theory of Landau damping of ion acoustic twisted modes is developed in the presence of orbital angular momentum of the helical (twisted) electric field in plasmas with kappa distributed electrons and Maxwellian ions. The perturbed distribution function and helical electric field are considered to be decomposed by Laguerre-Gaussian mode function defined in cylindrical geometry. The Vlasov-Poisson equation is obtained and solved analytically to obtain the weak damping rates of the ion acoustic twisted waves in a non-thermal plasma. The strong damping effects of ion acoustic twisted waves at low values of temperature ratio of electrons and ions aremore » also obtained by using exact numerical method and illustrated graphically, where the weak damping wave theory fails to explain the phenomenon properly. The obtained results of Landau damping rates of the twisted ion acoustic wave are discussed at different values of azimuthal wave number and non-thermal parameter kappa for electrons.« less